Non-headache manifestations of Migraine Dr Nicholas Silver Consultant Neurologist The Walton Centre...

Non-headache manifestations Non-headache manifestations of Migraineof Migraine

Dr Nicholas Silver

Consultant Neurologist

The Walton Centre for Neurology and Neurosurgery

BASH HULL 2011BASH HULL 2011

Copies of slides: [email protected]

Migraine Migraine Third National Morbidity SurveyThird National Morbidity Survey**

Primary care consultationsPrimary care consultations

> 300,000 person-years> 300,000 person-years

9.5% of population consult GP each year re: 9.5% of population consult GP each year re: neurological symptomneurological symptom

Top 5 symptoms:Top 5 symptoms:1.1. Headache/migraineHeadache/migraine

2.2. DizzinessDizziness

3.3. Syndromes related to the cervical or lumbar spineSyndromes related to the cervical or lumbar spine

4.4. Faints or fitsFaints or fits

5.5. Symptoms due to cerebrovascular disease. Symptoms due to cerebrovascular disease.

*Anthony Hopkins, JNNP 1989 Apr;52(4):430-3

Episodic MigraineEpisodic Migraine

Alcohol

Relief of stress /weekend

Caffeine

Triggers – additive effectTriggers – additive effect

headache

lifestyle

Preventative

Hormone fluctuation

The 4 stages of acute migraineThe 4 stages of acute migraine

Aura Aura (20%)(20%)

ProdromeProdrome PostdromePostdrome HeadacheHeadache

+ + AssociatedAssociated featuresfeatures

HoursHours Minutes Minutes Hours Usually 1-2 daysHours Usually 1-2 days to hoursto hours to daysto days

Acute Migraine – ProdromeAcute Migraine – Prodrome(premonitory features)*(premonitory features)*

Mental StateMental State NeurologicalNeurological GeneralGeneralFatigueFatigue

IrritabilityIrritability

Depressed moodDepressed mood

EuphoriaEuphoria

HyperactivityHyperactivity

RestlessnessRestlessness

DepersonalisationDepersonalisation

DerealisationDerealisation

YawningYawning

SomnolenceSomnolence

PhonophobiaPhonophobia

PhotophobiaPhotophobia

OsmophobiaOsmophobia

Restless LegsRestless Legs

LightheadedLightheaded

Food cravingFood craving

DizzinessDizziness

Neck pain / Neck pain / stiffnessstiffness

AnorexiaAnorexia

Frequent micturitionFrequent micturition

DiarrhoeaDiarrhoea

*prodrome seen in about 60% of patients*prodrome seen in about 60% of patients

Migraine - AuraMigraine - Aura

Only present in 20% of migraineursOnly present in 20% of migraineurs

Symptoms usually “evolve” over timeSymptoms usually “evolve” over time– Most commonly 20 to 30 minutesMost commonly 20 to 30 minutes– May persist hours to monthsMay persist hours to months

““cortical spreading depression” cortical spreading depression”

May occur without headacheMay occur without headache– ““acephalalgic” migraineacephalalgic” migraine

““A complex of focal neurological symptoms A complex of focal neurological symptoms (positive or negative phenomena) that (positive or negative phenomena) that precede or accompany an attack”precede or accompany an attack”

Migraine - AuraMigraine - AuraVisualVisual– ScotomaScotoma– Photopsia, phosphenesPhotopsia, phosphenes– Teichopsia (fortification Teichopsia (fortification

spectra)spectra)– Metamorphopsia, macropsia, Metamorphopsia, macropsia,

zoom or mosaic visionzoom or mosaic vision

SensorySensory– unilateral or bilateral (<50%), unilateral or bilateral (<50%),

slow migrating, positive slow migrating, positive phenomena phenomena

Cheiro-oral migrating Cheiro-oral migrating paraesthesiaeparaesthesiaeSensory ataxiaSensory ataxia

– Often reported as Often reported as weaknessweakness

– Olfactory hallucinationsOlfactory hallucinations

MotorMotor – WeaknessWeakness

True weakness is rare and always True weakness is rare and always unilateralunilateralDysarthriaDysarthria

– AtaxiaAtaxia– ChoreaChorea– Movement disordersMovement disorders

CognitiveCognitive– Dysphasia / aphasiaDysphasia / aphasia– ApraxiaApraxia– AgnosiaAgnosia

Disturbed consciousness / delusionsDisturbed consciousness / delusions– Acute confusional stateAcute confusional state– Multiple conscious trance-like Multiple conscious trance-like

statesstates– DeliriumDelirium– ComaComa– Déjà vu / Jamais vuDéjà vu / Jamais vu

What are What are migrainous migrainous features of features of headache ?headache ?

Throbbing / poundingThrobbing / pounding

Head, neck and / or faceHead, neck and / or face

Unilateral Unilateral oror bilateral bilateral

TendernessTenderness

Nausea +/- vomitingNausea +/- vomiting

Icepick (<40%)Icepick (<40%)(=primary stabbing headache) (=primary stabbing headache)

Stimulus SensitivityStimulus Sensitivity– Movement exacerbationMovement exacerbation– Noise (photophobia)Noise (photophobia)– Light (phonophobia)Light (phonophobia)– Smell (osmophobia)Smell (osmophobia)– Touch (allodynia)Touch (allodynia)

Relieving factorsRelieving factors– FlatFlat– StillStill– VomitVomit– SleepSleep

Non-headache symptoms Non-headache symptoms of acute migraineof acute migraine

Mental StateMental State NeurologicalNeurological GeneralGeneralDepressionDepression

DissociationDissociation

AnxietyAnxiety

FatigueFatigue

IrritabilityIrritability

AgitationAgitation

Anger Anger

RageRage

IncapacityIncapacity

ConfusionConfusion

ExhilarationExhilaration

HypomaniaHypomania

[constitutional and mental [constitutional and mental changes are almost changes are almost universal]universal]

Blurred visionBlurred vision

ParaesthesiaeParaesthesiae

FormicationFormication

VertigoVertigo

Acute confusionAcute confusion

DisorientationDisorientation

Word-finding difficultyWord-finding difficulty

StutteringStuttering

DysphasiaDysphasia

AutonomicAutonomic

SyncopeSyncope

HemiplegiaHemiplegia

ComaComa

LightheadednessLightheadedness

Flushing, Pallor, skin Flushing, Pallor, skin change, cold extremitieschange, cold extremities

Oedema / fluid retentionOedema / fluid retention

Scalp / face oedemaScalp / face oedema

Hair lossHair loss

Neck pain and stiffnessNeck pain and stiffness

AnorexiaAnorexia

GastroparesisGastroparesis

Food cravingFood craving

Nausea (90%)Nausea (90%)

Vomit (30%)Vomit (30%)

EructationEructation

Diarrhoea (16%)Diarrhoea (16%)

PolyuriaPolyuria

Epistaxis, EcchymosisEpistaxis, Ecchymosis

Migraine – postdromeMigraine – postdrome

Resolution often associated with:Resolution often associated with:FatigueFatigueListlessnessListlessnessFragilityFragilityScalp tendernessScalp tenderness

Also, following may occur:Also, following may occur:IrritableIrritableImpaired concentrationImpaired concentrationMuscle weakness and achingMuscle weakness and achingAnorexiaAnorexiaFood cravingsFood cravings

Distortion of realityDistortion of reality as a as a manifestation of migrainemanifestation of migraine“Alice in Wonderland Syndrome”“Alice in Wonderland Syndrome”

– Visual aura Visual aura

– Teleopsia - “zoom” visionTeleopsia - “zoom” vision

– Surroundings may appear Surroundings may appear very big or very smallvery big or very small

– Body image disturbances Body image disturbances body parts appear large, body parts appear large, small, distorted, reduplicated small, distorted, reduplicated or absentor absent

– Entomopia – “Insect eye” - Entomopia – “Insect eye” - multiple copies of same multiple copies of same image in grid-like patternimage in grid-like pattern

– Corona phenomenaCorona phenomena

– HallucinationsHallucinationsVisualVisualAuditoryAuditoryOlfactoryOlfactoryGustatoryGustatoryTactileTactile

– Cognitive deficitCognitive deficitapraxia, agnosiaapraxia, agnosiaacute confusional stateacute confusional state

– Delusions Delusions

– Paranoid psychosisParanoid psychosis

MacrosomatognosiaMacrosomatognosia

Macrosomatognosia of head, neck, both arms and hands.

(Podoll and Robinson, Acta Neurolo Scand 2000;101:413-416)

Migraine Autonomic SymptomsMigraine Autonomic Symptoms

Approx 20% of migraineursApprox 20% of migraineurs

Localised facial disturbanceLocalised facial disturbanceConjunctival injection (“red eye”)Conjunctival injection (“red eye”)Lacrimation (“tearing”)Lacrimation (“tearing”)Eyelid / facial swellingEyelid / facial swellingPeriorbital swelling and apparent enophthalmos as opposed to ptosis Periorbital swelling and apparent enophthalmos as opposed to ptosis Nasal congestion / rhinorrhoea (less common)Nasal congestion / rhinorrhoea (less common)ObjectiveObjective scalp or facial swellling (oedema) scalp or facial swellling (oedema)Flushing (may be unilateral)Flushing (may be unilateral)Fullness in earFullness in earEcchymosis (face or limbs)Ecchymosis (face or limbs)? Systemic oedema? Systemic oedema

““Migraine is the commonest cause of Migraine is the commonest cause of

facial autonomic disturbance”facial autonomic disturbance”

Differentiating Migraine from other Differentiating Migraine from other pathology with historypathology with history

Acute Migraine may masquerade as Acute Migraine may masquerade as – StrokeStroke– SAHSAH– Seizure / NEADSeizure / NEAD– Bells palsyBells palsy


Aura vs StrokeAura vs Stroke– Premonitory phasePremonitory phase– EvolutionEvolution– Spread of symptomsSpread of symptoms– Type of deficit (eg Type of deficit (eg

scotoma vs scotoma vs hemianopia)hemianopia)

– Positive symptoms Positive symptoms with aurawith aura


Episodic migraine vs SAHEpisodic migraine vs SAH– Often very difficultOften very difficult– Err on side of cautionErr on side of caution– Most useful question - ?Most useful question - ?

