Non-headache manifestations of Migraine Dr Nicholas Silver Consultant Neurologist The Walton Centre for Neurology and Neurosurgery BASH HULL 2011 Copies of slides: anne.mccann@thewaltoncentre.nhs.uk

Migraine Third National Morbidity Survey* Primary care consultations > 300,000 person-years 9.5% of population consult GP each year re: neurological symptom Top 5 symptoms: Headache/migraine Dizziness Syndromes related to the cervical or lumbar spine Faints or fits Symptoms due to cerebrovascular disease. *Anthony Hopkins, JNNP 1989 Apr;52(4):430-3

Episodic Migraine

Triggers – additive effect headache lifestyle Hormone fluctuation Preventative

The 4 stages of acute migraine Aura (20%) Prodrome Postdrome Headache + Associated features Hours Minutes Hours Usually 1-2 days to hours to days

Acute Migraine – Prodrome (premonitory features)* Mental State Neurological General Fatigue Irritability Depressed mood Euphoria Hyperactivity Restlessness Depersonalisation Derealisation Yawning Somnolence Phonophobia Photophobia Osmophobia Restless Legs Lightheaded Food craving Dizziness Neck pain / stiffness Anorexia Frequent micturition Diarrhoea *prodrome seen in about 60% of patients

Migraine - Aura “A complex of focal neurological symptoms (positive or negative phenomena) that precede or accompany an attack” Only present in 20% of migraineurs Symptoms usually “evolve” over time Most commonly 20 to 30 minutes May persist hours to months “cortical spreading depression” May occur without headache “acephalalgic” migraine

Migraine - Aura Motor Weakness Ataxia Chorea Movement disorders True weakness is rare and always unilateral Dysarthria Ataxia Chorea Movement disorders Cognitive Dysphasia / aphasia Apraxia Agnosia Disturbed consciousness / delusions Acute confusional state Multiple conscious trance-like states Delirium Coma Déjà vu / Jamais vu Visual Scotoma Photopsia, phosphenes Teichopsia (fortification spectra) Metamorphopsia, macropsia, zoom or mosaic vision Sensory unilateral or bilateral (<50%), slow migrating, positive phenomena Cheiro-oral migrating paraesthesiae Sensory ataxia Often reported as weakness Olfactory hallucinations

What are migrainous features of headache ? Throbbing / pounding Head, neck and / or face Unilateral or bilateral Tenderness Nausea +/- vomiting Icepick (<40%) (=primary stabbing headache) Stimulus Sensitivity Movement exacerbation Noise (photophobia) Light (phonophobia) Smell (osmophobia) Touch (allodynia) Relieving factors Flat Still Vomit Sleep

Non-headache symptoms of acute migraine Mental State Neurological General Depression Dissociation Anxiety Fatigue Irritability Agitation Anger Rage Incapacity Confusion Exhilaration Hypomania [constitutional and mental changes are almost universal] Blurred vision Paraesthesiae Formication Vertigo Acute confusion Disorientation Word-finding difficulty Stuttering Dysphasia Autonomic Syncope Hemiplegia Coma Lightheadedness Flushing, Pallor, skin change, cold extremities Oedema / fluid retention Scalp / face oedema Hair loss Neck pain and stiffness Anorexia Gastroparesis Food craving Nausea (90%) Vomit (30%) Eructation Diarrhoea (16%) Polyuria Epistaxis, Ecchymosis

Migraine – postdrome Resolution often associated with: Fatigue Listlessness Fragility Scalp tenderness Also, following may occur: Irritable Impaired concentration Muscle weakness and aching Anorexia Food cravings

Distortion of reality as a manifestation of migraine “Alice in Wonderland Syndrome” Visual aura Teleopsia - “zoom” vision Surroundings may appear very big or very small Body image disturbances body parts appear large, small, distorted, reduplicated or absent Entomopia – “Insect eye” - multiple copies of same image in grid-like pattern Corona phenomena Hallucinations Visual Auditory Olfactory Gustatory Tactile Cognitive deficit apraxia, agnosia acute confusional state Delusions Paranoid psychosis

Macrosomatognosia Macrosomatognosia of head, neck, both arms and hands. (Podoll and Robinson, Acta Neurolo Scand 2000;101:413-416)

