Approach to Headache

Approach to HeadacheProf. Kammant PhanthumchindaChulalongkorn University

Pain sensitive structures• Intracranial:dura, leptomeninges, large artery & vein• Paracranial structures:skull & scalp, sinus, eyes, neck, etc.• Referred pain:cardiovascular systemneck

Mechanisms of pain• Irritation & inflammation of pain sensitive structures• Traction of pain sensitive structures– Mass– Intracranial hypertension– Intracranial hypotension• Vascular pain– Collateral circulation– Venous pressure– Toxic vascular cause

Mechanisms of pain• Pressure in paracranial structures:– sinus, intraocular pressure• Neuralgic pain• Neuronal hyperexcitibility• Other mechanisms– Muscle-joint mechanism– Iatrogenic mechanism– Psychogenic mechanism

Sources of pain• Local disease– Superficial-deep structure• Referred pain–Intracranial• Leptomeinges-pachymeninges• Supratentorium -CN V• Infratentorium – Cervical root–Extracranial• Neck• Mediastinum

Area of PainLocalized painUnilateral painDiffuse•Small area:- paracranial structure•Unilateral•Bilateral•Large area:- intracranial structure•primary headache•Meningeal pain•Increased intracranial pressure•Low intracranial pressure•Toxic vascular headache•Primary headache

Localized headache• Maxillary division– Posterior ethmoidnerve– Posterior septum,parts of superior andmiddle turbinates• Ophthalmic division• Greater superficialpetrosal nerve

Unilateral headahe• Localized headache supplyby V1 or C2• Increased intracranialpressure• Focal neurological deficit

Classification of headache• Primary headache (functional headache)– Migraine– Tension- type– Cluster headache– Myofascial pain– Others• Secondary headache (organic headache)– Intracranial causes– Paracranial causes– Systemic diseases

Characters of primary headache• Recurrent attacks• Symptoms free between the attacks• Pain shift in side and location• Clinical syndromes fulfill IHS* criteria• Physical examination normal• No organic causes• Exception: drug-abuse headache*International Headache Society

Characters of secondary headache• Progressive course• Symptoms persist• Pain select to anatomical lesions• Side-locked• Physical examination usually abnormal

Characters of secondary headacheExceptions– Some anatomical lesions :pain can shift notside-locked• Sella, parasella• Sinus• Venous sinus– Some physiological mechanisms : symptomfree period may occur• Fluctuation of intracranial pressure• Dynamic flow in vascular system• Multiple intraventricular cystic lesions

.uperior sagittal sinus thrombus

Spontaneous low CSF pressure

Dural AVM

Pituitary lesion

Intraventricular lesions

Cervical spine lesion

Evaluation of headache• History• Physical examination– Neurological examination– General physical examination• Investigations• Criteria for diagnosis of headache

History• Location of pain– Diffuse– focal– Constant– Spreading• Natural history of pain wave– Fluctuation, constant,peak– Symptom free period– Time of day– Associated symptoms– Radiation of pain– Migration– Shifting– Secondary pain• myofascial pain• allodynia• sympatheticchange

History• Severity of pain• Characters of pain– Throbbing– Neuralgic– Dull aching– etc.• Precipitating and aggravating factors• Relieving factors & response to medications• Other neurological & systemic symptoms

Physical Examination• Systemic– Hypertension– Fever– Focal mass lesion– Bleeding tendency–HIV• Neurological examination– Cranial nerves & eye ground– Other neurological examination– Cranial bruit• Paracranial structures – eye, ear, nose• Correlation of headache & physical findings

Secondary headache– X-ray - Sinus–CT-Scan–MRI–ESR-Neck– Other laboratoryInvestigations• Correlation of headache & laboratory findings

Treatment• Secondary headache– Symptomatic treatment– Specific treatment for causes• Primary headache– Acute treatment– Preventive treatment• Medical treatment• Non-medical treatment

Eur J Neurol. 2004;11(9):577-81Evidence-based medicine• Rating of recommendation– Level A rating (established as effective, ineffective, orharmful) requires• at least 1 convincing class I study or• at least 2 consistent, convincing class II studies– Level B rating (probably effective, ineffective, or harmful)requires• at least 1 convincing class II study or• overwhelming class III evidence– Level C rating (possibly effective, ineffective, or harmful)requires• at least 2 convincing class III studies– Level U rating (data inadequate or conflicting, given currentknowledge, treatment is unproven) requires• class IV studies