Premonitory phasePremonitory phase– Check “true” thunderclap, not just Check “true” thunderclap, not just

like aftermath of being hit by a like aftermath of being hit by a baseball batbaseball bat


Seizure vs Migraine SyncopeSeizure vs Migraine Syncope – Is migraine syncope a common cause of blackout?Is migraine syncope a common cause of blackout?– Premonitory phase – often many minutes or hoursPremonitory phase – often many minutes or hours– Often dissociated and light headed before Often dissociated and light headed before

(eg 10 -15 minutes or more)(eg 10 -15 minutes or more)– Symptoms may resemble panic attack or Symptoms may resemble panic attack or

hyperventilationhyperventilation– May start with primary stabbing headacheMay start with primary stabbing headache– Often presence of pain before LOCOften presence of pain before LOC– Both often followed by migrainous headacheBoth often followed by migrainous headache


Bells Palsy vs MigraineBells Palsy vs Migraine – Migraine may cause facial drooping with apparent Migraine may cause facial drooping with apparent

weaknessweakness– Probable autonomic causeProbable autonomic cause– Loss of frontalis corrugator appearance – oedemaLoss of frontalis corrugator appearance – oedema– Apparent enophthalmos with periorbital oedemaApparent enophthalmos with periorbital oedema– Can close eye normally; normal blinkCan close eye normally; normal blink– Often with prominent numbness, tingling and Often with prominent numbness, tingling and

headacheheadache– May have other autonomic disturbanceMay have other autonomic disturbance

Chronic MigraineChronic Migraine

Markers to suggest Chronic Markers to suggest Chronic (vs episodic) Migraine(vs episodic) Migraine

1.1. Loss of prior efficacy ofLoss of prior efficacy of– Acute attack medications Acute attack medications (“painkillers stopped working”)(“painkillers stopped working”)– PreventativePreventative

2.2. Ask about number of “crystal clear” headache-free days Ask about number of “crystal clear” headache-free days per month and look for migrainous features in milder per month and look for migrainous features in milder less specific headachesless specific headaches

3.3. Multisymptomatic patient, even if does not present with Multisymptomatic patient, even if does not present with headacheheadachei.e. presenting withi.e. presenting with– FatigueFatigue– Other pain syndromes (neck pain, back pain, fibromyalgia, etc)Other pain syndromes (neck pain, back pain, fibromyalgia, etc)– Vertigo / dizzinessVertigo / dizziness– Insomnia Insomnia – Mood disturbanceMood disturbance– Poor memory Poor memory

Chronic MigraineChronic Migraine

Gradual characteristic evolution from acute to chronic stateGradual characteristic evolution from acute to chronic state

1.1. FrequencyFrequency increases increases

2.2. SeveritySeverity can increase or decrease can increase or decrease

3.3. GapsGaps “ “fill infill in” with milder migrainous headaches + PSH” with milder migrainous headaches + PSH

4.4. Acute attack medications lose efficacyAcute attack medications lose efficacy e.g. painkillers / triptanse.g. painkillers / triptans

5.5. Pervasive Pervasive non-headachenon-headache features features usually diminish / disappear on usually diminish / disappear on completecomplete headache-free days headache-free days

Frequent headaches with migrainous featuresFrequent headaches with migrainous features

++

< 15 days per month headache-free< 15 days per month headache-free

Medication OveruseMedication Overuse

? Main cause of lack of response to headache preventatives? Main cause of lack of response to headache preventatives

AllAll acute attack medications can cause medication overuse, acute attack medications can cause medication overuse, as can caffeineas can caffeine

Usually motivated by patient’s desire to treat their headachesUsually motivated by patient’s desire to treat their headaches

Commonest cause of chronic daily headache (IHS ICHD II):Commonest cause of chronic daily headache (IHS ICHD II):– ““The interaction between a therapeutic agent and a susceptible The interaction between a therapeutic agent and a susceptible

patient”patient”

If co-morbid neck pain, back pain or “fibromyalgia”, still worth If co-morbid neck pain, back pain or “fibromyalgia”, still worth stopping painkillers, as central sensitisation may heighten stopping painkillers, as central sensitisation may heighten other bodily pains.other bodily pains.

Escalation of acute attack medications, with loss of Escalation of acute attack medications, with loss of effectivenesseffectiveness is a big alarm bell to MOH or caffeine overuse is a big alarm bell to MOH or caffeine overuse headache and chronic as opposed to acute migraineheadache and chronic as opposed to acute migraine

““Tea and Coffee HeadachesTea and Coffee Headaches. –. – In the nervous, and often In the nervous, and often the gouty and rheumatic person, the use of tea and coffee the gouty and rheumatic person, the use of tea and coffee will cause violent headaches. These luxuries of life should will cause violent headaches. These luxuries of life should be discontinued for at least one month. An extra strong cup be discontinued for at least one month. An extra strong cup of black coffee, to be sure, will stop the headache for the of black coffee, to be sure, will stop the headache for the time being, but only adds fuel to the fire in the long run. We time being, but only adds fuel to the fire in the long run. We would strongly advise anyone that has constant or would strongly advise anyone that has constant or periodical headaches, if he uses either tea or coffee, and periodical headaches, if he uses either tea or coffee, and especially coffee, to leave them off entirely for three especially coffee, to leave them off entirely for three months. It may be the sole cause, and if caused by tea and months. It may be the sole cause, and if caused by tea and coffee, there is no possibility of their cure by medicines coffee, there is no possibility of their cure by medicines while you continue their use”while you continue their use”

Caffeine OveruseCaffeine OveruseVirtue’s Household Physician – circa 1920Virtue’s Household Physician – circa 1920

Chronic MigraineChronic MigraineTriggers and Perpetuating FeaturesTriggers and Perpetuating Features

An InheritedPredisposition:

A “genetic disorder”A “genetic disorder”

+/- Family history+/- Family history

Travel sicknessTravel sickness•ChildhoodChildhood•Adulthood – with readingAdulthood – with reading

+/- previous migraine+/- previous migraine

Migrainous hangoversMigrainous hangoversUndeserved hangoversUndeserved hangovers

Comorbid IBSComorbid IBS

Triggers:

HormonesHormones•PregnancyPregnancy•PostpartumPostpartum•OCPOCP•MenopauseMenopause

Viral infectionViral infectionHead injuryHead injurySystemic illnessSystemic illnessNeurological illnessNeurological illnessNeurosurgeryNeurosurgeryEmotional stressEmotional stressIdiopathicIdiopathic

Perpetuating Factors:

PainkillersPainkillers OpioidsOpioids ParacetamolParacetamol NSAIDSNSAIDS

Triptans / ErgotTriptans / Ergot

CaffeineCaffeine CoffeeCoffee TeaTea ColaCola ChocolateChocolate LucozadeLucozade

Chronic Migraine: Chronic Migraine: “More Than Just a Headache”“More Than Just a Headache”

Coathanger Neck Pain

Mood and Cognitive DisturbanceInsomnia, poor STM, word substitutions, irritability, emotionalism, depression, anhedonia

Chronic Fatigue

Migraine Vertigo;Visual Vertigo;

“Veering”

Reflex Syncope / POTS

+/- Frequent(+/-severe)Headache

Stimulus SensitivityLight, noise, smell

Sensory Disturbance(paraesthesiae / formication

Migraine-related dysequilibrium Dissociation, lightheaded, Etc.

“Evolving” Aura

Distortion ofReality – AIWS

Restless Legs / PLMS / PLMW

Autonomic symptomsStuttering

Back Pain, Diffuse

muscle tenderness

Myokymia

Chronic Migraine: Chronic Migraine: Migraine associated symptomsMigraine associated symptoms

e.g. Disappearance ofe.g. Disappearance of– Post-natal depressionPost-natal depression– ““Chronic fatigue syndrome” or “ME”Chronic fatigue syndrome” or “ME”– FibromyalgiaFibromyalgia– Mood disturbanceMood disturbance– VertigoVertigo– Neck painNeck pain

Ask about “brilliantly crystal clear”Ask about “brilliantly crystal clear” complete complete headache-freeheadache-free daysdays

Migraine and FatigueMigraine and Fatigue

Migraine and FatigueMigraine and Fatigue

Fatigue is common in chronic migraineFatigue is common in chronic migraine11::– 84% scored >3 on Fatigue Severity Scale (FSS) 84% scored >3 on Fatigue Severity Scale (FSS) 22

– 67% met CDC67% met CDC33 criteria for Chronic Fatigue Syndrome criteria for Chronic Fatigue Syndrome

Headache is commonly not volunteered by patients when Headache is commonly not volunteered by patients when presenting with other complaints presenting with other complaints

Chronic migraine should be considered in ALL patients Chronic migraine should be considered in ALL patients presenting with chronic fatigue – all such patients should presenting with chronic fatigue – all such patients should also have detailed sleep history.also have detailed sleep history.