Migraine Autonomic Symptoms “Migraine is the commonest cause of facial autonomic disturbance” Approx 20% of migraineurs Localised facial disturbance Conjunctival injection (“red eye”) Lacrimation (“tearing”) Eyelid / facial swelling Periorbital swelling and apparent enophthalmos as opposed to ptosis Nasal congestion / rhinorrhoea (less common) Objective scalp or facial swellling (oedema) Flushing (may be unilateral) Fullness in ear Ecchymosis (face or limbs) ? Systemic oedema

Differentiating Migraine from other pathology with history Acute Migraine may masquerade as Stroke SAH Seizure / NEAD Bells palsy

Differentiating Migraine from other pathology with history Aura vs Stroke Premonitory phase Evolution Spread of symptoms Type of deficit (eg scotoma vs hemianopia) Positive symptoms with aura

Differentiating Migraine from other pathology with history Episodic migraine vs SAH Often very difficult Err on side of caution Most useful question - ?Premonitory phase Check “true” thunderclap, not just like aftermath of being hit by a baseball bat

Differentiating Migraine from other pathology with history Seizure vs Migraine Syncope Is migraine syncope a common cause of blackout? Premonitory phase – often many minutes or hours Often dissociated and light headed before (eg 10 -15 minutes or more) Symptoms may resemble panic attack or hyperventilation May start with primary stabbing headache Often presence of pain before LOC Both often followed by migrainous headache

Differentiating Migraine from other pathology with history Bells Palsy vs Migraine Migraine may cause facial drooping with apparent weakness Probable autonomic cause Loss of frontalis corrugator appearance – oedema Apparent enophthalmos with periorbital oedema Can close eye normally; normal blink Often with prominent numbness, tingling and headache May have other autonomic disturbance

Chronic Migraine

Markers to suggest Chronic (vs episodic) Migraine Loss of prior efficacy of Acute attack medications (“painkillers stopped working”) Preventative Ask about number of “crystal clear” headache-free days per month and look for migrainous features in milder less specific headaches Multisymptomatic patient, even if does not present with headache i.e. presenting with Fatigue Other pain syndromes (neck pain, back pain, fibromyalgia, etc) Vertigo / dizziness Insomnia Mood disturbance Poor memory

Chronic Migraine Frequent headaches with migrainous features + < 15 days per month headache-free Gradual characteristic evolution from acute to chronic state Frequency increases Severity can increase or decrease Gaps “fill in” with milder migrainous headaches + PSH Acute attack medications lose efficacy e.g. painkillers / triptans Pervasive non-headache features usually diminish / disappear on complete headache-free days

Medication Overuse ? Main cause of lack of response to headache preventatives All acute attack medications can cause medication overuse, as can caffeine Usually motivated by patient’s desire to treat their headaches Commonest cause of chronic daily headache (IHS ICHD II): “The interaction between a therapeutic agent and a susceptible patient” If co-morbid neck pain, back pain or “fibromyalgia”, still worth stopping painkillers, as central sensitisation may heighten other bodily pains. Escalation of acute attack medications, with loss of effectiveness is a big alarm bell to MOH or caffeine overuse headache and chronic as opposed to acute migraine

Caffeine Overuse Virtue’s Household Physician – circa 1920 “Tea and Coffee Headaches. – In the nervous, and often the gouty and rheumatic person, the use of tea and coffee will cause violent headaches. These luxuries of life should be discontinued for at least one month. An extra strong cup 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 would strongly advise anyone that has constant or periodical headaches, if he uses either tea or coffee, and especially coffee, to leave them off entirely for three months. It may be the sole cause, and if caused by tea and coffee, there is no possibility of their cure by medicines while you continue their use”

Chronic Migraine Triggers and Perpetuating Features An Inherited Predisposition: A “genetic disorder” +/- Family history Travel sickness Childhood Adulthood – with reading +/- previous migraine Migrainous hangovers Undeserved hangovers Comorbid IBS Triggers: Hormones Pregnancy Postpartum OCP Menopause Viral infection Head injury Systemic illness Neurological illness Neurosurgery Emotional stress Idiopathic Perpetuating Factors: Painkillers Opioids Paracetamol NSAIDS Triptans / Ergot Caffeine Coffee Tea Cola Chocolate Lucozade

