UnderstandingNEUROLOGYa problem-orientated approachJohn GreeneConsultant NeurologistInstitute of Neurological Sciences, Southern General Hospital, GlasgowIan BoneProfessor of NeurologyInstitute of Neurological Sciences, Southern General Hospital, GlasgowMANSONPUBLISHING
Abbreviations 5AbbreviationsACE Addenbrooke’s CognitiveExamination/angiotensin-converting enzymeAChRAb anti-acetylcholine receptor antibodyACTH adrenocorticotrophic hormoneAD Alzheimer's diseaseAICA anterior inferior cerebellar arteryAION anterior ischaemic optic neuropathyALP alkaline phosphataseALS amyotrophic lateral sclerosisANA antinuclear antibodyAP antero-posteriorARAS ascending reticular activating systemAST aspartate aminotransferaseAVM arteriovenous malformationBIH benign intracranial hypertensionBOLD blood oxygen level dependentBPPV benign paroxysmal positional vertigoBSAEP brainstem auditory evoked potentialCADASIL cerebral autosomal dominantarteriopathy with subcortical infarcts andleucoencephalopathyCAT computer assisted tomographyCBD corticobasal degenerationCBF cerebral blood flowCBV cerebral blood volumeCho cholineCJD Creutzfeldt–Jakob diseaseCK creatine kinaseCMAP compound muscle action potentialCNS central nervous systemCOPD chronic obstructive pulmonary diseaseCr creatineCRP C-reactive proteinCSF cerebrospinal fluidCT computed tomographyCTA CT angiographyCTP CT perfusionCTV CT venographyDMD Duchenne muscular dystrophyDNA deoxyribonucleic acidDRG dorsal root ganglionDSA digital subtraction angiographyDWI diffusion-weighted imagingECG electrocardiographyEEG electroencephalogramEMG electromyographyENA extractable nuclear antigenENG electronystagmographyERG electroretinographyES epileptic seizureESR erythrocyte sedimentation rateFBC full blood countFLAIR (MRI) fluid-attenuated inversion recovery(MRI)fMRI functional magnetic resonance imagingFP-CIT fluoropropyl carboxymethoxy iodophenylnortropane spectroscopyGH growth hormoneGnRH gonadotrophin releasing hormoneGP general practitionerGT glutamyl transferaseHD Huntington’s diseaseHIV human immunodeficiency virusHMPAO hexamethylpropyleneamine oximeHMSN hereditary motor and sensory neuropathyHSV herpes simplex virusILAE International League against EpilepsyINR international normalized ratioIQ intelligence quotientJME juvenile myoclonic epilepsyLMN lower motor neuroneLP lumbar puncture
CHAPTER 1:HISTORY TAKING ANDPHYSICAL EXAMINATION7Ian Bone, John GreeneINTRODUCTIONCONCEPTS OF HISTORY TAKINGTAKING THE HISTORYNEUROLOGICAL EXAMINATIONCRANIAL NERVE EXAMINATIONMOTOR EXAMINATIONSENSORY EXAMINATIONCOORDINATIONSTANCE AND GAITREFERENCES
8INTRODUCTIONA logical framework of history taking and examinationis the basis of the discipline of clinical medicine. Theincreasing range, availability, and sensitivity ofdiagnostic tests should never replace this ‘clinicalacumen’. This text adopts the problem-orientatedapproach practised daily in clinics, surgeries, andwards worldwide. While investigative resources mayvary from country to country, these diagnostic skillsshould not. The nature of neurological disease is suchthat patients are often difficult to rouse, their intellector expression of language and memory impaired, orbehaviour inappropriate. In such circumstances,history taking may be impossible and an account froma family member or friend will be essential. Specificneurological deficits, e.g. anosognosia, may result in apatient denying any symptoms (such as nondominantlimb weakness). Finally, with increasing travel, alanguage barrier may present additionalcommunication problems.This initial chapter is a brief generic guide tohistory taking, examination, and the essentials offunctional neurology (neuroanatomy). The studentshould use this route map not in isolation, butalongside other texts such as NeurologicalExamination made easy (1) and Neurology andNeurosurgery Illustrated (2).CONCEPTS OF HISTORY TAKINGThe purpose of clinical examination is to diagnose thecondition responsible for the patient’s symptoms,which will subsequently dictate treatment. Inneurology, probably more so than in any othermedical specialty, the history is vital in narrowingdown the differential diagnosis.Ideally, using a hypothetico-deductive approach,each question should be a sort of ‘magic bullet’ bywhich the differential diagnoses are eliminated, untila unique diagnosis is reached. This approach,however, takes years to develop, and a student isadvised to follow a logical order of history taking, toensure that no important parts of the history aremissed. By following the same pattern of historytaking time and again, it is less likely that a studentwill miss out an important element in a stressfulsituation such as an exam. The history will usuallygive the clinician a likely diagnosis, and physicalexamination may then serve merely as confirmatory.There are two key questions to be asked: firstly,where in the neuraxis is a lesion likely to be, given thefindings on history taking and examination?Secondly, what is the nature of the causal lesioninferred by the tempo of illness presentation?Insidious and progressive symptoms may becompatible with tumour or degenerative illness. Asudden onset and improving symptoms could be dueto vascular disease. A subacute onset of symptomslasting a few weeks before resolving may be due todemyelinating disease such as multiple sclerosis.In order to answer these questions, it is importantto have a good understanding of the anatomy andphysiology of the nervous system. Once understood,neurology loses its mystery and is arguably the mostlogical of all the medical subspecialties in terms ofutilizing information available from clinicalexamination to localize the site and nature ofpathology.TAKING THE HISTORYTHE PRESENTING COMPLAINTEnquiry must be focused; a complaint of headacheshould not be met with an endless list of apparentlyunconnected questions about all other possiblesymptoms. This will tire both the patient and doctor.However, anticipating and enquiring into allpotentially relevant symptoms form a vital part ofhistory taking. For instance, memory loss,personality change, hearing loss, and double visionmay accompany headache (to name but a fewpossibilities). Each of these additional complaintscontributes importantly to defining a pathologicalprocess, anatomical localization, and targetedexamination.The pathological processes that affect the centraland peripheral nervous systems are relatively few.Pathological processesConditions can be inherited, developmental, oracquired:Infection (e.g. meningitis)Inflammation (e.g. multiple sclerosis)Ischaemic (trauma and stroke)Neoplastic (primary and secondary tumours)Degenerative (e.g. Parkinson’s disease)Toxic/metabolicKnowledge of these pathological possibilitiesleads to the first set of key questions.
10These five questions (onset, duration, frequency,associated symptoms, and aggravating or relievingfactors) should be applied to all the possibleneurological scenarios that commonly arise inpractice. The common scenarios are:❏ Headache.❏ Visual disturbance.❏ Loss of consciousness.❏ Dizziness.❏ Hearing loss.❏ Unsteadiness.❏ Memory loss.❏ Speech disturbance.❏ Numbness.❏ Weakness.❏ Bladder/bowel disturbance.Prior medical historyThis should be a standard component of all clinicalhistory taking. However, there are certain areas whereinformation is essential to the process of deriving theneurological differential diagnosis:❏ Prior neurological symptoms or diagnosis.❏ Exposure to, or possession of risk factors forneurological disease and occupational history.❏ History of head injury.❏ Alcohol or drug misuse.❏❏Psychiatric history.Other (e.g. clotting disorder, immunodeficiencyor at risk, thyroid disease).Family historyMany neurological illnesses have a hereditary basis.To explore this, a detailed family history is essential.Death of a parent or sibling at an early age from anunrelated cause may obscure this possibility. Thegenotype represents the actual genetic basis for anindividual; the term phenotype refers to the outwardexpression of the genotype. In some disorders, thevariability of the phenotype within a family mayresult in a significant family history being discounted.Also, with complex patterns of inheritance,tendencies and traits within a pedigree are at risk ofbeing overlooked.The student should have a working knowledgeof patterns of simple inheritance (dominant,recessive, and sex-linked) and complexinheritance (polygenic, multiple allelic,incomplete dominant, and sex-influenced trait).Social historyAwareness of social activities (smoking, drinking,recreational drug use, sporting interests) may behelpful to diagnosis. For instance, the mountain bikerpresenting with ulnar nerve palsy (deep branchcompression in the palm of the hand), the heavydrinker with seizures, or the drug user with HIVrelatedinfection.Employment history informs on educationalachievements, behavioural and cognitive decline,stigmatization due to illness (epilepsy), or progressionof physical disability (multiple sclerosis). Finally,certain employments carry inherent risks ofneurological disturbance (e.g. working withsolvents/petrochemicals). In patients with disabilityand handicap, the questioner should establish whothe main carer is, what level of care is required, howindependent an individual is in aspects of daily living(cooking, feeding, dressing, and bathing/showering).The following should also be documented: livingcircumstances (is housing appropriate to current andanticipated degree of future handicap?), provision ofstate benefits, social worker, and aids (wheelchairsand the like).Current drugs and allergiesMany common complaints such as muscle pain(myalgia), tingling (paraesthesia), headache, anddizziness are recognized side-effects of commonlyprescribed drugs. This is becoming increasinglyrecognized in the elderly who receive polypharmacy.The drug history should be ascertained in detail. Areall drugs required? Are there drug interactions thatcould be harmful? Does the current complaint relatein time to the commencement of a particular drug?These questions can result in the recognition of causeand halting a troublesome symptom without recourseto unnecessary investigations.The identification of allergies is vital to avoidrechallenging the patient with a potentially harmfuldrug. With the widespread use of contrast dye inimaging investigations (CT and MRI), a history ofprior contrast sensitivity should be sought. Finally, itis at this point that absolute or relativecontraindications to investigations should bedocumented. Ferro-magnetic foreign bodies,pacemakers, hip replacement, breast enhancement,pregnancy, or claustrophobia must all be documentedwhere MRI is considered necessary.
History taking and physical examination 11NEUROLOGICAL EXAMINATIONANATOMY OF THE NERVOUS SYSTEMThe nervous system is hierarchically organized. Thesensory and special sensory nervous systems provideascending input to higher centres regarding theposition of the individual in the environment. Thisincludes vision, touch, smell, joint position, pain, andhearing. Such modality-specific information is thenprocessed and coordinated in order to provide thehigher centres with a coherent model of theenvironment. On this basis, higher processes allowthe individual to decide on and initiate a particularresponse to the environment. This consideredresponse is then executed via the motor cortex,through the spinal cord and peripheral nerves toindividual muscles to allow appropriate action.Lesions to the nervous system may result in apathological excitation, such as a focal motor seizureor, alternatively, a pathological inhibition, e.g.paralysis due to stroke. These are termed positive andnegative phenomena.MENTAL STATUSLevels of consciousnessThe understanding of consciousness is madeconfusing by the use of terms such as stuporose orobtunded. These subjective terms are best avoided,and the following more meaningful terms should beused: consciousness is particularly difficult to define,but can be described as a state which allows theindividual to perceive and understand theenvironment, and to respond to what is perceived. Itrequires both arousal and awareness. Arousalindicates how well a subject appears to be able tointeract with the environment, e.g. whether they areawake or sleeping. Awareness, by contrast, relates tothe depth and content of the aroused state. Attention,in turn, depends on awareness.It is crucial for doctors to relay informationregarding a patient’s conscious state using reliablescales. Although the Glasgow Coma Scale was initiallydeveloped for patients with head trauma, it has proveda reliable means of assessing and reporting on patientswith reduced conscious level regardless of the aetiology,and has good inter-rater reliability. It comprises threecategories: eye opening, motor response, and verbalresponse (Table 1). Although the three components canbe added up, e.g. GCS 9, it is best to describe theindividual components, e.g. E3M4V2.Table 1 Glasgow Coma ScaleEye opening (E) Spontaneous 4To speech 3To pain 2None 1Motor response (M) Obeys commands 6Localizes to pain 5Flexion withdrawal to pain 4Abnormal flexion of upper limbs(decorticate rigidity) 3Extension (decerebrate rigidity) 2No response 1Best verbal response (V) Orientated and converses 5Disorientated and converses 4Inappropriate words 3Incomprehensible 2No response 1
12Anatomy of consciousnessConsciousness may be impaired by damage to thereticular formation in the midbrain and thalamus, orby bilateral damage to the cerebral hemispheresresulting in brain displacement, which therebyimpairs the function of the reticular formation (1–3).11 Diagram to show brain herniation, resulting in impaired consciousness.232 Magnetic resonance image illustrating central pontinemyelinolysis, a brainstem cause of reduced consciousness.3 Computed tomography scan showing subdural collection,resulting in impaired consciousness.
History taking and physical examination 13Loss of awareness in the context of being awakeis termed akinetic mutism, and can occur with frontallesions (4).Brainstem testsIn a patient with a reduced conscious level, it must beascertained whether coma is due to bilateralhemispheric disease or to brainstem pathology.Utilizing brainstem reflexes can assess the integrity ofthe brainstem. Pupillary responses to light ascertainwhether there is significant midbrain pathology. Thecorneal reflex tests brainstem integrity at the pontomedullarylevel. Gag reflex assesses the lowerbrainstem, while assessment of spontaneousrespiratory movements indicates the integrity of themedullary respiratory centres. These four clinicalassessments allow the clinician to interrogate theintegrity of the brainstem (5). If an unconsciouspatient exhibits normal brainstem reflexes, then it islikely that the impaired consciousness is due tobilateral hemispheric dysfunction.BehaviourIn the conscious patient, behaviour and cognitionmust be further addressed. Traditionally, behaviour ispart of the psychiatric examination, and in neurologyit is often neglected in favour of cognition. It is,however, worth commenting on the patient’sbehaviour. Mood should be noted, whetherdepressed, euphoric, or unduly anxious. Emotionallability may also occur, with sudden swings in mood.While taking the history, the organization andcontent of thought processes should also be noted.Muddled thinking may suggest a mild delirium.Thought content can highlight the presence ofdelusions (beliefs held which are at variance with thepatient’s environmental background) or illusions(misperception of stimuli, e.g. mistaking a bush indim light for a person). These differ fromhallucinations, in which the imagined object is notbased on a misperceived real object (e.g. hearingvoices, seeing Lilliputian figures and so on).45Pupillary responseMidbrain(Edinger–Westphal)nucleusCorneal V PontoreflexmedullaryVIIjunctionGagreflexIXXMedullaRespirationLower medulla4 Computed tomography scan showing frontal haemorrhage,resulting in the patient being awake but not aware.5 Diagram to illustrate the use of brainstem reflexes inassessing the integrity of the brainstem at different levels.
14The degree of psychomotor activity should alsobe assessed. Hyperalert patients are restless andexhibit increased motor activity, including speech thatmay be accompanied by autonomic overactivity. Bycontrast, hypoalert patients may sit motionless forhours without speaking.Cognitive functionThis aspect of neurological history taking andexamination was neglected for most of the twentiethcentury, and is still often poorly performed or evenomitted. Cognition embraces many higher orderactivities, including attention, memory, and language.It is difficult to examine adequately these complexskills within the confines of a busy neurology clinic.However, there are brief measures for assessingcognitive function such as the Addenbrooke’sCognitive Examination (ACE). While being no matchfor proper neuropsychological assessment, it is a verygood ‘snap-shot’ assessment of cognitive functions.Cognitive functions are best divided into those thatrequire an extensive anatomical network (distributed),and those utilizing a more localized brain area(localized) (Table 2). Impairment of a distributedfunction, such as attention, does not allow the clinicianto localize the lesion, but suggests that there is a deficitsomewhere in the network subserving attention, whichcan then be further localized with subsequent examinationand investigation. By contrast, a deficit in a localizedfunction such as language allows the lesion site tobe pinpointed from history and examination alone.Distributed cognitive functionsAttention/concentrationAttention is difficult to define, but impliesconcentration and persistence. Impaired attentionimplies inability to focus and selectively concentrateon a topic, with impersistence, distractibility, andoften disorientation, e.g. as seen in the acuteconfusional state. Anatomically, attention requires adistributed system including neocortex (especiallyprefrontal), thalamus, and brainstem, linked by thereticular activating system (6). Attention may bedisrupted by any focal lesion affecting this distributedsystem, or by a diffuse disturbance, such as metabolicupset or the effect of drugs.Table 2 Cognitive functionsDistributed Attention/concentrationMemoryHigher-order intellectual functionsLocalizedDominant LanguageCalculationPraxisNondominant Spatially-directed attentionComplex visuo-perceptual skillsConstructional abilities6Cortical areasPre-frontal, posterior parietal,and ventral temporalThalamusIntralaminar and reticular nucleiDopaminergic, cholinergic, andserotinergic pathwaysBrainstemnucleiReticular formation, midlineraphe, locus coeruleus, andtegmental nuclei6 Schematic diagram to show the anatomy of the reticularactivating system.
History taking and physical examination 15Bedside tests of attention/concentration includeorientation, digit span (i.e. asking the patient torepeat number strings), the ability to recite months ofthe year backwards (not forwards as this isoverlearned and not a true measure of attention), orserial sevens (i.e. asking the patient to subtract 7 from100 and keep subtracting 7).Higher cognitive processesThe frontal lobes are particularly involved inconceptual thinking, adaptation and set shifting (i.e.adjusting to a change in rules), planning and problemsolving, and personality, motivation, and socialbehaviour.Patients with frontal lobe damage show deficits inthe above, in particular poor planning and goal setting,distractibility, and perseveration (i.e. being unable todiscard old rules and start using new rules). Such socalledfrontal behaviour can be present long beforethere is any supporting evidence of frontal dysfunctionon neuropsychology or brain imaging (7).In addition to the above cognitive deficits, frontallobe damage also has behavioural consequences.Disinhibition may occur, resulting in social andsexually inappropriate behaviour. Aggression and lackof concern for others may be a feature. Loss of interestin the world also occurs, with increasing passivity.Applied anatomyAnatomy of the frontal lobes is described in (8). Thefrontal lobe syndrome may be further subdivided.Orbitomedial damage is said to result in personalityand behaviour change, while dorsolateral damagetends to have more effect on executive function, suchas problem solving. Such distinctions are rarelyclinically apparent.Frontal lobe function may be tested in the clinicby verbal fluency, e.g. FAS letter fluency (asking thepatient to generate as many exemplars [examplewords] beginning with F in 1 minute, then repeatingthis for both A and S). Asking patients what is meantby proverbs such as ‘A rolling stone gathers no moss’is also a measure of abstract reasoning and relies onthe frontal lobes. Motor sequencing, such as theAlternating Hand Movements Test, also assessesfrontal function.78SMAM1FEFDLBAOM8 Diagram of the anatomy of the brain frontal lobes. BA: Broca’s area;DL: dorsolateral pre-frontal area; FEF: frontal eye fields; M1: primarymotor cortex; OM: orbito-medial; SMA: supplementary motor area.7 Magnetic resonance image of a frontal brain tumour.
16MemoryMemory is not a unitary function, but is a broad termwhich includes many subcomponents. For instance,episodic memory refers to the ability to learn andretain new information. Asking a patient to repeat aname and address three times, and then asking thepatient to recall the name and address after at least 5minutes can assess this. The ability to do this task iscrucially dependent on the hippocampus and otherlimbic system structures. This is the first region of thebrain to be affected in Alzheimer’s disease, henceimpaired delayed recall is the earliest feature found ontesting patients with new-onset Alzheimer’s disease.Semantic memory, by contrast, is the database ofknowledge an individual draws on to give meaning toconscious experience, e.g. knowing the capital ofFrance or the boiling point of water. This can betested at the bedside by category fluency (e.g. namingas many animals in the next minute, object naming[whether real objects or line drawings], and reading).Memory will be addressed more fully in the sectionon Memory disorders (3.3).Localized cognitive functionsDominantLanguageLanguage is subserved by the left hemisphere innearly all right-handed people and in over 60% ofleft-handed people. Language comprehension isserved mainly by the dominant temporal lobe,especially Wernicke’s area (the posterior third of thesuperior temporal gyrus), while language expressionrelies on more anterior structures such as Broca’s area(the posterior third of inferior frontal gyrus).A full bedside assessment of language shouldinclude the following: spontaneous speech, naming,comprehension, repetition, reading, and writing. Thenature of any language impairment (aphasia) detectedby these determines the type of aphasia.Language is more fully addressed in the sectionon Speech and Language Disorders (page 94).CalculationPathology at the angular gyrus (the posterior Sylvianfissure straddling temporal and parietal lobes) of thedominant hemisphere can result in inability tounderstand or write numbers. This can be found inassociation with aphasia. When occurring inconjunction with the inability to write, right-leftdisorientation and finger agnosia (i.e. being unable tosay which of the patient’s or examiner’s fingers is themiddle one), this is termed Gerstmann’s syndrome.PraxisPraxis refers to the ability to perform and controlskilled or complex motor actions. Apraxia is theinability to execute such motor commands in thecontext of good comprehension and cooperation,together with functioning motor and sensory systems.Apraxia is further subdivided into ideomotor andideational apraxia, terms that can generate confusion.Ideomotor apraxia is the inability to carry outmotor acts to command, yet with preserved ability tocarry these out spontaneously, e.g. lighting a match. Itis thought that ideomotor apraxia occurs due tostored programmes for specific motor acts, calledengrams, being damaged or disconnected. It is usuallydue to dominant hemisphere, inferior parietal orprefrontal pathology.Ideational apraxia is the inability to synthesize theindividual components of a complex motor act intoone unified operation, with retained ability to performeach component, e.g. able to open a matchbox tocommand, strike a match to command, yet be unableto effortlessly carry out the entire motor repertoireseamlessly. It can occur with extensive left hemispheredisease or lesions affecting the corpus callosum (thefibres connecting the cerebral hemispheres).Apraxia may affect only selected movements. Forexample, orobuccal apraxia results in difficultyperforming motor commands involving buccal areas(such as whistling, chewing) and occurs with inferiorfrontal or insular lesions. Asking the patient to mimecertain actions, such as whistling, waving goodbye,and pouring tea may test praxis.Right hemisphere functionVisuo-spatial and perceptual function rely heavily butnot exclusively on the nondominant hemisphere.These are required for visual attention, i.e. the abilityto attend to the visual environment. The ability todress, construct objects, and ability to understandwhat one is seeing may be impaired with righthemisphere damage. Such patients may fail torecognize objects or people. They tend to ignoreobjects to their left side and may fail to identifyobjects or faces despite intact vision. Visuo-spatialand perceptual function may be tested at the bedsideby asking the patient to draw a clock face,overlapping pentagons, or a three-dimensional cube.
History taking and physical examination 17Damage to the right hemisphere can impairspatially directed attention leading to the disorder ofneglect, where patients attend less to left hemispace (9).This may amount to a complete denial of the left side(10), or lesser states such as sensory extinction where avisual or tactile stimulus, when administered bilaterally,fails to be perceived on the left side. Neglect usuallyoccurs due to right inferior parietal or prefrontalpathology, but occasionally results from damage to thethalamus, basal ganglia, or cingulate gyrus.That neglect occurs almost always to the left maybe due to the left hemisphere monitoring righthemispace, while the right hemisphere monitors bothhemispaces. Thus a right hemisphere lesion meansthat only right hemispace is monitored, while theconverse does not apply with a left hemisphere lesion.Dressing apraxia is not an apraxia as such, but avisuo-perceptual disorder in which the patient isunable to dress (becoming entangled in clothing),despite there being no motor disorder. It usuallyoccurs due to right posterior parietal damage.The ability to copy a shape, e.g. overlappingpentagons or a cube, requires vision, perception, andvisuo-motor output. Difficulties copying usuallyreflect right parietal dysfunction. Patients with rightsidedlesions tend to produce drawings with grosslyaltered spatial arrangements, while patients with leftsidedlesions make over-simplified drawings.910ExploresRExploresL+RLefthemisphereRighthemisphere9 Diagram to show the dominance of the right hemisphere fordirected attention.10 Unilateral visual neglect analysis. The patient neglects theleft hemispace due to a right hemisphere stroke. (The originaldrawing was of a double-headed daisy.)
18Difficulties in higher order visuo-perceptual skillsmay occur in right hemisphere damage. In visualobject agnosia, the patient is unable to identify anobject visually despite having normal basicperception. This does not represent a generalsemantic memory loss about the object, asidentification through tactile or auditory modalitiesresults in access to full semantic information aboutthe object. The deficit in access is therefore modalityspecific,i.e. inability to access semantic informationabout an object when this is presented visually.This deficit can apply specifically to personrecognition. In prosopagnosia, the patient is unable torecognize familiar faces. Knowledge about the personis not lost, however, as gait, voice, and so on cause thepatient to identify the person whose face is notrecognized. It is usually due to bilateral inferioroccipito-temporal lesions.COGNITIVE HISTORY TAKINGAlthough cognitive history taking broadly follows thegeneral principles of history taking, the presence ofcognitive deficits (not always noticed by the patientwhile causing them inexplicable distress) means thatthere are differences in the conduct of this part of theexamination. It is worthwhile trying to interview bothpatient and informant alone at some point; thisallows any sensitive issues to be mentioned by thepatient, and also allows the informant to give a clearhistory of the nature of the presenting complaintwithout risk of offending the patient. In view of thepossible lack of insight, it is worth asking the patientif they know why they have been referred to theclinic. In addition to the presenting complaintsthemselves, it is useful to ask how these difficultiesare impacting on daily living activities.A complaint such as ‘poor memory’ cannot beaccepted simply at face value, but the nature of thecomplaint must be determined further. Patients mayuse the term ‘poor memory’ to represent manyproblems, including failing to keep appointments orretain new information (true episodic memoryimpairment), forgetting objects’ and people’s names(anomia, usually in keeping with semantic memoryimpairment), or forgetting where they have left theirkeys or why they have gone into the kitchen (oftensimply slips of attention or concentration). Enquiriesabout anterograde memory (i.e. ability to retain newinformation), retrograde memory (ability to retrieveknowledge about previous holidays and so on), andsemantic memory (factual knowledge, knowing whatobjects are used for) are important.For language, in addition to asking whetherpatients have difficulty expressing themselves or inunderstanding others, it is also worth asking whetherthere has been any impairment of reading or writing.Difficulties with dressing, finding one’s way aroundthe house or the town, or difficulties constructingobjects suggest a visuo-spatial problem.THE INFORMANT INTERVIEWWhen speaking to the informant alone, informationon what was the initial symptom, and how symptomshave changed with time is important. For example,initial symptoms of no longer being able to retain newinformation indicate an anterograde episodic memorydeficit, which could be the beginnings of Alzheimer’sdisease. By contrast, an initial symptom of wordfindingdifficulty and forgetting the function ofobjects suggests a semantic memory deficit such ascan occur in fronto-temporal dementia. The tempo ofevolution of symptoms can help to determine theunderlying pathology. Sudden-onset symptoms withsubsequent improvement suggest a vascular cause.Insidious-onset progressive symptoms are more inkeeping with neurodegenerative disease, or perhaps aslow-growing tumour.Examples of how the cognitive deficit affects thepatient in the real world should be sought, such aswork, cooking and general household tasks, drivingand so on. The informant may well be able to providefurther history, which the patient cannot. Past historyshould enquire as to whether there have been anyprevious neurological or psychiatric illnesses, orwhether there has been any significant head trauma(i.e. sufficient at the time to result in loss ofconsciousness). An accurate drug history is essential,particularly as sedating drugs can be an easilyreversible cause of cognitive impairment. Familyhistory must be thorough, and diagnoses should notnecessarily be taken at face value; institutionalizationor ‘nervous breakdown’ may indicate a previouslyundetected neurological disease, while depressionmay be secondary to a neurodegenerative process.Social history provides the patient’s occupation,which is of use in estimating premorbid IQ. Alcoholhabits are particularly relevant here.
History taking and physical examination 19PHYSICAL EXAMINATIONIn a busy clinic, the clinician may be hard pushed toobtain a history from both patient and informant,perform bedside cognitive testing, and also conduct aphysical examination. A detailed neurologicalexamination is not routinely necessary, but thefollowing features may be of particular relevance.Visual field deficits may not be noticed by thepatient or relative, and can easily be screened for byconfrontation, preferably using a redheaded pin, butif necessary using a wiggling finger. Eye movements,both saccades (voluntary rapid movements) andpursuit (tracking the examiner’s finger) should bechecked. For example, inability to look down tocommand can occur in progressive supranuclearpalsy, while impaired pursuit movements can occur inbasal ganglia disorders such as Huntington’s disease.Specific signs of frontal disease can include thepresence of so-called primitive reflexes such as graspreflex (grip occurring due to stroking palm), poutreflex (puckering of lips when lips lightly tapped),and palmo-mental reflex (chin quivering when palmstroked) (11). Involuntary movements such asfidgeting, which could indicate Huntington’s disease,can be easily overlooked unless consciously lookedfor. Gait analysis can also be useful. The stoopingfestinant gait of Parkinson’s disease or the ‘feet gluedto the floor’ sign of normal pressure hydrocephaluscan be diagnostic.BEDSIDE COGNITIVE TESTINGThe assessment of higher cerebral function is carriedout during the neurological examination, but mayalso be supplemented by a more detailed assessmentof cognitive function performed by a neuropsychologist(if available). The extent to which theclinician is able to assess cortical function depends onthe time available in clinic, and also whether theclinician has the backup of a neuropsychologist, asthese services are not universally available. Theclinician should be able to sample various aspects ofcognitive function, such as general functioning,frontal function, memory, language, and visuoperceptualfunction.Pout reflexTap lips with tendonhammer –a poutresponseis observedGlabellar reflexPatient cannot inhibit blinking in response tostimulation (tappingbetween the eyes)11Grasp reflexPalmomental reflexStroking palm of handinduces ‘grasp’11 Diagram to illustrate primitive reflexes.Quick scratch on palm of handinduces sudden contraction ofmentalis muscle in face
20A standardized test such as the Mini-Mental StateExamination (MMSE) can be used to test aspects ofcognitive function. Although this was originallydevised to be used as a screening tool for dementia, itis of some use for a brief cognitive overview.Some criticisms of the MMSE are that thelanguage and visuo-perceptual items are too easy,there is not a proper test of delayed recall, and thereis no timed test to assess subcortical cognitiveslowing. In an effort to address these issues, theAddenbrooke’s Cognitive Examination (ACE)includes the 30 points of the MMSE, but theadditional 70 points improve the assessment ofmemory and language and include timed fluencytasks which are sensitive to subcortical dysfunction.CRANIAL NERVE EXAMINATIONCRANIAL NERVE I (OLFACTORY NERVE)The patient should be asked if taste and smell areaffected. Further testing is not necessary unless thepatient concurs or there is a special reason to testolfaction. Before testing, the airway should bechecked that it is clear. Each nostril is tested with anodour such as camphor or peppermint. Loss of smellis termed anosmia. If nasal disease is excluded, a lackof smell may be due to closed head injury or anteriorcranial fossa disease but is also a feature of certainneurodegenerative disorders such as Parkinson’sdisease.CRANIAL NERVE II (OPTIC NERVE)The basic tools for assessment are a bright light, anophthalmoscope, coloured pins, and a vision readingchart (e.g. Snellen). First assess visual acuity. Thepatient is asked if they are aware of reduced vision ineither or both eyes. Visual acuity should be testedwearing glasses if prescribed. Each eye is covered inturn and its neighbour tested separately. When usingthe Snellen chart, the patient stands 3–6 m from thechart and reads from largest to smallest print, visualacuity being measured as the distance from the chart(3 or 6 m) over the distance at which the lettersshould normally be seen, e.g. 6/6 for normal and 6/60for poor vision. Alternatively, a near vision chart isheld 30 cm from the patient and again they are askedto read the smallest print possible with each eye inturn. Results are expressed as N6 and so on.Visual fields testing requires a 7 mm coloured(red) pin. The patient is asked if they are aware of agap or ‘blindspot’ in either eye and the clincianestablishes that the red pin target is visible to eacheye. The patient should then look into the examiner’seyes, standing 1 m away. The field of vision of theexaminer can then be compared with that of thepatient (confrontation). The extent of visual field canbe ascertained by testing each eye from eachquadrant, asking the patient to state as soon as theycan see the pinhead at all (regardless of colour).Whether the patient can see red in central visionshould also be checked.The following findings may be demonstrated:❏ Constricted fields of vision, e.g. chronicpapilloedema, glaucoma, and functional illness(tunnel vision).❏ Central field defect (scotoma), e.g. optic neuritis,retinal haemorrhage.❏ Altitudinal (vertical) field defects in one eye, e.g.retinal infarction.❏ Hemianopia.❏ Bitemporal (defect in the temporal fields in botheyes), e.g. pituitary disease.❏ Homonymous (defect to the same side in botheyes), e.g. parietal, temporal, or occipital lobedisease.Quadrantanopia, congruous, and incongruousfield defects further localize defects (see page 104).FundoscopyThe ophthalmoscope is used to examine the fundus ofeach eye separately, while the patient fixates, in adarkened environment, into the distance. Theophthalmoscope should be adjusted for the clinician’sown vision. If myopic, the lens is turnedanticlockwise (red), if long-sighted clockwise (black).The patient’s eye is then approached approximately15° from the line of fixation and the disc, bloodvessels, and retina are assessed and findingsdocumented accordingly.The student should be aware of the followingfundoscopic findings:Optic disc: normal, pale, swollen.Blood vessels: normal, attenuated, swollen,nipped, absent, containing emboli, cholesterol.Retina: infarcts, haemorrhages, exudate,retinopathy.
History taking and physical examination 21CRANIAL NERVES III, IV, AND VI (OCULOMOTOR, TROCHLEAR,AND ABDUCENT NERVES)These nerves are responsible for all eye movements.The clinician should inspect for ptosis (droopingeyelid), pupil size, strabismus (squint), and proptosis(protuberance of the globe of the eye). If proptosis issuspected, the eye should be inspected from above,tilting the head back to contrast the prominence ofeach eye. The pupil light reaction should be tested ineach eye separately, checking both the direct(illuminated eye) and indirect (nonilluminated eye)responses. The pupils’ reaction to converging (whenlooking at the end of the nose the pupils constrict)should also be assessed. The patient should be askedif double vision is present; if so, confirmation that thedouble vision is binocular (requires both eyes to bepresent) can be obtained by covering one eye at atime. The patient should be asked whether the twoimages are separated vertically or horizontally, and inwhich direction the two images (true and false)maximally separate. The range of slow-pursuithorizontal and vertical eye movements is assessed byasking the patient to follow the clinician’s movingfinger or similar object. If double vision is present, inwhich direction of gaze double vision is maximalshould be determined.❏❏❏❏The following rules help assessment:Double vision is worse (maximal) in thedirection of the affected muscle.The false image is always the outermost one.The false image is the product of the affected eye.When evaluating eye movements:The position of the head should be noted(patients with double vision will often tilt thehead to minimize this).The eyes should be checked in the primaryposition (at rest) and ptosis or pupillaryasymmetry noted.The eyes should be assessed following an object.Are abnormal movements (nystagmus) present?Is there paralysis of one or more muscles? Alldirections of gaze must be tested and knowledgeof the specific muscle innervation is essential.Nystagmus is defined as a slow drift of the eyesto one side with a fast corrective movement inthe opposite direction. While physiological whenwatching an object moving rapidly by, thesemovements are generally abnormal and informon the presence of brainstem/cerebellar disease.The patient should be asked to follow a movingfinger and any jerky movements observed.Nystagmus can be:– Vertical. Upbeat: upper brainstem, e.g.pontine infarction. Downbeat: cervicomedullaryjunction, e.g. Arnold–Chiarimalformation.– Horizontal. Ataxic: greater in the abducting(looking outwards) rather than adducting(looking inwards) eye, e.g. multiple sclerosis.– Multi-directional. Present in all directions ofgaze (though maximal in one), e.g. druginduced.– Unidirectional. Peripheral: labyrinthinedisease. Central: unilateral cerebellar disease.CRANIAL NERVE V (TRIGEMINAL NERVE)The patient is asked if they are aware of altered facialsensation, and sensation of light touch with cottonwool is tested in each of the three sensory divisions(ophthalmic V1, maxillary V2, and mandibular V3).The corneal reflex (V1&V2) is tested with a wisp ofcotton wool, touching cornea not sclera. Next, thethree divisions are tested with a pin. When definingthe territories of sensory loss, the clinician shouldalways move from the abnormal to the normal.Evidence of wasting (temporalis muscles) shouldbe noted and motor function assessed. The pterygoidsare tested with the jaw open wide (thus avoiding anyminor deviation due to temperomandibular jointasymmetry), then jaw opening resisted by pressingagainst the joint. In order to test the jaw jerk, thepatient is asked to let the jaw hang loosely open anda tendon hammer is used to percuss on the clinician’sfinger placed on the patient’s chin.CRANIAL NERVE VII (FACIAL NERVE)The nasolabial folds (from the corner of the mouth tothe sides of the nose) should be observed andspontaneous movements such as blinking and smilingnoted. The following muscles are tested using theinstructions described: frontalis: ‘wrinkle theforehead’; orbicularis oculi: ‘screw up the eyes’;buccinator: ‘blow out the cheeks’; and orbicularisoris: ‘show the teeth’. Ptosis (drooping of an eyelid) isnot due to weakness of facial nerve muscles, andfacial asymmetries without weakness is common sothe clinician should not be misled. The patient shouldbe asked about taste (absence or distortion) andtested with a sugar or salt solution applied by acotton bud to the anterior two-thirds of the tongue.
22The facial nerve also supplies the muscle to thestapedius and the parasympathetic supply to thelachrymal gland, though neither is tested at thebedside. Four types of disturbance are found:❏ Unilateral lower motor neurone, e.g. Bell’s palsy.❏ Bilateral lower motor neurone, e.g. myastheniagravis.❏ Unilateral upper motor neurone, e.g. hemispherestroke.❏ Bilateral upper motor neurone, e.g. brainstemstroke (pseudobulbar palsy).Loss of emotional expression is a feature ofParkinson’s disease, while excessive emotionalexpression (emotional incontinence) occurs inpseudobulbar palsy.Distinction between unilateral upper and lowermotor neurone facial weakness is simple. In uppermotor neurone (UMN) weakness, forehead and eyeclosure is relatively spared (bilateral supranuclearinnervation) while these are affected with lowermotor neurone (LMN) lesions (the final commonpathway for all that travels to the facial nucleus).CRANIAL NERVE VIII (AUDITORY AND VESTIBULAR NERVES)Assessment requires a 256 or 512 Hz tuning fork andan auroscope. First, the patient is asked if they havenoticed any problem with their hearing. The clinicianthen speaks in a whisper (counting in numbers) atarm’s length from the patient, while occluding thenontested ear with the hand and notes if hearing lossis reported or demonstrated.Weber’s test involves striking a 256 or 512 Hztuning fork on the examiner’s knee and placing it onthe patient’s forehead. Normally this should be heardin the middle of the head and should not lateralize.When the sound does lateralize, it does so to the sideof greater conductive loss or that with the intactcochlea (to the opposite side) in sensori-neuralhearing loss.The Rinne test again utilizes the vibrating tuningfork. The tuning fork is applied firmly to the mastoidprocess behind the ear and is then held in front of theexternal auditory meatus. The patient is asked whichthey hear loudest. Patients with normal middle earfunction hear well by air rather than by boneconduction. Those with conductive deafnessexperience the reverse. The external auditory meatusand tympanic membrane are examined with theauroscope. Conductive deafness is common (wax,middle ear disease). Sensori-neural deafness is lesscommon and takes three forms:❏ Cochlea, e.g. noise, Ménière’s disease.❏ Nerve lesion, e.g. meningitis, acoustic neuroma.❏ Brainstem, e.g. vascular, demyelinating disease.Examination of the vestibular nerve includestesting gait, nystagmus, and caloric testing (seeChapter 2).CRANIAL NERVE IX (GLOSSOPHARYNGEAL NERVE)Sensation on the posterior wall of the tonsillar fossais examined with an orange stick. The motor(stylopharyngeus) and autonomic (parotid glands)components are not tested.CRANIAL NERVE X (VAGUS NERVE)Articulation, cough, and ability to elevate the softpalate (‘saying Ah!’) are tested. Touching theposterior pharyngeal wall on each side with a throatswab and comparing each response tests the gagreflex. The autonomic and sensory (external auditorymeatus/external ear) are not tested at the bedside.CRANIAL NERVE XI (ACCESSORY NERVE)The sternocleidomastoid muscle is tested by tilting thehead to the opposite side while applying resistanceagainst the examiner’s hand, pressing on the angle ofthe jaw. The muscle belly can be observed to standout. Asking the patient to shrug the shoulders againstresistance also tests the trapezius muscle.CRANIAL NERVE XII (HYPOGLOSSAL NERVE)The tongue at rest on the floor of the mouth isexamined for wasting and fibrillation. The patient isasked to protrude the tongue and any deviationnoted. The tongue should also be observed forreduced movement as seen in UMN lesions.Multiple cranial nerve palsiesPatterns of multiple cranial nerve palsies due to extraaxiallesions reflect their anatomical relationships(Table 3).
History taking and physical examination 23Table 3 Relationship between cranial nerve palsies and location of extra-axial lesionsIII, IV, VI, V1Superior orbital fissure or (anterior) cavernous sinusIII, IV, VI, V1, V2Posterior cavernous sinusV, VI Apex of petrous temporal boneVII, VIIIInternal auditory meatus or cerebello-pontine angleIX, X, XIJugular foramenIX, X, XI, XII, and sympathetic Below the base of the skull (retropharyngeal space)MOTOR EXAMINATIONEvaluation of patterns of limb weakness is essentialfor localizing disease. Weakness may affect a singlelimb (monoplegia), arm and leg on the same side(hemiplegia), or all limbs (tetraplegia). Weakness maybe proximal (muscle disease or inflammatoryneuropathy) or distal (axonal neuropathy).Observations on muscle wasting, abnormalmovements, tone, and reflex state help to differentiateUMN from LMN disorders. Finally, weakness thatdoes not follow a recognizable organic pattern maybe psychologically based. The components ofassessment are:OBSERVATION❏❏❏❏Involuntary movements, e.g. extrapyramidaldisease, fasciculation, myokymia.Muscle symmetry.Left to right (mononeuropathy, e.g. carpaltunnel).Proximal versus distal, e.g. myopathy orneuropathy.EXAMINATION OF MUSCLE TONEThe patient is asked to relax and the upper and lowerlimbs are tested. The patient’s fingers, wrist, andelbow are flexed and extended. Similarly, the patient’sankle and knee are flexed and extended. Normally, asmall, continuous resistance to passive movement isfelt, and decreased (flaccid) or increased(rigid/spastic) tone should be noted. Failure to relax isa common problem. A flaccid (weak) limb suggests aLMN disorder, while a spastic (weak) limb suggestsUMN problems. Rigidity occurs in extrapyramidaldisease and fluctuating stiffness (paratonia orGegenhalten) with diffuse frontal lobe disturbance.EXAMINATION OF MUSCLE STRENGTHMuscle strength is under corticospinal (UMN) andanterior horn cell/nerve root/nerve plexus/peripheralnerve/neuromuscular junction (LMN) control. Thetarget of all pathways is the muscle itself. Musclestrength is tested by having the patient move againstthe examiner’s resistance. One side is alwayscompared with the other and strength is graded on ascale from 0–5/5 (Table 4).When testing, the following should be considered:the overall distribution (proximal versus distal), thepattern (flexor versus extensor), and the grouping(single root versus multiple roots versus plexus versussingle nerve versus multiple nerves). There is noavoiding knowing the detailed innervation ofmuscles. In a minimal examination the followingshould be tested:Table 4 Grading of motor strengthGrade Description0/5 No muscle movement1/5 Visible muscle movement but nomovement at the joint2/5 Movement at the joint, but not againstgravity3/5 Movement against gravity, but notagainst added resistance4/5 Movement against resistance, but lessthan normal5/5 Normal strength
24Upper limbs❏ Flexion at the elbow (C5, C6, biceps).❏ Extension at the elbow (C6, C7, C8, triceps).❏ Extension at the wrist (C6, C7, C8, radialnerve).❏ Finger abduction (C8, T1, ulnar nerve).❏ Opposition of the thumb (C8, T1, mediannerve).Lower limbs❏ Flexion at the hip (L2, L3, L4, iliopsoas).❏ Adduction at the hips (L2, L3, L4, adductors).❏ Abduction at the hips (L4, L5, S1, gluteusmedius and minimus).❏ Extension at the hips (S1, gluteus maximus).❏ Extension at the knee (L2, L3, L4, quadriceps).❏ Flexion at the knee (L4, L5, S1, S2, hamstrings).❏ Dorsiflexion at the ankle (L4, L5).❏ Plantar flexion (S1).❏❏❏❏❏Triceps (C6, C7): the patient’s upper arm issupported and the patient’s forearm is allowedto hang free; the triceps tendon is struck abovethe elbow.Brachioradialis (C5, C6): the patient’s forearmrests on their abdomen or lap and the radius isstruck about 3–5 cm (1–2 inches) above the wrist.Abdominal (T8, T9, T10, T11, T12): a bluntobject is used to stroke the patient’s abdomenlightly on each side in an inward and downwarddirection above (T8, T9, T10) and below theumbilicus (T10, T11, T12), while notingcontraction of the abdominal muscles withdeviation of the umbilicus towards the stimulus.Knee (L2, L3, L4): the patient sits or lies downwith the knee flexed and the patellar tendon isstruck just below the knee.Ankle (L5 S1): the patient’s foot is dorsiflexed atthe ankle and the Achilles tendon struck.Pronator driftThe patient is asked to stand for 20–30 seconds withboth arms straight forward, palms up, and eyesclosed, keeping the arms still while the examinergently taps downwards. In pronator drift, the patientfails to maintain extension and supination (and thelimb ‘drifts’ into pronation). Pronator drift is seen inUMN disease.REFLEXESThe tendon reflex comprises a stretch sensitiveafferent (from muscle spindles) via a single synapse(anterior horn cell region) to the efferent (motor)nerve. These reflexes are accentuated in UMN diseaseand diminished or absent with LMN disorders.Deep tendon reflexPatients must be relaxed and positioned properlybefore starting the test. No more force with thetendon hammer should be used than is required toprovoke a definite response. Reflexes can be‘reinforced’ by asking the patient to performisometric contraction of other muscles groups(clenched teeth, upper limbs or pull on hands, lowerlimbs). Reflexes should be graded on a 0 to 4 ‘plus’scale (Table 5).The following reflexes should be tested:❏ Biceps (C5, C6): examiner’s thumb or finger isplaced firmly on the biceps tendon and theexaminer’s fingers are struck with the reflexhammer.CLONUSIf the reflexes are hyperactive, clonus is tested for.This can be done at any joint but is usually performedat the ankle. The knee is supported in a partly flexedposition and the foot then quickly dorsiflexed. Clonusis manifest by rhythmic sustained oscillations.PLANTAR RESPONSE (BABINSKI)A positive Babinski sign indicates UMN disease whilea negative test is normal. The lateral aspect of the soleof each foot is stroked with the end of a reflexhammer and movement of the toes noted. The normalmovement is that of plantar flexion. Extension of thebig toe with fanning of the other toes is abnormal, apositive Babinski.Table 5 Tendon reflex grading scaleGradeDescription0 Absent1+ or 1++ Hypoactive2+ or 2++ Normal3+ or 3++ Hyperactive without clonus4+ or 4++ Hyperactive with clonus
History taking and physical examination 25SENSORY EXAMINATIONThis is the most exacting and potentially misleadingpart of the neurological examination. There are fivecategories of sensation to test: pain, temperature(small fibre/spinothalamic tract/thalamus/diffuse +frontal cortex), vibration, joint position, and lighttouch (large fibre/dorsal column/medial lemnisci/parietal cortex). These anatomically separatepathways explain why sensory loss is oftenincomplete (dissociated).The examination requires a cooperative patientand an alert examiner! Each test should be explainedto the patient before it is performed. The patientshould have their eyes closed during testing.Symmetrical areas both sides of the body arecompared as well as distal and proximal areas of eachlimb. Where an area of sensory abnormality is found,the boundaries should be mapped out in detail,moving from the abnormal to the normal area.❏❏❏Distal and symmetrical impairment in limbssuggests sensory neuropathy.A level on the trunk below which sensationis lost localizes spinal cord disease.An area on the trunk or limbs confined toone side suggests nerve root or singleperipheral nerve disturbance.The five components of sensation are tested asfollows:VIBRATIONA low-pitched (128 Hz) tuning fork is used to testawareness at bony prominences such as wrists,elbows, medial malleoli, patellae, anterior superioriliac spines, spinous processes, and clavicles.Vibration is normally lost at the ankles in those over60 years. The patient must understand that it is thesensation of vibration rather than the sound from thefork that is being tested.SUBJECTIVE LIGHT TOUCHCotton wool is used to touch the skin lightly on bothsides. Sometimes when a stimulus is presentedsimultaneously on both sides it is not felt on one side,yet it is felt on that side when the stimulus ispresented separately (sensory inattention, suggestingparietal lobe disease). Several areas on both the upperand lower extremities are tested and the patient isasked if there is a difference from side to side.POSITIONAL SENSATIONThe patient’s big toe is held away from the other toesto avoid ‘cueing’ and is moved to demonstrate to thepatient what is meant by ‘up’ and ‘down’. Theexaminer then moves the toe and asks the patient toidentify the direction the toe has moved with eyesclosed. If position sense is impaired the ankle joint isthen tested and then the fingers in a similar fashion.The examiner should then move proximally to testthe metacarpophalangeal joints, wrists, and elbows.PAINA suitable sharp disposable object is used to test‘sharp’ sensation. The following areas are tested:❏ Shoulders (C4).❏ Inner and outer aspects of the forearms (C6 andT1).❏ Thumbs and fingers (C6 and C8).❏ Front of both thighs (L2).❏ Medial and lateral aspect of both calves (L4 andL5).❏ Little toes (S1).Remembering these particular dermatomal areasis helpful. Pinprick examination is critical to defininga ‘level’ when localizing spinal cord disease.TEMPERATUREThis is omitted if pain sensation is normal, but ishelpful in confirming the presence and distribution ofpinprick loss. A tuning fork heated or cooled bywater is used and the patient asked to identify ‘hot’ or‘cold’. Similar areas as above are tested. Temperatureloss is much less helpful when defining a precisespinal cord level.DISCRIMINATIONTests of discrimination are dependent on intact touchand position sense; they cannot be performed wherethese are clearly abnormal. These tests assess cortical(parietal) sensation.GraphaesthesiaWith the blunt end of a pen or pencil, a large numberis ‘drawn’ in the patient’s palm and the patient askedto identify the number.Stereognosis (an alternative to graphaesthesia)A familiar object is placed in the patient’s hand (coin,paper clip, pencil) and the patient then asked to namethe object.
26Two point discriminationAn opened paper clip or divider is used to touch thepatient’s finger pads, alternating irregularly betweenone point touch and touch in two placessimultaneously. The patient is asked to identify if theyfeel ‘one’ or ‘two’ points. The minimum distance atwhich the patient can discriminate is identified.COORDINATIONThese tests assess cerebellar function and requirerelatively intact motor power. To test for lack ofcoordination with weakness present is unsound, assuch tests cannot be performed to a level that allowsaccurate interpretation. Associated signs, dysarthria,and nystagmus are further pointers to cerebellardisease.RAPID ALTERNATING MOVEMENTSThe patient is asked to slap rapidly the palmar anddorsal surface of the hand alternately on the thigh. Inthe lower limbs, the patient taps the examiner’s handwith the sole of each foot.LIMB COORDINATIONThis is assessed by ‘point-to-point’ tests. The patientis asked to touch the tip of the examiner’s finger andthen their own nose. The accuracy in approachingeach target and the smoothness of movement betweenthe two targets is recorded (deficits being termedpast-pointing and dysmetria, respectively). In thelower limbs, the patient is asked to touch the front ofthe shin with each heel, and then to run the heel upthe front of the leg to the knee and similarobservations are made.STANCE AND GAITGENERALThe patient is asked to stand with feet together and,once they feel comfortable, to close the eyes. If thepatient cannot balance well with eyes open, theyshould not be asked to close the eyes. The clinicianstands close to the patient and must be ready tosupport them should they fall to either side.Instability with eyes open suggests cerebellar disease,and with the eyes closed afferent (sensory ataxia)disturbance. Unsteadiness only on eye closure is apositive Romberg test.POSTURAL STABILITY (THE RETROPULSION OR FORCEDPULL-BACK TEST)The patient is asked to stand with eyes open and feetapart. The clinician stands behind the patient andwarns that the patient will suddenly be pulledbackwards. An abnormal response should beanticipated and the clinician must be prepared tocatch the patient! An abnormal reaction is seen inextrapyramidal disorders (e.g. Parkinson’s disease)with retropulsion (taking several steps backwards andbeing unable to maintain stability).The student should be able to recognize certainwalking disorders: the hemiplegic, ataxic,extrapyramidal, and myopathic gaits; also thehigh ‘steppage’ gait of unilateral or bilateralfootdrop.REFERENCES1 Fuller G (2004). Neurological ExaminationMade Easy. Churchill Livingstone, London.2 Lindsay K, Bone I (2004). Neurology andNeurosurgery Illustrated. Churchill Livingstone,London.
CHAPTER 2:NEUROLOGICAL INVESTIGATIONS27Ian Bone, John GreeneINTRODUCTIONINVESTIGATING THE HEADINVESTIGATING THE SPINAL CORDINVESTIGATING THE PERIPHERAL NERVOUS SYSTEM(NERVE, NEUROMUSCULAR JUNCTION, AND MUSCLE)INVESTIGATING SPECIFIC SITES
28INTRODUCTIONThe evaluation of a clinical presentation often,though not invariably, leads to the formulation of an‘investigative pathway’. Thoughtful and thoroughhistory taking and examination are central todeciding not only ‘whether to investigate’ but also‘where to look’. Once the decision to investigate hasbeen reached the clinician must ask ‘Is it in the head,the spine, in nerve, or muscle?’ The answer is crucialas each of these sites or levels has specificinvestigations. Getting it right is not always easy. Forexample, the complaint of a ‘foot drop’ can indicatecerebral, spinal, or peripheral nerve disease, the skillbeing to decide from the history and examinationwhere the culprit lies and to investigate accordingly.In this chapter the student will be introduced tothe basics of neurological investigation as an aid tothe problem-oriented text that follows. Rather thanlist and describe these in order of complexity, cost, or12 X-ray tubemoving in10° stepsFixed arrayof detectors12 Diagram to illustrate a computed tomography gantry.availability, each compartment (head, spine, nerveand muscle) will be addressed separately. Obviouslysome disease processes will be multifocal, multisystem,and straddle compartments (e.g. thecraniocervical junction) or medical disciplines (e.g.the orbit and ear), and resultant investigations will bemore complex and diverse. What follows is thereforea ‘rough guide’ to introduce the student totechniques, indications, sensitivity, specificity, andpotential complications of the tools used to diagnoseand help treat neurological disease.INVESTIGATING THE HEADA computed tomography (CT) or magnetic resonanceimaging (MRI) scan is now indicated in most workupsof suspected intracranial disease. Indeed, it isdifficult to imagine practice without such imaging.Before the 1970s, the ability to image the braindepended on isotope studies, invasive injection of air(air encephalography), or contrast (angiography/myodil ventriculography). These techniques showedno more than outlines and shadows and were risky.As a result the clinician was much more conservativeand circumspect as to which patients were subjectedto such tests. The advent, easy availability, and lowrisk of cross-sectional imaging have undoubtedlydiluted clinical skills but the advances in diagnosisand improved patient care are well worth this price.The current danger is that of over-investigation andthat clinical skills are reduced such that investigationsare targeted to the wrong site or incidental imagingfindings are mistaken as relevant.COMPUTED TOMOGRAPHYAlso referred to as CAT (computer assistedtomography) scanning, this revolutionary techniquewas introduced into clinical practice in 1973. It is themost commonly used form of cranial imaging, beingavailable on a 24 hour basis in almost all hospitals.The word tomography refers to imaging of slices ofthe brain (or indeed any other organ). The patient isplaced in a gantry (12) and a thin beam of X-rays,created by a collimator, traverses each ‘slice’ to amultichannel ionization detector.The path from collimator to detector establishes asingle ‘beam’ passing though a patient’s tissues.During the scan the computer takes brief readingsfrom all detectors. In the earlier scanners bothcollimator and detector rotated around the patientwhereas in modern third and fourth generation unitsthe detectors are fixed with only the X-ray source
Neurological investigations 29moving. Computer processing with multiple beamsand detectors completely encircling the head allowsabsorption values for blocks of tissue (voxels) to beestablished. Reconstruction of this by twodimensionaldisplay (pixels) results in the eventual CTappearance (13). Slices studied can be varied inthickness (1–10 mm) and can be rendered parallel tothe orbitomeatal line (a reference line drawn throughthe orbit and ear), to allow anatomical interpretationand reproducibility for repeated studies. ‘Highdefinition’ (1–2 mm) scans give greater anatomicaldetail, take longer to acquire, and are reserved forexamination of specific sites (orbit, Circle of Willis,pituitary). Alteration of window level will change thecontrast appearance and allow more detailedassessment of bony structures or help visualize subtledifferences in tissue contrast, such as with an acutecerebral infarct.Frontal hornof lateralventricleSeptumpellucidumPineal glandFrontallobeLateralventricleParietallobeOccipitallobeFalx cerebriSulci133rd ventricleMidbrainQuadrigeminalcisternFrontal sinusFrontal lobeSylvian fissureOrbitalroofTemporal lobePonsCerebellum4th ventricleMastoid aircellsCerebellum13 Computed tomography of normal brain, illustrating landmark anatomical details.Temporallobe
30Knowledge of the display and normalappearance along with anatomical structures isessential.Because each slice is oriented along theorbitomeatal line, with the head tilted backwards,lesions appear more posterior than is the case. Scanscan be displayed in coronal (ear to ear) or sagittal(forehead to occiput) planes to look at specificregions (e.g. orbits or foramen magnum).Intravenous contrast medium should not be givenroutinely but only where a noncontrast scan hasshown an abnormality and clarification is required(e.g. a possible abscess, metastatic tumour, orvascular anomaly). Reactions occur in 5% ofexaminations, this being dose-dependent. Contrastwill show up areas of high vascularity and regions ofbreakdown of the blood–brain barrier, and willdemonstrate areas of altered blood perfusion (seelater). A contrast-enhanced scan also highlights up allthe major intracranial vessels (14).14The patient requires no special preparation forCT other than reassurance that the procedure is safe.Metal should be removed from the head (hairpins,dental bridgework) as this will cause signal scatterand result in artefacts. If contrast is to be given, theclinician must enquire after a history of previousreaction to injected contrast. Radiation dose iscomparable to a routine skull X-ray (now rarelyperformed). Pregnancy is not a contraindication asonly a very small quantity of radiation ‘scatters’ in thedirection of the abdomen and uterus. The limitationsof CT are listed below.Helical CT (spiral CT) is performed by ‘pulling’the patient though the scan field of the rotating X-raysource. This allows faster scanning time, better imagereformation, and the ability to perform newertechniques such as CT angiography (CTA).Limitations of CT imaging❏ Uses ionizing radiation.❏ Visualization of posterior fossa structures(e.g. brain stem or cerebellar pontine angle)inferior to MRI.❏ Less sensitive than MRI to acute changes(e.g. early infarction).CT angiographyThis examination uses X-rays to visualize blood flowin arterial vessels. CT venography (CTV) studiessimilar flow through veins (15). An automaticinjector controls the timing and rate of injectedcontrast, continuing through the initial imagerecording. The rotating scanner spins in a helicalmanner around the patient, creating a fan-shapedbeam of X-rays. As many as 1000 of these picturesmay be recorded in one turn of the detector. Onceacquired, processing these images requires a powerfulcomputer programme making it possible to displaycross-sectional slices or three-dimensional ‘casts’ ofthe blood vessels.CTA is used to study blood vessel wall disease(narrowing , dissection, atheroma, inflammation,and aneurysm). Both extracranial (aortic arch andbranches) and intracranial vessels (Circle of Willisand branches) can be studied. Intracranial aneurysmssized ≥3 mm can be detected.14 Contrast computed tomography scan showing left middlecerebral artery stenosis (arrow).
Neurological investigations 31CT perfusionCT perfusion (CTP) has been proposed as a methodof evaluating patients suspected of having an acutestroke where thrombolysis is considered. It mayprovide information about the presence and site ofvascular occlusion, the presence and extent ofischaemia, and tissue viability. CTP provides accuratemeasures of local cerebral blood volume (CBV),blood flow (CBF), and mean transit time (MTT).MAGNETIC RESONANCE IMAGINGThe millions of water molecules within the humanbody contain hydrogen ions which themselves haveprotons which act as microscopic magnets. Whenplaced in a magnetic field, the protons within anindividual will align in part to that field. If aradiofrequency (RF) pulse is then applied, theseprotons become excited, start spinning and ‘flip’ theirorientation. When the RF field is turned off, thespinning protons revert to their prior state (or15alignment), releasing energy. These microscopicmagnets, and the vectors that they set up byrealignment, form the basis for generating images.Variability of these ions from tissue to tissue as wellas their response to applied electromagnetic pulsescreates images of organs (brain and spine) in healthand disease.The student should understand two simple terms.The time it takes for a proton to recover most ofits longitudinal alignment (or magnetization) isreferred to as T1 or spin-lattice relaxation time.The time it takes for the proton to lose most of itstransverse alignment (or magnetization) isreferred to as T2 or spin-spin relaxation time.A bewildering variety of RF pulse sequences (spinecho, gradient echo, inversion recovery, andsaturation recovery) can be used, often with a specificpurpose (e.g. gradient echo to show previoushaemorrhage). The introduction of magnets withincreasing field strength (>1.5 Tesla) allows a bettersignal to noise ratio, and faster scanning with areduction of imaging time. By acquiring data morerapidly, these MRI scanners can perform MRangiography and gain functional information ondiffusion and perfusion, as well as images of thoseacutely ill patients whose physiological instabilitypreviously precluded lengthy investigations.161 215 Computed tomography venogram illustrating cerebralvenous drainage.16 Computed tomography angiogram illustrating left middlecerebral artery occlusion (1) and right middle cerebral arterynarrowing (2).
32ADVANTAGES AND DISADVANTAGES OF MRI(COMPARED TO CT)Advantages❏ Select any plane, e.g. oblique.❏ No ionizing radiation.❏ More sensitive (earlyischaemia/demyelination).❏ No bony artefacts (looking at sites adjacentto bone).Disadvantages❏ Cannot use with any ferromagnetic implant,e.g. pacemaker.❏ Claustrophobic.❏ Does show bony artefact.❏ Long-term hazards not known.T1 and T2 images can easily be distinguished. OnT1, CSF is black (hypointense) while on T2 it is white(hyperintense). Table 6 will help interpretation of MRimages (increase or decrease in signal is defined inrelation to normal grey matter). Figures 17–20present MRI images.Paramagnetic enhancementThe intravenous agents used (e.g. gadolinium) inducea strong local magnetic field effect that will shortenT1 signals. This will result in enhancement of theimage in areas of contrast leakage (across a damagedblood–brain barrier) or within the vascular compartment(arteries, microcirculation, and veins).Gadolinium and other such agents highlightischaemia, infection, and demyelination and can helpdistinguish tumours from surrounding oedema.Table 6 Guide to identifying the MRI sequenceT2-weighted image❏ CSF bright.❏ Grey matter brighter than white matter.Perfusion-/diffusion-weighted image❏ CSF grey.❏ Grey matter brighter than white matter.T1-weighted image❏ CSF dark.❏ White matter brighter than grey matter.CSF: cerebrospinal fluid.171817 T1 sagittal magnetic resonance image of the brain.18 T1 coronal magnetic resonance image of the brain.
Neurological investigations 3319a–d Axial magnetic resonance image(MRI) of the brain illustrating thesuperiority of MRI over computedtomography.19a19b19c19d20 T2 magnetic resonance image showing a primitive neuroepithelial tumour in theright anterior temporal lobe.20
34Fluid-attenuated inversion recoveryFluid-attenuated inversion recovery (FLAIR) MRIdepicts areas of tissue T2 prolongation whilesuppressing the signal from neighbouring cerebrospinalfluid (CSF). It is helpful in assessing lesions that areadjacent to CSF, such as at periventricular andsuperficial cortical sites (21, 22).Magnetic resonance angiographyMagnetic resonance angiography (MRA) can bebased on either time-of-flight methods (measuring thecontrast enhancement produced by inflowing blood),or phase contrast methods, which utilize the flowinducedvariations in signal induced by the motion ofblood alone. Time-of-flight measurements are bettersuited for imaging arterial wall morphology. MRAcan demonstrate extracranial and intracranialstenosis (narrowing) noninvasively, but tends tooverestimate the degree of a stenosis andconsequently misinterprets low flow through a tightstenosis as an occlusion. It is usually used inconjunction with ultrasound (or CTA) for thepresurgical evaluation of carotid artery stenosis (23).MRA is used to screen for intracranial aneurysms butwill not show all of those seen on intra-arterial digitalsubtraction angiography (see later). By selecting aspecific flow velocity, veins can also be imaged(MRV) (24).212221 Fluid-attenuated inversion recovery (FLAIR) magneticresonance image showing the white matter changes of multiplesclerosis. Note that cerebrospinal fluid (CSF) is dark on FLAIRunlike the bright CSF seen on T2.22 Fluid-attenuated inversion recovery (FLAIR) magneticresonance image showing left mesial temporal sclerosis causingepilepsy.
Neurological investigations 35Diffusion and perfusion MRIMR scanning is superior to CT scanning in thediagnosis of acute stroke. However, conventional MRIdoes not demonstrate early acute cerebral ischaemiaparticularly in a period when therapy may reverse orlimit the permanent brain injury. T2 sequences requireat least several hours from the onset of the strokebefore demonstrating signal change abnormalities.Water diffusion has been introduced as an additionalcontrast parameter in the MR imaging of acute stroke.Diffusion-weighted imaging (DWI) can demonstratealtered cellular metabolism and the reduction in themicroscopic water molecule motion (Brownianmotion) in acute and subacute stroke. Damaged tissuemay be visualized as early as 5–15 minutes after theonset of stroke.Perfusion-weighted imaging (PWI) allowsassessment of perfusion of the brain microvasculature.PWI requires intravenous gadoliniumcontrast (bolus tracking) that causes a paramagneticsusceptibility effect. Thus, MRI signal declines asgadolinium travels through the microvasculature.PWI is used to complement the information obtainedby DWI in acute stroke patients. PWI may showreduced perfusion in a larger area of tissue than thatshown on DWI. This indicates a significant area oftissue at risk of infarction, a diffusion–perfusionmismatch. Using PWI, various perfusion properties ofthe contrast bolus can be calculated, such as CBV,CBF, MTT, and time-to-peak (TTP) of contrastarrival. A very low CBV implies irreversibleischaemia.23 Magnetic resonanceangiogram of the carotidarteries.232424 Magnetic resonance venogram showing superior sagittalthrombosis.
3625 2625 T1 magnetic resonance image of asubcortical infarct.26 Diffusion-weighted imaging (DWI)magnetic resonance image of the samesubcortical infarct shown in 25.The combination of MRA to visualize vessels,and DWI and PWI to define early infarction and‘tissue at risk’ (‘the ischaemic penumbra’) representsan ideal ‘package’ to help plan acute stroketreatments (25–27).Functional MRIMRI is able to map functional cortical activity duringthe performance of tasks. This is achieved bydetecting regional cortical tissue changes in venousblood oxygenation. This technique is known as bloodoxygen level dependent (BOLD) imaging or simplyfunctional MRI (fMRI) (28). The key to fMRI is thatoxyhaemoglobin is diamagnetic whereas deoxyhaemoglobinis paramagnetic. The role of fMRI ismainly in research. It has, however, been used toguide surgical resection of brain in or adjacent toeloquent areas.MR spectroscopyProton MR spectroscopy (MRS) is a noninvasivemethod used to obtain a biochemical profile of braintissue (a biochemical biopsy). Although 31phosphorous ( 31 P) spectra are sometimes used, MRSstudies are usually obtained by proton spectroscopywith water suppression (protons are abundant inbrain tissue and have high nuclear magneticsensitivity compared with other magnetic nuclei).Single voxel spectroscopy can be performed in manyclinical 1.5T MR units using commercially availablesoftware. Two types of MRS finding are encountered.Either the spectrum reveals a metabolite that is notnormally present or, more commonly, an abnormalquantity of a normal metabolite is present.Metabolites studied are N-acetyl aspartate (NAA),choline (Cho), creatine (Cr), glutamate, and lactate.NAA is present exclusively in neurones and declineswith neuronal and axonal damage and death. Cholineis important in the myelination of nerves and isaltered by demyelinating diseases. Lactate is a markerof anaerobic respiration and increases in hypoxicischaemic states. In the future it is hoped for adiagnostic ‘biochemical biopsy’ for specific tumourtypes and other pathologies.SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHYSingle photon emission computed tomography(SPECT) utilizes a gamma camera that can rotate andcomputer reconstruction similar to CT, to produce atwo-dimensional image. Compounds labelled withgamma-emitting tracers (ligands) have been developedto study blood flow, map receptors, and evaluate
Neurological investigations 3727 2827 Apparent diffusion coefficient (ADC)magnetic resonance image of the samesubcortical infarct shown in 25.28 Functional magnetic resonance image of apatient performing left finger tapping, activatingright motor cortex.29 Ictal hexamethylpropyleneamineoxime (HMPAO)spectroscopy (axial slicein the long axis of thetemporal lobe) withinjection 25 secondsafter the onset of aright mesial temporallobe seizure, showinghyperfusion of thewhole temporal lobe.2930 3130 SPECT imaging showing reduced left hemisphere perfusion in primary progressive aphasia.31 Fluoropropyl carboxymethoxy iodophenyl nortropane spectroscopy (FP-CIT) showing reduced dopamine transport incorticobasal degeneration.tumour growth. While a rotating scanner is mostcommonly used, fixed multidetector systems producebetter image definition as well as axial, coronal, andsagittal views. Ligands are labelled with radioactiveiodine or thallium and are given intravenously.Radiation dose limits repeated investigations. SPECTscans are interpreted visually, usually in conjunctionwith structural imaging (CT or MRI), as ananatomical abnormality will influence ligand uptake.SPECT scanning is used to study cerebral bloodflow (in stroke, dementia, and seizures). CNSreceptors include benzodiazepine (epilepsy), glutamate(stroke), and dopamine (Parkinson’s disease andother movement disorders). Rates of tumour growthcan also be studied (high-grade thallium, low-gradetyrosine). The following figures illustrate the clinicalapplications of SPECT imaging (29–31).
38POSITRON EMISSION TOMOGRAPHYThe positron emission tomography (PET) techniqueuses positron-emitting isotopes (radionuclides). Thesehave a short half-life and have to be generated on-siteby a cyclotron. Imaging and display also involvecross-sectional data acquisition and reconstruction,much like CT scanning. When a positron encountersan electron (which will be almost immediately it isemitted from the source) mutual annihilation occurs,with the emission of photons (gamma rays). Multipledetectors enable detection and quantification ofradioactivity. Labelled oxygen, fluorine, or carbon isused given by intravenous bolus or by inhalation. Aswell as studying receptor sites and receptor binding,this technique can quantify CBF, CBV, and glucoseand oxygen metabolism. Lack of availability andcomplexity have limited the wider application of PET;however, it may be particularly helpful in detectingsmall tumours (e.g. small cell lung cancer inparaneoplastic syndromes).CEREBRAL ANGIOGRAPHYAngiography remains the ‘gold standard’ choice in theevaluation of arterial and venous occlusive disease,aneurysm (32), and arteriovenous malformation(AVM). It is also useful in defining the blood supply ofsome tumours (e.g. meningioma). Finally, it is necessaryfor interventional neuroradiologic procedures such ascoiling aneurysms, stenting stenosis, and deliveringintra-arterial thrombolysis. Contrast is injected via aflexible catheter introduced by the femoral artery, andrapid film changers are used to capture its flow throughextra- and intracranial vessels.Advances in the development of high-qualitydigital subtraction units provide instantaneousimages for view on a cathode ray tube. This digitalsubtraction angiography (DSA) utilizes analogue todigital image conversion with digital image display.Iodine-containing, water-soluble media provide thenecessary density to allow the visualization of thecerebral arterial, capillary, and venous systems. The3232 Angiogram showing intracerebral aneurysm (arrow).