Migraine

Migraine Syndrome• Premonitory phase– Mental-Hypothalamic-Autonomic syndrome• Aura phase– Neurological syndrome• Headache phase– Migration and increase in severity of headache– Associated symptoms: nausea, vomiting, photophobiaphonophobia• Resolution phase– Subsided of headache– Reversed of premonitory phase

Overview of migraine phenomena– Onset – gradual• Prodrome – Hours - days• Aura - onset to peak 5 to 40 minutes- last 5 to 60 minutes- visual aura may be abrupt and short duration in non headache attack– Duration of headache• 4-72 hours– Progression – migration of head pain and marching of aura– Postdrome – gradual– Content• Positive = negative phenomena (except motor usually negative)• Autonomic – behavioural syndrome – common• Brainstem syndrome – occasionally (except vertiginous syndrome common)• Aggravating – precipitation factor - common

Premonitory symptoms (prodrome(prodrome)Mental manifestationsDepressedHyperactiveEuphoricTalkativeIrritableRestlessDifficulty concentratingSluggishnessDrowsyHyperosmiaHypothalamic autonomic manifestationsYawningCold feelingFood cravingsAnorexiaDiarrheaConstipationThirstUrinationRetention

Aura – Neurological syndromeTypical auraVisualScintillating scotomaHemianopiaBlindnessBlurring of visionParaesthesiaAphasiaCombinedOther auraHemiplegiaBrainstem symptomDysarthriaOphthalmoplegiaNystagmusOther auraOculosympathetic palsyMydriasisConfusion-stuporDizzinessCyclical vomitingSeizureDeafnessRecurrent of old strokedeficit

Scintillation scotoma

Visual aura

Migraine sensory and visualaura

Migraine headache• Unilateral or bilateral location• Meningeal pain syndrome• Migratory of pain• Shifting of side in various attacks• Pulsating quality• Moderate or severe intensity (inhibit or prohibit dailyactivities)• Aggravated by walking stairs or similar routine physicalactivities• Headache lasts 4-72hr (untreated or unsuccessfullytreated)

Associated phenomena• Nausea• Photophobia• Dizziness• Phonophobia• Osmophobia• Allodynia– Pain from non-noxious heat, cold or pressure–Site• Trigeminal• Cervical• Rest of body

Postdrome• Reverse of prodrome– Feel tired - hyperactive– Irritable - sluggishness– Unusually refreshed – drowsy– Anorexia – food cravings– Diarrhea – constipation– Edema – urination– Other nonspecific symptoms

Aggravating factors• Diet– Hunger– Alcohol– Additives– Certain foods• Chronobologics– Sleep (too much or too little)– Schedule change• Hormonal change– Menstruation• Environmental factors– Light glare– Odors– Altitude– Weather change• Head or neck pain of another cause• Physical exertion– Exercise– Sex• Stress and anxiety• Head trauma• Relieving factors– Sleep– Dark environment– Quiet environment

Diagnosis of migraine• International Headache Society (IHS) classificationof headache system• To diagnose migraine, secondary headache causesis necessary to be excluded and other coexistingmedical problem should be considered• Coexisting primary headache e.g. tension type ofheadache should determined• Diagnostic testing may be recommended at anindividual level

Migraine without auraDiagnostic criteria:A. At least 5 attacks fulfilling criteria B-DB. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treateC. Headache has at least two of the following characteristics:1. unilateral location2. pulsating quality3. moderate or severe pain intensity4. aggravation by or causing avoidance of routine physical activity(eg, walking or climbing stairs)D. During headache at least one of the following:1. nausea and/or vomiting2. photophobia and phonophobiaE. Not attributed to another disorder

Migraine with auraDiagnostic criteria:A. At least 2 attacks fulfilling criteria B–DB. Aura consisting of at least one of the following, with or without speechdisturbance but no motor weakness:1. fully reversible visual symptoms including positive features (eg,flickering lights, spots or lines) and/or negative features (ie, loss ofvision)2. fully reversible sensory symptoms including positive features (ie,pins and needles) and/or negative features (ie, numbness)C. At least two of the following:1. homonymous visual symptoms and/or unilateral sensorysymptoms2. at least one aura symptom develops gradually over ≥5 minutesand/or different aura symptoms occur in succession over ≥5minutes3. each symptom lasts ≥5 and ≤60 minutesD. Headache does not occur during aura nor follow aura within 60minutesE. Not attributed to another disorder

