Mohammed T. Abou-Saleh

278 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYNEW VARIANT CJDThe first cases of new variant CJD appeared in 1995, whenindividuals under the age of 40 years developed a rapidlyprogressive dementing illness, and pathological analysis at postmortem confirmed the typical features of spongiform encephalopathy19 . There were a number of important differences to typicalsporadic CJD, however:1. Many of the cases presented with features of a psychiatricdisorder, such as anxiety, depression or hysteria.2. The development of the dementia was more slowly progressivethan in typical cases of CJD.3. The typical changes of triphasic complexes on the EEG werelacking.4. Brain microscopy revealed far more extensive PrP-positiveplaques.The evidence that these cases may be directly linked to BSE incattle is compelling in that the PrP protein in these cases isbiochemically very similar to that found in cases of BSE, and theincubation time of transmitted cases in transgenic mice expressingthe human PrP gene is identical to that of transmitted BSE cases 20 .Up to September 2001, 107 cases had been described, one ofwhich was in an elderly man aged 74.MULTISYSTEM ATROPHY (SHY–DRAGERSYNDROME), PROGRESSIVE SUPRANUCLEARPALSY (PSP) (STEELE–RICHARDSON–OLSZEWSKISYNDROME), DENTATOPALLIDO–LUYSIANATROPHY AND OLIVOPONTOCEREBELLARATROPHY (OPCA)Dementia is not an invariable accompaniment of any of theabove, but thorough cognitive testing will often reveal deficits,especially in late cases. The dementia may be of frontal lobe typeor sub-cortical but not severe, and may be masked by otherclinical features that are more prominent 21 .Nomenclature of the above conditions is subject to debate.Extrapyramidal features are seen in most, although a clinicalpresentation with prominent cerebellar features tends to result in apatient being labelled as OPCA and pronounced autonomicfailure as Shy–Drager syndrome, but the pathological changes ofcell loss and gliosis in all are similar and may also be present in thesame sites, although to varying degrees. Only in PSP is there aclearly distinct clinical presentation and histological appearance.The early signs in all the above conditions are usually rigidity inmuscle tone, bradykinesia of movement and postural instability.The signs are usually bilateral and progress over months andyears.In PSP, first described in 1964 22 , there is characteristically a lossof conjugate voluntary eye movements, beginning with verticalgaze. The range of eye movement is improved if the patient ismade to fixate on a target and the head moved. Upper motorneurone limb signs are common, and dystonic posturing of neckmuscles resulting in extension is often seen. Reduction in verbalfluency is a prominent feature of the condition, and it has beenpostulated that this is due to interruption of fronto-basalcircuitry 23 . The condition is confirmed pathologically by thefinding of neuronal loss, neurofibrillary tangles and gliosisprimarily affecting the subthalamic nucleus, globus pallidus,dentate, substantia nigra, locus coeruleus, periaqueductal greymatter and other brainstem nuclei.Multisystem atrophy (MSA) results in a degenerative processaffecting neurones throughout the central nervous system (CNS)and thus the signs may be widespread, with involvement ofcorticospinal tracts and especially the autonomic system. Diagnosisis usually clinical and may be strongly suspected when thereare additional signs, such as laryngeal stridor or denervation ofthe urethral sphincter on electromyography.Dentatorubral-pallido-luysian atrophy is an autosomal dominantdisorder that has been found to be linked with a trinucleotiderepeated on the B37 gene of chromosome 12. The clinical featuresinclude seizures, chorea, dementia, ataxia, mental retardation andpsychiatric disease. Abnormalities are seen in the subcorticalwhite matter.Other investigations in this group of conditions are usuallynormal, although evidence of cortical atrophy may be present inlate cases on the CT scan, and a case has been made for thedifferentiation of PSP from other causes of extrapyramidalsyndromes and dementia by subtle findings on CT 24 .The parkinsonian features in these disorders are often resistantto treatment with conventional anti-parkinsonian drugs. In thecase of MSA, L-dopa therapy can exacerbate symptoms ofpostural hypotension due to the coexistent autonomic neuropathy.The disorders are therefore treated along supportive lines,although MSA may require more specific drug therapy, directedat features such as postural hypotension.In all the above disorders, depression can be a commonaccompanying symptom, as patients are aware of the restriction inactivity caused by the disease. This may require separatetreatment.As mentioned earlier, a dementing illness may also occur,especially in the later stages. However, this may be overlooked ifpoor performance on a task is attributed to slowness of responseor the effects of drug therapy.MOTOR NEURONE DISEASEThis disorder, which primarily causes loss of both upper andlower motor neurones, can also be associated with a dementia.Dementia is detectable in approximately 5% of cases, although itsexistence may be obscured if the patient is rendered anarthric andparalysed. It may preceded the onset of the typical signs of motorneurone disease in about 50% of cases, and is more common inthose with a bulbar onset or in familial cases. Myoclonus has beennoted in up to 15% of cases and this is probably what has beenresponsible for the confusion with Creutzfeldt–Jakob disease—with many of these cases being previously labelled as the‘‘amyotrophic form of CJD’’, although the other clinical featuresof CJD, the typical EEG findings and laboratory transmission toanimals, were lacking 25 . The dementia is typically ‘‘frontal’’ intype, with deficits in attention, learning, naming, insight andjudgement 26 .ALS may also occur in association with both parkinsonism anddementia, with the dementia being indistinguishable from thatoccurring in Alzheimer’s disease. The age of onset was almost thesame for the parkinsonism, ALS and dementia, indicating thatthey are probably of the same aetiology.The studies in Guam 27 have shown the development of aparkinsonism–dementia–ALS disease on exposure of individualsto the toxins from the cycad plant. In the review by Hudson 28 ,itisproposed that this link between the three modes of presentationmay indicate that the disorders may be variants of the samedisease and not unique to Guam.NORMAL PRESSURE HYDROCEPHALUSThe title of this condition is a misnomer, as the cerebrospinal fluid(CSF) pressure is raised, but only intermittently, to produce whatare known as ‘‘B’’ waves on continuous CSF pressure recordings.However, classic symptoms of raised intracranial pressure are