Neurological investigations 39major complication of cerebral angiography is stroke,either from damaging the vessel wall (dissection) ordislodging thrombus (embolism). Meticulous care todetail is mandatory. With ectatic and tortuous arteriesit may be difficult to catheterize these selectively, andinjections at the origin of such vessels may be safest.Once the procedure is over, general care isimportant, particularly with regard to blood pressure.Elderly patients following a large contrast load maybecome hypotensive, and with haemodynamicallysignificant carotid artery stenosis, relativehypoperfusion will cause ischaemia and ‘watershed’infarction. Systemic reactions to contrast occur,ranging from urticaria to bradycardia and laryngealspasm. Local complications include haematoma atthe catheter site, femoral nerve damage, and arterialthrombosis with distal embolism.The appearances of a normal examinationshould be noted with regard to major vesselsand their divisions. Oblique views may be usedin assessing aneurysms and cervical views forevaluation (and precise measurement) of internalcarotid and vertebral artery disease.Interventional angiographyRecent advances in endovascular procedures nowplay an important part in patient management.Tumours, aneurysms, fistulas (acquired openingsbetween arteries and veins), AVMs, and narrowedintracranial arteries can be treated by an array ofparticles, glues, balloons, coils, and stents.ULTRASOUNDThis noninvasive technique utilizes a probe(transducer) that emits ultrasonic waves, usually atfrequencies of 5–10 MHz. When held over a bloodvessel these ultrasonic waves are reflected back to theprobe, which also doubles as a detector. Reflectedwaves can then be displayed as a two-dimensionalimage (B-mode). When the probe is held over amoving column of blood, the frequency shift ofreflected waves (Doppler effect) informs on thevelocity of the column. There are four types ofDoppler ultrasound:❏ Continuous wave Doppler measures howcontinuous sound waves change in pitch as theyencounter blood flow blockages or narrowedblood vessels. This is performed at the bedsideand provides a quick, rough guide of damage ordisease.❏❏❏Duplex Doppler produces a picture of a bloodvessel and the organs that surround it. Acomputer converts the Doppler signals into agraph that provides information about the speedand direction of blood flow through the bloodvessel being examined.Colour Doppler is computer assisted andconverts the Doppler signals into colours thatrepresent the speed and direction of flowthrough the vessel.Power Doppler is a new technique beingdeveloped that is up to five times more sensitivethan colour Doppler and is used to study bloodflow in vessels within solid organs.Ultrasound is used to assess extracranial (carotid)arterial disease (33).Transcranial Doppler ultrasoundTranscranial Doppler ultrasound (TCD) is a safe,reliable, and relatively inexpensive technology formeasuring intracranial blood flow velocities. Waveswith frequencies around 2 MHz are directed towardsintracranial vessels using a handheld probe. Thefrequency shift (Doppler effect) in the reflected soundindicates the velocity of the column of moving blood.33 Carotid Doppler ultrasound showing 70% right internalcarotid stenosis.33
40Images are reconstructed from the time-dependentintensity of the reflected sound, and vascular structuresvisualized. Altering transducer location and angle, andthe instrument’s depth setting obtains velocities frommost intracranial arteries. The cranial ‘windows’ usedare the orbit (anterior cerebral artery) and in temporal(middle cerebral artery) and suboccipital regions (basilarand posterior cerebral arteries). Age and skull thicknessmake insonation of vessels technically difficult. Theposterior circulation is more difficult to pick up signalsfrom than the anterior circulation. TCD is quick; 30–40minutes is sufficient for detailed studies. Theinstrumentation is inexpensive and portable to thebedside. The applications of TCD are in the assessmentof intracranial haemodynamics (measuring autoregulationbefore and after carbon dioxide inhalation orintravenous acetazolamide), detecting intracranialstenosis, spasm in subarachnoid haemorrhage, anddetecting right-to-left shunts (pulmonary fistula or atrialseptal defect) following the injection of intravenousagitated saline. Ultrasound may also have a therapeuticeffect on clot lysis (after embolic vessel occlusion).NEUROPHYSIOLOGYWhile imaging mainly informs on structure, thefunction of the brain can be assessed using variousneurophysiological techniques. Mostly this involvesrecording spontaneous electrical activity of the brain,but also uses evoked responses, where a stimulus isprovided and the brain’s response to that stimulus ismeasured.ELECTROENCEPHALOGRAPHYIn electroencephalography (EEG), electrodes are placedin arrays on the scalp, equidistantly and according toan international convention (34). Each electrode iswired to its own channel. Electrical differences betweenpairs of electrodes, or one electrode and a combinationof others, are recorded, and can be displayed on ascreen as a series of parallel lines, each line representingone electrode. A standard EEG takes about 30 minutesto perform. Patients are usually awake, lying downwith eyes closed. In addition to passive recording,provocation techniques are also routinely employed,usually hyperventilation and photic stimulation, whichcan sometimes induce epileptiform changes on EEG.Normal rhythmsDetailed EEG analysis is beyond the scope of thischapter, but Tables 7 and 8 summarize normal andabnormal electrical rhythms.123434a34 Diagram to show the placement of electroencephalographyscalp electrodes.Table 7 Normal electroencephalographyrhythmsAlpha rhythm❏ 8–13 Hz❏ Symmetrical❏ Seen posteriorly with eyes closedBeta rhythm❏ >13 Hz❏ Symmetrical❏ Present frontally, not affected by eye openingTheta and delta rhythms❏ Seen in children and young adults❏ Frontal and temporal predominance❏ Theta: 4–8 Hz❏ Delta:
Neurological investigations 41Clinical use of the EEGEEG is mainly of use in the diagnosis of alteredconscious states including epilepsy. Advances inimaging have largely supplanted its use in localizinglesions. It has a niche role in diagnosis of rare corticaldisorders such as Creutzfeldt–Jakob disease (CJD)and subacute sclerosing panencephalitis (SSPE), but isof little use in the differential diagnosis of dementingdisorders.EpilepsyIt must be stressed that the diagnosis of epilepsy is aclinical one. EEG is normal in 50% of patients withepilepsy, and is abnormal in 2–4% of the populationwho do not have epilepsy. Nevertheless, in a patientwho has had a single seizure, EEG can be of someprognostic value in predicting future seizures. Even indefinite seizure activity, the EEG can be of use inclassification. For example, an apparent tonic–clonicseizure may indicate primary generalized epilepsy, butmay also represent a focal seizure, which generalizesso rapidly that the focal onset cannot be appreciatedclinically. EEG may be helpful here in differentiatingbetween a focal (35) or generalized (36) epilepsydisorder, which has implications for the choice ofanticonvulsant.35 Electroencephalograph showing focalseizure onset (top two lines).3536 Electroencephalograph showinggeneralized seizure onset.36
42Other altered conscious statesEEG is particularly useful in other altered consciousstates (37). It may reveal the cause of coma, and can beof use prognostically. It may also suggest neurologicaldisorders mimicking unconsciousness such as locked-insyndrome, where the EEG will be normal.Sleep deprived EEGSleep deprived EEG involves the patient remainingawake overnight, and then having EEG done firstthing the following morning. Sleep can bring outepileptiform abnormalities on EEG, which may notbe apparent on routine EEG. The patient tends tobecome drowsy quickly, or to fall asleep. Its main useis in terms of seizure classification.Video-telemetryAs will be covered in the section on blackouts (page64), the diagnosis of epilepsy is a clinical one, andrelies on detailed questioning of the patient andrelatives as to what happened during the event. Therecan, however, arise times when a confident clinicaldiagnosis cannot be made from the informationavailable. If events are occurring sufficientlyfrequently, then the patient can be admitted forcontinuous video recording with simultaneous EEGrecording. Should the patient have an event whilebeing monitored, then careful analysis of behaviouras seen on video together with EEG data will almostalways yield a diagnosis.Short video-EEG with suggestibilityThe differential diagnosis of epilepsy includesnonepileptic attacks that are of psychological origin.These turns can be induced by suggestion. Onaccount of long waiting times for video-telemetry, it ispossible to make a diagnosis of nonepileptic attackson an outpatient basis by doing an EEG, but usingsuggestion techniques which increase the likelihoodof a patient having an attack while being recorded.Intracranial EEG recordingsIf a patient is being considered for epilepsy surgery, theclinician must be confident of the localization of thefocus of seizure activity. This is usually achieved usinga combination of supporting information, includingclinical semiology of the seizure, structural imaging,SPECT imaging of brain blood flow at the time of theseizure, and video-EEG. Sometimes, however, it isnecessary to obtain more detailed electrophysiologicaldata than is obtainable using surface recordings. It isthen necessary to record electrical data from the brainitself. While nasopharyngeal and sphenoidal electrodeswere used previously, increasing use is being made ofdepth electrodes, which are inserted through the brainsubstance. A clear hypothesis about possible sites ofseizure origin must be in place, and electrodes are thenplaced in appropriate structures. Each electrode hasseveral recording sites along its length. The informationis then summated as a stereo-EEG (SEEG).37Fp2 AVG 100.0 75 HzF8 AVG 100.0 75 HzT4 AVG 100.0 75 HzT6 AVG 100.0 75 HzC2 AVG 100.0 75 Hz13:43:1213:43:1513:43:18Page 137 Electroencephalograph inencephalopathy.Fp1F7T3T7C1F4C4P4F3C3F5AVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzAVG 100.0 75 HzEKG AVG 100.0 75 Hz
Neurological investigations 43In addition to recording passively from each ofthe electrode points, it is also possible to stimulate ateach of the points along the electrode. Shouldstimulation at one point result in a seizure, then thismakes it likely that the seizure focus is in closeanatomical proximity to the electrode point.POLYSOMNOGRAPHYSleep disorders are a major source of morbidity. Whilefacilities in the UK for the investigation of respiratorycauses of sleep impairment are well developed,facilities for the investigation of neurological causes ofsleep disorder are relatively poor.While some sleep disorders such asnarcolepsy–cataplexy can sometimes be diagnosedwith confidence in the clinic, polysomnography is theoptimal technique for the investigation of sleepdisorder. This involves the patient being admittedovernight, and various physiological parameters aremeasured during sleep. These include EEG todetermine the stage of sleep, chin electromyography(EMG), electrocardiography (ECG), respiratorymovements, and oxygen saturation.between retina and occipital cortex, and can be amanifestation of subclinical demyelination (38).Brainstem auditory evoked potentialsBrainstem auditory evoked potentials (BSAEPs) occurin response to an acoustic stimulus, usually a click,and arise from subcortical structures. On account oftheir very small size, many such stimuli must besummated in order to achieve a recordable signal.N75P100N145381200 ms 5 uV86(15)N145EVOKED POTENTIALSEvoked potentials are electrical signals produced bythe nervous system in response to external stimuli.The stimulation may be visual, auditory, orsomatosensory. Given the low voltages, it is oftennecessary to use computer averaging in order todiscriminate the evoked potential of interest frombackground noise.The main use of evoked potentials is in detectingwhat may be clinically silent neurologicaldysfunction. While they are useful for detectingabnormality in a set of brain structures, they areusually not helpful in determining the pathologicalcause of any such identified dysfunction.Right eyeN75P100N752200 ms 5 uV58(9)1200 ms 5u V86(15)N145Visual evoked potentialsIn this test, the patient is asked to look at a televisionscreen with a black and white chequer boardappearance. Pattern reversal of the image isemployed, and the neural signal generated isdetectable with scalp electrodes over the occipitalcortex as visual evoked potentials (VEPs). The clinicalinterpretation of the signal achieved relies primarilyon the latency of the signal and whether it is delayed.Reductions in amplitude are of lesser clinicalimportance. Delayed visual evoked responses (VERs)indicates nervous system dysfunction somewhereLeft eyeN75P100N145P1002200 ms 5 uV58(9)38 Visual evoked response showing delayed response on theleft due to optic neuritis.
cervical44While VIIIth nerve damage may impair BSAEPs, theirmain use is in assessing the integrity of the brainstem.Any such pathology there, such as pontine glioma ordemyelination, can result in abnormal signals.Somatosensory evoked potentialsUsing similar rationale to the above, the integrity of thesomatosensory system may be assessed by stimulatingsensory nerves peripherally, and measuring the time forsuch a signal to be recordable over the somatosensorycortex (somatosensory evoked potentials, SSEPs).Common sources of stimulation are the median nerve,common peroneal nerve, or posterior tibial nerve.Again, delayed SSEPs may occur due to disturbanceanywhere in the sensory system from peripheral nerve,through spinal cord, up to cortex, and can be due tomany different pathologies (39).NEUROPSYCHOLOGYCognitive function is investigated by the clinician aspart of the neurological examination, i.e. bedsidecognitive testing. Due to constraints of clinic time,this allows only a brief assessment of cognition. Aneuropsychologist, who has the time to fully assesscognition using standardized tests, does more detailedinvestigation of cognitive function.Traditionally, neuropsychological testingemployed a battery approach, where a standardized,well-validated test battery would be administered tothe patient. This results in collation of muchinformation regarding cognitive function, but is notspecific to the patient’s cognitive presentingcomplaint. An alternative approach is individualizedtesting, where the choice of tests is tailored to thepatient. Although such tests may not be as wellstandardized as in the battery of tests, it does allow adynamic, fluid approach to investigating patients.Often the neuropsychologist uses a combination ofthe two approaches. There are hundreds of individualneuropsychological tests, and the following onlyprovides a brief representative sample of what isavailable.39aLEG3TRUNKARMbLEGTRUNKARMNucleusgracilisThedorsalcolumnsthoraciclumbarPONSLOWERMEDULLAsacralSPINALCORDSPINAL CORD12FACEMediallemniscusInternalarcuatefibresNucleuscuneatusFasciculusgracilisFasciculuscuneatusSPINALCORDTHALAMUSMIDBRAINPONSMEDULLA123FACEAscendingreticularformationLateral lemniscusSpinothalamic tractcervicalthoraciclumbarsacralSomatotopicorganization(cervical level)39 Diagram to show the anatomy of the sensory system. a: dorsal columns; b: spinothalamic pathway.
Neurological investigations 45OrientationThis is usually assessed as part of bedside cognitivetesting, where it comprises a third of the total score ofthe Mini-Mental State Examination (MMSE). TheMMSE acts as a brief assessment of cognitivefunction, but is used more by the neurologist in clinicrather than by the neuropsychologist.AttentionA simple test of attention is digit span. While this maybe done forward or backward, backward digit spanalso involves short-term memory in addition toattention, and forward digit span is therefore thepurer test of attention. The examiner simply reads outa digit sequence, each number given at one-secondintervals. The length of the digit span is increaseduntil the patient makes errors. A nonverbal equivalentof the digit span test is the Corsi Block Test, in whichthe subject watches the examiner touching blocks in acertain order, and must reproduce the order.The Trail Making Test A involves connectingrandomly positioned numbered circles in numericorder as quickly as possible. The Letter CancellationTest involves cancelling selected letters from abackground of nontarget letters.Intellectual abilitiesIntelligence is thought to be the ultimate expression ofcognitive ability. The most widely used measure ofintelligence is the Wechsler Adult Intelligence Scale-Revised (WAIS-R). This comprises various subtests.Verbal scales comprise information, digit span,vocabulary, arithmetic, comprehension, andsimilarities, while performance scales comprise picturecompletion, picture arrangement, block design, objectassembly, and digit symbol. Given that a patient’scurrent performance may reflect impairment due toneurological disease, it is also worthwhile trying toestimate premorbid IQ (intelligence quotient). Onesuch measure is the National Adult Reading Test(NART). This utilizes the fact that IQ is correlatedwith the ability to pronounce irregular words, e.g.pint. It was previously thought that this ability topronounce words is insensitive to cerebral damage,and thus provides a measure of premorbid IQ.Concerns arise, however, that semantic memoryimpairment (as occurs in many neurodegenerativeillnesses such as Alzheimer’s disease) can lead to asurface dyslexia, which results in mispronunciation ofirregular words, thus leading to a false underestimateof premorbid IQ.Reasoning, problem solving, and executive functionExecutive function is complex, and involves manyabilities, such as formation and planning to achievegoals, set-shifting, and searching stimuli for relevanceto achieving goals. Measures of verbal reasoninginclude the comprehension and similarities subtests ofthe WAIS-R. Such tests involve questions such as‘What does ‘A rolling stone gathers no moss’ mean?’or ‘How are an orange and a banana alike?’Raven’s Progressive Matrices may measurenonverbal reasoning. In this test multiple designs arepresented, with a final design missing. The patient hasto choose from a series of alternative designs whichone should occupy the missing space.The Wisconsin Card Sorting Test involves thepatient being given four target cards with designs.Probe cards are then given to the patient, who isasked to sort these according to the target cardtemplate. There are three ways of sorting, but thepatient is free to sort by whichever strategy they firstadopt. The only feedback to the patient is whethertheir sorting is correct. In this way, set shifting is alsotested in addition to concept formation.The Stroop Test comprises three parts. Firstly, thepatient reads the names of colours printed in blackink. Secondly, the patient must name the colour ofcoloured dots as quickly as possible. Lastly, thepatient must name the colour of ink of colour namewords. Interference is caused by the colour name notmatching the colour of the ink. The ability to inhibitthis interference effect is a measure of frontalexecutive function.Verbal functionAn assessment of language should includespontaneous speech, naming, comprehension,repetition, reading, and writing. There exist aphasiabatteries such as the Boston Diagnostic AphasiaExamination, and aphasia screening tests such as theToken Test. In this latter test, the patient is givenvarious tokens of different shape, size, and colour.The patient is asked to point, touch, and pick upcertain tokens. It is a very sensitive test to impairedlanguage, but does not indicate which component oflanguage is impaired. Individual language componentsmay be tested by specific tests. An example isthe Boston Naming Test, where the patient is asked toname 60 line drawings.
46MemoryThere are many different forms of memory, bothconscious (explicit) and unconscious (implicit).Explicit memory may refer to episodic memories (i.e.learning new information, or recalling discreteepisodes such as previous holidays), or semanticmemory (i.e. the database of knowledge we draw onto give meaning to our conscious experience).Practically, assessing memory as part of neuropsychologicaltesting usually involves asking thepatient to learn new information, and then testingrecall after a delay. Semantic memory is also assessed,but there is considerable overlap with language.The Wechsler Memory Scale-Revised comprisesvarious subscales, which assess different componentsof memory. Verbal memory is tested using logicalmemory, which involves the patient reading a storyparagraph, and then having to recall as much aspossible. Verbal paired associates involve thepresentation of pairs of words. At recall, one word isshown, and the patient must provide the other wordin the pair. Nonverbal memory may be assessed in asimilar fashion, but by asking for recall of sequencesof taps rather than a story. Short-term verbal memoryis assessed using digit span.A further measure of nonverbal memory is theRey–Osterrieth complex figure (40). This is anabstract design, which is not easily encoded verbally.The ability to copy the Rey figure is a measure ofvisuo-perceptual function. The ability to draw frommemory after a 30-minute delay is a measure ofdelayed nonverbal memory.Perception and construction abilitiesWhile perception involves all sensory modalities, inpractice the neuropsychologist is interested in visualand auditory perception.Visual perception and constructionObject and face recognition, colour perception, andvisual search activities may all be assessedneuropsychologically.The Benton Facial Recognition Test involves thepatient being shown one face, with six others on theadjacent page, one of which matches the target, andis a measure of facial recognition. The Judgement ofLine Orientation Test involves a test line having to bematched for orientation with one of a series of linesarranged like a protractor. The Line Bisection Testrequires the patient to put a cross halfway alongseveral lines. It is sensitive to patients with neglect.The Clock Drawing Test is a measure of visualconstruction (41).4040 Diagram of the Rey–Osterrieth figure.
Neurological investigations 47SPECIFIC LABORATORY TESTSWhile the diagnostic sieve usually involves the abovemodalities to narrow down the differential diagnosis,there is a place for specific blood tests, which eitherconfirm or refute specific diagnostic possibilities. Anexample of this would be dementia, where it wouldbe appropriate to perform a blood screen to look fortreatable causes of dementia, such as vitamin B 12deficiency and thyroid function. Depending on theclinical presentation, there may be a need to look forspecific diseases. For example, if abnormalmovements accompanied dementia, this would raisethe possibility of Huntington’s disease, and thereforegenetic screening for this disorder would be necessary.In similar vein, if there were a family history ofdementia, migraine, and stroke-like episodes, and ifcharacteristic white matter lesions were seen on MRI,then it would be appropriate to test for the notch 3mutation on chromosome 19, which would lead to adiagnosis of cerebral autosomal dominant arteriopathywith subcortical infarcts and leucoencephalopathy(CADASIL).INVESTIGATING THE SPINAL CORDNORMAL ANATOMYThe vertebral column comprises 7 cervical, 12thoracic, 5 lumbar, 5 sacral, and 4 coccygealvertebrae. The sacral bones fuse to form the sacrumand the coccygeal bones the coccyx (42).With the exception of both the atlas (C1) and theaxis (C2), all vertebrae share common anatomicalfeatures. Each is made up of a body, pedicles, and pairsof facets. The superior facet articulates with the inferiorfacet by means of the pars interarticularis (pars: part;inter: between; articularis: articulating surface). Finally,each vertebra possesses two laminae and a spinousprocess. The spinal cord, conus, and cauda equina liewithin the vertebral canal and emerging nerve rootspass within the neural foramina. The C1 nerve rootIntervertebralforamina42CervicalsegmentsCervicalroots1–841ThoracicsegmentsLumbarsegmentsSacralsegmentsCoccygealsegmentThoracicroots1–12Lumbarroots1–5Sacralroots1–5Coccygeal root41 Clock drawing by a patient exhibiting neglect to the lefthemisphere.42 Sagittal diagram of the spine and spinal cord, illustratingthe levels of exit for the nerve roots.
48passes superiorly above the atlas, the C5 root passesabove the body of C5 into the C4–5 neural foramen, theC6 root passes above C6 into the C5–6 foramen, and soon. The lowest cervical nerve root, C8, passes below thebody of C7 and outwards through the neural foramenof C7–T1. The presence of the C8 root means that theT1 thoracic nerve root passes below the body of T1through the foramen of T1–2 and all subsequent nerveroots in this manner. The last (T12) nerve root similarlypasses below its vertebral body and then through theforamen of T12–L1. The first lumbar root likewisepasses below L1 into the L1–2 neural foramen and theL5 root passes below the body of L5 into the L5–S1neural foramen.In adults, the tip of the conus lies at or above theL2–L3 intervertebral disc space. The filum terminale,a thin glial-ependymal cord, is a direct continuationof the conus terminating in the posterior aspect of thecoccyx. It measures
Neurological investigations 4943Vertebral arteryL5T1107Cervical arteries arise from vertebraland subclavian vessels, form plexusesand supply the cervical and upperthoracic cordIntercostal artery branches supplythe midthoracic cordAnterior spinal artery is at itsnarrowest at T8. This level of thespinal cord is liable to damageduring hypertension – watershedareaArtery of Adamkiewicz, the largestradicular artery, supplies the lowthoracic and lumbar cord. It usuallyarises around T9–T12 levels and ison the left side in 70% of thepopulationSacral arteries arise from thehypogastric artery and supply thesacral cord and cauda equinaAnterior radicular branches joining anterior spinal artery44Posterior spinal arteryterritory– Posterior one-third ofspinal cord– Dorsal columnVirtually noanastomoticcommunicationAnterior spinal artery territoryPenetrating branches – anterior and part of posterior greymatterCircumferential branches – anterior white matter.– Anterior two-thirds of spinal cord44 Axial figure of the spinal cord, illustrating anterior andposterior spinal artery territories.43 Sagittal diagram of the blood supply to the spinal cord.45 Myelogram showingspondylolisthesis at L4–L5 andL5–S1 with crowding of nerveroots.454646 Coronal computed tomography scan of thespine showing a fracture at C7 not visible onplain X-rays.
50body disease (tumours and infections) and may becomplementary to MRI, but the latter is generally thespinal imaging modality of choice.SPINAL MRIMRI has revolutionized the investigation of disease ofthe spinal cord, and recent advances have shorteneddata acquisition times and reduced artefacts. Itsnoninvasive ability to image the spinal cord andsurrounding structures (CSF, dura, and ligaments)makes it indispensable in the investigative workup.Classically there are three locations for spinalneurological disease, extradural, intradural/ extramedullary,and intramedullary (47). MRI has thecapability to evaluate all three locations.A good working knowledge of basic MRimaging principles and spine anatomy is essentialfor understanding the imaging observations seenin various spine lesions.For example, because of their anterior obliqueorientation, the neural foramina in the cervical spineare exceedingly difficult to see on a sagittal image andare best seen on oblique sagittal or axial views.Conversely in the lumbosacral region, the neuralforamina are laterally orientated and therefore areproperly visualized on a sagittal T1-weighted image(48). Anatomic changes inevitably occur to the neuralforamen with ageing. Posterior disk bulge, lateralherniated disk, together with vertebral bodyosteophytes can encroach on the neural foramen andits contents. Although MRI is poor in showing densenormal cortical bone, it shows infiltrative/infectivedisease well. Contrast-medium enhanced imaging canhelp differentiate tumours, inflammation, and activedemyelinating diseases.A common mistake is failure to order views thatdisplay the likely site(s) of the lesion. In most cases,careful history and examination will decide which ofcervical, thoracic, or lumbosacral levels are to beimaged. However, this is not always possible and ‘fullspinal imaging’ should then be requested. Somedisease processes can be multilevel (multiple sclerosis[MS]) and, on occasion, the common (lumbar discdisease) and the rare (thoracic meningioma) maycoexist. In any patient with a spinal cord syndrome ofunknown cause, the clinician must consider thepossibility of a lesion at the level of the foramenmagnum, a level that is neither spinal nor cranial andconsequently is often overlooked. Imaging hereshould pay particular attention to the possibility ofmalformations (Chiari malformations) and thelocation of the odontoid process (rheumatoidarthritis). A benign tumour of the foramen magnumsuch as meningioma can be confused with MS ordegenerative cord diseases and, prior to correctdiagnosis, progressive disability passes beyond thepoint of reversibility.47EXTRADURALINTRADURALPartial block Extramedullary Intramedullaryblockblock47 Illustration of extradural andintradural (extramedullary andintramedullary) spaces.Cord displacedto one sideDura lifted offContrast material isvertebral body ‘Shoulder’ of splayed around thecontrast materialdilated cord
Neurological investigations 51SPINAL ANGIOGRAPHYWhile in the head CT and MR angiography haveincreasingly replaced digital subtraction angiography(DSA), this is not the case with the spine. Resolutionand the complexity of the spinal circulation mean thatconventional angiography still remains the goldstandard. However, the indications for spinalangiography are few (spinal vascular lesions such asdural fistula). This infrequently performed investigationrequires considerable technical skill, and on occasion,selective cannulation of several radicular vessels may berequired to demonstrate a dural fistula. CT angiographymay show large dural fistulas (49).NEUROPHYSIOLOGYNeurophysiological investigations such as EMG canbe helpful in localizing the level of a lesion if this isnot apparent on imaging. It is a valuable adjunct toimaging where there is uncertainty about the truesignificance of a compressed nerve root (cervical orlumbar radiculopathy).Nerve conduction studies are of value indifferentiating peripheral nerve from nerve root(radicular) lesions. Radicular lesions cause asegmental distribution of muscle involvement, i.e.affect muscles supplied by the same root, whereasperipheral nerve lesions may affect muscles suppliedby that nerve, which may be innervated by severalnerve roots. Reduction in nerve conduction velocitymay indicate peripheral neuropathy. Fasciculationand fibrillations can be detected in muscles that484948 Magnetic resonance image of the lumbar spineshowing lumbar canal stenosis.49 Computed tomography angiogram showing a dural fistula.
52appear clinically not involved, e.g. certain conditionsthat appear purely spinal may have an anterior horncell component (motor neurone disease/amyotrophiclateral sclerosis [MND/ALS]) and neurophysiologycan be diagnostic where imaging has been normal.SOMATOSENSORY EVOKED POTENTIALSSomatosensory evoked potentials (SSEPs) test theintegrity of the afferent sensory pathways, principallythe large nerve fibre dorsal column–medial lemniscalpathway. They are elicited by electrical stimulation ofthe median and posterior tibial nerves. Evoked peaksfrom median nerve stimulation are detected in thebrachial plexus (Erb’s point), central grey matter ofthe cervical cord, medial lemniscus, and primarysomatosensory cortex. Abnormalities of SSEPs resultfrom single level (e.g. cervical spondylosis) or diffuse(e.g. MS) disease states. SSEPs can be used to monitorthe integrity of the spinal cord during spinal surgery.LUMBAR PUNCTURELumbar puncture (LP) is a useful test for measuringCSF pressure and obtaining CSF samples, importantin the diagnosis of inflammatory disorders(oligoclonal bands [OCBs] in MS) and infections(borreliosis, syphilis, viral infections, spinaltuberculosis) (50). If, however, a mass lesion issuspected, particularly if it is high in the vertebralcanal, LP, without provision for prior spinal imagingand ‘on-site’ surgical decompression, may becontraindicated. Some patients with compressive cordlesions become abruptly worse after LP due toshifting of the cord, and they may show signs of acomplete cord syndrome. If the lesion is cervical,respiratory paralysis may occur suddenly.If spinal MRI is performed after LP, bleeding orleakage of CSF into the epidural space may result inmeningeal enhancement after contrast, erroneouslyinterpreted as part of the disease process underinvestigation. It is therefore normally preferable toobtain imaging prior to CSF examination.INVESTIGATING THE PERIPHERAL NERVOUSSYSTEM (NERVE, NEUROMUSCULAR JUNCTION,AND MUSCLE)The investigation of disorders of the peripheralnervous system relies primarily on neurophysiology,with selected use of more invasive nerve and musclebiopsy.50L1L2DuraL3Extradural fatL4Ligamentum flavumL550 Sagittal diagram of lumbar spine.NEUROPHYSIOLOGYThe use of nerve conduction studies to investigateperipheral nerve function, and EMG to investigatemuscle disease, allows extensive investigation of theperipheral nervous system noninvasively.Nerve conduction studiesBy administering an electrical stimulus to a peripheralnerve, it is possible to measure signal conduction in thenerve, and thus deduce how the nerve is functioning.Motor and sensory nerves may be studied by recordingthe distal latency (latency from stimulus to recordingelectrodes), evoked response amplitude, and conductionvelocity (51). Normal conduction velocity valuesvary depending on age and body temperature.Significant delay indicates impairment in nerveconduction, as is seen in demyelinating neuropathiessuch as Guillain–Barré syndrome or multifocalneuropathy, and in nerve entrapments.
Neurological investigations 5351 Diagram of nerve conductionstudies.51–+Stim. 1Stimulus 110 mVStim. 2–+Stimulus 210 mVRecordhypothenareminence(surface orneedleelectrode)10 msF waves and H wavesWhile neurophysiology is mainly directed at disordersof nerve and muscle, it is possible to obtain indirectevidence of spinal or nerve root impairment by meansof F and H waves (52). F waves require the motornerve to be stimulated antidromically, i.e. from distalto proximal. The stimulus then travels proximally upthe motor nerve axon, and then returnsorthodromically (i.e. proximal to distal) back downto the initial stimulation point.H reflexes differ in that the initial nervestimulated is a sensory nerve. The signal in conductedproximally up to where the sensory nerve synapseswith the motor nerve. The signal then returns downthe motor axon and is recorded peripherally.These F-response and H-reflex studies can be ofuse in peripheral neuropathies, particularly when thepathological process is too proximal to be detectableby conventional nerve conduction studies. However,in conditions such as radiculopathy, while responsesmay be abnormal, EMG would also be abnormal,such that F and H studies would not usually add anyadditional diagnostic value to EMG.Blink reflexIn this test, the supraorbital nerve is stimulated, andactivity in orbicularis oculi is recorded. An abnormalblink reflex can be helpful in showing evidence of asubtle trigeminal or facial nerve lesion.ab52 Diagram to show F and H reflexes in nerve conductionstudies. a: in F waves, the signal travels from distal toproximal up the motor nerve, and then from proximal to distaldown the same motor nerve; b: in H waves, the signal travelsfrom distal to proximal up the sensory nerve, and thenproximal to distal down the motor nerve.52SensoryMotorSensoryMotor
54ElectromyographyIn EMG, a fine bore needle is inserted directly intomuscle. The needle comprises a central recordingelectrode, and the outer casing acts as a reference.The potential difference between the two provides ameasure of spontaneous muscle activity.Normal muscle is electrically silent. When muscleis contracting normally, there appear motor unitpotentials. As more of these are recruited, aninterference pattern arises, which is the summation ofmany motor unit potentials (53). Abnormalitiesdetected during EMG include the following:spontaneous rest activity, motor unit potentialabnormalities, interference pattern abnormalities,and other phenomena, e.g. myotonia.5354An interference pattern20 ms200 µV53 Diagram to show normal interference picture in nerveconduction.Spontaneous rest activityFibrillation potentials are due to single muscle fibrescontracting, and indicate active denervation, asoccurs in neurogenic disorders such as neuropathy.Sharp positive spikes may be seen in chronicallydenervated muscle, such as in motor neurone disease,but also occur in acute myopathy (54).Motor unit potential abnormalitiesIn neuropathy, collateral reinnervation causespotentials of large amplitude and long duration (55).This is in contrast to myopathies and musculardystrophies, where potentials are of small amplitudeand short duration (56).Abnormalities of the interference patternNeuropathy leads to a loss of motor units undervoluntary control, hence a reduction in interference.By contrast, in myopathy, recruitment of motor unitsand the interference pattern are normal.Special phenomenaIn myotonia, voluntary movement results in highfrequency repetitive discharges. The amplitude andfrequency of the potentials fluctuate, resulting in thetypical ‘dive bomber’ sound on audio monitor (57).55100 µV–200 µV+10 ms20 ms54 Diagram illustrating positive sharp waves in nerveconduction.56200 µV55 Diagram illustrating polyphasic, large amplitude, longduration motor unit potentials, commonly seen in neuropathy.57200 µV20 ms56 Diagram illustrating polyphasic, small amplitude, shortduration potentials seen in myopathies and musculardystrophies.57 Diagram illustrating myotonic discharge onelectromyography as seen in myotonia.20 ms
Neurological investigations 55Repetitive nerve stimulation/jitterThe neuromuscular junction may be specificallyinvestigated using these techniques. In normal subjects,repetitive stimulation of a motor nerve results in aconstant muscle potential, and decrement in theamplitude only occurs when the rate of stimulation is>30 Hz. Abnormalities on repetitive stimulationindicate neuromuscular junction dysfunction. Inmyasthenia, there occurs a decremental response atstimulus rates as low as 3–5 Hz (58). InEaton–Lambert syndrome, an incremental responseoccurs with rapid stimulation, i.e. at 20–50 Hz.Single fibre EMGA further way of investigating the neuromuscularjunction is using single fibre EMG. This requires avery fine needle, which records from approximately1–3 muscle fibres from a single motor unit, ratherthan the 20 or so motor units sampled when using astandard EMG needle. There is normally a degree ofvariability in the action potentials recorded fromdifferent muscle fibres in a single motor unit, onaccount of variation in neuromuscular transmission.In myasthenia, there is increased jitter due to greatervariability in neuromuscular transmission (59). Thiscan be helpful in supporting the diagnosis in thosecases of myasthenia where repetitive stimulation mayhave been normal.NEUROPATHOLOGYNerve biopsyAlthough nerve conduction studies often givesufficient information to result in the diagnosis of aperipheral nerve disorder, it is occasionally necessary58 Electromyograph in myasthenia showingdecremental response on repetitive stimulation.5859 Diagram illustrating jitter on single fibre electromyography.The gap between the two muscle action potentials is variable,i.e. jitter.59
56to proceed to biopsy. It may be of use in trying todistinguish between segmental demyelination andaxonal degeneration, and also in the diagnosis of anumber of specific disorders such as amyloidosis,vasculitis, and sarcoidosis. The decision to biopsymust take into account the likelihood of the biopsyleading to a change in treatment, and this must bebalanced against the morbidity which can beassociated with this test.Traditionally, the sural nerve was biopsied. Thisleads to permanent numbness affecting the lateralborder of the foot. Sometimes, this can result inpersistent unpleasant dysaesthesia, which can beworse than the initial symptoms. Biopsies nowadaystend to be fascicular, which at least spares a portionof the nerve, with less attendant morbidity. Normally,the specimen is analysed using light and electronmicroscopy, often with immunohistochemistry.Muscle biopsyThis should only be considered after a fullneurological examination, supplemented byappropriate blood tests, and often EMG. A muscleappropriate to the patient’s symptoms must bechosen, and biopsy should only take place in centreswhere the specimen can be processed and analysedfully, i.e. histochemistry, electron microscopy, andspecial studies such as immunohistochemistry.The issue of whether open or needle biopsy isbetter is still controversial. Open biopsies provide alarger specimen, which can be fixed at itsphysiological length. Needle biopsy, however, resultsin less scarring, and the ability to sample multiplesites. The specimen is, however, smaller and it ismore difficult to orientate.Specific laboratory testsAntibodiesIn myasthenia, the presence of acetylcholine receptorantibodies is diagnostic, although antibody-negativemyasthenia may occur, especially in more restrictedforms such as ocular or bulbar myasthenia. Voltagegated calcium channel antibodies are detected in90% of patients with Eaton–Lambert syndrome,which can superficially mimic myasthenia. In certainof the hereditary motor and sensory neuropathies(HMSN some types termed Charcot– Marie–Toothdisease), it has been possible to identify the geneticmutations. Of those HMSN with a known geneticbasis, HMSN types 1 and 3 have been associatedwith mutations in one of several genes expressed inSchwann cells, which produce myelin for theperipheral nervous system.Mitochondrial diseases are a diverse group ofconditions resulting from impairment ofmitochondrial function, and leading to a wide rangeof clinical disorders. Some patients have symptomsthat fulfil clearly delineated syndromes, such asmitochondrial encephalopathy, lactic acidosis, andstroke-like episodes (MELAS) or myoclonic epilepsyand ragged red fibres syndrome (MERRF), but mostdo not. Molecular genetic studies of deoxyribonucleicacid (DNA) from blood may be analysed formitochondrial DNA mutations. Nearly all pointmutations may be detected from blood, but majorstructural mutations, such as deletions, requireskeletal muscle for analysis.Ischaemic lactate testThis is a physiological test of muscle function. Thepatient is asked to grip repeatedly, with a cuff occludingthe circulation. Blood is drawn at regular intervals inorder to assess lactate levels. Normally, when exercise isrelatively anaerobic, then anaerobic metabolism shouldproduce lactate. In patients with deficits in theglycolytic pathway, there is no rise in lactate levels withischaemic exercise. In contrast, in mitochondrialdisease, there can be excess lactate production.INVESTIGATING SPECIFIC SITESCertain constellations of clinical features are of greatlocalization value. The tempo of onset of symptoms isthen of use in determining the type of pathologicalprocess responsible for these anatomically localizablesyndromes.CRANIO-CERVICAL JUNCTIONLesions at the cranio-cervical junction may result insymptoms of poor balance (60). There may be ahistory of loss of function on one side followed byprogression to signs to all four extremities.Neurological examination may reveal ataxia andcerebellar signs, together with brisk reflexes andupgoing plantars. Down-beating nystagmus, ifpresent, points to the cranio-cervical junction.Although CT may be sufficient, the cranio-cervicaljunction is best imaged with MRI (61).CEREBELLO-PONTINE ANGLEA common cause of lesions at the cerebello-pontineangle is acoustic neuroma or other tumours such asmeningioma (62, 63). Patients with lesions here tend
Neurological investigations 57Type I Type II Type III60MedullaMeningomyelocele60 Diagram to show three types of Chiari malformation.61VIII nerveV nerve62Aqueduct andfourth ventricleVII nerveIX, X, XI nerves61 Magnetic resonance image showing Chiari malformationresulting in secondary hydrocephalus.62 Diagram of a cerebello-pontine angle tumour, compressingadjacent structures.63 Magnetic resonance image of cerebello-pontine angle lesions(vestibular schwannoma).63
58to present with mild vertigo or ataxia, and there maybe accompanying ipsilateral occipital pain.Examination often reveals asymmetrical sensorineuralhearing loss on examination. In the event ofdelayed diagnosis, as the tumour progresses theremay be facial pain, numbness, and paraesthesia dueto involvement of the trigeminal nerve. Depressedcorneal reflex will be evident. Should the tumourresult in hydrocephalus, the symptoms and signs ofraised intracranial pressure will appear.PITUITARY/CAVERNOUS SINUSLesions of the pituitary fossa may present with localspace-occupying effects, or with endocrine symptomsdepending on whether an active hormone is beingreleased. Local mass effect can result in nonspecificheadache. On examination, the finding of a visual fielddefect should raise suspicion of a pituitary lesion.Pressure on the inferior aspect of the optic chiasmresults in a superior temporal quadrantanopia, buttumour progression will lead to bitemporalhemianopia. In some instances, lateral expansion willlead to compression of nerves lying in the walls of thecavernous sinus, especially the third nerve (64, 65).Endocrine effects depend on whether there ishypersecretion or hyposecretion of hormones, and onwhich hormone is being affected. Should there behypersecretion of growth hormone (GH), then thiswill result in acromegaly. This presents clinically withenlargement of face, hands, and feet, with coarseningof the skin. A tumour producing increased prolactinwill result clinically in women with infertility,amenorrhoea, and galactorrhoea. In men, impotencemay occur. An adrenocorticotrophic hormone-(ACTH) producing pituitary tumour will result in thefeatures of Cushing’s syndrome. This includes facialmooning, hirsutism, central obesity, and muscleweakness.Investigation of lesions affecting the pituitary orcavernous sinus primarily involves neuroimaging andtests of endocrine function. The imaging modality ofchoice for investigating pituitary lesions is MRI (66).This gives excellent anatomical detail, and can showwhether there is suprasellar extension and whetheradjacent structures such as the walls of the cavernoussinus are involved. Given the close proximity of thepituitary to the optic chiasm, it is important to testvisual fields as a means of monitoring involvement ofvisual pathways. This is best done at the bedside byassessing peripheral visual fields using a red hatpin. Itmay be supplemented by more detailed Goldmannperimetry, available in ophthalmology clinics.Hypersecretion may be diagnosed by measuringblood levels of the relevant hormone. While manyendocrine presentations of pituitary tumours are dueto hypersecretion, it is also possible for pituitarylesions to present clinically with signs of impairmentof pituitary secretion. This may present clinically asadult GH deficiency syndrome (weight gain, loss oflibido, fatigue), muscle weakness and fatigue, or withthe symptoms of hypothyroidism. Low levels ofpituitary hormone in the presence of low target glandhormones confirm hyposecretion. This can be further6564Cavernous sinusCarotid arteryIII nerveIV nerveV nerveVI nerveSphenoid sinus64 Diagram to show the anatomy of the cavernous sinus.65 Computed tomography scan of cavernous sinus thrombosis.
Neurological investigations 59investigated by combined pituitary functionstimulation tests comprising the insulin tolerance test,also with gonadotrophin releasing hormone (GnRH)and thyrotrophin releasing hormone (TRH) injection.66DISEASE AT ‘SHARED’ SITESOrbitOrbital disorders may present to the neurologist aswell as to the ophthalmologist, and it important thatneurologists are aware of the appropriateinvestigations for this area.Methods of visual field testingIt must be remembered that confrontation using a redpin is a relatively crude means of mapping visualfields, both for peripheral vision and for assessing theblind spot. Peripheral visual fields are better testedwith a Goldmann perimeter (67). Here, a movingtarget is brought in from the periphery, and thepatient must indicate as soon as he is aware of thetarget. It is thus possible to map out peripheral visualfields well.While central fields may be assessed using aGoldmann perimeter, this is more accurately doneusing the Humphrey field analyser, which records thethreshold at which a static light source is seen atvarious central points.66 Magnetic resonance image of a pituitary tumour (arrow).Fixationpoint67Peripheral120 105 90 75 6070field1354560501504030 Central field16530201510180 90 80 70 60 50 40 30 20 10 10 20 30 40 50 60 70 80 90 01020195345Blind spot3021040503302256070315240 255 270 285 300 Right eye67 Diagram to demonstrate Goldmann perimetry.Goldmann perimeter
60686969 Computed tomography scan showing a left optic nervemeningioma. (Note Left is left on this scan.)The earMany conditions such as dizziness may presentequally to a neurologist as to an ear nose and throatsurgeon. One should therefore be familiar with therelevant investigations.68 Magnetic resonance image showing a small tumoursuperior to the left eye.ImagingTumours of the orbit, or inflammatory conditions,are best visualised using MRI (68) rather than CT(69).NeurophysiologyVisual evoked responses (VERs) have been describedabove, but are a useful means of assessing theintegrity of the visual pathway from retina tooccipital cortex.Electroretinography (ERG) is a means ofassessing rod and cone photoreceptor function, and isof use in assessing retinal degeneration anddystrophy.Fluorescein angiographyThis involves intravenous injection of aqueousfluorescein. A photograph of the fundus is taken beforeand after injection. This technique demonstrateschoroidal and retinal vasculature, and can detectvascular occlusion and retinal haemorrhages. Trueoptic disc swelling results in leakage of fluorescein,while pseudopapilloedematous discs do not leak.Auditory systemWeber’s and Rinne’s tests done as part of theneurological examination will usually allowclassification of hearing impairment as beingsensorineural or conductive, and will localize which isthe impaired ear. These tests are, however,supplemented with further investigations includingaudiometry. Pure tone audiometry involves airconduction by means of a pure tone administeredthrough headphones, with masking noise applied tothe contralateral ear (70). Bone conduction is assessedby means of an electromechanical vibrator. Airconductedsound requires a functioning ossicularsystem as well as cochlea and VIII nerve, while boneconduction bypasses the ossicles.Speech audiometry uses pretaped words rather thantones, but involves the same principles as the above.Stapedial reflex decayNormally, a loud stimulus causes reflex contractionof stapedius, with subsequent reduced compliance ofthe tympanic membrane. In this test, an activatingtone is applied to the ear under test, and the tympanicmembrane impedance is monitored in thecontralateral ear. Rapid decay of the reflex responsesuggests an auditory nerve lesion.
Neurological investigations 61Normal hearing Conductive deafness Sensorineural loss70–100Air–100Bone–100AirdBBonedBdBBoneAir100100100125 250 500 1000 2000 4000 8000 125 250 500 1000 2000 4000 8000 125 250 500 1000 2000 4000 8000Hz Hz Hz70 Audiograms of normal hearing, conductive deafness, and sensorineural loss.Auditory brainstem evoked potentialThis has been covered earlier in the chapter.Vestibular systemCaloric testingThe vestibular system may be tested clinically usingthe Hallpike manoeuvre. Further investigation of thevestibular system relies on caloric testing, whichutilizes the vestibulo-ocular reflex. In this test, waterat 30°C (86°F) is irrigated into the ear. Nystagmususually occurs after 20 seconds, and lasts for morethan 1 minute. The test is then repeated 5 minuteslater with water at 44°C (112°F). Cold water reducesvestibular output from one side, causing an imbalanceand producing eye drift towards the irrigated ear,with rapid corrective movements to the opposite ear.Hot water reverses this, increases vestibular outputand changes the direction of nystagmus. Time untilcessation of nystagmus is plotted for each ear, at eachtemperature (71).Reduced duration of nystagmus is termed canalparesis. This may be due to a peripheral or centrallesion. A more prolonged duration of nystagmus inone direction than the other is called directionalpreponderance. It can be due to a central lesionipsilateral to the preponderance, or from acontralateral peripheral lesion.Combined with audiometry, these tests shoulddifferentiate peripheral from central lesions.ElectronystagmographyAlthough nystagmus may be observed clinically, it isNormalresponseL30°RL44°RDamage to the labyrinth, vestibular nerveor nucleus results in one of two abnormalpatterns, or a combination of both.1. Canalparesis2. DirectionalpreponderanceL30°RL44°RL30°RL44°RLeftcanalparesisminmin71 Caloric testing illustrating normal response, canal paresis,and directional preponderance.possible to assess nystagmus in a more quantitativemanner by means of electronystagmography (ENG).These studies of eye movements are performed indarkness, in order to eliminate the stabilizing effectsof visual fixation.71Directionalpreponderanceto the right
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CHAPTER 3:THE PROBLEMS63DISORDERS OF CONSCIOUSNESSBLACKOUTS: EPILEPTIC SEIZURES AND OTHER EVENTSACUTE CONFUSIONAL STATESDISORDERS OF COGNITIONMEMORY DISORDERSSPEECH AND LANGUAGE DISORDERSDISORDERS OF SPECIAL SENSESVISUAL LOSS AND DOUBLE VISIONDIZZINESS AND VERTIGODISORDERS OF MOTILITYWEAKNESSTREMOR AND OTHER INVOLUNTARY MOVEMENTSPOOR COORDINATIONDISORDERS OF SENSATIONHEADACHESPINAL SYMPTOMS: NECK PAIN AND BACKACHENUMBNESS AND TINGLING
64Disorders of consciousnessBLACKOUTS: EPILEPTIC SEIZURESAND OTHER EVENTSRod DuncanINTRODUCTIONClinicians in the Western world work in a diagnosticenvironment in which tests of one kind or anotherplay an increasingly important diagnostic role.Disorders such as epilepsy, which manifest asrecurrent, paroxysmal dysfunction of the centralnervous system, continue to pose diagnosticdifficulties. Why should this be?The problem is simple to state. Between events,there are usually no abnormal examination findings,and those tests that can be applied are limited interms of sensitivity, specificity, or both. The mostaccurate diagnostic tests depend on recording thedisordered physiology at the time of the event (e.g.recording the changes in the electrical activity of thebrain during an epileptic seizure). This type of testrequires that events are frequent enough for there tobe a realistic chance of capturing them, and that theresources are available to allow this. For thesereasons, the use of such investigations is notpractical for the majority of patients and thediagnosis of epilepsy and other disorders that comeinto its differential diagnosis, remains primarily aclinical one.The differential diagnosis of epileptic seizures iswide, but this chapter will deal principally withconditions commonly considered at neurology or firstseizure clinics: epilepsy, syncope, psychogenicnonepileptic seizures (PNES, previously termed‘pseudoseizures’), cardiogenic syncope, and panic orhyperventilation attacks.The most common and important diagnosticdistinction is between vasovagal syncope andepileptic seizure. It is thought that 80% of people willexperience syncope at least once in the course of theirlives. Epilepsy has an incidence of approximately 50per 100,000 per year in the teenage and adultpopulations, with higher incidences in the paediatricand elderly populations. PNES make up 10–20% ofpatients who are thought to have uncontrolledepilepsy (or 2–4% of all patients thought to haveepilepsy). For the nonspecialist, distinguishing PNESfrom epilepsy may be enormously difficult. PNESmay coexist with hyperventilation or panic attacks.Cardiogenic syncope presents less commonly toneurological services, but has an importance out ofproportion to its incidence, as it is potentially fatal.CLINICAL ASSESSMENTThe diagnostic approachThe principle of the diagnostic method is that theaccount of the patient and that of the eyewitness allowthe clinician to put together a ‘video’ in his or her mindof what happens to the patient during the event. Thisvirtual video can then be compared with the clinicalfeatures of different types of event in order to try tomake a match. An understanding of the pathophysiologyof disorders such as epilepsy and syncope,and how that pathophysiology produces signs andsymptoms, can also provide a framework for diagnosisfrom first principles. This can especially help whereevents are atypical. In this chapter, pathophysiologywill, as far as possible, be related to the clinical features(sometimes called the clinical semiology) of events.In taking the history of an event, it is importantto be systematic. The account from the patient shouldinclude the circumstances of the event (i.e. what thepatient was doing at the time of onset of the event,and for a few minutes before), the patient’s experienceof the onset of the event, the patient’s experience ofthe event itself (if any), and the patient’s symptomsafter the event, up to the point where the patient feelsback to normal. It is important that the duration ofeach stage is established as accurately as possible. Intaking the history from the eyewitness, it is importantto begin at the point when the eyewitness firstrealized something was amiss, and again to take thewitness stage by stage through the event, once moretaking care to establish durations. It is important toestablish whether all the events are the same. Adistinction must be made between events that vary inseverity, and events that are completely different inkind. If there are both mild and severe events, it mustbe established whether the severe events lead on frommild ones, or occur independently.While this chapter will deal mainly with theclinical features of the events themselves, the overallhistory of the disorder, and more specifically thedistribution in time of the events may bediagnostically useful to some degree. Triggering ofevents may be seen in a number of disorders, and iscrucial to the diagnosis of vasovagal syncope. In
Disorders of consciousness 65contrast, information relating to the background ofthe patient should not be given inappropriatediagnostic weight. A teenage patient with one firstdegreerelative with epilepsy, for example, has anincreased risk of having epilepsy, but the absolute riskis of the order of a few percent, and syncope remainsthe most common diagnosis in this population.Where several first-degree relatives are affected, theincreased risk becomes more significant, and moreweight may be given to family history. Similarly, ahistory of mild head injury is associated only with asmall increase in liability to develop epilepsy, andshould probably not be given significant diagnosticweight (the more so as >50% of patients with PNESgive a history of mild head injury prior to the onset ofthe disorder). If, however, the head injury involved adepressed fracture with craniotomy, the risk ofepilepsy is substantial.The role of clinical examinationNeurological signs suggestive of a cortical lesionindicate a potential cause for epileptic seizures, butshould not be given undue weight in deciding whetherevents are seizures or not. Cardiovascularexamination can, however, be important, and is dealtwith under the relevant disorders.Mechanisms of altered consciousnessMechanisms in the brainstem are thought todetermine consciousness, but it is not clear how thisapplies to disorders such as syncope and epilepsy. Insyncope, the whole brain is ischaemic and thereforedysfunctional. In seizures, the whole brain may beinvolved (the cortex being responsible for generatingthe seizure discharge, which is then conducted downsubcortical pathways, presumably including thebrainstem reticular formation), or specific parts of thebrain may be involved. In the latter case, the historymay well fail to determine whether the patient isamnesic for a period of time, or has beenunconscious. Unresponsiveness may be misleading:patients not infrequently remember some of theirjerking movements. The author is aware of one casewhere a patient claimed to be aware during histonic–clonic seizure and to remember this after theevent, and indeed could recount informationpresented to him during generalized seizures. Theseizures presumably only appeared to be generalized,in reality affecting only the motor strips bilaterally,causing unresponsiveness.Syncopal attacksVasovagal syncope can be provoked by a number ofstressors, physiological and psychological:❏ Postural change.❏ Medical procedures.❏ Physical trauma.❏ Psychological trauma (sight of blood, bad news).❏ Micturition.❏ Defecation.❏ Eating.❏ Swallowing.More than one factor may operate: for example,postural change may provoke vasovagal syncope incombination with predisposing factors such as heat,stress, or alcohol. Some medications such asantidepressant and antihypertensive drugs predisposeto syncope. If a predisposing factor such as heat ispresent, then maintaining the upright posture for aprolonged period may result in spontaneous syncope.Postural syncope may be one of several symptomsthat might suggest disordered autonomic function.Triggering is crucial to the diagnosis of syncope.Without establishing the existence of a credibletrigger for each attack, the diagnosis cannot be madewith confidence.Postural dizziness and ‘presyncope’A change in posture to the standing position causes arise in the orthostatic pressure in the veins. The veinspassively dilate, accommodating a greater volume ofblood so that circulating volume to the rest of thebody falls. Cardiac output and perfusion pressure tothe head and brain therefore fall also. The brain haseffectively no metabolic reserve, so that symptomaticdysfunction occurs within seconds. Where syncope istriggered by a ‘noxious stimulus’ such as the sight ofblood, the pathophysiological sequence begins withvagal overactivity, leading to bradycardia andreduced blood pressure.The initial symptoms (prodrome) of loss ofperfusion pressure to the head are also crucial to thediagnosis of syncope. The retina is as sensitive to lossof perfusion pressure as the brain, so visual symptomsare common. Usually, these consist of blurring, darkspots, or darkening of the visual image. However, awide variety of effects may occur, and the author hasencountered almost every elemental visualmodification imaginable: bright spots, colouredspots, darkening from the periphery inward, from the
66top down, and so on. Dizziness is usual (the wordmay be the patient’s interpretation of unsteadiness,disorientation, a feeling of unreality, or othersensations). Auditory effects may occur, a buzzingnoise being the most common. Reduced perfusionpressure in the carotid arteries activates the carotidbaroceptors. Signals are sent to the heart, to increasecardiac output, and to the peripheral veins to increasetone in their walls. In normal circumstances, this willrestore perfusion pressure to the head and anysymptoms will resolve. Symptoms may also resolve ifthe patient sits with the head between the legs (sittingupright is usually not sufficient) or lies down.Postural dizziness provides a useful tool in thediagnosis of syncope. Almost everybody experiencespostural dizziness at some point in their lives, andtherefore knows what it feels like. When a patientpresents with an episode of loss of consciousness witha prodrome, the patient can be asked to compare theprodrome with the feeling they get if they ‘stand uptoo quickly’. Clearly, the duration and severity of thefeelings can vary, but if the patient identifies them asqualitatively the same, then the clinician can beclinically confident that the patient has lostconsciousness because of lack of perfusion pressure tothe brain. During presyncope, an eyewitness may notnotice anything at all, or may note that the patientlooks dazed or confused.Vasovagal syncopeIn some circumstances, the above sequence of eventsmay either be insufficient to restore cerebralperfusion, or may trigger vagal overactivity, resultingin loss of consciousness and fall. In elderly patientsand those with neuropathy involving loss of controlof blood pressure, a change to the upright positionmay directly cause loss of perfusion pressure to thehead, and the onset of syncope may be rapid, with noremembered prodromal symptoms. However, it ismore usual, especially when the trigger is posturalchange, for the process to take some time. Thus, if aperson gets up from a chair to leave the room, theonset of symptoms may be delayed for a few steps,and loss of consciousness typically does not occuruntil the patient has reached the next room. It istherefore important in taking the history to be sure togo back to precisely what the patient was doing andwhat his or her posture was at least 1 minute or sobefore the onset of symptoms.When loss of consciousness occurs, the patientnormally falls. The orthostatic pressure differentialbetween the head and the legs is then lost, perfusionpressure to the brain is restored, and the patientrecovers. Typically, therefore, the duration ofunconsciousness in syncope is short. However, if forsome reason a fall is prevented or if the patient ispropped up in the sitting position, then perfusionpressure to the brain may not be restored, and thepatient may not regain consciousness for some time.During syncope, brain ischaemia may besufficient to cause seizure-like manifestations, such asbrief stiffening and a few jerks. If the patient does notfall or if hypotension is severe, then thesemanifestations may be quite marked. The accurateidentification of this situation as an effect of syncopedepends crucially on obtaining a clinical history ofthe triggering factor, and of the prodromal symptomstypical of syncope.Cardiogenic syncopeIn cardiogenic syncope, the patient losesconsciousness when perfusion pressure to the brain islost due to arrhythmia or cardiac outflowobstruction. However, because perfusion pressuretends to be lost much more quickly, there may be noprodrome. If loss of perfusion pressure is severe thenstiffness may occur, but a simple fall to the groundwith no convulsive movements is usual.Cardiogenic syncope should be suspected in thefollowing situations:❏ If the eyewitness account suggests syncope,but no history of triggers can be elicited.❏ If there is a history of cardiac disease.❏ If there are additional cardiac symptoms.❏ If there is a family history of suddenunexplained death.❏ If loss of consciousness is provoked byexercise (very important).Cardiogenic syncope presents relativelyuncommonly to neurology clinics; long QT syndromeusually presents in childhood (72). It may bemisdiagnosed as epilepsy and subsequently present aslongstanding epilepsy in an adult, probably because ofits tendency to cause loss of consciousness with a tonicphase. It is important to identify, as it is associated withattacks of ventricular fibrillation and death.Carotid sinus hypersensitivity may cause episodesof loss of consciousness. An exaggerated response tophysical stimulation of the carotid sinus, in somecases provoked even by turning the head, may cause
Disorders of consciousness 67sinus arrest. It occurs mainly in the elderly. Thepatient often has no warning, is aware of a gap intheir awareness, and then of coming round with rapidreturn to normality. An eyewitness seeing such acollapse notes the patient lying still, withoutconvulsive movements, for a short period. Sometimesthe patient notes an association with head turning, ora particular position of the neck.72 Interictal encephalographicrecording in a boy aged 11years, showing focal frontalspikes on the right (second andthird channels from the top).The electrocardiographicrecording (9th channel fromthe top) shows normal sinusrhythm but a prolonged QTinterval of 0.52 seconds (upperlimit of normal is 0.46seconds). The spikes werethought to be incidental as thepatient had never beenwitnessed to have had anepileptic seizure. He haddocumented episodes of cardiacarrest (ventricular fibrillation,'torsades de pointe' pattern),manifesting as loss ofconsciousness with stiffnessand cyanosis. The diagnosiswas long QT syndrome.FP2–F4F4–C4C4–P4P4–O2FP1–F3F3–C3C3–P3P3–O1ECGFP2–F8F8–T4T4–T672T6–O2FP1–F7F7–T3T3–T6T6–O1100 µV1 sec
68EPILEPTIC SEIZURESClassification of seizuresEpilepsy is usually defined as a tendency to haverecurrent epileptic seizures (ESs). It follows from thisthat to diagnose epilepsy the patient’s events must beidentified as being epileptic seizures, and more thanone has to have occurred. The classification of theepilepsy depends on identifying the type(s) of seizuresthe patient suffers from. Table 9 identifies commonseizure types.The relationship between the pathophysiology ofseizures and their clinical manifestations is mosteasily illustrated by considering focal motor seizures.A ‘spike’ refers to a phenomenon seen on electroencephalographic(EEG) recording, and is the basic‘unit’ of seizure activity. It is a sudden and briefincrease in the measured voltage at an electrode orelectrodes. It is due to an aggregate of neurones firingsimultaneously, or nearly so. The voltage and currentproduced are much higher than those which occurduring normal brain function. If the current isproduced in a given part of the brain (for examplethat part of the right motor cortex which correspondsto the left hand), then it is conducted down pathwayswhich impulses from that cortex would normally beconducted down. In the case of the motor cortex, theimpulse is conducted through the relevant parts of theinternal capsule, basal ganglia, brainstem, spinalcord, brachial plexus, and peripheral nerves to themuscles. The result is a jerk (a movement with a fastcontraction phase and a slower relaxation phase[clonus or a clonic movement]) (73).If the discharge takes the form of a series of spikesvery close together, the jerks will occur too frequentlyfor the muscle to relax between, and the result will bea sustained contraction (stiffness, or tonus). If thedischarge consists of repetitive spikes (of whateverfrequency), then areas of cortex adjacent to thatoriginally involved may begin to be ‘recruited’. In thisway, as a discharge spreads (or propagates) along themotor strip, the jerks or tonus correspondingly spreadto the parts of the body served by the cortex. ForTable 9 Common types of seizureSeizure type Description EEG discharge Type of epilepsyPrimary Tonic–clonic seizure (vocalization, stiffness Generalized from onset, Primary generalizedgeneralized followed by generalized jerks, with postictal spike, spike/wavetonic–clonic stupor and confusion). No focal onsetPrimary Also called petit mal: short interruption of Generalized 3/sec spike and Primary generalizedgeneralized activity and contact waveabsenceMyoclonic Jerk, usually of 1 or more limbs Generalized or focal spike Primary generalized or focalAtonic Abrupt loss of muscle tone and drop to Variable. May be generalized Primary generalized or focalthe groundor focal spikeSimple partial Focal seizure with no disturbance of May have no detectable Focalconsciousness (usually clonic movements surface EEG change. Mayof limbs or sensory symptoms)show focal change (spike,slow wave)Complex partial Focal seizures with disturbance of Focal onset, usually with Focalconsciousness (usually arrest of activity, bilateral spreadloss of contact with automatic movements)Secondary Simple or complex partial seizure evolving Focal onset then generalized Focalgeneralized to clonictonic–clonic
Disorders of consciousness 69example, if a seizure discharge begins in that part ofthe motor cortex serving the hand, as it spreadsupward and downward through the cortex, the jerks(or stiffness if the spikes are frequent enough) willgradually spread to involve the rest of the arm, theface, and the leg. This phenomenon is called the‘Jacksonian March’. The discharge may then go on toinvolve the whole brain, producing a generalizedseizure. In this event, the spikes are synchronousthroughout the motor cortex, are conducted downmotor pathways, and reach the muscles simultaneously,producing a jerk that is synchronous in allfour limbs.These are the basic processes by which the positiveelements of clinical seizure semiology are produced.They are translatable pretty much directly to otherprimary cortices (sensory and visual principally). Incortices with complex integrative functions, ‘simple’epileptic discharges feed in to networks, producingcomplex effects that may mimic or parody normalbrain function. These complex effects may consist oforganized automatic movements, complex hallucinations,or other effects and behaviours.Seizure discharges produce not only positivephenomena (e.g. jerks) but also negative phenomena,as they will prevent normal function. Dysfunctionmay also occur in the postictal phase, thought to bedue to neuronal exhaustion. If a focal motor seizureinvolves one arm, for example, then the arm may beweak for a period postictally. If the seizure activityinvolves Broca’s area, then the postictal deficit islikely to be dysphasia. Seizures may be followed bywidespread brain dysfunction, causing effects such asconfusion and drowsiness.Seizure discharge and the clinical manifestations oftonic–clonic seizuresDuring a tonic–clonic seizure, the EEG shows an initialdischarge of high frequency generalized spikes, whichthen gradually breaks up into frequent discrete spikes,slowing as the seizure progresses. Once the spikes havestopped, there is absence of, then slowing of, cerebralrhythms. The clinical correlate of this is direct. The fastdischarge of spikes coincides with the tonic phase of theseizure. As the fast discharge begins to break up intodiscrete spikes, the tonic phase gives way to persistingstiffness but with a superimposed fine jerky tremor. Thetremor and stiffness gradually break up further intodiscrete jerks, which slow down as the seizureprogresses. The absence or slowing of rhythms in thepostictal period reflects cortical dysfunction, which isclinically associated with confusion, drowsiness, andheadache. In the aftermath of the seizure, the patientmay report incontinence and having bitten the side ofthe tongue or the cheek. The next day, the patient maycomplain of myalgia.7373 Recording from a subdural grid of electrodes placed over the lateral frontal cortex just anterior to the motor strip. Theelectrical manifestations of the seizure begin in channels 35–36, 36–37, and 37–38 as a high frequency spike discharge (arrow).As the seizure progresses, the discharge spreads to adjacent cortical areas (arrows). The discharge evolves into a slower spikewaveform and terminates (last arrow) with postictal flattening of the trace most severe in the channels most affected by theseizure discharge (28–29, 29–30, 30–31, 31–32, 36–37, 37–38, 38–39). Clinically, the fast spike discharge was associatedwith stiffening of the contralateral upper limb, and the spike-wave discharge with jerks. The postictal flattening representsneuronal dysfunction, and was associated with weakness (i.e. Todd's palsy).
70An understanding of this pathophysiologicalsequence has an important clinical implication. Ageneralized spike produces a jerk that is necessarilysynchronous in all four limbs, and is not capable ofproducing alternating movements of limbs or side-tosidemovements of the head. If an event appears to bea generalized seizure but the movements arealternating, then the event is likely to be a PNES(Table 10). It should nevertheless be remembered thatcomplex movements might occur during complexpartial seizures or during postictal confusion, againillustrating the importance of having an eyewitnessaccount of the whole event.Classification of the epilepsiesThe International League against Epilepsy (ILAE)classification of epilepsies includes a large number ofsyndromes. However, many are relevant primarily toepilepsies presenting in childhood, and in adolescentsand adults by far the most important classificationissue is whether the epilepsy is primary generalized orfocal. The importance of making this distinction liesin the fact that primary generalized epilepsies respondonly to certain anticonvulsant drugs, tend not toremit, and tend to relapse on withdrawal of currenttreatment.Primary generalized epilepsies make up 10% ofadult epilepsies as a whole, but up to 50% ofepilepsies presenting in the late teens. The mostcommon phenotype is juvenile myoclonic epilepsy(JME). This presents with tonic–clonic convulsions incombination with myoclonic jerks, which usuallyoccur in the morning. Some patients have aphotoconvulsive response (74), which may manifestas a tendency to have seizures in response to flashesof certain frequencies. A minority of patients alsohave true petit mal absence seizures; these consist ofarrest of activity and loss of contact lasting severalseconds (75). In some patients, seizures occur in thecontext of sleep deprivation, or following alcoholexcess. Other phenotypes, such as early morningtonic–clonic seizures in adolescence, may beencountered. It is rare for primary generalizedepilepsies to present after the age of 25 years.AurasThe aura of a seizure is a subjective feeling that thepatient associates with the beginning of the seizure. Itis in fact the very beginning of the seizure, reflectingthe effects of the seizure discharge while it remainsvery localized, and therefore is usually a feature offocal or secondary generalized seizures. Auras are747574 Interictal electroencephalographic recording with photicstimulation at 19/second (flashes are marked on the trace atthe bottom of the picture). Photic stimulation induces ageneralized spike-wave discharge, typical of a primarygeneralized epilepsy such as juvenile myoclonic epilepsy.75 Electroencephalographic recording during a generalized'petit mal' seizure, showing generalized 3/second spike andwave discharges.
Disorders of consciousness 71particularly common where the seizure originates incortex with sensory or associative functions. If aseizure originates in the sensory cortex, the aura islikely to be one of tingling, the tingling being felt inthat part of the body served by the part of the sensorycortex that is affected. If a seizure originates in theprimary visual cortex, then the aura is likely toconsist of an elementary visual hallucination, seen inthe contralateral visual field. In temporal lobeseizures, a number of auras may occur, the mostcommon being a feeling of déjà vu and an abdominalsensation of butterflies rising up through the chest.Auras consisting of smells and sounds may occur.Complex partial seizuresComplex partial seizures may originate from any partof the cortex, but most commonly originate in thetemporal lobe. From the eyewitness point of view,there is an interruption of activity and a loss ofcontact. The patient tends to stare into space, andmay remain motionless. Automatic activity mayoccur. This most commonly consists of chewing or lipsmacking movements of the mouth, or fiddlingmovements of the hands, whereby the patient willpluck at his clothing or fiddle with some object nearhim. The seizure typically lasts 30–90 seconds, with avariable phase of postictal confusion, drowsiness, orsometimes headache.Table 10 Factors which may lead to a clinicalsuspicion of PNES❏❏❏❏❏❏❏❏‘Fall down, lie still’ type attacks lasting >2 minutes*Recurrent attacks in medical situations (in scanner,clinics)Many major attacks in the day with no morbidityAlternating movementsSide-to-side head movementsEmotional outburst associated with attackSituational responseEyes closed during attack*If shorter may be syncope or cardiac syncope.Frontal lobe complex partial seizures may beassociated with bizarre automatisms, causing them tobe mistaken for PNES, or may simply consist of shortperiods of immobility.PANIC AND HYPERVENTILATION ATTACKSHyperventilation is a common reaction to anxiety.Hyperventilation decreases carbon dioxide levels inthe plasma and induces respiratory alkalosis. Thiscauses instability of excitable membranes and resultsin a number of symptoms, including light-headedness,or a sensation of unreality. Excitability of peripheralnerves causes peripheral paraesthesiae. Wherehyperventilation is marked, spasm of some musclesmay occur, particularly those of the hands andoccasionally the eyes. Rubefaction may be marked.Hyperventilation may induce vasovagal syncope,confusing the diagnostic picture. If it is rememberedthat it is often not possible to obtain a clear history ofa precipitating situation, the history is usually fairlyclear. While there is no diagnostic test as such, thepatient can be asked to hyperventilate underobservation, and the effects then compared to thoseof the events complained of by the patient.PSYCHOGENIC NONEPILEPTIC SEIZURESConfirmation of the diagnosis of PNES is the functionof the specialist, but it is important that all clinicianscoming in contact with epilepsy and similar disordersknow when to suspect PNES (Table 10).Most patients with PNES are young and most(75%) are female. Only 10–15% have epilepsy. Asignificant proportion (probably approximately50%) has a background of sexual or physical abuse,and psychopathology is common. While useful inunderstanding the condition, these factors should beused with care in diagnosing PNES, as theirdiscriminatory value is poor.While the occurrence of social triggering is auseful pointer to PNES, its absence should not allaydiagnostic suspicion; in many patients with PNESthere is no discernible social triggering. There is adistinct tendency for PNES to occur in medicalsituations, and the diagnosis should be considered inpatients who have a history of events during scans,hospital outpatient visits and so on. Patients withPNES may well have events in response to photicstimulation.