Treatment of Migraine

Keys for Management• Correct diagnosis• Appropriate investigations• Proper choices of symptomatic and preventivemanagement• Prevention and treatment of migraine progression• Critical evaluation and follow-up

Target of acute treatment

EFNS guideline on the drug treatment of migraineSubstanceDoseLevelCommentAcetylsalicylic acid (ASA)1000 mg (oral)1000 mg (intravenous [i.v.])AAGastrointestinal side effects, risk ofbleedingIbuprofen200 – 800 mgASide effects as for ASANaproxen500 – 1000 mgASide effects as for ASADiclofenac50 – 100 mgAIncluding diclofenac-KParacetamol1000 mg (oral)1000 mg (suppository)AACaution in liver and kidney failureASA plus, paracetamol plusand caffeine250 mg (oral),200 – 250 mg and 50 mgAAs for ASA and paracetamolMetamizol1000 mg (oral)1000 mg (i.v.)BBRisk of agranulocytosisRisk of hypotensionPhenazon1000 mg (oral)BSee paracetamolTolfenamic acid200 mg (oral)BSide effects as for ASARating of RecommendationsLevel A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at leasttwo consistent, convincing class II studies. Level B rating (probably effective, ineffective, or harmful) requires at least oneconvincing class II study or overwhelming class III evidence. Level C rating (possibly effective, ineffective, or harmful)requires at least two convincing class III studies.

EFNS guideline on the drug treatment of migraine - triptansSubstanceDoseLevelCommentSumatriptan25, 50 and 100 mg (oral including rapidrelease)25 mg (suppository) A 100 mg sumatriptan is reference to alltriptans10 and 20 mg (nasal spray)AA6 mg (subcutaneous)AZolmitriptan2.5 and 5 mg (oral including disintegratingform)2.5 and 5 mg (nasal spray)AANaratriptan2.5 mg (oral)ALess but longer efficacy than sumatriptanRizatriptan10 mg (oral including wafer form)A5 mg when taking propranololAlmotriptan12.5 mg (oral)AProbably less side effects than sumatriptanEletriptan20 and 40 mg (oral)A80 mg allowed if 40 mg not effectiveFrovatriptan2.5 mg (oral)ALess but longer efficacy than sumatriptanRating of RecommendationsLevel A rating (established as effective, ineffective, or harmful) requires at least one convincing class I study or at leasttwo consistent, convincing class II studies. Level B rating (probably effective, ineffective, or harmful) requires at least oneconvincing class II study or overwhelming class III evidence. Level C rating (possibly effective, ineffective, or harmful)requires at least two convincing class III studies.

Triptans – onset and half-lifeOnset ofactionDrugTime to peak plasma(h)Half life (h)Sumatriptan2.52Zolmitriptan3.32.5-3.0FastRizatriptan1.22.0-3.0Almotriptan1.4-3.83.2-3.7Eletriptan1.0-2.03.6-5.5SlowNaratriptanFrovatriptan2.0-3.02.0-4.05.0-6.325Tepper SJ. Acute treatment of migraine. Continuum 2006;12:87-105

New coming agentsClassCompoundStudy phaseResultCGRP antagonistOlcegepant (BIBN4096)Phase III clinicalEffective(parenteral use only)CGRP antagonistTelcagepant (MK-0974)Phase III clinicalEffectiveTRPV1 antagonist:SB-705498Phase II(non-migraine pain)EffectiveEP4 receptorantagonistCJ-023423BGC20-1531Pre-clinicalVasoconstriction5-HT1F agonistLY334370Phase IIIEffective(Study suspended due to nonhumantoxicity)Nitric oxide inhibitors546C88Phase IIEffectiveNitric oxide inhibitorsGW274150GW 273629PreclinicalEffective

Indication for Migraine prophylaxis1. Two or more attacks a month that produce disability2. Failure of, contraindication to or troublesome sideeffects from acute medication3. Very frequent headaches (> 2/week) with the risk ofrebound headache4. Overuse of acute medications5. Patient preference6. Special circumstances- Hemiplegic migraine- Basilar migraine- Migraine with prolonged aura- Migrainous infarction