11Peres et al (Cephalagia 2002:22:720-724)Peres et al (Cephalagia 2002:22:720-724)22c.f. normal (<2.8), MS (5-6.5), depression (4.5), CFS c.f. normal (<2.8), MS (5-6.5), depression (4.5), CFS

(6.1)(6.1)33Center for Disease Control and PreventionCenter for Disease Control and Prevention

1994 CDC Criteria for 1994 CDC Criteria for Chronic Fatigue SyndromeChronic Fatigue Syndrome

Primary symptomsClinically evaluated, unexplained, persistent or relapsing chronic fatigue that is:Clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is:

– of new or definite onset of new or definite onset – Not result of ongoing exertion;Not result of ongoing exertion;– Not substantially alleviated by rest; andNot substantially alleviated by rest; and– Results in substantial reduction in previous levels of functionResults in substantial reduction in previous levels of function

Additional requirementsAdditional requirementsConcurrent occurrence of Concurrent occurrence of >> 4 of following symptoms 4 of following symptoms::

– Self-reported impairment in short term memory / concentrationSelf-reported impairment in short term memory / concentration – Muscle painMuscle pain– Joint pain without joint swelling or redness;Joint pain without joint swelling or redness;– Headaches of a new type, pattern, or severity;Headaches of a new type, pattern, or severity;– Unrefreshing sleepUnrefreshing sleep– Post-exertional malaise lasting more than 24 hoursPost-exertional malaise lasting more than 24 hours– sore throatsore throat;;– tender cervical or axillary tender cervical or axillary lymph nodeslymph nodes;;

Final requirementFinal requirement– All other known causes of chronic fatigue must have been ruled outAll other known causes of chronic fatigue must have been ruled out

http://en.wikipedia.org/wiki/Sore_throat

http://en.wikipedia.org/wiki/Lymph_nodes

IHS ICHD-IIIHS ICHD-II

““Headaches attributed to the following Headaches attributed to the following disorders are not sufficiently validated:disorders are not sufficiently validated:

– Chronic fatigue syndromeChronic fatigue syndrome– Fibromyalgia”Fibromyalgia”

Migraine Migraine andand

Migraine and CorpalgiaMigraine and Corpalgia

Cases of acute “migraine of the legs”Cases of acute “migraine of the legs”

Cuadrado et al (Cephalalgia 2008) Cuadrado et al (Cephalalgia 2008) – 3 patients presenting with spontaneous body pain in 3 patients presenting with spontaneous body pain in

association with migraine attacks. All patients had association with migraine attacks. All patients had allodynia to mechanical stimuli over the painful areas.allodynia to mechanical stimuli over the painful areas.

Lovati et al (Expert Review of Neurotherapeutics Lovati et al (Expert Review of Neurotherapeutics 2009) 2009) – hypothesised that extracephalic allodynia mediated by hypothesised that extracephalic allodynia mediated by

mechanism of thalamic sensitization mechanism of thalamic sensitization

Migraine and Fibromyalgia (FMS)Migraine and Fibromyalgia (FMS)

Comorbidities of Fibromyalgia Syndrome (FMSComorbidities of Fibromyalgia Syndrome (FMS) 1:) 1:

– DepressionDepression– AnxietyAnxiety– Headache; migraine and tension-typeHeadache; migraine and tension-type– IBSIBS– Chronic Fatigue SyndromeChronic Fatigue Syndrome– VertigoVertigo– ““Sinus” problemsSinus” problems– TMJ dysfunctionTMJ dysfunction– POTSPOTS

Peres (Neurology 2001) reported high rates of FMS in Peres (Neurology 2001) reported high rates of FMS in transformed (chronic) migraine patientstransformed (chronic) migraine patients

11 Waylonis and Heck, Am J Phys Med Rehab 1992 Waylonis and Heck, Am J Phys Med Rehab 1992


PeresPeres (Curr Neurol Neuroscience Rep 2003), and (Curr Neurol Neuroscience Rep 2003), and CentonzeCentonze (Neurol Sci 2004) (Neurol Sci 2004)

– suggest episodic migraine, chronic daily headache and FMS are suggest episodic migraine, chronic daily headache and FMS are continuum of same disorder. continuum of same disorder.

– Arguments based upon theories of central sensitisationArguments based upon theories of central sensitisation

– Patients with FMS show increased sensitivity to mechanical, Patients with FMS show increased sensitivity to mechanical, thermal and electrical stimuli, with abnormal central pain thermal and electrical stimuli, with abnormal central pain mechanisms and augmented pain experience.mechanisms and augmented pain experience.

Medication overuse and Medication overuse and other bodily painsother bodily pains

Overuse of painkillers is a risk factor for developing chronic Overuse of painkillers is a risk factor for developing chronic neck and back painneck and back pain1. 1. The study of 51,383 patients concluded:The study of 51,383 patients concluded:

““Overuse of analgesics strongly predicts chronic pain and chronic Overuse of analgesics strongly predicts chronic pain and chronic pain associated with analgesic overuse 11 years later, especially pain associated with analgesic overuse 11 years later, especially among those with chronic migraine” among those with chronic migraine”

Reports of refractory neck and/or back pain in patients with Reports of refractory neck and/or back pain in patients with migraine – same or improved following AAM withdrawalmigraine – same or improved following AAM withdrawal

1 1 Zwart et al, Head Hunt study, 2003Zwart et al, Head Hunt study, 2003


De Tommaso et al (Cephalalgia 2008)De Tommaso et al (Cephalalgia 2008)– FMS in 36% of patients with primary headacheFMS in 36% of patients with primary headache– Those with comorbid FMS had:Those with comorbid FMS had:

Highest level of migraine severityHighest level of migraine severityPoor sleep qualityPoor sleep quality

– Headache severity heightened intensity of diffuse pain Headache severity heightened intensity of diffuse pain and fatigueand fatigue

Pamuk and Cakir (Clin Exp Rheumatol 2005)Pamuk and Cakir (Clin Exp Rheumatol 2005)– Increased FMS symptoms with menses (pain / Increased FMS symptoms with menses (pain /

fatigue)fatigue)– Increased prevalence of FMS starting at menopauseIncreased prevalence of FMS starting at menopause

FMS pathophysiologyFMS pathophysiology

Abnormal CNS functionAbnormal CNS function11

– Supraspinal central sensitizationSupraspinal central sensitization– fMRI – cortical and subcortical augmentation of pain fMRI – cortical and subcortical augmentation of pain

processingprocessing– Evidence for role of autonomic nervous systemEvidence for role of autonomic nervous system– Best treatments = antidepressant and anticonvulsant Best treatments = antidepressant and anticonvulsant

medications. NB One small trial of beta blockers medications. NB One small trial of beta blockers suggested possible effectsuggested possible effect

11Thimineur and De Ridder, Pain Medicine 2007Thimineur and De Ridder, Pain Medicine 2007

Migraine and Migraine and Restless Legs (RLSRestless Legs (RLS))

Chronic Migraine and RLS / PLMChronic Migraine and RLS / PLM [Personal view][Personal view]

Recognised in my clinic as major factor in CM (> 7 yrs)Recognised in my clinic as major factor in CM (> 7 yrs)Commonly comorbid with chronic migraine and Commonly comorbid with chronic migraine and caffeine/medication overuse (approx 80%)caffeine/medication overuse (approx 80%)Also provoked by caffeine and painkillersAlso provoked by caffeine and painkillersDisappears after full detox in approx 80%Disappears after full detox in approx 80%Frequently see CM in those that Frequently see CM in those that presentpresent with RLS with RLS

Disrupts normal sleep architecture and leads to sleep Disrupts normal sleep architecture and leads to sleep deprivationdeprivation– Wake unrefreshedWake unrefreshed– Frequent wakening and dreamingFrequent wakening and dreaming– Diurnal variation of RLS symptoms (worst towards evening)Diurnal variation of RLS symptoms (worst towards evening)– PLMS often not obviousPLMS often not obvious

? Caused by or provokes migraine? Caused by or provokes migraine

Migraine and RLSMigraine and RLS

If disappears with detox, typically returns in acute episodic migraine If disappears with detox, typically returns in acute episodic migraine attacksattacks

If persists after detox, worth treating before adding migraine If persists after detox, worth treating before adding migraine preventativepreventative

– Pregabilin / Gabapentin – restore normal sleep architecturePregabilin / Gabapentin – restore normal sleep architecture– Sinemet CR – beware augmentation – ? less likely if Rx breaks every Sinemet CR – beware augmentation – ? less likely if Rx breaks every

6/126/12– Dopamine agonist (beware impulse control disorder and counsel patient)Dopamine agonist (beware impulse control disorder and counsel patient)– High remission rate with RxHigh remission rate with Rx

– Beware RLS / PLM provoked by tricyclic antidepressants and SSRI drugs Beware RLS / PLM provoked by tricyclic antidepressants and SSRI drugs – cause poor sleep architecture– cause poor sleep architecture

– Full and prolonged replacement of iron if Ferritin <50ng/ml Full and prolonged replacement of iron if Ferritin <50ng/ml – Replace B12 / folate and exclude renal impairmentReplace B12 / folate and exclude renal impairment

Restless Legs SyndromeRestless Legs Syndrome

““Wherefore to some, when abed they betake Wherefore to some, when abed they betake

themselves to sleep, presently in the arms themselves to sleep, presently in the arms

and legs, leapings and contractions of the and legs, leapings and contractions of the

tendons, and so great a restlessness and tendons, and so great a restlessness and

tossing of their members ensue, that if the tossing of their members ensue, that if the

diseased are no more able to sleep, than if diseased are no more able to sleep, than if

they were in the place of the greatest torture”they were in the place of the greatest torture”

Sir Thomas Willis, Sir Thomas Willis,

16721672

A medical condition?A medical condition?