72The clinical semiology of PNESPNES are usually frequent. Two types of event areparticularly common. They may be labelled‘convulsive’, where patients have variable movementsof limbs, head, and trunk, and ‘swoon’ where patientsfall down and lie still. PNES tend to be longer thanepileptic seizures, though the ranges overlap. Wherethere are ‘convulsive’ movements, the observation ofalternating limb movements and side-to-side headmovements, especially with coordinated alternatingagonist and antagonist activity (effectively a tremor)or thrashing movements, are highly suggestive ofPNES. Jerking movements do occasionally occur, butare asynchronous. Forward pelvic thrusting is seen ina variable proportion of patients. Signs of emotionaldistress during or after the event suggest PNES.‘False friends’Some clinical features widely thought to indicateepilepsy do in fact occur in PNES, in particular urinaryincontinence and injury (with the exception of thermalburns). PNES are often said not to be stereotyped, buta number of studies have shown this not to be true.Patients may have PNES while appearing to be asleep,and a history of events arising during sleep should notbe taken as conclusive evidence for ES.INVESTIGATIONSRoutine (interictal) EEG should be used with care inthe diagnosis of epilepsy. A single recording has afalse-negative rate of at least 50%. The test istherefore of absolutely no use at all in excluding adiagnosis of epilepsy, and should not be requested forthis purpose. Nonspecific abnormalities are common,especially in certain patient groups (e.g. the elderly,history of brain trauma) and should not be regardedas relevant to the diagnosis of epilepsy. Epileptiformabnormalities (76) occur rarely (1%) in the young,healthy, nonepileptic population, although they areless specific for epilepsy in the elderly and in patientswith a history of brain trauma.EEG should be used as a diagnostic test when thepatient history and eyewitness account are suggestiveof epilepsy, but the clinician is not quite sure. Wherethe history indicates some other type of event (e.g.faint), then the prevalence of epilepsy in thispopulation will be low: few positives will beobtained, and a high proportion of them will be falsepositives. The test should not be carried out in thiscircumstance.There is no point in carrying out an EEGrecording for diagnostic purposes in a patientwho has an unequivocal history of seizure.Neither a positive nor a negative result willchange the diagnosis.In patients in whom the diagnosis of seizure ismade, however, EEG may usefully be carried out forthree indications other than diagnosis. It may aid theclassification of the epilepsy where that is clinicallyuncertain. It can detect a photoconvulsive response,7676 Interictal electroencephalographic recordingshowing left fronto-temporal spikes, maximal inchannel T3, typical of interictal discharge seen inmesial temporal lobe epilepsies.
Disorders of consciousness 73allowing the patient to be advised to avoid certainsituations. If carried out soon after a first seizure, thefinding of epileptiform abnormalities indicates anincreased probability of recurrence.In patients presenting diagnostic difficulties,simultaneous video and EEG recording of events isusually diagnostic. Events do, however, have to bereasonably frequent for this to be practicable.Ambulatory EEG recording may also be used, and insome circumstances simple video recording may beuseful. Electrocardiography (ECG) should be carriedout in any patient whose attacks include loss ofconsciousness. If the clinical picture indicates asignificant possibility of cardiogenic syncope (seebelow), then ambulatory ECG monitoring may beindicated. Referral to a cardiologist should beconsidered. Patients who have had a seizure shouldhave cranial imaging, to exclude a structural causethat may require treatment. MRI is recommended, inview of its greater sensitivity, though CT is moregenerally performed.SUMMARY❏❏❏❏❏❏The diagnosis of epilepsy is normally made onclinical grounds alone.Knowledge of and the ability to diagnose othercommon attack disorders are required.Vasovagal syncope may present featuressuggestive of epilepsy; the key to diagnosis is toidentify triggering factors and the aura.Cardiac syncope should be suspected whenattacks are provoked by exercise or when thereis a family history of sudden unexplained death.Psychogenic nonepileptic seizures are commonamong patients who are thought to haveintractable epilepsy. It is important to knowwhat factors should trigger referral forreassessment of diagnosis.Standard EEG can be useful in diagnosis andclassification, but should never be used to‘exclude’ epilepsy.CLINICAL SCENARIOSCASE 1A 35-year-old male had an episode of loss ofconsciousness. The general practitioner obtainedan account of the event from the man's wife. Shesaid that he had been sitting on the couch theprevious evening, had lost consciousness,slumping to one side. He went stiff, and had hada few jerks, and gradually came round, feelinggroggy for a few minutes.At this point, the diagnosis is one of epilepticseizure. However, it is important to be clear onthe circumstances of any attack, so furtherquestioning is indicated.The general practitioner had not unreasonablydiagnosed epileptic seizure. At the clinic, however,the patient was asked how he had been feelingthat night. He said that he had a cold. He hadbeen sitting on the couch in front of a warm fire,drinking a glass of whisky. He had got up to refillhis glass, and approximately half way to the livingroom had felt unwell.There were three factors that might predisposeto syncope. Firstly, the patient had a cold. Secondly,he had consumed a small amount of alcohol.Thirdly, he was in a warm environment. A change inposture interacted with three predisposing factors toproduce syncope. The initial history placed the onsetof the event on the couch. In reality, the onset wasafter the patient had got up and walked a few steps,and it was necessary to go back a few minutes intime to elicit the history of postural change.He turned round, and went back and sat on thecouch. There was then a gap in his awareness untilhe came round. He was asked in what way he hadfelt unwell just after he got up from the couch. Hesaid that he felt dizzy, and that his vision hadbecome blurred. He identified this feeling as beingsimilar to the one he had on standing up tooquickly, a feeling of dizziness accompanied byblurring and darkening of the vision.The patient fainted in the sitting position,preventing an immediate fall, and preventingrestoration of perfusion to the brain.Unconsciousness and recovery were longer thanusual, and the patient had stiffness and jerks.
74CASE 2A 27-year-old female presented with a history ofepisodes of loss of consciousness. These hadstarted when she was 6 years old and hadoriginally been infrequent, at one or two per year.Over the preceding year, the frequency hadincreased to the point where she was having threeor four per week.At this point the disorder appears likeworsening intractable epilepsy, but a change in thebehaviour of epilepsy should prompt areassessment.She herself had no warning of the attacks.Following them, she felt drained, but had no specificpostictal symptoms. Her husband gave a description.She would become agitated, with a progressivelysevere tremulous movement involving both arms.This would increase over several minutes, andspread to the point where she had violent alternatingmovements of all four limbs, with side-to-sidemovements of the head. This would go on forseveral minutes, occasionally for longer. There wasno cyanosis, tongue biting, or incontinence.This description is not compatible withtonic–clonic seizures, and suggests PNES, possiblyof recent onset on the background of alongstanding seizure disorder.She was admitted for video EEG recording,and several attacks were recorded in the first 3days. All corresponded to the husband’sdescription, and all were PNES. Enquirydiscovered a background of childhood sexualabuse. No interictal EEG abnormalities weredetected.The diagnosis of PNES is established, butthe possibility of a background epilepsyremains. Onset of PNES aged 6 years is notusual, and the events were infrequent for manyyears, suggesting another cause.Her medication was gradually withdrawnafter her discharge from hospital. On review at1 month, her husband said that the attacks hadgreatly reduced, but said that he now realizedthere had been two types of attack, the morerecent, frequent attacks being different fromthe original ones. A detailed description of themore recent attacks was obtained. Thepatient would fall abruptly to the ground,initially floppy, then stiff. She would then goblue. After 30 seconds or so, she wouldrecover her colour, then relax and graduallyrecover consciousness, with a short phase ofconfusion.When different attacks are occurring eyewitnessesmay find it difficult to distinguish between them. Inthis case, it was only when the frequent type of eventceased that the husband could give a clear descriptionof the less frequent type. In this case it was notpossible to establish the diagnosis definitively, but theeyewitness description of the recent attacks is highlysuggestive of cardiac arrest. The fact that the patienthad a history of sexual abuse illustrates the diagnosticlimitations of background factors.An ECG was performed urgently, and showed aprolonged QT interval.There is a good argument for performing routineECG in all patients presenting with attacks of loss ofconsciousness.
Disorders of consciousness75CASE 3A 55-year-old female presented to the neurology clinic complaining of memory difficulties over theprevious few months. On taking a detailed history, it became clear that her problem was intermittent. Shewas actually complaining of short gaps in her memory, at intervals of every few hours or so, thoughsometimes with gaps of a few days. The gaps in memory were brief, lasting 2 or 3 minutes at most.According to her own account, she behaved completely normally during these gaps, and appeared to carryon normal activity. She felt completely normal before the attacks and after.While the initial complaint was of poor memory suggesting a cognitive problem, a paroxysmaldisturbance of memory over a time of seconds or minutes should always arouse suspicion of seizures.The eyewitness account was obtained. It transpired that most of the gaps in memory passed withoutan eyewitness being aware of anything amiss. However, on one occasion she had a gap in her memorywhile driving. The eyewitness reported that she had become disoriented, and seemed unaware of where shewas. She continued to drive, but could not carry on a sensible conversation for 30 seconds or so.This illustrates the tendency for focal epileptic seizures to vary in severity (reflecting a variation in theextent of the propagation of the discharge). In this case, it was only when a more severe seizure occurredthat it became evident that the functional disturbance extended beyond memory.A standard EEG was normal. Ambulatory EEG monitoring was carried out. This showed frequentspike discharges over the left temporal region, which correlated with periods of loss of memory.REVISION QUESTIONS1 Vasovagal syncope:a Presents with lateralized visual aura.b Causes biting of the tip of the tongue.c Is usually infrequent.d May cause myoclonic jerks.e May be provoked by exercise.2 True petit mal seizures:a Are associated with a generalized spike-wavedischarge.b Usually last 30–60 seconds.c Usually originate in the temporal lobe.d May occur many times per day.e May occur in juvenile myoclonic epilepsy.3 Psychogenic nonepileptic seizures:a Are usually frequent.b May cause injury.c Are not stereotyped.d Are associated with synchronous clonicmovements.e Are associated with head injury.Answers1 a False. Lateralized visual aura suggestsepileptic seizure.b True. In tonic–clonic seizures, tongue biting isusually lateral, or the inside of the cheek isbitten.c True.d True.e False. Provocation by exercise should suggestcardiogenic syncope.2 a True.b False. Seizures last several seconds at most.c False. They are generalized seizures.d True.e True.3 a True.b True, though in a minority of patients.c False.d False. Movements are normally alternating ortremulous. Asynchronous jerks mayoccasionally occur.e True. A history of minor head injury is elicitedin approximately 50% of patients.
76ACUTE CONFUSIONAL STATESMyfanwy ThomasINTRODUCTIONAbout 20% of acute medical admissions come underthe broad heading of neurology, though not necessarilydue to a precise and easily defined primary neurologicalcondition. Alerted arousal (coma) and disturbedcontent of consciousness (e.g. confusional states) areencountered on a daily basis in the acute medical wards.Many patients, particularly the elderly, have comorbidillnesses that cross medical disciplines. This isparticularly true of the acute confusional state, whichcan be produced by a systemic illness and disordersremote from the central nervous system; in practice,more than half of elderly patients with a confusionalstate have a non-neurological disease underlying it.However, the same is not true of younger persons whereprimary neurological disease must be the prime suspect.Definition of the acute confusional stateConfusional states are behavioural syndromes, whichcan be caused by a number of physical illnesses.Confusion results in the patient being unable toformulate thoughts coherently; concentration isimpaired, attention cannot be maintained or isconstantly shifting, and thought processes are slowedand disorganized. Orientation for time, place, andperson is disturbed. The immediate world becomes abewildering place as patients cease to comprehend andregister what is happening around them, put this incontext, draw inferences from such happenings, andplan appropriately taking account of changingcircumstances. Sometimes, this is accompanied byvisual or auditory hallucinations. The sleep–wake cycleis disturbed and there is either increased (agitated) ordecreased (hypoactive) psychomotor activity. Theonset is almost always acute or subacute. Once theunderlying physical cause is treated, confusion rarelylasts more than 1 week. The prognosis depends oncausation, but if the underlying cause is eradicated thenrecovery can be expected to be complete.Some diseases which lead to stupor or comahave as part of their evolution an acute confusionalstate. Confusion is a characteristic feature indementia, but dementia is a chronic disorder anddoes not form part of this chapter. Finally, it isworth remembering that intense emotion mayinterfere with coherence of thought.Sometimes there is a practical difficulty in decidingbetween confusion and dysphasia (see page 94).However, features central to discriminating betweenthe confused and the dysphasic are retention ofconcentration and the speed of attempting a reply. Theexaminer should ask ‘are they able to listen attentivelyto what is being asked?’; ‘Do they struggle to replywhile concentrating?’ If so, they are dysphasic ratherthan confused.Anatomy of attentionThe ascending reticular activating system (ARAS) inthe upper brainstem and the polymodal associationareas of the cortex must be intact for normalattention (77). The function of the ARAS in thiscontext is to prime the cortex for stimulus reception.However, a lesion of the ARAS produces sleep orcoma rather than impaired attention or a confusionalstate. Once primed, the polymodal association cortexfocuses this arousal energy for attention, and lesionsin these cortical areas will affect selective attention.Other areas feed into these polymodal areas; theprefrontal cortex is particularly involved in77Primarysensory cortexLimbicsystemPolymodalassociationcortexThalamicnucleiReticularsystemSensoryinput77 Diagram to show the parameters of attention.
Disorders of consciousness 77maintaining attention. The limbic system and theprimary sensory cortex also feed into these polymodalareas. It is thought that the limbic system has quite amajor role in delirium because of its connections withthe temporal lobe polymodal areas.As well as maintaining attention to the subject inhand, the attention system must also monitor theenvironment to detect any new or changing factors towhich the brain must respond, must decide whichneed a response and which can be ignored, and thenmust be able to shift attention to any of these newstimuli. Blood flow studies have shown that thepolymodal cortical areas are the regions of monitoringand shifting. Specifically, the posterior parietal cortexand other polymodal areas feed back to the reticularnucleus of the thalamus, which itself modulatessensory input to the cortex from the thalamus.In summary, sensory input arrives in thethalamus, which relays it to the primary sensorycortex from where it is relayed to the polymodalassociation areas (prefrontal cortex and posteriorparietal cortex) where selective attention takes place.Additional input arrives directly from the reticularsystem and the limbic system.PathophysiologyTheoretically, a structural lesion in the attentionsystem (though never in the ARAS) may cause aconfusional state, but the vast majority of cases aredue to a diffuse metabolic or infective cause. Thepathological changes found at postmortem areminimal and entirely nonspecific. The diffuse causesand the fact that there is a universal susceptibility todeveloping acute confusional states (it can happen toall of us) suggest that there is biochemical orenzymatic impairment to a common metabolicpathway in neurones. A diffuse metabolic cause caninterrupt neurotransmitters such as acetylcholine andnoradrenaline. These two neurotransmitters areperhaps particularly significant, since acetylcholineincreases the responsivity of cortical neurones toother inputs. Noradrenaline increases postsynapticevoked responses. Anticholinergic drugs, which werewidely used to treat Parkinson’s disease, areparticularly likely to induce confusion, suggestingthat perhaps cholinergic function is the keydysfunctional neurotransmitter in the acuteconfusional state. Furthermore, the pathwaysinvolving the ARAS and the polymodal cortex may beespecially vulnerable, since these two areas have themost polysynaptic chains.Anatomy and pathophysiologyThere is no one single abnormal finding in theconfused state; the pathology depends on theunderlying cause. For example, in a patient who isconfused as part of an evolving brain disorder such asa metabolic disturbance or a severe systemic infectionsuch as pneumonia, there may be few or nopathological changes in the brain. The electroencephalogram(EEG), however, may show markedslowing, with the predominant rhythm being in theslow theta (4–8 Hz) or, not uncommonly, the deltarange (
78words beginning with a certain letter or from specificsemantic categories, e.g. animals. Patients withimpaired attention can produce few examples, andmay return to a previous category or perseverate.Disorientation for time is always present at somepoint in acute confusion and is usually an earlyfeature. There is invariably a disturbed appreciationof the passage of time. As the confusional stateworsens, there is disorientation for place, and laterfor person.The memory disturbance is mainly due to poorattention. New material or incoming stimuli are notappropriately registered. Therefore, immediaterepetition of a name and address will be poorlyperformed and the clinician may need to repeat theinformation several times before the patient cancorrectly or even approximately repeat. Long-termmemory is intact; the problem is to access it in thepresence of impaired attention. Sometimes confabulation(a wildly inaccurate account of events) occursas part of a confusional state.FluctuationsDuring the confusional state there are sometimesmarked swings in attention and arousal. These mayoccur unpredictably and irregularly during the dayand worsen at night. ‘Sundowning’ with restlessnessand confusion at night is frequent. Sometimes aconfusional state is only apparent at night when thesleep–wake cycle is disturbed, with drowsinessoccurring during the day and wandering at night.Once the patient has recovered from the acute state,there is a dense amnesia for the period of the illness,though if the illness has been marked by fluctuationsthere may be islands of memory remaining.Thought and speechThe organization and content of thought aredisturbed. In the lethargic subtype, the stream ofthought is slowed. In delirium, the stream ofthought may be accelerated but, in both subtypes,there is difficulty in ordering thoughts to carry outa sequenced activity and goal-directed behaviour.Even mildly confused patients will have problemsformulating a complex idea and sustaining a logicaltrain of thought. Confusion can be understood asan inability to maintain a stream of thought withthe usual coherence, clarity, and speed. The patienthas problems with concept-formation and tendstowards a rather concrete type of thinking. Askingthe patient to explain a proverb such as ‘a rollingstone gathers no moss’ can test this. The cliniciancan test to see whether the patient can detectdifferences and similarities between classes ofobject (similarity judgement), and whether they candefine single words.Sometimes, the thought content has a dream-likequality and it may be dominated by the patient’sconcerns, beliefs, and desires. There are often brief,poorly elaborated, and inconsistent delusions whichhave a paranoid content, such as that their life is indanger or that relatives have been killed.The patient’s speech may reflect this muddledthinking, in that it is imprecise, shifting from subjectto subject, is usually circumlocutory and goes off at atangent. There are hesitations, repetitions, andperseverations. Often the rate is abnormal andhurried with a dysarthria.Perceptual deficitsPerception refers to the ability to extract appropriateinformation from the environment and one’s ownbody and to integrate this information so that it canbe useful and is meaningful. Clearly an attentiondeficit accounts for many of the perceptualdisturbances; the most common disturbance isdecreased perception: the patients are missing thingsgoing on around them. However, there may bedisturbances of vision and hearing, visualhallucinations occurring particularly in the youngerpatient. These are vivid and coloured. Sounds may bedistorted or accentuated. Body image may be affectedwith a perceived alteration of size or shape. Feelingsof unreality and depersonalization are common, butpsychotic auditory hallucinations with voicescommenting on behaviour do not generally occur inthe acute confusional state. Generally, patients withdelirium rather than the lethargic subtype develophallucinations and those patients who are alcohol- orbenzodiazepine- dependent and have been withdrawnfrom them are particularly likely to hallucinate.There are some additional perceptual phenomenaworth mentioning: an altered time sense whennonrelated events are juxtaposed. Sometimes theunfamiliar is mistaken for the familiar. Bizarrereduplicative phenomena may occur, when a patientperceives a person with two heads but one body.Similarly, reduplicative paramnesia, or the replacementof persons or places, occurs because of an inability tointegrate recent observations with past memories.
Disorders of consciousness 79Emotion and behaviourEmotional disturbances are common: there isemotional lability with swings from agitation andfearfulness to apathy or depression. Generally, theimpression is of someone who is rather perplexed, butthis can suddenly change to a frightened, angry, andaggressive patient. The mood changes occur withdelusions and impaired perception. It has beensuggested that these are a direct result of aconfusional state on the limbic system and itsregulation of emotions.As described earlier in this chapter, behaviouralchanges are always present with two contrastingpatterns. These patterns are not fixed and patientscommonly alternate between them. The first patternis the hyperalert state: this is the excitable patientwhose gaze and attention are constantly shifting.These are the patients who develop vividhallucinations. Any stimulus will receive animmediate and excessive response with pressure ofspeech and abnormal and excess emotion such ascrying or laughing inappropriately. This isaccompanied by increased physical activity andrepetitive and purposeless behaviour such as pluckingat the bedclothes repeatedly. Attempts to restrain thepatient if they try to get out of bed produce anaggressive outburst. Coupled with this is evidence ofautonomic hyperactivity such as pupillary dilatationand tachycardia. The lethargic subtype is quitedifferent: these patients drift in and out of sleep if notstimulated and lie quietly. Their replies are slow andtheir speech is often incoherent. Although they maybe hypoalert, such patients can be experiencingdelusions.CAUSES OF THE ACUTE CONFUSIONAL STATEThe easiest way to classify causes and formulate aninvestigative approach is to subdivide causes into fourgroups (Table 11).Infectious non-neurological illnessConfusion can be an accompaniment to an infectiousnon-neurological illness, particularly pneumonia or aurinary infection in the elderly. Confusion oftenaccompanies a septicaemia and forms part of thepostoperative state. It is also worth remembering thatan acute confusional state in a child can be due to alobar pneumonia. Focal or localizing neurologicalsigns do not accompany this type of acute confusionalstate.Neurological diseaseNeurological diseases producing focal or lateralizingsigns on neurological examination can causeconfusion. Vascular disease, particularly the so-called‘top of the brainstem’ syndrome, often due to smallinfarcts involving the posterior circulation, where thebasilar artery divides to form the two posteriorcerebral arteries, is an example. There are small endarteries,the mesencephalic arteries that supply theposterior part of the thalamus. Infarction of thesepresents with a confusional state. Almost anyinfarction or haemorrhage of the temporal or parietallobes (but particularly involving the right parietallobe) can present with confusion, as can lesions of theupper brainstem. As this is ‘site-sensitive’ rather than‘pathology-sensitive’, any pathology, be it vascular,neoplastic, or infective in this area may causeconfusion. Cerebral trauma with concussion canproduce acute confusion with disorientation.Acute bacterial meningitis presents with headacheand increasing confusion. Tuberculous meningitis hasa rather more gradual onset than does bacterial orpurulent meningitis, and often presents with fatigue,apathy, lethargy, and somatic symptoms, sometimesTable 11 Causes of acute confusional statesAcute non-neurological illness:❏ Commoner in the elderly❏ No focal neurological signsNeurological disease:❏ Focal or lateralizing signs❏ Vascular disease❏ Trauma❏ Meningitis❏ Encephalitis❏ Subarachnoid haemorrhage❏ Drugs and alcohol❏ Postictal confusionChronic confusion with lethargy or retardation:❏ Metabolic disease❏ Hypoxia❏ Severe infectious disease❏ Post-operativelyDrug intoxication
80over days or even weeks. The somatic symptoms(headache, neck stiffness, and vomiting) tend to bepredominant in bacterial meningitis, particularly inyounger patients, whereas confusion may outweighthe somatic symptoms in the elderly, but this is not anabsolute rule.Herpes simplex virus (HSV) encephalitis usuallybegins with a seizure and lateralizing signs but otherviral causes may not, e.g. the encephalitis associatedwith infectious mononucleosis or measles.In subarachnoid haemorrhage, the accompanyingneurological signs should be apparent, but it is worthremembering that in a young person rupture of a smallaneurysm along the course of the middle cerebralartery as it winds along the Sylvian fissure mayproduce no or very little neck stiffness. This is becausethe reactive swelling of the brain surrounding theaneurysm presses on the aneurysm and prevents muchblood leaking into the subarachnoid space. Postictalconfusion is usually short and should be self-limiting.Drugs and alcoholMore correctly, this should really be ‘withdrawal fromdrugs and alcohol’. In the chronically habituated oraddicted patient, the withdrawal from alcohol willproduce an acutely delirious state, delirium tremens,as described earlier. (Although benzodiazepinewithdrawal does not produce an acute confusionalstate remember that acute withdrawal in a chronicallydependent patient can produce seizures.) The use ofbarbiturates is now rare. Acute withdrawal producesan initial improvement for 8–12 hours. This is rapidlyfollowed by tremor, nervousness, and insomnia, butthe initial improvement may last up to 2 or even 3days in the chronically addicted patient. Thesesymptoms can be associated with generalized seizuresand these may be followed by a state very similar todelirium tremens. This though is variable and somepatients have seizures without delirium while othersdevelop delirium without seizures. Acute psychosisshould make the clinician consider the possibility ofdrug abuse. Opiates in large doses can produce aclouded, agitated state of consciousness. Some of thedrugs previously commonly prescribed forParkinson’s disease, such as the anticholinergics, cancause confusion. Also, unfortunately some of thedrugs which are currently used, such as L-dopapreparations and dopamine agonists, have similarside-effects.Confusion with lethargy or retardationConfusion can occur with an underlying medical orsurgical disorder and can occur with any of themetabolic disorders such as hepatic encephalopathy,uraemia, or hypoglycaemia. It can arise as a part ofthe hypoxic state following resuscitation after cardiacarrest, or indeed in hypoxia of any cause such ascongestive cardiac failure. Equally, confusion mayoccur in CO 2retention. This type of confusion canoccur as part of severe infectious diseases (the list ofpotential infections is vast but rare ‘opportunisticinfections’ need to be considered in theimmunosuppressed).Postoperatively, particularly in the elderly orfrail patient, confusion may be seen. Thepathophysiological basis for this is commonly amixture of drug (sedatives/analgesics)intoxication and (possibly) a degree of hypoxia.SUMMARY❏❏❏❏❏❏In an elderly patient who has become confused,consider an underlying infection.If there is no infection, look at the drugs theymay have been taking.In a young patient, consider a neurologicalcause.Remember that an acute confusional state canpresent either with agitation and tremulousnessor with lethargy.There are no typical postmortem features in theacute confusional state; any pathologicalchanges are minimal and nonspecific.Remember that Wernicke’s encephalopathy doesnot just occur in the alcoholic patient but canoccur in the context of repeated vomiting andpoor nutritional intake.
Disorders of consciousness 81CLINICAL SCENARIOSCASE 1A 77-year-old right-handed male was admitted to the Acute Medical Receiving Unit in his local hospital fromhome. He was unable to give any information himself but was accompanied by his son and daughter-in-law.They said that he was normally an independent man, looking after himself and, since being widowed, livingon his own. His health was good for a man of his age.This is therefore a sudden change and not someone who has slowly deteriorated over a period of weeksor months. There is no suggestion that he has a dementing illness nor is there any suggestion of an acutedeterioration in a chronic disease.He had telephoned them complaining of chest pain and when they arrived at his house, found he hadvomited and he said he had been off his food. His relatives were alarmed that he could give them no otherinformation and he did not seem able to answer their questions at all so they brought him to the localhospital.His symptoms suggest an acute physical cause plus some other factor.When he was admitted to the ward he was conscious, but made no spontaneous complaints. When askeddirectly whether he had any chest pain, or whether he had been sick, he gazed around him and eventuallyreplied 'yes' to the questions but was quite unable to add further details. When pressed for furtherinformation he could not supply any, tending to ignore the questions and gaze around the ward (an oldfashionedNightingale ward) which seemed to surprise him. It became clear that he was vague and distracted.Attempts at a formal neurological examination were fruitless as he either ignored requests (e.g. to follow amoving finger) or turned towards some other stimulus such as a noise outside the curtain. Intermittently, hewould make a brief effort to concentrate, only to be distracted by a fresh stimulus. However, when askedwhether he drank a lot, he indignantly denied this and his relatives equally indignantly denied this.This man is not dysphasic. In spite of being distracted, it is clear that he comprehends and is capable ofa response, although intermittently. His distractedness, his vagueness and, most importantly, the testimonyof close relatives that this is quite unlike his usual behaviour, suggest that this is an acute confusional state.An attempt was made to carry out some tests of higher cortical function. When asked to name the daysof the week, he gazed around before settling himself back on the pillow. He did not seem to understand whenasked to name five animals and became irritated when pressed to try. When asked where he thought he was,he said 'the market' (he had been an auctioneer). He then started giving a rambling and confused story aboutsomething being found in his garage but he could not elaborate on this. When his son tried to assure hisfather that everything there was safe, the patient became agitated and accused him of stealing something, itwas not clear what, and he tried to get out of bed. At this point he started accusing the admitting clinicianand became more restless and difficult to manage. Further attempts at formal examination were fruitless.This is now quite clearly an acute confusional state. Formal examination is often difficult, in factsometimes impossible. But we still have no clue as to why it has occurred. Earlier in the history he hadmentioned chest pain, when he phoned his relatives. It is possible he may have had a myocardial infarct (MI),perhaps with hypotension.At this point, noticing that he had Dupuytren's contractures, he was asked whether he would like adrink. He brightened up immediately and said yes. On examination of his respiratory system, he was foundto have coarse crepitations bilaterally but particularly at the left base. Abdominal examination showed hisabdomen to be soft and his liver was not enlarged.This seems to be an elderly man who drank regularly. Some of the clinical picture may be alcoholwithdrawal, perhaps combined with chest infection, although a MI has not been ruled out.(Continued overleaf)
8278CASE 1 (continued)An MI screen was negative. However, 48 hours afteradmission, he became agitated and confused. Hisrelatives admitted at that point that he consumedalcohol on a regular basis; they thought this might be asmuch as half a bottle of whisky per day and he wastherefore treated as having alcohol withdrawal.However, on the following day when it was realizedthat his liver function tests were normal, neurologicalreview was requested. On the assumption that hisconfusion was due to alcohol withdrawal, he had beengiven a benzodiazepine and had become very drowsy,making assessment difficult.On examination, he was an elderly rather plethoricman who said that he had no complaints about hishealth. When asked, he said that he had worked as anauctioneer for many years but gave no other detailsabout himself although pressed to do so. Hiscerebration was slow and he tended to perseverate. Hehad recurrence of all primitive reflexes (pout, glabellartap, and palmo-mental responses). His fundi werenormal with rather attenuated arteriosclerotic vesselsand he had a full range of ocular movements. However,he had neglect of his left visual field. There was noobjective weakness of his limbs. Sensory testing wascarried out and it was not possible to say whether ornot he had neglect, because by that stage of theexamination the patient was not able or willing tocooperate. His reflexes were all very sluggish apart fromhis ankle jerks, which were absent. His plantarresponses were abnormal in that his left plantarresponse was extensor, the right equivocal.Sensory testing is often considered the most difficultpart of the neurological examination, as the patientmust first comprehend what is being done, must be ableto cooperate with the examination, and be able toformulate an appropriate reply, clearly not possible in aconfused patient. The focal signs, with visual neglect,hint of a right parietal lesion in an elderly man with aprevious history of steady alcohol intake and signs of achest infection. His chest X-ray and his computedtomography scan (78) confirmed this.78 Computed tomography scan of right parietalstroke.
Disorders of consciousness 83CASE 2A 54-year-old female with long-standing anxiety and depression was admitted to the Medical Unit at hergeneral practitioner’s (GP) request. Her husband provided all information on admission.This is unusual for a woman of 54 years and immediately alerts the clinician to a new situation.Whether it is an organic change or a functional change is as yet unknown.He said that over the previous 6 months his wife had slowed down and she had started to shuffle. Hermobility had deteriorated quite dramatically over 3 days and, because she had fallen many times at home,he asked the GP for a home visit. He added that although her walking and her behaviour had beenunusual in the past, he had never seen his wife like this. Over 48 hours she had become confused and thenmute. The patient herself made no complaints of any sort but sat gazing in front of her. She could not orwould not answer any questions. In reply to a series of standard questions, her husband said that she hadnot vomited, nor had she complained of headache and had never had a seizure.This is a subacute situation. It is clear that this patient has been deteriorating gradually until the 3days before admission, when matters had accelerated. This is not the history of a bacterial or a viralinfection, but could be due to trauma. Her GP thought that for some reason her chronic psychotic statehad decompensated, although he also wondered about a hysterical fugue state. Both these are goodsuggestions, but the question is then, why should her psychotic state have decompensated?Her husband was adamant that although she had fallen many times, she had not hit her head and hadnever been unconscious.Therefore, the recent deterioration is not due to trauma and there is no explanation for her symptomsover the past few months. It is possible that due to her long history of anxiety and depression, drugtherapy may be relevant. Or the possibility of some superadded infection?Her husband said that she had been taking phenelzine (45 mg) each day, zopiclone (15 mg) everynight, and one tablet of diazepam (5 mg) and one of prochlorperazine (5 mg) each three times a day. Onchecking the referring letter from her GP, it emerged that she was also taking tramadol (50 mg), MSTContinus (15 mg), a cox-2 inhibitor, and beclomethasone and seretide inhalers.Finally, the possibility of an inherited disorder should be pursued; this patient had no family history ofany neurological disease. There is now a good history, and an account of a gradual deterioration with amore rapid change over the past few days. Trauma has been ruled out, and the history does not sound likeinfection.On examination, she was conscious, agitated, groaning, and sweating profusely, with a tachycardia of128 per minute. Her temperature was 37.7°C (99.9°F). Her eyes were open and her pupils reacted to lightdirectly and indirectly. Her neck, trunk, and limbs were rigid with clonus in both legs and a generalizedhyperreflexia with extensor plantar responses. She moved around the bed spontaneously. There was nofacial weakness. There was a pout reflex but no other primitive reflexes. There was no rash, althoughlivedo reticularis was noted over the abdomen. Heart sounds were normal and her chest was clear. Therewas no lymphadenopathy and no abdominal masses. Although the patient was conscious, she made noverbal response to either questions or commands. Her concentration was limited and she was easilydistracted, repeatedly trying to sit up.It was thought that infection was a possibility and so following a CT scan, which showed some atrophy,her cerebrospinal fluid (CSF) was examined, and a range of blood tests were requested. Clinically, the picturelooked like the neuroleptic malignant syndrome, although the drugs and doses the patient had taken did notwholly support this diagnosis.(Continued overleaf)
84CASE 2 (continued)Initial investigations:WCC: 13.3 × 10 9 /l ALP: 306 IU/lESR: 3.2 mm/h AST: 167 IU/lCRP: 21 mg/l CK: 9499 IU/lBilirubin: 30 µmol/lWCC: white cell count; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; ALP: alkalinephosphatase; AST: aspartate aminotransferase; CK: creatine kinase.Although the initial diagnosis clinically was thought to be a septicaemic illness, the very high CK levelsuggested the neuroleptic malignant syndrome. The prochlorperazine was stopped and she was givensupportive treatment with a rapid improvement in her clinical state from admission, to being symptomfree,apart from her depression.CASE 3A 55-year-old female presented to a District General Hospital with a week’s history of a flu-like illness.During the first 3 days she had been very lethargic and rather drowsy, but brightened up on the fourth dayand so returned to work the following day. At work she had had a seizure; eyewitnesses said she had becomevery pale, her eyes rolled up, and she fell, becoming rigid. The seizure lasted about 1 minute and anambulance was called and she was brought to the Accident and Emergency Department. The informationwas given by her daughter, the patient herself being very drowsy. The patient had no history of epilepsy, hadnot had a head injury and her general health was excellent. She had not vomited and her complaints duringthe previous few days had been of feeling 'shivery' and aching all over, including a headache.This is not just a postictal state, though part of the confusion may be related to the seizure. This patienthas never had a seizure before and it was preceded by a febrile illness with an alteration in her alertness. Nomedical help was sought initially as her family assumed she had the flu until she had the seizure.On examination, she was confused and drifted into sleep unless stimulated. She answered questionsslowly but appeared to have little understanding. Her temperature was 37.7°C (99.9°F). There was no neckstiffness; Kernig’s sign was negative. Her fundi were normal and there were no focal neurological signs.There is the hint of a subacute confusional state; there is no clinical evidence of meningitis.Over the next few hours there was no improvement in the patient’s clinical state, she remained drowsy andconfused, and her initial blood tests were normal apart from a gamma-glutamyl transferase (GT) of 87 IU/l.Over the next few hours her temperature rose slightly to 38°C (100.4°F) and later that day to 39°C (102.2°F).These results provide further confirmation that this is not a postictal confusion, but there is anadditional illness, which does not clinically look like acute meningitis, although this has to be considered.There is no history of head injury or of any drug ingestion. The course and tempo of the illness suggest anencephalitic illness.A CT scan shortly after admission was normal and lumbar puncture was carried out. The CSF had amild increase in protein of 0.77g and WCC of 457 × 10 9 /l, 99% of these were lymphocytes. Staining andculture for bacteria were negative.(Continued on page 85)
Disorders of consciousness 8579CASE 3 (continued)This is very suggestive of encephalitis, witha mildly raised protein and a lymphocytosis.Could this be tuberculous meningitis, which inreality is a meningoencephalitis and often has asubacute or even a gradual onset? This isunlikely given the short history and the clinicalexamination gave no hint of any meningiticfeatures. Moreover, tuberculous meningitis ispredominantly basal meningitis with a highCSF protein and cranial nerve signs. PositiveHSV polymerase chain reaction (a sensitive andspecific test for herpes simplex) and a magneticresonance image (79) showing swelling of theright temporal lobe confirmed the clinicalsuspicion of herpes simplex encephalitis. HerEEG showed the classical periodic slow waveand sharp wave discharges over the righttemporal region.79 Diffusion-weighted magnetic resonanceimage of herpes simplex virus encephalitis,showing temporal lobe involvement.REVISION QUESTIONS1 In an acute confusional state the stream ofthought can be either slowed or accelerated.2 A lesion of the ascending reticular activatingsystem may cause a confusional state.3 Fluctuations in a confusional state may occur byday and by night, but are more marked by night.4 In an acute confusional state, remote memory isintact.5 There is no universal susceptibility to developingan acute confusional state.6 The predominant EEG rhythm in an acuteconfusional state is fast theta or alpha rhythm.7 Autonomic hyperactivity, e.g. a tachycardia, isusually present.8 The acute confusional state is alwaysaccompanied by increased psychomotor activity.9 Visual hallucinations are rarely seen in the acuteconfusional state.10 In an acute confusional state there isdisorientation for time before that for place orperson.11 The two subtypes of a confusional state nevercoexist in the same patient.12 Following recovery from an acute confusionalstate, the patient has an amnesia for the periodof confusion.13 There are specific features found at postmortemfollowing the acute confusional state.14 Emotional lability is a frequent accompanimentto the acute confusional state.15 The acute confusional state lasts
86Disorders of cognitionMEMORY DISORDERSJohn GreeneINTRODUCTIONPerhaps the commonest cognitive complaintpresenting in the clinic is gradually worseningmemory. Symptoms of forgetfulness may simply bedue to mild depression, but equally can be theharbinger of neurodegenerative illness such asAlzheimer’s disease. In order to exploit fully theclinical examination in making the diagnosis, it isessential for the clinician to have a detailedunderstanding of the anatomy, physiology, andpathology of memory. There are many different typesof memory, e.g. learning a name and address,recalling a previous holiday, knowing the capital ofFrance. These different types of memory rely ondifferent brain structures. Disease affecting differentareas of the brain can therefore result in differenttypes of memory impairment.MEMORY AND ITS DIVISIONSThe taxonomy of memory is complex, but thebroadest distinction is between explicit and implicitmemory (80). Explicit memory refers to memorieswhich can reach consciousness. By contrast, implicitmemory refers to unconscious learned responses,including conditioning and motor skills, which relyon cerebellum and basal ganglia.Knowledge of the neural substrates underlyingthe above subcomponents of memory allows theclinician detecting a memory deficit to knowwhich brain structures are affected.Explicit memory is divided into short-term (orworking) and long-term memory. Strictly speaking,short-term memory refers to a system that retainsinformation for seconds at most, while long-termmemory refers to memories held even for as short asa few minutes. These terms are widely misused byclinicians, who use short-term memory to meanevents of a few weeks’ or months’ standing, and longtermmemory to refer to memories of years’ standing.The terms will be used here as correctly defined byneuropsychologists.Short-term memory can be tested by digit span orby asking a patient to immediately repeat a name andaddress. Working memory requires the frontal lobes,language areas for verbal material such as digit span,80Explicit(declarative)MemoryImplicit(procedural)80 Diagramto show thecomponentsof memory.LTM: longtermmemory;STM: shorttermmemory.STM(working)LTM Conditioning Priming Motor skillsVerbalSpatialEpisodic(event)Semantic(fact)
Disorders of cognition 87and nondominant hemisphere for visual material.Asking a patient to recall a name and address given10 minutes previously, or anything longer tests longtermmemory. Long-term memory is furthersubdivided into episodic and semantic memory:episodic memory refers to personally experiencedevents (e.g. recalling a conversation earlier in the dayor a previous holiday), while semantic memory refersto facts, concepts, and words and their meaning (e.g.boiling point of water, capital of France). Episodicmemory and semantic memory require different brainregions. While semantic memory utilizes mainlydominant temporal neocortex, the structures crucialfor establishing and retrieving episodic memoriesappear to be components of the limbic system (81).The limbic system comprises the hippocampus,the thalamus and mamillary bodies, and the basalforebrain. Although all limbic structures are involvedin episodic memory, different components havediffering roles (Table 12). The hippocampus isprimarily involved with laying down new memories,and consolidating recently acquired ones.Hippocampal pathology can cause difficulty encodingnew ongoing memories (i.e. an anterograde amnesia)and impaired consolidation of those very recentlyacquired, before injury (i.e. a temporally-limitedretrograde amnesia). The thalamus, by contrast, isinvolved not only in laying down new memories, butalso in retrieving previously acquired memories.Thalamic pathology (e.g. Korsakoff’s syndrome,thalamic infarction) will manifest clinically as ananterograde amnesia with a temporally extensiveretrograde amnesia, i.e. patients have difficulty inrecalling events which occurred years or decadesbefore the onset of the pathology.CingulateCorpusgyruscallosum81FornixMemory disordersThe practical relevance of knowing the above anatomyis that identifying a specific type of memory disorderwill allow the clinician to localize the site of thepathology. Accepting the above subdivisions, it shouldbe noted that there are many different types of memorydisorder, the commonest of which will be describedhere. Memory disorders may be pure (i.e. amnesias) ormixed (with additional cognitive deficits, i.e. confusionif acute, dementia if chronic). Table 13 presents thecauses of memory impairment.MamillothalamictractAnteriornucleus ofthalamusHippocampusMamillary body81 Diagram illustrating the anatomy of the limbic system.Table 12 Divisions within long-term memoryType Role Neural substrateEpisodic New learning, retrieval Limbic systemof autobiographicaleventsSemantic Knowledge of Temporal neocortexthe worldImplicit Motor skills, Basal ganglia,e.g. playing acerebellummusical instrumentTable 13 Causes of memory impairmentType Pure amnesia MixedTransient Transient global amnesia DeliriumTransient epileptic amnesiaDrugsPsychogenic amnesiaPersistentDementiaHippocampal❏ Early Alzheimer's disease❏ HSV encephalitisDiencephalic❏ Korsakoff's syndromeHSV: herpes simplex virus.
88Acute transient disorders of episodic memoryMany pathological conditions are responsible fortransient impairment of episodic memory. Any disorderthat transiently impairs medial temporal function willresult in a reversible episodic memory deficit.Transient global amnesia is a disorder in whichthe patient becomes acutely amnesic for severalhours, usually with a cycle of repetitive questions. Itis benign, tends not to recur, and is thought to have amigrainous basis. Psychogenic amnesia results in lossof previous autobiographical memory and may resultin loss of personal identity, which almost never occursin organic disease. There is usually a majorprecipitating life event, and usually a psychiatricbackground. The condition may last for up tomonths. Epilepsy can occasionally present astransient episodes of pure amnesia, but this usuallyoccurs in the context of more obvious seizures.Chronic disorders of episodic memory – the amnesicsyndromeHere, there is inability to learn new information, butthere can also be a retrograde amnesia of variableduration. It is broadly divided into hippocampal anddiencephalic amnesia. Hippocampal damage results indense anterograde amnesia with temporally limitedretrograde amnesia, while parahippocampal pathologycan cause a more extensive retrograde amnesia.Hippocampal pathology may arise as a result ofconditions as varied as herpes simplex virus (HSV)encephalitis, hypoxia, or early Alzheimer’s disease.In diencephalic amnesia, in addition toanterograde amnesia, there is an extensive retrogradeamnesia with a temporal gradient (i.e. relativepreservation of distant memories). A classic exampleof this is Korsakoff’s syndrome, in which acutethiamine deficiency results in damage to themamillary bodies. Bilateral thalamic infarcts or thirdventricle tumours may also damage the diencephalon.Disorders of semantic memoryDamage to temporal neocortex classically occurs insemantic dementia (temporal variant fronto-temporaldementia) (82). The pathology affects the temporalneocortex and tends to spare the hippocampus,resulting in profound semantic memory impairmentwith relative sparing of episodic memory. Onoccasion, HSV encephalitis or stroke may selectivelyimpair semantic memory.Mixed disorders of episodic and semantic memoryThe above discrete syndromes are useful fordelineating the functional neuroanatomy of memory.In practice, mixed episodic and semantic memorydisorders are more common, such as occur in neurodegenerativedisease such as Alzheimer’s disease.CLINICAL ASSESSMENTHistory taking from the patient and relative is crucialto the diagnostic process for memory disorders. Inassessing a patient complaining of memoryimpairment, the following questions need to beaddressed:❏ Is there a memory problem?❏ If yes, what aspect(s) of memory is/are affected?❏ What is the neuroanatomical substrate?❏❏❏❏❏❏Is the memory problem transient or chronic?Is it a pure amnesia or a mixed picture (i.e. is itpurely a memory problem, or are others aspectsof cognition such as language or visuoperceptualfunction also impaired)?Are the memory complaints organic?Does the tempo of the illness suggest the likelypathological process?If the clinical picture suggests dementia, is thepathology likely to be cortical or subcortical?Which disease is causing the dementia?The patient interviewPatients with memory complaints are often awarethat the possibility of dementia is being considered.Initial questions regarding background (occupation,family circumstances) will establish rapport, andestablish whether history taking from the patientsthemselves will be informative. It is helpful toestablish whether the patient knows why they havebeen referred to the clinic. Further open-endedquestions regarding how symptoms began, whatcurrent difficulties there are, and the effect this hashad on activities are worth recording, as theyillustrate the extent of the problem.It is imperative to know what is meant by ‘poormemory’. This can be used to mean forgetting thenames of things or people (semantic memory),forgetting new information or past events (episodicmemory), or forgetting what one has gone into aroom to get (attention). A further useful distinction isbetween memories acquired before and after onset ofpathology (i.e. anterograde and retrograde). It is,however, not always easy to determine the date ofonset of pathology, especially in early dementia,
Disorders of cognition 89whereas this is straightforward in the case of headinjury or acute stroke. Specific probing questions canelucidate which aspects of cognition are impaired.With regard to the subdivisions within memory, themost important issue is whether the patient can learnnew information, as impaired anterograde episodicmemory is the first manifestation of Alzheimer’sdisease. This can be assessed by whether the patientcan recall conversations, describe current affairs, orcurrent TV programmes. Has the patient started tomake lists, become repetitive, or started frequently tolose things at home? Retrograde memory can beassessed by asking autobiographical questions (e.g.holidays, previous houses) or asking about old newsevents, which occurred before the onset of symptoms.Semantic memory can be assessed by testinggeneral factual knowledge (e.g. capitals of countries,names of people, places, and things). Is there a recenthistory of word-finding and naming problems, or loss8282 Magnetic resonance image showing anterior temporal lobeatrophy in semantic dementia, i.e. temporal variant frontotemporaldementia.of meaning of less common words? The patient’semployment, education, and premorbid intelligencequotient (IQ) must be taken into account in assessinga patient’s cognitive status, especially when testingsemantic memory. Specific difficulties indicating alanguage disorder include word-finding problems,word errors, grammatical mistakes, difficultyunderstanding words and grammar, or problems withreading and writing. Ability to dress and routefinding are a measure of visuo-spatial function. It isalways worth enquiring about mood, energy, sleepingand eating patterns, as depressive pseudodementiacan superficially resemble early dementia.The informant interviewRelatives can often identify when symptoms were firstnoted, and what the initial symptom was. This is ofdiagnostic use as different dementias presentspecifically, while latterly they merge. The suddennessof onset and rate of progression are againdiagnostically useful. How symptoms sequentiallyhave affected activities of daily living is alsoinformative.Other historyPast medical history should pay particular attentionto previous head trauma, epilepsy, meningitis, orpsychiatric illness. Drug history is important, as isfamily history. Alcohol and other drug consumptionis also relevant.Clinical examinationIn addition to the general and neurologicalexaminations, the bedside cognitive examination iscrucial in the patient with memory disorder. While itis important to assess all aspects of cognition (e.g.language, visuo-spatial function) to see if the memorycomplaint is part of a more widespread dementingillness, the following will focus on memory inparticular.The Mini-Mental State Examination (MMSE) is awidely used test, initially developed as a screeningtool for dementia. Due to its brevity it has severallimitations. In terms of this chapter, it has deficienciesin assessing memory. The ability to learn and retainnew information is very important in bedsidecognitive testing of memory, as impaired delayedrecall is often the first indication of early Alzheimer’sdisease. In the MMSE, the patient is asked toremember three items. The ability to subtract 7 from100 repeatedly is then tested, and then the patient is
90asked to recall the three items. This is not properlydelayed recall, as insufficient time is allowed to passbefore testing recall. An intelligent patient may doserial 7s very quickly, and may in fact have beenholding the three items in working memory duringthis task, so that recall of three items is not in facttesting true delayed episodic memory.In an effort to improve on this, theAddenbrooke’s Cognitive Examination (ACE)significantly expands on bedside testing of memory.In addition to the MMSE, the patient is also given aname and address to remember. To ensure that theyhave had a chance to register the new information,the address is given three times. Secondly, delayedrecall is not tested until towards the end of the ACE,with many intervening items having been given in theinterim. It is thus a proper test of delayed recall.The ACE also assesses semantic memory throughcategory fluency (as many animal names in 1 minute),and in more rigorous testing of object naming. It isbrief enough to use in a busy outpatient setting. It isclearly shorter than a full neuropsychologicalassessment but serves to screen those patients whomight require more detailed neuropsychology.Bedside cognitive function comprises tests oforientation, attention, frontal executive function,memory, language, calculation, and praxis and righthemisphere function. Given that this chapter refers toforgetfulness, comment is restricted to thosecomponents that assess memory.Working (or short-term memory) may be assessedusing digit span, with items presented at one persecond. The patient should be able to repeat at leastfive digits. For practical purposes, the most importantpart of memory testing is whether the patient canlearn and retain new information. This is best doneby giving a name and address three times, testingimmediate registration after each presentation, andthen testing recall after an interval of not less than 5minutes. True hippocampal pathology, such as earlyAlzheimer’s disease, should result in a patient scoring7/7 on each of the trials of immediate recall, yetscoring 0/7 on delayed recall. By contrast, subcorticalpathology, such as depressive pseudodementia, resultsin impaired immediate registration, e.g. 1, 3, 5/7, yetthe proportion retained after an interval is abovebaseline, e.g. 3/7. This distinction is by no meansabsolute, but is a useful clinical pointer. Quizzing thepatient about previous conversations and so on mayalso test anterograde memory.Should a patient fail to recall a name and address,this may be due to either impaired encoding of thisinformation, or failure to retrieve it. By then giving achoice of three items, should the patient tend tochoose correctly, then a retrieval defect seems likely.If, however, they score at no more than chance, thenit is likely that information was not encoded in thefirst place. More detailed assessments of anterogradeverbal memory include story recall and word-listlearning.Anterograde nonverbal memory impairmentusually parallels that of verbal memory disturbance.Damage to nondominant hippocampus can causeanterograde nonverbal memory impairment, butthere is no easy bedside test of this. Walking a routeoutside the clinic and asking the patient to repeat itcan suffice. Delayed recall of the Rey figure (anabstract design, see 40), also tests nonverbal memory.Remote memory may also be assessed, e.g. previousmajor news events, but also autobiographicalmemory. This is necessarily more subjective and thereis significant variation in individuals’ knowledge offamous events. Autobiographical memory alsorequires cross-verification with relatives to ensurethat plausible responses are not merely confabulation.Semantic memory may be assessed by categoryfluency, asking for the names of as many exemplars aspossible in 1 minute, e.g. animals. Object naming alsotaps semantic memory.SUMMARY❏❏❏❏The clinician cannot accept a complaint of ‘poormemory’ at face value, but must further clarifywhat this means.Different areas of the brain subserve differentaspects of memory.It is often best to interview the patient andinformant separately for part of theexamination, as the presence of the patient caninhibit the informant from relaying a clearaccount of the symptoms.It is necessary to ascertain whether the cognitivedeficit is restricted to memory, or whether otherareas of cognition are involved.❏ Inability to recall a name and address given 10minutes previously is a useful screening test,which can be of some use in detecting patientswith early Alzheimer’s disease.
Disorders of cognition 91CLINICAL SCENARIOSCASE 1A 66-year-old male presents to the Memory and Cognitive Disorders Clinic complaining that hismemory is failing. He has been troubled with this for a few months. He has been failing to keepappointments and finds it difficult to follow weekly TV series from one week to the next. He hasstarted using lists for the first time. He denies low mood. His wife has noted forgetfulness for over ayear. It was of insidious onset, and is progressing. He has become repetitive, and does not learn newinformation. He appears otherwise unchanged, with no alteration of personality.Insidious progressive forgetfulness is very suggestive of early dementia. Examples of his memoryproblems are of failing to keep appointments or to remember TV programmes from one week to thenext, i.e. true episodic memory deficit. The patient denies low mood, making depressivepseudodementia less likely. No early change in personality makes a frontal dementia unlikely.On bedside cognitive examination, he was oriented except for the date. Cognitive deficits wererestricted to memory. While immediate registration of name and address was normal, delayed recallwas poor at 0.Normal bedside cognitive testing with very poor delayed recall demonstrates a specific deficit ofepisodic memory. As definitions of dementia require impairment in at least two areas of cognition, heis not by definition demented. However, the very early changes of Alzheimer’s disease affect theperihippocampal areas, resulting in a pure amnesia initially. He thus is not demented, but hisprogressive amnesia is likely to be due to Alzheimer’s disease.Magnetic resonance imaging (MRI) showed bilateral hippocampal atrophy (83), while singlephoton emission computed tomography revealed bilateral temporo-parietal hypoperfusion (84). Hewas commenced on anticholinesterases.838483 Magnetic resonance image showing medialtemporal atrophy in Alzheimer's disease.84 Single photon emission computed tomography scanshowing temporo-parietal hypoperfusion in Alzheimer'sdisease.
92CASE 2A 55-year-old female presented complaining ofpoor memory and concentration. This had comeon fairly suddenly 6 months previously. Sheadmitted to early morning wakening and poorappetite. She felt low, but was adamant that thiswas a consequence of her poor memory. She wasworried she had the beginnings of dementia. Herfamily described her as having become veryapathetic and no longer attending to much aroundher. She had also become more irritable.Subacute onset of symptoms is not in keepingwith early dementia. She has some somaticmarkers of depression, as well as low mood.Apathy and irritability are in keeping withdepression.On cognitive assessment, she was poorlyoriented for time. She had difficulty with serial 7s,could not spell WORLD backwards and digit spanwas reduced to four. Category and letter fluencywere both reduced. Anterograde memory wasimpaired: she had great difficulty with immediateregistration of name and address. She had atendency to answer, 'I don’t know' to manyquestions.She has problems with tests of attention andconcentration. The tendency to say, 'I don’t know'or to give up easily is suggestive of depressivepseudodementia. In organic pathology such asdementia, the patient will usually try to do thetest, even if they subsequently fail. This is typicalof depressive pseudodementia. Imaging wasnormal, and she responded well to antidepressants.CASE 3A 60-year-old male was admitted with acuteconfusion under the influence of alcohol. He wasfound to be dehydrated, and was given intravenousdextrose infusion. On recovery, it was noted that hetended to ask nursing staff the same questionsrepeatedly. He also insisted that he was 25 years old,and needed to go back to his army base.Repeated questioning suggests that he is amnesic.His insistence that he is 25 indicates that theamnesia also has a significant retrogradecomponent. The sudden onset of his symptomsprecipitated by alcohol raises the possibility ofWernicke’s encephalopathy followed by Korsakoff’spsychosis.His sister commented that he was sure it wasthe 1960s, and he appeared to have no knowledgeof his personal life events since then. He wasunable to learn new information about the family,which she had told him. He had been living aloneon an inadequate diet, and had been drinkingheavily before admission.Inability to learn new information shows thathe has anterograde amnesia. His lack ofknowledge of personal events since the 1960sdemonstrates retrograde amnesia. Theinadequate diet suggests that he may havethiamine deficiency. Administration ofintravenous dextrose in hospital can precipitateWernicke–Korsakoff syndrome.On general examination, he had evidence ofa mild peripheral neuropathy, but also had abroad based gait, and was unable to tandem gait. Onbedside cognitive examination, he was disoriented fortime, thinking it was 1968. Letter fluency was reducedwith perseverations. On testing memory, he registeredname and address, but delayed recall was 0. He had anextensive retrograde memory deficit, and could notdescribe public or autobiographical events more recentthan the 1960s. Language and visuo-spatial functionwere normal.(Continued on page 93)
Disorders of cognition 93CASE 3 (continued)His cognitive deficit is restricted to memory.Absent delayed recall confirms anterogradeamnesia. This is acute onset anterograde amnesia.There is also a significant retrograde amnesia,extending back 40 years. MRI showed alteredsignal in the periaqueductal grey matter of themidbrain (85). It transpired that when presentingto the Accident and Emergency Department, hehad been given IV dextrose but no thiamine cover,and this had precipitated acute Wernicke’sencephalopathy with subsequent Korsakoff’ssyndrome. Ataxia and peripheral neuropathy alsooccur in this condition.85REVISION QUESTIONS1 All memories reach conscious awareness.2 Remembering last month’s holiday is short-termmemory.3 Premorbid intelligence does not affect bedsidecognitive performance.4 It is easy to determine the time of onset ofneurodegenerative disease.5 A normal Mini-Mental State Examination scoreexcludes Alzheimer’s disease.6 Digit span is a useful bedside test of short-termmemory.7 Korsakoff’s syndrome results in a significantretrograde amnesia.8 With memory impairment, loss of personalidentity usually indicates a nonorganic cause.9 Herpes encephalitis may selectively impair eitherepisodic or semantic memory.10 Insight may be retained early in Alzheimer’sdisease.85 Magnetic resonance image showing increasedsignal in periaqueductal grey matter of themidbrain, consistent with Korsakoff's syndrome.11 Depression can superficially resemble earlydementia.12 Hippocampal pathology primarily results in ananterograde rather than retrograde amnesia.13 Short-term memory relies on the frontal lobes.14 Retrograde memory can be tested by askingabout autobiographical memories, and also byasking about famous public events.15 Semantic memory can become impaired only ifthere is also episodic memory impairment.Answers1 False.2 False.3 False.4 False.5 False.6 True.7 True.8 True.9 True.10 True.11 True.12 True.13 True.14 True.15 False.
94SPEECH AND LANGUAGE DISORDERSJohn GreeneINTRODUCTIONSpeech and language are crucially important foreveryday life. The student must therefore have a goodgrasp of the anatomy and physiology of language,how the process may be upset by disease, and how toassess the patient with a possible speech or languageproblem. The role of clinical examination inneurological diagnosis involves two stages. The first isto know what level in the nervous system isresponsible for the symptoms. This can be at the levelof brain, spinal cord, peripheral nerve,neuromuscular junction, or muscle. The second stageis to ascertain the nature of the pathology responsiblefor the symptoms. The tempo of onset of thesymptoms is of use here in that sudden onsetsymptoms may well have a vascular basis, whileinsidious onset of progressive symptoms may be dueto tumour or neurodegenerative disease.In order to be able to deduce from the nature ofa language disorder where in the nervous systemthe symptoms are arising from, the student mustfirst study normal language.Anatomy and physiology of languageIt is important firstly to distinguish between languageand speech. Language refers to the entire system usedfor communication, including understanding others’speech, reading, speech output and writing, as well asother forms of expression such as gesticulation andsign language. Speech simply refers to the oralproduction (the mechanics) of language.The understanding and production of languageutilize brain regions specializing in language workingin unison with the motor system responsible for thearticulation and expression of speech. The languagecentres are located in the left hemisphere in nearly allright-handers, and in about 60% of left-handers. Thefollowing account of language is necessarilysimplistic. In truth, the brain does not work througha linear set of actions, but functions through multipleparallel streams of processing (parallel distributedprocessing). Having said that, the following remains aclinically useful teaching aid.The comprehension of language will be describedfirst. The heard word is initially processed byauditory cortex in the temporal lobes. The signal isthen sent upstream to Wernicke’s area in the superiortemporal gyrus. This area allows comprehension oflanguage and initiation of speech output. This is thenpassed forward to Broca’s area (inferior frontalgyrus), which is responsible for supervising theproduction of language (86). Adjacent motor cortexthen prepares the motor act of speech, and signals aresent down cortico-bulbar fibres to the musclescontrolling speech. These descending fibres aremodulated by the cerebellum and basal ganglia andterminate on motor nuclei of cranial nervescontrolling tongue and larynx. The appropriatemuscle action results in desired articulation andspeech (87).Reading and writingReading differs from listening in that the occipitalcortex processes language visually. Information isthen passed forward to Wernicke’s area forunderstanding of what is being read. Normalprocessing of written material involves two processes.One is a superficial system in which words are readand pronounced simply on the basis of the letterstrings, e.g. MINT is pronounced as one wouldexpect from the component letters. For the other(deep) system, correct pronunciation is intimately tiedup with meaning, e.g. PINT can only be correctlypronounced if the patient knows the meaning of theword. With a regular word such as MINT, there is nodisparity between the superficial and deep systems.With irregular words such as PINT, there is adisparity in pronunciation between the surface and86BAAFSMGWAAG86 Diagram illustrating the principal language areas of thebrain. AF: arcuate fasciculus; AG: angular gyrus; BA: Broca’sarea; SMG: supra marginal gyrus; WA: Wernicke’s area.
Disorders of cognition 9587 Diagram to illustrate theanatomy of articulation.CerebellumRB4A3L211 Speech initiated87234Descending cortico-bulbar pathway from lefthemisphere to nuclei X and XIIConnection through corpus callosum to motorcortex of right hemisphereDescending cortico-bulbar pathway from righthemisphere to nuclei X and XIIA - Cortico-bulbar pathwayB - CerebellumC - Extrapyramidal systemD - Nuclei of lower neurons of X, XII cranial nervesCAHypoglossal nucleus andnerve (XII) to tongueDNucleus ambiguus ofvagus nerve (X)supplying soft palate,pharynx and larynxThe extrapyramidal andcerebellar systems modulatearticulatory muscle actiondeep systems, but the deep system overrules, and theword is pronounced correctly (88). Should readingaloud be required, Broca’s area is activated, and theabove cascade occurs. Writing requires motor areascontrolling hand movements to be involved in theproduction of written symbols.Written wordVisual analysis88Pathology of language and speechIn caring for a patient with an apparent disorder ofspeech or language, the clinician must first establishwhether there is a true language impairment (i.e. adysphasia), or whether the deficit is due to moreperipheral damage. If there is an apparent deficit incomprehension of language, it is important toestablish whether basic hearing and vision aresufficient to allow the heard or seen word to bepassed upstream to become accessible to language, orwhether it is a true language deficit. Similarly, interms of speech output, it is again important toestablish whether there is a true language outputdisorder (i.e. expressive dysphasia), or whether theproblem is more peripheral (i.e. impaired motorcontrol of facial and vocal musculature to allowspeech expression). Dysphasia refers to a loss ofcomprehension, production, or both of spoken(and/or written) language. Dysarthria refers to poorarticulation of speech yet with language intact.Analysis bymeaningSpeech outputSpoken wordAnalysis bysound88 Diagram to illustrate the dual route hypothesis of reading.
96Dysphonia refers to impaired vocal cord control,which affects speech. Pathology affecting anyindividual part of this extensive system can result inspecific language or speech impairment. The nature ofthe language deficit varies depending on the site ofpathology. Thus clinical examination can help theclinician to localize what level in the neuraxis isresponsible for the impairment.DISORDERS OF LANGUAGEClassification of aphasiasGiven the understanding of the systems involved inlanguage, it is possible to address how selective lesionsto the language and speech regions result in specificaphasia syndromes. The prime factors to be assessed indetermining the type of aphasias are: fluency,repetition, comprehension, and naming (89).Fluent speech is of normal rate and normal phraselength. Damage to anterior language areas results innonfluent (or expressive) aphasia, in which speech isslow, and said to resemble ‘telegraphic’ communication.Fluency is impaired in Broca’s aphasia, but isspared in Wernicke’s aphasia.Impaired repetition indicates pathology in theperisylvian language areas. An isolated impairmentof repetition is called conduction aphasia, whileselective sparing of repetition occurs in thetranscortical aphasias.Comprehension is impaired in Wernicke’saphasia, and relatively spared in Broca’saphasia.While naming is impaired in all the aphasias,the nature of the naming defect can provide clues asto the type of aphasia, e.g. phonemic paraphasias inBroca’s aphasia.Neuroanatomy of the aphasiasWernicke’s aphasiaLesions to Wernicke’s area produce problems withdecoding of spoken and written language (fluentdysphasia). Here, speech is fluent and there is littleeffort in speaking. Paraphasias (i.e. word errors)occur. These may be semantic paraphasias (e.g.APPLE for ORANGE), or new words (neologisms)may occur in the acute stage. The disorder issometimes described as jargon aphasia (or a wordsalad). Syntax (correct use of grammar andnonsubstantive words) is relatively preserved.Auditory comprehension is always impaired andrepetition is impaired. For instance: ‘We redo, er, theplace, em, near the nettek, thing with wheels’, insteadof ‘We went to the seaside by car’.Transcortical sensory aphasiaTranscortical sensory aphasia is identical toWernicke’s aphasia, except repetition is preserved.The pathology usually involves cortical or deep whitematter damage at the periphery of the perisylvianlanguage areas.89FluencyComprehensionRepetitionWernicke’sImpairedReducedTranscortical sensoryFluentNon-fluentPreservedImpairedNormalReducedNormalConductionAnomicGlobalPreservedReducedBroca’sNormalTranscortical motor89 Diagram to show the classification tree of aphasias.
Disorders of cognition 97Conduction aphasiaSpeech is fluent but paraphasic, with significantimpairment of repetition, and is due to perisylvianpathology. Asking the patient to repeat ‘No, ifs, andsor buts’ can test this.Broca’s aphasiaBroca’s aphasia is nonfluent, with distorted languageoutput and disturbed syntax. Speech is slow andlaboured, often described as telegraphic speech, withphonemic paraphasias (e.g. SITTER for SISTER).Broca’s aphasia occurs due to damage to the frontoparietalregion in general, rather than specificallyisolated damage to Broca’s area. For instance: ‘Thetea in, um, cup. Put on tagle.’ instead of ‘Put the cupof tea on the table’.Transcortical motor aphasiaThis is similar to Broca’s aphasia except thatrepetition is preserved.Anomic aphasiaAnomia is a poor localizing sign, and is present in allaphasias. For instance: ‘It’s a, er, the thing you putwater in to, a cup’ instead of ‘It’s a glass’.DISORDERS OF READING, WRITING, AND SPEECHThe dyslexiasAbility to read is one of the most sensitive markers oflanguage dysfunction, and in aphasia there is nearlyalways some impairment of reading aloud orcomprehension of text.There are several different types of readingdisturbances (dyslexias). Analysis of the type ofreading deficit allows classification of the dyslexia,aiding anatomical localization. Broadly speaking,dyslexia may be peripheral (i.e. due to impaired visualdecoding of the written word) or central (due to abreakdown in true language resulting in deviationfrom the normal meaning of words).Peripheral dyslexiasAlexia without agraphiaIn this disorder, written material cannot beunderstood, yet the patient can recognize words speltaloud. Writing is preserved, but patients cannot readwhat they have written. It is usually due to disease(usually infarction) of the medial aspect of the leftoccipital lobe and splenium of the corpus callosum,and there is normally an accompanying righthomonymous hemianopia (see page 104). Due to theleft occipital insult, visual information is only relayedto the right occipital cortex (90). The signal cannot beconveyed from there to Wernicke’s area, thus thepatient cannot read. Pathways from right occipitalcortex can, however, reach more anterior languageand motor areas, and the patient is therefore able towrite down what is being seen.Neglect dyslexiaHere, the patient does not attend correctly to lefthemispace, and the inability to read the left side ofwords is therefore part of the more generalphenomenon of neglect.Central dyslexiaIt is possible to understand subtypes of centraldyslexia, by referring to the above dual routehypothesis of reading. If there is damage to the deepsystem, then the ability to pronounce irregular wordscorrectly will be impaired. Words can then only bepronounced by the superficial system, i.e.phonetically based on letter strings. PINT will betherefore pronounced to rhyme with MINT, i.e. aregularization error. Regularization errors areInsulaWernicke’sareaLSite of lesionproducing purealexia90 Diagram to show alexia without agraphia due to leftoccipital lesions involving the splenium of corpus callosum.R90VentricleCorpuscallosumSpleniumPrimaryvisualcortex
98therefore a sign of damage to the deep semanticsystem. (Semantics is the referential meaning of words,the database on which one draws to give meaning toconscious experiences.) If the surface system isimpaired, words can no longer be processed letter-byletter.The only way words may be read is thereforethrough meaning. Patients with such a deficit will beunable to pronounce words for which they do notknow the meaning. (They will also be unable topronounce plausible nonwords, e.g. CHOG, but thisonly becomes apparent on bedside testing.)The dysgraphiasDrawing analogies with reading, writing disorders(dysgraphias) may be due to true languageimpairment, or may be peripheral in origin.Central dysgraphiaSimilar to reading impairment, damage to the deepsemantic system results in difficulties with spellingirregular words, e.g. PINT. By contrast, damage tothe surface writing system results in patients onlybeing able to spell words they know the meaning of,and they are unable to spell nonwords.Peripheral dysgraphiaIn a patient who has difficulty writing, thepreservation of oral spelling informs the clinician thatlanguage is not impaired, so the dysgraphia must bedue to peripheral mechanisms. In dyspraxicdysgraphia, written letters show errors, often invertedor reversed, with abnormal copying. It usually occurswith dominant parietal lobe damage, e.g. M Tinstead of MEAT. Should writing exhibit a wide leftmargin, or a tendency to miss out the first few lettersof individual words (e.g. WER instead of FLOWER),this suggests that the dysgraphia is simply onemanifestation of a bigger picture of neglect, i.e.neglect dysgraphia.AEDysarthriaDysarthria refers to impaired articulation of speech inthe context of normal language. Pathology at anylevel below the language centres may be responsible.Damage to cortex or cortico-bulbar fibres (the bulbarupper motor neurones) results in spastic dysarthria.Speech is strained, sometimes said to resemble thespeech of Donald Duck.Cerebellar pathology results in scanning speech,where syllables are not correctly spaced, and speech isslow. This is called ataxic dysarthria. Basal gangliadisorders result in monotonous quiet speech, socalledhypokinetic dysarthria. Damage to X or XIInuclei or nerves results in a flaccid dysarthria. Speechis nasal, and ultimately progresses to total anarthria(loss of speech).CAUSES OF LANGUAGE DISORDERWhile the above classification helps to localize wherethe problems causing language and speech disorderare, the rate of evolution of the symptoms helps todetermine the nature of the pathologic process (Table14). For example, sudden onset of speech or languageimpairment is often due to stroke, which is thecommonest cause of speech and language impairment.Twenty to 30% of all strokes have some degree oflanguage or speech impairment, and this can be theonly symptom, with no evidence of hemiparesis orother neurological impairment. By contrast, insidiousonset and progressive impairment are suspicious oftumour or neurodegenerative disease.CLINICAL ASSESSMENTSpecific ‘focused’ history takingThe patient and carer should be asked specificallyabout problems understanding others’ speech andwriting, and also whether the patient has a problemTable 14 Causes of language impairmentAphasia ❏ Focal lesions– Stroke– Tumour– Abscess❏ Dementia– Alzheimer's– Fronto-temporalDysarthria ❏ Spastic– UMN, e.g. stroke, tumour❏ Ataxic– Cerebellar lesion❏ Hypokinetic– Basal ganglia, e.g. Parkinson'sdisease❏ Flaccid– LMN, e.g. MNDLMN: lower motor neurone; MND: motor neurone disease;UMN: upper motor neurone.