Episodic migraine preventive treatmentRating ofrecommendationDrug Comorbidity Contraindicationvel AAntidepressantsAmitriptyline 10-150 mgBeta-blockersPropanolol 40-320 mg,metoprolol 50-200 mg(betaloc)Depression, anxiety,insomnia, other painHTN, angina, Anxiety, tremorGlaucoma, obesity,mania, BPH, heartblock, epilepsy, bipolaDepression, Asthma,CHF, heart block, DM,Raynaud’s, obesityCalcium antagonistsFlunarizine 5-10 mgAntiepileptic drugsValproic acid 500-1500mgTopiramate 50-200 mgHTN, vertigo, angina,Raynaud’sMania, anxiety, bipolar,epilepsyMania, anxiety, bipolar,epilepsy, Obesity, tremorDepression, PD,obesityLiver disease, bleedingdisorder, obesity,tremorKidney stones,Glucoma, memoryimpairment

Rating ofrecommendationEpisodic migraine preventive treatmentDrug Comorbidity Contraindicationevel BAntidepressantsSSRI: fluoxetine 10-80 mgDepression, anxiety,insomnia, other painmania, epilepsy, liver orhepatic disease, heartblockBeta-blockersAtenolol 50-200 mg, bisoprolol5-10 mg (concor)HTN, angina, Anxiety,tremorAsthma, CHF, heartblock, DM, Raynaud’sCalcium antagonistsVerapamil 120-640 mg,nimodipine 60-120 mgAntiepileptic drugsGabapentin 600-2400 mgNSAIDsHTN, vertigo, angina,Raynaud’sEpilepsy, tremor,other painHeart block,hypotension, liverdiseaseCKDASA 300 mg, Naproxen 500-1000 mg, Ketoprofen 150 mgOthersMg2+ 600 mg, B12 400 mg

Tension-type headache

Prior terminology for TTH• Ordinary headache • Stress headache• Essential headache • Depressive headache• Idiopathic headache • Anxiety headache• Muscle contraction • Psychogenic headacheheadache• Conversion headache• Psychomyogenic headache• Somatoform disorder• Tension headacheheadache

General clinical features oftension-type type headache• Pure tension-type headache• Bilateral, non-throbbing, plus absence of nausea,vomiting, photophobia, phonophobia, movementexacerbation• Tension-type headache is seen in migraine• Probable mild migraine

Association of tension-typetypeheadache and muscle contraction• Pericranial muscle disorder– Increased tenderness of pericranial muscles– Increased level of electromyographic (EMG) activities• Tension-type headache– Associated with disorders of pericranial muscles– Not associated with disorder of pericranial muscles

Pericranial tenderness• Frontalis• Temporalis• Lateral and medial pterygoid• Messeter• Sterocleidomastoid• Trapezius

Pericranial muscle

Subtypes of tension-typetypeheadache1. Infrequent episodic tension-type headache1.At least 10 episodes occurring on < 1day per monthon average (

Character of tension-typetypeheadacheC. Headache has at least two of the followingcharacteristics:1. Bilateral location2. Pressing/tightening (non-pulsating) quality3. Mild or moderate intensity4. Not aggravated by routine physical activitysuch as walking or climbing stairs

Character of tension-typetypeheadacheD. Both of the following:1. No nausea or vomiting (anorexiamay occur)2. No more than one of photophobia orphonophobiaE. Not attributed to another disorder

Abortive therapy for episodic tension-typeRating of recommendationDrugvel ANSAIDsAcetaminophen 1000 mg,ASA 1000 mg, Ibuprofen 200-400 mg, diclofenac 12.5-25 mg, naproxen220-500 mg, metamizole 500-1000 mg, ketoprofen 12.5-50 mgCombination drugsIbuprofen 400 mg + caffeine 200 mg (NA)vel Bvel UNSAIDsmefenamic acid 250 mg, nimesulide (nidol)Metamizole 1000 mg iv, Ketorolac 60 mg imCOX-2 inhibitorLumiracoxib 200, 400 mg (withdrawn)Combination drugsAcetaminophen 325 mg + caffeine 40 mg (NA)indomethacin + prochlorperazine + caffeine (NA)OthersChlorpromazine 0.1 mg/kg ivMuscle relaxants, Opioids, sedatives