On Hypochondria:On Hypochondria:Virtue’s Household Physician, a twentieth century medica: Virtue’s Household Physician, a twentieth century medica:

““The skin will twitch in different parts, or feel numb, or have the The skin will twitch in different parts, or feel numb, or have the sensation of spiders crawling on it”sensation of spiders crawling on it”

? Associations with migraine:? Associations with migraine:

““bright sparks are seen before the eyes…..at one time the bright sparks are seen before the eyes…..at one time the person will feel as large as a barrel, at other times not larger person will feel as large as a barrel, at other times not larger than a whip-stock, the head will feel light or heavy, large or than a whip-stock, the head will feel light or heavy, large or small. The smell becomes perverted; the hypochondriac will small. The smell becomes perverted; the hypochondriac will smell odors where there are none,,,,the persons are subject to smell odors where there are none,,,,the persons are subject to fainting turns…..they are irritable, fretful, peevish and fickle”fainting turns…..they are irritable, fretful, peevish and fickle”

““Eminent Authorities Consulted”Eminent Authorities Consulted” included Frances Dercum, William Gowers, F Savary included Frances Dercum, William Gowers, F Savary Pearce, Ludwig Hirt, Charles L Dana, early 1920’sPearce, Ludwig Hirt, Charles L Dana, early 1920’s

RLSRLS1800’s 1800’s “Anxietas Tibiarum”“Anxietas Tibiarum”

sign of sign of hysteriahysteria and/or neurosis and/or neurosis

19441944 EkbomEkbom “Asthenia Crurum Paraesthetic” “Asthenia Crurum Paraesthetic” (irritable legs) Acta Med Scand(irritable legs) Acta Med Scand

Published observational review of 34 casesPublished observational review of 34 casesCharacterised salient features:Characterised salient features:Diurnal pattern of lower extremity paraesthesia Diurnal pattern of lower extremity paraesthesia coupled with compulsion to move, worsening with coupled with compulsion to move, worsening with rest and alleviated by movementrest and alleviated by movement

NB not same as Ekbom’s syndrome referring to NB not same as Ekbom’s syndrome referring to delusional parasitosis, same Ekbom though!delusional parasitosis, same Ekbom though!

RLS - DiagnosisRLS - Diagnosis

4 essential criteria4 essential criteria1.1. An urge to move the legs, usually accompanied by An urge to move the legs, usually accompanied by

uncomfortable / unpleasant sensations / uncomfortable / unpleasant sensations / paraesthesiaeparaesthesiae

2.2. Onset or worsening of symptoms at rest, not Onset or worsening of symptoms at rest, not associated with any specific body positionassociated with any specific body position

3.3. Rapid relief by movement such as walking or Rapid relief by movement such as walking or stretchingstretching

4.4. Marked diurnal / circadian pattern, worse in the Marked diurnal / circadian pattern, worse in the evening or night. Note that patient may however evening or night. Note that patient may however wake in am with painful legs that disappears on wake in am with painful legs that disappears on getting up and movinggetting up and moving

EkbomEkbom

Considerable clinical morbidityConsiderable clinical morbidity

No objective evidence of neurological No objective evidence of neurological abnormalityabnormality

Common – 5% of populationCommon – 5% of population

Often family historyOften family history

Noted associations withNoted associations with– PregnancyPregnancy

– Iron deficiency anaemiaIron deficiency anaemia

– Blood donorsBlood donors

– CarcinomaCarcinoma

RLSRLS

RLS and sleepRLS and sleep

RLS is a major cause RLS is a major cause of insomniaof insomnia

Reduced time asleepReduced time asleep

Frequent wakeningFrequent wakening

Fragmentation of Fragmentation of normal sleep normal sleep architecturearchitecture

RLS – clinical featuresRLS – clinical features

Characterised by unpleasant, deep within Characterised by unpleasant, deep within lower legs, most commonly distal to lower legs, most commonly distal to kneesknees– May note sensations in thighs, feet, armsMay note sensations in thighs, feet, arms– If occur in arms, usually less severe thereIf occur in arms, usually less severe there

Most commonly bilateralMost commonly bilateral– May be unilateralMay be unilateral

Only experienced after restOnly experienced after restAlmost irresistible urge to move legs or Almost irresistible urge to move legs or stretchstretch– May need to walk around to get reliefMay need to walk around to get relief

Most severe in late evening (diurnal)Most severe in late evening (diurnal)May complain of true pain / dull acheMay complain of true pain / dull ache

RLS - descriptionsRLS - descriptions

CreepingCreepingCrawlingCrawlingItchingItchingBurningBurningSearingSearingTuggingTuggingDrawingDrawingAchingAchingElectric currentElectric currentWant to take legs offWant to take legs off

Supportive clinical featuresSupportive clinical features

Family historyFamily history– 60-80% of cases are 60-80% of cases are

familialfamilial– autonomic dominant autonomic dominant

with variable with variable penetrancepenetrance

Response to Response to dopaminergic Rxdopaminergic Rx

PLMW or PLMSPLMW or PLMS

Iron deficiencyIron deficiency– Reduced ferritin, often normal Hb Reduced ferritin, often normal Hb – Rx if ferritin less than 50ng/ml – prolonged courseRx if ferritin less than 50ng/ml – prolonged course

Pregnancy - Pregnancy - especially last trimester / ferritin < 50ng/mlespecially last trimester / ferritin < 50ng/mlBlood donationBlood donationRenal failure - Renal failure - eeffective Rx with IV Feffective Rx with IV FeFibromyalgiaFibromyalgiaMigraineMigraineDepressionDepressionRheumatoid arthritisRheumatoid arthritisB12 / folic acid deficiency (occasional)B12 / folic acid deficiency (occasional)Parkinsons disease, essential tremorParkinsons disease, essential tremor

Secondary causes and Secondary causes and associationsassociations

Restless Legs and MigraineRestless Legs and Migraine

17% of migraine vs 5% of controls had RLS17% of migraine vs 5% of controls had RLS11

RLS reported in 22% migraine subjects vs 8% of controlsRLS reported in 22% migraine subjects vs 8% of controls22

> 60% of RLS patients affected by MOH> 60% of RLS patients affected by MOH

Increased dopaminergic premonitory features in those with Increased dopaminergic premonitory features in those with comorbid RLScomorbid RLS33

RLS and PLMS recognised to be also associated with RLS and PLMS recognised to be also associated with fibromyalgiafibromyalgia44

Caffeine is “the major aetiological factor in the causation of Caffeine is “the major aetiological factor in the causation of restless legs syndrome”restless legs syndrome”55

1 1 Rhode et al. Cephalalgia 2007;27(11)1255-60Rhode et al. Cephalalgia 2007;27(11)1255-602 2 d’Onofrio et al. Neurol Sci 2008 May;29 Suppl1:S169-172d’Onofrio et al. Neurol Sci 2008 May;29 Suppl1:S169-1723 3 Cologno et al. Neurol Sci 2008 May; 29 Suppl 1: S166-168Cologno et al. Neurol Sci 2008 May; 29 Suppl 1: S166-1684 4 Yunus and Aldaq. BMJ 1996. May 25;312(7042):1339Yunus and Aldaq. BMJ 1996. May 25;312(7042):1339 55 Lutz. J Clin Psychiatry 1978;39(9)693-8 Lutz. J Clin Psychiatry 1978;39(9)693-8

Periodic Limb Movements and Periodic Limb Movements and migrainemigraine

Reported in association with migraineReported in association with migraine11

Other sleep disorders associated with migraine Other sleep disorders associated with migraine includeinclude22

OSAOSA

InsomniaInsomnia

Restless LegsRestless Legs

Circadian rhythm disorder Circadian rhythm disorder

HypersomniaHypersomnia

1 1 Bokkala et al. Bokkala et al. Pediatr Neurol. 2008 Jul;39(1):33-92 2 Rains and Poceta. Headache. 2006 Oct;46(9):1344-63

Migraine and DizzinessMigraine and Dizziness

Migraine-related dizzinessMigraine-related dizziness[Personal view][Personal view]

1.1. Migraine-related disequilibrium [commonest]Migraine-related disequilibrium [commonest]LightheadedLightheadedDissociation - depersonalisation / derealisationDissociation - depersonalisation / derealisationHot, sweaty, flushedHot, sweaty, flushedBlurred, dim, or spotty visionBlurred, dim, or spotty visionMute and buzzy hearingMute and buzzy hearing+/- secondary panic+/- secondary panic+/- situation-specific – hot, bright, noisy, crowded+/- situation-specific – hot, bright, noisy, crowded