Disorders of cognition 99with speech or written output. Problems inunderstanding language may first arise during threewayconversations, or when on the phone (due to thelack of nonverbal cues). Enquiries regarding readingand writing should also be made.Bedside cognitive testing of languageIt is essential to cover the following areas:spontaneous speech, naming, comprehension,repetition, reading, and writing.Spontaneous speechThis is the most important aspect of languageexamination. In particular, attention should be paid tofluency, grammar, any paraphasias (incorrect words),word finding, and articulation. Fluency refers to phraselength. This should not be confused with pauses due toword-finding difficulty. The nature of any paraphasiasmay also be illuminating. Phonemic paraphasias (e.g.SPORAGE for ORANGE) occur in damage to anteriorlanguage areas, as may neologisms (new words).Semantic paraphasias (e.g. FRUIT or ORANGE forAPPLE) are indicative of semantic memory impairment.NamingNaming should comprise items of varying degrees offrequency, e.g. nib, hand, as well as watch, as lowfrequency words may be lost before high frequencywords. The type of naming error varies depending onthe type of aphasia. Patients with Broca’s aphasiaproduce phonemic paraphasias, while semanticparaphasias may occur in Wernicke’s aphasia.ComprehensionComprehension needs to be assessed at differentlevels of complexity, e.g. ‘Point to the coin’, then ‘Putthe watch on the floor’ then ‘Point to the item usedfor telling the time’.RepetitionThis should be tested for monosyllabic single words,then polysyllabic single words, and finally sentences.Phrases using small grammatical function words,such as ‘No ifs, ands or buts’, are particularly difficultfor patients with conduction aphasia. Impairedrepetition indicates perisylvian pathology.ReadingImpaired reading aloud does not necessarily implyimpaired reading comprehension. Asking the patientto read, ‘Close your eyes’, may test the latter. Whilereading skills usually parallel spoken languageabilities, this is not always the case. If a readingproblem is identified, it is important to then establishwhat type of dyslexia is present. Although this isbeyond the scope of the undergraduate, analysis ofperformance on letter identification, readingexception words and nonwords, and analysis of thetype of reading errors allow subclassification of thetype of dyslexia.WritingScreening for the presence of dysgraphia may beachieved by asking the patient to write a few sentences.If a deficit is detected, then the ability of the patient towrite regular and exception words to dictation allowsfurther subdivision of the dysgraphia. If the formationof letters hints at a motor problem in writing, then thesubsequent finding of normal oral spelling indicatesthat this is a peripheral dysgraphia and is not truelanguage impairment.InvestigationsBedside cognitive testing allows the clinician todetermine whether there is language impairment, andwhat type of dysphasia is present. The choice ofinstrument that the clinician should use depends onavailable time.The Mini-Mental State Examination (MMSE) is awidely used test, originally designed to screen fordementia in the community. On account of its brevityit has several limitations. One major drawback of theMMSE is that the language items are too easy, suchthat a patient with early language impairment maystill perform at ceiling on the language items of theMMSE. The Addenbrooke’s Cognitive Examination(ACE) includes and expands on the MMSE. Withregard to language, it incorporates timed tests (verbalfluency, producing as many exemplars in 1 minute).Naming, comprehension, repetition, and reading aremore fully addressed.While it is difficult for the clinician to do muchbeyond this in the busy outpatient clinic, the idealmeasure of language performance would encompass aformal neuropsychological assessment. This resourceis, however, scarce. Although clinical classification ofthe aphasia should result in a confident localization ofthe lesion, imaging is invariably done. Althoughcomputed tomography (CT) is more widely available,magnetic resonance imaging (MRI) remains theimaging modality of choice for localizing brain lesionsand determining their type. Such structural imaging
100can be complemented by functional imaging such assingle photon emission computed tomography(SPECT), which shows cerebral blood flow. FunctionalMRI (fMRI) identifies which parts of the brain areactive when performing a particular cognitive task, butthis is primarily used on a research basis.SUMMARY❏A logical approach to history taking and clinicalexamination will allow the student to determineand classify the nature of a language or speechdisorder, as well as narrowing the list ofdiagnostic possibilities.❏❏❏It is important to distinguish between truelanguage impairment (aphasia) and disorders ofspeech articulation (dysarthria).All clinicians should be competent at bedsidecognitive testing, as back-up neuropsychology isnot universally available.A competent bedside examination of languageshould comprise the following areas:spontaneous speech, naming, comprehension,repetition, reading, and writing.CLINICAL SCENARIOSCASE 1A 60-year-old right-handed female presented suddenly with inability to speak or to understand languageand a right hemiplegia. She was hypertensive, diabetic, and a smoker. As she slowly recovered, she seemedto comprehend language, but still had major difficulties communicating.Sudden onset hemiplegia and language impairment in a right-handed patient are strongly suggestive of astroke affecting the left hemisphere. The return ofcomprehension but with significant language outputdifficulties suggests Broca’s aphasia.On bedside cognitive assessment, she had reduceddigit span, and also had markedly reduced verbalfluency. On examining language, spontaneous speechwas nonfluent, with impaired articulation andgrammatical errors. There were also phonemicparaphasias. Although comprehension wassuperficially spared, it was poor for command withcomplicated syntax. Naming was poor, but improvedsomewhat with phonemic cues. Repetition was poorfor sentences. On testing reading, surface dyslexiawas seen. Writing involved simplified grammar.This is all as would be expected in Broca’saphasia. The impairment of repetition shows thatthis is not transcortical motor aphasia. In summary,the aphasia is characterized by being nonfluent,with impaired repetition and relatively wellpreservedcomprehension. This is characteristic ofBroca’s aphasia. CT showed a left fronto-parietalstroke (91). Although she improved gradually overthe months, she was left with significantimpairment of speech output.9191 Computed tomography scan showing extensive lefthemisphere stroke resulting in Broca's aphasia.
Disorders of cognition 101CASE 2A 65-year-old male presented to the Accident andEmergency Department with acute confusion. Thepatient was unable to give a history, but his familydescribed him as waking up talking gibberish, andunable to understand them. His behaviourotherwise seemed appropriate. He washypertensive and diabetic, but otherwise well.Although he initially appeared to be in anacute confusional state, his otherwise normalbehaviour suggests that this may be a disorderspecifically of language comprehension.On cognitive assessment, he was talkingconstantly, and unable to carry out commands.Testing of cognition was difficult on account oflack of patient cooperation. It was, however, notedthat spontaneous speech was fluent, but withnumerous neologisms. He was unable to obeycommands. Naming was markedly impaired, andhe could not comply with repetition. Readingand writing could not be assessed.It is difficult to assess nonlanguagecognitive function in the presence oflanguage impairment, as conveying what isrequired relies so heavily on language.However, the neologisms, anomia, andimpaired repetition are compatible with aprimary language disorder. Thisconstellation indicates Wernicke’s aphasia.The combination of fluent aphasia,impaired comprehension, and repetition ischaracteristic of Wernicke’s aphasia. CTconfirmed a left hemisphere haemorrhageundercutting Wernicke’s area (leftsuperior temporal region) (92).9292 Computed tomography scan showing left hemispherehaemorrhage resulting in Wernicke's aphasia.
102CASE 3A 55-year-old male and his wife presented to the clinic,complaining that his speech had been gradually deteriorating overthe last year. He was still able to understand others’ speech, andcould read. His own speech was becoming increasingly slurredand unintelligible to others. His writing had also become rathermessy, and he felt less steady on his feet.Slurred speech is in keeping with dysarthria rather thandysphasia. Although dysarthria can be due to lesions at severalareas (cerebellum, basal ganglia, cranial nerves), the involvementof writing and gait suggests cerebellar (or possibly basal ganglia)involvement. The tempo of insidious progressive symptoms iscompatible with neurodegenerative illness or a slow-growingtumour.On bedside cognitive testing, his speech was slurred and slow,and syllables were not clearly distinguishable. Naming,comprehension, repetition, and reading were normal. Writing wasuntidy. There were no other specific cognitive deficits. Theneurological examination revealed bilateralpapilloedema. There was gaze-evoked nystagmuson left lateral gaze. Finger–nose impairment andtruncal ataxia were both evident.CT scan showed a low-grade tumour in thecerebellum (93). Although this man presentedwith speech problems, he had a dysarthria ratherthan aphasia. Other neurological findings were inkeeping with his dysarthria being of cerebellarorigin.9393 Computed tomography scan showing a left cerebellartumour.
Disorders of cognition 103REVISION QUESTIONS1 The right hemisphere is dominant for languagein the majority of left-handers.2 Phonemic paraphasias (spoonerisms) tend tooccur with Broca’s aphasia.3 Repetition ability allows discrimination betweenconduction aphasia and the transcorticalaphasias.4 Reading ability is often spared in the aphasias.5 The ability to write, yet be unable to read whathas been written, indicates functional ratherthan organic disease.6 Slow monotonous speech occurs inextrapyramidal disease.7 Language impairment cannot be due to strokeunless there is also evidence of hemiparesis.8 If a patient cannot write, yet has preserved oralspelling, then their symptoms are not organic inorigin.9 The ability to converse by phone is a verysensitive marker of early language dysfunction.10 Analysis of the type of naming error can identifywhich part of the language system is impaired.11 If reading aloud is impaired, then readingcomprehension must be impaired.12 The ability to correctly read irregular words islinked with knowledge of meaning of the word.13 Normal performance on the Mini-Mental StateExamination excludes the possibility of languageimpairment.14 Difficulty naming objects occurs in mostaphasias.15 Clinical classification of an aphasia renderssubsequent imaging unnecessary.Answers1 False.2 True.3 True.4 False.5 False.6 True.7 False.8 False.9 True.10 True.11 False.12 True.13 False.14 True.15 False.
104Disorders of special sensesVISUAL LOSS AND DOUBLE VISIONJames Overell, Richard MetcalfeINTRODUCTIONMost people take good vision for granted. Such is itsimportance in everyday life that disturbance or loss ofvision, even for seconds, often causes major alarm. Itcan be very difficult for even the articulate witness todescribe visual disturbances, particularly transientepisodes. Particular care should be taken whenlistening to visual complaints. This chapter willconsider simple and relatively common disorders ofvisual sensory and oculomotor function. It assumesthat there is no optical or retinal disorder, and doesnot attempt any discussion of either visual integrativefunction beyond the primary visual cortex, or morecomplex disease of the oculomotor system above thebrainstem nuclei, concerned with eye movements.The student must remain aware that patients do notrespect such artificial constraints.Once the image of an object is centred on the foveaof the retina, assuming there is no optical defect, thehigh definition colour-sensitive cones of that regionprovide neural information to the primary visualcortex. Here, features of the object such as shape,colour, and motion are encoded for use in those partsof the occipito-parietal and occipito-temporal corticesconcerned with the integration of vision with otheraspects of sensation, both past and present.Functional anatomy and physiologyRetina and optic nerveLight (‘information’) is detected by the retina, andpassed to the optic nerve, the head of which is visibleon fundoscopy as the optic disc (94). Information fromthe temporal (outer) visual field is detected by the nasal(inner) portion of the retina, while information fromthe nasal visual field is detected in the temporal retina(95). Similarly, light from the top half of the visual fieldpasses to the bottom half of the retina, and vice versa.Retinal and optic nerve lesions can produce severalpatterns of visual deficit, the common examples ofwhich are shown in 96.Optic chiasm and optic tractThe anatomy of the visual field pathways andresultant visual field defects are shown in 97. Theoptic nerve leaves the orbit through the optic foramenand passes posteriorly to unite with the opposite optic94a94b94c94d94 Fundoscopy. a:normal fundus;b: papillitis in apatient with acuteoptic neuritis;c: papilloedema(swelling of theoptic disc) in apatient with raisedintracranialpressure from abrain tumour;d: Optic atrophy ina patient withmultiple sclerosisand multipleprevious episodesof optic neuritis.
Disorders of special senses 105Leftvisualworld95RightvisualworldLaMaculaBlind spotR96bcLefttemporalretinaLLeft andright nasalretinaRRighttemporalretinaL R L R96 Diagram to show patterns of monocular visual field loss.a: central scotoma (a round defect centred at fixation),commonly seen in optic neuritis; b: centrocaecal scotoma (acentral defect that extends to involve the blind spot),commonly caused by toxins such as alcohol or tobacco;c: arcuate scotoma (an arc-shaped defect extending from theblind spot), common in glaucoma.95 Diagram to show the relationship between anatomy andphysiology of the visual fields. Light information from thetemporal (outer) portion (shown in black) of both left and rightvisual fields is detected by the left and right nasal retina. Neurones carrying this information go on to decussatein the optic chiasm. Light information from the nasal (inner) portion (shown in red) of both visual fields isdetected by the temporal retina on each side.97 Diagram to show visualfield pathways (a) andvisual field defects (b).A’: monocular visual losssecondary to optic nerveor retinal disease. May becomplete or may followone of the patterns shownin 96; B’: bi-temporalhemianopia due to a lesionof the optic chiasm. Theupper quadrants areusually affected first;C’: left homonymoushemianopia from a lesionof the optic tract. The fielddefect is often incongruous(the shape of the defect isdifferent in the two halffields); D’: superior lefthomonymousquadrantanopia from alesion of the lower fibresof the optic radiation inthe temporal lobe;12349a5L786B'F'E’: inferior left homonymous quadrantanopia from a lesion of the upper fibresof the optic radiation in the parietal lobe; F’: macula-sparing, left homonymoushemianopia from an anterior visual cortex lesion. 1: retina; 2: optic nerve;3: optic chiasm; 4: optic tract; 5: lateral geniculate body; 6: optic radiation (7: lower fibres in temporal lobe; 8: upper fibres inparietal lobe); 9: occipital cortex; L: left; R: right.C'RA'E'D'bLLLLLLA'B'C'D'E'F'97RRRRRR
106nerve at the optic chiasm. Here partial decussationoccurs, and it is this anatomical arrangement thatleads to both bitemporal hemianopia from lesions atthe chiasm, and to the various types of homonymoushemianopia, when the pathology is posterior to thechiasm. Axons that derive from the ganglion cells ofthe nasal portion of the retina (and which carryinformation from the temporal field of vision )cross to the contralateral side of the chiasm, and goon to form the optic tract with axons from thetemporal side of the ipsilateral retina (97a).Thus, the left optic tract contains visualinformation from the right field of vision (nasalfield of the left eye and temporal field of the righteye), and the right optic tract contains visualinformation from the left field of vision (nasalfield of right eye and temporal field of left eye).Visual field defects that derive from lesions atboth the chiasm and optic tract are shown in 97b.Optic radiationThe optic tract continues posteriorly to the lateralgeniculate body, where the axons synapse with cellbodies whose subsequent axons go on to form theoptic radiation. These pass backwards, coursing deepthrough the parietal and temporal lobes. Because thearrangement of axons within the optic radiationcontinues to follow the distribution that originated inthe optic nerve, the superior fibres (in the parietallobe) contain information from the superior retinalganglion cells, which comes from the lower half of thevisual field. Hence parietal lobe lesions, rather thancausing a full hemianopic defect, affect just theinferior quadrant of the homonymous half visual field(a homonymous inferior quadrantanopia). Similarly,temporal lobe lesions affect just the superior quadrant(a homonymous superior quadrantanopia). Thesepatterns are depicted in 97b.Occipital cortexThe two bundles of optic radiation meet again at thetemporo-parietal junction, and go on to terminate inthe visual cortex of each occipital lobe. Total loss ofthe visual cortex on one side produces a completecongruous homonymous hemianopia. Mostcommonly, the macular area (central vision), whichtransmits information to the occipital pole or tip, isspared because so much of the visual cortex subservesthis important central vision (97b). This isparticularly the case in vascular disease because theoccipital lobe receives blood from both the middleand posterior cerebral arteries; if the posteriorcerebral artery is occluded, the posterior visual cortexcontinues to receive blood from the middle cerebralartery and so the macula is spared.CLINICAL ASSESSMENTFocused history takingInitial localization of the pathological processinvolves the distinction of monocular from binocularvisual loss. Detailed enquiry is worthwhile as veryoften the history will initially be misleading, and thepossibility that the patient may have lost vision in halfof their visual field rather than in one eye will nothave occurred to them. Asking about the effect ofshutting either eye is helpful. Monocular pathologymust lie anterior to the chiasm (97a). Unless there isa history suggestive of a process affecting both opticnerves, the pathological process causing binocularvision loss must lie where information from both eyesis in close proximity, either at or posterior to the opticchiasm. The pattern of binocular disturbance leads tomore precise localization (97).The usual complaint is of loss of all or part ofvision (negative symptoms). Transmission ofinformation has been disturbed and the patient seesnothing in all or part of their visual field. There arefewer possibilities when symptoms are positive (forexample flashing lights); assuming there is no retinaldisorder, such problems are likely to be due tomigraine or epilepsy. Common aetiologies of visualloss, divided by anatomical location and speed ofsymptom onset, are described in Table 15. Thedivisions charted should be applied with somelatitude; patients’ recollection of their story can beuncertain, and often diagnoses are complicated bycoexistent pathology.Clinical context is the final step in the solution ofthe clinical problem. Various other aspects of thepatient’s history lead to modification of the list ofpossibilities reached on the basis of tempo:Age of onset: optic neuritis tends to occur betweenthe ages of 20 and 40 years. It may be the firstsymptom of demyelination. Vascular disease tends tobe a disease of older people. Temporal arteritis occursin patients over 50 years. Tumours can occur at anyage, but specific examples present in childhood andyoung adulthood (for example optic nerve glioma),and in the older age group (for example metastaticcarcinoma).
Disorders of special senses 107Past history: previous episodes of transientneurological disturbance may have been caused byprevious episodes of demyelination (raising thepossibility of multiple sclerosis [MS]). Vascular riskfactors increase the likelihood that the currentcomplaint has a vascular basis. Atrial fibrillation is arisk factor for embolism both to the middle andposterior cerebral arteries (causing cerebral infarctionand hemianopia), and the ophthalmic or retinal artery(causing amaurosis fugax), though this is a problemmore commonly seen as a consequence of embolismfrom a carotid stenosis.Evolution: sudden and static, or sudden andimproving describe acute insults, which are usuallyvascular, and their aftermath. Level of improvementafter a vascular insult varies, but maximal disability isreached at onset, usually over seconds. Anteriorischaemic optic neuropathy (AION), which may besecondary to vasculitis (arteritic), tends to follow thisclassic vascular pattern.Sudden and worsening generally describes asituation in which the onset seemed sudden (‘I noticedit one day’; ‘I woke up with it’), but progression hascontinued. Generally an active pathological process iscontinuing to cause clinical worsening, and anyprogressive problem should raise the suspicion ofneoplasia, e.g. chronic progressive monocular visualloss is indicative of ocular nerve compression.Demyelination will worsen over days beforetypically showing improvement, which often startsbetween 1 and 3 weeks after onset.Associated ophthalmic history: a history of decreasedvisual acuity and colour vision and pain, especially onmoving the eye, suggests optic neuritis. Symptomsfollowing optic neuritis are often worse in the heat orwith exercise (Uhthoff’s phenomenon).Altitudinal defects (loss of either the upper or thelower field in one eye) suggest a vascular cause. Oftenthe patient will describe ‘a shutter’ descending orascending over their vision. In AION, visual losstends to be more severe and complete in the arteriticthan in the nonarteritic form.Bitemporal visual field loss caused by chiasmallesions may be accompanied by more profound visualloss unilateral (suggesting unilateral optic nervepathology) if the lesion also compresses the opticnerve on one side. Symptoms can develop veryinsidiously, causing difficulties that are difficult tocharacterize on history alone. Careful examination ofvisual fields (see later) is important. Sometimessymptoms caused by instability of the two preservednasal fields abutting the midline occur, and objectsTable 15 Common aetiologies of visual lossOnset Optic disc Optic nerve Chiasm/tract Radiation/occipital lobeSudden ❏ Ischaemic optic ❏ Ischaemia ❏ Pituitary apoplexy ❏ Stroke(seconds to neuropathy ❏ Trauma ❏ Strokeminutes)❏ TraumaHours to ❏ Optic neuritis (papillitis) ❏ Optic neuritis ❏ Pituitary tumourdays ❏ Ischaemic optic ❏ Aneurysm (aggressive)neuropathy❏ Toxic❏ AneurysmDays to ❏ Glaucoma ❏ Tumour (glioma, ❏ Tumours (pituitary ❏ Tumours (glioma,months ❏ Tumour pituitary tumour, adenoma, glioma, metastasis)❏ Sarcoidosis craniopharyngioma) craniopharyngioma,❏ Sarcoidosismetastasis)❏ Thyroidophthalmopathy❏ Toxic (alcohol,tobacco)Months to ❏ Carcinoma-associated ❏ Tumour (meningioma) ❏ Tumour (meningioma) ❏ Tumour (meningioma)yearsneuropathy
108may briefly double or the left side of images may slidein relation to the right. Often close visual work suchas threading a needle is impossible.Papilloedema (optic disc swelling secondary toraised intracranial pressure) may be associated with ahistory of visual blurring on changing posture (visualobscuration), and loss of peripheral vision. Usually,however, it is asymptomatic. Proptosis indicates anenlarging lesion within the orbit.Associated neurological history: damage to the optictract or radiation is often seen in the context of eitherhemiparesis, aphasia, hemisensory loss, or neglect, andthese features both aid the process of localization (seeabove), and narrow the differential diagnosis. Tumoursencroaching on visual pathway structures can causepain in that area; they may be associated withheadache worse in the morning and on lying, stooping,bending, and coughing (‘pressure headache’).The presence of ‘pressure headache’ (andpapilloedema) in the absence of structural pathologyraises the possibility of cerebral venous thrombosis(causing a blockage to the venous drainage system ofthe brain) or idiopathic intracranial hypertension,which is often seen in association with obesity.Temporal arteritis (causing AION) is usuallyassociated with a headache, often temporal andunilateral. Scalp tenderness, jaw claudication, andaching shoulders are specific symptoms that should besought as supportive evidence.Migraine can cause various visual disturbances(often positive, see above), which usually precedesevere throbbing unilateral headache, photophobia,and nausea.Hemianopia can be caused by degenerativeconditions, such as Alzheimer’s disease (AD) andCreutzfeldt–Jakob disease (CJD), but this isuncommon. Agnosia (failure to recognize stimuli in theenvironment) and syndromes of visual disturbancecaused by higher cortical dysfunction (Table 16) aremore common in these conditions, and occur in thecontext of cognitive decline and other cortical featuressuch as apraxia and aphasia (in AD) or myoclonus andseizures (in CJD).Examinations (Table 17)General examinationPulse rate and rhythm should be assessed, and bloodpressure should be documented. Lymphadenopathymay signify metastatic tumour or sarcoidosis.Temporal arteries should be palpated to determinewhether they are patent (temporal arteritis can causeTable 16 Visual disturbance resulting fromhigher cortical dysfunctionAlexia without agraphia (able to write but not read)❏ Damage to connections between primary visualcortices and angular gyrus❏ Accompanied by right homonymous hemianopiaBalint’s syndrome❏ Gaze apraxia (inability to direct voluntary gaze)❏ Visual disorientation❏ Optic ataxia❏ Simultanagnosia (loss of panoramic vision)❏ Bilateral posterior watershed infarctionProsopagnosia (inability to recognize faces)❏ Bilateral inferior temporal lobe lesions❏ May have superior quadrantinopic defectsCentral achromatopsia (central colour vision loss)❏ Bilateral inferior temporal lobe lesions❏ May accompany prosopagnosiaAnton’s syndrome (blindness, but denial of blindness)❏ Normal pupillary response❏ Bilateral damage to occipital and parietal lobesTable 17 Examination for visual lossAssessmentGeneralOcularFundoscopyNeurologicalCranial nervesMotor nervesSensory systemExaminationPulse (rhythm, rate)Blood pressureLymphadenopathyTemporal arteriesProptosisPeriocular inflammationAnisocoria and pupillary responseVisual fieldsVisual acuityColour vision (Ishihara plates)Anterior chamberVenous pulsation and vesselsOptic discRetinaMaculaOcular movementsLateralized weaknessReflexesPlantar responsesVibration and position sense testingLateralized pain and temperature lossSensory inattention and corticalsensory loss
Disorders of special senses109occlusion and pulseless temporal arteries) orthickened, tender or tortuous, which can also befeatures of arteritis.Ocular assessmentProptosis is assessed by standing behind the patientand looking downwards over the patient’s brows,comparing the positions of the two corneas relativeto each other and to the superior orbital rims. Pupilsshould be assessed in a step-by-step process. Minordegrees of anisocoria (pupillary inequality) arecommon in the general population; acquired (new)anisocoria indicates a disruption of efferent supply(sympathetic or parasympathetic) to that pupil. Thedirect light response is first assessed by shining abright light into one pupil (98a). The light source isthen removed and the procedure repeated with theexaminer concentrating on the other pupil to assessthe consensual response (98b). A brisk constrictionof the pupil should be seen in both eyes when lightis shone in either. Finally, the swinging light testshould be performed to determine the presence of arelative afferent pupillary defect (RAPD), or MarcusGunn pupil (98c). An optic nerve lesion will disturbthe pupillary light reaction (causing an RAPD) oftenpermanently, and will usually reduce visual acuity.Asking the patient to fix on a far and then a neartarget assesses pupillary responses to accommodation:the pupils should constrict and the eyesshould converge.a b c988L R L R L R714632598 Diagram to show pupillary response testing. The direct light response (a) impulses are conveyed in the left optic nerve (1) toboth Edinger–Westphal nuclei (2) in the midbrain (3). From here efferent fibres pass in the oculomotor nerve (4) to constrict theleft pupil. Since impulses from the left eye are relayed to both nuclei, efferent impulses also pass in the right oculomotor nerve toconstrict the right pupil, the ‘consensual light response’ (b). The swinging light test (c) assesses the relative power of the rightand left afferent response. Light is rapidly alternated between right and left eyes, and the response from an eye affected by anoptic nerve lesion will be shorter, slower, and less complete. 5: superior colliculi; 6: lateral geniculate body; 7: ciliary ganglion;8: ciliary nerve.
110Visual fields are assessed by the technique ofconfrontation (99). The examiner should be directlyin front of the patient, sitting about 1 metre away. Aninitial screening examination to detect homonymoushemianopic defects is useful, particularly if such aproblem is suggested by the clinical history. Static andmoving targets are presented in the four quadrants ofbinocular vision (99a). If fields have been found to beintact by this technique, simultaneous binoculartargets are presented and the patient is asked whichthey see: only seeing one indicates a deficit of visualattention, seen in lesions of the nondominant parietallobe (99b). More detailed testing should follow,particularly if the history suggests a chiasm or opticnerve disorder; the patient’s left eye visual field willcorrespond with the examiner’s right eye visual field.The examiner and the patient each close or cover oneeye, and concentrate on the opposite pupil. Thepatient is then asked to indicate when they can see avisual target, and a red pin is advanced diagonallyacross each visual quadrant, half way betweenexaminer and patient. The examiner’s field is thuscompared to that of the patient (99c, d). In thetemporal field of either eye the normal visual field ofboth examiner and patient will extend beyond thereach of even the longest arm, and so the target isusually advanced from a position slightly behind thepatient. This is well within the examiner’s visual field,and so an absolute comparison of examiner andpatient is impossible (in this part of the visual field),but asymmetry and abnormalities become evidentwith experience.For central defects (central scotoma) a small pinis used to map out any area of visual loss. In AION,visual field loss tends to be altitudinal and has a sharpdemarcation at the horizontal meridian, whereasoptic neuritis is commonly associated with a centralarea of field loss (scotoma) (96). In the temporalportion of the visual field lies the physiological blindspot: again a pin is used to compare the size of thisarea between examiner and patient. This techniquerequires cooperation on the part of the patient,practice by the examiner, and the patience of both.The patient’s gaze must not deviate from theexaminer’s pupil (99e). Papilloedema causes anenlarged blind spot and constriction of the visualfield. Visual fields are more accurately tested with aGoldmann perimeter machine or other types of visualanalyser. This is useful to confirm findings fromconfrontation, especially the presence of central fielddefects or an enlarged blind spot, and also to assesschange in visual fields over time.Visual acuity should be tested in each eye with aSnellen chart (for far vision) and a near reading cardfor near vision. Each assessment is recorded in astandard way. For neurological purposes it isimportant that the patient wears glasses that theyhave been prescribed, to correct any refractive error.If these are unavailable, then looking through a smallpinhole in a piece of paper or card will eliminatemajor refractive errors. If patients are severelyvisually impaired, an assessment of whether they cansee how many fingers the examiner is holding up, orcan appreciate movements of the hand or a lightshone in the eye, is performed. Colour vision isassessed using specialist colour charts known asIshihara plates. These were designed to detectcongenital colour vision disorders, but are also usefulfor acquired defects.Fundoscopy is a key skill in visual assessment. Itis easier when the pupil has been dilatedpharmacologically. The ophthalmoscope is held in theexaminer’s right hand, and the examiner’s right eye isused to examine the patient’s right eye. The left handand eye are used for the patient’s left eye. The patientis asked to fixate on a distant target and keep botheyes open, and a strong positive lens is initially usedto examine the anterior chamber. The retina is thenbrought into focus by reducing the lens strength. Thesetting required to examine the retina will depend onany refractive errors that the patient and/or examinermay have. The retinal vessels are traced back to theoptic disc, and examined for nipping (which indicateshypertensive eye disease) and venous pulsation(which is lost early in disc swelling). The clarity of thedisc edge is then assessed, along with the disc colourand pallor. The retina is examined for haemorrhagesand exudates (seen in hypertension and diabetes) bysystematically panning from disc to periphery in aclockwise manner around the fundus. Finally, thelight beam of the ophthalmoscope is set to narrowand the patient is asked to look directly into the light,which brings the macula into view. Lesions in thisarea tend to cause serious loss of vision.A normal optic disc is shown in 94a. Myopiamakes the disc look enlarged and pale, andhypermetropia makes it look pink and small. Fundalexamination in the acute phase of optic neuritis isusually normal but sometimes shows swelling of theoptic nerve head (papillitis) (94b). Swelling may alsobe seen in AION, often associated with pallor andhaemorrhages in the arteritic form. Optic disc
Disorders of special senses 11199a99b99c99d99 Visual field testing. The initial screening assessment to detect(gross) hemianopic defects involves presenting targets separatelyin the fields of binocular vision (a). Simultaneous bilateraltargets are presented to test for visual inattention (b).During uniocular testing, a target is advanced diagonally fromperiphery to centre across each visual field (c, d). Small centraldefects (scotoma) and the size of the physiological blind spot areassessed as shown in (e).a: binocular (screening) testing: a moving target in the patient’supper left field; b: testing for visual inattention; c: unioculartesting: the upper temporal field of the left eye; d: unioculartesting: assessing the lower nasal field of the left eye;e: mapping out the blind spot of the left eye.99e
112swelling in the presence of normal visual acuity istypically papilloedema (94c), which should bepresumed to be due to raised intracranial pressureunless proved otherwise. Optic atrophy (94d) is theend stage of a range of different optic nervepathologies.Fundal and pupillary examination in patientswith visual defects caused by pathologyposterior to the chiasm that has not caused anybrain swelling will be normal.Neurological examinationCranial nerves III, IV, and VI should be examinedcarefully in all cases of visual loss (see later fordetails). Diplopia is sometimes mistaken for visualloss or blurring and vice versa. Lesions posterior tothe chiasm will often be associated with lateralizedweakness, and so testing for tone and power may helpin localization (see page 148). Reflex asymmetry oran extensor plantar may be present in the absence ofmotor weakness. Long tract motor signs may indicateprevious lesions in other parts of the nervous systemin a patient with optic neuritis (indicating MS) orAION (indicating possible previous vascular events).Similar principles apply to the sensory examination(see page 214). Testing for sensory inattention isimportant in patients with a visual deficit that ishemianopic, and other features of cortical sensoryloss such as astereognosis (inability to recognizeobjects by touch) and agraphaesthesia (inability torecognize numbers traced on the palm) may bepresent. Various syndromes of higher corticaldysfunction are associated with visual disturbance(Table 16).InvestigationsThese are guided by history and examinationfindings. Specific tests that are useful in certainsituations are illustrated in Table 18.Table 18 Clinical syndromes and their investigationAcute monocular visual lossFBC, ESR, CRP, glucose, cholesterolECGCarotid DopplerEchocardiographySubacute monocular visual loss FBC, ESR, CRP, glucose, cholesterol, vitamin B 12VERMRILumbar puncture for OCBMitochondrial DNA analysis (Leber’s hereditary optic neuropathy)Progressive monocular visual lossBinocular visual lossChiasmHomonymousWith associated higher cortical dysfunctionFunctional visual lossVERMRI of orbits, orbital apex, and chiasmMRI suprasellar space, pituitary fossa, and sphenoid sinusCT or MRI of parietal, occipital, and temporal lobesECGFBC, ESR, CRP, glucose, cholesterolCarotid DopplerEchocardiographyEEG (if suggestive of visual seizure)CT or MRINeuropsychological evaluationVERGoldmann perimetryCRP: C reactive protein; CT: computed tomography; ECG: electrocardiogram; EEG: electroencephalogram; ESR: erythrocytesedimentation rate; FBC: full blood count; MRI: magnetic resonance imaging; OCB: oligoclonal bands; VER: visual evoked response.This table excludes the investigation of ophthalmological disorders. In case of doubt, always consult an ophthalmologist.
Disorders of special senses113CLINICAL SCENARIOSCASE 1A previously healthy, 28-year-old female computerprogrammer noticed that she was having difficultyseeing fine lines and small computer text with her lefteye. The symptoms progressed slowly over the nextday, so that she had difficulty discriminating betweenletters in newspaper headlines.These symptoms denote a clear history of amonocular alteration of vision in a young patient withno previous visual or neurological problems. Themanner in which the problem has been noted (readingor looking at a screen) and has progressed suggests asubacute onset (hours to days).Two days after the onset of her symptoms shenoted altered perception of colours and developed painin her left eye, but no swelling or redness. The painwas worse with eye movement or pressure on theglobe.These complaints are more specific, and suggestoptic neuritis.On examination, her Snellen visual acuity was6/36 in the left eye and 6/5 in the right eye.Confrontation visual fields were normal on theright, but demonstrated a central scotoma on theleft. Colours were less intense in the left eye, andshe could only read 7/13 Ishihara plates in thateye. There was an afferent pupillary defect onthe left. Fundoscopy was normal bilaterally. Therest of her neurological examination wasnormal.Afferent pupillary defects occur with anyoptic nerve injury. Similarly, marked reductionin visual acuity, central scotoma, and alteredcolour vision merely denote optic nerve injury,rather than its cause, but the combination offeatures is characteristic of optic neuritis.Examination will usually be normal in opticneuritis, but in about one-fifth of casespapillitis (swelling of the optic nerve head)will be seen. Eventually the disc will appearpale (optic atrophy), especially the temporal aspect. Thefact that the rest of the neurological examination wasnormal is extremely important, because optic neuritis is acommon presentation of MS, and a previous neurologicalevent at a different site may have been subclinical (i.e.may not have caused symptoms).Lumbar puncture was normal. Visual evoked potentials were delayed in theleft eye but normal on the right. Magnetic resonance imaging (MRI) was normal.MRI shows no evidence of previous episodes of demyelination, andoligoclonal bands (which are commonly detected in MS and reflectimmunoglobulin response to central nervous system [CNS] antigens) are notpresent. This diminishes the likelihood that the optic neuritis was secondary tounderlying MS, and makes it less likely that the patient will go on and havefurther episodes of optic neuritis or CNS inflammation / demyelinationelsewhere. It does not, however, guarantee freedom from further episodes.She was not treated, and after 2 weeks her visual symptoms graduallyimproved. After 3 months, her vision was 6/6 in both eyes, and the centralscotoma was gone. Colour perception remained slightly reduced on the left.
114CASE 2A 62-year-old male retired postman awoke with‘darkened’, impaired vision in the upper half of thevisual field of his left eye 3 days prior to evaluation.He described the onset of symptoms as ‘like a shadebeing pulled down’ over the visual picture. He did notcomplain of eye pain.While the problem is again monocular, there areother specific features here, and the patient is mucholder than in Case 1. Patients that wake with symptomsmay have developed them suddenly or over hours (theydon’t know, they were asleep). Vascular problems are,however, common on waking. Altitudinal defects (fromthe bottom up, or the top down) are common invascular disorders of the optic nerve head.He had noted a headache for 6 weeks beforehand,and had consulted his general practitioner (GP) onthree occasions about this. He was told that he wassuffering from tension headache, and was prescribedsimple analgesics. When questioned specifically he100100 Pallidoedema ofthe opticdisc.reported pain at each side of his jaw when he ate,especially towards the end of the meal. He washypertensive, and on treatment with a beta-blocker.He had never smoked.This shows the importance of backgroundhistory, and the patient being given the opportunityto relate it. Symptoms that his GP has diagnosed astension headache take on a new importance whenconsidered in the context of his visual loss. Jawclaudication as described above is pathognomonic oftemporal arteritis, which usually causes troublesomeheadache. The concern in temporal arteritis is thedevelopment of arteritic AION, and this must bethe suspicion even before the patient is examined.Examination revealed corrected visual acuity of6/9 in the right eye and 6/36 in the left eye. Thetemporal arteries were nonpulsatile, thickened, andtender; there were no carotid bruits. A left afferentpupillary defect was present. The left optic nervehead demonstrated diffuse, pale swelling (100);small haemorrhages were visible at the superiordisc margin and retinal arteriolar narrowing was noted.Confrontation testing revealed a superior altitudinal visualfield defect in the left eye. The remainder of theneurological examination was normal.The reduced visual acuity in the left eye is consistentwith optic nerve injury, and not secondary to a refractiveerror (because refractive deficits were corrected). Theafferent pupillary defect confirms an optic nerve problem.Temporal arterial pulsation is sometimesdifficult to feel in normal patients, but in this case thickening andtenderness imply an inflammatory process occurring in the vessel that may also have led to occlusion andpulselessness. Disc swelling is classically pale in AION, but may be hyperaemic (red and swollen), particularlyin the nonarteritic form. The disc swelling is most often diffuse, with a segment of more prominent involvementfrequently present. The field defect suggests an anterior problem (since it is monocular and altitudinal). Thenormal neurological examination provides further reassurance that the problem is anterior.Full blood count revealed mild normochromic, normocytic anaemia, and a raised erythrocytesedimentation rate (ESR) of 89 mm/hr in the first hour. Methylprednisolone (1 g) was infusedintravenously immediately after the receipt of the ESR result, and the following day his headache hadresolved. Further doses of methylprednisolone over the subsequent 2 days were followed by high-dose oralprednisolone. Left temporal artery biopsy conducted on the second day of admission revealed areas ofintimal proliferation with a tunica media infiltrated with lymphocytes, plasma cells, epithelioid cells, andmultinucleated giant cells, consistent with a diagnosis of temporal arteritis.It is important to recognize temporal arteritis quickly, and to treat it on suspicion, because continuedischaemia (of the same or of the other eye) could further jeopardize sight.Over the next week visual acuity stabilized at 6/24 on the left. At 2 months following onset of visualloss, the optic disc became atrophic, worse in the inferior half, with complete resolution of disc oedema.Oral prednisolone was subsequently reduced over the ensuing weeks and months with no return of visualdisturbance.
Disorders of special senses 115CASE 3A 56-year-old male with lifelong myopia had anumber of ‘near misses’ while driving his car and hiswife noticed that he was apparently not seeing vehiclesapproaching from the left which were very obvious toher. He had no difficulty seeing road signs or withreading but was persuaded to go to see his optician tocheck his glasses prescription.The symptoms suggest a loss of the peripheralvisual field that could be due to a large number ofdifferent causes. For example, glaucoma results in lossof peripheral vision, secondary to raised intraocularpressure at the optic nerve head, and retinitispigmentosa causes similar loss due to a retinaldegeneration. The difficulty seeing to the left would beconsistent with a left homonymous hemianopia due toa lesion affecting the right optic tract, radiation, orvisual cortex. The fact that the patient did not notice aspecific time of onset argues against a sudden lesionsuch as a right occipital lobe infarct.His optician found normal corrected visualacuity, a normal fundal appearance, and normalintraocular pressures. He did find some peripheralvisual field defects in both eyes and recommended areferral to an ophthalmologist.The findings of the optician suggest that theproblem is not ocular, and suggest that theproblem is not confined to one optic nerve orpathway. They do not localize the lesion, but theyexclude anterior causes: the problem is binocular,and is therefore either at the chiasm or posteriorto it.The ophthalmologist confirmed the visualacuity findings and arranged visual field testing(101). The patient had no other complaints orproblems and the past medical, family, andsocial histories were unremarkable.(Continued overleaf)101120 105 90 75 60120 105 90 75 601357045135704560I 604E1505030 1505030I404E4030I 30165152E151652020I 2E1018010180 90 80 70 60 50 40 30 20 10 10 20 30 40 50 60 70 80 90 90 80 70 60 50 40 30 20 10 10 20 30 40 50 60 70 80 90 0100101952102020345 19530304040330502105034533022560603157022570315240 255 270 285 300240 255 270 285 300101 Visual field charts showing bi-temporal hemianopia, consistent with a lesion at the optic chiasm.
116102CASE 3 (continued)The visual fields show a bitemporal fielddefect that is consistent with a lesion at theoptic chiasm. Subsequent MRI showed ameningioma pressing on the optic chiasm(102). Lesions of the optic chiasm, mostcommonly arising from the pituitary gland,classically produce a bi-temporal hemianopiadue to interruption of the crossing fibres inthe chiasm. This can involve peripheraland/or central retinal fibres. If the lesionaffects the anterior chiasm then one opticnerve and the crossing fibres from the nasalretina of the other eye may be affected,whereas a posterior placed lesion mayproduce an incongruous hemianopia due tooptic tract involvement.The lesion was successfully removedwith considerable resolution of visual fieldloss.102 Magnetic resonance image showing a meningioma,pressing on the optic chiasm from below.CASE 4A 74-year-old male retired lawyer with a historyof hypertension and hypercholesterolaemiapresented to the Accident and EmergencyDepartment complaining of visual loss to the left,which had developed suddenly while he wasgardening 6 hours previously. The visual loss waspresent when he shut either eye.The background of vascular risk and suddenonset immediately raises suspicion of a vascularcause. The history also suggests that the problem isbinocular (because it was present when he shut eithereye), and hemianopic (‘to the left’). Often the historywill be much more vague (‘there’s something wrongwith my vision’), and this useful information will onlybe available after careful probing.He had no other symptoms at the time of visualloss, but had recently been discharged from aneighbouring hospital. He had presented there withvomiting and imbalance 4 weeks previously, and hadbeen diagnosed with an ischaemic cerebellar strokeafter having a brain scan. He had slowly recovered,had been started on aspirin and increased antihypertensives,and had received a course of physiotherapy.His symptoms at the time of this first event arecertainly suggestive of posterior circulation stroke,and the slow recovery after sudden initialpresentation is consistent with this diagnosis. Thefact that both events occurred in quick successionsuggests they may be connected. Moreover, if thevisual defect is consistent with the suggesteddeficit of hemianopia, both could result fromposterior circulation ischaemia, since infarction ofthe posterior cerebral artery causes occipital lobeinfarction and hemianopia.Examination revealed xanthelasma andhypertension (176/92 mmHg [23.5/12.3 kPa]).Corrected visual acuity was 6/9 in each eye, andpupillary and fundal examination was normal.Confrontation visual field testing revealed a lefthomonymous hemianopia. Goldmann perimetrysubsequently showed this to spare the macula. Theremainder of the neurologic examination revealedpast pointing and intention tremor, most markedin the left upper limb. He was mildly ataxic onheel-to-toe walking.(Continued on page 117)
Disorders of special senses 117103aCASE 4 (continued)He has physical markers of vascular risk(xanthelasma and hypertension). The visualdeficit is homonymous and hemianopic, whichplaces the lesion in the optic tract, radiation, orcortex. In keeping with this, examination of opticnerve function (acuity, pupils, and fundi) isnormal. The congruous nature and fact that themacula is spared suggest an anterior visual cortexlesion. His cerebellar signs are likely to besequelae of the first event 4 weeks previously.Computed tomography (CT) scanningrevealed two discrete infarctions (103a, b). Thefirst, older and more circumscribed, was locatedin the left cerebellar hemisphere. The second,poorly defined and associated with someswelling, affected the right occipital lobe in theterritory of the posterior cerebral artery.Angiography revealed atherosclerosis of thebasilar artery, a proximal embolic source for bothof these arterial lesions. Echocardiography wasnormal. The patient was treated withantithrombotics to protect against further events.Proceeding to vascular imaging is importantbecause two events occurred in the same vascularsystem. It was important to investigate for acommon proximal embolic source (in this caseatherosclerosis in the basilar artery).103b103 Computed tomography scan of vascular disease. a: olderinfarction in the territory of the left superior cerebellar artery;b: newer infarction in the territory of the right posteriorcerebral artery.
118DOUBLE VISIONDiplopia means double vision. Diplopia can behorizontal (one image beside the other) or vertical (oneimage on top of the other). Abnormalities of the ocularmedia (e.g. cornea and lens) create monoculardiplopia, in which when the patient covers the normaleye the double vision persists. Misalignment of eyescauses binocular diplopia; covering either eye abolishesthe double vision. Neurological causes of double visionare almost exclusively binocular. The physicalexamination usually reveals the location of theabnormality, and the history indicates its aetiology.Disorders of the extraocular muscles, III, IV, and VIcranial nerves and brainstem oculomotor pathwayscause binocular diplopia. Rarely, cerebral corticallesions can cause multiple images (polyopia). Manypatients with misalignment of the eyes beginning inchildhood (secondary to strabismus or ‘squint’) do notexperience diplopia because the image from thedeviated eye is suppressed (amblyopia or ‘lazy eye’).Functional anatomy and physiologyExtraocular musclesSix muscles control eye movement. Each moves theeyeball or globe in a specific direction. Thesedirections of action are illustrated in 104, along withthe specific nerve supply of each muscle (see later).Vertical is more complex than horizontal gaze with theoblique muscles moving the eye up and down when itis turned in (ADduction) and the recti moving the eyeup and down when it is turned out (ABduction). If anextraocular muscle is weak, movement of the eye inthe direction of the muscle’s action will be impaired,and the patient will see double when looking in thatdirection, because conjugate eye movement has beendisrupted. The false image lies outermost and comesfrom the underacting eye (105). Extraocular musclesmay be affected directly by muscle (e.g. myositis) orneuromuscular junction (NMJ) disorders (e.g.myasthenia gravis) that make the muscles weak orrestricted.OrbitThe optic nerve enters the orbit through the opticforamen, alongside the ophthalmic artery. The nervesthat supply ocular movement (see below) enter theorbit through the superior orbital fissure. Orbitalapex anatomy is illustrated in 106. Masses (whichmay be inflammatory, infective, or neoplastic) in theorbit may displace the globe (causing proptosis orforward displacement of the globe), maymechanically interfere with the extraocular muscles,or may compress the nerves supplying ocularmovement, so causing cranial nerve palsy. They mayalso cause visual loss, due to interference with theoptic nerve at the orbital apex.104 Superior rectus (oculomotor) Inferior oblique (oculomotor) Inferior oblique (oculomotor)Superior rectus (oculomotor)Lateral rectus(abducens)Medial rectus(oculomotor)Inferior rectus (oculomotor) Superior oblique (trochlear) Superior oblique (trochlear)Inferior rectus (oculomotor)104 Diagram to show the line of action of individual ocular muscles and their nerve supply. Medial and lateral rectus move theeye medially and laterally, respectively. With the eyes in midposition, superior rectus and inferior oblique move the eye up, andinferior rectus and superior oblique move the eye down. The oblique muscles move the eye up and down when it is turned in(medially). The recti move the eye up and down when it is turned out (laterally).
Disorders of special senses 119105123Looking Looking Lookingright straight ahead left105 Diagram showing left abducens palsy, illustrating the mechanism of diplopia. When looking right and straight ahead, theextraocular muscles adjust the alignment of the eyes to maintain centring of the visual object on the macula. Since the left eyecannot look out (abduct), the image cannot be maintained on the macula of the left eye when the patient looks left. Thus theimage falls on the nasal retina and is projected into the temporal half field. 1: optic nerve; 2: macula; 3: extraocular muscles.106 Diagram to show theneuromuscular anatomy ofthe orbit and orbital apex.The orbital apex is shown incross-section in the box.1: superior oblique, suppliedby the trochlear nerve (2);3: optic nerve; 4: superiororbital fissure; 5: superiorrectus and 6: medial rectus(supplied by the oculomotornerve); 7: superior andinferior divisions of theoculomotor nerve; 8: lateralrectus, supplied by theabducens nerve (9); 10: opticforamen; 11: ophthalmicartery.1 2356431110 7910628
120Cranial nervesThree nerves supply the muscles that serve eyemovement. Their anatomical path towards the orbitalapex (106) is shown in 107.The oculomotor (III) nerve is the major nervesupplying eye movement, controlling the superior,inferior and medial recti, and the inferior oblique(106, 107). It also innervates levator palpebraesuperioris (which elevates the eyelid) and carries theparasympathetic nerve supply to the pupil. Onleaving the midbrain anteriorly, the nerve passesthrough the interpeduncular cistern in close relationto the posterior communicating artery and runsthrough the cavernous sinus. From here it enters theorbit through the superior orbital fissure.The trochlear (IV) nerve supplies the superioroblique muscle, which depresses the eye when it isturned in (or ADducted, (106, 107). It emergesdorsally from the midbrain and passes laterallyaround the cerebral peduncle to enter the cavernoussinus. From here it enters the orbit through thesuperior orbital fissure.The abducens (VI) nerve supplies the lateralrectus muscle, which ABducts the eye (106, 107).After emerging from the pons, the nerve runs anteriorto the pons before piercing the dura at the basilarportion of the occipital bone. Under the dura thenerve runs up the petrous portion of the temporalbone and, at its apex, passes through to the lateralwall of the cavernous sinus. From here it enters theorbit through the superior orbital fissure.107Midbrain41512201619Midbrain2 2471518153Pons91081123 171612 107 Schematic diagram to show the anatomy of the oculomotor (1),trochlear (2), and abducens (3) nerves. Axial sections of each relevant13 brainstem level are shown on the left. The cavernous sinus is shown incross-section in the box. The three nerves pass forward to the superior143orbital fissure (see 106). 4: aqueduct; 5: red nucleus; 6: cerebralpeduncle; 7: medial lemniscus; 8: trochlear nucleus; 9: cortico-bulbarand cortico-spinal tracts; 10: medial longitudinal bundle; 11: abducensnerve nucleus; 12: facial nerve nucleus; 13: facial nerve; 14: trigeminal nucleus and tract; 15: internal carotid artery; 16: externalcarotid artery; 17: common carotid artery; 18: sphenoidal sinus; 19: trigeminal nerve; 20: pituitary.
Disorders of special senses121Many diseases or disorders can disrupt cranialnerve functions, so causing diplopia. The nerves maybe compressed by neoplasms occurring at any pointalong their anatomical path, by aneurysms ofadjacent vascular structures (for example a posteriorcommunicating artery aneurysm causing a third nervepalsy), or by raised intracranial pressure causingtranstentorial herniation. Their blood supply maybecome disrupted (microvascular occlusion), and theymay be affected by inflammatory and infectivedisorders. As they pass into the cavernous sinus andsuperior orbital fissure, function may be disrupted byinflammatory masses, neoplasm, aneurysms, fistulae(between carotid artery and cavernous sinus), or bythrombosis of the cavernous sinus itself.BrainstemEach of the three cranial nerves supplying eyemovement (III, IV, VI) originates in the brainstem.The oculomotor nucleus lies immediately anteriorto the cerebral aqueduct in the midbrain at the levelof the superior colliculus (107). Nerve fibres passanteriorly through the red nucleus and substantianigra to emerge medial to the cerebral peduncle.The trochlear nucleus lies immediately anterior tothe cerebral aqueduct in the midbrain at the level ofthe inferior colliculus (107). The nerve passesposteriorly to decussate in the dorsal midbrain. Itemerges on the posterior aspect of the midbrain.The abducens nucleus lies in the floor of the fourthventricle within the inferior portion of the pons (107).It lies in close relation to the facial nerve nucleus andfacial nerve axons loop around it. The nerve passesanteriorly to emerge from the brainstem on theanterior surface of the pons without decussating.Vertical and horizontal movements are initiatedvia gaze centres in the brainstem, and the actions ofthe three nerves supplying ocular movement areunited to produce a coordinated response. So when,for example, the left eye adducts (to look right), anaction of the left medial rectus, the right eye abducts(to look right), an action of the right lateral rectus.Brainstem lesions can cause diplopia by affectingthe cranial nerve nucleus, or the cranial nerve fascicle(nerve trunk). Common aetiologies includedemyelination and ischaemia or infarction. Infections(encephalitis or abscess), haemorrhage, and neoplasmmay also affect the brainstem. Often nonocularsymptoms or signs, as a result of disturbance ofclosely related structures, will accompany the eyemovement problem. Lesions affecting the structureswhich control coordinated gaze (for example themedial longitudinal fasciculus) can also produce thesymptom of diplopia, though they frequently do not.CLINICAL ASSESSMENTFocused history takingInitial confirmation that the problem is indeeddiplopia must be obtained. Often patients use theterm ‘visual blurring’ or shadowing to mean a varietyof complaints. Diplopia means seeing two objects;these may not be equally distinct, but there are two.The clinician should then ascertain the effect ofeye closure. Binocular diplopia is caused bymisalignment of the images obtained from each eye; itwill be abolished by closure of either eye. Thepresence of this feature (or confirmation of itspresence on examination) establishes the cause of thediplopia as neurological. Monocular diplopia willcontinue when the normal eye is covered anddisappear when the abnormal eye is covered.The direction of the diplopia must beinvestigated. Disorders of muscles or nerves supplyingmuscles, that act in a vertical (up and down) planewill cause vertical diplopia, while problems withthose that act in a horizontal (side-to-side) plane willcause horizontal diplopia. Diplopia is maximal in thedirection of action of a paretic muscle. Thus trochlearnerve palsy causes vertical diplopia maximal on downgaze, for example when going down stairs, because itaffects the superior oblique muscle, which makes theeye look down when ADducted.Sudden onset implies a vascular or traumaticcause. An expanding aneurysm causing compressionof a cranial nerve tends to occur suddenly or worsenover hours. Gradual onset over days may occur ininfective, inflammatory, or demyelinating disorders.Gradual onset over weeks commonly occurs inneoplastic processes.Progressive, relentless worsening implies aprogressive pathology: an expanding aneurysm, agrowing tumour, or worsening cavernous sinusthrombosis. Vascular (arterial) occlusion causingmicrovascular cranial nerve palsy or brainstemstroke, tends to occur suddenly, and either remainsstatic or improves. Myasthenia, causing extraocularmuscle weakness, tends to worsen as the day goes onor as a specific task (for example reading) continues.Inflammatory diseases may have a progressive orvarying course.
122Myasthenia and demyelination are usually painless.Microvascular occlusion of a cranial nerve may beaccompanied by retro-bulbar pain. Local infective orinflammatory diseases tend to be accompanied by pain;thus granulomatous inflammation at the superiororbital fissure or cavernous sinus in the Tolosa–Huntsyndrome causes multiple cranial nerve palsies withsevere pain. Encephalitis and meningitis are usuallyaccompanied by more diffuse headache. Expandinganeurysmal or neoplastic pathologies produce pain:painful third nerve palsy should be assumed to be dueto compression by an aneurysm of the posteriorcommunicating or basilar artery until proved otherwise.Other ocular symptoms should be investigated.Proptosis and periocular oedema imply the presence ofan orbital or retro-orbital mass that may be infectiveor inflammatory. It may also be caused by caroticocavernousfistula (in which case it may be pulsatile),cavernous sinus thrombosis, and thyrotoxic eyedisease, which causes enlargement of extraocularmuscles. Loss of vision (see earlier) accompanyingdiplopia occurs in the context of diseases of the orbitthat affect ocular movement, such as inflammatory orgranulomatous conditions, primary and metastatictumours, orbital cellulitis, and orbital wall fractures.Weakness of eye closure is a clue that a NMJ ormuscle disease causing extraocular muscle weaknessmay be the cause of the diplopia.Ptosis can accompany disorders of the extraocularmuscles, for example myasthenia gravis (oftenfatiguable) or chronic progressive externalophthalmoplegia (progressive). Rarely, it accompaniesdiseases that affect the cavernous sinus, becausesympathetic fibres to the eyelid and pupil are intimatelyassociated with the internal carotid artery, whichpasses through the cavernous sinus. In this instance,pupillary constriction may also be present (Horner’ssyndrome). Ptosis is also a feature of third nerve palsy,because the third nerve supplies fibres to the levatorpalpebrae superioris, which elevates the eyelid.Pupillary dilatation occurs as a feature of thirdnerve palsy, due to disruption of parasympatheticsupply to the pupil: it tends to be an early feature ofthird nerve palsy if this is secondary to compressionby aneurysm or infiltration. Microvascular thirdnerve palsy usually spares pupillary reactions. Thisdifference in presentation is explained by thesuperficial arrangement of pupillary fibres within thenerve trunk: they are affected first by extrinsiccompression and tend to be spared by central nervetrunk infarction.Other neurological symptoms can occur. Facialsensory disturbance (V nerve dysfunction) incombination with diplopia suggests either brainstemor cavernous sinus disease. Facial weakness occurswith diplopia in two contexts. Unilateral dysfunctionof facial power may accompany abducens nerve palsyor internuclear ophthalmoplegia in brainstem lesionsbecause of the close proximity of the two structures inthe pons. Neuropathies, NMJ disorders (myasthenia)and myopathies may result in facial and extraocularmuscle weakness. In these instances, the facialweakness will usually, but not always, be bilateral.Hemiparesis or hemisensory loss again usuallyimplies damage to the motor or sensory tracts thatpass through the brainstem in close proximity tonerves III, IV, and VI. Ataxia in combination withdiplopia can occur due to damage to the cerebellarpeduncles or lobes from an ischaemic ordemyelinating event that has also affected thestructures involved in eye movement. It may alsooccur due to Wernicke’s encephalopathy (caused byacute thiamine deficiency, and often seen inalcoholics), when it will usually be accompanied byconfusion and amnesia.It is important to establish the patient’s medicalhistory and background. Vascular disorders, such asmicrovascular cranial nerve palsy, tend to occur in thecontext of vascular risk factors (age >60 years,diabetes, hypertension, hyperlipidaemia). Inflammatorydisorders of the orbital apex or cavernous sinustend to occur in middle age. Expanding aneurysmscausing cranial nerve palsy, myasthenia, metastaticand most primary neoplasms tend to occur in middleand old age. Demyelination is usually a disease ofyoung adults, and previous episodes suggestive oftransient neurological disturbance may have occurredin the past.ExaminationsFocused examinationDirected clinical examination of the patientpresenting with diplopia is summarized in Table 19.Other aspects of the history may have raisedquestions that need to be answered by a morecomprehensive general or neurological examination.General examinationArrhythmias may suggest cardiac disease or embolicsource, and tachycardia occurs in the context ofsystemic infection in association with fever.Hypertension is the major risk factor for stroke,
Disorders of special senses123aneurysm formation, and microvascular cranial nervepalsy. Raised intracranial pressure impairsconsciousness, increases blood pressure, and slowsthe pulse (Cushing’s response). A goitre should raisesuspicion of thyroid eye disease or myasthenia, whichcan occur in association with thyroid disorders.Lymphadenopathy occurs in metastatic neoplasm andlymphomas, sarcoidosis, and lupus. Patients withparetic eye muscles often compensate for theirproblem by tilting or turning their head away fromthe direction of action of the paretic muscle, since thisminimizes the diplopia they experience. This isdiscussed further below.Table 19 Examination for diplopiaAssessmentGeneralOcularDiplopiaNeurologicalCranial nervesMotor systemExaminationPulse (rhythm, rate)Blood pressureGoitre/lymphadenopathyCompensatory head positionVisual acuityFundoscopyVisual fieldsAnisocoria and pupillary responsesPtosis/eyelid retractionPeriocular inflammationProptosisMonocular occlusionRange of motionCover test (tropia)SaccadesDoll's eye testFacial weakness/palsyFacial sensory loss and corneal reflexHearingLateralized weaknessReflexesPlantar responsesCerebellar system Finger-to-nose testingRapid alternating movement testingHeel-shin testingSensory system Vibration and position sense testingLateralized pain and temperature lossOcular assessmentVisual fields, fundi and acuity should be assessed asdiscussed in the first section of this chapter. Pupillarysize, anisocoria (unequal pupils), and response tolight and accommodation are assessed. Pupillarydilatation can be subtle, and may not be fixed (inother words the response is sluggish and abnormal,but present). It occurs in (complete) third nervepalsies (because the third nerve carriesparasympathetic nerves which constrict the pupil),and should raise suspicion of a compressive aetiologybecause pupillary fibres lie superficially in the nervetrunk and are often affected first. Horner’s syndrome(a small pupil [miosis] more evident in the dark andptosis) indicates disruption of sympathetic nervesupply to the eye and, in the context of diplopia,raises suspicion of pathology at the cavernoussinus/superior orbital fissure or brainstem. Ptosis(drooping of the eyelid) should be looked for and thepalpebral aperture (distance between the eyelids)measured with a ruler to compare the two sides.Asking the patient to look upwards for 30 secondsbefore returning to the primary position andremeasuring assesses fatiguable ptosis. Cogan’s lidtwitch sign is a useful addition: the patient is asked tolook down for 10 seconds, and then quickly up to acentral target; the upper eyelid overshoots its normalposition and then comes down like a shutter to itsresting state. Fatiguable ptosis indicates a NMJdisorder, most commonly myasthenia. It is often, butnot exclusively, bilateral. It also occurs congenitallyand in chronic progressive external ophthalmoplegia.Unvarying ptosis may be due to mechanical disorders,a Horner’s syndrome (incomplete and with miosis) oroculomotor nerve palsy (typically more severe, andwith a normal or dilated pupil). Lid retraction occursin thyroid eye disease, in association with lid lag(lagging behind of the eyelid as it is shut). Proptosis isbest assessed by standing behind the patient andlooking downwards over the patient’s brows,comparing the positions of the two corneas relative toeach other and the superior orbital rims.Diplopia examinationA specific diplopia examination should also beperformed. Monocular occlusion is performedinitially, either looking straight ahead or in whicheverdirection the diplopia occurs, to determine whetherthis does abolish the double vision. For range ofmotion (duction testing) the patient is asked to a)look at the target, b) follow the target with their eyes
124and not by moving their head, c) and to report if theysee double at any point. These instructions should beclear and often need to be reiterated. The target(preferably a light to allow observation of the corneallight reflex) is held at arm’s length from the patient’seyes. It is moved upwards, downwards, to the left, tothe right, and then upwards and downwards whenthe patient is looking to the left and to the right. Aftertesting with both eyes open (versions), it is useful totest each eye separately, the other being covered bythe examiner’s hand (ductions). Often, duction failure(loss of movement) of the eye in a certain direction orseries of directions is obvious. The common patternsof ophthalmoplegia (failure of eye movement)associated with III, IV, and VI cranial nerve palsies aredemonstrated in 108. Also illustrated is the patternseen in internuclear ophthalmoplegia; although thisoften does not cause diplopia, it is an importantpattern to recognize, and denotes a lesion of themedial longitudinal fasciculus in the brainstem.If double vision is present, the examiner shouldestablish in which direction the images are maximallyseparated. In this position the most peripheral(outermost) of the two images is the false image (105).By covering the eyes alternately and asking the patientto say when the outermost (normally also the faintest)image disappears, it is possible to establish which eye isat fault (‘the bad eye’). The weakened muscle is thatwhich normally moves the bad eye in the direction inwhich maximal diplopia occurs.A tropia is a misalignment of the eyes duringbinocular vision. The cover test is a useful addition, asit will detect subtle misalignment that may beassociated with diplopia, but which is not evidentwhen testing for range of motion as described above.The patient is asked to fixate on a target straightahead, one eye is covered and the examiner watches theother eye. If that eye makes a refixation movement, itwas not aligned on the target. If the eye moves nasally(in), it was misaligned temporally (out) and so on.108abcLooking straight aheadLooking down andto the rightLooking straight ahead=108 Diagram to show the common patterns of ophthalmoplegia.: indicate the movements that are lost in each presentation.a: left oculomotor palsy: there is ptosis, pupillary dilatation, anddiplopia in all directions except on lateral gaze (since lateralrectus function is intact). When the patient attempts to lookdown, the eye intorts (inwardly rotates, ). Superior oblique(intact since it is supplied by the trochlear nerve) has a rotatoryaction when the eye cannot be adducted; b: left trochlear palsy:frank diplopia occurs when the patient looks down and awayfrom the side of the affected eye; c: left abducens palsy: diplopiais maximal when looking to the paralysed side; d: leftinternuclear ophthalmoplegia is a disorder of conjugate gaze,causing the eyes to move independently on lateral gaze. Onlateral gaze away from the side of the lesion (which lies in themedial longitudinal fasciculus) the adducting eye fails to adduct,and the abducting eye demonstrates coarse jerky nystagmus( ). a: Looking straight ahead; b: Looking down and tothe right; c: Looking straight ahead; Looking to the left; d:Looking to the right.dLooking to the leftLooking to the right
Disorders of special senses 125Different patterns are illustrated in Table 20. If the eyedoes not refixate, the same procedure is carried out forthe other eye, after a momentary pause to allowbinocular vision to be re-established. Nonparalyticstrabismus beginning in childhood commonly causestropia; in this situation there is no diplopia, because theimage from the deviated eye is suppressed or vision inone eye is poor (amblyopic). If the patient has a nerveor muscle weakness causing diplopia, the tropiaincreases when the patient is asked to look in thedirection of action of the paretic muscle. Testing forphorias (misalignment of the eyes during monocularvision), which do not cause diplopia under normalconditions, is beyond the scope of this text.Saccades are rapid conjugate voluntary eyemovements between objects. The examiner holdstheir right fist 30° to the patient’s left, and their leftpalm 30° to the patient’s right. The patient is thenasked to look quickly back and forth between the fistand the palm. The test is repeated with the fist held30° above the patient’s line of vision and 30° below it.Normal saccades have high velocities and areaccurate. Any ophthalmoplegia will cause slowing ofsaccades: the examiner detects that the paralysed eyereaches the target after the normal eye when thepatient is asked to look in the direction of action of aweak muscle. This again is a more sensitive sign thanrange of motion testing. It is particularly useful in thedetection of internuclear ophthalmoplegia.The Doll’s eye test (vestibulo-ocular reflex) is usefulfor evaluating eye movements when the patient isunconscious, but is also helpful in the distinction ofsupranuclear gaze palsy from nuclear gaze palsy. Theexaminer rapidly oscillates the head horizontally andvertically. The normal response is for the eyes to rotatein the opposite direction, maintaining fixation. If a gazepalsy has been identified on range of motion testing, buton Doll’s eye testing the eyes move normally in the‘paralysed’ direction, then the problem must lie instructures that control voluntary gaze, superior to thecranial nerve nucleus that actually subserves movement,with vestibular input being preserved.Neurological examinationCranial nerves V and VII should be examined carefully.Cranial nerve V lies near the floor of the fourth ventriclein the lateral part of the pons and so may be affected bypontine lesions that also affect the medial longitudinalfasciculus (causing internuclear ophthalmoplegia), andcranial nerve VI. Only the first (ophthalmic) division ofthe trigeminal nerve will be affected in cavernous sinusTable 20 Classification of tropiaType Misalignment Cover testExotropia Temporal (outward) Nasal movementEsotropia Nasal (inward) Temporal movementHypertropia Superior (upward) Downward movementHypotropia Inferior (downward) Upward movementlesions, and the corneal reflex will often be depressed.Cranial nerve VII loops around the VI nerve nucleus,and so is commonly affected by processes disturbing theVI nerve and nucleus in the pons. A contralateralhemiplegia may accompany this pattern. It is alsoimportant to examine facial power in patients suspectedof having myasthenia or generalized neuropathy ormyopathy: often facial weakness will be bilateral, andthis can make it more difficult to detect since there is noasymmetry. Asking the patient to screw their eyes uptight and to whistle can uncover mild bilateral weaknessin this situation.A motor system examination should beperformed (see page 148). Long tract signs may occurin pontine or midbrain lesions because the corticospinaltracts run through these structures in closeproximity to cranial nerve nuclei and fascicles. Lowermotor neurone weakness may occur in the context ofgeneralized neuropathies that affect eye movementand skeletal muscle power (for exampleGuillain–Barré syndrome), and both NMJ disorders(e.g. myasthenia) and myopathies may affect limbpower as well as eye movements.The integrity of the cerebellar system is alsoassessed (see page 176). The patient should be testedfor upper limb cerebellar signs (finger-nose-finger testand rapid alternating movements [dysdiadochokinesis]),lower limb cerebellar signs (heel-shin test)and asked to tandem walk. Abnormalities indicatedisease of the cerebellum or its connections, and tendto occur ipsilateral to any cerebellar lesion. It iscommonly seen in association with diplopia or eyemovement disorders in alcoholics who have developedWernicke’s syndrome and in multiple sclerosis (MS).In the sensory system (see page 214), lateralizedsensory disturbance may occur in brainstem disease.Peripheral loss of pain and temperature sensation iscommonly seen in neuropathies. Posterior columnsensation (vibration) is often particularly affected byspinal MS, that may be subclinical.