Prophylactic therapy treatment ofepisodic tension-typetypeRating ofrecommendationevel CDrug Comorbidity ContraindicationTCA: Amitriptyline 25 mgSSRI: Fluoxetine 20 mgSNRI: Venlafaxine XR 150mg,mirtazapine 15-30 mgDepression, anxiety,insomnia, other painDepression, anxiety,insomnia, other painDepression, anxiety,panicdepressionGlaucoma, obesity, mania,BPH, heart block, epilepsy,bipolarmania, epilepsy, liver orhepatic disease, heart blockMania, epilepsy, recent MI,severe HTN, liver, kidneydiseaseGlaucoma, liver, kidneydisease, cardiac disease,epilepsy, DM, schizophreniapsychosisAmitriptyline + tizanidineadjunctive therapy

Trigeminal autonomiccephalalgia

Trigeminal autonomic cephalalgia• Cluster headache– Episodic/chronic cluster headache• Paroxysmal hemicrania– Episodic/chronic Paroxysmal hemicrania• Short-lasting unilateral neuralgiform headache attacks withconjunctival and tearing (SUNCT)• Probable trigeminal autonomic cephalalgia

Clinical features of Trigeminalautonomic cephalalgia• Headache– Orbital– Supraorbital–Temporal• Parasympathetic stimulation–Lacrimation– Conjunctival injection– Nasal congestion• Sympathetic signs– Horner’s syndrome

Mechanism of Trigeminal autonomiccephalalgia• Activation of trigeminal brainstem complex• Autonomic nervous system involvement• Hypothalamic mechanism

Common features• Headche– Orbital, supraorbital, temporal area• Prominent Cranial parasympathatic features– Conjunctival injection– Lacimation–etc

Mechanism• Activating of Trigeminal parasympathatic reflex• Secondary clinical signs of cranial sympathaticdysfunction• Hypothalamic generator

Cluster headacheDiagnostic criteriaA. At least 5 attacks fulfilling criteria B-DB. Severe or very severe unilateral orbital, supraorbital and/ortemporal pain lasting 15-180 minutes if untreatedC. Headache is accompanied by at least one of the following:1. Ipsilateral conjunctival injection and/or lacrimation2. Ipsilateral nasal congestion and/or rhinorrhea3. Ipsilateral eyelid edema4. Ipsilateral forhead and facial sweating5. Ipsilateral miosis or ptosis6. A sense of restlessness or agitationD. Attacks have a frequency from one every other day to 8 perdayE. Not attribute to another disorder

Differential diagnosis for clusterheadache involves the other knowntrigeminal autonomic cephalgiasFeatureClusterCPHEPHSUNCTGender (M:F)4:11:31:12.3:1Attackduration15–180 min2–30 min1–30 min5–240 sAttackfrequency1–8/day1–40/day3–30/day1/day–30/hAutonomic features++++Alcohol PPT++++Indomethacin effect+/−++−

Abortive therapy treatment ofepisodic cluster headacheRating ofDrugrecommendationevel A 100% Oxygen with flow rate of at least 7L/min in 15minutes via non-rebreathing facial maskTriptans:Sumatriptan 6 mg sc; 20 mg nasal sprayZolmitriptan 5, 10 mg nasal sprayevel BZolmitriptan 5, 10 mg oral4-10% Lidocaine intranasal 1 ccOctreotide 100 micrograms sc

Prophylactic treatment ofepisodic cluster headacheRating ofrecommendationDrug Contraindication Remarkvel AVerapamil 240-960 mgCorticosteroid:Prednisone 60-100 mg/d for at least5 days then taper 10 mg/d until therest of 30 mg/dDexamethasone 2 mg x 4Heart block,hypotension, liverdiseasePU, DM, HTN, CHF,CKD, systemic fungalinfection, TB, glaucoma,psychosisTitration of 40mg/d weeklyTime to haveefficacy of 2-3weeksMonitoringECG: PRprolongedvel BLithium carbonate 600-1500 mgMethysergide 6-12 mg (not available)Topiramate at least 100 mgErgotamine 2 mg hsIntranasal civamide 50 micrograms(capsaicin isomer) (not available)CKD, hypothyroidism,CVDMonitoringBlood level,BUN/Cr, LFT,TFT, electrolyte

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