2.2. Migraine vertigoMigraine vertigo3.3. Visual vertigoVisual vertigo4.4. Unexplained veeringUnexplained veering

Migraine-related dizzinessMigraine-related dizziness

0.89% of population has migraine vertigo0.89% of population has migraine vertigoTotal 1 year prevalence of vertigo = 4.9%Total 1 year prevalence of vertigo = 4.9%Prevalence of BPPV = 1.6% Prevalence of BPPV = 1.6% 11

Motion sickness may be treated effectively with Rizatriptan in Motion sickness may be treated effectively with Rizatriptan in migraineurs with migraine vertigomigraineurs with migraine vertigo22

NB Motion sickness often associated with stimulus sensitivity to NB Motion sickness often associated with stimulus sensitivity to noise, light and smellnoise, light and smell

Migraine vertigo presents usually as attacks of spontaneous or Migraine vertigo presents usually as attacks of spontaneous or positional vertigo lasting seconds to days and usually with positional vertigo lasting seconds to days and usually with accompanying migrainous symptomsaccompanying migrainous symptoms22

Treat with standard approaches for chronic migraine – lifestyle, Treat with standard approaches for chronic migraine – lifestyle, preventative (topiramate, beta blocker, flunarizine, etc,)preventative (topiramate, beta blocker, flunarizine, etc,)

11 Neuhauser. Current Opin Neurol 2007 Neuhauser. Current Opin Neurol 200722 Eggers. Curr Neurol Neurosci Rep 2006 Eggers. Curr Neurol Neurosci Rep 2006

FMS and neurotologic symptomsFMS and neurotologic symptoms

Fibromyalgia (FMS) (Bayazit et al, 2002)Fibromyalgia (FMS) (Bayazit et al, 2002)– 50% otologic symptoms, predominant 50% otologic symptoms, predominant

dizzinessdizziness

Rosenhall et al (1996)Rosenhall et al (1996)– Vertigo / dizziness in 72%Vertigo / dizziness in 72%– Auditory evoked potentials suggested Auditory evoked potentials suggested

brainstem dysfunctionbrainstem dysfunction

Considering Migraine in Differential DiagnosisConsidering Migraine in Differential Diagnosis“The Chameleon in the Neurology Clinic”“The Chameleon in the Neurology Clinic”

Dizziness and VertigoDizziness and Vertigo

Blackouts / SyncopeBlackouts / Syncope

Sensory disturbanceSensory disturbance

FatigueFatigue

InsomniaInsomnia

Panic Attacks (+/- panic)Panic Attacks (+/- panic)

Depression / anxietyDepression / anxiety

Chronic PainChronic Pain

– Neck pain / BrachalgiaNeck pain / Brachalgia

– Facial painFacial pain

– ““Fibromyalgia”Fibromyalgia”

? MS? MS

? Epilepsy? Epilepsy

? NEAD? NEAD

? TIA? TIA

? Stroke? Stroke

Chronic Fatigue SyndromeChronic Fatigue Syndrome

““ME”ME”

? Conversion disorder? Conversion disorder

DementiaDementia

PsychosisPsychosis

Approaches toApproaches tosuccessful successful

management management of chronic migraineof chronic migraine

Selling the conceptSelling the conceptBehaviour modificationBehaviour modification

Preventative

Sleep

Lifestyle

Chronic Migraine - RxChronic Migraine - Rx1.1. Acute abrupt withdrawalAcute abrupt withdrawal

– All acute attack medication (long term)All acute attack medication (long term)triptans, analgesics, NSAIDStriptans, analgesics, NSAIDS

– All caffeine All caffeine – Warn headaches typically worsen+++ for 5-7 daysWarn headaches typically worsen+++ for 5-7 days

2.2. LifestyleLifestyle – sleep, hydration, meals – sleep, hydration, meals

3.3. Rx Restless Legs / Periodic Limb MovementsRx Restless Legs / Periodic Limb Movements if persist after detox if persist after detox (disappear in most patients)(disappear in most patients)

4.4. After withdrawal, add After withdrawal, add “preventative”“preventative” for 1 year for 1 year– Beta blocker (eg propranalol)Beta blocker (eg propranalol)– AED (eg valproate, topiramate, gabapentinAED (eg valproate, topiramate, gabapentin– Tricyclic antidepressantTricyclic antidepressant

5.5. Change preventative if no response at 4/12Change preventative if no response at 4/126.6. Aim for maximum “tolerated” dose – reduce if persistent sedationAim for maximum “tolerated” dose – reduce if persistent sedation

The “foundation”1. No painkillers2. No caffeine3. Good fluids4. Regular meals5. Regular sleep

Migraine PreventativesMigraine PreventativesReasons for failureReasons for failure

1.1. Ineffective Ineffective – Acute attack drugs still usedAcute attack drugs still used– CaffeineCaffeine

2.2. Not used to high enough doseNot used to high enough dose– Aim for “maximum tolerated dose”Aim for “maximum tolerated dose”

3.3. Used at too high doseUsed at too high dose– Often ineffective if patient persistently sedatedOften ineffective if patient persistently sedated– Fatigue with migraine distinguished by pre-existing before drug Fatigue with migraine distinguished by pre-existing before drug

started or absence of fatigue on headache-free daystarted or absence of fatigue on headache-free day

4.4. Not used for long enough, i.e. 4 months at top level Not used for long enough, i.e. 4 months at top level reached reached

5.5. Underlying sleep disorder – RLS, PLM, OSAUnderlying sleep disorder – RLS, PLM, OSA

Chronic Migraine Chronic Migraine

PreventativesPreventatives

EvidenceEvidence

Poor evidence for many traditionally used preventative Poor evidence for many traditionally used preventative drugsdrugs

Best evidence for topiramate and propranalolBest evidence for topiramate and propranalol

Licensing varies between countriesLicensing varies between countries

Poor evidence for any individual approaches to Rx for Poor evidence for any individual approaches to Rx for migraine variantsmigraine variants

Much anecdotal “advice”Much anecdotal “advice”

Rationale in Clinical SituationsRationale in Clinical SituationsPoor sleepPoor sleep – insomnia, RLS, PLMS, – insomnia, RLS, PLMS, wake unrefreshed wake unrefreshed

– Gabapentin to 900-1200mg tds, Gabapentin to 900-1200mg tds, Pregabilin to 300-400mg bdPregabilin to 300-400mg bd

– AVOID tricyclics and SSRI drugsAVOID tricyclics and SSRI drugs

Obesity, weight gain on Obesity, weight gain on preventativespreventatives

– TopiramateTopiramate

Eating disorderEating disorder– Use most weight-neutral drugsUse most weight-neutral drugs

Pregnancy / planning pregnancyPregnancy / planning pregnancy– Avoid all preventatives if possibleAvoid all preventatives if possible– Consider GON BlockConsider GON Block– If necessary, amitryptilline or If necessary, amitryptilline or

propranalolpropranalol

Females of reproductive ageFemales of reproductive age– Avoid Sodium Valproate and other Avoid Sodium Valproate and other

anticonvulsants if possibleanticonvulsants if possible– Counsel all patients who intend to use Counsel all patients who intend to use

anticonvulsants to take good anticonvulsants to take good contraceptive measures, take regular contraceptive measures, take regular folate 5mg, and beware induction of folate 5mg, and beware induction of OCP (eg topiramate)OCP (eg topiramate)

Major DepressionMajor Depression– Consider avoiding beta blockersConsider avoiding beta blockers

Agitated psychiatric state and/or Agitated psychiatric state and/or suicidal ideationsuicidal ideation

– Consider short term olanzepineConsider short term olanzepine

Severe migraine vertigo – short Severe migraine vertigo – short term helpterm help

– Consider olanzepine short termConsider olanzepine short term

Severe anxiety or hypertensionSevere anxiety or hypertension– Consider beta blockerConsider beta blocker

Hemiplegic MigraineHemiplegic Migraine– Consider topiramate, acetazolamideConsider topiramate, acetazolamide– FlunarizineFlunarizine

Migraine vertigoMigraine vertigo– Consider topiramate, flunarizineConsider topiramate, flunarizine

Comorbid diabetes or OSAComorbid diabetes or OSA– topiramatetopiramate

SummarySummary

Chronic Migraine accounts for more than 90% of Chronic Migraine accounts for more than 90% of referrals to a specialist headache clinicreferrals to a specialist headache clinicIt is frequently misdiagnosed in hospital and primary careIt is frequently misdiagnosed in hospital and primary careChronic migraine may present with features other than Chronic migraine may present with features other than headacheheadacheAlways consider sleep disorders in your historyAlways consider sleep disorders in your historyIt is highly worthwhile taking full migraine history in It is highly worthwhile taking full migraine history in patients presenting with unexplained neurological patients presenting with unexplained neurological symptomssymptomsIt is worth treating chronic migraine with lifestyle It is worth treating chronic migraine with lifestyle strategies, attention to sleep quality / disorder, and strategies, attention to sleep quality / disorder, and rational approach to drug use and preventative rational approach to drug use and preventative strategies, even if headache is not a main presentationstrategies, even if headache is not a main presentation

Copies of slides: [email protected] info sheets - http://www.thewaltoncentre.nhs.uk/patients-and-visitors/patient-leaflets.asp#