Chronic Migraine: “More Than Just a Headache” Migraine Vertigo; Visual Vertigo; “Veering” Migraine-related dysequilibrium Dissociation, lightheaded, Etc. “Evolving” Aura Stimulus Sensitivity Light, noise, smell Chronic Fatigue Myokymia +/- Frequent (+/-severe) Headache Coathanger Neck Pain Sensory Disturbance (paraesthesiae / formication Back Pain, Diffuse muscle tenderness Reflex Syncope / POTS Distortion of Reality – AIWS Restless Legs / PLMS / PLMW Mood and Cognitive Disturbance Insomnia, poor STM, word substitutions, irritability, emotionalism, depression, anhedonia Stuttering Autonomic symptoms

Chronic Migraine: Migraine associated symptoms Ask about “brilliantly crystal clear” complete headache-free days e.g. Disappearance of Post-natal depression “Chronic fatigue syndrome” or “ME” Fibromyalgia Mood disturbance Vertigo Neck pain

Migraine and Fatigue

Migraine and Fatigue Fatigue is common in chronic migraine1: 84% scored >3 on Fatigue Severity Scale (FSS) 2 67% met CDC3 criteria for Chronic Fatigue Syndrome Headache is commonly not volunteered by patients when presenting with other complaints Chronic migraine should be considered in ALL patients presenting with chronic fatigue – all such patients should also have detailed sleep history. 1Peres et al (Cephalagia 2002:22:720-724) 2c.f. normal (<2.8), MS (5-6.5), depression (4.5), CFS (6.1) 3Center for Disease Control and Prevention

1994 CDC Criteria for Chronic Fatigue Syndrome Primary symptoms Clinically evaluated, unexplained, persistent or relapsing chronic fatigue that is: of new or definite onset Not result of ongoing exertion; Not substantially alleviated by rest; and Results in substantial reduction in previous levels of function Additional requirements Concurrent occurrence of > 4 of following symptoms: Self-reported impairment in short term memory / concentration  Muscle pain Joint pain without joint swelling or redness; Headaches of a new type, pattern, or severity; Unrefreshing sleep Post-exertional malaise lasting more than 24 hours sore throat; tender cervical or axillary lymph nodes; Final requirement All other known causes of chronic fatigue must have been ruled out

IHS ICHD-II “Headaches attributed to the following disorders are not sufficiently validated: Chronic fatigue syndrome Fibromyalgia”

Migraine and

Migraine and Corpalgia Cases of acute “migraine of the legs” Cuadrado et al (Cephalalgia 2008) 3 patients presenting with spontaneous body pain in association with migraine attacks. All patients had allodynia to mechanical stimuli over the painful areas. Lovati et al (Expert Review of Neurotherapeutics 2009) hypothesised that extracephalic allodynia mediated by mechanism of thalamic sensitization

Migraine and Fibromyalgia (FMS) Comorbidities of Fibromyalgia Syndrome (FMS) 1: Depression Anxiety Headache; migraine and tension-type IBS Chronic Fatigue Syndrome Vertigo “Sinus” problems TMJ dysfunction POTS Peres (Neurology 2001) reported high rates of FMS in transformed (chronic) migraine patients 1 Waylonis and Heck, Am J Phys Med Rehab 1992

Migraine and Fibromyalgia (FMS) Peres (Curr Neurol Neuroscience Rep 2003), and Centonze (Neurol Sci 2004) suggest episodic migraine, chronic daily headache and FMS are continuum of same disorder. Arguments based upon theories of central sensitisation Patients with FMS show increased sensitivity to mechanical, thermal and electrical stimuli, with abnormal central pain mechanisms and augmented pain experience.

Medication overuse and other bodily pains Overuse of painkillers is a risk factor for developing chronic neck and back pain1. The study of 51,383 patients concluded: “Overuse of analgesics strongly predicts chronic pain and chronic pain associated with analgesic overuse 11 years later, especially among those with chronic migraine” Reports of refractory neck and/or back pain in patients with migraine – same or improved following AAM withdrawal 1 Zwart et al, Head Hunt study, 2003

Migraine and Fibromyalgia (FMS) De Tommaso et al (Cephalalgia 2008) FMS in 36% of patients with primary headache Those with comorbid FMS had: Highest level of migraine severity Poor sleep quality Headache severity heightened intensity of diffuse pain and fatigue Pamuk and Cakir (Clin Exp Rheumatol 2005) Increased FMS symptoms with menses (pain / fatigue) Increased prevalence of FMS starting at menopause