126InvestigationsThese are guided by history and examinationfindings. Specific tests that are useful in certainsituations are illustrated in Table 21.SUMMARY❏❏The speed of onset of visual symptoms is thebest indicator of the underlying pathology.Monocular visual loss is caused by pathologyanterior to the optic chiasm.❏❏❏❏Lesions at or posterior to the optic chiasm affectthe visual fields in both eyes.Neurological diplopia is binocular.A painful third (oculomotor) nerve palsy is aneurological emergency due to an aneurysmuntil proven otherwise.Neurological diplopia can be caused by nerve,muscle, or neuromuscular junction disorders.Think about the latter two if the first doesn’t fit.Table 21 Investigation of clinical syndromesIsolated diplopiaAcute diplopiaSubacute diplopiaChronic progressive diplopiaGlucose, FBC, ESR, CRP, ANA, RF, ENA, cholesterolCT +/- MRIAngiographyAChRAbTensilon test, EMGInfection screen (Lyme, tuberculosis)TFT, thyroid autoantibodiesESR, CRP, ANA, RF, ENA, ACECSF including OCB and pressureMRI +/- gadoliniumAngiographyAChRAbTensilon test, EMGTFT, thyroid autoantibodiesCSF including OCBMRI +/- gadoliniumNonisolated diplopiaDiplopia + signs of raised intracranial pressure MRI or CT +/- contrast+ proptosis and/or papilloedema MRI (with gadolinium) of orbits, orbital apex andcavernous sinus+ combination (2 or more) of MRI (with gadolinium) of orbits, orbital apex andHorner’s, III, IV, V, or VI palsycavernous sinus+ multiple other cranial nerve palsies MRI (with gadolinium) of posterior fossa and meningesCSF+ brainstem or long tract signs MRI (with gadolinium) of posterior fossa+ generalized weakness or bulbar weakness AChRAb, Tensilon test, NCS, EMGACE: angiotensin-converting enzyme; AChRAb: anti-acetylcholine receptor antibody; ANA: antinuclear antibody;CRP: C-reactive protein; CSF: cerebrospinal fluid; CT: computed tomography; EMG: electromyography; ENA: extractablenuclear antigen; ESR: erythrocyte sedimentation rate; FBC: full blood count; MRI: magnetic resonance imaging; NCS: nerveconduction study; OCB: oligoclonal bands; RF: rheumatoid factor; TFT: thyroid function test.
Disorders of special senses 127CLINICAL SCENARIOSCASE 1A 30-year-old female with no relevant past medicalhistory presented with acute, binocular, horizontaldiplopia and severe headache.Almost every word here is important innarrowing a differential that initially seemsunmanageably broad. This is an acute (therefore, inthe absence of trauma, probably vascular andunlikely to be tumour related) event in a youngwoman with no previous history (therefore unlikelyto have generalized vascular disease or vascular riskfactors). Thus the vascular event is less likely to bean infarction (though it could be), and more likely tobe related to an aneurysm or vascular malformation.The diplopia was binocular (therefore neurological),horizontal (therefore, if neural rather than muscle,the problem affects nerves that move the eye in ahorizontal plane [oculomotor or abducens]), andwas associated with severe headache (which makesdemyelination and myasthenia unlikely).On examination, there was a partial ptosis on theleft and a dilated and unreactive left pupil. The left eyewas abducted when looking straight ahead. Eyemovement testing revealed moderate underaction ofadduction, elevation, and depression of the left eye.The right eye moved normally. There was intorsion ofthe left eye in down gaze, suggesting an intact fourthcranial nerve. The rest of the neurologicalexamination, including fundal examination, wasnormal. Blood pressure and blood glucose testing werenormal.These are the physical signs of completeoculomotor palsy. Microvascular oculomotor palsy(often secondary to hypertension or diabetes)normally spares the pupil. The fact that these verydistinct signs are present in isolation is important:posterior circulation stroke would affect otherstructures and so cause other signs, as wouldlesions in the cavernous sinus or orbital apex.A diagnosis of an isolated, pupil-involved, leftthird nerve palsy was made. A CT scan of the headwas normal, but a CT cerebral angiogram revealedan aneurysm of the left posterior communicatingartery (109). This was successfully obliterated byinsertion of a coil the following day.Painful acute oculomotor palsy shouldalways prompt urgent investigation and vascularimaging: the presence of pain in this situationimplies that the aneurysm is expanding and mayrupture.31091109 A computed tomography angiogram showing an aneurysmof the left posterior communicating artery (1). 2: basilar artery;3: left middle cerebral artery.2
128CASE 2A 72-year-old male with a history of hypertension anddiabetes presented with acute, painless, binocular,horizontal diplopia worse on looking to the left.This is a completely different context to Case 1.One of the key skills of a good physician is toappreciate that ‘common things are common’, whilealways looking for warning signs that might push himor her away from the common and straightforwardanswer and towards a less obvious diagnosis. Thiscould have the same cause as Case 1, and that wouldalways be something that the astute doctor wouldhave in mind. However, a number of features make amore benign aetiology more likely. This is a patientwith a considerable vascular risk profile and hisproblem is painless. The problem again soundsvascular, but an ischaemic basis is more likely in thistype of patient.On examination, his blood pressure was 190/96mmHg (25.3/12.8 kPa) and his random blood glucosewas 13.4 mmol/l (241 mg/dl). The left eye was slightlyadducted when looking straight ahead. On testing eyemovements, he was unable to abduct the left eye, andsaw two images side by side when asked to look tothe left. The outer, more faint image disappearedwhen the left eye was occluded. The remainder of thecranial nerve tests and ophthalmologic and generalexaminations were normal.It is important to appreciate the generalmedical context in which neurological eventsoccur; this patient’s hypertension and diabetes areboth poorly controlled. Eye abduction is anabducens nerve function, and diplopia occurs onlooking in the direction of action of the leftabducens nerve. The fact that the false imagedisappears on occluding the left eye confirms thatthis is a problem with left lateral rectus (suppliedby the left abducens nerve), not right medialrectus (supplied by the right oculomotor nerve),which also acts in this direction. No oculomotorfunctions are affected and the pupils are normal,further reassurance that the diagnosis as in Case1 is unlikely. Again the problem is isolated,making structural pathology in the brainstemor cavernous sinus unlikely.A diagnosis of an isolated, presumedmicrovascular left sixth nerve palsy was made.A CT scan of the head was normal. He wasstarted on low-dose aspirin, and hishypertension and diabetes were controlled byadditional antihypertensives and gliclazide.For 2 weeks the patient wore a patch overthe left eye to alleviate his symptoms, but by4 weeks both his symptoms and signs hadcompletely resolved.Microvascular nerve palsy generally has abenign prognosis, and patients normally recoverfully. Patches are a simple and useful short-termmeasure to obliterate the false image.CASE 3A 54-year-old male was referred to his local Ophthalmology Department complaining of double vision. Thishad come on quite suddenly, but image separation (which was horizontal) increased over 48 hours. He had noother complaints. He had hypertension (which was well controlled), but had been otherwise well in the past.If this is binocular diplopia (as seems likely), the patient will need to be examined to identify theaffected muscles. Horizontal image separation suggests involvement of the medial and/or lateral rectus.Diplopia noted to be worse on lateral gaze to the right or left can give clues as to the affected muscles,but this information is not available here.On examination, the abnormalities were confined to the left eye. The left eye was turned out in theprimary position (exotropia) and there was weakness of ADduction, elevation and depression. There wasa partial ptosis but the pupil was normal.This looks like an isolated third nerve palsy, sparing the pupil and therefore likely to be due toischaemia of the nerve and is perhaps related to his hypertension.(Continued on page 129)
Disorders of special senses129CASE 3 (continued)Blood glucose (to investigate for diabetes), inflammatory markers (to investigate for arteritis), andangiography (to investigate for a compressive vascular lesion) were all normal. On review 3 weeks later,the symptoms had improved and, presuming that this was indeed due to microvascular disease of thenerve, he was told that there was a good chance of complete recovery.Most ischaemic mononeuropathies do recover well and at the present time there is nothing to suggestany other disorder.One month later, his diplopia had returned with both horizontal and vertical image separation anddrooping of both eyelids. On examination, he had weakness of varying degrees affecting all eye movements,bilateral ptosis, and also weakness of eye closure. His symptoms were worse at the end of the day.It appears that the initial diagnosis was incorrect. He now has widespread weakness, which cannot beexplained by a disorder of one or even two or three nerves. This, together with the weakness of eye closure,suggests a disorder of muscles and the diurnal variation is highly suggestive of ocular myasthenia. The initialpresentation had been deceptive.This diagnosis was confirmed by a dramatic response to intravenous edrophonium (Tensilon test) andsingle fibre electromyography. He was subsequently treated with steroids and azathioprine, resulting in agood clinical response.REVISION QUESTIONS1 Five lesion sites (a–e) and five visual losspatterns (1–5) are stated below. Match the sitewith the visual deficit that a lesion at that sitecommonly produces:a Right optic 1 Left incongruousnerve.homonymoushemianopia.b Optic chiasm. 2 Left macular sparinghomonymoushemianopia.c Right optic tract. 3 Right central scotoma.d Right temporal 4 Bitemporal hemianopia.optic radiation.e Right visualcortex.5 Left superiorhomonymousquadrantinopia.2 Which of the following statements about themedical history of a patient with visual loss aretrue:a Binocular visual loss will be abolished byshutting one eye.b Optic neuritis characteristically occurs inpatients over 60 years.c Tumours tend to cause progressive visualdisturbance over days or months.d Migraine causes monocular or binocularvisual disturbance normally followed bysevere headache.e Temporal arteritis usually causes ahemianopic visual disturbance.
1303 During a focused assessment for visual disturbance:a A left relative afferent pupillary defectsuggests disease of the left optic nerve.b Visual field testing may be omitted if visualacuity is normal.c An enlarged blind spot and constriction of thevisual field are features of papilloedema.d Finding associated lateralized motor weaknessand upper motor neurone signs suggests thatthe lesion lies in the optic chiasm.e ESR and carotid Doppler should be orderedto investigate acute monocular visual loss in a70-year-old male.4 Neurological diplopia:a Is abolished by shutting either eye.b Always results in images appearing side byside.c Can be caused by a lesion affecting theoculomotor, trochlear, or abducens nerves, orthe muscles that they supply.d Occurs only as a symptom of brainstemdisease.e Remains a lifelong problem for patients withcongenital strabismus (‘squint’).5 Which of the following statements about thehistory of a patient with diplopia are true?a Isolated trochlear palsy causes verticaldiplopia maximal when looking down.b Myasthenic symptoms will be most markedwhen the patient wakes up.c Proptosis suggests aneurysmal expansioncausing diplopia.d Unilateral ptosis indicates that the patientmust be suffering from an oculomotor nervepalsy.e Diplopia is maximal in the direction of actionof a paralysed muscle.6 Which of the following investigation andmanagement plans, formulated by a Casualtyofficer, would you agree with?a A patient with a painful complete oculomotornerve palsy (pupil involved) was reassuredand sent home for review in the neurologyclinic the following week.b A patient with diplopia and ophthalmoplegiawhich worsened as the day progressed wasreferred for a Tensilon Test.c A patient with a sudden abducens nerve palsyand a history of hypertension, whose CT scanwas normal, was started on aspirin, given apatch to wear over his right eye, andreassured. Plans were made for clinic review.d A 20-year-old patient was found onexamination to have a left internuclearophthalmoplegia and a relative afferentpupillary defect in the right eye. The patientwas told that he had probably suffered astroke and was referred for a CT scan.e A patient with symptoms of unilateral painbehind the eye, and a combined oculomotorand abducens palsy and tingling on theirforehead, was referred for an MRI scan oftheir orbital apex and cavernous sinus.Answers1 a with 3b with 4c with 1d with 5e with 22 c,d3 a True.b False.c True.d False.e True.4 a True.b False.c True.d False.e False.5 a, e6 b, c, e
Disorders of special senses131DIZZINESS AND VERTIGOJames Overell, Richard MetcalfeINTRODUCTIONDizziness and vertigo are common problems both inprimary and secondary care. Both are terms thatmean different things to different people, and theinitial objective of the physician must be to identifythe exact nature of the patient’s complaint. Thisrequires patience, careful listening and questioning,and a willingness not to jump to a (often incorrect)conclusion. Even after a measured assessment of theproblem, both dizziness and vertigo have a number ofdiverse aetiologies: serious and life-threateningproblems such as cardiac dysrhythmia need to bedistinguished from the more common vestibulardisorders. Anxiety may be both a cause and an effectof dizziness, and patients with chronic problems oftendevelop a vicious cycle of anxiety and dizziness thatcan be difficult to disentangle, and may preventresolution of symptoms long after any pathologicalproblem has resolved (110).Sensory inputs (visual, vestibular, and jointposition – see below) are normally combined toprovide an accurate model of the physical world.Symptoms can normally occur in the healthy individualwhen exposed to an unusual combination of sensoryinputs triggered by exposure to odd visual stimuli, suchas flickering images on screen or fast-moving traffic.This leads to a mismatch between visual, vestibular,and proprioceptive inputs, and to symptoms that aretermed visual vertigo. These occur in the absence ofdemonstrable vestibular disease. This phenomenon isthe basis for the lay perception of vertigo as meaning‘being scared of heights’: a mismatch between sensoryinputs causes troublesome symptoms at the top of tallbuildings. Medical meanings are discussed below.Dizziness is a broad and nonspecific termdescribing an unpleasant sensation of imbalance oraltered orientation in space. When using the term‘dizziness’, patients may mean that they are sufferingfrom vertigo, disequilibrium, presyncope, or symptomsthat stem from psychological disturbance. Vertigodescribes an illusion of movement in relation to theenvironment. It is usually rotatory (a sensation of‘spinning round the room’ or ‘the room spinningaround me’), but also sensations of body tilting,swaying, or forceful movement (impulsion) may occur.Disequilibrium is a sensation of altered static(standing) or dynamic (walking) balance; commonterms used by patients are unsteadiness and loss ofbalance, and they may fall as a consequence. Ataxiameans an unsteady gait, often described as ‘walking as110 Diagram to show theinterrelationship betweendizziness and anxiety. A patientmay be dizzy because they areanxious or fearful, or becomeanxious because of an attackof dizziness, particularly if thisoccurs in a public place. Avicious cycle may ensue. If thepatient eventually becomesasymptomatic due toresolution of the cause ofdizziness or cerebralcompensation for the alteredsensory inputs being received,symptoms may return (i.e. thepatient may decompensate)during anxiety-provokingsituations or due topsychological distress.VestibulardysfunctionDIZZINESSAnxietyCerebralcompensationPsychological distressStressful situationsRapid movementsAsymptomaticstate110
132though I am drunk’. Presyncope is a sensation ofimpending loss of consciousness (or syncope). Theterms ‘light-headedness’, ‘feeling faint’, or ‘feelingwoozy’ are often used to describe this sensation. It iscommonly associated with sweating, nausea, pallor,visual dimming or blurring, and generalized weakness.Anxiety may cause aspects of all the sensationsdescribed above, but generally causes a vague ‘giddy’,‘woozy’, or light-headed sensation that is typicallyprotracted with periodic exacerbations. It may causepatients to hyperventilate, and this can result inpresyncopal and other frightening sensations. Anxietymay exacerbate symptoms from other causes or lead todecompensation and recurrence of symptoms inpatients who have recovered (110).Functional anatomy and physiologyThe vestibular system is a special sensory system thatdetects rotational and linear acceleration. Along withinputs from the visual system and joint and bodyposition sense from the proprioceptive system, bodyorientation in space (equilibrium) is maintained. Lossof any one of these three systems will produce clinicalsymptoms referable to that system (for examplefunctional loss of the vestibular system will producevertigo), but loss of two of the systems will produceprofound imbalance and falling. Thus a patient withsevere proprioceptive disturbance will fall if vision iseliminated (the basis for the Romberg sign, seebelow). Mild impairment of all three systems is acommon cause of dizziness in older patients(‘multisensory disequilibrium of the elderly’).The vestibular apparatus is a series ofintercommunicating sacs and ducts filled withendolymphatic fluid, otoliths (granules), and hair cells,the movement of which generates sensory actionpotentials. The functional units of the system aredivided into the utricle, the saccule, and the semicircularcanals. The semicircular canals are arranged in threedifferent planes; this arrangement ensures that angularmovement in any direction results in displacement ofthe hair cells imbedded in the endolymph (111a, b).Linear acceleration results in displacement of otolithswithin the utricle and/or saccule, which again isdetected by the hair cells. Action potentials from thehair cells are transmitted to the vestibular division of theVIIIth cranial nerve. This travels (along with acousticinformation transmitted from the cochlea) through the111a Ampulla of semicircularcanalSemicircularcanalsCupulaHair cellsAnteriorHorizontalPosteriorVestibularnerveb SacculeHead held uprightGelatin layerOtoconiaSupportingcellsUtricleHead held bent forwardSacculeVestibular nerveCochleaHair cells bendunder gravitationalforce111 Diagram of the vestibular apparatus, comprising the semicircular canals, the utricle, and the saccule. The six semicircularcanals (three on each side) work as three matched pairs in three planes. a: The ampulla, a swelling at the end of each canal,contains the sensory apparatus, comprising the cupula and hair cells. As the head moves, movement of endolymph causes thecupulae on both sides of the head to bend in opposite directions. The difference in activity between the paired ampullae results inthe sensation of movement. b: The utricle and saccule contain the otolith organs. The organ in the saccule senses angularacceleration of the head. Forward movement forces the crystals to attempt to slide down the slope, proportional to the speedand angle of the movement. This displaces the hair cells, which is transmitted in turn to the vestibular nerve.
Disorders of special senses133petrous temporal bone to the internal auditory meatus.From here the VIIIth cranial nerve passes through thesubarachnoid space in the cerebellopontine angle tosynapse in the vestibular nuclei (located on the floor ofthe fourth ventricle at the pontomedullary junction) andcerebellum. This arrangement is illustrated in 112.The vestibular nuclei project the sensoryinformation to the following functional systems:❏ Cerebellum. Spatial and motion sensation fromthe vestibular system is transmitted to thecerebellum, which is the functional centre forbalance and coordination. Ataxia (see below)occurs as a result of disturbed sensory input tothis system.❏ Parieto-temporal cortex. These projections areresponsible for the conscious perception ofmotion and spatial orientation. A disturbance inthe inputs to this system will produce thesensation of vertigo. Such a disturbance may bedue to disordered vestibular afferent information(for example discordant information from thetwo vestibular apparatuses), or a conflictbetween vestibular and other sensory inputs.❏❏Oculomotor nuclei. These mediate vestibuloocularreflexes: eye movements in the orbit areproduced that are equal in amplitude andopposite in direction to head movements, so thatgaze remains steady. Vestibular nystagmus (seebelow), a physical sign that often accompaniesvertigo, is produced by a disturbance in thisreflex system.Spinal cord. Projections to the spinal cord formthe vestibulo-spinal tract, which mediates thevestibulo-spinal reflexes that assist inmaintaining posture and balance, particularly onthe muscle groups that act against gravity. Thepostural imbalance that often occurs investibular disease is caused by abnormalactivation of these pathways.Traditionally, the anatomical characteristics of thevestibular system have led to the distinction ofperipheral (labyrinthine or vestibular nerve) fromcentral (brainstem or vestibular connections) vertigo.The timing, context, and accompanying symptomatologyusually lead to proper classification into oneIV ventricleSemicircularcanals112Vestibular nucleiCochlear nucleiVestibularganglionVestibular nerveUtricleOliveInternalauditorymeatusCochlear nerveSaculeMedial lemnisciCochlea112 Diagram to show the central connections of the vestibular system. Information from the utricle, saccule, and semicircularcanals is relayed to first-order vestibular neurones. The cochlea (acoustic) and vestibular divisions of cranial nerve VIII travelthrough the internal auditory meatus, and then pass through the subarachnoid space in the angle between the pons andcerebellum. Each enters the brainstem separately at the pontomedullary junction.
134of these two categories, and to the correct diagnosis ofthe cause of the vertigo. The nature and direction (113)of the vertigo itself cannot be relied on absolutely tomake this distinction, but generally peripheral rotationalvertigo is in a yaw plane. Vertigo in other planes shouldraise the suspicion of a central disorder.CLINICAL ASSESSMENTFocused history takingThere are numerous potential causes of dizziness andvertigo, and the process of obtaining a history needsto be primarily one of listening and understanding theexact nature of each symptom. The standard patternof localization followed by pathophysiology (beyondthe distinction of central from peripheral above) tendsto lead to mistakes.113YawPitchRoll113 Diagram to illustrate the three planes of head movement.Yaw (horizontal about a vertical axis) is the common plane ofrotation in peripheral vertigo. Pitch (flexion and extensionabout a vertical axis) and roll (lateral head tilt about ahorizontal axis) are less common in peripheral vertigo.DefinitionThe specific meaning of the terms vertigo,disequilibrium, and presyncope are described above.It is very important to determine which of these broaddistinctions applies, since localization and pathologicalpossibilities follow on from this. Nonspecificcomplaints (‘dizziness’, ‘giddiness’, ‘woozy’, ‘lightheadedness’)should be explored. Direct and leadingquestions may be necessary, but should be viewed andrecorded as such. Sometimes, despite the bestattempts of the physician to classify thesymptomatology more closely, it is impossible todetermine the specific complaint; in this situation it ismore sensible to enquire about the other features ofthe problem described below than to ‘pigeonhole’ thepatient into a category that may lead to inappropriateinvestigations and treatments.Symptom complexesMedical dizziness and vertigo often have specificsituational features or present as part of a group ofsymptoms. It is useful to consider these ‘symptomcomplexes’ as an aid to reaching a differentialdiagnosis. The possibilities for each complex areshown in Table 22, along with other features specificto each diagnosis.❏ Acute severe vertigo refers to sudden, usuallyvery disabling, vertigo accompanied by nauseaand often profound vomiting. Often there willbe a history of such an attack in a patient whogoes on to develop positional vertigo: suchpatients have partially compensated (adapted),but continue to have symptoms when thevestibular system is provoked.❏ Positional vertigo (bed spins). Patients complainof brief spells of rotatory vertigo on changingposition, typically when getting into or out ofbed, or on rolling from one side to the other.Most patients with this symptom will havebenign paroxysmal positional vertigo (BPPV).❏ Vertigo with headache. The characteristics of theheadache may give more clues to the diagnosis(for example vertebrobasilar migraine causingrecurrent throbbing headache or Chiarimalformation causing headache on stooping orcoughing) than the vertigo.❏ Hydrops (hearing disturbance, vertigo, tinnitus).Patients complain of recurrent periods of vertigo,tinnitus (ringing or roaring in the ears), andtransient hearing loss, often preceded by a feelingof fullness in the ear. Most patients with thissymptom complex will have Ménière’s disease.❏ Medical dizziness. A ‘nonspecific’ and generallyacute presentation of giddiness, light-headedness,or presyncopal symptoms caused by low bloodpressure, low blood glucose, and/or metabolicderangements associated with systemic infectionor medications.
Disorders of special senses135Table 22 Differential diagnosis of vertigo and dizziness symptom complexesSymptom complex Diagnostic possibilities Other featuresAcute severe vertigo ❏ Acute peripheral vestibulopathy (often ❏ Nausea, vomiting, ataxia, and nystagmusreferred to as labyrinthitis, vestibularneuronitis, or vestibular neuritis)❏ Posterior circulation stroke ❏ Other symptoms of acute brainstem disease;focal brainstem signsPositional vertigo ❏ BPPV ❏ Lack of other symptoms; short lived;vertigo induced by changing head position;Dix–Hallpike test❏ Vestibular decompensation ❏ History of acute event before positionalsymptoms❏ Central vertigo ❏ Other symptoms of brainstem disease; focalbrainstem signs❏ Postural hypotension ❏ Getting out of bed, rather than turning inbed; systolic blood pressure drop of>20 mmHg (2.7 kPa) on standingVertigo or dizziness ❏ Vertebro-basilar migraine ❏ Severe throbbing episodic headache;with headacheassociated photophobia❏ Post-traumatic vertigo ❏ History of moderate to severe trauma;associated memory disturbance and ataxia❏ Chiari malformation ❏ Posterior headache with pressure features;down-beat nystagmus❏ Central vertigo ❏ Other symptoms of brainstem disease; focalbrainstem signs❏ Anxiety ❏ Headache, often with tension featuresHydrops ❏ Ménière's disease ❏ Vertigo duration usually a few hours; low(hearing disturbance,tone sensorineural hearing lossvertigo, tinnitus) ❏ Post-traumatic hydrops (Ménière's variant) ❏ Significant ear trauma❏ Syphilis ❏ Bilateral hearing loss; risk factors for syphilisMedical dizziness ❏ Postural hypotension ❏ Occurs on standing; systolic blood pressuredrop of >20 mmHg (2.7 kPa) on standing;may relate to medications❏ Cardiac arrhythmia ❏ Palpitations, breathlessness, chest pain,autonomic symptoms❏ Hypoglycaemia ❏ Osmotic symptoms; history of diabetes❏ Medication effect ❏ May also present with true vertigo;hypotensives, sedatives, antiepileptics,vestibular suppressants❏ Systemic infection ❏ Fever, malaise, myalgia, arthralgia❏ Hyperventilation ❏ Paraesthesiae around the mouth and in thefingersBPPV: benign paroxysmal positional vertigo.Timing and durationAre the symptoms episodic or constant? If they areepisodic, how long do they last? Many of theconditions causing vertigo will occur episodically(many times per day or week), and the duration of thesymptomatology when it occurs is a key factor inreaching a diagnosis. Vertigo can occur suddenly orappear gradually, and once present can disappearquickly, resolve over minutes, hours, or days, remainstatic, or progress. Some illnesses may only occur once(monophasic), but their diagnosis may have majorimplications because the physician must concentrateon preventing further episodes (for example transientischaemic attacks, or TIAs). If such problems becomerecurrent, perhaps occurring two or three times onspecific occasions rather than the episodic patterndescribed above, accurate diagnosis becomes evenmore important. Progressive disequilibrium is likely to
136have a toxic cause (for example persistent treatmentwith intravenous gentamicin, which is oto- andvestibulo-toxic), and progressive vertigo is likely tooccur in the context of other worsening brainstemneurology, raising the possibility of a neoplastic lesion.Table 23 shows the diagnostic possibilities that areraised by each type of presentation.Triggering or exacerbating factorsDizziness on standing up suggests postural hypotension.Changes in the position of head or body oftenexacerbate vertigo (see positional vertigo symptomcomplex above). Walking in the dark will exacerbatevestibular disturbances, but dizziness or imbalance onlyin the dark suggests a problem with proprioceptiveinputs (a sensory ataxia). Coughing, sneezing, bendingdown, or straining at stool raises intracranial pressure,and so may worsen symptoms from a posterior fossamass lesion or malformation (for example Chiarimalformation). Situations or times when vertigo occursmay lead to a pattern suggesting a relationship tocertain foods or medications (for example alcohol) or tosituational anxiety. Symptoms of dizziness and vertigomay cause acute anxiety and hyperventilation, butanxiety and hyperventilation can be the root of theproblem itself, and should be enquired about sensitively.Associated otologic historyHearing loss and tinnitus generally imply peripheraldysfunction, usually involving the inner ear. It isimportant to enquire closely about the components ofthe hydrops symptom complex above. Acuteperipheral vestibulopathy (often attributed, thoughwithout much evidence, to a viral infection of thevestibular nerve – so called vestibular neuritis) presentswith vertigo, nausea, vomiting, ataxia, and nystagmus.When combined with tinnitus and/or hearing loss it isknown as labyrinthitis. Tumours compressing theVIIIth nerve (the most common example being acousticneuroma) generally produce progressive asymmetrichearing loss and mild ataxia rather than vertigo.Associated general and neurological historyA history of diabetes raises the possibility ofhypoglycaemia and a history of cardiac diseaseshould alert the physician to the possibility of cardiacarrhythmia (see medical dizziness symptom complexabove). Systemic infection may cause medicaldizziness, and may be accompanied by either general(fever, malaise) or specific (diarrhoea, cough) signs ofinfection. Vascular risk factors (age, smoking,diabetes, hypertension, hyperlipidaemia) increase thelikelihood of TIA or stroke as the cause of vertigo ordizziness. A history of previous focal neurologicalevents raises the possibility of demyelination(multiple sclerosis, MS). A history of migraine iscommon in patients with Ménière’s disease.Any of the following ‘brainstem’ symptoms implya central basis for vertigo: diplopia, facial numbness,dysarthria, dysphagia, lateralized limb weakness ornumbness, and lateralized incoordination. Since facial(VII) nerve fibres travel in close proximity to theVIIIth nerve in the internal auditory canal,cerebellopontine angle and brainstem, complete facialnerve palsy can occur in conjunction with vertigo andthis indicates disease of one of these structures.Ataxia (unsteadiness of gait) is very commonlyassociated with both peripheral and central vertigo, isfrequent with cerebellar disease and diseases causingloss of proprioceptive input, but is uncommon inmedical dizziness. Nausea and vomiting accompanydizziness and vertigo in all contexts, but tend to be moremarked and dramatic in peripheral vertigo than incentral vertigo. Patients may experience oscillopsia,which is an awareness of jumping of the environment.This may occur as a consequence of rapid jerking eyemovements (nystagmus) or because of failure of thevestibulo-ocular reflex. The complaint of unsteadinessand imbalance (disequilibrium) may be caused byvestibular dysfunction, but may also be secondary tocerebellar disease or impaired proprioception due tolarge fibre peripheral nerve or spinal cord posteriorcolumn dysfunction. Presyncope is often accompaniedby visual dimming, palpitation, sweating and pallor,and suggests one of the causes of the medical dizzinesssymptom complex. Hyperventilation may beaccompanied by paraesthesiae around the mouth and inthe fingers. Enquiring about the symptoms of anxiety ismandatory in the dizzy patient, but is particularly usefulin a patient who may be hyperventilating.AgeCommon causes of vertigo in the elderly include BPPV,acute peripheral vestibulopathy, trauma, medication(see below), and ischaemia of either the posterior(brainstem) circulation or the labyrinthine system.Common causes of vertigo in younger adults includeMénière’s disease, acute peripheral vestibulopathy, headtrauma, and medication. Causes of medical dizzinesstend to occur more often in the older age group, sinceheart disease, prescription of antihypertensivemedication, and diabetes are more common.
Disorders of special senses 137Family historyA family history of vascular disease or risk factors,Ménière’s disease, autoimmune disease in a patientwith Ménière’s disease, or migraine may be obtained.Medication historySome medications are toxic to the vestibular nerve,the most common example being aminoglycosideantibiotics. Numerous medications can make patientsfeel dizzy and unsteady, including anticonvulsants(carbamazepine, phenytoin), antihypertensives(which can cause symptomatic hypotension andmedical dizziness), antidepressants (which can havecardiovascular side-effects including posturalhypotension), and sedatives (benzodiazepines,narcoleptics). Drugs can also cause ataxia,anticonvulsants being the most common example.Substance abuse historyAlcohol causes dizziness and vertigo during acuteingestion. Heroin, benzodiazepines, and othersedatives can cause dizziness, as can amphetaminebaseddrugs and lysergic acid diethylamide (LSD).Chronic use of alcohol producing a cerebellarsyndrome is the most common cause of ataxia in theUnited Kingdom.Table 23 Differential diagnosis of dizziness and vertigo by timing and duration of symptomsPresentationCourseDuration Onset Episodic Monophasic Recurrent Progressive
138ExaminationsFocused examinationThe focused physical examination of the dizzy orvertiginous patient is outlined in Table 24. The variouscomponents of the assessment are discussed below.General examinationPresence of a tachy- or bradyarrhythmia raises thepossibility that symptoms of medical dizziness areattributable to cerebral hypoxia as a consequence ofreduced cardiac output and consequent hypotension. Afall in systolic blood pressure of >20 mmHg (2.7 kPa)on standing constitutes significant posturalhypotension. The presence of a third or fourth heartsound may imply heart failure (leading to hypotension),or significant hypertension (increasing vascular risk),respectively. Heart murmurs can be caused by valvulardisease, which may be an embolic source. Arterial bruits(carotid, subclavian, femoral) imply major vesselstenotic arterial disease, which increases the probabilitythat symptoms are attributable to ischaemia, while notbeing directly implicated in the aetiology of theproblem. Carotid sinus massage is useful if carotid sinushypersensitivity is suspected.Balance assessmentThe gait pattern of particular importance in theassessment of dizziness and vertigo is the ataxic gait:wide-based, stumbling, and unstable. Any instabilitywill be exaggerated by tandem walking (walking withone foot in front of the other ‘as if on a tightrope’).Young, fit patients should be able to do thisbackwards as well as forwards. Ataxia can be causedby significant cerebellar disturbance, significant(particularly acute) vestibular disturbance, orsignificant (particularly acute) proprioceptivedisturbance. Romberg’s test (illustrated in 114)should be performed with the eyes open and thenwith the eyes shut. Vision tends to compensate forchronic vestibular and especially proprioceptivedeficit, so difficulty standing with the eyes closed (ora ‘positive Romberg’s test’, 114) specifically indicatesa deficit in one or both of these systems.Otologic examinationA brief assessment of hearing (for example rubbingthe thumb and forefinger beside each ear) is useful asa screening test for hearing disturbance. Normallyyoung persons should be able to perceive this at arm’slength from their ear, and elderly patients should beable to perceive it at 15 cm (6 inches). An audiogram(see below) quantifies and characterizes the hearingloss, but simple clinical tests can be helpful. Adistinction is made between conductive (related todisease or blockage in the external auditory meatus,eardrum, or ear ossicles) and sensorineural (cochlear,VIIIth nerve or brainstem) hearing loss. Thisdistinction is made clinically using Rinne’s andWeber’s tests, illustrated in 115a, b. During Rinne’stest, a vibrating high frequency tuning fork(preferably 512 Hz) is held close to the ear, and thepatient is asked to compare the volume of the soundTable 24 Examination for vertigo and dizzinessAssessmentGeneralBalanceOtologicalNeurologicalCranial nervesMotor systemCerebellar systemSensory systemNystagmusExaminationPulse (rhythm, rate)Blood pressure lying and standingCardiac auscultationArterial bruitsCarotid sinus massageGaitTandem walkingRomberg’s testHearingRinne and Weber testsTympanic membranesFundoscopyEye movementsVestibulo-ocular reflexesFacial movementFacial sensation and corneal reflexLateralized weaknessReflexesPlantar responsesFinger-to-nose testingRapid alternating movement testingHeel-shin testingVibration and position sense testingSpontaneous nystagmusGaze-evoked nystagmusHallpike manoeuvreHead shake testVestibulo-ocular system testing
Disorders of special senses 139a b c114Feet together Eyes open Eyes shut114 Diagram to illustrate Romberg's test. The patient should be asked to stand upright, with feet together and eyes open (a).Staggering and unsteadiness with the eyes open suggest a cerebellar lesion (b). The patient is then asked to shut their eyes;unsteadiness at this stage is strongly suggestive of a defect of joint position sense, but can also occur in patients with vestibularimpairment (c).abNormal115115 Diagram to illustrate conductive and sensorineural hearingloss tests. a: Rinne's test. The volume of the note from a256 Hz or 512 Hz tuning fork is compared during air (left) andthen bone (right) conduction. In conductive deafness, boneconduction is better than air conduction. b: Weber's test. Thetuning fork is placed on the vertex and the sound should beheard equally in both ears. In conductive deafness, the sound isheard louder in the affected ear. In nerve deafness, the sound isperceived less well on the affected side.Left conductivedeafnessLeft sensorineuraldeafness
140heard with that perceived when the tuning fork ispressed against the mastoid bone. Normally airconduction of sound is more efficient than boneconduction, but when there is conductive deafness thereverse is the case. In Weber’s test, the vibratingtuning fork is applied to the midline of the foreheadand the patient is asked whether they hear the soundin the middle of their head, or in either ear.If a patient has sensorineural deafness in one earthe sound will appear to arise on the healthyside (in the good ear). Conversely, if there isconductive hearing loss on one side, the soundwill appear to arise from the affected side (thebad ear): it is for this reason that Rinne’s testmust be performed first to exclude conductivehearing loss before proceeding to Weber’s test.Causes of hearing loss associated with vertigotend to be sensorineural. Tympanic membranesshould be inspected for wax, perforation, otitis, andmass lesions, particularly if conductive hearing loss isdetected by Rinne’s test.Neurological examinationCranial nervesFundoscopy should be performed to look for signs ofraised intracranial pressure and vascular changesassociated with diabetes and hypertension. Opticatrophy (seen as a pale optic disc) should be sought asevidence of previous, possibly subclinical,demyelination. Eye movements should be examined,firstly to look for nystagmus (see below), but also toseek evidence of gaze palsy, internuclearophthalmoplegia, or III, IV, or VI cranial nerve palsy,any of which would indicate structural brainstemdisease and a central cause of vertigo. Examinationfor these problems is discussed in more detail onpages 104–112. Facial nerve palsy accompanyingvertigo indicates structural disease of the internalauditory canal, cerebellopontine angle, or brainstem.The fifth (V) cranial nerve may also be affected bylesions in the cerebellopontine angle, hence theimportance of testing for facial numbness and absentcorneal reflex. Generally, cerebellopontine anglelesions (common examples being acoustic neuroma,meningioma, and metastasis) present with hearingloss rather than vertigo.Motor system (see page 148)Testing for long tract motor signs (tone, power, andreflexes) is important to document any subclinicaldisease affecting the pyramidal tracts. This localizesthe cause of vertigo or imbalance in the brainstem(for example in brainstem stroke or Arnold–Chiarimalformation), or indicates pyramidal pathologyelsewhere in the nervous system, which can occur indemyelination.Cerebellar system (see page 176)Cerebellar disease causes unsteadiness and ataxia,rather than the sensations of dizziness or vertigo, butbecause of the close interrelationship between thecerebellar and vestibular systems both functionallyand neuroanatomically, it is mandatory to test forupper limb cerebellar signs (finger-nose-finger testand rapid alternating movements [dysdiadochokinesis])and lower limb cerebellar signs (heel-shintest) in all dizzy and vertiginous patients.Abnormalities indicate disease of the cerebellum or itsconnections, and tend to occur ipsilateral to anycerebellar lesion.Sensory system (see page 214)Proprioception (joint and position sense), mediatedby large fibre peripheral nerves and the posteriorcolumns of the spinal cord, is fundamental tomaintaining equilibrium. If reduced it will causeimbalance and unsteadiness; this may be initiallyapparent only in the dark because vision compensatesfor any deficiency. Minor reductions inproprioception, common as people age, mayexacerbate dizziness from other causes.Nystagmus assessmentNystagmus is an involuntary oscillation of the eyes.Nystagmus may be pendular (equal velocity andamplitude in both directions of movement[sinusoidal]) or jerk (slow phase drift in one direction,then a corrective quick phase in the other). The fastphase of jerk nystagmus is used to define the directionof the nystagmus, though the pathological movementis the slow one. Nystagmus usually involves a to-andfrooscillating movement of the eyes, but there may betorsional or rotatory components. Torsionalmovements (around the viewing axis of the eye) areseen with both end-organ and brainstem vestibular
Disorders of special senses 141disturbance. Rotatory nystagmus (a variety ofpendular nystagmus, but occurring in two planes)usually implies brainstem disease. A full discussion ofnystagmus is beyond the scope of this chapter, but adistinction should be made between spontaneousnystagmus and that observed on provocative testing.Spontaneous nystagmus. Nystagmus seen in theprimary position is usually either congenital or due toan acquired vestibular disturbance. Vestibularnystagmus is typically brought out by the eliminationof visual fixation (e.g. covering one eye while viewingthe other with an ophthalmoscope), congenital thereverse. Nystagmus only seen on eccentric gaze ismost often gaze-evoked nystagmus, and is commonlyseen in drug intoxication and cerebellar disease.Provocative testing. Dix–Hallpike’s test for positionalnystagmus is vital to diagnose BPPV (116).Headshake testing involves vigorously shaking thehead from side to side some 20 times. It stimulates thevestibular system, and may ‘bring out’ a latentasymmetry of the vestibular apparatuses, manifest asa short-lived vestibular nystagmus.The integrity of the vestibulo-ocular system canbe assessed in a number of ways. In the Doll’s eyemanoeuvre, the head is oscillated vertically orhorizontally, and normally a fully correctivemovement of the eyes in the opposite direction isobserved. This is particularly helpful in theunconscious patient (to demonstrate intact vestibuloocularreflexes) or when looking for supranucleargaze disorders. The head thrust test involves a morerapid head movement with the eyes fixed on a pointahead. Abnormality of the reflex is demonstrated bylagging eye movements relative to the head shift.Dynamic visual acuity is an assessment of anyalteration in visual acuity when the head is turnedback and forth (at approximately 2 Hz). Normalsubjects drop a maximum of one line of Snellen visualacuity with head movement.ab116116 Diagram to illustrate the Dix–Hallpike positional test. Thepatient is positioned so that when lying flat, the head extendsover the end of the table. With the patient sitting upright, thephysician turns and holds the patient's head at 45° to the side(right or left). The patient is then rapidly laid down with thehead extended over the edge of the table (a, b). The eyes arecarefully observed for the development of positionalnystagmus, which is usually not immediate. Severe vertiginoussymptoms usually accompany a positive test. Finally, thepatient should be sat upright and the eyes observed fornystagmus.
142InvestigationsThese are guided by history and examinationfindings. Specific tests that are useful in differentclinical situations are illustrated in Table 25.SUMMARY❏❏Dizziness is a nonspecific term which shouldprovoke further enquiry to establish what thepatient means.Vertigo is an illusion of movement due todisturbance of the vestibular system or itsconnections.❏❏❏❏Normal balance requires inputs from the visual,proprioceptive, and vestibular systems;impairment of any can contribute to impairedbalance. Assess all three.Brief episodes of rotatory vertigo lasting secondsare usually due to benign paroxysmal positionalvertigo or vestibular decompensation.If the history suggests syncope or presyncope, acardiovascular cause should be sought.Dizziness makes people fearful and anxious;anxiety and concern can make people feel dizzy.Sorting out the physical and emotional issues isa challenge for the physician.Table 25 Clinical syndromes and their investigationAcute severe vertigoPositional vertigoVertigo or dizziness with headacheHydrops (hearing disturbance, vertigo, tinnitus)Medical dizzinessFBC, ESR, CRP, cholesterol, glucoseECG, echocardiogramMRI posterior fossa +/- gadoliniumAudiogram (if hearing disturbance)MRI posterior fossa +/- gadoliniumTilt table testingMRI head +/- gadoliniumAudiogram (if hearing disturbance)AudiogramTFT, ESRVDRL / FTAFBC, ESR, CRP, cholesterol, glucoseECG, echocardiogram24-hr Holter monitorTilt table testingAutonomic function testsCRP: C-reactive protein; ECG: electrocardiogram; ESR: erythrocyte sedimentation rate; FBC: full blood count; MRI: magneticresonance imaging; TFT: thyroid function test; VDRL/FTA: serological tests for syphilis.
Disorders of special senses 143CLINICAL SCENARIOSCASE 1A previously well 58-year-old female bank clerk wasreferred by her general practitioner (GP) to the hospitalcomplaining of recurrent attacks of dizziness.The nature of the problem is at present unclear.‘Dizziness’ can mean many things and requires closerinvestigation.Her problems had started 5 months previouslywhen she developed an illness over days, consisting of asensation that the room was moving around her,nausea, vomiting, and malaise. Her GP had seen her,told her that she had a viral infection, and had treatedher with antibiotics and a vestibular sedative(betahistine). At the start she had been unable to movebecause it made her so dizzy. Her symptoms slowlyimproved over 2 weeks, and she was then able to returnto work at the bank.Careless questioning or very directed inquiry into thepresent problem may have missed this vital aspect of thehistory. The major symptom of this illness, which appearsto have been monophasic, sounds like vertigo. It isdifficult to be absolutely certain merely on the basis ofthis history whether the vestibular disturbance causingthe vertigo was peripheral or central: histories recalledsome time after the event are likely to be a littleuncertain. The other symptoms of nausea, vomiting, andmalaise can occur in both peripheral and centraldisturbances, but there are no specific brainstem featuresto suggest that she may have suffered a stroke, and theonset was not sudden. Her symptoms slowly resolvedover 2 weeks, and the onset, timing, and nature of theillness seem most consistent with acute peripheralvestibulopathy, presumed secondary to viral infection.Since that time she complained of recurringattacks of the room spinning around her in ahorizontal (yaw) plane. This was happening onmultiple occasions every day. Each attack lastedabout 10 seconds and seemed to occur whenevershe turned in bed, lay down, or sat up from thesupine position.This disorder is episodic, and the complaintis specifically one of vertigo. The problem isclearly positional, which immediately narrowsthe possibilities (for example cardiacarrhythmias are unlikely to be positional). Itdoes not appear to be a postural problem(suggesting postural hypotension), becauseturning and lying down cause difficulties asmuch as standing up. The duration of eachepisode is extremely short, and this is verycharacteristic of BPPV. It can also occur investibular decompensation after acute events.There were no other associatedsymptoms, including no visual symptoms, nonumbness, and no weakness. Her generalhealth was excellent in the past. She was ateetotal nonsmoker who exercised regularlyand lived with her husband. She was takingno medication when seen.These are important negatives: centraldisorders affecting vestibular tracts usually(but not always) cause other brainstemsymptoms. The lack of past history andlow vascular risk again make strokeunlikely as the cause of her initial illness.She had equal and reactive pupils. Extraocular movements were full and there was no spontaneousnystagmus. Visual fields were full and fundoscopy was normal. There was no facial weakness or sensorydisturbance and hearing was normal. Motor examination showed normal bulk, tone, and powerthroughout. There were no upper limb cerebellar signs and tandem gait was normal. Reflexes weresymmetric and plantar responses were flexor.These are all important negatives: standard neurological examination was normal. The symptoms,however, are clearly provoked by positional change, and so it is mandatory to perform positionalmanoeuvres.A Dix–Hallpike manoeuvre performed with the head turned toward the right did not produce anynystagmus. On repetition with the head turned toward the left, she developed an up-beating torsionalnystagmus after a period of 5 to 10 seconds. This subsided after an additional 10–15 seconds. Repetitionof the manoeuvre resulted in identical symptoms of lesser severity. (Continued overleaf)
144CASE 1 (continued)These findings on examination establish a diagnosis of BPPV referable to her left posteriorsemicircular canal.After a single Epley repositioning procedure (a postural means of treating this condition), no morepositional vertigo and nystagmus could be provoked and symptoms resolved.It is important to realize that 50–80% of patients with BPPV are cured by a single Epley manoeuvre.If it is unsuccessful, the procedure should be immediately repeated, and this increases the success rate toapproximately 90%.CASE 2A 51-year-old diabetic female developed episodes ofdizziness and falling, and was referred to the hospitalfor investigation. She had been diabetic for 30 years,and had been treated with subcutaneous insulin forthat time. She had a history of depression, and herdiabetes had been poorly controlled for many years,in part due to poor compliance with medication. Forthe last 3 years she had been on peritoneal dialysisfor end-stage renal disease, and she was awaiting akidney transplant. She had hypertension and haddeveloped numerous diabetic complications includingretinopathy, peripheral vascular disease, andcerebrovascular disease. She had recently been inhospital after a right subcortical stroke that hadcaused a minor left hemiparesis.It is often rewarding to enquire about complexmedical histories such as these at the start ofconsultations, since this kind of background is likelyto have such an important bearing on theinterpretation of the current problem. Diabeticpatients can become dizzy because of hypoglycaemia,and patients with renal disease (particularly those ondialysis which involves large fluid shifts) often havedifficulties with blood pressure control. Retinopathymay affect the visual component of the sensorysystem, peripheral vascular disease may affectsensation from the feet, and diabetic patients oftenhave peripheral neuropathy, which commonly affectsjoint position sense. The patient’s recent stroke willhave affected motor control, making her more proneto falls. Interpretation of the current problem ismuch more straightforward if it is considered in thecontext of the past medical history.About 3 weeks previously, she haddeveloped episodes of weakness, dizziness,and lightheadedness. Her symptoms wereintermittent, unrelated to time of day or mealtimes, and variable in duration and severity.She felt that nearly all of the episodes hadoccurred when she was standing, and that anumber had occurred shortly after she hadstood up from sitting down. When she feltdizzy her vision had become blurred and darkon a number of occasions and friends had saidshe had been pale. She felt that she wasunsteady and losing her balance, and said thatwhen she was walking she veered from side toside. She had had a number of sudden andunexpected falls. Her blood glucose readingshad been either normal or high.She has a number of symptoms. She hassymptoms of presyncope that seem to bepostural, she has symptoms of disequilibrium,and her loss of balance and walking difficultyraise the possibility that she is ataxic. She doesnot describe vertigo. The events are notoccurring at particular times of the day, andmonitoring of her glucose had not shownanything to suggest hypoglycaemia, so thisseems unlikely. Because her medical history is socomplex and could affect so many systems, it isvery possible that a number of aetiologies arecontributing to the clinical picture here.(Continued on page 145)
Disorders of special senses 145CASE 2 (continued)She was taking oral iron, multivitamins, anangiotensin-converting enzyme (ACE) inhibitor(enalapril 10 mg/day), subcutaneous insulin, andwarfarin adjusted to her international normalizedratio (INR). This had been recently introducedbecause her subcortical stroke had occurred whileshe was taking aspirin and the physician in chargeof her care wanted a stronger treatment toprevent further cerebrovascular events occurring.She had also been taking amitryptiline (100 mg)at night for depression, but had recentlydiscontinued this on her own, having beenconcerned that this may be causing her to feeldizzy. This had improved her dizziness markedly,and she had had no further falls.Often the patient will be an excellent judge ofboth the nature and cause of the problem:discontinuing the amitryptiline has helped hersymptoms. This agent is known to cause posturalhypotension, and probably caused more problemsbecause she was also taking enalapril. Dialysispatients are more prone to postural hypotension,as mentioned above. The warfarin prescription isa concern. Patients who are prone to falls shouldonly be prescribed warfarin after very carefulconsideration because it makes them more likelyto have major haemorrhage if they sustainsignificant trauma.She was in sinus rhythm. Blood pressure was146/92 mmHg (19.5/12.3 kPa) supine, and 138/86mmHg (18.4/11.5 kPa) when standing. There wereno murmurs or bruits. Pulses in the legs wereabsent below the femoral. She was unable totandem walk, and Romberg’s test was positive.Corrected visual acuity was 6/24 on both sides.Fundoscopy revealed dot and blot haemorrhagesand hard exudates around the macula. Eyemovements were normal. She had a minor leftfacial weakness and mild left hemiparesis with thearm worse than the leg. Reflexes were absent atthe ankles, but otherwise present withreinforcement. Her left plantar response wasextensor. She had marked reduction in sensation topin prick and temperature distally up to mid shin,and markedly decreased joint position sense lossand vibration sense loss in the feet.There is no significant blood pressure fall onstanding now, but this does not negate thehistory of postural events, and the symptomaticimprovement on stopping amitryptiline. She hassevere peripheral vascular disease, andretinopathy that appears to be affecting hermacula and acuity. The left hemiparesis andextensor plantar response are consistent with theknown history of recent right subcortical stroke.The new and pertinent finding is of signsconsistent with a diabetic peripheral neuropathy.A selective serotonin reuptake inhibitor(citalopram) was introduced for depression inplace of amitryptiline. Anticoagulation wasdiscontinued (there was no real indication for it,and it posed significant risk if falls recurred), andshe was started on a statin and clopidogrel asvascular prophylaxis. She was assessed by aphysiotherapist and provided with a stick.Several factors contributed to the dizzinessand falls in this case, including presyncope fromorthostatic hypotension, motor disequilibriumrelated to her hemiparesis, and sensorydisequilibrium related to her neuropathy andimpaired proprioception.
146CASE 3A 34-year-old female was referred for aneurological opinion because of persistentdizziness. She described a constant feeling of beingdizzy with fluctuating severity over the past 6months. The problem had begun while in ashopping centre when she felt very unwell, thoughtshe would faint, became very frightened, and hadto be helped to the car and driven home by herhusband. Ever since she had been reluctant to goshopping on her own.So far there is nothing in this history tosuggest an obvious cause. As previouslymentioned, patients who experience dizziness fromwhatever cause find the experience frightening,and anxious patients frequently complain ofdizziness. One possibility is that this was anepisode of presyncope but more information isneeded.On direct questioning, it was clear that shehad never experienced vertigo either in relation tothe present symptoms or in the past, had nosymptoms to suggest middle or inner ear disease,and nothing to suggest a brainstem disorder. Therewas no history of cardiac arrhythmia and noprevious faints or migraine.Again, no history to give a clear pointer as toa cause for her dizziness. The medical interviewshould also involve an attempt to get to know alittle about the patient as a person, what ishappening in their lives, how they are feeling inthemselves, and what their concerns are. It seemsas if this may be particularly important here.On gentle enquiry, it emerged that she wasunder great strain at the present time. She was amother of three young children and also ran apreschool nursery. Her husband was a busyaccountant, and she had to care for her elderlymother who lived nearby and who had becomeincreasingly infirm. She prided herself on herability to cope with all these pressures, but hadrecently begun to feel tired during the day and tohave disturbed sleep. She had found the episode inthe shopping mall very frightening, and specificallyhad thought she was going to die of a stroke likeher father. When concern about this abated shebecame convinced that she had a serious disordersuch as a tumour or MS.The neurological and general medicalexaminations were normal. Specifically,there was no evidence of vestibular disorder,nothing to suggest other neurologicaldisease, and the cardiac examination wasunremarkable.All of the above suggests that thecomplaint of dizziness is related to her lifesituation and not disease of the nervoussystem. The strict psychiatric terminologyfor her symptoms would require expertassessment and a great deal moreinformation, but physical symptoms of‘stress’ are very common, especially inpatients who ‘cope’ with difficult andstressful lives. Such patients are oftenresistant to a psychological or stress-relatedinterpretation of their symptoms, largelybecause they seem so real and serious.Terminology in this area is notoriouslydifficult. ‘Somatization’ refers to the processwhereby mental distress is expressed inphysical symptoms. ‘Functional neurologicalsymptoms’ is a better term, implying adeficit of functioning of the nervous system,rather than a structural disorder of it. Thebrain can frequently produce physicalsymptoms that suggest a disorder of thebody and hence cause illness withoutevident disease.An explanation that there was no signof serious disease as feared by the patientproduced a degree of relief but thesubsequent suggestion that the symptomsmight be stress-related was met withconsiderable scepticism. Eventually normalinvestigations including cerebral imagingtogether with the support of her family andphysician encouraged her to makealterations in her life that led to theultimate resolution of her symptoms.
Disorders of special senses 147REVISION QUESTIONS1 Which of the following statements are true?a Dizziness often coexists with vertigo, but isnot the same as vertigo.b Dizziness always implies neurological disease.c The vestibular apparatus projects sensoryinformation to the cerebellum and parietotemporalcortex.d Peripheral vertigo is often rotational and in ayaw plane.e Vestibular sensory information is conveyedwith sensory information from the cochlea(hearing) in the VIIIth cranial nerve.2 Five ‘symptom complexes’ and five common‘disease processes’ are shown below. Match eachsymptom complex with a disease process that isa common cause:a Acute severe 1 Migraine with aura.vertigo.b Positional vertigo. 2 Ménière’s disease.c Vertigo with 3 Postural hypotension.headache.d Hydrops (hearing 4 Acute peripheraldisturbance, vestibulopathy.vertigo, tinnitus).e Medical dizziness. 5 Benign paroxysmalpositional vertigo.3 Which of the following statements about theassessment of a patient complaining of dizzinessare true?a Cardiovascular examination may be omittedif there is no history of altered consciousness.b Weber’s test lateralizes to the right in a patientwith conductive hearing loss on the right.c In a patient with benign paroxysmalpositional vertigo, Hallpike’s test usuallyreproduces the symptoms.d A history of imbalance in the dark issuggestive of a proprioceptive (joint positionsense) deficit.e Sudden severe vertigo in combination withdiplopia is most likely to be caused by acuteperipheral vestibulopathy.Answers1 a, c, d, e2 a with 4b with 5c with 1d with 2e with 33 b, c, d
148Disorders of motilityWEAKNESSRichard PettyINTRODUCTIONThe assessment of a complaint of weakness iscritically dependent on the correct interpretation ofpatients’ subjective symptoms. The term weaknessmeans a reduction in strength but is rarely used in thismedical sense (Table 26); it is more often used todescribe a feeling of fatigue. The most important stepwith complaints of weakness is to be certain tounderstand what the patient is trying to describe. Acomplaint of weakness and malaise is common butdisorders producing weakness are relativelyuncommon; motor neurone disease (MND) has aprevalence of 1:20,000 and Duchenne musculardystrophy (DMD), the commonest musculardystrophy, is present in 1:3,500 male births. Nonneurologicaldisease may also result in complaints ofweakness and fatigue (Table 27). Table 28 indicatesthe range of symptoms arising from weakness indiffering distributions. Asking specifically about theseabilities will help to clarify the clinical problem.Table 26 Symptoms giving rise to complaintsof ‘weakness’❏❏❏❏❏❏FatigueFeelings of tiredness/sleep disordersDepressive illnessNumbness leading to motor dysfunctionIncoordinationStiffness in Parkinson’s diseaseTable 27 Non-neurological causes ofcomplaints of weakness and fatigueCardiac diseasePulmonarydiseaseSystemic diseaseIschaemic cardiac disease: anginapectorisLow-output cardiac failure, congestivecardiomyopathiesLow output secondary to obstruction:aortic stenosisGas exchange failure: pulmonaryfibrosisBellows failure (diaphragm orintercostals weakness) may be aneuromuscular causeAnaemiaCachexia in malignancyDepression with complaints ofweaknessTable 28 Symptoms resulting from weakness indiffering distributionsDistal upperlimbProximal upperlimbDistal lowerlimbProximal lowerlimbUnable to open door handlesDifficulty with zips and buttonsUnable to carry shoppingDeterioration in handwritingCannot put on shirt/jacketUnable to lift objects down from a highshelfDifficulty in combing hairEasy tripping if ankle dorsiflexors areweakInability to run if ankle plantarflexorsare weakInstability over rough groundDifficulty in rising from a low chair orbathDifficulty ascending the stairs (glutei)Difficulty descending the stairs(quadriceps)Waddling gait
Disorders of motility 149Functional anatomy and physiologyThe motor unit comprises the anterior horn cell ormotor neurone, its axon, and the muscle fibresinnervated by that axon (117). The number of musclefibres supplied by a single motor neurone is variableand is dependent on the function of the muscle. Largemuscles such as the quadriceps have motor unitscomprising many hundreds of muscle fibres, whereasin the facial muscles there may be single numbers. Themovement of interdigitating filaments of myosin andactin generate muscle contraction (118). Theinteraction of actin with myosin is triggered by the117 Diagram of a motorunit showing axonsupplying many musclefibres.Spinal cordMuscle fibres117NeuromuscularjunctionMotor neuroneMotor axonMuscle fibres118 Diagram of asarcomere withsubcomponents.ActinTitin118MyosinNebulinZ discZ discM lineI band A band I bandSarcomere
150release of calcium from the specialized endoplasmicreticulum termed the sarcoplasmic reticulum (119).This calcium release is triggered by the passage of an119A bandSarcoplasmicreticulum119 Diagram of the sarcoplasmic reticulum.SarcolemmaI bandT tubuleelectrical impulse along the muscle membrane.Neuromuscular transmission is a complex processinvolving influx of calcium into the terminal motoraxon, which then triggers the release of acetylcholinestored in presynaptic vesicles. Acetylcholine diffusesacross the synaptic cleft, activates the acetylcholinereceptor on the muscle membrane to allow ingress ofsodium, and sets off the electrical impulse in the musclefibre. The energy for muscle contraction is generatedby glycolysis (the breakdown of glucose) occurring inthe sarcoplasm and by oxidative phosphorylationtaking place in the mitochondria.The pattern of innervation determines manyphysiological and biochemical characteristics of themuscle fibre. The major division is between fasttwitch, glycolysis-dependent fibres and slow twitch,fatigue-resistant, oxidative fibres. Disease ordysfunction of any component may result inweakness and it can be hard in practice to distinguishbetween weaknesses due to the individualcomponents. Many systems determine the activity ofthe motor unit, and dysfunction of these systems mayalso give rise to weakness (120).120Conscious thoughtto move120 Diagram to showthe anatomy of motorcontrol.Motor cortexBasal gangliaCerebellumMotor unitContraction/movement
Disorders of motility 151A critical distinction that has to be made isbetween weakness resulting from a motor unit(lower motor neurone [LMN]) weakness andfrom the upper motor neurone (UMN).The distinction rests on aspects of theexamination and the presence or absence ofadditional features (Table 28; see Introduction).The following terms are used to describe thelocalization of weakness and reflect importantanatomical distinctions:❏ Intracranial; remember the cranial nerve nucleiare within the skull.❏ Spinal; taken to mean the process is localizedbelow the foramen magnum but with no betterlocalization.❏ Disorders of the motor neurone itself arereferred to as motor neuronopathies.❏ Disorders of the emerging motor axons (forexample disc protrusions) within the spinal canalare referred to as root lesions or radiculopathies.❏ A plexus lesion (often infiltrative) is due todamage to all or part of the brachial orlumbosacral plexus.❏ Peripheral nerve disorders are classifiedaccording to whether a single nerve is involved:a mononeuropathy (often mechanical); manyindividual nerves at discrete sites (mononeuritismultiplex, seen in inflammatory diseases); or, ifall nerves are involved, a diffuse peripheralneuropathy (as in diabetes mellitus). Furtherrefinements in description refer to theinvolvement of sensory, motor, or autonomicfibres. On occasion it is also possible to describewhether the axon or myelin sheath is the site ofpathology, axonal or demyelinatingneuropathies.❏ The neuromuscular junction is a potential site of❏pathology.A myopathy is any disease where the musclecells are the primary site of pathology. Amuscular dystrophy is a genetically determined,progressive disorder of muscle characterized bymuscle fibre necrosis.CLINICAL ASSESSMENTFocused history takingHistory taking from a patient with a complaint ofweakness must start by characterizing the severityand pattern of the weakness. The problems shown inTable 28 offer a guide, but patients should beencouraged to elaborate on the difficulties they have.It is also critical in formulating a diagnosis to becertain about the timing of onset of symptoms andthe pattern of evolution. Questions should be askedof early development (of parents if necessary) andabilities at games at school. Lost skills or abilitiesnoted either by the patient or other family memberwill give an index of the rate of evolution of theillness. In addition, the specific aspects describedbelow should be covered.PainPain arising as a direct consequence of primarymuscle disease is usually precisely localized by thepatient to muscle. They know it is muscle pain andnot joint or nonspecific deep pain. In metabolicdefects such as McArdle’s disease (a disorder ofglycogen breakdown), it is clearly related to exercise:severe pain with contracture develops often within 1minute of ischaemic exercise and affects theexercising muscle only.CrampMuscle cramps are universal and normal and aremost often felt in the calf muscles. They areassociated with high frequency, irregular bursts ofmuscle fibre activity and originate in distal motoraxons. Fasciculations are the spontaneous dischargeof all the muscle fibres in a motor unit and arecommon in motor unit diseases such as amyotrophiclateral sclerosis (i.e. MND). Patients may be aware ofthis spontaneous activity. Painful cramps on exerciseare a feature of some metabolic myopathies and, ifcramps are complained of, the relationship to exerciseshould be clarified.FatiguabilityThis is another term rarely used in the medical senseof an excessive failure of strength on repeatedcontraction. It is more often used in the context ofsystemic disorders such as anaemia or nonspecificfeelings of exhaustion. True fatigue is a feature ofneuromuscular transmission disorders and is also amajor feature of disorders of energy metabolism (suchas mitochondrial disorders), where it is oftenassociated with malaise, headache or nausea and(sometimes) vomiting, reflecting an exercise-inducedlactic acidosis. The word is also often used to describethe exercise limitation occurring in disordersassociated with cardiomyopathies or respiratorymuscle weakness (which may exist without clinically
152obvious limb muscle involvement) such as myotonicdystrophy or acid maltase deficiency.It is also important to then ask about any possiblesymptoms of weakness elsewhere that the patient maynot recognize as due to weakness, or may not haverecognized as important.Complaints of double vision occur when controlof eye movement is lost. This can be as a result ofbrainstem disease, a lesion affecting the oculomotornerves, a neuromuscular transmission disorder, or aprimary myopathy. Changes in the quality of speechhave been discussed in the Introduction, but it is oftenhelpful to ask the patient to talk for a period of timeif weakness of the bulbar muscles is suspected.Relatives may also comment on a change not notedby the patient. Changes in swallowing, like doublevision, can be due to problems at many sites but it isimportant to ask directly whether the patient hasnoted change. Questions concerning family history,drug history, and social history are also critical:❏ Family history. Inherited disorders of peripheralnerve and muscle are among the most commoninherited disorders. It is important when takinga history to ask about other family members.Some disorders are mild and it may be necessaryto examine other family members to establishthe diagnosis of an inherited disorder.Table 29 Myotomes of importanceC5 Deltoid, bicepsC6 Biceps, brachio-radialisC7 TricepsC8 Finger flexorsT1 All intrinsic hand musclesL1, 2 Hip flexionL3 Knee extensionL4 Knee extension, hip flexion, ankle dorsiflexionL5 Ankle dorsiflexion and eversion, hip extension,knee flexionS1 Ankle plantarflexion❏❏Drug history. Drug toxicities are a major causeof peripheral nerve disease. Some cytotoxicdrugs used in cancer treatment will almostinvariably cause some damage to peripheralnerves. A full current and recent past drughistory must be taken. Steroid drugs are acommon cause of a proximal muscle weaknessalthough muscle toxicity is an unusual drug sideeffect.Occupational history. This is important not onlyin establishing prior levels of physical ability butwill also determine the impact of a particulardeficit on an individual. Questions should alsobe asked of current domestic circumstances andhow people are managing daily tasks within thehome.Questioning should then return to the presentingcomplaint and should involve direct questionspertinent to the possible localization of the problem.Such questions might include:❏ Cortical: lateralized weakness may be due to acortical lesion where questions about headacheor focal seizures are important. A frontal lesionmay give rise to anosmia.❏ Hemisphere: movement disorder if basal gangliaare involved, headache if a mass lesion issuspected.❏ Brainstem: many possible features includingdiplopia, dysarthria, dysphagia, facial sensoryabnormalities, vertigo, and disequilibrium.❏ Spinal cord: the important observation is thatsymptoms can be localized to a level; there willbe no symptoms or signs referable above and theproblems can be accounted for by disease at onelevel. Problems may include sensory loss (whichmay be dissociated, see below) and bladderdysfunction (see below).❏ Nerve root: symptoms and signs may involve asensory disturbance in the territory of theaffected root (121) and discomfort in theinnervated myotome, i.e. the muscles innervatedby that root (Table 29). The reflex arc subservedby that root may be depressed or absent as theprocess affects both afferent and efferentpathways (122).
Disorders of motility 153C5T2C6 T1121aC3C4T2T3T4T5T6T7T8T9L1L2T11T12S3S4L3S5S4L3L1L2S3S2L2121bC6T10T11T12L1C7C8L5L4121 Diagram to show the dermatomal supply of the upper (a)and lower (b) limbs.S1S1 L5S1L5122 Diagram to show the anatomy ofthe spinal cord.Lateralcorticospinal tractRubrospinaltractOlivospinaltractVestibulospinaltractTectospinal tractDorsolateral tractAnterior corticospinal tractFasciculus gracilis122Fasciculus cuneatusGelatinous substancePosteriorspinocerebellartractAnteriorspinocerebellartractLateralspinothalamic tractFasciculus propriusAnterior spinothalamic tract
154❏❏❏Peripheral nerve: symptoms and signs will berestricted to the distribution of the affectednerve. Again, motor and sensory function will beaffected (Table 30, 123).Neuromuscular junction: symptoms and signs willbe purely motor. Fatiguability, if sought, is usuallya prominent feature. These disorders, despiteaffecting all muscles, may present with very focalsymptoms. Reflexes are usually preserved.Muscle: problems will be purely motor.Weakness and wasting are prominent features.Reflexes are usually unaffected; there is nodamage to the reflex arc. The distribution of theweakness will be critical in making a diagnosis:is it proximal, distal, or selective?Focused examinationObservationIt is important to watch someone walking. This mayshow the scissoring gait of spasticity, reveal a foot dropgait, or the slow initiation and turning of a movementdisorder such as Parkinson’s disease. If specific tasksare described as difficult then the patient should beasked to perform them if possible, and any difficultyobserved. It is also critical to examine for musclewasting; the upper limbs should be first examined frombehind the shoulders so that the periscapular musclescan be seen. The arms, forearms, and hands are thenlooked at. These muscles are usually larger in thedominant arm. The hands should be held supinated tolook at the forearm flexor muscles. The first dorsalinterosseus and thenar eminence should be examinedwith care; wasting is easily missed. The limbs should beexamined for any evidence of joint contracture.PalpationThis is less important in the assessment of weakness,though inflammatory disorders may cause indurationand muscle tenderness.PowerTable 31 lists the muscles that should be routinelytested. This allows the major roots and peripheralnerves to be included in the assessment. It is importantto recognize that the lower limb muscles are, in thenormal situation, much stronger than the examiner’supper limb muscles, and mild weakness will not bedetectable when testing strength on the couch. In thissituation, other tests are needed. Asking the patient torise from a crouch tests hip extensors and kneeextensors; to stand on tiptoes tests ankle plantarflexion;to walk on the heels tests dorsiflexion.Table 30 Patterns of deficit in major peripheralnerve lesionsRadial nerve in radial groove on humerus❏ Weakness of wrist extension❏ Weakness of finger extension❏ Loss of sensation in anatomical snuffboxUlnar nerve at elbow❏ Weakness of flexor digitorum profundus III, IV❏ Weakness of interossei in hand❏ Sensory loss as shown (123)Median nerve at wrist❏ Weakness of abductor pollicis brevis❏ Sensory loss as shown (123)Lateral popliteal nerve at knee❏ Weakness of ankle dorsiflexion❏ Weakness of eversionTable 31 Movements to be routinely testedPeripheralMovement Muscle(s) nerve(s) Root(s)Shoulder Deltoid Axillary C5abductionElbow flexion Biceps Musculocutaneous C5,6Brachioradialis RadialElbow Triceps Radial C7extensionFinger flexion Long flexors Anterior C8interosseusUlnarFinger Interossei Ulnar T1abductionThumb Abductor Median T1abduction pollicis brevisHip flexion Iliopsoas L1,2Hip extension Gluteus Sciatic L5,S1maximusKnee flexion Hamstrings Sciatic S1Knee extension Quadriceps Femoral L3,4Ankle Tibialis Deep peroneal L4,5dorsiflexion anteriorAnkle Gastrocnemius Tibial S1,2plantarflexion Soleus
Disorders of motility 155123a123b123 Diagram to show the sensory loss in lesions to the radial(a), ulnar (b), and median (c) nerves.123c
156Tone, coordination, reflexes, and plantar responsesMuscle tone should assessed at the elbow, knee, andankles. The assessment of coordination is usuallyregarded as part of the assessment of the motorsystem. It is important to remember, however, thatcoordination depends on an intact sensory system,brainstem, and cerebellum as much as on musclepower. Coordination can appear impaired if there issevere weakness. The reflexes that should always beassessed are shown in Table 32 with the localizationof the reflex arc.The investigation of complaints of weakness isclearly critically dependent on accurate anatomicallocalization. It is usually possible to make adistinction between upper and lower motor neuronepatterns (Table 33). Furthermore, careful historytaking and examination should allow a judgement tobe made as to whether a purely motor disorder ispresent or one involving sensory or autonomicfunction. If an anatomical localization is possible anda structural lesion is suspected, then imaging can bedirected to that area. If muscle is thought to be thesite of pathology the investigations described belowmay be considered.Serum creatine kinaseCreatine kinase (CK) is an enzyme localized to themuscle sarcoplasm. A process leading to a loss ofintegrity of the muscle cell membrane will allowleakage of CK. CK levels can be measured in blood;however, it is important to recognize that the normaldistribution in the population is skewed and althoughnormal ranges are often quoted as 170 IU/l, manynormal individuals will have levels between 200 and300 IU/l. It is also a very sensitive test. Unaccustomedexercise can provoke a rise from normal to upwardsof 1000 IU/l. This means that an isolated elevationmust be interpreted with caution. Indeed, the changesin muscle arising from loss of the nerve supply(denervation) can be associated with rises of CK to500–1000 IU/l.Electromyography and nerve conduction studiesThese neurophysiological studies address differentquestions. Electromyography (EMG) detects theelectrical activity of muscle fibres using a needleinserted into resting and active muscle. The pattern ofactivity changes if there is ongoing denervation,damage to muscle membranes, or abnormally smallmuscle fibres. It also allows the detection of the largemotor units seen in disorders where denervation isfollowed by reinnervation by surviving motor axons(124). Nerve conduction studies (NCS) use electrodesto record from both motor and sensory nerves. Inusual practice, only myelinated axons are studied.Information is gathered on conduction velocity andthe amplitude of the nerve impulse under study. Thefindings often allow a distinction to be made betweendisorders affecting the axon and those affecting themyelin sheath. They also allow motor and sensoryfibre populations to be studied independently.Muscle biopsyPathological examination of muscle is used if aprimary disorder of muscle is suspected. It allows thespecific diagnosis of some metabolic disorders andmuscular dystrophies and is also important in thediagnosis of inflammatory muscle disease. The biopsycan be obtained by use of a wide bore needle (needlebiopsy) or under direct vision (open biopsy).Table 32 Reflexes routinely assessedReflexNerve root levelBiceps C5, 6TricepsC7Finger jerksC8Knee jerk L3,4Ankle jerk S1,2Table 33 Clinical features of upper and lowermotor neurone weaknessUpperLowermotor neurone motor neuronePower Weakness of Weakness restrictedextensor muscles to musclesin the upper limbs innervated byand flexors in the affected lowerlower limbs motor neurone(s)Tone Increased with Normal or reducedspastic quality if marked wastingis presentReflexes Increased May be reduced orabsentPlantar Extensor FlexorresponsesBulk Normal Wasting
Disorders of motility 157124a124b124 Electromyography studies in myopathy, showingmyopathic potentials (a) and large neurogenic potentials (b).SUMMARY❏❏❏❏❏❏Time must be given to listen to and understandthe quality of the symptoms the patient isdescribing.The rate of evolution and date of onset ofsymptoms must be carefully documented; it maybe longer than at first apparent.Any family history should be documented.The distinction between upper and lower motorneurone weakness is critical to accuratediagnosis.Fatiguable disorders kept in the waiting areaprior to seeing the clinician may return tonormal.A diagnosis should be formulated and localizedprior to requesting imaging orneurophysiological studies.❏❏❏❏The motor unit is the functional lower motorcomponent; differentiating neurogenic frommyopathic weakness can be very difficult.It is necessary to remember that the spinal cordterminates at the level of L1 or L2; lumbardisease cannot produce upper motor neuronesigns in the legs.The patient should be observed walking.The shoulder and periscapular muscles shouldalways be examined from behind.