AppendixAppendix

Alice in Wonderland syndromeAlice in Wonderland syndromeMigraine postdromal featuresMigraine postdromal featuresMigraine Variants (basilar migraine, FHM, Migraine Variants (basilar migraine, FHM, ophthalmoplegic migraine etc)ophthalmoplegic migraine etc)FatigueFatiguePLMSPLMSMedication and caffeine overuseMedication and caffeine overuseWalton Centre Audit of non headache symptoms Walton Centre Audit of non headache symptoms of migraineof migraineGuides for detoxificationGuides for detoxification

Alice in Wonderland SyndromeAlice in Wonderland SyndromeLippman 1952Lippman 1952:: Certain Hallucinations peculiar to Migraine Certain Hallucinations peculiar to Migraine

– 1 patient with left ear ballooning out 6 inches or more1 patient with left ear ballooning out 6 inches or more– Body split in 2 halves as if by vertical line, with right size twice the size of Body split in 2 halves as if by vertical line, with right size twice the size of

left.left.Syndrome named by Syndrome named by Todd, 1955Todd, 1955, in relation to migraine and epilepsy:, in relation to migraine and epilepsy:

– Characterised by body schema disturbances and facultative symptoms, Characterised by body schema disturbances and facultative symptoms, including depersonalisation, derealisation, visual illusions and illusory including depersonalisation, derealisation, visual illusions and illusory alterations in the passage of timealterations in the passage of time

Bizarre visual illusions and spatial distortionsBizarre visual illusions and spatial distortions– MacropsiaMacropsia – – world appears larger than normal / subject appears smallerworld appears larger than normal / subject appears smaller– MicropsiaMicropsia – – opposite of macropsiaopposite of macropsia– MetamorphosiaMetamorphosia - - sensation of formed body distortionssensation of formed body distortions– Zoom visionZoom vision (e.g. teleopsia (e.g. teleopsia))

Sense of time speeding up or slowing downSense of time speeding up or slowing down

More commonly reported in childrenMore commonly reported in childrenOften before the headacheOften before the headache

Also reported with infectious mononucleosis, epilepsy, Also reported with infectious mononucleosis, epilepsy, and drugs and drugs

Migraine VariantsMigraine VariantsMigraine variant or migraine equivalent are terms applied to migraine Migraine variant or migraine equivalent are terms applied to migraine exhibiting itself predominantly in form other than head painexhibiting itself predominantly in form other than head pain

Characterized by paroxysmal episodes ofCharacterized by paroxysmal episodes of– prolonged visual auras, prolonged visual auras, – atypical sensory, motor or visual aura, atypical sensory, motor or visual aura, – confusion, dysarthria, focal neurological deficits, confusion, dysarthria, focal neurological deficits, – gastrointestinal symptoms,gastrointestinal symptoms,– other constitutional symptoms other constitutional symptoms

with or without headachewith or without headache

Many migraine variants recognised in IHS IHCD-II, including: Many migraine variants recognised in IHS IHCD-II, including: – hemiplegic migrainehemiplegic migraine– basilar migrainebasilar migraine– childhood periodic syndromeschildhood periodic syndromes– retinal migraineretinal migraine– complicated migrainecomplicated migraine– ophthalmoplegic migraine ophthalmoplegic migraine

Migraine VariantsMigraine Variants

Basilar MigraineBasilar MigraineOphthalmoplegic MigraineOphthalmoplegic MigraineHemiplegic MigraineHemiplegic MigraineEpisodic ataxiaEpisodic ataxiaVertiginous MigraineVertiginous MigraineAlternating Hemiplegia of ChildhoodAlternating Hemiplegia of ChildhoodCyclical Vomiting SyndromeCyclical Vomiting SyndromeConfusional MigraineConfusional MigraineAbdominal MigraineAbdominal MigraineBenign paroxysmal vertigo of childhoodBenign paroxysmal vertigo of childhoodRetinal migraineRetinal migraineMigraine infarctionMigraine infarction? Migraine-triggered seizures (Migralepsy)? Migraine-triggered seizures (Migralepsy)

Migraine VariantsMigraine VariantsBasilar MigraineBasilar Migraine

Aura usually < 1 hour, headache typically followsAura usually < 1 hour, headache typically followsTypical hemianopia expands to all visual fields, Typical hemianopia expands to all visual fields, sometimes temporary blindnesssometimes temporary blindnessMany neurological features are bilateralMany neurological features are bilateralVisual deficit typically followed by one or more of:Visual deficit typically followed by one or more of:

VertigoVertigoTinnitusTinnitusDecreased hearingDecreased hearingDiplopiaDiplopiaAtaxiaAtaxiaBilateral paraesthesiae, weaknessBilateral paraesthesiae, weaknessImpaired cognitionImpaired cognitionconfusionconfusion

Migraine VariantsMigraine Variants Confusional MigraineConfusional Migraine

Boys > girlsBoys > girlsUsually in childrenUsually in childrenAuraAuraHeadache (may be insignificant)Headache (may be insignificant)ConfusionConfusion

InattentionInattentionDistractibilityDistractibilityDifficulty maintaining speech / activitiesDifficulty maintaining speech / activitiesSedationSedationAgitation / violent behaviourAgitation / violent behaviour

Usually relieved by sleepUsually relieved by sleep

Migraine VariantsMigraine Variants Ophthalmoplegic MigraineOphthalmoplegic Migraine

At least 2 attacks with ocular palsyAt least 2 attacks with ocular palsyTypically IIIrd nerve with dilated pupil and unilateral eye painTypically IIIrd nerve with dilated pupil and unilateral eye painIV and VI palsy (occasional)IV and VI palsy (occasional)Ophthalmoplegia – hours to monthsOphthalmoplegia – hours to months

Differential diagnosis includesDifferential diagnosis includesTolosa-HuntTolosa-HuntAneurysmAneurysmCavernous sinus / middle cranial fossa lesionCavernous sinus / middle cranial fossa lesionSphenoid sinusitisSphenoid sinusitisLyme, syphilis, coccidiomycosis, HIVLyme, syphilis, coccidiomycosis, HIVSarcoid, Leukaemia, CNS inflammatory disorderSarcoid, Leukaemia, CNS inflammatory disorder

Needs intensive investigation Needs intensive investigation – MRI+Gd and MRAMRI+Gd and MRA– DSADSA– LPLP– Bloods Bloods

Migraine VariantsMigraine Variants Hemiplegic MigraineHemiplegic Migraine

Sporadic or FamilialSporadic or Familial

Often starts in childhoodOften starts in childhoodAttacks frequently precipitated by minor head injuryAttacks frequently precipitated by minor head injuryChange in conscious level often seen (confusion to coma)Change in conscious level often seen (confusion to coma)

Differential diagnosis includesDifferential diagnosis includesFocal seizureFocal seizureStrokeStrokeMELASMELASHomocystinuriaHomocystinuria

FHMFHM

Autosomal Dominant with variable penetrationAutosomal Dominant with variable penetrationIncludes episodes with or without motor auraIncludes episodes with or without motor auraEpisodesEpisodes

– Days to weeksDays to weeks– May include reduced conscious level (confusion to coma), fever, meningismMay include reduced conscious level (confusion to coma), fever, meningism– May occur without headacheMay occur without headache

20% of families have patients who develop fixed cerebellar deficits (linked to Chr 19, eg 20% of families have patients who develop fixed cerebellar deficits (linked to Chr 19, eg CACNA1A) CACNA1A) Other gene mutations also recognised (eg on Chr 1, ATP1A2 gene mutations)Other gene mutations also recognised (eg on Chr 1, ATP1A2 gene mutations)

Migraine VariantsMigraine Variants Episodic Ataxia type 2Episodic Ataxia type 2

Autosomal dominantAutosomal dominant

Paroxysmal ataxiaParoxysmal ataxia

Provocation:Provocation:– Physical, emotional stress, alcohol, caffeinePhysical, emotional stress, alcohol, caffeine

Interictal nystagmusInterictal nystagmus

Responds to acetazolamideResponds to acetazolamide

Chr 19 (CACNA1A)Chr 19 (CACNA1A)

Migraine VariantsMigraine Variants Vertiginous MigraineVertiginous Migraine

Vertigo present in approx 1/3 of Vertigo present in approx 1/3 of migraineursmigraineurs

Recurrent vertigo episodes with or without Recurrent vertigo episodes with or without other migraine features, e.g.other migraine features, e.g.– Prodromal symptomsProdromal symptoms– NauseaNausea– Stimulus sensitivity to noise, light, smellStimulus sensitivity to noise, light, smell– Autonomic disturbance, etc.Autonomic disturbance, etc.