FMS pathophysiology Abnormal CNS function1 Supraspinal central sensitization fMRI – cortical and subcortical augmentation of pain processing Evidence for role of autonomic nervous system Best treatments = antidepressant and anticonvulsant medications. NB One small trial of beta blockers suggested possible effect 1Thimineur and De Ridder, Pain Medicine 2007

Migraine and Restless Legs (RLS)

Chronic Migraine and RLS / PLM [Personal view] Recognised in my clinic as major factor in CM (> 7 yrs) Commonly comorbid with chronic migraine and caffeine/medication overuse (approx 80%) Also provoked by caffeine and painkillers Disappears after full detox in approx 80% Frequently see CM in those that present with RLS Disrupts normal sleep architecture and leads to sleep deprivation Wake unrefreshed Frequent wakening and dreaming Diurnal variation of RLS symptoms (worst towards evening) PLMS often not obvious ? Caused by or provokes migraine

Migraine and RLS If disappears with detox, typically returns in acute episodic migraine attacks If persists after detox, worth treating before adding migraine preventative Pregabilin / Gabapentin – restore normal sleep architecture Sinemet CR – beware augmentation – ? less likely if Rx breaks every 6/12 Dopamine agonist (beware impulse control disorder and counsel patient) High remission rate with Rx Beware RLS / PLM provoked by tricyclic antidepressants and SSRI drugs – cause poor sleep architecture Full and prolonged replacement of iron if Ferritin <50ng/ml Replace B12 / folate and exclude renal impairment

Restless Legs Syndrome “Wherefore to some, when abed they betake themselves to sleep, presently in the arms and legs, leapings and contractions of the tendons, and so great a restlessness and tossing of their members ensue, that if the diseased are no more able to sleep, than if they were in the place of the greatest torture” Sir Thomas Willis, 1672

A medical condition? On Hypochondria: Virtue’s Household Physician, a twentieth century medica: “The skin will twitch in different parts, or feel numb, or have the sensation of spiders crawling on it” ? Associations with migraine: “bright sparks are seen before the eyes…..at one time the 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 small. The smell becomes perverted; the hypochondriac will smell odors where there are none,,,,the persons are subject to fainting turns…..they are irritable, fretful, peevish and fickle” “Eminent Authorities Consulted” included Frances Dercum, William Gowers, F Savary Pearce, Ludwig Hirt, Charles L Dana, early 1920’s

RLS 1800’s “Anxietas Tibiarum” sign of hysteria and/or neurosis 1944 Ekbom “Asthenia Crurum Paraesthetic” (irritable legs) Acta Med Scand Published observational review of 34 cases Characterised salient features: Diurnal pattern of lower extremity paraesthesia coupled with compulsion to move, worsening with rest and alleviated by movement NB not same as Ekbom’s syndrome referring to delusional parasitosis, same Ekbom though!

RLS - Diagnosis 4 essential criteria An urge to move the legs, usually accompanied by uncomfortable / unpleasant sensations / paraesthesiae Onset or worsening of symptoms at rest, not associated with any specific body position Rapid relief by movement such as walking or stretching Marked diurnal / circadian pattern, worse in the evening or night. Note that patient may however wake in am with painful legs that disappears on getting up and moving

RLS Ekbom Considerable clinical morbidity No objective evidence of neurological abnormality Common – 5% of population Often family history Noted associations with Pregnancy Iron deficiency anaemia Blood donors Carcinoma

RLS and sleep RLS is a major cause of insomnia Reduced time asleep Frequent wakening Fragmentation of normal sleep architecture

RLS – clinical features Characterised by unpleasant, deep within lower legs, most commonly distal to knees May note sensations in thighs, feet, arms If occur in arms, usually less severe there Most commonly bilateral May be unilateral Only experienced after rest Almost irresistible urge to move legs or stretch May need to walk around to get relief Most severe in late evening (diurnal) May complain of true pain / dull ache

RLS - descriptions Creeping Crawling Itching Burning Searing Tugging Drawing Aching Electric current Want to take legs off

Supportive clinical features Family history 60-80% of cases are familial autonomic dominant with variable penetrance Response to dopaminergic Rx PLMW or PLMS

Secondary causes and associations Iron deficiency Reduced ferritin, often normal Hb Rx if ferritin less than 50ng/ml – prolonged course Pregnancy - especially last trimester / ferritin < 50ng/ml Blood donation Renal failure - effective Rx with IV Fe Fibromyalgia Migraine Depression Rheumatoid arthritis B12 / folic acid deficiency (occasional) Parkinsons disease, essential tremor