158CLINICAL SCENARIOSThe following case histories illustrate how this approach allows localization and diagnosis in neurologicalpractice.CASE 1A 56-year-old female seeks advice because of a 3-year slowly worsening problem with her legs.She says ‘they won’t go’. Friends have told her she is dragging her legs and looks as if she islimping. Things feel worse on the right than the left and she has decided to ask for help as shehas begun to trip up over her right ankle.This history gives some useful information. It sounds like an acquired disorder, coming on inmid life and progressing. There is involvement of both lower limbs, and the right is more affectedthan the left. The problem cannot be localized at present but further questioning reveals moreinformation.She does not think her arms are weak but has had some discomfort between her shoulderblades for the past 6 months. This is worse at night and feels like a band around her chest goingto the right hand side. When asked to describe what is wrong with her legs she says they don’tfeel right, they are ‘stiff, like tree trunks. I am walking like a robot’. Further questioning revealsshe cannot feel the temperature of the bath water properly; it feels suddenly very hot when sheputs her hands in, having previously tested it with her left foot. She is sure her upper limbs arenormal, she has had no symptoms referable to her cranial nerves, and there is no history ofheadache.The words she uses to describe her problems suggest an increase in muscle tone. The sensorystory is striking and suggests that the process is involving both motor and sensory systems. Thisimplies an upper motor neurone (UMN) disturbance and that the problem also affects sensorypathways. There are no associated features to suggest that the UMN pathway (the pathway fromthe motor cortex to the anterior horn cell) is being affected within the head, and the upper limbsare normal. The history of chest pain is interesting as a lesion in the thoracic cord at that levelcould involve the UMN pathway to the lower motor neurones as it traverses the thoracic cord.The examination confirmed a gait abnormality and she walked with a scissoring motion,tending to scuff her right toe on the ground. The cranial nerves and upper limbs were normal.A spastic gait disorder has been confirmed and no abnormalities have been found to implydisease above the site of her pain.Examination of her trunk showed that pinprick sensation was felt normally above the levelof T7 (121) but below this level was felt only as a prod on her left-hand side. Examination of herlegs showed no wasting. She had a spastic increase in tone more marked on the left than theright and there was clonus elicitable at both ankles, which was sustained on the right. She hadweakness diffusely in both legs, more marked on the right with relative sparing of antigravitymuscles.A UMN problem is being confirmed. The pattern of weakness is also typical of involvementof the UMN.The reflexes were all brisk and both plantar responses were extensor. Sensory examinationshowed she had reduced joint position sensation at the right great toe, with reduced vibrationsensation.(Continued on page 159)
CASE 1 (continued)Disorders of motility 159Bilateral disease has been confirmed and a pattern ofsensory loss demonstrated that can be explained on thebasis of a lesion affecting the spinal cord. A mass lesioncompressing the spinal cord from the right side would beexpected to:• Damage the UMN pathways more on the right thanleft.• Damage the ipsilateral ascending posterior columns,which contain fibres subserving joint positionsensation and proprioception.• Damage ascending but crossed pain fibres in thelateral spinothalamic tract.• Damage descending fibres controlling bladderfunction.All of these findings have been demonstrated, apattern referred to as a Brown-Séquard syndrome.Figures 125 and 126 show the MRI scans demonstratinga neurofibroma at T6 compressing the cord from theright.125 Sagittalmagneticresonanceimageshowingthoracicneurofibroma.125126126 Axial magnetic resonance image showing the dumb-bellappearance of thoracic neurofibroma.
160CASE 2A 65-year-old male smoker presents with a 2-month history of soreness in his right arm and apoor grip. He had sought help because he could nolonger turn his car key in the lock. Furtherquestions revealed a story of a 1-stone (6 kg)weight loss over the previous 4 months. He hadalso felt nonspecifically unwell. He gave no storyof weakness elsewhere, but on direct questioningremarked that sensation on the inner side of hisright arm was odd.The story with weight loss is, in this context,suggestive of an underlying neoplasm. The story isprogressive and localized to the right arm. Thepain implies the involvement of either sensorypathways or non-neurological structures.General examination was normal other thansome tenderness in the right supraclavicular region.The left arm and lower limbs were normal. Cranialnerve examination was normal with the exception ofa right-sided mild and partial ptosis and the rightpupil was smaller than the left. Both reacted to lightand accommodation. The right arm had weaknessand wasting involving all the small hand muscles.The forearm muscles were of normal bulk andpower. The biceps, triceps, and supinator reflexeswere normal. There was loss of sensation to pinprickover the medial right arm and forearm.The weakness and wasting of the hand musclesindicate a lower motor neurone (LMN) problem.This is localized and while a combined median andulnar nerve problem peripherally could account forthis, the sensory loss corresponds to a T1distribution. Note that the dermatome of T1 (theskin area corresponding to the sensory fibres enteringthe spinal cord at T1) does not overlie the myotome(the muscles innervated by the T1 motor fibres). TheT1 root supplies all the intrinsic muscles of the handso there may be localization. The ptosis on the rightcan be explained. The eyelid is maintained inposition by the action of levator palpebrae superioris(innervated by the IIIrd cranial nerve). Thesympathetic nerves also innervate fibres within thismuscle. These fibres also act as pupil-dilating. Theconsequence of damage to the sympathetic nervefibres going to the eye is thus partial ptosis andmiosis. Additional effects of damage to these fibresinclude a lack of sweating over the face andenophthalmos, but these are less often clinicallyapparent. These sympathetic fibres reach the orbithaving exited the spinal cord at the T1 root. Theysynapse in the stellate ganglion and reach the orbitby travelling in the sheath of the internal carotid andophthalmic arteries. Thus a lesion involving the T1root could account for this clinical picture.The tenderness in the right supraclavicularregion corresponds to the erosion of this area by alung tumour arising at the apex of the right lung,as was seen on chest X-ray and MRI (127, 128).This complex of symptoms and signs is referred toas a ‘Pancoast’ tumour.127128128 T2magneticresonance imageshowing softtissue massinvolving C7,T1, and T2 withvertebralcollapse andmoderate cordcompression.127 Chest X-ray showing right apical opacity due to aPancoast tumour, with partially destroyed second andthird ribs.
Disorders of motility 161CASE 3A 57-year-old female who has been well in the past gives a 6-month story of a problemwith her left foot. She says it won’t work and she has begun to trip over on it. It isbecoming a little more troublesome but she has only attended at her relative's insistence.She denies any weakness elsewhere and is not aware of any sensory problems or changein bladder control.This sounds like a purely motor problem so far and it seems to be localized butthere is very little else to help make the diagnosis. Tripping up usually means weaknessof the ankle dorsiflexors, but these muscles will become weak in the context of anevolving UMN lesion as well as with L5 root disease or a lesion of the lateral poplitealnerve.There is no story of pain and she is otherwise medically well and on no drugtherapy. She does, however, say that she has noticed a lot of cramps recently, not only inher calf but also in both thighs and across her shoulders. Examination of the cranialnerves is normal. In the limbs there are widespread twitching movements visible. Thesehave the appearance of fasciculations. She does have mild proximal weakness diffuselyin the arms. The legs show weakness of plantar and dorsiflexion on the left. There iswasting of all the muscles below the knee of the left leg and again widespread twitchingis visible. The reflexes are all intact including the left ankle jerk where the wasting ismost clearly seen. Both plantar responses are extensor. Sensation is normal.This is a slightly confusing array of signs. The wasting and weakness imply LMNpathology. The fasciculations also may be due to anterior horn cell disease; moreextensive abnormalities are present that cannot be explained on the basis of either an L5root or lateral popliteal nerve lesion. Abnormalities are present in both upper and lowerlimbs so a focal lesion is impossible. A disease process involving the spinal cord fromthe cervical region to the lumbar expansion could produce such widespread LMN signs,but some sensory features or bladder disturbance might be expected. The reflexes,however, are brisk and the plantar responses extensor, implying UMN pathology.The investigating physicians were concerned that the spinal cord may be diseasedalong its length but images and examination of cerebrospinal fluid were normal. EMGstudies were arranged to identify the extent of LMN involvement and she alsounderwent NCS to examine motor nerve function. EMG demonstrated evidence ofongoing denervation in the muscles of her neck, arms, and legs. This was present in allsites and on right and left. NCS showed normal sensory function and no evidence ofdamage to the myelin sheath of the motor fibres, but did show evidence of motoraxonal loss.This clinical scenario is of a woman with motor neurone disease (MND). This is adegenerative process involving the upper and lower motor neurones. It is progressiveand incurable leading to slowly increasing weakness of all striated muscle. It will beimportant when speaking to her about the diagnosis to recall her lack of initial concern;the giving of bad news when unanticipated requires great tact and delicacy.
162REVISION QUESTIONS1 A lesion of the left S1 root would be expected toreduce or abolish the left ankle jerk reflex.2 Muscle wasting is a characteristic feature oflower motor neurone weakness.3 An elevation of serum creatine kinase activity totwice the upper limit of normal invariablyindicates neuromuscular disease.4 Extensor plantar responses are not a feature ofupper motor neurone weakness.5 A motor nerve always innervates a single musclefibre.6 A defect in oxidative muscle metabolism wouldbe expected to produce limitation of sustainedexercise rather than brief intense exercise.7 Disorders of neuromuscular transmission may beassociated with fatigue.8 Cramps may be a prominent feature of motorneurone disease.9 A lesion of the right C5 sensory root would beexpected to be associated with sensory loss inthe axilla.10 A lesion in the spinal cord may produce bothupper and lower motor neurone features.11 It is appropriate to image the lumbar spine of apatient with spastic leg weakness and numbnessinvolving the legs and up to just below theumbilicus.12 Transection of the ulnar nerve at the elbow willcause weakness of all the intrinsic hand muscles.13 Diseases of the motor unit would be expected togive rise to sensory symptoms.14 Some inherited neuromuscular disorders are somild affected individuals may never seek medicaladvice.15 Steroid administration may cause muscleweakness.Answers1 True.2 True.3 False.4 False.5 False.6 True.7 True.8 True.9 False.10 True.11 False.12 False.13 False.14 True.15 True.
Disorders of motility 163TREMOR AND OTHER INVOLUNTARYMOVEMENTS Vicky Marshall, Donald GrossetINTRODUCTIONDisruption of the basal ganglia and extrapyramidalsystem causes abnormal involuntary movements thatare either reduced (hypokinetic) or increased andexcessive (hyperkinetic). The general lack ofmovement seen in Parkinson’s disease (PD) is anexample of a hypokinetic disorder. Chorea is anexample of a hyperkinetic movement disorder,characterized by excessive involuntary movements.This chapter covers clinical aspects of involuntarymovements, and how to use the clinical examinationto differentiate between the different types ofmovement disorder. It provides anatomical andphysiological insights into the mechanisms of controlof movement, and therefore disturbance ofmovement. Tremor disorders will be considered in themain, but information on the taxonomy of otherinvoluntary movements will be provided.TREMORTremor, as defined by the Movement Disorder Society,is a rhythmical, involuntary, oscillatory movement of abody part. It is the rhythm that distinguishes tremorfrom other abnormal involuntary movements. Usuallythe differentiation of types of tremor is straightforwardbased on history and examination, although difficultiesmay be met particularly in the early stages of tremor.Tremor classificationTremors are most commonly classified according tocauses or clinical characteristics, but as the aetiology ofmany tremors is not fully understood and needs to becontinuously updated, use of the clinical characteristicstends to be favoured and is more clinically useful. Table34 defines each tremor type (rest and action, posturaland kinetic) and details the main conditions in whichthese tremors commonly occur. It should be recognizedthat different tremor conditions may be ‘mixed’comprising more than the main tremor typeTable 34 Tremor classificationCharacteristicsDisorderRest Occurs when a body part is not voluntarily Parkinson's disease: may also have postural and intentionactivated and is fully supported against gravity, components but usually rest tremor is more prominente.g. arms and hands resting in the lapDrug-induced parkinsonism (dopamine antagonists,e.g. neuroleptics)Drug-induced tremorPalatal tremorSeldom occurs in other conditionsActionAny tremor occurring during voluntary contraction of muscle. Includes postural, kinetic (which includes intention), andisometric tremorPostural, present while maintaining position againstgravity, e.g. arms maintaining outstretched positionEnhanced physiological tremorEssential tremorDrug-induced tremorOrthostatic tremorNeuropathic tremor syndromeDystonic tremorPsychogenic tremorKinetic, present during any voluntary movement; target (intention tremor) or nontarget directed movementIntention tremor, e.g. finger–nose testTask-specific kinetic tremor(Disturbances of cerebellar pathways)Cerebellar tremorDrug-induced tremorHolmes tremorDystonic tremorPrimary writing tremor
164characteristic for that condition. For example, althougha rest tremor is characteristic for PD, actioncomponents to the tremor can coexist.Specialist anatomy and physiologyThe basal ganglion is a term which refers to four mainsubcortical nuclei that regulate and coordinatemovement: the striatum (comprising the putamen andcaudate), globus pallidus, subthalamic nucleus, andthe substantia nigra (129, 130). These grey matternuclei maintain muscle tone needed to stabilize jointpositions or inhibit muscle tone during initiation ofmovement. PD is a neurodegenerative disease ofunknown aetiology, in which degeneration ofdopaminergic neurones projecting from the substantianigra pars compacta to the striatum occurs, resultingin deficiency of dopamine within the striatum. Thedegeneration of the neurones within the substantianigra causes loss of the characteristic black (‘nigra’)pigmentation. Clinical symptoms occur when there isdepletion of 50–70% of striatal dopamine.129CortexStriatumGlobuspallidusThalamusSubthalamicnucleusCaudatePutamenExternaInternaSubstantia nigra129 Neuroanatomical schematic diagram of extrapyramidalstructures.130CORTEXGlutamateTHALAMUSEncephalin/GABASTRIATUMGABAGlutamateSUBTHALAMIC NUCLEUSInhibitory neuroneExcitatory neuroneGABAInterna ExternaGlobus pallidusSUBSTANTIANIGRAParkinson’s diseaseDisruption here ofdopaminergic fibresfrom the substantianigra to the striatumDopamineAcetylcholineHuntington’s diseaseDegeneration of fibresfrom the striatum to theglobus pallidus externa.(loss of neurones in thecaudate nucleus)130 Schematic representation of the interaction between basal ganglia, thalamus, and cortex. GABA: gamma amino-butyric acid.
Disorders of motility 165SPECIFIC TREMOR DISORDERSParkinson’s disease and ‘Parkinson’s plus’ disordersPD has a prevalence of approximately 1% in thoseover 65 years, but occasionally has younger onset aslow as 30 years (juvenile PD). In early disease,patients may describe small handwriting(micrographia), rest tremor, or stiffness of a limb.Relatives may note a reduced facial expression,diminished blinking, or an arm that does not swingon walking. Some patients may notice a reduction insense of smell. Features are typically asymmetricaland include bradykinesia, rigidity, tremor, andpostural instability (Table 35). Tremor is the firstsymptom in up to 75% of patients with PD, but 20%of patients never develop tremor. Up to 25% ofpatients diagnosed with PD in life have an incorrectdiagnosis.The characteristic tremor usually has a frequencyof 4–6 Hz, starting in an arm and spreading to the legon the same side then to the contralateral limbs. It isalso called a ‘pill-rolling’ tremor on account of itbeing a back-and-forth motion of the thumb andindex finger occurring at rest. It becomes less duringposture holding and intention (movement).Sometimes tremor is the most prominent feature withlittle in the way of other features, and this is referredto as benign tremulous PD. In other cases, wheretremor is absent, the patient is described as having theakinetic-rigid form of PD. Primitive reflexes may bepresent. Patients may be stooped. Walking may beaffected; patients may stop in mid stride withdifficulty in restarting movement, called ‘freezing’.When a patient walks with small steps as if hurryingforward to keep balance it is known as festination.Patients may have reduced facial expressioncausing some people to think they are depressed, anda soft voice. Other symptoms that patients maycomplain of are depression, emotional changes andmemory loss, constipation and urinary problems,sexual difficulties, and sleep difficulties. As thedisease progresses, some patients may have troubleswallowing or chewing and may develop dementia,hallucinations, or delusions (caused by acombination of medication and disease). Involuntarychoreiform movement of trunk, limbs, or headusually occurs after many years of drug treatment,and is referred to as dyskinesia.‘Parkinson’s plus’ disorders consist ofparkinsonism plus additional features, which resultfrom neuronal degeneration outwith the basalganglia. ‘Parkinson’s plus’ should be considered aconcept rather than a diagnosis. These conditionsonly respond to antiparkinson drugs in the first fewyears, unlike PD where a long-term treatmentresponse is maintained. Progressive supranuclearpalsy (PSP), previously known as Steele–Richardson–Olszewski syndrome, is characterized by axial rigidity(particularly neck rigidity), ophthalmoplegia (thesupranuclear palsy component of the name) withreduced vertical eye movements (reduced downwardgaze is more specific), and early and frequent falls.Multiple system atrophy (MSA) is classifiedaccording to whether patients demonstrate primarilyparkinsonism (MSA-P) or cerebellar (MSA-C)features, in which speech and limb movementsbecome ataxic. Autonomic features (e.g. posturaldizziness, bladder and sexual dysfunction) may beprominent in either. Corticobasal degeneration (CBD)may have limb dystonia, myoclonus, apraxias, andthe ‘alien limb’ phenomenon in addition toparkinsonism. All the Parkinson’s plus disorders areless common than PD and all have uniqueneuropathological findings.Drug-induced parkinsonismThe signs of PD may be mimicked by the use ofmedications that cause dopamine depletion. Theseinclude some antipsychotics (although the neweratypical antipsychotics are less likely to cause thesame problems) and antiemetics such asmetoclopramide and prochlorperazine. The signs arereversible on drug withdrawal and usually take weeksto a couple of months to resolve. Occasionally, theuse of dopamine-depleting drugs may ‘unmask’ PD inpatients with preclinical disease (when clinical signswere not present prior to drug treatment).Table 35 Cardinal criteria for parkinsoniansyndrome❏❏BradykinesiaAnd at least one of the following:– Muscular rigidity– 4–6 Hz rest tremor
166Many additional conditions can haveparkinsonian signs associated with them:cerebrovascular disease affecting the subcortical areas(causing lower body parkinsonism which, as thename suggests, affects legs more than arms, while PDis the other way around), hydrocephalus (a classicaltriad of gait disorder, urinary incontinence, anddementia), encephalitis, hypoxic brain injury; andtoxin exposure (e.g. carbon monoxide).Table 36 Criteria for classic essential tremorInclusion criteria❏ Bilateral, largely symmetrical postural or kinetictremor, involving hands and forearms that is visibleand persistent❏ Additional or isolated tremor of the head may occurbut in the absence of abnormal posturingExclusion criteria❏ Other abnormal neurological signs, especially dystonia❏ Presence of known causes of enhanced physiologictremor❏ History or evidence of psychogenic tremor❏ Convincing evidence of sudden onset or evidence ofstepwise deterioration❏ Primary orthostatic tremor❏ Isolated voice tremor❏ Isolated position-specific or task-specific tremors❏ Isolated tongue or chin tremor❏ Isolated leg tremorEssential tremorEssential tremor is at least 2–3 times commoner thanPD, though only about 10% of patients with essentialtremor seek medical advice. It is often a hereditarydisorder; autosomal dominance is common but manycases are sporadic. Typically, there is a symmetricaltremor of the upper limbs, with insidious onset andslow progression. The tremor is worse on postureholding and intention, and is rarely prominent at rest.Patients may describe difficulty in holding a cupwithout spilling it and are often embarrassed by thetremor. The head, chin, jaw, and lips may be affectedand occasionally the legs, but never in isolation (Table36). The tremor may be transiently improved withalcohol. Parkinsonian signs are typically absent, butin the older population a degree of age or arthritisrelatedslowing may cause difficulty in distinguishingthis from parkinsonian disorders (Table 37).OTHER TREMORS (131)Physiological tremor occurs in every normal subjectaround every joint that is free to move. It is of lowamplitude and of high frequency in the fingers andhand (just visible to the naked eye) and low inproximal joints, and is enhanced by muscular fatigueand anxiety. It is called enhanced physiologicaltremor when it is easily seen by the eye, usuallypostural and of high frequency, and is reversible if acause is found (such as thyrotoxicosis, phaechromocytoma,drug withdrawal states, caffeine excess, andalcohol intoxication).Table 37 Typical features which aid differentiation between Parkinson’s disease andessential tremorParkinson's diseaseEssential tremorTremor character Rest; 4–6 Hz Postural, kinetic; 6–12 HzSite Hands, legs Hands, head, voiceOnset Unilateral BilateralOther features Bradykinesia Postural instabilityRigidityFamily history Usually negative Positive 50%Alcohol No effect Marked reduction in tremorBeta-blocker May reduce tremor EffectiveLevodopa Effective No effect
Disorders of motility 167Cerebellar tremor syndromes include intentiontremor and titubation. Many medications may causedrug-induced tremor, e.g. amiodarone, lithium,sodium valproate, prednisolone, and selectiveserotonin reuptake inhibitors (SSRIs). A clear causalrelationship with onset of medication is sought but notalways found as tremor onset may be delayed. Thesetremors are usually kinetic in nature. Drug-inducedparkinsonism has already been mentioned above.Holmes tremor was previously labelled as rubral,thalamic, and midbrain tremor and is caused by alesion of the brainstem/cerebellum and thalamus. It isa slow (
168nonrhythmic, involuntary, purposeless motion whichprimarily involves the face or extremities and mayflow from one body part to another. Movements maybe jerky and relatively rapid. If several choreicmovements are present, they may appear slow andwrithing, resembling athetosis (choreoathetoid).Some causes of chorea are listed in Table 38.Huntington’s diseaseHuntington’s disease (HD) is a progressive disordercharacterized by chorea and dementia. It is due to anexpanded and unstable trinucleotide repeat (CAG) onchromosome 4, which is inherited in an autosomaldominant manner. Mean age of onset is 40 years oldand survival time 15–18 years after onset. This diseaseis characterized neuropathologically by striataldegeneration. It manifests with problems of voluntaryand involuntary movements (typically choreiform),emotional control, and cognitive ability. Patientsdescribe clumsiness with motor speed; fine motorcontrol and gait are affected. Choreiform movementsmay be of distal muscles such as quick jerkingmovements of the fingers resembling cigarette flicking;later they may become slower and continuous (choreoathetoid)or flinging movements resembling ballism.Other involuntary movements such as bradykinesia,rigidity, and dystonia can occur with advancing diseaseduration. Speech problems occur early and swallowingdifficulties later in disease duration. Death usuallyoccurs as result of infectious complications ofimmobility. HD can usually be distinguished from otherdiseases causing chorea based on family history, courseof disease, and associated findings.Table 38 Causes of chorea❏❏❏❏❏❏❏❏Sydenham’s chorea: sporadic, postinfectious choreaassociated with rheumatic feverChorea gravidarum (chorea of pregnancy)Drug-induced (e.g. contraceptives, levodopa,neuroleptics)Structural lesions of subthalamic nucleus(e.g. cerebrovascular accident)Systemic lupus erythematosusMetabolic disorders: thyrotoxicosis, Wilson’s diseaseHuntington’s diseaseNeuroacanthocytosisOther basal ganglia dysfunctional disordersAthetosis (derived from the Greek word ‘withoutposition’) is characterized by slow, writhing,continuous movements of the distal parts of theextremities. It is often associated with chorea(choreoathetosis). Ballism (derived from the Greekword for ‘jump or throw’) demonstrates abrupt,flailing, and violent involuntary movements ofproximal muscles. Movements are often unilateral(hemiballismus), contralateral to a lesion within thesubthalamic nucleus.Involuntary and inappropriate musclecontractions of agonist/antagonist muscles whenchanging or maintaining posture cause a twistingmovement with abnormal posture that may bepainful, dystonia. An example is cervical dystonia.Movements are usually slow but may be more rapidand repetitive. Motor tics are abrupt and rapidpurposeless involuntary movements that are repetitiveand irregular. Examples are eye blinking or shouldershrugging. They may be suggestible, worsened withanxiety, and partially suppressible. Most are benign. Achronic and severe type of motor and vocal tics(including involuntary swearing) associated withbehavioural disturbance is Tourette’s syndrome.OTHER INVOLUNTARY MOVEMENTSClonus, asterixis, and myoclonus are all involuntarymovements whose primary pathology is not diseasewithin the basal ganglia and are sometimes mistakenfor tremor. Clonus is rhythmic movement elicitedthough the stretch reflex around a joint and is mostoften looked for around the ankle by sharpdorsiflexion of the foot, the presence of whichsignifies an upper motor neurone (UMN) lesion. It isusually associated with increased muscle tone.Asterixis may resemble an irregular tremor. Asterixismay be unilateral (caused by focal hemisphericlesions) or bilateral (endocrine, metabolic dysfunction[e.g. hepatic encephalopathy], intoxication, or focalbrainstem disease). It has a characteristic flappingpattern during tonic contraction (noted for examplewith dorsiflexion of the wrist), due to sudden lapsesof innervation. Patients may have other physical signssuch as those associated with liver failure. Myoclonusis an intermittent, sudden, abrupt, brief muscle jerkwhich may be irregular or rhythmic and of slowfrequency arising from the central nervous system.
Disorders of motility 169CLINICAL ASSESSMENTFocused history takingInitial history taking should concentrate on onset ofinvoluntary movement (sudden or gradual), duration,location and spread, and whether the condition isprogressive or intermittent. Family or friends may beable to report if the disorder was present prior to thepatient noticing it. A family history is important asmany movement disorders have a familial tendency,e.g. tremor of early adult onset suggests essentialtremor; a family history of chorea (and mentalimpairment) suggests Huntington’s disease.Medication and illicit drug history is necessary, as isnoting a response to alcohol (essential tremorimproves with alcohol; the tremor of PD does not).History should be focused according to tremor type,e.g. a patient with a fine, symmetrical, posturaltremor should be questioned about symptoms ofthyrotoxicosis. History taking has been covered inprevious chapters of this book and so this chapterconcentrates on clinical aspects of involuntarymovements, especially using clinical examination todifferentiate between movement disorders.Examination of tremorWhile taking the medical history, the clinician shouldwatch for tremor unobtrusively, as the characteristicsof tremor may change if the patient is aware of beingscrutinized. An affected limb should be watched whilefully supported against gravity (at rest), whilemaintaining a position against gravity (postural), andduring target directed movements (intention) (Table34). When writing a sentence, micrographia may benoted in a patient with PD, while in patients withessential tremor the writing will be tremulous but notsmall (132). Alternative measures to assess essentialtremor are by copying a spiral, which can be used toassess progression or therapy response at intervals(133). If appropriate from the history, an attempt tobring on the tremor in a task-specific manner, e.g.writing or in a standing position for orthostatictremor should be made. For any tremor, neurologicalexamination should look particularly for thefollowing signs:Bradykinesia (slowness of movement). Assessmentis made of repeated finger and heel taps,watching particularly for reduction in amplitude or132a133132 Tremulous writing in a patient with essential tremor.b133 Normal Archimedes spiral (a) and abnormal tremulous spiral in a patient withessential tremor (b).
170hesitation, and reduced arm swing on walking.Bradykinesia may occur to an extent in elderlypatients due to coexistent disease such as arthritis.Rigidity. Assessment is made of passivemovements around joints. The patient should be asrelaxed as possible. Cogwheeling is a rhythmic briefincrease in resistance during passive movement.Froment’s sign is increased tone felt during voluntarymovement of the other limb. Voluntary resistance topassive movements may be found in psychogenictremors.Postural instability. Typically found in PD,impaired balance may cause patients to fall easily ordevelop a forward or backward lean. If pulled gentlyby the shoulders from behind and told to try to keeptheir balance (the ‘pull’ test), patients with PD have atendency to step backwards (retropulsion) or fall (thetest must be fully explained to the patient and theclinician must be ready to catch if necessary).Gait. A shuffling gait with short steps anddifficulty turning corners or going throughdoorways is seen in PD.Bradykinesia, rest tremor, rigidity, and posturalinstability are features of PD and atypicalparkinsonian disorders (MSA, PSP, CBD) and in otherdisorders such as dementia with Lewy bodies.Medication use with dopamine depletors (e.g.antipsychotics or some antiemetics) may mimic PD.Cerebellar signs. Essential tremor often has anintention component to the tremor. The presence ofother cerebellar signs, e.g. dysdiadochokinesis, poorcoordination on heel–shin testing, nystagmus,cerebellar speech disturbance, raises the possibility ofa structural disorder and suggests neuroimaging andother investigations. Cerebellar features may representMSA in the presence of parkinsonian signs.Pyramidal signs. These may raise the possibilityof cerebral disorders of many aetiologies and shouldprompt further investigation, such as structural brainimaging. Pyramidal signs (e.g. brisk reflexes orextensor plantar responses), in the context of aparkinsonian disorder may be due to MSA.Primitive reflexes. While no primitive reflex isspecific, the presence of them adds weight to adiagnosis of PD in a patient with a tremor disorder.The glabellar tap, pout, and palmomental reflexesshould be assessed.Evidence for neuropathy, such as chronicdemyelinating neuropathies, polyneuropathies(diabetes, uraemia), should be sought.General examination. Signs of metabolic upset(e.g. hyperthyroidism, hypocalcaemia, alcoholism,and hepatic disturbance) should be looked for.InvestigationsBlood tests and structural brain imaging (CT or MRI)are often needed to exclude metabolic disorders orstructural brain disease as a cause of tremor or otherinvoluntary movement. Functional neuroimagingmay be used to assess the integrity of the pre- orpostsynaptic dopaminergic neurone with SPECT orPET. Nerve conduction studies or electromyographymay be required in some cases to clarify the diagnosis.SUMMARY❏ History taking in movement disorders shouldinclude rate of onset, position, precipitants andrelievers, and full drug and family history.❏ A full neurological examination is important toperform in patients with tremor, for evidence ofother extrapyramidal signs, cerebellar features,and pyramidal signs for instance.❏ Tremor should be described in terms of site andtype (rest or action [postural and kinetic]) andamplitude of movements.❏ PD is due to degeneration of the dopamineneurones from the substantia nigra in themidbrain to the striatum. The aetiology isunknown.❏ PD is typically of unilateral onset spreading tobecome bilateral and most patients will presentwith resting tremor.❏ The cardinal features of PD are bradykinesia,tremor, rigidity, and postural instability.❏ Mimics of PD include Parkinson’s plus disorders,drug-induced parkinsonism, and vascularparkinsonism.❏ Essential tremor presents with postural andintention tremor and often shows transientimprovement with beta-blockers or alcohol.❏ Movement disorders presenting in earlyadulthood should prompt a screen for Wilson’sdisease.❏ Chorea may be due to metabolic disturbances,structural lesions, inflammatory disorders,medications, and neurodegenerative disorders.❏ Huntington’s disease presents with chorea anddementia and is an autosomal dominantdisorder.
Disorders of motility 171CLINICAL SCENARIOSCASE 1A 72-year-old female is referred by her GP having noticed a tremor of insidious onset inher right (dominant) hand over the previous year. Within the last 4 months it has begunto affect the left hand as well. Initially it was intermittent but now it is continuous, andinterfering with her ability to cook and write. Tremor is more apparent when she issitting watching television and is worse with anxiety. She notices a general slowing thatshe puts down to ‘age’ but denies any stiffness. She has had no falls. Handwriting isshaky but no smaller than usual. Past medical history includes osteoarthritis of shoulders,elbows, and hips with a left hip replacement. She takes negligible alcohol and is an exsmoker.Currently she takes an anti-inflammatory painkiller for joint ache. Previously shetried a beta-blocker for the tremor without any benefit. Family history is negative for anytremor disorders.Tremor had an asymmetrical onset and is worse at rest, both suggesting PD. Anxietyworsens tremor regardless of cause. Essential tremor often improves with beta-blockersbut the nonresponse does not exclude the diagnosis, neither does the lack of familyhistory. There is no information on response to alcohol. Slowing may representbradykinesia but may also be found in an older patient, to which arthritis maycontribute.As the patient walked into the room a reduction in arm swing on the right wasapparent. She was slightly stooped, which may have been normal for her age. Walkingwas slow with small steps, with no freezing, shuffling, or festination. Facial expressionwas a little reduced. General examination was normal. While sitting with her hands fullysupported on her lap, there was no tremor initially but when she was asked to countdown from 20, a bilateral rest tremor was present, more obvious in the right arm. It wasa coarse tremor with a rubbing action between the thumb and index finger but alsoinvolved other fingers. On passive movement around her right wrist no rigidity wasnoted unless she performed voluntary movement in the left arm (Froment’s sign). Mildrigidity was present around the right knee and ankle joints. Bradykinesia was noted inthe right arm as assessed by finger taps; although initial taps were quick and with goodamplitude they quickly fatigued with some hesitation. There was no rigidity orbradykinesia in the left arm or leg. The ‘pull’ test was performed and retropulsion wasapparent. There was a positive glabellar tap and positive palmomental reflexes bilaterally.Limb power, sensation, and reflexes were all normal. There were no cerebellar signs.The diagnosis is likely to be PD. Examination reveals a very asymmetrical patternwith all the cardinal signs present: rest tremor, bradykinesia, rigidity, and posturalinstability. Abnormal primitive reflexes lend weight to the diagnosis.Patients with PD often interpret their initial slowness as being due to age. Tremorbecame more apparent as she concentrated upon subtracting numbers, a technique thatcan be used to make tremor more apparent. (Tremor may also be noted in a hand andarm when walking.)(Continued overleaf)
172CASE 1 (continued)When there is clinical uncertainty over the presence ofparkinsonian features a FP-CIT SPECT brain scan showspresynaptic dopamine deficit in PD and Parkinson plus disorders,and is normal in essential tremor (134). Structural imaging (CTor MRI) is usually not performed unless there are atypical clinicalfeatures. As PD is functionally interfering with her life, treatmentshould be offered with, for example, levodopa (Sinemet orMadopar) or a dopamine agonist (Pramipexole or Ropinirole). Asignificant improvement in symptoms was noted after startingtreatment (in keeping with idiopathic PD) with resultingimproved quality of life.134a134b134 Dopamine transporter imaging (presynaptic): FP-CIT single photon emissioncomputed tomography scans. a: normal uptake of ligand with bright signal in caudate(anteriorly) and putamen (posteriorly). Uptake is normal in essential tremor, druginducedparkinsonism, and vascular parkinsonism (unless there is a focal infarctionwithin the striatum which then shows a 'punched out' lesion atypical of trueparkinsonian syndrome); b: abnormal with reduced uptake bilaterally in caudate andputamen, but more reduced in left than right putamen. Asymmetrical finding is typicalof Parkinson's disease as dopaminergic neurones are lost in the putamen before thecaudate and on the side contralateral before ipsilateral to the affected side. Abnormaluptake is also found in Parkinson's plus disorders thus this imaging technique will notdifferentiate between Parkinson's and Parkinson's plus disorders.
Disorders of motility 173CASE 2The pregnant daughter of a 46-year-old maleraised concerns about his abnormal movementswith the GP. These movements had occurredgradually over 5 months and were becoming morenoticeable. They consisted of quick involuntarymovements of his fingers and hands that she felthe tried to disguise, incorporating some of thesemovements into purposeful activity, such as tidyinghis hair. He was unaware of any involuntarymovements. Facial grimacing had been noted. Hehad attended a psychiatrist with depression,anxiety, and irritability over the last 2 years withone recent episode of psychosis for which he wastaking a neuroleptic drug. Adopted at birth, hisfamily history was unknown.HD is a possibility in the context of psychiatricdisturbance and involuntary movements that soundchoreiform in the extremities. Some patients mayshow no awareness of involuntary movements. Thepresence of a positive family history would havebeen helpful confirmatory information, but nofamily history is available in this case. Tardivedyskinesia, a condition which can be caused byneuroleptic medication, manifests as involuntaryfacial movements, with grimacing, lipsmacking, andchewing movements and can occasionally beaccompanied by choreoathetoid movements of thetrunk, arms, and legs. Other possibilities includeWilson’s disease. A rare autosomal dominantcondition known as neuroacanthocytosis maypresent with chorea and dementia, and should beconsidered if evidence of muscle wasting andneuropathy is present; it can be diagnosed byfinding acanthocytes (derived from the Greek word'acantha' meaning thorn) which are abnormallyshaped red blood cells with finger-like projectionsdue to membrane instability, in a thick, wet, bloodfilm smear. Thyrotoxicosis needs to be excludedwhich can also present with chorea and mayaccount for his anxiety and irritability; associatedfindings in history (diarrhoea, weight loss, heatintolerance) and examination (postural tremor,tachycardia) should be apparent.Positive findings on examination wereintermittent choreiform movements of the fingersand hands. Facial grimacing was present butwithout the stereotyped movements typical oftardive dyskinesia. Reflexes were generallybrisk. He scored poorly on cognitive tests andhad no insight into this. MRI of brain showedbilateral atrophy of caudate and putamen. Testsof copper metabolism and thyroid functionwere normal and no acanthocytes were found.This man should be referred for counsellingprior to genetic testing for HD. DNA-basedtesting is currently 98.8% sensitive for HD anddetects the CAG repeat length. His test waspositive. The daughter was referred forcounselling as she has a 50% chance of havinginherited the gene and her unborn baby 25%.She opted not to have the test (135).135 Schematic diagram of thetrinucleotide cytosine-adenineguanine(CAG) repeat in the shortarm of chromosome 4, whichencodes the protein Huntingtin.The repeat is present in normalalleles with up to 35 repeats.Patients with >39 repeats willdevelop Huntington's disease; thosewith 35–39 repeats are'indeterminate' and may or maynot develop the disease. The lengthof the repeats determines the ageof onset.5`135Huntington’s disease (Huntingtin gene)AAAAA(CAG) up to 35 repeats = normal alleles35–39 repeats = indeterminate39+ repeats = Huntington’s disease
174CASE 3A 65-year-old male presented with stiffness andslowness of movement coming on gradually over 9months in all limbs. This was particularly noticedon walking; his wife noticed he took slowshuffling steps and had reduced arm swingbilaterally. He reported no tremor. He hadexperienced several falls. He noticedlightheadedness over the same time period onstanding from a sitting position and thiscontributed to his falls. He had urinary symptomsof dribbling incontinence and frequency. His GPhad started a levodopa preparation as she foundfeatures of parkinsonism; the initial benefit tomotor movements was mild and short-lived andthe treatment worsened his lightheadedness. Hehad hypertension and was a smoker. He has beenon aspirin and an ACE inhibitor for 4 years.The lack of good response to levodopa,absence of tremor, and bilateral onset of symptomssuggest that PD is unlikely and one of the‘Parkinson’s plus’ disorders is more likely. Theearly autonomic (dizziness and bladder) symptomssuggest the autonomic variant of MSA rather thana drug side-effect, as the onset did not coincidewith drug initiation. A pseudoparkinsonian statemay be caused by cerebrovascular disease. BothMSA and vascular parkinsonism may have apartial response to levodopa.On examination he had parkinsonian facieswith positive frontal reflexes; moderately severebradykinesia and rigidity were found symmetricallyin all limbs but not the neck. He was stooped witha shuffling gait and postural instability. There wasno tremor; he had normal reflexes and no cerebellarfeatures. Eye movements were normal. There wasevidence of postural hypotension with a lying bloodpressure of 110/60 mmHg (14.7/8.0 kPa) and astanding blood pressure of 80/50 mmHg (10.7/6.7kPa) from which he was symptomatic. MRI brainwas normal.The autonomic variant of MSA is the likeliestdiagnosis. Vascular parkinsonism is typically lowerbody which is not the pattern seen here and theMRI brain showed no evidence of ischaemiclesions. Antihypertensive drugs are likely to beaggravating his hypotension and should bephased out. A D2 SPECT brain scan that reflectsthe integrity of postsynaptic dopaminergicneurones is abnormal in ‘Parkinson’s plus’disorders and normal in PD and may be used ifthere is difficulty distinguishing the disordersclinically (136). Use of antiparkinsonian drugswas avoided because of the poor response andworsening of hypotension. Deterioration in hiscondition occurred over 4 years with gaitdisorder and falls contributed to by hispostural hypotension.136a136b136 Dopamine 2 receptorimaging (postsynaptic):iodobenzamide (IBZM) singlephoton emission computedtomography scans. a: normaluptake of ligand as seen inParkinson's disease;b: bilaterally reduced uptakecompatible with multiplesystem atrophy (and otherParkinson's plus syndromes).
Disorders of motility 175REVISION QUESTIONS1 Parkinson’s disease typically presents withunilateral postural arm tremor.2 Essential tremor typically presents with bilateralpostural arm tremor.3 Huntington’s disease is inherited in anautosomal recessive manner.4 Wilson’s disease often presents in patients agedover 50 years.5 A fine bilateral postural arm tremor can becaused by sodium valproate.6 An ischaemic lesion in the subthalamic nucleuscould be the cause of acute onset hemiballism.7 Imaging of the presynaptic dopaminergicneurone is expected to be abnormal in essentialtremor.8 Everybody with chorea should undergo genetictesting for Huntington’s disease.9 Thyroid function tests are indicated in a patientpresenting with bilateral postural tremor andweight loss.10 Structural brain imaging is not indicated whenpyramidal signs (e.g. hyper-reflexia and extensorplantars) are found in conjunction withparkinsonian signs.11 Antiemetic medications may cause parkinsonism.12 Dopamine-depleting medications may causeHuntington’s disease.13 Beta-blockers may cause tremor.14 Lithium may cause tremor.15 Essential tremor responds to levodopa.Answers1 False.2 True.3 False.4 False.5 True.6 True.7 False.8 False.9 True.10 False.11 True.12 False.13 False.14 True.15 False.
176POOR COORDINATION Abhijit ChaudhuriINTRODUCTIONCoordination is an essential requirement for anypurposeful, goal-directed, motor movements. Poorcoordination or loss of coordination is known asataxia, which literally means ‘without order’. Patientsrecognize ataxia as clumsiness of movement or poorbalance that is distinct from weakness. In clinicalpractice, it is usual to restrict the term ataxia todescribe movements characterized by ‘motor error’,i.e. an inaccuracy of movements and gait in theabsence of obvious paralysis, involuntary movementsof the limb, or visual impairment. A patient with aweak arm from a corticospinal lesion or with athetoidarm movements will appear clumsy, but these shouldnot be termed ataxia. Similarly, disturbed vision dueto blindness or squint will limit one’s ability to targetmotor activities because of an inability to appreciatethe position of an object in space. As a corollary,ataxia is always made worse under conditions ofvisual deprivation and this is often an importantclinical observation in ataxia caused by the loss ofproprioceptive input (sensory ataxia).Ataxia due to cerebellar lesions (cerebellarataxia), unlike that due to the involvement ofthe sensory pathway, is always present evenwhen the eyes are open.After weakness and tremors, poor coordination isthe next most common symptom of disorders thataffect the motor system. In a number of commonneurological conditions, ataxia is the dominantsymptom. Ataxia may also be the consequence of ageneral medical disorder or a medication side-effect.Alcohol misuse is the commonest toxic cause of ataxia.ClassificationDisorders of the cerebellum or its connections andproprioceptive sensory pathway are not the onlycauses of poor coordination. Some authors havedescribed an additional type of ataxia in frontal lobedisorders, characterized by disturbed standing andwalking. This has been termed gait ataxia, but it isprobably more appropriate to consider it as anapraxia of gait rather than a true ataxia. Middle eardiseases affecting vestibular function may also causeproblems of balance. Destruction of the hair cells ofthe vestibular labyrinth from advanced Ménière’sdisease or after prolonged administration ofaminoglycoside antibiotics results in vestibularataxia. Patients with vestibulopathy due to these andother causes are unsteady while standing and walkingand usually find it very difficult to climb down thestairs without holding the bannister. Frequently, theycomplain of a sense of imbalance even when lying orstanding still and are liable to be dismissed ashysterical. However, just like patients with cerebellarand sensory ataxia, their staggering and unsteadinessincrease in the dark, occasionally to the point ofactual falling. This type of ataxia is caused by the lossof vestibular input necessary for ocular fixation and isa not uncommon problem in the elderly. For theremainder of this chapter, however, only cerebellarand sensory ataxias will be discussed, as these aremost common in neurological practice.PathophysiologyCerebellar anatomy and physiologyThe cerebellum regulates movement, posture, andgait. It does so indirectly by influencing the output ofthe descending motor tracts (e.g. corticospinal tract)that are directly involved in voluntary movements.Cerebellar lesions do not cause motor weakness(paralysis) but disrupt the smooth execution ofnormal movements. This leads to poor coordinationof limb, eye, and trunk movements, impaired balance,and unsteady gait. A simple way to understand thefunction of the cerebellum is to consider it as anintegrator that corrects errors in voluntary movementby constantly comparing intended action with theactual performance (137).Anatomically, the cerebellum occupies most of theposterior cranial fossa. It has an outer mantle of greymatter (cerebellar cortex), internal white matter, and aset of deep nuclei. There are two cerebellar hemispheresconnected by a midline strip termed the cerebellarvermis. The part of the hemisphere closest to the vermisis called the intermediate region and the rest of thehemisphere comprises the lateral region. The cerebellumreceives input from all levels of the central nervoussystem, mostly by way of two pairs of large fibre tractsknown as inferior and middle cerebellar peduncles. Thepaired superior cerebellar peduncles comprise the majorcerebellar outflow tracts to the motor regions of thecerebral cortex and brainstem. These fibres originate inthe deep cerebellar and vestibular nuclei before relayingthrough the Purkinje cells.The cerebellum receives its blood supply from theposterior circulation. The vertebral and basilararteries give rise to three paired branches: thesuperior (SCA), the anterior inferior (AICA) and the
Disorders of motility 177posterior inferior cerebellar arteries (PICA). These areinterconnected by extensive arterial anastomoses.There is a topical representation of individualbody parts within the cerebellum (the cerebellarhomunculus), and certain cerebellar regions arecorrelated with distinct function. This may have somesignificance in localizing lesions in cerebellar ataxia.Midline cerebellar lesions affect stance, gait, andtruncal posture. Lesions in the lateral part produceipsilateral limb ataxia (this occurs because of adouble crossing effect of the superior cerebellarpeduncle and the corticospinal tracts respectively).Cerebellar signs by themselves do not distinguishlesions in the cerebellar hemispheres from lesions inany of the cerebellar pathways; however, most severecerebellar dysfunction is often seen in the lesionsaffecting the cerebellar outflow (deep cerebellarnuclei and the superior cerebellar peduncle).Proprioceptive sensory pathwayPosition and vibration sensations comprise the twomost important proprioceptive inputs. Proprioceptionis carried by the large, myelinated, fastconductingsensory fibres in the peripheral nerves.These afferent fibres comprise the axons of thebipolar nerve cells located in the dorsal root gangliaoutside the spinal cord. In the spinal cord,proprioceptive fibres collect into a bundle in theposterior part of the cord (dorsal column) ipsilaterallyand ascend to the lower medulla, where they synapseinto the second order neurones (within the nucleigracilis and cuneatus). Axons from these nuclei crossover to the other side as arcuate fibres and ascend tothe thalamus as a large fibre bundle known as themedial lemniscus. Third order sensory neurones fromthe thalamus then pass through the posterior limb ofthe internal capsule before reaching the primarysensory (parietal) cortex (138).Middle cerebellar peduncle137SuperiorcerebellarpedunclePosterior columnFasciculus Fasciculuscuneatus gracilisC 4 C 8 T 3 T 6 T 1 T 12 L 1 S 1 S 2138TemperatureInferiorcerebellarpedunclePainSpinothalamic tractTouchPressure137 A schematic diagram of the anatomy of the cerebellarpeduncles that carry the afferent and efferent fibres. Theinferior peduncle mostly contains all afferents, e.g. from thevestibular system and the spinal cord. The middle pedunclecontains only afferents from the pontine motor nuclei, and thesuperior peduncle contains mostly efferent fibres. Becauseboth the entering fibres (in the inferior and middle peduncle)and the exiting fibres (in the superior peduncle) cross to theother side, the cerebellar output control is ipsilateral due tothe double decussation.138 A schematic diagram showing lamination of the ascendingsensory fibres in the posterior column of the spinal cord. C:cervical; L: lumbar; T: thoracic; S: sacral nerve roots. Thesensations of temperature, pain and nondiscriminatory touchare carried in the anterolateral system (spinothalamic tract).
178A lesion in the peripheral nerve, dorsal root ganglia,the dorsal column within the spinal cord, medulla,medial lemniscus, thalamus, or parietal cortex maycause a similar sensory ataxia. Essentially, thesymptoms are due to loss of position sense and can becompensated by normal visual input with informationinforming on the position of the body in space.It is only in the absence of the visual input onbody position that sensory ataxia becomesobvious.Differential diagnosis of ataxiaAtaxia needs to be distinguished from loss ofdexterity due to motor weakness (paralysis),restricted movement due to pain, involuntarymovements, and from lack of cooperation due tocognitive or behavioural problems. The nature ofataxia (cerebellar, sensory, or vestibular) can usuallybe identified from the history and neurologicalexamination. Poor coordination is only a symptomand is not a syndrome or disease in itself. It is theunderlying problem or disease that needs to beidentified and the symptom of ataxia only provides aclue in this exercise.CLINICAL ASSESSMENTFocused history takingThe onset, natural history, and the associatedsymptoms of ataxia are of diagnostic relevance. Inparticular, the effect of eye closure on ataxia must bedetermined. Motor symptoms such as dysarthria (seepage 163) are invariably associated with cerebellarataxia and symptoms of peripheral sensorydisturbance (burning hands and feet, numbness) arecommon with sensory ataxia. Age of onset and familyhistory are very important in slowly progressivecerebellar ataxia as so many of these rare syndromeshave a hereditary basis. Cerebellar ataxia may beacute, subacute, or chronic and a list of possiblecauses is provided (Table 39). Rarely, patients mayexperience symptoms of an intermittent ataxia,appearing normal in between attacks (episodicataxia). Sensory ataxia may be acute (e.g. brainstemstroke or demyelination), subacute (e.g. vitamin B 12deficiency, paraneoplastic neuropathy) or part of achronic progressive myelopathy (e.g. tabes dorsalis,demyelination) or neuropathy (e.g. demyelinatingperipheral neuropathy). Common causes of sensoryataxia are listed (Table 40).ExaminationFocused examinationThe examination of the ataxic patient should be partof a general medical and neurological examination.At the outset, it is important to emphasise that testsfor coordination are only meaningful in the presenceof retained power (MRC grade 4 or above). Ataxiamay be most obvious to the patient when he/she triesto button or unbutton their shirt, fasten clothes, oruse a knife and a fork or, in the case of sensory ataxia,in the dark or when the eyes are closed.A general medical examination is importantbecause it may aid in the aetiological diagnosis ofataxia. Some examples are middle ear disease (with orwithout cerebellar abscess), bradycardia (hypothyroidismor raised intracranial pressure), papilloedema(posterior fossa tumours), short neck, low hairline, and related dysmorphic features (developmentalanomalies of the craniocervical junction such as Chiarimalformation), pes cavus (Friedreich’s ataxia andhereditary neuropathy), scoliosis (Friedreich’s ataxia,syringomyelia, and neurofibromatosis), cutaneoustelangiectasia (ataxia-telangiectasia) and dermatitisherpetiformis (associated with coeliac disease).Neurological examinationThis includes special attention to the testing ofspeech, external eye movements, upper and lowerlimb coordination, assessment of involuntarymovements, and observation of gait. The anatomicallocalization of ataxia is only possible by means of athorough neurological examination. The degenerativehereditary and familial cerebellar ataxias havecerebellar signs that may be marked or slight but, inaddition, patients also show posterior column,corticospinal, and/or neuropathic signs (characteristicof Friedreich’s ataxia). Thrombosis of the posteriorinferior cerebellar artery due to vertebral occlusion isthe commonest vascular lesion of the cerebellum, andpresents with acute vertigo and distinctive medullarysigns (cranial nerve IX/X palsy, Horner’s syndrome,impairment of facial and contralateral pain andtemperature sensations). These features occur inaddition to more obvious cerebellar features ofnystagmus and limb ataxia. The same artery alsosupplies the lateral part of the medulla.Cerebellar dysarthriaThere are two types of cerebellar dysarthria, onecharacterized by ‘explosive’ speech as if the patientwas speaking with his mouth full of marbles. The
Disorders of motility 179Table 39 Presentations of cerebellar ataxiaAcute (over hours to days)Acute, reversible Viral and postinfective cerebellitis (Case 1)Acute, relapsingEpisodic ataxiasMultiple sclerosisMetabolic encephalopathies (hyperammonaemias)Toxic (alcohol, phenytoin, barbiturates)Acute, persistentCerebellar infarctsCerebellar haemorrhage (e.g. hypertensive), abscess, or metastasesWernicke–Korsakoff syndromeHyperthermiaOpsoclonus-myoclonusSubacute (over days to weeks) or chronic (months)Pure cerebellar syndromeParaneoplastic (associated with gynaecological or small-cell lung tumours)Alcohol–nutritionalToxic (lithium, mercury, gasoline, glue, cytotoxics)Cerebellar syndrome associated Posterior fossa tumours (medulloblastoma, astrocytoma, haemangioblastoma,with additional signs or symptoms acoustic Schwannoma)Chronic subdural haematomaMultiple sclerosisHypothyroidismHashimoto's encephalomyelitisLyme diseaseCoeliac diseaseSuperficial siderosisCerebellar syndrome with dementia Creutzfeldt–Jakob diseaseChronic (months to years)Childhood or early-onsetCongenital cerebellar ataxiaHeredofamilial (e.g. Friedreich's ataxia)Ataxia-telangiectasiaAtaxia associated with hereditary metabolic diseasesCerebellar syndrome with myoclonic epilepsy (e.g. Lafora body disease,Unverricht–Lundborg syndrome)Adulthood or late-onsetSporadic (olivopontocerebellar atrophy and inherited spinocerebellar degenerationspinocerebellar ataxia 1,2,3 etc.)Multiple system atrophyAny ageCraniocervical junction anomalies (Chiari malformation, Dandy–Walker syndrome)Table 40 Causes of sensory ataxiaDemyelinating peripheral neuropathies ('sensory ataxicneuropathy'):❏ Chronic inflammatory demyelinating neuropathy❏ Inherited neuropathy (Charcot–Marie–Tooth disease)❏ Paraproteinaemic neuropathy❏ SarcoidosisDorsal root ganglionopathy❏ Infective (syphilis, Lyme disease)❏ Toxic (e.g. pyridoxine)❏ Paraneoplastic (subacute sensory neuropathy)❏ Sjögren’s syndromeLesions affecting dorsal column in the spinal cord❏ Compression of the cervical or thoracic spinal cord (e.g.meningioma)❏ Inherited spinocerebellar degeneration (e.g. Friedreich’sataxia)❏ Multiple sclerosis❏ Syphilis❏ Vitamin B 12deficiencyLesions affecting medial lemniscus or its centralprojection❏ Multiple sclerosis❏ Vascular (infarct)❏ Tumours
180other type of speech is much slower with undueseparation of the syllables, known as staccato orscanning speech (from a resemblance to the scanningof the Greek verse). The former is more characteristicof an acquired cerebellar problem (e.g. multiplesclerosis) and occurs because the patient attempts tospeak normally but suffers from poor coordination ofthe muscles of articulation of speech and control ofbreathing. Scanning speech is relatively morecommon in either a developmental cerebellar disease(congenital or the early-onset type of heredofamilialataxia) or a lesion acquired early in childhood.Cerebellar disease is often associated with distinctiveeye movement abnormalities and nystagmus; theseare discussed elsewhere (page 104).Cerebellar ataxia is associated with reducedmuscle tone and this, together with the errorsimposed in the direction, range, speed, and force ofmovements, results in a characteristic set of clinicalsigns. A failure to integrate conjugate eye movementsproduces nystagmus. Heel-to-knee and finger-to-nosetests are the usual ways to demonstrate cerebellarincoordination in the lower and upper limbsrespectively (Chapter 1). Sometimes, however, moredelicate movements are necessary to unmask theimpaired coordination, such as asking the patient tomake imaginary finger movements as if playing thepiano. Other examples include asking the patient tobring the tip of each finger rapidly in turn to touchthe thumb of his own hand, or to pat the dorsum ofhis clenched fist first with the palmar aspect and thenthe dorsal aspect of his opposite hand with increasingspeed, repeating the manoeuvre with the other hand.A number of terms have been used in theliterature to qualify cerebellar incoordination. Theseinclude dyssynergia (a lack of synergy or coordinatedmovements of synergistic muscles), dysmetria (anineffectual range of movement, often resulting intarget overshooting or hypermetria [‘past-pointing’]),dysdiadochokinesia (inability to perform complexrepetitive movements smoothly and rapidly such assupination and pronation of forearms) and reboundphenomenon (a failure to brake movement smoothly,for example, when the external resistance to theforearm kept flexed at 90º is suddenly released, apatient with cerebellar disturbance may fail to checkthe unopposed flexion movement and may be hit byhis own arm).In mid-line cerebellar lesions, the trunk muscles aremore severely affected than the limbs and the ataxiabecomes obvious when the patient is asked to walk.With a cerebellar lesion, the patient walks with a broadbase in order to maintain his balance. Often this is bestdemonstrable when a patient is asked to turn suddenly,when they tend to sway, reel to either side, or fallbackwards. This is especially so with lesions in thecerebellar vermis. In less severe cases, as the patientturns on a wide base they abduct their lower limbsexcessively to compensate for hypotonicity and thenreplace the foot on the ground away from the intendedposition (due to dysmetria). This results in the typicaldecomposition of gait seen in cerebellar disorders.Because such clumsiness is not corrected by vision(unlike the patient with a posterior column disease), apatient with cerebellar ataxia does not look to theground while walking but instead looks straight ahead.In pure cerebellar lesions uncomplicated by centralnervous system involvement at other sites, reflexes arenot overtly affected but the tendon jerks may be mildlyaffected qualitatively. When the knee jerk is tested withthe patient sitting at the edge of the bed, the knee mayswing back and forth three times or more due to acombination of muscle hypotonia and reboundphenomenon. This is known as a pendular knee jerkand must not be interpreted as a sign of pathologicalhyperreflexia associated with corticospinal lesions.Testing for joint position sense and vibration iscovered elsewhere in the book (Chapter 1). Patientswith sensory ataxia may have muscle hypotonia anddiminished reflexes when the pathological process isat the level of the peripheral nerves, dorsal rootganglia or, rarely, in the posterior column withoutextending into the corticospinal tracts. Inuncomplicated sensory ataxia, the patient walks on abroad base in order to maintain their centre ofgravity. Limbs are lifted abnormally high due to theinability to appreciate the normal range ofmovements at the joints as a result of lack ofproprioception. For the same reason, the heels areslammed back to the ground with excessive force,resulting in a ‘stamping’ gait, originally describedwith tabes dorsalis (literally meaning wasting of theposterior column), a form of neurosyphilis. Acombination of proprioceptive loss, painless jointdeformity (Charcot joints), and perforating ulcers ofthe lower limbs was virtually diagnostic of thelocomotor ataxia of neurosyphilis, a condition that isnow seldom seen but contributed a great deal to theunderstanding of sensory ataxia. In patients withsensory ataxia, the heels of the shoes tend to get wornmore quickly as this part of the foot strikes theground with so much force.
Disorders of motility 181A positive Romberg’s test refers to the situationwhere a patient is completely steady when standingon a normal base with eyes open and the feet drawntogether but becomes unsteady as soon as the eyes areclosed.Obviously, Romberg’s test cannot be performed(or is meaningless even if performed) in a patientwith cerebellar ataxia who is unsteady even withhis eyes open.In the upper limbs, sensory ataxia is bestdemonstrated by asking the patient to shut their eyeswhile keeping their pronated arms outstretched in theforward position. Since in sensory ataxia one cannotappreciate the limb position if the eyes are closed, thepatient’s forearms will drift away from the originalposition in an athetoid movement (pseudoathetosis orsensory limb ataxia). This swaying of the sensoryataxic arms must be distinguished from the sidewaysdrift seen in the presence of motor weakness incorticospinal lesions (pronator drift sign).InvestigationsAs a general rule, all patients with progressive cerebellarataxia must be considered for imaging (preferablymagnetic resonance imaging [MRI]) scans of theposterior fossa and the craniocervical junction (Table41). Computed tomography (CT) scan of brain isparticularly useful in an acute setting when patientspresent with increasing signs of ataxia due to cerebellarinfarction with oedema, cerebellar haemorrhage,posterior fossa subdural haematoma, obstructivehydrocephalus, cerebellar tumours, and metastases.The utilization of more specific investigations forcerebellar ataxia depends on the age of symptomonset, positive family history, additional neurologicalsigns, and the potential differential diagnosis. A slowlyprogressive cerebellar syndrome with bilateralsymmetrical involvement suggests a biochemical(metabolic), toxic, or inherited cause. Genetic tests arecurrently available for Friedreich’s ataxia and anumber of inherited spinocerebellar ataxias (SCAmutations) and should only be considered after acareful review of the family history with appropriatepretest counselling. Chronic gait ataxia of months’ oryears’ duration usually suggests a metabolic orinherited ataxia; hypothyroidism should also beexcluded in cases with a shorter history. Multiplesclerosis may present with cerebellar and/or sensoryataxia and the diagnosis is usually confirmed by MRIscans (brain and cervical spinal cord) and, if required,cerebrospinal fluid (CSF) examination and evokedresponse studies. In a patient over the age of 40 yearswho develops a subacute and progressive cerebellarataxia and has negative family history, a normal MRIscan and normal CSF, and if alcohol and toxic causeshave been excluded, underlying malignancy requiresconsideration. Paraneoplastic cerebellar degenerationis a recognized presentation of breast and ovariancarcinoma and in such cases serum samples should betested for paraneoplastic antibodies (anti-Yoantibody). These are named after index cases. Anotherparaneoplastic (or occasionally, postinfectious)syndrome, opsoclonus-myoclonus, is associated withincapacitating gait ataxia. Folic acid, vitamin B 12andB 1concentrations in the blood should be measured inpatients in whom alcohol or a nutritional cause ofataxia is suspected. The electroencephalogram (EEG)Table 41 Initial investigations of an ataxicpatientCerebellar ataxiaAll cases:❏ Cranial CT and/or MRI of head❏ Thyroid function testSelected cases:❏ CSF❏ Genetic tests❏ Toxicology or metabolic screen❏ Paraneoplastic antibody (anti-Yo)❏ Serology for coeliac disease❏ Vitamin B 1❏ EEGSensory ataxiaAll cases:❏ Vitamin B 12and folic acid levels❏ Syphilis serologySelected cases:❏ MRI (head and/or spinal cord)❏ Nerve conduction studies❏ CSF❏ Paraneoplastic antibody (anti-Hu)Serology for Sjögren’s syndrome, Lyme diseaseCSF: cerebrospinal fluid; CT: computed tomography;EEG: electroencephalogram; MRI: magnetic resonanceimaging.
182is a valuable investigation in patients with myoclonusand cerebellar ataxia (mitochondrial encephalopathies,inherited myoclonic epilepsies, andCreutzfeldt–Jakob disease).Nerve conduction studies and CSF examinationare indicated in patients with peripheral neuropathyand sensory ataxia; these patients have absent ordiminished tendon reflexes (areflexic ataxia).Conversely, sensory ataxia with hyperreflexia requiresMRI scanning of the spinal cord or lower brainstem(medulla and the region of foramen magnum)depending on the anatomical localization, often basedon the level of concomitant sensory loss. Rarely,sensory ataxia produces lateralized imbalance thatinvolves one side of the body only. In such cases,symptoms can be caused by lesions in the parietal lobeor thalamus but alternatively may also be due tounilateral posterior column disease affecting the spinalcord as seen in Brown-Séquard syndrome (see page148). Patients with sensory ataxia without a structurallesion in the brain and spinal cord should have bloodsamples tested for folic acid and vitamin B 12, serumprotein electrophoresis, markers for Sjögren’ssyndrome, syphilis, and Lyme serology. Adult patientswith a smoking history and a progressive ataxicneuropathy (Denny–Brown sensory neuropathy) willrequire screening for small-cell lung tumour and serumparaneoplastic antibody (anti-Hu antibody).SUMMARY❏❏❏❏❏The patient’s symptoms of poor coordinationshould be interpreted as part of a widerneurological or medical problem.While specific attention should be given toidentifying the nature of ataxia, a completeneurological examination is essential for theclinical diagnosis of the ataxic patient.Type of ataxia (i.e. sensory or cerebellar) as wellas its possible anatomical localization isimportant in choosing the right investigation ina given patient.In rare cases (Case 3), cerebellar and sensoryataxia may coexist in the same patient.The treatment is directed to the underlying causerather than to the ataxia itself.CLINICAL SCENARIOSCASE 1A 12-year-old female presented with an abruptonset of limb and gait ataxia over a period of 24hours. She was well and attending her classes 2weeks previously when she had developed a mildfever with generalized skin rash. This wasdiagnosed to be chicken pox and she was kept athome. Her fever settled within a day or two andshe did not have any other problem due to herchicken pox. She did not have any symptoms ofdouble vision, lower cranial nerve symptoms, orvomiting but did have a mild headache with herataxia. She had fallen twice while trying to go tothe toilet since her balance became poor. She wasalso unable to hold a cup without spilling itscontents. She also required assistance with feedingbecause of her inability to coordinate her handmovements by using a fork and a knife.She was born full-term, normal delivery, andher developmental milestones were normal. Shewas an intelligent girl and did not have any othersignificant past medical history. She was not onany regular medications. She has two brothers(aged 9 and 16 years) who are healthy. There is nofamily history of cerebellar ataxia.On examination, she was afebrile. Her generalphysical examination showed healed skin marks ofchicken pox with one or two lesions where thescabs were still present. She appeared cheerful buthad cerebellar dysarthria as she spoke. Her opticdiscs were normal and pupils were equal as wellas reactive. External ocular movements showedbilateral jerk nystagmus in the horizontal plane.Her lower cranial nerves were intact. Motorexamination showed normal limb tone, briskreflexes, and flexor plantar responses. She hadataxia of both her arms and legs with quitemarked ataxia of gait.(Continued on page 183)
Disorders of motility 183CASE 1 (continued)Clinically, a diagnosis of acute ataxia of childhood was made. This was considered to be due to anacute cerebellitis that is well recognized after chicken pox in children.To exclude other possibilities such as a cerebellar tumour (medulloblastoma) and demyelination, MRIbrain scan was advised. This was found to be entirely normal. She also had CSF examination by lumbarpuncture for inflammatory causes of her ataxia. Her CSF showed 20 lymphocytes (normally less than 5)/mm 3with a protein of 0.65 g/l. CSF polymerase chain reaction (PCR) was negative for Varicella zoster virus.The patient and her parents were told that her ataxia was not due to a tumour, infection or braininjury and was probably caused by local inflammation in her cerebellum as a reaction to her recent viralexanthem (chicken pox). They were also told that she was expected to make a slow but full recoveryspontaneously and she did so in 6 months’ time. In a child who presents with acute cerebellar ataxia, thefirst concern is to exclude a structural lesion (tumour or an abscess) in the posterior fossa or cerebellum.CASE 2A 52-year-old businessman of Indian originpresented with a 10-week history of frequent falls,poor balance, fatigue, and impaired short-termmemory. For about 6 months prior to thesesymptoms he was experiencing painful sensationsaffecting his feet and, to a lesser extent, his arms. Hewas also known to be mildly diabetic for the past 2years and was managed on diet alone. It wasthought that his sensory symptoms were due todiabetes. He was advised to lose weight and domore physical activities. However, he discovered thathe fell easily on a treadmill if he did not look downand had great difficulty in taking a walk because ofpoor balance. There was no other medical history ofimportance. He had no history of bowel surgery. Hehad a family history of diabetes. He was a strictvegetarian because of his faith for a number ofyears. He did not smoke or drink alcohol.Clinical examination showed normal cranialnerves, pupils, and optic discs. Motor examinationshowed increased tone in his legs with normalpower, absent ankle jerks, but brisk knee jerksbilaterally. Both his plantar responses wereextensor. Sensory examination showed markedhyperalgesia of feet, proprioceptive loss to thelevel of his hips, and a strongly positive Romberg’stest. His upper limb motor and sensoryexaminations were normal and he did not haveany cerebellar signs.A diagnosis of subacute combineddegeneration of the spinal cord due to dietaryvitamin B 12deficiency was considered.This was confirmed by low levels of serumvitamin B 12(110 pmol/l), and supported byincreased mean cell volume (105 fl), macrocytosis,and hypersegmented neutrophils in the peripheralblood smear. MRI of his spinal cord showed anarea of patchily increased signal within the cervicalsegment of the cord. His CSF was normal andperipheral electrophysiology (nerve conductionstudies) could not demonstrate any abnormality.He was found to be weakly positive forantiparietal cell antibody.The patient was commenced immediately onintramuscular vitamin B 12injections and hissensory symptoms, fatigue, and poorconcentration resolved rapidly. He made a goodrecovery from his sensory ataxia by 3 months.Vitamin B 12deficiency is not uncommon in thesetting of a strict vegetarian diet or in patientswith bowel problems (chronic gastritis orCrohn’s disease). Neurological symptoms ofvitamin B 12deficiency may appear before anyhaematological changes.