Migraine VariantsMigraine Variants Retinal MigraineRetinal Migraine

Not uncommon cause of transient monocular blindness Not uncommon cause of transient monocular blindness in young adultsin young adults

Recurrent attacks of unilateral visual disturbance / loss Recurrent attacks of unilateral visual disturbance / loss with minimal or no headachewith minimal or no headache

Gradual enlarging scotoma enlarging to total monocular Gradual enlarging scotoma enlarging to total monocular visual lossvisual loss

? Due to transient vasospasm of choroidal or retinal ? Due to transient vasospasm of choroidal or retinal arteriesarteries

Need to exclude vascular (carotid) disease and other Need to exclude vascular (carotid) disease and other ocular conditionsocular conditions

Fatigue Severity Scale Fatigue Severity Scale

During the past week, I have found that: Score

1. My motivation is lower when I am fatigued. 1 2 3 4 5 6 7

2. Exercise brings on my fatigue. 1 2 3 4 5 6 7

3. I am easily fatigued. 1 2 3 4 5 6 7

4. Fatigue interferes with my physical functioning. 1 2 3 4 5 6 7

5. Fatigue causes frequent problems for me. 1 2 3 4 5 6 7

6. My fatigue prevents sustained physical functioning. 1 2 3 4 5 6 7

7. Fatigue interferes with carrying out certain duties and responsibilities.

1 2 3 4 5 6 7

8. Fatigue is among my three most disabling symptoms. 1 2 3 4 5 6 7

9. Fatigue interferes with my work, family, or social life. 1 2 3 4 5 6 7

MOH - How much is overuse?MOH - How much is overuse?Limitations of IHS guidanceLimitations of IHS guidance

Dietary caffeine not included as component of overuse in IHS Dietary caffeine not included as component of overuse in IHS guidanceguidance

Increased caffeine consumption has been associated with increased Increased caffeine consumption has been associated with increased risk of developing chronic daily headacherisk of developing chronic daily headache11

Literature on detoxification from AAM does not take account of dietary Literature on detoxification from AAM does not take account of dietary caffeinecaffeine

How much is overuse according to IHSHow much is overuse according to IHS22??– Simple analgesics > 15 days per monthSimple analgesics > 15 days per month– Triptans or combination analgesicsTriptans or combination analgesics33 > 10 days per month > 10 days per month– Opioids or ergotamine > 10 days per monthOpioids or ergotamine > 10 days per month

? Depends on individual pharmacogenetics? Depends on individual pharmacogenetics

1 1 Sholz et al, 1988 Sholz et al, 1988 2 2 Mathew et al, 1990, Diamond and Dalessio 1982, Mathew 1990, Saper 1987, Wilkinson 1988, Mathew et al, 1990, Diamond and Dalessio 1982, Mathew 1990, Saper 1987, Wilkinson 1988, 3 3 i.e. with caffeinei.e. with caffeine

How much is overuse?How much is overuse?

All types of analgesic and acute attack medications reported to be All types of analgesic and acute attack medications reported to be associated with MOHassociated with MOH

– Paracetamol, NSAIDS, OpioidsParacetamol, NSAIDS, Opioids– All known triptansAll known triptans– ErgotamineErgotamine

Rebound headache may occur acutely in single attack Rebound headache may occur acutely in single attack – stopping AAM = recognised use in first line Rx of stopping AAM = recognised use in first line Rx of status migrainosus:status migrainosus:

1.1. Stop acute attack drugsStop acute attack drugs2.2. RehydrationRehydration3.3. Treatment of nausea and vomiting Treatment of nausea and vomiting 4.4. (+/- later IV steroid, neuroleptic, IV dihydroergotamine)(+/- later IV steroid, neuroleptic, IV dihydroergotamine)

Anecdotally, patients who stop using analgesics or triptans often Anecdotally, patients who stop using analgesics or triptans often report shorter attacks of acute migraine following detoxreport shorter attacks of acute migraine following detox

Clinical Features of rebound headacheClinical Features of rebound headache

Analgesic rebound headacheAnalgesic rebound headache - No - No placebo-controlledplacebo-controlled trials trials

Caffeine rebound headacheCaffeine rebound headache:: stopping low dose caffeine frequently results in withdrawal headachestopping low dose caffeine frequently results in withdrawal headache11

– Double blind placebo-controlled short-term caffeine withdrawal study Double blind placebo-controlled short-term caffeine withdrawal study – N = 64, subjects with low to moderate caffeine intakeN = 64, subjects with low to moderate caffeine intake– 32 – placebo; 32 – continued caffeine32 – placebo; 32 – continued caffeine– 50% of those given placebo had headache by day 250% of those given placebo had headache by day 2– 6% of those continuing caffeine had headache by day 26% of those continuing caffeine had headache by day 2– Nausea, depression, flu-like symptoms common in placebo (detox) groupNausea, depression, flu-like symptoms common in placebo (detox) group– Does not indicate long term consequences of detoxificationDoes not indicate long term consequences of detoxification

11 Silverman et al 1992 Silverman et al 1992

Caffeine OveruseCaffeine Overuse

Not “proven”, but long recognised to cause Not “proven”, but long recognised to cause headaches, especially on withdrawalheadaches, especially on withdrawal

Caffeine regarded as acute attack medicationCaffeine regarded as acute attack medication

Often in combined analgesicsOften in combined analgesics

Mild headaches (e.g. regarded as TTH) almost Mild headaches (e.g. regarded as TTH) almost always disappear with complete elimination of always disappear with complete elimination of acute medication and caffeineacute medication and caffeine

Caffeine withdrawal - first line for treatment-Caffeine withdrawal - first line for treatment-resistant depressionresistant depression

Caffeine content in drinksCaffeine content in drinks12 oz drink12 oz drink mgmg

Red BullRed Bull (8oz)(8oz) 8080LucozadeLucozade 4646Diet cokeDiet coke 4646Dr PepperDr Pepper 4141PepsiPepsi 3838Diet pepsiDiet pepsi 3636Coca colaCoca cola 3434

8 oz drink8 oz drink mgmg

CoffeeCoffee 70-13570-135TeaTea 40-6040-60CocoaCocoa 1414Decaf coffeeDecaf coffee 2-32-3

Horlicks, sprite etc are caffeine free

Walton Centre Audit on Walton Centre Audit on Non-headache manifestations of Non-headache manifestations of

migrainemigraine

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AppendixAppendixMigraine treatment & preventativesMigraine treatment & preventatives

Approach to successful treatment of chronic migraineApproach to successful treatment of chronic migraine

The withdrawal:The withdrawal:Warn of possible severe worsening for 1-2 weeksWarn of possible severe worsening for 1-2 weeksWorsening is a good sign and usually heralds reverse to acute migraineWorsening is a good sign and usually heralds reverse to acute migraineAdmit for in-patient detoxification if elderly, diabetes, severe triptan or opioid Admit for in-patient detoxification if elderly, diabetes, severe triptan or opioid overuse, severe depression and/or suicidal ideationoveruse, severe depression and/or suicidal ideation– May assist withdrawal with:May assist withdrawal with:

Fluids (+/- IV)Fluids (+/- IV)Oral / rectal domperidone up to 120mg per dayOral / rectal domperidone up to 120mg per day5/7 - Naproxen 500mg 8am + 4pm5/7 - Naproxen 500mg 8am + 4pmClonidine (if opiates ++)Clonidine (if opiates ++)5/7 - IM Chlorpromazine @ 10pm5/7 - IM Chlorpromazine @ 10pmIV DihydroergotamineIV DihydroergotamineSteroidsSteroids

Combined pain syndromes:Combined pain syndromes:Advise that other pains often eventually improve Advise that other pains often eventually improve offoff painkillers (especially painkillers (especially neck and back), due to cessation of central sensitisationneck and back), due to cessation of central sensitisationConsider other measures for other pains:Consider other measures for other pains:– Back pain – Pilates, Extensor stretch exercises, swimming, pain clinic – epidurals Back pain – Pilates, Extensor stretch exercises, swimming, pain clinic – epidurals

etcetc– Neck Pain – usually improves ++Neck Pain – usually improves ++– Arthritis – glucosamine, large joint revision etc.Arthritis – glucosamine, large joint revision etc.

Preventative Drugs for MigrainePreventative Drugs for MigraineLicensedLicensed Unlicensed Unlicensed

Beta Blockers*Beta Blockers*– PropranalolPropranalol (best evidence for use) (best evidence for use)– Timolol, MetoprololTimolol, Metoprolol

Antiepileptic Drugs (AED)Antiepileptic Drugs (AED)– TopiramateTopiramate******

OthersOthers– ClonidineClonidine (antihistamine and serotonin (antihistamine and serotonin

antagonist) – of no proven efficacy (BNF antagonist) – of no proven efficacy (BNF states “Clonidine is not recommended and states “Clonidine is not recommended and may aggravate depression and cause may aggravate depression and cause insomnia”) insomnia”)

– PizotifenPizotifen - evidence for effectiveness is poor; - evidence for effectiveness is poor; adverse effects severely limit use adverse effects severely limit use

– MethysergideMethysergide*** – considered very effective *** – considered very effective but concerns about about ergot side effects but concerns about about ergot side effects (retroperitoneal fibrosis etc)(retroperitoneal fibrosis etc)

Beta BlockersBeta Blockers– AtenololAtenolol (not licensed, but commonly used) (not licensed, but commonly used)– NadololNadolol

Tricyclic antidepressants**Tricyclic antidepressants**– AmitriptylineAmitriptyline (best studied) (best studied)– DosulepinDosulepin (commonly used; potentially better (commonly used; potentially better

tolerated – beware cardiac arrhythmias)tolerated – beware cardiac arrhythmias)– Nortryptilline Nortryptilline (often better tolerated)(often better tolerated)