Restless Legs and Migraine 17% of migraine vs 5% of controls had RLS1 RLS reported in 22% migraine subjects vs 8% of controls2 > 60% of RLS patients affected by MOH Increased dopaminergic premonitory features in those with comorbid RLS3 RLS and PLMS recognised to be also associated with fibromyalgia4 Caffeine is “the major aetiological factor in the causation of restless legs syndrome”5 1 Rhode et al. Cephalalgia 2007;27(11)1255-60 2 d’Onofrio et al. Neurol Sci 2008 May;29 Suppl1:S169-172 3 Cologno et al. Neurol Sci 2008 May; 29 Suppl 1: S166-168 4 Yunus and Aldaq. BMJ 1996. May 25;312(7042):1339 5 Lutz. J Clin Psychiatry 1978;39(9)693-8

Periodic Limb Movements and migraine Reported in association with migraine1 Other sleep disorders associated with migraine include2 OSA Insomnia Restless Legs Circadian rhythm disorder Hypersomnia 1 Bokkala et al. Pediatr Neurol. 2008 Jul;39(1):33-9 2 Rains and Poceta. Headache. 2006 Oct;46(9):1344-63

Migraine and Dizziness

Migraine-related dizziness [Personal view] Migraine-related disequilibrium [commonest] Lightheaded Dissociation - depersonalisation / derealisation Hot, sweaty, flushed Blurred, dim, or spotty vision Mute and buzzy hearing +/- secondary panic +/- situation-specific – hot, bright, noisy, crowded Migraine vertigo Visual vertigo Unexplained veering

Migraine-related dizziness 0.89% of population has migraine vertigo Total 1 year prevalence of vertigo = 4.9% Prevalence of BPPV = 1.6% 1 Motion sickness may be treated effectively with Rizatriptan in migraineurs with migraine vertigo2 NB Motion sickness often associated with stimulus sensitivity to noise, light and smell Migraine vertigo presents usually as attacks of spontaneous or positional vertigo lasting seconds to days and usually with accompanying migrainous symptoms2 Treat with standard approaches for chronic migraine – lifestyle, preventative (topiramate, beta blocker, flunarizine, etc,) 1 Neuhauser. Current Opin Neurol 2007 2 Eggers. Curr Neurol Neurosci Rep 2006

FMS and neurotologic symptoms Fibromyalgia (FMS) (Bayazit et al, 2002) 50% otologic symptoms, predominant dizziness Rosenhall et al (1996) Vertigo / dizziness in 72% Auditory evoked potentials suggested brainstem dysfunction

Considering Migraine in Differential Diagnosis “The Chameleon in the Neurology Clinic” Dizziness and Vertigo Blackouts / Syncope Sensory disturbance Fatigue Insomnia Panic Attacks (+/- panic) Depression / anxiety Chronic Pain Neck pain / Brachalgia Facial pain “Fibromyalgia” ? MS ? Epilepsy ? NEAD ? TIA ? Stroke Chronic Fatigue Syndrome “ME” ? Conversion disorder Dementia Psychosis

Approaches to successful management of chronic migraine

Selling the concept Behaviour modification

Chronic Migraine - Rx Acute abrupt withdrawal The “foundation” No painkillers No caffeine Good fluids Regular meals Regular sleep Acute abrupt withdrawal All acute attack medication (long term) triptans, analgesics, NSAIDS All caffeine Warn headaches typically worsen+++ for 5-7 days Lifestyle – sleep, hydration, meals Rx Restless Legs / Periodic Limb Movements if persist after detox (disappear in most patients) After withdrawal, add “preventative” for 1 year Beta blocker (eg propranalol) AED (eg valproate, topiramate, gabapentin Tricyclic antidepressant Change preventative if no response at 4/12 Aim for maximum “tolerated” dose – reduce if persistent sedation

Migraine Preventatives Reasons for failure Ineffective Acute attack drugs still used Caffeine Not used to high enough dose Aim for “maximum tolerated dose” Used at too high dose Often ineffective if patient persistently sedated Fatigue with migraine distinguished by pre-existing before drug started or absence of fatigue on headache-free day Not used for long enough, i.e. 4 months at top level reached Underlying sleep disorder – RLS, PLM, OSA