184CASE 3A 35-year-old female was seen in the neurology outpatient clinic because of her history of poorcoordination affecting her right arm, developing over the past 6–8 hours. She realized this as she wastrying to brush her teeth. She was unable to appreciate what she was holding with her right hand unlessshe had looked at it. Three years previously, she had an acute attack of cerebellar ataxia from which shehad made a good recovery with some residual symptoms in her left arm and left leg. She was treated withlarge doses of intravenous steroids at that time. About 10 years before the present episode, she had suddenloss of vision in her right eye but had made a full recovery without any treatment. When she wasinvestigated on the last occasion, her MRI brain scans were found to be abnormal and the observedchanges were consistent with a diagnosis of multiple sclerosis (MS). This diagnosis was further supportedby additional tests. Visual evoked response from her right eye was delayed and her CSF was positive foroligoclonal bands.On this occasion, the patient was concerned that she might have had a relapse of her MS. She was alsofeeling increasingly tired. As a single mother, she was finding it increasingly difficult to cope with herhousehold work, full-time job as a receptionist, and also to look after her 5-year-old daughter.She admitted that she was under 'a lot of stress' inthe recent weeks. She took simple analgesics forpain relief but otherwise was not on any regularmedication. There was no other contributory pastor family medical history. She did not smoke andtook alcohol only on rare social occasions.Neurological examination showed somereduction of visual acuity in her right eye, a relativeafferent right pupillary defect, jerk nystagmus of theabducting eyes in the horizontal plane bilaterally,and brisk jaw jerk. Motor examination showedminimally increased tone in the legs with reducedtone in the arms, normal power, brisk reflexes (armsand legs), ankle clonus, and extensor plantarresponse bilaterally. Her left heel–knee test wasabnormal and she had past pointing with her leftarm. In addition, she had marked proprioceptiveloss in her right arm with pseudoathetosis.The present problem was attributed to thesensory ataxia of her right arm due to a newdemyelinating event. Her neurological examinationalso showed features of previous optic neuritis in theright eye, bilateral internuclear ophthalmoplegia,and left-sided cerebellar hemiataxia.MRI scans of her cervical cord and lowerbrainstem revealed an area of demyelinationinvolving the upper two segments of the cervicalcord and extending to the right side of the medullain its lower half (139).This lesion was considered adequate to explainthe sensory ataxia in the right arm. She wastreated with a short course of intravenous steroidinjections for her relapsing MS symptoms. She wasadvised to take time off her work and part-timechild care for her daughter was arranged. Shemade a reasonable recovery from her upper limbsensory ataxia and was able to return to work 4months later. Unilateral or upper limb sensoryataxia without lower limb involvement issuggestive of a lesion in the central nervoussystem. A patient may have symptoms of bothcerebellar and sensory ataxia.
Disorders of motility 185139139 Magnetic resonance image of spinal cord of a patient withmultiple sclerosis similar to Case 3, showing plaques in thecervical spinal cord and medulla.REVISION QUESTIONS1 The final common pathway in the cerebellaroutput involves:a Red nucleus.b Purkinje cell.c Dentate nucleus.d Granule cell.2 Ataxia on eye closure but not with open eyes issuggestive of:a Cerebellar ataxia.b Sensory ataxia.c A positive Romberg’s test.d Middle ear disease.3 Neurological symptoms of vitamin B 12deficiency may present:a As noncompressive myelopathy, i.e. spinalcord disease.b With symptoms of burning feet.c Without haematological changes ofmegaloblastic anaemia.d With cerebellar symptoms.4 Paraneoplastic neurological diseases affectingcoordination may manifest as:a Weakness of neuromuscular junction(antivoltage gated calcium channel antibody).b Subacute sensory neuropathy (anti-Huantibody).c Opsoclonus, truncal ataxia (anti-Ri antibody).d Cerebellar ataxia (anti-Yo antibody).5 Blood supply of the cerebellum is derived fromthe branches of:a Carotid artery.b Vertebral artery.c Basilar artery.d All of the above.6 Within the spinal cord, fibres carryingproprioception are located in the:a Spinocerebellar tract.b Spinothalamic tract.c Posterior column.d None of the above.
1867 Ataxic hemiparesis refers to:a Ipsilateral corticospinal weakness andcontralateral ataxia.b Corticospinal weakness and ataxia on thesame side.c Neither (a) nor (b).d Both (a) and (b).8 Sudden dizziness and vomiting, along withmarked truncal ataxia in a hypertensive patientwho is unable to stand upright, suggest adiagnosis of:a Ménière’s disease.b Cerebellar haemorrhage.c Internal capsular haemorrhage.d Subarachnoid haemorrhage.9 Ataxic neuropathies may be associated with:a Monoclonal or polyclonal gammopathy.b Paraneoplastic antibody.c Sjögren’s syndrome.d Inflammatory demyelinating neuropathy.10 Cerebellar features present in conjunction with arapidly deteriorating level of consciousness issuggestive of:a Expanding posterior fossa mass.b Posterior inferior cerebellar artery infarct.c Anterior inferior cerebellar artery infarct.d Viral encephalitis.12 Cerebellar ataxia is inherited as an autosomalrecessive disorder in:a Hypothyroidism.b Friedreich’s ataxia.c Spinocerebellar ataxia.d Ataxia-telangiectasia.13 A combination of cerebellar and sensory ataxiamay be seen in:a Coeliac disease.b Alcohol abuse.c Lyme disease.d B-vitamin deficiency.14 Vertigo is a side-effect of toxicity from:a Phenytoin.b Aminoglycoside antibiotics.c Salicylates.d Alcohol.15 The preferred neuroimaging for acute cerebellarataxia is:a MRI.b CT.c CT followed by MRI.d Plain X-ray of the skull base.11 The following clinical signs would suggest adiagnosis of acoustic neuroma (vestibularSchwannoma):a Hearing loss.b Cerebellar ataxia.c Nystagmus.d Decreased facial sensation.Answers1 b2 b, c3 a, b, c4 b, c, d5 b, c6 a, b, c7 b8 b9 a, b, c, d10 a11 a, b, c, d12 b, d13 a, c14 a, b, c, d15 c
Disorders of sensation 187Disorders of sensationHEADACHEStewart WebbINTRODUCTIONHeadache is a common disorder, with 70% of thepopulation having at least one episode every month.For most it is a benign self-limiting symptom, whichdoes not cause concern. However, it may be adisabling complaint and, for a few, an indication ofpotentially life-threatening disease. The question forevery doctor at some time is when to reassure, treat,and investigate. This chapter will discuss the clinicalapproach to patients with insidious worseningheadache who commonly present to the outpatientclinic, and patients with acute onset headache whorequire urgent hospital admission and assessment toexclude potentially life-threatening conditions. Auseful division of headache is into primary andsecondary types (Tables 42 and 43).ClassificationThe International Headache Society have classifiedand produced diagnostic criteria for both primaryand secondary headache disorders. Although theseTable 42 Primary headache disordersLasting >4 hours Lasting
188can be helpful in clinical practice, they are mainlyused for clinical trials (Table 44) and represent workin progress rather then criteria that are written instone.Anatomy and pathophysiology of headachePain of both primary and secondary type headachesoriginates from either extra- or intracranialstructures. The brain itself has no pain receptors andtherefore lesions within brain parenchyma do notproduce headache unless they directly or indirectlystretch or compress surrounding pain sensitivestructures (Table 45).CLINICAL ASSESSMENTHistory takingThe history is the most important part of theassessment process (Table 46), as there are nodiagnostic tests for the primary headache disordersand it is impractical, unwise, and anxiety provokingto investigate all patients.Persons may have more then one type ofheadache (mixed) and, although it is reasonable toconcentrate on the most troublesome, it is importantto get a clear description of each type. It is crucial, inpatients who report a recent onset of headache, todetermine if the headache is new, or whether it is anTable 44 Abbreviated International Headache Society criteria for common primary headachesEpisodic tension type headache❏ 60 minutesheadache follows aura within 60 minutes (theheadache may also begin before or with the aura)Familial hemiplegic migraine❏ Fulfils the criteria for migraine with aura❏ Aura includes some degree of hemiparesis and may beprolonged❏ At least one first degree relative with identical attacksBasilar migraine❏ Fulfils the criteria for migraine with aura❏ Two or more aura symptoms of the following type:visual symptoms in both the temporal and nasal fieldsof both eyesdysarthriavertigotinnitusdecreased hearingdouble visionataxiabilateral paraesthesiabilateral paresesdecreased level of consciousnessIn all criteria secondary causes must be excluded; this isusually on clinical grounds but where indicated, followsinvestigations.
Disorders of sensation 189existing headache which has become more frequentor severe. Patients may consider some headache asnormal and fail to mention their ‘sinus headache’,which has been present for several years. Thepossibility of having a serious cause does not increasein proportion to the severity, frequency, or durationof the headache. Severe headache may be due tomigraine, while patients with tumours rarely presentwith headache alone and then only occasionallycomplain of having a dull or muzzy head on directquestioning. Patients should be asked about the onset,progression, frequency, and duration of eachheadache (it may be useful for the patient to keep adiary). The site and spread of the headache should beestablished, its quality (e.g. dull, sharp, throbbing, orpressure) and intensity (is the patient’s activity orfunction limited?). Patients should be asked aboutany associated features, in particular the presence orabsence of nausea, vomiting, visual disturbance,photophobia, phonophobia, dysarthria, or ataxia andshould also report any precipitating, aggravating, orrelieving factors (e.g. lying, standing, movement,coughing, stooping, or straining). Medication historyshould be described, i.e. which drug(s) has been or isbeing used, in what dose, frequency and duration,and effect. It is also useful to enquire aboutoccupation, family history, level of stress anddepression, and any concerns or anxieties the patientmay have about the headache.Table 45 Pain sensitive structures of the headIntracranial❏ Dura at the base of the brain❏ Venous sinuses❏ Arteries (including): proximal part of anterior andmiddle cerebral arteriesintracranial segment of theinternal carotid artery❏ Middle meningeal artery❏ Cranial nerves: Optic (II)Oculomotor (III)Trigeminal (V)Glossopharyngeal (IX)Vagus(X)Extracranial❏ Skin and subcutaneous tissue❏ Muscle❏ Extracranial arteries❏ Periosteum of the skull❏ First three cervical nerves❏ Eyes❏ Ears❏ Nasal cavities❏ SinusesTable 46 Questions to ask the patient withheadache❏❏❏❏❏❏❏❏❏❏❏❏❏❏Onset of headacheFrequency and progression of headacheDuration of headacheSite and radiationQuality of headacheAssociated featuresPrecipitating factorsAggravating factorsRelieving factorsDrug historyOccupationFamily historyLevel of stress and depressionConcerns or anxieties
190ExaminationA thorough, thoughtful examination is essential toreassure patients with primary headache, eliminatesecondary causes, and identify comorbid disease suchas infection, hypertension, and depression (Table 47).After taking the history the examiner should be in aposition to decide if the headache is of primary orsecondary type and, if secondary, if the underlyingpathology is likely to be intra- or extracranial orsystemic. Decisions made will then help in directing amore focused neurological examination. In allTable 47 Minimum examination in patientswith headachePossible abnormal findingsCranial nervesFundoscopy PapilloedemaVisual fields Visual field defects(to confrontation)PupilsEqual and reactive to lightEye movements NystagmusDiplopiaAbnormal pursuit movementsFacial movements Asymmetrical weaknessLimbsReflexesBrisk/asymmetryFinger–nose test AtaxiaPlantarsExtensor plantar responseGaitSpasticity/ataxiaTandem gait AtaxiaScalpTemporal arteries In patient >50 yearsTenderness and absent pulsationAdditional examination depending on historyScalpTendernessCervical spine TendernessRestricted neck movementsTemporomandibular TendernessjointClickSinusTendernessNasal obstructionEarsDeafnessInfectionTeethPoor dentitionWearpatients, blood pressure should be recorded. Theoptic discs should be examined for evidence ofpapilloedema. The pupils should be noted to be equaland reactive to light. Eye movements should be fullwith no evidence of nystagmus or diplopia. Upperand lower limbs should be assessed for focalweakness and ataxia, asymmetry of reflexes, andplantar responses. Both gait and tandem walkingshould be assessed. Further examination will dependon the patient’s symptoms and may includeassessment of neck movements, pain and stiffness,local pain and tenderness (neck, occiput, scalp,temporal arteries, sinuses, eyes, temporomandibularjoint), infection, and inflammation (meninges, eyes,ears, nose, throat, teeth).InvestigationsPatients in whom a diagnosis of primary headache iscertain do not require investigation (Table 48). Thehistory and examination should identify thosepatients with ‘red flag’ symptoms and signs (Table 49)who need investigation.Table 48 Investigation of headacheCommentBloodsESRTemporal arteritisThyroid function Thyroid disease24 hour VMA PhaeochromocytomaImagingCTCompared to MRI it is poor invisualizing the posterior fossa, baseof skull and foramen magnum. Itcannot exclude subarachnoidhaemorrhage completelyCT with contrast Suspected mass lesion on plain CTMRIAvailability limitedCT/MRI venography Venous sinus thrombosisCT/MRI angiography Cerebral vasculitis or vascularmalformationsLumbar puncture To exclude meningitis and tomeasure CSF pressureCSF: cerebrospinal fluid; CT: computed tomography; ESR:erythrocyte sedimentation rate; MRI: magnetic resonanceimaging; VMA: Vanillyl-mandelic acid.
Disorders of sensation 191INSIDIOUS WORSENING HEADACHEBoth primary and secondary headache disorders maypresent to the clinician with insidious worseningheadache.Primary headache disordersTension type headacheThis is the commonest type of primary headache (lifetimeprevalence 78%). Starting at any age, it cancontinue throughout life. It is separated into episodicand chronic forms, depending on whether patientshave periods of freedom. The headache isnonpulsating and is described as a bilateral pressureor tight sensation of mild to moderate severity thatmay inhibit but not prohibit daily activities. Physicalactivity does not aggravate the headache and there isno associated vomiting. However, mild nausea,photophobia, or phonophobia may occur. Patientsmay also complain of being giddy, light-headed, andhave difficulty concentrating. In the episodic form itmay develop during, after, or in anticipation of stress,and tends to last 55 years❏ Developing after head injurySigns❏ Fever❏ Neck stiffness❏ Papilloedema❏ Drowsiness❏ Neurological deficit (e.g. weakness, ataxia, cognitivedysfunction)❏ Local tenderness (e.g. temporal arterytenderness)In the chronic form, patients may awaken withheadache, which then persists throughout the dayregardless of activity or stress. Four different varietiesmaybe distinguished. Chronic daily headache istension type headache, which has become daily oftenas a result of analgesia overuse or depression.Transformed migraine applies to those patients withtypical migraine headaches that increase in frequencyuntil they are occurring daily, but still retain some ofthe features of migraine such as unilaterality ornausea. New daily persistent headache (Table 50)applies to patients who were previously headache freebut who develop headache without any obviousphysical or psychological factor to account for theheadache. In this situation secondary causes (Table43) need to be ruled out. Hemicrania continuum is aconstant unilateral headache of uncertain causeresponsive to indomethacin.MigraineMigraine headache affects between 10 and 20% ofthe population and is more common in females.Problems with diagnosis often arise because typicalfeatures are absent or atypical migraine features arepresent. Migraine may be associated with changes inmood (irritability, depression, or elation), alertness(drowsiness, yawning) and appetite (craving for sweetfoods), which may precede the onset of headache byup to 24 hours.Table 50 Causes of new daily persistentheadachePrimarySecondaryMigraineTension typeSAHLow CSF volume headacheHigh CSF volume headachePost traumatic headacheChronic meningitisCSF: cerebrospinal fluid; SAH: subarachnoid haemorrhage.
192Classical migraine is unilateral, fronto-temporaland ocular in site and throbbing in nature. It builds upover 1–2 hours, often progressing posteriorly andbecoming diffuse and typically lasts >4 hours orsubsides with sleep. However, migraine may alsopresent with a pressure-type pain deep behind the eyes(orbital migraine), which can radiate backwards to theocciput, neck, or shoulders or it may start as a dullache in the neck and radiate forward behind the eyes(occipital-orbital migraine). With both these patternsthe pain is often bilateral. The pain can also affect theface (facial migraine) involving the nostrils, cheek,gums, and teeth. Rarely, it may affect the upper andlower limbs on the side of the headache, suggestingthalamic involvement. Attacks commonly occur duringthe day but may wake the patient from sleep or bepresent on wakening. Movement normally aggravatesthe pain and patients prefer to lie quietly. This is incontrast to tension headache, which is usually mildenough for patients to carry on their normal activities,or cluster headache where patients are usually restless.As migraine without aura (‘common migraine’) isat least three times as common as migraine with aura(‘classical migraine’), visual disturbance is not afeature in all. Visual aura generally arises in theoccipital lobe and is therefore hemianopic andconsists of hallucinations (fortification spectra, zigzaglines, incomplete jagged circles, unformed flashesof light) or scotomas (holes in central vision). Thehallucinations are white more often than coloured,and commonly shimmer or jitter as they graduallyenlarge leaving behind an area of impaired vision(scintillating scotoma). These visual symptomsusually evolve over 5–10 minutes and clear graduallyafter 20–30 minutes. Less frequently, the aura mayarise from other areas of the cortex or brainstem andproduce symptoms such as dysphasia with unilateralparaesthesia and hemiparesis, déjà vu and dreamlikestates, olfactory and gustatory hallucinations(temporal lobe), distortions of body image (parietallobe), diplopia, vertigo, ataxia, and dysarthria(brainstem). The hemiparesis is often described as asense of heaviness without true weakness of the limbsand is usually associated with sensory symptomsbeginning in the hand and then spreading to the arm,face, lips, and tongue. As with visual aura, thesesensory symptoms may take 10–20 minutes to evolveand positive symptoms (tingling) are typicallyfollowed by negative symptoms (numbness). The aurain migraine may precede or accompany the headache,or may occur in isolation (a so-called migraineequivalent) often seen in middle age. In some patients,migraine aura may be difficult to distinguish fromtransient ischaemic attack (TIA) or epilepsy.However, migraine aura is usually positive, of gradualonset (5–10 minutes) and accompanied or followedby migraine headache. Although a TIA may beaccompanied by headache, it is distinguished by itsnegative symptoms (loss of vision, weakness, ornumbness), abrupt, nonevolving/spreading onset andits confinement to a single blood vessel territory.Photophobia, phonophobia, dizziness, and vertigoare also commonly reported. However, in patientswith long-standing migraine, the development of newor more severe headache with vomiting, particularlyif related to positional change or accompanied byacute vertigo, should be treated with suspicion, andscanning to exclude a posterior fossa lesion carriedout.Specific forms of migraine can be identifiedsymptomatically:Hemiplegic migraineHemiplegic migraine is a rare, but frequently overdiagnosed, autosomal dominantly inherited disorder.The migraine aura is often associated with transientfocal weakness or other cortical symptoms (e.g.dysphasia, dysarthria, drop attacks) that resolvewithin 24 hours, usually without evidence ofinfarction. These transient deficits may occur withoutaura or headache and diagnosis of migraine may bedifficult unless there is a clear family history.Vertebrobasilar migraineThis is associated with prodromal symptoms arisingfrom the vertebrobasilar territory: brainstem (vertigo,tinnitus, diplopia, ataxia, dysarthria, cranialneuropathies, pyramidal dysfunction); mid brainreticular formation (fainting, sudden loss ofconsciousness, agitation, acute confusion, orprolonged stupor and coma); occipital lobe (bilateralvisual disturbance). These prodromal symptoms mayalso occur without subsequent headache.Ophthalmoplegic migraineHere patients present with unilateral, periorbitalheadache followed within hours by a third nervepalsy with an enlarged pupil. Less commonly, thefourth or sixth cranial nerve may be involved or apartial Horner’s syndrome may occur. The resultantdouble vision usually outlasts the headache by daysor weeks and can even become permanent.
Disorders of sensation193Retinal migrainePatients experience recurrent monocular visual losslasting 5 per day on most days) andare responsive to treatment with indomethacin.Hypnic headacheThis benign headache disorder occurs mainly inelderly patients. The attacks occur during sleep andpatients wake with a medium or severe generalizedheadache, unaccompanied by autonomic features.Attacks typically occur at fixed times each night, lastfor 1 hour and respond well to indomethacin orlithium (cautiously used).Secondary headache disordersSinusitisSinusitis may cause pain in the affected sinus, and bereferred to other areas of the face and head. However,pain in the affected sinus should be identifiable andthere should be evidence of nasal discharge or nasalblockage. Chronic, subclinical sinus infection as acause of recurrent severe headache does not occur,although so often headache is attributed to this.Refractory errorsRefractory errors may cause mild periorbital orfrontal headache, but cannot account for intermittentsevere headache that is not linked to prolonged visualtasks at a distance or angle where vision is impaired.Apart from pain, patients will have evidence of anuncorrected refractive error and may also complain ofvisual blurring, ‘swimming’, or double vision.Cervical spineA number of conditions affecting the cervical spine,such as osteo- and rheumatoid arthritis, cervicalinstability following trauma, and Paget’s disease mayirritate the upper three cervical roots; pain arises inthe neck and back of the head on the ipsilateral sidewith forward radiation to the orbits and frontalregions. Certain neck movements may be painful andrestricted. Careful palpation of the occipital nervesmay produce local tenderness and induce the occipitalheadache.Post-traumatic headachePost-traumatic headache may vary from mild tosevere. The intensity and duration of the headache donot correlate with the severity of the head injury and,indeed, some studies have suggested an inverserelationship with mild head injury causing moreproblems. The headache may be either acute orchronic (persisting >8 weeks) and begins within 2weeks of the injury (or termination of post-traumaticamnesia). The chronic form evolves into a dailyheadache and can be complicated by analgesia misuseheadache. The headache is variably characterized as atension type headache, a migraine type headache, ora combination of both. It is often associated withother post-traumatic problems such as dizziness,depression, and cognitive impairment.Analgesia misuse headacheThis is perhaps the most common association withchronic daily headache. Patients report that theirheadache is frequently improved by analgesia, only toreturn (rebound) as the drug effect wears off. Thisleads to a vicious cycle, and it is not uncommon forpatients with chronic daily headache to end up takinglarge doses of analgesia. Most analgesics have been
194implicated, particularly over-the-counter treatmentscontaining aspirin or paracetamol with caffeine orcodeine phosphate, as well as triptan preparations.After stopping the offending drug, the headache cantake some weeks to settle down.Giant cell arteritisGiant cell arteritis (or temporal arteritis) is aninflammatory disorder affecting medium-sized, extracranial arteries, and should be considered in anypatient presenting with new headache over 50 yearsof age. The affected arteries are painful, tender,swollen, and pulseless. Although the temporal arteriesare commonly affected, other scalp arteries may beinvolved and occipital pain with tenderness is notuncommon. Tenderness of the scalp may causedifficulty with washing or brushing the hair. Patientsmay complain of ‘jaw claudication’ when talking orchewing, with pain in masseter muscles. Generalunwellness with muscle aching, anorexia, weight loss,and even low-grade pyrexia is common. Patients mayalso develop monocular blindness or carotid andvertebrobasilar territory transient ischaemic attacks.Blindness occurs in 50% of patients if untreated, andurgent investigations and treatment with steroids areindicated. A raised erythrocyte sedimentation rate(ESR) can help confirm the diagnosis but a nearnormal ESR does not exclude it. Temporal arterybiopsy (140) may confirm the diagnosis, but a normalbiopsy again will not completely exclude it, as vesselinvolvement is patchy. A dramatic immediateresponse to steroids is also diagnostic.140a140b140 Temporal arteritis. a: biopsy of a temporalartery in transverse section, showing thickening ofthe intimal layer with stenosis of the vessel lumen.There is also disruption of the internal elastic laminawith thickening of the inner layers of the media(haematoxylin and eosin, low power); b: higherpower magnification of the vessel wall at the junctionbetween intima and media, showing disruption of theinternal elastic lamina, multinucleated giant cellformation, and a chronic inflammatory cell infiltrate.
Disorders of sensation195Raised crebrospinal fluid pressure headacheRaised intracranial (cerebrospinal fluid [CSF])pressure headache is characterized by a burstingsensation in the head that is normally present onwaking, aggravated by bending or coughing andassociated with visual obscuration (Table 51). Itresponds poorly to analgesia. Although patientspresenting with these symptoms need furtherinvestigation to exclude potentially serious disease(Table 43), many of these features occur in migraineand many patients with new onset migraine areextensively investigated without any abnormalitybeing found. There are a number of ‘red flags’ orwarnings (Table 49) which should raise suspicion butparticular pointers to serious intracranial pathologyare the presence of very short-lived headaches with apounding quality related to changes in position orstraining, with no headache at other times, andrecent onset headache associated with positionalvertigo and repeated vomiting. Focal signs orpapilloedema may or may not be present but mustalways be examined for.Table 51 Causes of raised cerebrospinal fluid(CSF) pressure headacheMass lesionsCSF circulation blockCerebral oedemaRaised CSF proteinDisorders of circulationSystemic causesTumoursHaematomasAbscessAqueductal stenosisIntraventricular tumourFourth ventricular outflow blockPost head injuryPost cerebral anoxiaBenign intracranial hypertensionSAHPost meningitisGBSSpinal cord tumoursLateral sinus thrombosisJugular vein thrombosisSuperior vena cava obstructionMalignant hypertensionHypercapniaPosterior fossa lesionsAn evolving mass lesion in the posterior fossa (141),with foramen magnum herniation, may present withcontinuous neck and occipital pain. This can beassociated with neck stiffness, head tilt (for comfortand to offset double vision), paraesthesia of theshoulders, dysphagia, and loss of upper limb reflexes.In more acute lesions, there may be episodes of tonicextension and arching of the neck and back,extension and internal rotation of the limbs,respiratory disturbances, cardiac irregularity, and lossof consciousness.141 Axialcomputedtomographyscans withcontrast,showing a leftposterior fossatumour withobstructivehydrocephalus(a). There isenlargement ofthe temporalhorns, lateral,third, andfourth ventricles(b). There isalso mid-lineshift, with thefourth ventriclepushed to theright andeffacement ofthe normalsulcal pattern.141a141bGBS:Guillain–Barré syndrome; SAH: subarachnoidhaemorrhage.
196Low cerebrospinal fluid pressure headacheAlthough spontaneous CSF leaks can occur inpatients with low CSF pressure headache, mostdevelop after a lumbar puncture (LP), epiduralinjection, or Valsalva manoeuvre (during lifting,straining, coughing, or clearing the eustachian tubes).The headache occurs daily, is not present on wakingbut increases towards evening, and is relieved by lyingdown to be aggravated again by standing up.Benign intracranial hypertensionBenign intracranial hypertension typically occurs inyoung, overweight females. Patients present withraised intracranial pressure headache, visual142142 Right VI nerve palsy, with failure of the eye to abduct.Table 52 Secondary causes of benignintracranial hypertensionVascularDrugsEndocrineRenalCardiovascularRespiratoryHaematologyOtherCerebral venous sinus thrombosisJugular vein thrombosisTetracyclineVitamin AAnabolic steroidsGrowth hormoneNalidixic acidLithiumNorplant levonorgestrel implantAddison’s diseaseHypoparathyroidismRenal failureRight heart failureCOPDSevere iron deficiency anaemiaSleep apnoeaCOPD: chronic obstructive pulmonary disease.obscuration or loss, bilateral papilloedema and,occasionally, a sixth nerve palsy (142). Theneurological examination is otherwise normal.Alternative diagnoses such as mass lesions, ventricularenlargement, and venous sinus thrombosis must beexcluded by imaging. CSF pressure is >200 mm ofCSF, with a normal or low protein concentration andnormal cell count. Weight gain and drugs (e.g.tetracycline) may be incriminated, but the majority ofpatients have no identifiable underlying cause.However, other secondary causes (Table 52) should beconsidered, particularly in patients who do not fit thenormal expected phenotype.ACUTE ONSET HEADACHEAcute onset headache which is normally encounteredin the Accident and Emergency Department, with orwithout neurological deficit and, regardless of theseverity, needs urgent assessment and investigation. Athird of these patients will have a potentially fatal ordisabling intracranial condition. Althoughsubarachnoid haemorrhage (SAH) is the immediateconcern of most clinicians, a number of causes shouldbe considered (Table 53). Many of these conditionscan be excluded on the basis of the history,examination, and investigations. However, somepatients require more directed investigations, such ascomputed tomography (CT) or magnetic resonanceimaging (MRI) venography in patients suspected ofhaving cerebral venous sinus thrombosis.Table 53 Causes of acute onset headache❏❏❏❏❏❏❏❏❏Subarachnoid haemorrhageCerebral venous sinus thrombosisSpontaneous intracranial hypotensionPituitary apoplexyCarotid or vertebral artery dissectionMigraineAcute hypertensive crisisCoital/cough/exertional/weight lifter’s headacheThunderclap headache
Disorders of sensation197Subarachnoid haemorrhageSAH (143) presents with headache, reaching itsmaximum intensity instantaneously or at most over acouple of minutes. The pain usually lasts more then 1hour. Apart from headache, patients can be otherwisewell and the absence of neck stiffness, reduced level ofconsciousness, focal deficit, vomiting, or photophobiais no indication of a more benign condition. Inthe investigation of SAH (144) the sensitivity of bothCT and LP is largely dependent on the timing of thetests and the methods used in acquiring and analyzingthe CSF sample. CT scanning should always be donebefore a LP is performed. CT is reported to be95–98% sensitive in detecting SAH if performedwithin 12–24 hours of clinical onset. However, thissensitivity decreases rapidly with time and by the endof the first week is
198Cerebral venous sinus thrombosisCerebral venous sinus thrombosis (145) should besuspected in any patient with a hypercoaguable stateor infection of the paranasal sinuses, middle or innerear presenting with features of stroke or raisedintracranial pressure without ventricular enlargement(Table 54). The presence of multiple cerebral infarctsoutwith arterial territories, the slower evolution ofsymptoms, seizures, and a clotting disorder favourvenous over arterial thrombosis. In some patients,thrombosis of a particular venous sinus can besuggested from the clinical presentation.Cavernous sinus thrombosis (146) presents withchemosis, proptosis, and multiple cranial nerveinvolvement (III, IV, VI, and ophthalmic division ofV). Saggital sinus thrombosis presents withheadaches, seizures, and a hemiparesis thatpredominantly affects the leg. Later in the course ofthe disease both lower limbs are often involved.Posterior cavernous sinus and inferior petrosal sinusthrombosis may present with multiple cranial nervepalsies (V, VI, IX, X, and XI).145a145bPituitary apoplexy syndromeWhen a pituitary adenoma has outgrown its ownblood supply it infarcts. This life-threateningcondition presents with acute onset headache,ophthalmoplegia, bilateral blindness, reduced level ofconsciousness, and pituitary failure. A CT scan showsinfarction and often haemorrhage within the tumour(147).Table 54 Causes of cerebral vein thrombosisInfectionsHaematologicalCancerCardiacDrugsOthersEar (middle and inner ear)Paranasal sinusesSickle cell anaemiaPolycythaemiaThrombocytopeniaParoxysmal nocturnal haemoglobinuriaAntiphospholipid antibody syndromeProtein S and C deficiencyCyanotic congenital heart diseaseOral contraceptive pillPost partumPost operative states145 Axial contrast-enhanced computed tomographyscans, showing cerebral venous sinus thrombosis.Note the filling defects within the right transversesinus (a, arrow) and superior sagittal sinus (deltasign) (b, arrow), diagnostic of venous thrombosis.
Disorders of sensation199146a147a146b147b146 Axial computed tomography scans showingcavernous sinus thrombosis secondary to sphenoidsinusitis. The cavernous sinus on the left side is expandedwith clot, causing a number of filling defects (a, arrows).There is also extension of thrombosis to involve the lefttransverse sinus, and thrombosis in the left superiorophthalmic vein (b). Enhancement in the left cerebellarpontine angle reflects concomitant meningitis (arrow).147 Pituitary apoplexy. a: axial postcontrast computedtomography (CT) scan, showing a pituitary and suprasellarhigh attenuation mass with focal haemorrhage (arrow);b: postcontrast corneal CT scan confirming the pituitary andsuprasellar mass with invasion of the left cavernous sinus.
200Acute hypertensive crisisChronic arterial hypertension of mild or moderatedegree does not cause headache. However,hypertension may be a cause of headache incircumstances where there is an acute, severe, andprolonged elevation in diastolic blood pressure. Inmalignant hypertension, diastolic blood pressure is>120 mmHg (16 kPa), there is evidence of grade 3 or4 retinopathy, the patient may be encephalopathic,and the headache is temporally related to the rise inblood pressure and disappears within 2 days of theblood pressure normalizing (7 days if encephalopathyis present). Patients with a phaeochromocytoma maypresent with headache when there is an acute rise(>25%) in diastolic blood pressure. This may beassociated with sweating, palpitations, or anxiety.The headache disappears within 24 hours of bloodpressure normalization. Patients with pre-eclampsiaand eclampsia may also present with headache whichis associated with oedema or proteinuria, and a bloodpressure rise of 15 mmHg (2 kPa) from the prepregnantlevel or a diastolic pressure of 90 mmHg (12kPa). The headache disappears within 7 days of bloodpressure normalization or termination of thepregnancy. Some toxins or medications may cause anacute rise (>25%) in diastolic blood pressureassociated with headache. The headache willdisappear within 24 hours of blood pressurenormalization.StrokeCarotid and vertebral artery dissection may cause astroke or TIA and is commonly associated withsudden onset headache ipsilateral to the affectedartery.Coital headacheCoital headache is bilateral at onset, precipitated bysexual excitement, prevented or eased by ceasingsexual activity before orgasm, and is not associatedwith intracranial pathology such as an aneurysm.There are three forms: dull, explosive, and posturaltypes. The dull form is characterized by a dull ache inthe head and neck that intensifies as sexualexcitement increases. In the explosive form, there is asudden severe headache that occurs at the time oforgasm, and in the postural form the headachedevelops after coitus and resembles that of low CSFpressure headache.Benign cough headacheCough headache is bilateral, of sudden onset, and isprecipitated by coughing. It may be diagnosed onlyafter structural lesions have been excluded byneuroimaging.Benign exertional headacheBenign exertional headache is specifically brought onby any form of physical activity. Patients complain ofbilateral, throbbing pain that normally lasts between5 minutes and 24 hours. It is prevented by avoidingexcessive exertion and is not associated with anysystemic or intracranial disorder.Idiopathic stabbing headacheIdiopathic stabbing headache is predominantly felt inthe orbit, temporal or parietal region. It is stabbing innature, lasts a fraction of a second, and recurs atirregular intervals. It should only be diagnosed afterstructural lesions have been excluded byneuroimaging.Thunderclap headacheThunderclap headache refers to patients who presentwith suspected SAH but who have a normal CT scanand CSF examination performed within theappropriate time window. This is considered to be arelatively benign condition, which does not requireany further investigations.SUMMARY❏❏❏❏❏❏❏Headache is common and for most is a benignself-limiting symptom.It is crucial to determine if the headache is newor the exacerbation of an existing headache,which has become more frequent or severe.The possibility of having a serious cause doesnot increase in proportion to the severity,frequency, or duration of the headache.Patients with tumours rarely present withheadache alone.History and examination should identify thosepatients with red flag symptoms and signs whoneed investigation.Sudden onset headache should be investigatedurgently.All patients over the age of 50 years with newonset daily headache should have their ESRchecked.
Disorders of sensation201CLINICAL SCENARIOSCASE 1A 69-year-old woman presented to Accidentand Emergency with a 12-day history of painand tenderness diffusely affecting her scalpand associated with jaw claudication.This elderly woman is presenting withnew daily persistent headache (Table 50).Scalp tenderness and jaw claudication suggestan extracranial vascular cause.Five days later she developed diplopia andcomplete ptosis of the right eyelid.Diplopia and complete ptosis of the righteyelid suggest III cranial nerve palsy. Thismay be due to compression of the nerve by ananeurysm or ischaemia of the nerve due tonarrowing of the blood vessel that supplies it.On examination, she had a right III nervepalsy with pupillary sparing. The righttemporal artery pulsation was absent, butthere was no overlying tenderness.A III nerve palsy with pupillary sparingsuggests ischaemia of the nerve rather thencompression, and taken together with absenceof the temporal artery pulsation suggeststemporal arteritis.On investigation, she had a normal full bloodcount and glucose. Her C-reactive protein (CRP)was 17 mg/l (normal
202CASE 2 (continued)She is over-using both naratriptan and Solpadol medication. Although Solpadol is giving hergood symptomatic relief, she has developed rebound headache and is requiring increasing dosesof analgesia to control her headache.On examination there was no focal neurological deficit and fundoscopy was normal.She was diagnosed with migraine headaches complicated by analgesic and naratriptanmisuse. She was advised to stop both her naratriptan and Solpadol medication. After 4 monthsher headaches had improved significantly and she was having only two attacks of migraine amonth. Subcutaneous sumatriptan was added to her prophylactic treatment and she was advisedto limit its use to twice a month.CASE 3A 55-year-old male, admitted to his district generalhospital, was referred to the visiting neurologist with ahistory of new onset headache that had been constantfor 10 days, with only temporary relief from simpleanalgesia. There was no history of head injury. He had apast history of rheumatic fever and had a prostheticheart valve replacement 10 years earlier for which hewas on warfarin. He was also being investigated for araised prostate specific antigen.This man is presenting with new daily persistentheadache (Table 50). Although there is no history ofhead injury, he is at risk of intracranial haemorrhageand subdural haematoma because of his anticoagulationtherapy. He is under investigation for raised prostatespecific antigen (a tumour marker) and the headachemay be a presentation of cerebral metastasis.His headache had come on instantaneously whilewatching television with his wife. There were noassociated symptoms, precipitating, or aggravatingfeatures. On examination he was alert and orientated.There was no neck stiffness and Kernig’s sign wasnegative. Cranial nerves, fundoscopy, and upper andlower limb examination were normal. A CT scan of hisbrain performed on admission was normal.The sudden onset suggests a vascularcause and SAH needs to be excludedurgently. The normal CT scan and lack offocal deficit, neck stiffness, and reducedlevel of consciousness are not totallyreassuring and do not exclude SAH.Following the administration of freshfrozen plasma to temporarily reverse hiswarfarin, he had a LP performed whichwas abnormal and consistent with a latediagnosis of SAH. Four-vessel cerebralangiography was performed, but noevidence of cerebral aneurysm orarteriovenous malformation was found. Hisheadache settled spontaneously andcompletely.Some patients with proven SAH do nothave a radiologically demonstrable aneurysmor vascular malformation; prognosis here isfavourable with negligible recurrence rates.
Disorders of sensation203REVISION QUESTIONS1 In the assessment and investigation ofsubarachnoid haemorrhage, which of thesestatements is true?a The headache reaches its maximum intensityinstantaneously or at most over a couple ofminutes.b Meningism is an important sign.c A normal CT scan done within the first12 hours of ictus excludes the diagnosis.d A normal lumbar puncture done within thefirst 12 hours of ictus excludes the diagnosis.e A normal lumbar puncture done a week afterthe ictus excludes the diagnosis.f A patient who presents with coital headachefor the first time can be reassured.3 Which of these statements is true?a Subarachnoid haemorrhage may present withnew-onset, chronic, daily headache.b Sudden-onset, unilateral headache associatedwith ipsilateral Horner’s syndrome andcontralateral hemiparesis suggests carotiddissection ipsilateral to the headache.c A normal temporal artery biopsy excludes thediagnosis of temporal arteritis.d Patients with cluster headache prefer to liestill.e Alcohol may precipitate a cluster headacheduring periods of remission.f Chronic arterial hypertension of moderatedegree does not cause headache.2 In patients with chronic daily headache, whichof these statements is true?a Patients presenting to Casualty with chronicdaily headache are unlikely to have migraine.b Patients over the age of 50 years who presentwith a new-onset, focal, daily headacheshould be considered to have temporalarteritis until proven otherwise.c Migraine prophylactic medication is effectivein patients with migraine and analgesiainducedheadache.d Analgesia-induced headache may take up to 6months to settle down after stopping theoffending agent.e All analgesic and triptan medications can beassociated with analgesia-induced headache.f Migraine may present with chronic dailyheadache.Answers1 a, e2 b, d, e, f3 a, b, f
204SPINAL SYMPTOMS: NECK PAIN AND BACKACHEJohn Paul LeachINTRODUCTIONNeck pain and backache are common causes of selfreferralin primary care, but are much less frequentvisitors to neurology outpatients, being seen mainly inorthopaedic clinics. Almost anyone over the age of 40years will be able to give a history of back or neck painat some point in their lives, as it would appear that oneof the flaws inherent in the design of the human spineis the frequency with which it will produce pain,stiffness, and a general creaking as age advances.Among men over the age of 50 years, 90% will displayradiographic evidence of degenerative changes.As a result of the profusion of frequent, oftennonspecific symptoms, spinal disease is one of the fewareas in clinical neurology where history taking seemssecondary to examination in terms of importance.Since neck and back pain are common enough to bealmost physiological states, the role of the neurologistis to determine which patients warrant furtherinvestigation and which require reassurance alone.Most cases of neck and back pain will have nodemonstrable neurological deficit. Localization ofspinal pathology on the basis of neurological findingscan be challenging, despite the common anatomy (abundle of nerves and nerve roots encased in asegmented bony canal) (148). The patterns of deficitcaused by cervical, thoracic, and lumbar spinaldisease are different, and here will be addressed asupper (cervical and thoracic) and lower (lumbar andsacral) spinal syndromes.may provide vital clues to multilevel neurologicaldisease, or the intracranial masquerading as spinalpathology. Abnormal eye movements, fundalchanges, pupillary abnormalities, and lower cranialnerve/cerebellar signs should be particularly sought.Subtle eye movement disorders may betray theexistence of multiple sclerosis presenting withmyelopathy, while cerebellar ataxia suggests posteriorfossa disease. Horner’s syndrome can be a helpfullocalizing sign, ipsilateral to weakness at the cervicallevel while contralateral at the cranial level.Upper limb examinationIf there is significant cervical root compression, motorsystem examination may show signs of lower motorneurone (LMN) involvement (wasting, weakness,poor reflexes) which will vary with the level of thelesion (Table 55).Sensory examination can help elucidate the level(149) although it should be stressed that it is motorinvolvement (weakness and wasting) and radiology148Cervical segmentsIntervertebralforaminaCervicalroots1–8CLINICAL ASSESSMENTWhile patients’ histories may dwell on limbsymptoms and localized pain, care should be taken toelicit any complaint of sphincter disturbance ortruncal sensory disturbance. General examination isabsolutely essential as this may identify featuressuggesting generalized conditions in which the spinalcord may be secondarily involved, e.g. neurofibromatosis,adrenal insufficiency, or primaryneoplasm. Such findings expand the differentialdiagnosis of underlying spinal pathology. As with allpatients referred for an opinion, while the emphasis ison possible spinal disease, a full neurologicalexamination is mandatory.Cranial nerve examinationIn patients with arm and/or leg symptoms, cranialnerve examination may seem irrelevant. However, itThoracicsegmentsLumbar segmentsSacral segmentsCoccygealsegmentThoracicroots1–12Lumbarroots1–5Sacralroots1–5148 Diagram of sagittal spinal cord, illustrating nerve roots inrelation to vertebral bodies.
Disorders of sensation205that will motivate the surgeon when to operate. Anylesion above C8 may be associated with some evidenceof upper motor neurone (UMN) dysfunction in one orboth arms. In general, the higher the cervical lesion, themore probable that there will be UMN signs in thearms, often with a clear reflex level (absent or reducedat the level, and brisk below the level).Lower limb examinationAssessment of lower limbs in patients with upperspinal cord lesions will show UMN signs. These takethe form of brisk reflexes, spread of reflexes bothabove and below the tested level, clonus withincreased tone, and extensor plantar responses. Itwould seem logical (although not definitive) thatpatients with cervical vertebral problems will be morelikely to experience lumbar spine disease. Widespreadspinal degenerative disease is one of the recognizedcauses of mixed UMN and LMN signs.An additional test of lower spine function involvesstretch testing to indicate nerve root compression/irritation. The commonest such test is straight legraising. This involves an assessment of the discomfortand pain induced by hip flexion, when the knee is eitherflexed or fully extended. When the leg is raised and theknee extended, stretching of the nerve roots will cause ashooting pain in the distribution of the affected nerveroots. This pain will not occur (or will be much less)when the knee is flexed during leg raising.Sphincter and perineal examinationIn patients with sacral root lesions, anal sphinctertone may be lost. When there is suspectedinvolvement of these lower spinal roots, assessment ofanal tone is necessary. Where a central (within thecord) spinal lesion is present, the positioning of thespinothalamic pathways (more caudal fibres lyingmost peripherally within the spinal cord) will meanthat there is widespread caudal loss of pinpricksensation that spares the perianal region. This iscalled ‘sacral sparing’. The reverse pattern of sensory149 Dermatomal mapshowing lesionlocalization.VVVC2 C3T2T3T4T5T6T7T8T9T10T11T12L1L2C4C5T2T1C6C8C7149Table 55 Reflexes and rootsReflexLevelJaw jerkTrigeminal nervesPectoral jerksC3, C4TricepsC6, C7BicepsC5, C6SupinatorsC5, C6Abdominal reflexes Thoracic rootsCrossed adductorsL2, L3KneesL3, L4AnklesL5, S1L3L4 L5C7,6C6,7,8T1C8T1C6,7
206loss occurs when the cord is compressed fromwithout (150).When there are symptoms suspicious of spinaldisease with accompanying neurological symptoms,the main questions to be addressed are:❏ At what level in the neuraxis is the lesion? (Useof cord and radicular signs.)❏ Where is the lesion: intramedullary,extramedullary intradural or extradural (seepage 207)?❏ What is the lesion (see page 209)?Lesion level localizationThis may be ascertained by differentiating the cord ornerve roots signs. The constellation of symptoms willvary depending on the region affected. In upper spinaldisease (cervical and thoracic spine), the spinal cordor nerve roots may be affected.At upper levels, therefore, the potential effects are:❏ Upper motor problems in the legs.❏ Lower motor neurone problems in the arms.❏ Truncal sensory level changes.❏ Sphincter disturbance.❏ Horner’s syndrome (with cervical lesions).The spinal cord finishes at approximately L1level. As a result, neurological effects of lumbar orsacral spine disease almost exclusively involve aradicular pattern.Pressure on the lower spinal cord and caudaequina causes:❏❏❏LMN problems in the legs, with clinical featuresdependent on the particular roots affected.Truncal or sacral sensory level changes.Sphincter disturbance.Cord involvement will cause LMN lesions at thelevel of the lesion, with UMN signs below.Involvement of the cauda equina (i.e. below the levelof L1) will cause only LMN symptoms.Localization by cord symptomsA lesion produces neurological deficit at or below itslevel. Sometimes, however, a lesion may be at a higherlevel than is apparent clinically, i.e. a sensory levelsuggesting a thoracic level may be being produced bya cervical lesion ( a ‘dropped level’). At the level of thelesion, motor signs may be of a LMN type, given thedirect destructive effect on anterior horn cells.Sensory signs may be soft or absent, but there may bea band of dysaesthesia round the truncalcircumference at the level of spinal involvement.Below the lesion, sensory changes will usually becomemore likely and more severe. Motor signs will be ofUMN type below the level of any spinal lesion.Bladder symptoms only occur where the cord isaffected bilaterally. Such cord lesions will initiallyleave an atonic bladder, with absence of sensation offullness. With time, the bladder begins to undergoTable 56 Pitfalls in root/peripheral nerve lesiondifferentiation150UpperlesionL5–S1 versus peroneal nerve:❏ Both will cause weakness of ankle dorsiflexion andsensory changes over anterior shin and foot❏ Peroneal nerve lesion may be associated with Tinel’ssign round the fibular neck❏ L5–S1 lesion may cause reduced ankle jerk andweakness of foot inversion (and possibly a positivestraight leg raising test)LowerlesionS3–S5‘Saddle’ area150 Diagram of cauda equina lesions, illustrating the affectedsaddle area.S2C8–T1 versus ulnar nerve❏ Both will cause weakness of intrinsic muscles of thehand❏ Isolated ulnar lesions should cause only hypothenareminence and interossei wasting. Sensory changes areusually confined to the hand❏ C8–T1 lesions may cause wasting also at the thenareminence and may have associated sensory changealong the medial border of the forearm
Disorders of sensation207reflex emptying causing urinary urgency and urgeincontinence. In general, a hypertonic bladderindicates a UMN lesion, e.g. a lesion affecting thespinal cord or brain.Autonomic fibres in the cervical cord supply sympatheticfunction which can be clinically assessed bychecking sweating in limbs, trunk, and face. Anothermeasure of spinal sympathetic function is the presenceor absence of a Horner’s syndrome. There will sometimesbe a localized pain or even tenderness overlyingcord pathologies which can help with localization.Localization by radicular symptomsRadicular localization can be done on the basis ofsensory or motor changes. Knowledge of the basicdermatomal pattern (see below) will allow inference tobe drawn on the level of involvement. Sensory changeis usually a subjective electric shock-like pain along theaffected dermatome, although more chronic lesionscan lead to numbness in the affected area. Motorchanges will usually involve reduction or loss of therelevant reflexes on the affected side (Table 55).Differentiation of radicular symptoms fromperipheral nerve-related symptoms can only be donewhen there is a knowledge of the characteristicpatterns of innervation of each of the peripheralnerves and the functions supplied by each spinal root.This can be difficult, however, and somecharacteristic pitfalls are listed (Table 56). Directpressure on the sacral roots by a lumbar or sacrallesion causes a LMN bladder, with loss of sensationof fullness and an atonic overfilling bladder.Lesion anatomical localizationThe extent and pattern of involvement of the spinalcord in disease may result in characteristic patterns ofdeficit, which can give further clues to the nature ofthe pathological process (151).Sensory deficit Useful localizing Lesion sitefeatures (if present)CONTRALATERALSPINOTHALAMICTRACT LESIONLoss of pain, temperature and light touchbelow a specific dermatome level (mayspare sacral sensation)Loss of all modalities at one or severaldermatome levelsLoss of pain and temperature below aspecific dermatome level(Partialspinothalamictract lesion)BROWN-SÉQUARD SYNDROME151Loss of proprioception and‘discriminatory’ touch up to similar leveland limb weakness(Partial cord lesion)Bilateral loss of all modalities.Bilateral leg weaknessCOMPLETE CORD LESION‘Suspended’sensory lossBilateral loss of pain and temperature.Preservation of proprioception and‘discriminatory’ sensationCENTRAL CORD LESION151 Diagram to show the characteristic patterns of sensory loss in various spinal cord lesions.
208Brown-Séquard syndromeLesions affecting one or other half of the spinal cordwill cause UMN weakness and spasticity below thelesion. There occurs typically a mixed bilateralsensory deficit of spinothalamic loss (pain andtemperature) below and contralateral to the lesion,and dorsal columnar loss (proprioception andvibration) below and ipsilateral to the lesion (152).Complete transverse lesionsThese result in bilateral UMN weakness andspasticity below the lesion. There may be LMN signsat the level of the lesion which can help inlocalization. Corticospinal, spinothalamic, and dorsalcolumn tracts are affected (153). All modalities areaffected (there may frequently be sphincterinvolvement, and sometimes Lhermitte’s sign).152CorticospinaltractLATERAL COMPRESSIVE LESIONDorsal columns – gracileand cuneate nucleiTumourCentral cord lesionsEarliest motor effects of central cord lesions will involveanterior horn cells at the levels of the lesion, with aresultant LMN lesion pattern. Later, with furtherexpansion, the corticospinal tracts can be involved andcan cause caudal UMN signs. Early decussation near thepoint of entry by spinothalamic fibres means that morerostral fibres layers tend to be more centrally placed inthe cord. This explains why central cord lesions maytherefore spare spinothalamic fibres below the level ofthe lesion (sacral or abdominal pinprick) (154). Centralcord lesions which extend anteriorly may also affectsecond order spinothalamic fibres as they decussate infront of the anterior ventral commissure.Lateral spinothalamic tractBROWN-SÉQUARDSYNDROMEIpsilateralroot/segmentalsigns153TumourImpairment of allsensory modalitiesup to the level ofthe lesionContralateralimpairmentof pain andtemperaturesensationIpsilateralpyramidalweakness andimpaired jointposition senseand accuratetouchlocalizationBladderdilatedLimbsflaccid152 Diagram of an incomplete lateral compressive lesion, withthe attendant pattern of sensory impairment.153 Diagram of a complete extrinsic spinal cord lesion, withattendant clinical features.
Disorders of sensation209Anterior spinal cordThrombosis of the anterior spinal artery damagesanterior spinal cord only. The effects on corticospinaltracts leave bilateral spasticity and weakness belowthe lesion with, sometimes, LMN weakness at thelevel of the lesion. There is a dissociated sensory loss,i.e. there is a bilateral decrease in pinprick andtemperature sensation with sparing of light touch,joint position sense, and vibration sense. This isbecause of selective damage to the spinothalamictracts: dorsal column sensation is supplied by theposterior spinal arteries, and is therefore unaffected.Nature of the lesionThe nature of onset and rate of progression willsuggest the nature of the lesion; for example, vascularlesions will occur abruptly, while demyelinatinglesions may demonstrate a more subacute onset.Metastatic lesions will usually be slowly progressive,CENTRAL CORD LESION154and may cause pain secondary to local destruction.Pathologies around the spinal cord may be referred toas either intrinsic to the spinal cord (intramedullary)or extrinsic to the cord (extramedullary) (Table 57).Extramedullary lesions may in turn be intradural orextradural.InvestigationsAs stated above, minor ‘wear and tear’ is seen in themajority of plain X-rays of cervical and lumbar spinein middle age. Plain X-rays of spine will be usefulwhere there has been acute spinal trauma, but nototherwise. The imaging regime of choice is magneticresonance imaging (MRI). This will give both axial(transverse cuts) and sagittal (longitudinal cuts) viewsof the affected region, which will allow a goodassessment both of any spinal cord compression andany root canal stenosis that may correlate withradicular symptoms. In patients where MRI iscontraindicated (e.g. patients with prostheses in situ)then computed tomography myelogram is a helpfulalternative. In differentiation of peripheral nerve androot lesions, nerve conduction studies andelectromyography can be useful.SUMMARY❏❏Minor spinal symptoms are common,neurological sequelae are not.Imaging is best done where there is a possibilityof surgery; or where symptoms or signs suggestserious neurological disease.‘CAPE’ sensorydeficitTable 57 Causes of spinal cord pathologySacralsparing154 Diagram of a central cord lesion, with sensory findings.Pathology around the cordVertebral/spinal column disease:❏ Degenerative❏ Infiltrative (neoplastic)❏ Infective❏ Dural disease❏ NeoplasticPathology within the cord:❏ Inflammatory❏ Neoplastic (primary or secondary)❏ Ischaemic/haemorrhagic❏ Developmental (syringomyelia)❏ Degenerative
210CLINICAL SCENARIOS155CASE 1A 66-year-old female was referred for an inpatientneurology review. She had a long history of backand neck pain over the previous 30 years, but hadsustained a fall the week previously. Prior to thefall, she could do her own shopping, but was nowunable to walk. She was unable to dress herselfand could not brush her hair as her arms were soweak. She complained of dyspnoea on mildexertion. She was also being treated for apresumed urinary tract infection on account ofurinary symptoms. The attending physicians wereconcerned initially that she had sustained a strokeand had organized a CT scan of brain, whichproved normal.The sudden deterioration in walking wasoriginally thought to be due to stroke; theinvolvement of both legs and both arms,however, should immediately raise suspicion of acervical spinal lesion. The onset of dyspnoea inthe absence of any history of chest disease mayalso relate to an upper cervical lesioncompromising diaphragmatic function. Herbladder symptoms may represent a hyperactivebladder secondary to spinal pathology ratherthan being indicative of infection.155 Sagittal magneticresonance image ofcervical spine, showingsevere cord compressionat C3–C5 levels.The patient was alert and fully orientated.Cardiovascular and respiratory examinationswere normal although the patient was breathlesson minimal exertion. Cranial nerve examinationwas unremarkable. Examination of the upperlimbs revealed increased tone bilaterally,symmetrically reduced power of all movements,and brisk biceps, supinator, and triceps jerks.Sensory testing was normal. In the lower limbs,tone was increased, and there was mildweakness of all movements with increasedreflexes and upgoing plantars.Examination confirmed UMN signs involvingall four limbs: together with the sphincterdisturbance (mid-stream specimens of urine wereconsistently sterile) this would immediately alertthe clinician to a spinal cord lesion at the cervicallevel. Dyspnoea had become prominent and wasanother localizing symptom (muscles ofrespiration are supplied at C3,4, and 5 levels).Speed of onset was quicker than would beexpected for a demyelinating or inflammatorylesion. (In any event, demyelination is rare at thisage.) The timing of the weakness, comingimmediately after a fall, was felt to be more thancoincidental, and it appeared likely that therehad been significant mechanical damage to thecervical spine sustained during (or perhapscontributing to) her fall.MRI of cervical spine showed there to besevere spondylitic and degenerative changes, mostpronounced at higher levels (155). Referral wasmade to the neurosurgeons, who initially refusedto offer operation in view of the risk ofexacerbation. She deteriorated over the next fewweeks, with increasing weakness in both armsand a worsening in respiratory function.It was decided that a conservative policyposed an unacceptably high risk to herrespiratory function. Decompression was carriedout in order to prevent further deterioration, butshe did surprisingly well; she regained hermobility, and has now begun to mobilizeoutdoors with the aid of a zimmer frame.
Disorders of sensation211CASE 2A previously well 45-year-old female wasadmitted to the medical wards after a collapse athome. She remembers having a sudden onset ofneck pain followed by a weakness on the rightside. She had been diagnosed as having a strokeand had undergone a (normal) CT of brain. Shecomplained of some weakness and numbness ofboth legs and her right arm, which had beenascribed to her stroke. She gave no history ofprevious back or neck problems.The sudden onset of symptoms would beconsistent with cerebrovascular disease, but acrucial part of the history was the initial neckpain: the abrupt onset of this pain withoutpreceding trauma is suggestive of a vascularlesion or a haemorrhage.Cardiological and respiratory examinationswere normal. The patient was alert andorientated. The pupil was smaller on the rightside, but both pupils were reactive to light andaccommodation. There was a slight right-sidedptosis, but a full range of eye movements.Acuities were normal and cranial nerve functionwas otherwise normal. She had a spastic catch inthe right arm and had grade 4 weakness of herright arm and mild weakness in the right leg.Sensory testing was inconsistent. Pinprick wasaltered in all limbs, but less noticeably in the leftleg. Vibration testing was absent to the left ankleand right knee.A helpful localizing sign was the Horner’ssyndrome: it would be very unusual for a stroketo cause an isolated Horner’s syndrome. Thedissociated sensory loss (not quite the classicalpattern) was clue to the spinal origin of hersymptoms.MRI scanning showed very markeddegenerative cervical spine disease (156).After surgical review, the patient underwentcervical spine decompression with good effect.The Horner’s syndrome eventually resolved.156 Sagittalmagneticresonanceimage ofcervicalspine,showingsevere cordcompressionat levelC4–C7,withmarkedbulging ofdisc atC6–7.156CASE 3A 61-year-old male presented to the neurology services after a subacute onset of leg weakness 10days previously. After the leg weakness had evolved, he began to notice some terminal dribblingon micturition. There was no recent onset of altered sensation, although 3 years previously hehad been diagnosed as having a peripheral neuropathy ‘of abrupt onset’ which affected the legs.There were no cranial or upper limb symptoms, and no history of back pain or trauma.The limitation of symptoms to legs and bladder is a clue to a spinal pathology. The historyof previous leg symptoms suggests that current symptoms may be a further manifestation of apre-existing lesion. Stepwise progression of such deficits can occur due to piecemeal infarctioncaused by dural arteriovenous fistulae.(Continued overleaf)
212CASE 3 (continued)Examination revealed normal cranial nerveand upper limb function. Tone was reduced inthe legs, with weakness of hip flexion to grade3, and grade 4 weakness elsewhere. The rightknee jerk and both ankle jerks were lost andboth plantars were upgoing. Sensory testingshowed subjective distal sensory change; therewas a loss of vibration to both knees and lostpinprick to mid shins.Abrupt onset of neuropathy is rather rare.The mixture of LMN and UMN signs limits thediagnosis to a short list of possibilities. Giventhese signs, imaging of the spine is essential.Nerve conduction studies appeared toconfirm the presence of a peripheral neuropathy,but other tests did not reveal any systemic ornutritional cause of such a neuropathy. MRI andCT scanning showed some serpiginous flowvoids over the lower thoracic cord and caudaequina (157–159).Such changes were consistent with thepresence of a dural arteriovenous fistula. Glueembolism was attempted with someradiographic success, but it had no effect on hisclinical symptoms. Further scans showed arecurrence. Further surgical ligation wasundertaken with good effect.157157 Sagittalmagneticresonanceimage,showingdural fistula(arrowheads).158 158 Magneticresonance angiogramof spinal vasculature,hunting for the sourceof dural fistula.159159 Computedtomographyangiogramillustrating thelength of duralfistula.
Disorders of sensation 213REVISION QUESTIONS1 In cervical spine disease which of the followingstatements are true?a A ‘clicking’ or ‘crunching’ sensationexperienced by the patient is a symptom ofserious pathology.b Bony change on X-ray is unusual in patientsof middle age.c Cranial nerve examination can provide usefulinformation.d Jaw jerk is a sign of cervical myelopathy.e Hyper-reflexia in the legs is a reliable sign ofmyelopathy.3 In lumbar and thoracic spine disease which ofthe following statements are true?a Hyper-reflexia is a common sign of lumbarspine involvement.b A normal straight leg raising test precludessurgical intervention.c Loss of knee jerks is a sign of L5radiculopathy.d Unilateral lesions commonly cause bladdersymptoms.e A lower motor neurone bladder is small andhas a small residual volume whencatheterized.2 In thoracic spine disease which of the followingstatements are true?a The sensory level is a reliable pointer to thelevel of the involvement.b Urinary urgency and incontinence is a sign ofradiculopathy.c Loss of perianal sensation is a sign ofpathology in the central cord.d Unilateral cord pathology causes loss of painand temperature sensation inferior andipsilateral to the lesion.e Anterior cord lesions cause loss of vibrationand proprioception.Answers1 c, e2 None, all false.3 None, all false.
214NUMBNESS AND TINGLING Colin O’LearyINTRODUCTIONNumbness and tingling are frequently reportedsymptoms. They occur not only in neurologicaldisorders, but are a feature of metabolic disturbancessuch as hypocapnia (e.g. due to over-breathing inpanic attacks) or hypocalcaemia; most people haveexperienced these symptoms following either a dentalor other local anaesthetic, or resulting from lyingawkwardly on a limb. Thus, these are familiarsensations. In neurological disorders, sensorysymptoms are frequent presenting complaints, eventhough on examination patients may have evidence ofextrasensory involvement, or may subsequentlydevelop extrasensory symptoms. There are, however,some disorders that can singularly or predominantlyaffect the sensory system.ANATOMY AND PHYSIOLOGYA detailed consideration of the complexities andfunction of sensory pathways is beyond the remit ofthis chapter; what follows is a simplified overviewpertinent to clinical practice in facilitating thelocalization and nature of a lesion(s). Special senses(sight, hearing, smell, taste) are not considered here.Sensation begins as a stimulus to a sensoryreceptor; this message is then conveyed by peripheraland central neuronal pathways back to the brain.Disorders of sensation can be due to lesions at anypoint along these pathways. Within this sensorynetwork, there are anatomical and physiologicaldivisions, a working knowledge of which permitsclinical localization. These factors are consideredbelow from a physiological viewpoint.Sensory receptorsThere are many different sensory receptors subservingsuperficial and deep sensation. These include touchand pressure receptors, Pacinian corpuscles(vibration), pain and temperature receptors, andstretch receptors in muscle spindles. These receptorsare the starting points of the sensory pathways andconvey different sensory information from the skin(touch, pain, temperature), and deep structures suchas muscles, joints, ligaments, and organs(proprioception [joint position sense], pressure, pain).The receptors synapse with sensory nerve endingsthat merge to form peripheral nerves.Peripheral nervesPeripheral nerves comprise many thousands ofindividual nerve axons, and are mainly mixed, i.e.contain motor nerves supplying muscles, sensorynerves, and autonomic nerves. These axons vary indiameter and in their degree of myelination, factorswhich determine the speed at which impulses areconducted through the nerve; the largest and mostheavily myelinated fibres conduct most quickly (up to130 m/second), and unmyelinated fibres are theslowest (2 m/second) (Table 58). Different sensationsare subserved by differing populations of nerves andthis determines how quickly these sensations areperceived, e.g. proprioception is conveyed veryquickly and pain/temperature relatively slowly. Apractical example of this is that when touchingsomething very hot, one appreciates the sensation oftouch before one is aware of the temperature. Manyperipheral nerves lie deep and are well protected, butsome are prone to pressure damage at particular sites,e.g. the median nerve at the wrist (deep to the flexorretinaculum), the ulnar nerve at the elbow (medialepicondyle), and the common peroneal nerve behindthe knee (neck of the fibula).Nerve plexusesThe innervation of limbs and limb girdles is viaplexuses (brachial and lumbo-sacral) formed byspinal nerves, which allows nerves from severaldifferent spinal levels to form peripheral nerves. Thetrunk (cage) is supplied by spinal nerves only: visceraare supplied by the vagus nerve (X cranial nerve).Spinal nerves and rootsAt each level of the spinal cord, a pair of nerve rootsemerge on both sides, posterior and anterior. Thesejoin together to form spinal nerves that then exit thespinal canal as a pair at each level, right and left. Theanterior spinal nerve root conveys motor axons only.All sensory nerves enter the spinal cord via theposterior roots. The nerve cell bodies of all peripheralsensory axons are in a ganglion protruding from eachposterior spinal root, the dorsal root ganglion (DRG).These nerve roots and spinal nerves are particularlyprone to injury within the spinal canal and as theyexit it via the intervertebral foramina.
Disorders of sensation 215Table 58 Classification of sensory nerve fibresMaximumFibre Maximum conduction Degree oftype diameter (µ) velocity (m/second) myelination FunctionIa 22 120 +++ Muscle spindle primary afferentsIb 22 120 +++ Golgi tendon organs, touch and pressurereceptorsII 13 70 ++ Muscle spindle secondary afferents,touch and pressure receptors, Paciniancorpuscles (vibratory receptors)III 5 15 + Touch, pressure, pain, temperatureIV 1 2 - Pain, temperatureSpinal cordUp to the spinal cord, sensation follows a commonpathway (although the differing morphology ofperipheral axons renders them susceptible to differentpathological processes). In the spinal cord, the nervesentering via the posterior spinal root (via theposterior root entry zone) divide into two mainbundles. Those nerves subserving proprioceptionascend in the ipsilateral (same side) posterior columnsto the mid medulla oblongata, where they terminatein the cuneate and gracile nuclei. From these nuclei,second order neurones decussate and ascend to thecontralateral thalamus in the medial lemniscus. Fibressubserving touch, pain, and temperature synapse withsecond order sensory nerves and traverse the spinalcord, anterior to the central canal. The fibres ascendto the thalami as the anterior spino-thalamic tracts,those nerves entering the more distal spinal cordmost, lying more superficially. Thus, within the cord,there is functional and anatomical separation that isof significance in localizing lesions (160).PrimarysomatosensorycortexLowermedullaSpinalcord448753261160ProprioceptionPainTemperature160 Diagram to show a simplified outline of major sensorypathways. 1: dorsal root ganglion; 2: fasciculus cuneatus;3: fasciculus gracilis; 4: lateral spino-thalamic tract; 5: mediallemniscus; 6: nucleus cuneatus; 7: nucleus gracilis;8: thalamus.
216Facio-cranial sensationThe face and deep cranial structures receive theirsensory supply via the V (trigeminal) cranial nerve (alsomotor to the muscles of mastication) (161). The uppercervical roots supply the posterior scalp. The cellbodies of the sensory afferents of the trigeminal nerveare contained in the trigeminal (gasserian) ganglion,the equivalent of the spinal nerve DRG. The trigeminalnerve enters the brainstem at the level of the mid ponswhere the proprioceptive (and motor) nuclei arelocated, and the second order sensory axons thentraverse the pons to ascend to the thalamus. Fibressubserving pain, temperature, and touch descend as thespinal tract of the trigeminal nerve to the ipsilateralmedulla and upper cervical cord where they form thenucleus of the spinal tract of V. Second order sensoryneurones then traverse the cord/medulla and ascend tothe thalami. Thus, unilateral lesions in the uppercervical spine/medulla can give rise to contralateraltrunk and limb pain, temperature and touch loss(ascending spino-thalamic tract), as well as facial lossof the same sensory modalities (descending spinal tractand nucleus). This feature is characteristic of lowerbrainstem lesions.ThalamiThese large, deep-brain nuclei are the first level atwhich one becomes conscious of sensory stimuli.Unilateral lesions here and above, give rise to partialor complete hemi sensory syndromes. Lesions of thethalami are often associated with pain (thalamicsyndrome). Third order neurones project from thethalami to the ipsilateral sensory cortex via theposterior limb of the internal capsule.161abTrigeminal nervedivisions:12345678Trigeminal nervedivisions:321Sensory cortexThe primary sensory cortex is located at thepostcentral gyrus, and is where integrated finesensation (i.e. the texture and temperature of objects)is appreciated (162). Associated sensory areas in theparietal cortex are responsible for integratedsensations such as stereognosis (the ability torecognize objects through touch), graphaesthesia (theability to identify characters traced on the skin), andtwo-point discrimination (the ability to recognize twoadjacent stimuli as separate). Clearly, these functionsdepend on intact peripheral sensation.161 Diagram to show the somatotrophic organization of thetrigeminal system. a: peripheral innervation territories of thetrigeminal nerve. 1: ophthalmic; 2: maxillary; 3: mandibulartrigeminal nerve; 4: innervation by cervical sensory roots.b: organization of the spinal trigeminal tract in relation to thethree trigeminal nerve divisions and the glossopharyngealnerves for the portion of the medulla that includes the caudalnucleus. 5: spinal trigeminal nucleus; 6: cuneate nucleus;7: gracile nucleus; 8: glossopharyngeal nucleus.
Disorders of sensation 217Other sensory pathwaysThe brainstem and cerebellum also receive sensoryinput via specific spinal tracts. These subserve themaintenance of smooth movements, balance, andcoordination, and are subconscious. These are notconsidered further here.CLINICAL ASSESSMENTHistory and examinationHistory taking is particularly important when itcomes to elucidating sensory symptoms, as in manycases there may be few, if any, objective neurologicalsigns. Although the history should focus on thepresenting complaint(s), it is important to ask aboutother neurological symptoms, as well asencompassing non-neurological causes. It is alsoimportant to be aware that patients may describenonsensory symptoms in sensory terms: a commonexample is the patient who describes weakness of alimb as numbness. Equally, it is important tocomplete a full neurological examination.It is important to interrogate the patient as to theprecise nature of their sensory symptoms. As sensorysymptoms are often vague in nature, a superficialhistory will lead to imprecise localization anddifferential diagnosis. Armed with basic anatomicophysiologicalconcepts, it is important to detailimportant negatives in the history, in addition torecording the positive findings. For example, insomeone presenting with symptoms suggestive of162232425262728202117 161819221311 9 7615 1210 8514 4321162 Penfield homunculus: the primary somatic cortex(postcentral gyrus). 1: genitalia; 2: toes; 3: foot; 4: leg; 5: hip;6: trunk; 7: neck; 8: head; 9: shoulder; 10: arm; 11: elbow;12: forearm; 13: wrist; 14: hand; 15: little finger; 16: ringfinger; 17: middle finger; 18: index finger; 19: thumb; 20:eye; 21: nose; 22: face; 23: upper lip; 24: lower lip; 25: teeth,gums, jaw; 26: tongue; 27: pharynx; 28: intra-abdominal.