Antiepileptic Drugs (AED)Antiepileptic Drugs (AED)– Sodium ValproateSodium Valproate****– GabapentinGabapentin (limited evidence of efficacy – 1 (limited evidence of efficacy – 1

study)study)– ZonisamideZonisamide

Neuroleptics Neuroleptics – OlanzepineOlanzepine– amisulpirideamisulpiride

Calcium AntagonistsCalcium Antagonists– VerapamilVerapamil– FlunarizineFlunarizine

SSRI’s, Venlafaxine, Levetiracetam, SSRI’s, Venlafaxine, Levetiracetam, Tizanidine, ACE II antagonistsTizanidine, ACE II antagonists

AlternativeAlternative– Butterbur, coenzyme Q10, riboflavin, feverfewButterbur, coenzyme Q10, riboflavin, feverfew* Partial agonists unhelpful; ideal beta blocker is hydrophilic and cardioselective* Partial agonists unhelpful; ideal beta blocker is hydrophilic and cardioselective

** Unlicensed, but recommended for use in BNF!** Unlicensed, but recommended for use in BNF!*** Hospital Supervision or Specialist Introduction only*** Hospital Supervision or Specialist Introduction only

First LineFirst LineNortryptilline / Amitryptilline / DosulepinNortryptilline / Amitryptilline / DosulepinPropranalol (Inderal LA)Propranalol (Inderal LA)

Second LineSecond LineEpilim ChronoEpilim ChronoTopiramateTopiramate

Third LineThird LineGabapentin (first line if sleep disorder)Gabapentin (first line if sleep disorder)ParoxetineParoxetine

Refractory casesRefractory casesFlunarizineFlunarizineOlanzepineOlanzepineMethysergideMethysergideBotulinum toxinBotulinum toxinGON Block / GON stimulatorGON Block / GON stimulator

Alternative agentsAlternative agentsPizotifenPizotifenLisinoprilLisinopril, , CandesartanCandesartanClonidineClonidineLamotrigineLamotrigine, , verapamilverapamil, , carbamazepinecarbamazepineButterburButterbur, , coenzyme Q10coenzyme Q10, , riboflavinriboflavin, , feverfewfeverfew

First LineFirst LineDosulepinDosulepin

– 25mg 7-8pm, increase 25mg each 2/52, aim 1mg/kg or maximum tolerated dose; reduce 25mg 7-8pm, increase 25mg each 2/52, aim 1mg/kg or maximum tolerated dose; reduce dose if persistent side effects other than dry mouthdose if persistent side effects other than dry mouth

– Consider ECGConsider ECG– Beware, may exacerbate restless legs syndrome and poor sleep and be counterproductiveBeware, may exacerbate restless legs syndrome and poor sleep and be counterproductive

Propranalol (Inderal LA)Propranalol (Inderal LA)– 80mg, increase 160-240mg80mg, increase 160-240mg– Avoid if severe depression Avoid if severe depression

Second LineSecond LineEpilim ChronoEpilim Chrono

– 200mg, increase 200mg / week, aim 400-800mg bd200mg, increase 200mg / week, aim 400-800mg bd– + Folic acid and contraception if young female+ Folic acid and contraception if young female– Warn – side effects: weight gain, hair loss, tremor (10%), polycystic ovariesWarn – side effects: weight gain, hair loss, tremor (10%), polycystic ovaries– Beware teratogenic++ (learning disabilities etc)Beware teratogenic++ (learning disabilities etc)

TopiramateTopiramate– 25mg, increase each week 25mg, aim 50-150mg bd25mg, increase each week 25mg, aim 50-150mg bd– 20% - cognitive side-effects or reduced speech – 20% - cognitive side-effects or reduced speech – must stopmust stop– Approx 10% - Approx 10% - severesevere mood disorder (depressed / agitated / aggressive / suicidal) mood disorder (depressed / agitated / aggressive / suicidal) must must

stopstop– Tingling at higher doses (usually settles). Tingling at higher doses (usually settles). – Risk of renal calculi, acute glaucoma (if myopic)Risk of renal calculi, acute glaucoma (if myopic)– Drink > 3 Litres per day Drink > 3 Litres per day – Occasional hair lossOccasional hair loss– Beware induces POP and COCPBeware induces POP and COCP– Beware teratogenicBeware teratogenic

Third LineThird Line

GabapentinGabapentin– Some evidence of benefit Some evidence of benefit

– Well tolerated in mostWell tolerated in most

– Useful if comorbid restless legs Useful if comorbid restless legs my first line if RLS persists after detoxmy first line if RLS persists after detox

– 600-1200mg tds 600-1200mg tds

ParoxetineParoxetine– SSRI’s not likely to be as useful as tricyclic antidepressantsSSRI’s not likely to be as useful as tricyclic antidepressants

– 10mg, increase 20mg after 1 week10mg, increase 20mg after 1 week

– Warn side-effects (dizzy, nausea, drowsy) typically last only 2/52Warn side-effects (dizzy, nausea, drowsy) typically last only 2/52

– May exacerbate poor sleepMay exacerbate poor sleep

Refractory casesRefractory cases

FlunarizineFlunarizine– Off licence calcium antagonistOff licence calcium antagonist– Licensed in some European countries where may be one of first line drugsLicensed in some European countries where may be one of first line drugs– Anecdotal benefits in prolonged aura and migraine-related dizzinessAnecdotal benefits in prolonged aura and migraine-related dizziness– Useful in refractory patientsUseful in refractory patients– Beware tardive (extrapyramidal) side effects, weight gain and severe depressionBeware tardive (extrapyramidal) side effects, weight gain and severe depression

OlanzepineOlanzepine– Very helpful in emergency situationsVery helpful in emergency situations

very resistant cases (in specialist clinics only)very resistant cases (in specialist clinics only)Short term for important timeShort term for important timeBeware weight gain, diabetes and tardive movement disorderBeware weight gain, diabetes and tardive movement disorder

MethysergideMethysergide– Good anecdotal evidenceGood anecdotal evidence– Useful for refractory casesUseful for refractory cases– Safe if <12mg daily dose, drug holidays (1 month off every 5 months)Safe if <12mg daily dose, drug holidays (1 month off every 5 months)– Monitor U+E, FBC, ESR, CXR (6 monthly) and echocardiograms yearlyMonitor U+E, FBC, ESR, CXR (6 monthly) and echocardiograms yearly

Alternative agentsAlternative agents

PizotifenPizotifen– Very poorly tolerated – weight gain and sedationVery poorly tolerated – weight gain and sedation– If tolerated, works reasonablyIf tolerated, works reasonably– Rarely used in headache clinicsRarely used in headache clinics

LisinoprilLisinopril, , CandesartanCandesartan– Small evidence, small effectSmall evidence, small effect

ClonidineClonidine– Licensed, but never been studiedLicensed, but never been studied

LamotrigineLamotrigine, , verapamilverapamil, , carbamazepinecarbamazepine– Unlikely to work as migraine preventativesUnlikely to work as migraine preventatives

Alternative drugs – Alternative drugs – butterburbutterbur, , coenzyme Q10coenzyme Q10, , riboflavinriboflavin, , feverfewfeverfew– Small studies, some evidenceSmall studies, some evidence– Lack of systematic safety dataLack of systematic safety data– Inconsistency of preparations (espec butterbur)Inconsistency of preparations (espec butterbur)

Alternative treatmentsAlternative treatments

Greater Occipital Nerve (GON) BlocksGreater Occipital Nerve (GON) Blocks– Not provenNot proven– Appear very effective for <3-4/12 in approx 40-50%Appear very effective for <3-4/12 in approx 40-50%– Useful as stopgap strategyUseful as stopgap strategy

IV DihydroergotamineIV Dihydroergotamine– Not provenNot proven– Appear very effective for <3-4/12 in approx 40-50%Appear very effective for <3-4/12 in approx 40-50%– Useful as stopgap strategyUseful as stopgap strategy

Botulinum toxinBotulinum toxin– ? Role in chronic migraine (ineffective in acute migraine)? Role in chronic migraine (ineffective in acute migraine)– Studies have blinding issuesStudies have blinding issues

Occipital Nerve StimulationOccipital Nerve Stimulation– ExperimentalExperimental– Anecdotal benefit in number of primary headache disorders including Anecdotal benefit in number of primary headache disorders including

migraine, cluster headache, SUNCT and hemicrania continuamigraine, cluster headache, SUNCT and hemicrania continua

Migraine PreventativesMigraine PreventativesReasons for failureReasons for failure

1.1. Ineffective Ineffective – Acute attack drugs still usedAcute attack drugs still used– CaffeineCaffeine

2.2. Not used to high enough doseNot used to high enough dose– Aim for “maximum tolerated dose”Aim for “maximum tolerated dose”

3.3. Used at too high doseUsed at too high dose– Often ineffective if patient persistently sedatedOften ineffective if patient persistently sedated– Fatigue with migraine distinguished by pre-existing before drug Fatigue with migraine distinguished by pre-existing before drug

started or absence of fatigue on headache-free daystarted or absence of fatigue on headache-free day

4.4. Not used for long enough, i.e. 4 months at top level Not used for long enough, i.e. 4 months at top level reached reached

5.5. Underlying sleep disorder – RLS, PLM, OSAUnderlying sleep disorder – RLS, PLM, OSA

Non-headache manifestations of Migraine Dr Nicholas Silver Consultant Neurologist The Walton Centre...

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Transcript of Non-headache manifestations of Migraine Dr Nicholas Silver Consultant Neurologist The Walton Centre...