218spinal disease, it is vital to enquire about bladderfunction. The main points of the history are asoutlined in Table 59. Thus, for example, with apatient presenting with tingling of the hand, it isimportant to describe what part of the hand isaffected, which digits, the frequency and duration ofthe symptoms, whether the patient awakes at nightwith the symptoms, or whether it is worsened bycertain wrist postures (as in carpal tunnel syndrome).Sensory examination can be laborious. It shouldfollow a general neurological examination and bedirected to the presenting complaint. Table 60indicates the main features of the sensoryexamination. The following points should beconsidered when carrying out a sensory examination:❏❏Ensure the patient is relaxed and not distracted.Explain to the patient what to expect and whatis expected of them prior to each component ofthe examination; demonstrate initially (on anarea of normal sensation).Table 59 Sensory history and lossHistory Define Additional ExamplesWhere? Focal Specify Root or peripheral nerve lesionMultifocal Timing: simultaneous, ❏ Mononeuritis multiplexevolutionary, migratory ❏ PolyradiculopathyDistal limb Ascending, which limbs? PolyneuropathyTruncal level Upper level, lower level, pain? ❏ Spinal cord lesion❏ Suspended sensory level withcentral cord lesionHemisensory Face involved? ❏ Stroke❏ TumourFace/contralateral limb Other brainstem features? StrokeOnset/progression How long?Acute How sudden, pain? ❏ Trauma❏ Vascular lesionSubacute Rate of evolution? Inflammatory processesChronic Stable, progressive, stepwise? Degenerative processesImproving monophasicNature Episodic Frequency, duration, nocturnal? ❏ Multiple sclerosis❏ Carpal tunnel syndromeConstantVariability?Precipitating/provoking Postural, coughing, ❏ Compressive radiculopathyfactors exercise, temperature? ❏ Uhthoff's phenomenonAssociated features Pain At onset, distribution? ❏ Radiculopathy – 'sciatica'❏ Thalamic syndromeWeaknessBladder symptoms ❏ Cord/cauda equina lesion❏ Uncommon with peripheralneuropathiesAtaxia ❏ Large fibre polyneuropathy❏ Posterior column disease❏ Vitamin B 12deficiencyTrauma Acute, chronic? ❏ Saturday night radial nerve palsy❏ Ulnar nerve palsy at elbowOthers
Disorders of sensation 219Table 60 Testing for sensory lossModality Tool/technique Testing CommentsTouch Fingertip ❏ Medium-large, myelinated ❏ Light touch only, otherwise testingperipheral nervespressure receptorsCotton wool ❏ Spino-thalamic tract ❏ Do not strokePain Neuro-tip ❏ Small, lightly myelinated ❏ Avoid too much pressureperipheral nerves❏ Spino-thalamic tracts ❏ Do not use hypodermic needles❏ Do not reuse neuro-tips❏ Never use hat pinsTemperature Universals with hot and ❏ Small, lightly myelinated ❏ Do not use very hot watercold waterperipheral nervesTuning fork❏ Spino-thalamic tractsJoint position Fingers and toes ❏ Avoid using pressuresense❏ Start with small joints, e.g. ring fingerDIP, 2nd toeVibration 128 Hz tuning fork ❏ Medium-large, myelinated ❏ Start distally, use bony eminencesperipheral nerves ❏ Unilateral loss on rib cage and cranium is❏ Posterior columnssuspicious of nonorganic diseasePseudoathetosis Arms extended, fingers ❏ Large, myelinated ❏ Observe spontaneous athetototicabducted, eyes closed peripheral nerves movements of the fingers❏ Posterior columnsPronator drift Arms extended, hands ❏ Contralateral fronto- ❏ Observe slow, downward drift of affectedsupine, eyes closed parietal lobe arm, with pronation of the wrist❏ Lack of pronation reduces the strength ofthe signSensory Eyes closed, stimulate each ❏ Contralateral parietal lobe ❏ Subject will report stimulus from bothinattention side independently, then sides when tested independentlysimultaneously❏ Only from unaffected side when testedsimultaneouslyStereognosis Eyes closed, present key ❏ Contralateral parietal lobe ❏ Assumes normal peripheral sensationor similar to handGraphaesthesia Eyes closed, draw letter/ ❏ Contralateral parietal lobe ❏ Use continuous characters, e.g. S, O, 3, 8digit on palm❏ Assumes normal peripheral sensation2-point Dividers ❏ Contralateral parietal lobe ❏ Light touch onlydiscrimination❏ Varies 1 cmon backReflexes Tendon hammer ❏ Large, myelinated ❏ Frequently lost early in peripheralperipheral nerves, sensory neuropathies(afferent)and motor ❏ Retained or exaggerated with central(efferent)sensory loss (due to associated UMNdisease)Romberg's sign Stands with feet together, ❏ Large, myelinated ❏ Subject falls (prevent fall): a sign ofhands by side, then closes peripheral nerves sensory (not cerebellar) ataxiaeyes❏ Posterior columnsFinger–nose Extended arm, touches nose ❏ Large, myelinated ❏ Stop if at risk of injuring eyeswith index finger, repeats peripheral nerveson eye closure❏ Posterior columnsHeel–shin Lifts heel onto opposite knee ❏ Large, myelinated ❏ Avoid letting subject use shin as a guide,and runs down shin, lifts and peripheral nerves i.e. repeated passes up and downrepeats with eyes closed ❏ Posterior columnsDIP: distal inter-phalangeal; UMN: upper motor neurone.
220❏ The following line of questioning is useful –‘Can you feel this? Does it feel normal? Does itfeel the same on both sides?’.❏ Avoid using excessive pressure when testing lighttouch, pain, and proprioception.❏ Testing superficial sensation should be random,and encompass radicular (nerve root) andperipheral nerve territories.❏ Remember that there is considerable overlapbetween root territories and, to a lesser extentperipheral nerve territories, resulting in areas ofsensory loss less than anticipated; e.g. a singletruncal root lesion may not result indemonstrable sensory loss.❏ Also, there is some crossover at the mid line,such that in a unilateral lesion sensoryimpairment may not reach the mid line.❏ Always map an area of sensory loss from thecentre of the deficit outwards; doing theopposite tends to underestimate the area ofdisordered sensation.❏ Always repeat the examination of a deficit,preferably in a different order/direction toconfirm the findings.❏ When testing proprioception:– Ask the patient to close their eyes (or lookaway).– Start with small joints to elucidate the mostsubtle deficits (e.g. ring finger, distalinterphalangeal joint or second toe) beforemoving on to larger joints or joints withgreater cortical representation (e.g. the indexfinger).❏❏– After demonstrating, ask the patient toindicate the last direction of movement, notthe final position.– Avoid applying too much pressure on the digitto indicate the direction of movement.– Move the digit by holding it by the sides.The majority of the sensory examinationdepends on the patient’s replies, and is thereforesubjective and relatively soft; associated motorsigns and reflex changes are therefore valuable.Certain sensory tests are useful as a screenbefore embarking on a more detailedexamination, especially pain and proprioception.Recording the history and findings is important.It is usually best to record the patient’s owndescription, especially when this is particularlyillustrative. The terminology of sensory symptoms isextensive and there is an overlap between what isreported and what is found on examination (Table61). In general terms, sensory modalities may benormal, reduced, absent, altered, or increased. Someof these are described in Table 61, in addition to thoseoutlined in Table 60. Table 62 provides a list of usefulanatomical reference points.Classification of sensorynerves is presented in Table 63.Table 61 Sensory disturbance terminologyTerm Meaning ExampleHypoaesthesia, anaesthesia Reduced/loss of sensation NumbnessHypodynia/allodynia Reduced/loss of pain sensation Can result in painless burns, Charcot jointsParaesthesiae Positive sensory phenomena Pins and needlesDysaesthesia Altered interpretation of sensory stimulus Feeling hot as cold, touch as painAstereognosis Unable to recognize an object through Subject unable to find keys in pocket, correcttouch alonecoinsAgraphaesthesia Unable to recognize a character traced on Examined for: e.g. trace a figure 8 on patient’sthe skinpalmSensory neglect Ignores sensory stimuli to one side, with Parietal lobe infarctintact peripheral sensation
Disorders of sensation221Nonorganic sensory lossSensory loss is a frequent manifestation of nonorganicor elaborated disease, either as a feature ofconversion syndromes or in the malingerer. The lackof objective clinical signs often makes this difficult toexclude, and making a diagnosis of nonorganicsensory loss depends a lot on clinical experience. Theclinician should beware of discounting sensorysymptoms too rapidly; nonorganic disease should bea diagnosis of exclusion. However, there are a fewuseful pointers:❏ Nonorganic sensory loss frequently:– Is complete, i.e. totally numb.– Affects all modalities of sensation, i.e. smalland large fibre, spino-thalamic, and posteriorcolumn.– Does not respect anatomical/physiologicalboundaries.❏– Has circumferential cut-off on the limbs.– Completely respects the mid line.– Respects patients’ modesty!– Is associated with unusual (nonorganic)postures and movements.– Has absent associated features/signs.On examination it is worth checking for:– Vibration loss that respects the mid line onface and thorax; in genuine sensory lossvibration can be appreciated by thecontralateral (normal) side.– Nonpronating arm drift.– Withdrawal or an emotional response topainful stimuli, while denying appreciation.– Lack of trophic changes.– Consistent reporting of the direction oppositeto the direction of actual movement whentesting proprioception.Table 62 Selected sensory localizationreference pointsSite Area subserved AdditionalC4 root ShoulderC7 Middle finger Triceps reflexT4 Trunk: nipple levelT8 Trunk: costal marginT10 Trunk: umbilical levelL3 Leg: over kneeS1 Foot: sole Ankle reflexS2 Buttocks: over ischial Stand on S1; sit ontuberositiesS2None of these features individually points tononorganic sensory loss, and some are features oftrue sensory loss. In addition, patients often try tohelp or impress the examiner by elaborating theirsigns. Also, patients manifesting gross nonorganicfeatures may have a genuine, often minor underlyingdisorder. However, usually an overall pattern emergessuggesting nonorganic disease.Patterns of sensory disturbancePatterns of sensory loss, taking into account theirdistribution and evolution, suggest the site and natureof the lesion. Single-site focal loss suggests a root orperipheral nerve lesion. Compressive causes arefrequently painful (e.g. sciatica). AssociatedTable 63 Classification of sensory nerve fibresMaximum fibre Maximum conduction Degree ofType diameter (µ) velocity (m/sec) myelination FunctionIa 22 120 +++ ❏ Muscle spindle primary afferentsIb 22 120 +++ ❏ Golgi tendon organs❏ Touch and pressure receptorsII 13 70 ++ ❏ Muscle spindle secondary afferents❏ Touch and pressure receptors❏ Pacinian corpuscles (vibratory sense)III 5 15 + ❏ Touch, pressure, pain, and temperatureIV 1 2 - ❏ Pain and temperature
222weakness, wasting, or reflex loss should be assessedfor. Nerve stretching manoeuvres (e.g. straight legraising) may exacerbate pain, as may certain postures(bending over). Percussion or compression of nervesover entrapment sites (Tinel’s sign) may increaseparaesthesiae or numbness, and/or cause pain.Multiple focal sites can be affected in mononeuritismultiplex, often sequentially, sometimes flitting, and itis frequently due to vasculitis. Multiple spinal roots canbe affected by infiltrative disease within the spinalcanal/dura, often affecting the lumbo-sacral roots as inlepto-meningeal carcinomatosis.Distal limb sensory loss, progressing proximally, isa feature of dying-back polyneuropathies, such asthose due to vitamin deficiencies and diabetes.Pathologically, there is axonal degeneration affectingthe axon most distal to the cell body initially. Usuallythere is sensory loss to the level of the knee before theupper limbs are involved. Exceptions to this ruleinclude the sensory neuronopathy associated with thesicca syndrome and paraneoplastic sensory neuropathy(dorsal root ganglionopathies). Reflexes are frequentlylost early in peripheral polyneuropathies. A pseudoneuropathic(peripheral) pattern can be seen in cervicalcord compression whereby patients present with distallimb paraesthesiae. On examination however, therewill be upper motor neurone signs (i.e. brisk reflexesrather than depressed or absent reflexes). Distal limbparaesthesiae can also be a feature of multiple sclerosis.Sensory loss affecting the perineum suggests aconus medullaris or cauda equina lesion. This isassociated with loss of sphincter control, i.e. bladderand bowel dysfunction. Sensory loss with a level onthe trunk indicates spinal cord disease. Often patientscomplain of pain or heightened sensation at the upperlevel. Causes include cord compression (e.g. tumour ordisc protrusion), inflammation (transverse myelitis),and vascular disease (anterior spinal artery syndrome,posterior column function preserved). Hemicordsyndromes can present with ipsilateral posteriorcolumn (proprioceptive loss), and contralateral spinothalamicloss (Brown-Séquard syndrome); there maybe ipsilateral motor loss. Central cord lesions (e.g.intrinsic cord tumours and syringomyelia) tend tocause bilateral spino-thalamic loss initially, due tointerruption of the decussating fibres, followed bymotor loss. These lesions may present with asuspended sensory loss, i.e. with preserved sensationdistally. An example of this is a syrinx affecting thecervical spinal cord that presents with ‘cape’distribution spino-thalamic sensory loss.The hallmark of brainstem sensory loss is crossedspino-thalamic sensory loss, i.e. trigeminal (facial)sensory loss ipsilateral to the lesion, with limb/trunkloss on the contralateral side. The lateral medullarysyndrome of Wallenburg is a good example of this.Thalamic lesions are associated with hemipaindisturbances (thalamic syndrome, is often burning innature), often with retained simple sensations.Cortical sensory syndromes are again characterizedby unilateral symptoms (unless bilateral corticallesions), intact simple sensations (appreciated at thethalamic level), but impaired integrated sensorymodalities (Table 60).The handSensory examination of the hand deserves particularattention. Peripheral nerve lesions, especially thosedue to trauma (acute and chronic), and less frequentlyas a result of vasculitis and granulomatous disorders,are especially common in the upper limb. Partial andchronic lesions often present with sensory symptomsprior to the onset of weakness and wasting. Radicularand brachial plexus lesions are more unusual, andoften have coexisting motor features at presentation.The hand receives its sensory innervation from threeperipheral nerves: median (C5–T1), ulnar (C8, T1),and radial (C6, 7, 8) nerves, derived from three spinalroots (C6, 7, 8) (163, 164). The median nervesupplies the radial three and a half digits andassociated palmar surface; the ulnar nerve the littleand half of the ring finger, as well as the ulnar surfaceof the palm. Sensation from the dorsal surface of thehand and digits as far as the distal phalanges ismediated via the radial nerve (may be more proximalin ulnar innervated digits).Sensory loss splitting the ring finger is a usefulfeature to distinguish median and ulnar nerve lesionsfrom more proximal lesions (plexus and root), but ina small percentage of people the ring finger issupplied by either nerve completely. The median andulnar nerves supply the intrinsic muscles of the hand:the median nerve supplies the two radial lumbricalmuscles and the muscles of the thenar eminence barthe adductor pollicis and flexor pollicis brevismuscles; these and the rest of the intrinsic handmuscles are supplied by the ulnar nerve. Themyotomal innervation of the hand muscles is via theC8 and T1 nerve roots. Thus, wasting in specificmuscle groups may be an aid to diagnosing focallesions and may precede frank symptomaticweakness. Advanced ulnar nerve lesions will produce
Disorders of sensation223163 Diagram to illustratesomatic innervation of thehand.C8C8C7C6Median nerveC6C7C8C8163C6C6Ulnar nerve Radial nerve Ulnar nervePalm of handDorsum of handcharacteristic clawing of the hand; median nervelesions cause wasting of the thenar eminence.The commonest median nerve lesion is carpaltunnel syndrome, where the median nerve is chronicallycompressed under the flexor retinaculum at the wrist.This condition can occur spontaneously, be bilateral, ismore common in women, and is associated with anumber of conditions, e.g. hypothyroidism, pregnancy,rheumatoid arthritis, and acromegaly. It typicallypresents as a painful sensory syndrome, patients oftencomplaining initially of pain and paraesthesiae in themedian innervated digits and hand, awakening them atnight. As the condition progresses, patients complain ofexercise- or posture-induced pain and numbness, oftenradiating into the radial aspect of the forearm andcentred about the index finger in the hand. Typically,these symptoms progress over many months or years.Patients may have objective median territory sensoryloss on examination. Percussion over the flexorretinaculum (Tinel’s sign) may reproduce thesymptoms, as may hyperextension of the wrist. Nerveconduction studies confirm the diagnosis bydemonstrating slowing of conduction in the mediannerve across the wrist. Conservative managementincludes treating any underlying disorder and wristsplinting; surgical division of the flexor retinaculumwill relieve the symptoms.NucleuscuneatusDorsal columnsThalamusNucleusgracilisLateral spinothalamictract164164 Schematic diagram of the spinal cord sensory pathways.
224The ulnar nerve is most prone to injury where itpasses across the medial epicondyle at the elbow (the‘funny bone’). Elbow fractures or repeated chronictrauma (e.g. leaning on the elbows) can cause ulnardistribution sensory symptoms and loss, progressingto ulnar weakness. Compressing the ulnar nerve atthe medial epicondyle may reproduce thesesymptoms. Radial nerve lesions rarely present assensory syndromes.SUMMARY❏❏Numbness and tingling may arise from lesionsdirectly affecting the neuraxis, from the level ofthe peripheral nerve and sensory receptor throughthe spinal cord to cortical level: these symptomsmay be secondary to non-neurological disorders.Distinct patterns of sensory loss and associatedfeatures facilitate clinical localization of thelesions: an understanding of the basicneuroanatomical pathways subserving sensationand their physiology enables this.CLINICAL SCENARIOS❏❏❏❏Separation of sensation into large fibre/posteriorcolumn function versus small fibre/ spinothalamicfunction helps in considering peripheralnerve and spinal lesions; assessment ofproprioception and pain are useful screeningexaminations.Cortical and subcortical lesions produce loss ofintegrated sensory functions but these functionsdepend on intact spinal and peripheral sensorypathways: gross sensation may be intact withthese higher level lesions.Sensory symptoms must not be considered inisolation: enquiry regarding motor andautonomic symptoms should be made whereappropriate, and a full neurological examinationshould be conducted.An accurate sensory assessment may avoidunnecessary investigation.CASE 1A 60-year-old, right-handed female presented tothe neurology clinic with a 6-month history ofascending paraesthesiae, affecting her feetinitially, but then progressing to a level below theknees. These symptoms were most noticeable inbed at night. She had also become aware of beingslightly unsteady, especially in the dark. Shedenied any weakness, upper limb symptoms, orbladder symptoms. Past medical history wasunremarkable, and she was not taking anyregular medications. She was a nonsmoker, anddrank
Disorders of sensation225CASE 1 (continued)The differential diagnosis of peripheral neuropathy is extensive, but clinical features help to narrow thefield. Neuropathies are classified according to aetiology (e.g. diabetes, vitamin B 12deficiency), pathologicalprocess (demyelinating, axonal, neuronal) and functional loss (motor, sensory, mixed, autonomic).Demyelinating neuropathies usually have prominent motor features. Predominantly or purely sensoryneuropathies tend be axonopathies or, less commonly, neuronopathies. Frequently these are subacute orchronic processes.The investigation of peripheral neuropathy is initially directed towards the most likely causes.Electrophysiological examination (nerve conduction studies and electromyography [EMG]), although moreuseful in motor neuropathies, can provide information about the pathophysiology of the neuropathyfacilitating the targeting of subsequent investigations. However, delays in obtaining electrodiagnostic studiesoften result in blood tests being requested first. In brief, nerve conduction studies can demonstrate slowingof conduction (due to demyelination), or conduction block (demyelination or vasculitis), or reduction in theamplitude of the compound muscle action potential (CMAP) with normal velocities (axonopathy) and lossof sensory nerve action potentials (SNAPs) (axonopathy/neuronopathy).In this case, the nerve conduction studies demonstrated loss of distal lower limb SNAPs, with relativelynormal motor studies and EMG. Initial investigations demonstrated a high random serum glucose that wasconfirmed on a fasting sample. Haemoglobin A1c was raised and glucose tolerance test was abnormal,confirming a diagnosis of diabetes.Thus, a diagnosis of diabetic neuropathy was confirmed and the patient was initiated on appropriatemedical treatment.165CASE 2A 45-year-old, right-handed male plumber presented with a 2-year history of slowlyevolving numbness and pain affecting both hands, beginning on the ulnar bordersand progressing up the forearms. He noted impaired dexterity in carrying out hisoccupation, which he considered threatened by his disability. He was still able to feelobjects but found it difficult to discern texture. On questioning, he also describedloss of temperature sensation, and had unknowingly burnt his right index andmiddle fingers while smoking. He did not describe any positive sensory symptomssuch as pain or paraesthesiae. He did not describe any weakness, or neurologicalsymptoms elsewhere.Progressive symmetric distal upper limb only, spino-thalamic (pain, temperature,and touch) sensory loss is being described. This would be an unusual pattern for aperipheral sensory polyneuropathy (legs spared; other poorly myelinated/unmyelinated fibres not symptomatically affected as no autonomic features, e.g.bladder/postural hypotension). However, rare sensory neuronopathy associated withSjögren/ sicca syndrome frequently affects the upper limbs first. Considerdegenerative/metabolic/deficiency state, given the slow evolution. A possiblediagnosis is spinal cord disease, but there are no long tract symptoms, e.g.mobility/bladder features.Neurological examination of the cranial nerves and lower limbs was normal.Examination of the upper limbs showed normal tone and power, with somesuggestion of early intrinsic hand muscle wasting. Upper limb reflexes were reduced.Sensory testing showed preserved proprioception and vibratory sensation. However,pain (sterile neurotip), was reduced bilaterally from the shoulders to nipple level(C4–T4), including the upper limbs. Temperature sensation was also reduced in thisdistribution, with lesser impairment of touch (165).(Continued overleaf)165 Diagram to illustratesuspended sensory loss insyringomyelia. Syringomyeliaresults in cape-like sensoryimpairment selectively for painand temperature, oftenaccompanied by loss of reflexesin the upper limbs.
226CASE 2 (continued)Examination confirms a suspended sensory loss, which is strongly indicative of central spinal corddisease. The signs extend over multiple adjacent dermatomes. Truncal sensory loss is unusual inpolyneuropathies (but sometimes seen in obese people in the periumbilical area). The confluence of thesigns and slow evolution suggest a slowly progressive structural lesion. Clinically, the lesion is now localizedto the upper dorsal and cervical cord. Thus, the most appropriate investigation is to image this area andthis is best achieved by MRI.The MRI (166) demonstrates a central cavity within the spinal cord and herniation of the cerebellartonsils through the foramen magnum (a Chiari malformation).These conditions are frequently associated and it is believed that the congenital cranio-cervicalmalformation (the Chiari malformation) predisposes to the development of the syrinx. As the syrinx (thefluid filled cavity positioned centrally in the cord) expands and extends, it transects the decussating spinothalamicfibres resulting in the suspended spino-thalamic pattern sensory loss (165). With further expansionanterior horn cells are destroyed, resulting in muscle wasting, weakness, and areflexia. At this stage theascending and descending long tracts become involved, giving rise to lower limb upper motor neurone signsand sensory loss. This patient was referred for neurosurgical decompression of the foramen magnum, andhis condition subsequently stabilized.On cranial nerve examination, she had unsustained end-gaze nystagmus on lateral gaze bilaterally.Ophthalmoscopy showed pallor of the temporal portion of the right optic disc and colour vision testing(Ishihara chart) demonstrated impairment in the right eye. Jaw jerk was positive. Examination of the upperlimbs showed hyper-reflexia only. In the legs, the reflexes were brisk, with minimal weakness of left ankledorsiflexion and an extensor left plantar response. Sensory testing showed impaired vibratory sensation atboth ankles only. Gait was normal, apart from minor difficulty with tandem walking (heel–toe) andRomberg’s sign was negative. Abdominal reflexes were absent.The examination findings ‘outweigh’ the clinical symptoms and provide evidence for multifocaldisease: right optic neuropathy (pale disc and impaired colour vision), upper motor neurone signs (hyperreflexiaand extensor left plantar response), and sensory impairment (impaired distal lower limb vibratorysensation). In addition, the history suggests disordered bladder control.As the history suggests a multifocal disorder of the central nervous system, involving at least an upperlevel of the brainstem (eye movement control), an MRI of brain was requested. This demonstrated multiplewhite matter lesions, both recent (gadolinium enhancing) and established (167). This provided strongsupportive evidence for the diagnosis of multiple sclerosis. Visual evoked responses demonstrated significantslowing of conduction in the right visual pathways, consistent with demyelination. Cerebrospinal fluid (CSF)examination (obtained by lumbar puncture) demonstrated 7 lymphocytes per mm 3 , normal protein andglucose, but the presence of isolated oligoclonal bands in the CSF alone, a finding consistent with andsupportive of a diagnosis of MS (168).In the 6 months following presentation, the patient suffered two further relapses (symptomatic left opticneuritis and mild partial transverse myelitis), and was commenced on interferon-beta therapy.
Disorders of sensation22716616716812166 Magnetic resonance image ofsyringomyelia. 1, descended cerebellartonsils; 2, syrinx.167 Gadolinium-enhanced T1-weightedmagnetic resonance image of the brain inmultiple sclerosis, demonstrating enhancing(acute) lesions (arrows), established lesions(short arrow), and 'black holes'(arrowheads).1 2 3 4168 Cerebrospinal fluid (CSF)IgG oligoclonal bandingpatterns. Lanes 1 and 2demonstrate isolated oligoclonalbands, consistent with anintrinsic central nervous systemresponse, the usual responseindicative of multiple sclerosis.Lanes 3 and 4 show bothpaired and isolated bands.(Lanes 1, 3: CSF; lanes 2,4: serum.) (Courtesy ofMrs J Veitch, NeuroimmunologyLaboratory, INS, SouthernGeneral Hospital, Glasgow.)CASE 3A 25-year-old, left-handed, Caucasian female presented with a 3-month history of intermittent tinglingaffecting both hands and feet. She was most aware of this in the evenings, especially on retiring to bed.However, she has also noted a worsening of her symptoms following a jog or a hot bath. These symptoms didnot interfere with her normal activities. On questioning, she did admit to some urinary urgency that hadpersisted following the birth of her first (only) child 3 years earlier. She also recalled an episode of transient leftleg heaviness (possibly weakness), in her late teens, which resolved over a couple of weeks. She had no othersignificant past medical history, and there was no relevant family or social history. She was taking no regularmedication, apart from the oral contraceptive pill.In addition to the presenting sensory symptoms, a number of potentially important other symptoms aredescribed: previous leg weakness and on-going bladder symptoms. The intermittent nature of the sensorysymptoms, together with heat sensitivity (Uhthoff’s phenomenon), is more suggestive of a central rather than aperipheral cause. Bladder symptoms suggest spinal cord disease. The history suggests remitting disease,possibly at different sites within the central nervous system. Her age (gender), race, and symptoms postpartumsuggest multiple sclerosis (MS).
228REVISION QUESTIONS1 Pain is mediated by fast-conducting, peripheralsensory neurones.2 Proprioception is impaired early in central corddisease.3 A (lateral) hemicord lesion will cause loss ofspino-thalamic sensation ipsilaterally below thelesion.4 Sensation can only be appreciated at a corticallevel.5 Stereognosis depends on intact peripheralsensory pathways.6 Dorsal root ganglia contain the nuclei ofproprioceptive nerves.7 Romberg’s sign is a test of proprioceptivefunction.8 Sensory loss in the ulnar two digits withweakness of finger flexion suggests an ulnarneuropathy.9 In sensory inattention, the patient is unable toappreciate a sensory stimulus when presented tothe affected side only.10 Pseudoathetosis can be caused by a dorsal rootganglionopathy.11 In suspended sensory loss, pain and temperaturesensation are retained until advanced disease.12 C7 root usually mediates sensation from the ringfinger.13 An infarct of the anterior limb of the internalcapsule causes contralateral hemisensory loss.14 Lateral pontine lesions may cause ipsilaterallimb sensory loss.15 Ataxia worsening on eye closure suggests asensory cause.Answers1 False.2 False.3 False.4 False.5 True.6 True.7 True.8 False.9 False.10 True.11 False.12 False.13 False.14 False.15 True.
CHAPTER 4 MULTIPLE CHOICE QUESTIONS229Note: answers are on page 234BLACKOUTS: EPILEPTIC SEIZURES AND OTHER EVENTS1 Vasovagal syncope:a Presents with lateralized visual aura.b Causes biting of the tip of the tongue.c Is usually infrequent.d May cause myoclonic jerks.e May be provoked by exercise.2 True petit mal seizures:a Are associated with a generalized spike-wavedischarge.b Usually last 30–60 seconds.c Usually originate in the temporal lobe.d May occur many times per day.e May occur in juvenile myoclonic epilepsy.3 Psychogenic nonepileptic seizures:a Are usually frequent.b May cause injury.c Are not stereotyped.d Are associated with synchronous clonic movements.e Are associated with head injury.ACUTE CONFUSIONAL STATES1 In an acute confusional state the stream of thought canbe either slowed or accelerated.2 A lesion of the ascending reticular activating systemmay cause a confusional state.3 Fluctuations in a confusional state may occur by dayand by night, but are more marked by night.4 In an acute confusional state, remote memory is intact.5 There is no universal susceptibility to developing anacute confusional state.6 The predominant EEG rhythm in an acute confusionalstate is fast theta or alpha rhythm.7 Autonomic hyperactivity, e.g. a tachycardia, is usuallypresent.8 The acute confusional state is always accompanied byincreased psychomotor activity.9 Visual hallucinations are rarely seen in the acuteconfusional state.10 In an acute confusional state there is disorientation fortime before that for place or person.11 The two subtypes of a confusional state never coexist inthe same patient.12 Following recovery from an acute confusional state, thepatient has an amnesia for the period of confusion.13 There are specific features found at postmortemfollowing the acute confusional state.14 Emotional lability is a frequent accompaniment to theacute confusional state.15 The acute confusional state lasts
2307 Language impairment cannot be due to stroke unlessthere is also evidence of hemiparesis.8 If a patient cannot write, yet has preserved oral spelling,then their symptoms are not organic in origin.9 The ability to converse by phone is a very sensitivemarker of early language dysfunction.10 Analysis of the type of naming error can identify whichpart of the language system is impaired.11 If reading aloud is impaired, then readingcomprehension must be impaired.12 The ability to correctly read irregular words is linkedwith knowledge of meaning of the word.13 Normal performance on the Mini-Mental StateExamination excludes the possibility of languageimpairment.14 Difficulty naming objects occurs in most aphasias.15 Clinical classification of an aphasia renders subsequentimaging unnecessary.VISUAL LOSS AND DOUBLE VISION1 Five lesion sites (a–e) and five visual loss patterns (1–5)are stated below. Match the site with the visual deficitthat a lesion at that site commonly produces:a Right optic nerve. 1 Left incongruousb Optic chiasm. homonymousc Right optic tract. hemianopia.d Right temporal 2 Left macular sparingoptic radiation. homonymouse Right visual hemianopia.cortex.3 Right central scotoma.4 Bitemporal hemianopia.5 Left superiorhomonymousquadrantinopia.2 The following statements about the medical history of apatient with visual loss are true:a Binocular visual loss will be abolished by shuttingone eye.b Optic neuritis characteristically occurs in patientsover 60 years.c Tumours tend to cause progressive visual disturbanceover days or months.d Migraine causes monocular or binocular visualdisturbance normally followed by severe headache.e Temporal arteritis usually causes a hemianopic visualdisturbance.3 During a focused assessment for visual disturbance:a A left relative afferent pupillary defect suggestsdisease of the left optic nerve.b Visual field testing may be omitted if visual acuity isnormal.c An enlarged blind spot and constriction of the visualfield are features of papilloedema.d Finding associated lateralized motor weakness andupper motor neurone signs suggests that the lesionlies in the optic chiasm.e ESR and carotid Doppler should be ordered toinvestigate acute monocular visual loss in a 70-yearoldmale.4 Neurological diplopia:a Is abolished by shutting either eye.b Always results in images appearing side by side.c Can be caused by a lesion affecting the oculomotor,trochlear, or abducens nerves, or the muscles thatthey supply.d Occurs only as a symptom of brainstem disease.e Remains a lifelong problem for patients withcongenital strabismus (‘squint’).5 Which of the following statements about the history ofa patient with diplopia are true?a Isolated trochlear palsy causes vertical diplopiamaximal when looking down.b Myaesthenic symptoms will be most marked whenthe patient wakes up.c Proptosis suggests aneurysmal expansion causingdiplopia.d Unilateral ptosis indicates that the patient must besuffering from an oculomotor nerve palsy.e Diplopia is maximal in the direction of action of aparalysed muscle.6 Which of the following investigation and managementplans, formulated by a Casualty officer, would youagree with?a A patient with a painful complete oculomotor nervepalsy (pupil involved) was reassured and sent homefor review in the neurology clinic the following week.b A patient with diplopia and ophthalmoplegia whichworsened as the day progressed was referred for aTensilon Test.c A patient with a sudden abducens nerve palsy and ahistory of hypertension, whose CT scan was normal,was started on aspirin, given a patch to wear over hisright eye, and reassured. Plans were made for clinicreview.d A 20-year-old patient was found on examination tohave a left internuclear ophthalmoplegia and arelative afferent pupillary defect in the right eye. Thepatient was told that he had probably suffered astroke and was referred for a CT scan.e A patient with symptoms of unilateral pain behindthe eye, and a combined oculomotor and abducenspalsy and tingling on their forehead, was referred foran MRI scan of their orbital apex and cavernoussinus.
Multiple choice questions 231DIZZINESS AND VERTIGO1 Which of the following statements are true?a Dizziness often coexists with vertigo, but is not thesame as vertigo.b Dizziness always implies neurological disease.c The vestibular apparatus projects sensoryinformation to the cerebellum and parieto-temporalcortex.d Peripheral vertigo is often rotational and in a yawplane.e Vestibular sensory information is conveyed withsensory information from the cochlea (hearing) in theVIII cranial nerve.2 Five ‘symptom complexes’ and five common ‘diseaseprocesses’ are shown below. Match each symptomcomplex with a disease process that is a common cause:a Acute severe 1 Migraine with aura.vertigo.2 Ménières disease.b Positional vertigo. 3 Postural hypotension.c Vertigo with 4 Acute peripheralheadache.vestibulopathy.d Hydrops (hearing 5 Benign paroxysmaldisturbance,positional vertigo.vertigo, tinnitus).e Medical dizziness.3 The following statements about the assessment of apatient complaining of dizziness are true:a Cardiovascular examination may be omitted if thereis no history of altered consciousness.b Weber’s test lateralizes to the right in a patient withconductive hearing loss on the right.c In a patient with benign paroxysmal positionalvertigo, Hallpike's test usually reproduces thesymptoms.d A history of imbalance in the dark is suggestive of aproprioceptive (joint position sense) deficit.e Sudden severe vertigo in combination with diplopiais most likely to be caused by acute peripheralvestibulopathy.WEAKNESS1 A lesion of the left S1 root would be expected to reduceor abolish the left ankle jerk reflex.2 Muscle wasting is a characteristic feature of lowermotor neurone weakness.3 An elevation of serum creatine kinase activity to twicethe upper limit of normal invariably indicatesneuromuscular disease.4 Extensor plantar responses are not a feature of uppermotor neurone weakness.5 A motor nerve always innervates a single muscle fibre.6 A defect in oxidative muscle metabolism would beexpected to produce limitation of sustained exerciserather than brief intense exercise.7 Disorders of neuromuscular transmission may beassociated with fatigue.8 Cramps may be a prominent feature of motor neuronedisease.9 A lesion of the right C5 sensory root would be expectedto be associated with sensory loss in the axilla.10 A lesion in the spinal cord may produce both upper andlower motor neurone features.11 It is appropriate to image the lumbar spine of a patientwith spastic leg weakness and numbness involving thelegs and up to just below the umbilicus.12 Transection of the ulnar nerve at the elbow will causeweakness of all the intrinsic hand muscles.13 Diseases of the motor unit would be expected to giverise to sensory symptoms.14 Some inherited neuromuscular disorders are so mildaffected individuals may never seek medical advice.15 Steroid administration may cause muscle weakness.TREMOR AND OTHER INVOLUNTARY MOVEMENTS1 Parkinson’s disease typically presents with unilateralpostural arm tremor.2 Essential tremor typically presents with bilateralpostural arm tremor.3 Huntington’s disease is inherited in an autosomalrecessive manner.4 Wilson’s disease often presents in patients aged over 50years.5 A fine bilateral postural arm tremor can be caused bysodium valproate.6 An ischaemic lesion in the subthalamic nucleus could bethe cause of acute onset hemiballism.7 Imaging of the presynaptic dopaminergic neurone isexpected to be abnormal in essential tremor.8 Everybody with chorea should undergo genetic testingfor Huntington’s disease.9 Thyroid function tests are indicated in a patientpresenting with bilateral postural tremor and weightloss.10 Structural brain imaging is not indicated whenpyramidal signs (e.g. hyper-reflexia and extensorplantars) are found in conjunction with parkinsoniansigns.11 Antiemetic medications may cause parkinsonism.12 Dopamine-depleting medications may causeHuntington’s disease.13 Beta-blockers may cause tremor.14 Lithium may cause tremor.15 Essential tremor responds to levodopa.
232POOR COORDINATION1 The final common pathway in the cerebellar outputinvolves:a Red nucleus.b Purkinje cell.c Dentate nucleus.d Granule cell.2 Ataxia on eye closure but not with open eyes issuggestive of:a Cerebellar ataxia.b Sensory ataxia.c A positive Romberg’s test.d Middle ear disease.3 Neurological symptoms of vitamin B 12deficiency maypresent:a As noncompressive myelopathy, i.e. spinal corddisease.b With symptoms of burning feet.c Without haematological changes of megaloblasticanaemia.d With cerebellar symptoms.4 Paraneoplastic neurological diseases affectingcoordination may manifest as:a Weakness of neuromuscular junction (antivoltagegated calcium channel antibody).b Subacute sensory neuropathy (anti-Hu antibody).c Opsoclonus, truncal ataxia (anti-Ri antibody).d Cerebellar ataxia (anti-Yo antibody).5 Blood supply of the cerebellum is derived from thebranches of:a Carotid artery.b Vertebral artery.c Basilar artery.d All of the above.6 Within the spinal cord, fibres carrying proprioceptionare located in the:a Spinocerebellar tract.b Spinothalamic tract.c Posterior column.d None of the above.7 Ataxic hemiparesis refers to:a Ipsilateral corticospinal weakness and contralateralataxia.b Corticospinal weakness and ataxia on the same side.c Neither (a) nor (b).d Both (a) and (b).8 Sudden dizziness and vomiting, along with markedtruncal ataxia in a hypertensive patient who is unable tostand upright, suggests a diagnosis of:a Ménière’s disease.b Cerebellar haemorrhage.c Internal capsular haemorrhage.d Subarachnoid haemorrhage.9 Ataxic neuropathies may be associated with:a Monoclonal or polyclonal gammopathy.b Paraneoplastic antibody.c Sjögren’s syndrome.d Inflammatory demyelinating neuropathy.10 Cerebellar features present in conjunction with rapidlydeteriorating level of consciousness are suggestive of:a Expanding posterior fossa mass.b Posterior inferior cerebellar artery infarct.c Anterior inferior cerebellar artery infarct.d Viral encephalitis.11 The following clinical signs would suggest a diagnosis ofacoustic neuroma (vestibular Schwannoma):a Hearing loss.b Cerebellar ataxia.c Nystagmus.d Decreased facial sensation.12 Cerebellar ataxia is inherited as an autosomal recessivedisorder in:a Hypothyroidism.b Friedreich’s ataxia.c Spinocerebellar ataxia.d Ataxia-telangiectasia.13 A combination of cerebellar and sensory ataxia may beseen in:a Coeliac disease.b Alcohol abuse.c Lyme disease.d B-vitamin deficiency.14 Vertigo is a side-effect of toxicity from:a Phenytoin.b Aminoglycoside antibiotics.c Salicylates.d Alcohol.15 The preferred neuroimaging for acute cerebellar ataxiais:a MRI.b CT.c CT followed by MRI.d Plain X-ray of the skull base.HEADACHE1 In the assessment and investigation of subarachnoidhaemorrhage, which of these statements is true?a The headache reaches its maximum intensityinstantaneously or at most over a couple of minutes.b Meningism is an important sign.c A normal CT scan done within the first 12 hours ofictus excludes the diagnosis.d A normal lumbar puncture done within the first 12hours of ictus excludes the diagnosis.e A normal lumbar puncture done a week after theictus excludes the diagnosis.
Multiple choice questions 233f A patient who presents with coital headache for thefirst time can be reassured.2 In patients with chronic daily headache, which of thesestatements is true?a Patients presenting to Casualty with chronic dailyheadache are unlikely to have migraine.b Patients over the age of 50 years who present with anew-onset, focal, daily headache should beconsidered to have temporal arteritis until provenotherwise.c Migraine prophylactic medication is effective inpatients with migraine and analgesia-inducedheadache.d Analgesia-induced headache may take up to 6months to settle down after stopping the offendingagent.e All analgesic and triptan medications can beassociated with analgesia-induced headache.f Migraine may present with chronic daily headache.3 Which of these statements is true?a Subarachnoid haemorrhage may present with newonset,chronic, daily headache.b Sudden-onset, unilateral headache associated withipsilateral Horner’s syndrome and contralateralhemiparesis suggests carotid dissection ipsilateral tothe headache.c A normal temporal artery biopsy excludes thediagnosis of temporal arteritis.d Patients with cluster headache prefer to lie still.e Alcohol may precipitate a cluster headache duringperiods of remission.f Chronic arterial hypertension of moderate degreedoes not cause headache.SPINAL SYMTOMS: NECK PAIN AND BACKACHE1 In cervical spine disease:a A ‘clicking’ or ‘crunching’ sensation experienced bythe patient is a symptom of serious pathology.b Bony change on X-ray is unusual in patients ofmiddle age.c Cranial nerve examination can provide usefulinformation.d Jaw jerk is a sign of cervical myelopathy.e Hyper-reflexia in the legs is a reliable sign ofmyelopathy.2 In thoracic spine disease:a The sensory level is a reliable pointer to the level ofthe involvement.b Urinary urgency and incontinence is a sign ofradiculopathy.c Loss of perianal sensation is a sign of pathology inthe central cord.d Unilateral cord pathology causes loss of pain andtemperature sensation inferior and ipsilateral to thelesion.e Anterior cord lesions cause loss of vibration andproprioception.3 In lumbar and thoracic spine disease:a Hyper-reflexia is a common sign of lumbar spineinvolvement.b A normal straight leg raising test precludes surgicalintervention.c Loss of knee jerks is a sign of L5 radiculopathy.d Unilateral lesions commonly cause bladdersymptoms.e A lower motor neurone bladder is small and has asmall or undetectable residue.NUMBNESS AND TINGLING1 Pain is mediated by fast-conducting, peripheral sensoryneurones.2 Proprioception is impaired early in central cord disease.3 A (lateral) hemicord lesion will cause loss of spinothalamicsensation ipsilaterally below the lesion.4 Sensation can only be appreciated at a cortical level.5 Stereognosis depends on intact peripheral sensorypathways.6 Dorsal root ganglia contain the nuclei of proprioceptivenerves.7 Romberg’s sign is a test of proprioceptive function.8 Sensory loss in the ulnar two digits with weakness offinger flexion suggests an ulnar neuropathy.9 In sensory inattention, the patient is unable toappreciate a sensory stimulus when presented to theaffected side only.10 Pseudoathetosis can be caused by a dorsal rootganglionopathy.11 In suspended sensory loss, pain and temperaturesensation are retained until advanced disease.12 C7 root usually mediates sensation from the ring finger.13 An infarct of the anterior limb of the internal capsulecauses contralateral hemisensory loss.14 Lateral pontine lesions may cause ipsilateral limbsensory loss.15 Ataxia worsening on eye closure suggests a sensorycause.
234ANSWERSBLACKOUTS1 b, c, da False. Lateralizedvisual aura suggestsepileptic seizure.b True. In tonic–clonicseizures, tonguebiting is usuallylateral, or the insideof the cheek isbitten.c True.d True.e False. Provocationby exercise shouldsuggest cardiogenicsyncope.2 a, d, ea True.b False. Seizures lastseveral seconds atmost.c False. They aregeneralized seizures.d True.e True.3 a, b, ea True.b True, though in aminority of patients.c False.d False. Movementsare normallyalternating ortremulous.Asynchronous jerksmay occasionallyoccur.e True. A history ofminor head injury iselicited inapproximately 50%of patients.ACUTE CONFUSIONAL STATES1 True.2 False.3 True.4 True.5 False.6 False.7 True.8 False.9 False.10 True.11 False.12 True.13 False.14 True.15 False.MEMORY DISORDERS1 False.2 False.3 False.4 False.5 False.6 True.7 True.8 True.9 True.10 True.11 True.12 True.13 True.14 True.15 False.SPEECH AND LANGUAGEDISORDERS1 False.2 True.3 True.4 False.5 False.6 True.7 False.8 False.9 True.10 True.11 False.12 True.13 False.14 True.15 False.VISUAL LOSS ANDDOUBLE VISION1 a with 3b with 4c with 1d with 5e with 22 c, d3 a, c, e4 a, c5 a, e6 b, c, eDIZZINESS AND VERTIGO1 a, c, d, e2 a with 4b with 5c with 1d with 2e with 33 b, c, dWEAKNESS1 True.2 True.3 False.4 False.5 False.6 True.7 True.8 True.9 False.10 True.11 False.12 False.13 False.14 True.15 True.TREMOR AND OTHERINVOLUNTARY MOVEMENTS1 False.2 True.3 False.4 False.5 True.6 True.7 False.8 False.9 True.10 False.11 True.12 False.13 False.14 True.15 False.POOR COORDINATION1 b2 b, c3 a, b, c4 b, c, d5 b, c6 a, b, c7 b8 b9 a, b, c, d10 a11 a, b, c, d12 b, d13 a, c14 a, b, c, d15 cHEADACHE1 a, e2 b, d, e, f3 a, b, fSPINAL SYMTOMS1 c, e2 All false.3 All false.NUMBNESS AND TINGLING1 False.2 False.3 False.4 False.5 True.6 True.7 True.8 False.9 False.10 True.11 False.12 False.13 False.14 False.15 True.
Index 235IndexNote: page numbers in bold refer tothe main discussion of a topic; thosein italic refer to content of tablesabdominal reflex 24abducens nerve (VIth cranial nerve)21, 120, 121, 128accessory nerve (XIth cranial nerve)22acetylcholine 77, 150acetylcholine receptor antibodies 56achromatopsia, central 108acoustic neuroma 56–8acromegaly 58Adamkiewicz, artery 48, 49Addenbrooke’s CognitiveExamination (ACE) 14, 20, 90, 99adrenocorticotrophic hormone(ACTH) 58age 9, 136, 204agnosia 108agraphaesthesia 112, 220akinetic mutism 13alcohol use 81–2, 122, 137, 176, 181alcohol withdrawal 80alexia without agraphia 97, 108allergies 10Alzheimer’s disease 16, 18, 89, 90, 91,108amaurosis fugax 107amblyopia 118, 125aminoglycosides 176analgesics, overuse 193–4, 201–2aneurysms, cerebral 32–3, 80, 121,127angiographycerebral 38–9CT 30digital subtraction (DSA) 38–9fluorescein 60interventional 39magnetic resonance (MRA) 34spinal 48–9, 51angular gyrus 94anisocoria 109anklemovements 154reflexes 24, 156anosomia 152anterior ischaemic optic neuropathy107antibody tests 56anticholinergic drugs 77, 80antipsychotics 165Anton’s syndrome 108anxiety 71, 131, 132, 136, 137,146–7aphasias 45, 96–8, 101apraxias 16, 17arcuate fasciculus 94arousal 11arrhythmias, cardiac 135, 137, 138arteriovenous fistula, dural 51,211–12arteriovenous malformations 38–9ascending reticular activating system(ARAS) 76–7astereognosia 112, 220asterixis 168ataxia 122, 131–2, 136, 176–81acute of childhood 182–3aetiologies 122, 137cerebellar 133, 176, 178, 179, 180,204clinical scenarios 182–5differential diagnosis 178examination 178, 180–1Friedreich’s 178investigations 181–2, 181sensory 178, 179, 180–1, 182vestibular 176atherosclerosis, basilar artery 115–16athetosis 168atrial fibrillation 107attention/concentration 11, 14anatomy 76–7assessment 15, 45, 77–8audiometry 22, 60–1, 138, 139auditory/vestibular nerves 22, 132–3aura, migraine 188, 192auras, epileptic seizures 70–1awareness 11, 13Babinski sign 24back pain 204balance 133, 170, 176assessment 138, 139Balint’s syndrome 108ballism 168barbiturates 80basal ganglion 164behavioural changes 13–14, 15, 79benign intracranial hypertension 196Benton Facial Recognition Test 46benzodiazepines 80biceps reflex 24, 156bladder function 152, 159, 206blink reflex 53blood oxygen level dependent (BOLD)imaging 36Boston Diagnostic AphasiaExamination 45Boston Naming Test 45brachial plexus 222brachioradialis reflex 24brainanatomical landmarks 29herniation 12perfusion pressure 65–6tumours 15, 56–8, 102, 187, 195,195see also named parts of the brainbrainstem auditory evoked potentials(BSAEPs) 43–4brainstem lesions 121brainstem reflexes 13Broca’s aphasia 97, 99Broca’s area 69, 94, 95Brown–Séquard syndrome 159, 182,208, 222bulbar muscles 152C-reactive protein 112, 126, 142calcium, muscle contraction 150calcium channel antibodies 56calculation, ability 16caloric testing 61CAPE sensory deficit 209carbon dioxide retention 80cardiac disease 122altered consciousness 64, 66, 66–7,67, 74confusional states 80dizziness/vertigo 135, 136, 137, 138weakness/fatigue 148carotid artery stenosis 34, 107carotid sinus hypersensitivity 66–7,138carpal tunnel syndrome 223cauda equina lesions 205–6, 222cavernous sinus 58thrombosis 122, 198, 199cerebellar disorders 170, 176, 177cerebellar systemfunction, assessment 26testing 125cerebellar tremor syndromes 167cerebello-pontine angle 56–8cerebellum 102, 133, 140, 176–7, 178
236cerebral arteriesatherosclerosis 115–16CT angiography 30–1cerebral ischaemia 35cerebral oedema 187, 195cerebral venous thrombosis 108cerebrospinal fluid (CSF)blood in sample 197lumbar puncture 52obstruction 187oligoclonal banding 227pressure 195, 195, 196protein level 187cerebrospinal fluid (CSF) examination181cerebrovascular disease 35–7, 81–2,100, 200cervical spine disorders 193, 204–5,210–11Charcot joints 180Charcot–Marie–Tooth disease 56Chiari malformations 56–7, 225–6,227chickenpox 182–3choline 36chorea 163, 167–8Clock Drawing Test 46–7clonus 24, 168Cogan’s lid twitch sign 123cognitive function 14distributed 14–16, 14history taking 18, 88–9localized 14, 16–18cognitive testing 19–20, 44–6, 89–90language assessment 99colour vision 108, 110computed tomography (CT) 28–30angiography 30brain anatomical landmarks 29spinal cord 49–50computed tomography perfusion(CTP) 31concentration seeattention/concentrationconfabulation 78confrontation 59, 110, 111confusional states 76causes 79–80, 79clinical assessment 77–9clinical scenarios 81–5definition 76fluctuations 78with lethargy/retardation 77, 80pathophysiology 77consciousnessanatomy 12–13brainstem tests 13levels of 11consciousness, altereddiagnosis 42, 65mechanisms 65see also epilepsy; syncopeconus medullaris 222coordination 156, 176–85tests 26copying, shapes 17corneal reflex 13, 21, 140corpus callosum 16, 97Corsi Block Test 45corticobasal degeneration 165cramps 151, 161cranial nervesexamination 20–2, 112, 125, 140,190, 204eye movements 120–1palsies 22, 23, 128, 196see also individual nervescranio-cervical junction lesions 56–7creatine kinase (CK) 84, 156Creutzfeldt–Jakob disease 108Cushing’s syndrome 58cytotoxic drugs 152deafness see hearing lossdelirium 13, 77, 78delirium tremens 80delusions 13dementia 16, 18, 47, 88, 89–90, 91,108demyelination 107, 121, 122Denny–Brown sensory neuropathy 182depression 91–2, 144–5dermatomes 152–3dextrose, intravenous infusion 92–3diabetes mellitus 128, 136, 144, 224–5diet 9, 181, 183digit span 45, 77, 86, 90digital subraction angiography (DSA)38–9diplopia see double visiondiscrimation tests 25disequilibrium 131, 136disinhibition 15Dix–Hallpike positional test 141, 143dizziness 131–42anatomy and physiology 132–4and anxiety 131, 132, 136, 137clinical scenarios 143–6examinations 138–41history taking 134–7postural 65–6, 73, 132, 144–5specific investigations 141symptom complexes 134, 135timing/duration of symptoms 135–6,137Doll’s eye test 125, 141dopaminergic neurones 164, 172, 174Doppler ultrasound 39–40, 112dorsal root ganglion 214, 215double vision (diplopia) 21, 112,118–29, 192causes 121, 152clinical scenarios 127–9examinations 21, 122–5history taking 121–2investigations 126, 126drug abuse 80, 137drug history 10, 18, 89drugsanalgesia overuse 191, 193–4,201–2causing confusional states 77, 80,83–4causing dizziness/imbalance 137,176causing headache 187, 196causing weakness/fatigue 152inducing tremor/parkinsonism 165,167and syncope 65Duchenne muscular dystrophy (DMC)148dural venous sinuscavernous 58thromboses 122, 198, 199dysaesthesia 220dysarthria 95, 98, 102, 178, 180dysdiadochokinesia 125, 180dysgraphia 98, 99dyskinesia 165dyslexias 97–8dysphasias 76, 95, 96dyssynergia 180dystonia 168ear disorders 60–1, 176, 178Eaton–Lambert syndrome 55, 56echocardiography 112eclampsia 200elaborated disease 221elbow movement 154electrocardiography (ECG) 66, 67, 73,112, 142electroencephalography (EEG) 40–3abnormal rhythms 40ataxia 181–2confusional states 77epilepsy 41–2, 68, 68, 69, 70, 72–3intracranial recordings 42normal rhythms 40sleep-deprived 42video 42, 73visual loss 112electromyography 54–5, 156–7
Index 237electronystagmography 61electroretinography (ERG) 60embolism, cerebral arteries 107emotion 13, 76, 79expression 22, 165employment history 10, 152encephalitis, HSV 80, 84–5epilepsy 64classification of seizures 68–71classification of syndromes 70–1clinical diagnosis 64–5diagnostic difficulties 42, 64EEG diagnosis 41–2, 68, 68, 69,72–3memory disorders 75, 88risk factors 65Erb’s point 52erythrocyte sedimentation rate (ESR)112, 114, 142, 194evoked potentials 43–4, 52executive function 45extraocular muscles 118–19eye movementsdisorders 124–5, 152, 204examination 21, 140muscles 118–19nerve supply 120–1F waves 53facial expression 22, 165facial muscles 21, 22, 122facial nerve (VIIth cranial nerve)21–2, 136, 140facial recognition 18, 46, 108facial sensation 122, 216falls 66, 83family, reporting of signs/symptoms18, 89family history 10, 18ataxias 181epilepsy 65weakness 152FAS letter fluency 15fatigue 148, 151–2finger-to-nose test 180, 219fingersmovements 154reflexes 156sensory loss 222–3folic acid 181forced pull-back test 26, 170frontal lobe 15, 19, 176full blood count 112, 114, 142functional neuroimaging 36–7, 100,170, 172, 174fundoscopy 20, 104, 110, 112, 140gag reflex 13gait 19, 26, 154ataxic 180Parkinson’s disease 165, 170spinal cord lesion 158–9gamma camera 36–7Gerstmann’s syndrome 16giant cell (temporal) arteritis 106,108–9, 114, 194, 201glabellar reflex 19Glasgow Coma Scale 11, 11glossopharyngeal nerve (IXth cranialnerve) 22Goldmann perimetry 58graphaesthesia 25, 219grasp reflex 19growth hormone 58Guillain–Barré syndrome 52H waves 53Hallpike manoeuvre 61hallucinations 13, 78, 192hands 154, 154, 155, 222–3headinjury 65, 79, 193pain sensitive structures 188, 189sensory innervation 216see also brainheadache 187acute onset types 196–200analgesic overuse 191, 193–4,201–2classification 187, 187clinical assessment 188–90, 189,190, 191clinical scenarios 201–2diagnostic criteria 187–8, 188with dizziness/vertigo 134, 135, 142insidious worsening types 191–6red flag symptoms/signs 191, 195hearing loss 136assessment 22, 60–1, 138–40conductive 22, 61sensorineural 22, 61, 140with vertigo 140heel-shin test 219heel-to-knee test 180hemianopia 58, 104–6, 108bitemporal 105, 106, 115–16homonymous 97, 105, 106hemicrania, chronic paroxysmal 191,193hemiparesis/hemiplegia 100, 192hereditary motor and sensoryneuropathies (HMSN) 56herpes simplex virus (HSV)encephalitis 80, 84–5hip flexion/extension 154hippocampus 16, 87, 90history taking 8–10cognitive disorders 18, 88–9concepts 8informant interview 18, 89Holmes tremor 167Horner’s syndrome 122, 123, 192,204, 207, 211Humphrey field analyser 59Huntingtin gene 173Huntington’s disease (HD) 19, 47,164, 168, 173hydrocephalus 57, 58hydrops 134, 135, 142hyperalert state 79hyperalertness 14hyperreflexia 182hypertension 122–3, 128benign intracranial 196causing headache 200malignant 200hyperventilation 71, 136, 137hypoaesthesia 220hypodynia/allodynia 220hypoglossal nerve (XIIth cranialnerve) 22hypotension, postural 65–6, 138,144–5hypoxia 80infective diseases 79–80, 84–5, 182–3,187inflammatory disorders 187informant interview 18, 89inherited disorders 10ataxias 178, 181migraine 192peripheral nerves/muscle 152insight, loss of 18intellectual ability 45ischaemic lactate test 56Ishihara plates 110‘Jacksonian March’ 69jaw claudication 114, 194jaw jerk 21joint position sense 219Judgement of Line Orientation Test46kneemovements 154reflexes 24, 156, 180Korsakoff’s syndrome 87, 88,92–3laboratory tests 47double vision 126headache 190
238laboratory tests (continued)peripheral nervous system disorders56visual loss 112lactate levels 36, 56language 16anatomy and physiology 94–5pathology 95–6language disorders 89, 96–7causes 98, 98clinical assessment 16, 18, 45,98–100clinical scenarios 100–2stroke 100left hemisphere function 16, 96–8Letter Cancellation Test 45lid retraction 123limb coordination 26limb examination 190muscle power 23–4, 23reflexes 24, 156, 156, 219spinal cord lesions 204–5limbic system 16, 77, 87long QT syndrome 66, 67, 74lower motor neurone (LMN)disorders 156, 161, 204–5, 206,207, 209lumbar puncture 52, 112, 197lung tumour 160lymphadenopathy 123McArdle’s disease 151magnetic resonance angiography(MRA) 34magnetic resonance imaging (MRI)31–6advantages/disadvantages 32Alzheimer’s disease 91dementia 88, 89, 91diffusion and perfusion-weighted 35fluid-attenuated recovery (FLAIR)34functional 36, 100Korsakoff’s syndrome 93language disorders 99–100paramagnetic enhancement 32–3pituitary lesions 58spinal cord 50–1, 209syringomelia 226magnetic resonance spectroscopy(MRS) 36mamillary bodies 87, 88Marcus Gunn pupil 109mass lesionscausing headache 195see also tumoursmedian nerve lesions 154, 155, 223medications see drugsmemory 16and attention 78episodic 16, 18, 87, 88semantic 16, 45, 87, 88, 89, 90short-term 86–7, 88taxonomy 86–7memory disorders 86–93causes 87clinical assessment 16, 18, 46,88–90clinical scenarios 91–3in epilepsy 75, 88types 87–8Ménière’s disease 135, 136, 137, 137,176meningioma, optic chiasm 115–16meningitis 79–80mental status, assessment 11–20mesencephalic arteries 79metabolic disorders 80, 151, 170, 214migraine 9, 108, 188, 191–3, 201–2Mini-Mental State Examination(MMSE) 20, 45, 89–90, 99mitochondrial diseases 56mononeuritis multiplex 222mood 22, 76, 79assessment 13motor neurone disease (MND) 148,161motor sequencing 15motor systemanatomy 150examination 23–4, 140, 154, 154,156, 156motor tics 168motor unit, structure 149–50movementsinvoluntary 19, 167–8see also tremorroutine tests 154, 154multiple sclerosis (MS) 9, 52, 104,107, 181, 184–5, 204, 227multiple system atrophy (MSA) 165,170, 174musclebiopsy 56, 156contraction 149–50cramps 151, 161fasciculations 51–2, 151, 161structure 149tone 23, 112, 156, 180muscle strength 23–4, 23, 154, 154muscle wasting 154, 161myasthenia 55, 56, 121, 122, 123,128–9myelography, contrast 48myoclonus 168myopathy 151, 156, 157myotomes 152, 152myotonia 54N-acetyl aspartate (NAA) 36naming 45, 99National Adult Reading Test (NART)45nausea 135, 135neck pain 204neglect 17, 97, 220nerve biopsy 55–6nerve conduction studies 40, 51–2,52–3, 156nerve plexuses 214lesions 151, 222nerve roots 207, 214, 215lesions 151, 152, 206, 206–7nervous system, anatomy 11neurofibroma, thoracic 158–9neuroleptic malignant syndrome 83–4neuromuscular junction (NMJ)disorders 55, 122, 123, 154neurophysiology 40, 156–7peripheral nerve disorders 52–3spinal cord lesions 51–2neuropsychology 44–6noradrenaline 77numbers, understanding 16numbness and tingling 214, 217–24nutritional disorders 181, 183nystagmus 21, 136, 180dizziness/vertigo 138, 140–1down-beating 56quantitative assessment 61occipital cortex 97, 105, 106occupational history 10, 152oculomotor nerve (IIIrd cranial nerve)21, 120nucleus 121, 133palsy 127oedemacerebral 187, 195periocular 122olfactory nerve (Ist cranial nerve) 20onset of symptoms 9ophthalmoplegia 124–5opiates 80opsoclonus-myoclonus 181optic chiasm 58, 104–6, 107, 115–16optic disc 104, 108optic nerve (IInd cranial nerve) 20,104, 109optic neuritis 106, 113optic radiation 106orbit 59–60, 118–19orbital apex 118, 119orientation, tests 45
Index 239oscillopsia 136pain, muscular 151pain sensitivity 25, 219palmomental reflex 19Pancoast tumour 160panic attacks 71papillitis 104papilloedema 104, 108paraneoplastic syndromes 181, 182paraphasias 97, 99parieto-temporal cortex 133parkinsonism, drug-induced 165, 167Parkinson’s disease (PD) 19, 22, 163,164, 165, 171–2drugs 80tremor 165, 166Parkinson’s plus disorders 165–6, 174paroxysmal disorders 9perception 78perfusion, cerebral 65–6perineum, sensation 205–6, 222peripheral nerve disordersclassification 151differentiation from root lesions206, 206–7investigations 52–6patterns of deficits 154–5, 154,222–3peripheral nerves 214, 215peroneal nerve lesions 206petit mal seizures 68, 70phaeochromocytoma 200physical examination 19pinprick examination 25pituitary apoplexy syndrome 198–9pituitary fossa 58plantar response 24, 156point-to-point test 26polymodal association cortex 76polyneuropathies 222, 224–5polyopia 118polysomnography 43popliteal nerve, lateral 154positional sensation 25positron emission tomography (PET)38postoperative confusion 80postural dizziness/hypotension 65–6,73, 132, 144–5postural stability 26, 170pout reflex 19praxis 16pre-eclampsia 200presenting complaint 8–10presyncope 65–6, 73, 136, 144–5primary sensory cortex 76–7prochloroperazine 83–4, 165progressive supranuclear palsy (PSP)165prolactin 58pronator drift 24, 181, 219pronunciation 45, 94–5, 97proprioception 177–8, 215deficits 132, 140testing 220proptosis 21, 108, 109, 122, 123prosopagnosia 18, 108pseudoathetosis 181psychogenic nonepileptic seizures(PNES) 64, 65, 71, 71–2psychomotor activity 14pterygoids 21ptosis 21, 122, 123pull-back test 26, 170pulmonary disease 148, 160pupil, responses 13, 21, 109, 122, 123pyramidal signs 170quadrantanopia 58, 105, 106radial nerve lesions 154, 155radiculopathies 151, 152radiology, spinal cord 48, 209Raven’s Progressive Matrices 45reading 45, 94–5, 97–8, 99rebound phenomenon 180recall, delayed 89–90reduplicative phenomena 78reflexes 24, 156, 156, 219brainstem 13loss 222primitive 19, 170spinal roots 207repetition 96, 99respiratory alkalosis 71respiratory movements 13reticular activating system 14retina 60, 104Rey–Osterrieth complex figure 46, 90right hemisphere function 16–18rigidity 23, 170Rinne’s test 22, 60, 138–40Romberg’s test 26, 132, 138–9, 181,219saccades 125sacral root lesions 204–5sarcomere, structure 149–50sarcoplasmic reticulum 150scalp 190, 194, 216scotoma 110, 192seizurespsychogenic nonepileptic 64, 71,71–2, 74see also epilepsysemantic memory 16, 45, 87, 88, 89,90semicircular canals 132sensory cortex 216sensory loss 17, 125, 140, 214–28assessment 25–6, 112, 217–24, 219and dizziness 140nonorganic (elaborated) disease 221peripheral nerve lesions 154–5,224–5spinal cord lesions 158–9, 207,221–2terminology 220sensory nerve fibres, classification 215sensory pathways 214–17sensory receptors 214septicaemia 79serial 7’s 90shoulder abduction 154single photon emission computedtomography (SPECT) 36–7, 100,172, 174sinusitis 193sleep disorders 43smoking 182Snellen chart 20, 110social history 10, 18somatosensory evoked potentials(SSEPs) 44, 52speechanatomy and physiology 94–5assessment 98–9disorders 78, 95–8, 102, 152, 178,180fluency 15, 99sphincter function 205–6, 208, 222spinal cordanatomy 47–8, 153, 204, 215dermatomes 152–3imaging/investigations 47–51sensory pathway 214–17spinal cord lesionsanatomical localization 207–9clinical scenarios 210–12, 225–7investigations 48–52, 209level localization 206–7sensory loss 158–9, 207, 205,221–2tumours 158–9weakness 152, 153, 158–9, 160spinal sympathetic function 206spino-thalamic tracts 209, 215stance 26stapedial reflex decay 60–1Steele–Richardson–Olszewekisyndrome 165stereognosis 25, 219sternocleidomastoid muscle 22
240steroids 152strabismus 125straight leg raising 205stress 146–7see also anxiety‘stretch’ tests 205stroke 35–7, 81–2, 100, 200Stroop Test 45subarachnoid haemorrhage (SAH) 80,197, 202substantia nigra 164‘sundowning’ 78sural nerve, biopsy 56swallowing disorders 152sweating 206symptomsaggravating/relieving factors 9associated 9duration 9frequency 9mode of onset 9, 18syncopal attacks 65–7, 71syringomelia 225–6, 227systemic diseasecausing headache 195causing weakness/fatigue 148taste 21temperature sensation 25, 158, 219temporal arteries 190temporal arteritis 106, 108–9, 114,194, 201tendon reflexes 24, 180, 182thalamic nuclei 216thalamus 77, 79, 87, 88, 164thiamine 88, 181thought, content/organization 13, 78thrombosisanterior spinal artery 209dural venous sinus 122, 198, 199thumb abduction 154thyroid disorders 123thyroid function tests 142time orientation 78, 92Tinel’s sign 206, 222, 223tinnitus 136Token Test 45Tolosa–Hunt syndrome 122tongue, examination 22‘top of the brainstem’ syndrome 79touch sensitivity tests 25, 219Tourette’s syndrome 168Trail Making Test 45transient ischaemic attack (TIA) 192trauma, head 65, 79, 193tremor 163classification 163–4, 163clinical assessment 169–70tremor (continued)essential 166, 166, 170Parkinson’s disease/Parkinson’s plusdisorders 165–6, 166, 171–2physiological 166–7triceps reflex 24, 156trigeminal nerve (Vth cranial nerve)21, 140, 216trochlear nerve (IVth cranial nerve)21, 120, 121tropia 124–5, 125tumoursbrain 15, 56–8, 102, 187, 195, 195headache 195, 195lung 160orbit 60paraneoplastic syndromes 181spinal cord 158–9visual loss 106, 107, 115–162-point discrimination 26, 219Uhthoff’s phenomenon 107, 227ulnar nerve lesions 154, 155, 206,222–3, 224ultrasound 39–40, 112upper motor neurone (UMN)disorders 156, 158–9, 205, 206,207, 208vagus nerve (Xth cranial nerve) 22,214vascular diseaseconfusional states 79double vision 121, 122, 127, 128headache 187, 195, 200, 202spinal 51, 211–12visual loss 107, 116–17vasovagal syncope 64, 65–6, 71verbal fluency 15, 99verbal function, assessment 45verbal reasoning 45, 78vertebrobasilar migraine 192vertigo 131benign positional 134, 135, 143–4clinical assessment 134–41defined 131symptom complexes 134, 135vestibular nerve 22, 132–3vestibular systemanatomy 132–4disorders 176testing 61vestibulo-ocular reflex 61vestibulo-spinal tract 133vestibulocochlear nerve (VIIIth cranialnerve) 22, 132–3, 136vibration, sensitivity 25, 219video-telemetry 42vision, and headache 193visual acuity testing 10, 20, 110visual evoked responses 43, 60, 112visual field defects 19, 58, 104–6visual field testing 20, 58–9, 110–11,115visual lossaetiologies 106, 107clinical assessment 106–12, 112clinical scenarios 113–17with diplopia 122higher cortical dysfunction 108,108, 112temporal arteritis 114, 194visual neglect 17visual object agnosia 18visual symptomsepilepsy 71migraine 192presyncope 65–6visuo-perceptual function 16–18,46–7, 89vitamin B 1(thiamine) 88, 181vitamin B 12181, 183vomiting 135, 136Wallenburg, lateral medullarysyndrome 222weaknessanatomical localization 151, 152–4,156clinical assessment 151–7clinical scenarios 158–61non-neurological causes 148symptoms arising from differingdistributions 148Weber’s test 22, 60, 138–40Wechsler Adult Intelligence Scale-Revised (WAIS-R) 45Wechsler Memory Scale-Revised 46Wernicke’s aphasia 96, 99, 101Wernicke’s area 16, 94, 97Wernicke’s encephalopathy 80, 92–3,122Wilson’s disease 167Wisconsin Card Sorting Test 45writing disorders 16, 98, 99xanthochromia 197