Chronic Migraine Preventatives

Evidence Poor evidence for many traditionally used preventative drugs Best evidence for topiramate and propranalol Licensing varies between countries Poor evidence for any individual approaches to Rx for migraine variants Much anecdotal “advice”

Rationale in Clinical Situations Poor sleep – insomnia, RLS, PLMS, wake unrefreshed Gabapentin to 900-1200mg tds, Pregabilin to 300-400mg bd AVOID tricyclics and SSRI drugs Obesity, weight gain on preventatives Topiramate Eating disorder Use most weight-neutral drugs Pregnancy / planning pregnancy Avoid all preventatives if possible Consider GON Block If necessary, amitryptilline or propranalol Females of reproductive age Avoid Sodium Valproate and other anticonvulsants if possible Counsel all patients who intend to use anticonvulsants to take good contraceptive measures, take regular folate 5mg, and beware induction of OCP (eg topiramate) Major Depression Consider avoiding beta blockers Agitated psychiatric state and/or suicidal ideation Consider short term olanzepine Severe migraine vertigo – short term help Consider olanzepine short term Severe anxiety or hypertension Consider beta blocker Hemiplegic Migraine Consider topiramate, acetazolamide Flunarizine Migraine vertigo Consider topiramate, flunarizine Comorbid diabetes or OSA topiramate

Summary Chronic Migraine accounts for more than 90% of referrals to a specialist headache clinic It is frequently misdiagnosed in hospital and primary care Chronic migraine may present with features other than headache Always consider sleep disorders in your history It is highly worthwhile taking full migraine history in patients presenting with unexplained neurological symptoms It is worth treating chronic migraine with lifestyle strategies, attention to sleep quality / disorder, and rational approach to drug use and preventative strategies, even if headache is not a main presentation Copies of slides: anne.mccann@thewaltoncentre.nhs.uk Patient info sheets - http://www.thewaltoncentre.nhs.uk/patients-and-visitors/patient-leaflets.asp#

Appendix Alice in Wonderland syndrome Migraine postdromal features Migraine Variants (basilar migraine, FHM, ophthalmoplegic migraine etc) Fatigue PLMS Medication and caffeine overuse Walton Centre Audit of non headache symptoms of migraine Guides for detoxification

Alice in Wonderland Syndrome Lippman 1952: Certain Hallucinations peculiar to Migraine 1 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 left. Syndrome named by Todd, 1955, in relation to migraine and epilepsy: Characterised by body schema disturbances and facultative symptoms, including depersonalisation, derealisation, visual illusions and illusory alterations in the passage of time Bizarre visual illusions and spatial distortions Macropsia – world appears larger than normal / subject appears smaller Micropsia – opposite of macropsia Metamorphosia - sensation of formed body distortions Zoom vision (e.g. teleopsia) Sense of time speeding up or slowing down More commonly reported in children Often before the headache Also reported with infectious mononucleosis, epilepsy, and drugs

Migraine Variants Migraine variant or migraine equivalent are terms applied to migraine exhibiting itself predominantly in form other than head pain Characterized by paroxysmal episodes of prolonged visual auras, atypical sensory, motor or visual aura, confusion, dysarthria, focal neurological deficits, gastrointestinal symptoms, other constitutional symptoms with or without headache Many migraine variants recognised in IHS IHCD-II, including: hemiplegic migraine basilar migraine childhood periodic syndromes retinal migraine complicated migraine ophthalmoplegic migraine

Migraine Variants Basilar Migraine Ophthalmoplegic Migraine Hemiplegic Migraine Episodic ataxia Vertiginous Migraine Alternating Hemiplegia of Childhood Cyclical Vomiting Syndrome Confusional Migraine Abdominal Migraine Benign paroxysmal vertigo of childhood Retinal migraine Migraine infarction ? Migraine-triggered seizures (Migralepsy)

Migraine Variants Basilar Migraine Aura usually < 1 hour, headache typically follows Typical hemianopia expands to all visual fields, sometimes temporary blindness Many neurological features are bilateral Visual deficit typically followed by one or more of: Vertigo Tinnitus Decreased hearing Diplopia Ataxia Bilateral paraesthesiae, weakness Impaired cognition confusion

Migraine Variants Confusional Migraine Boys > girls Usually in children Aura Headache (may be insignificant) Confusion Inattention Distractibility Difficulty maintaining speech / activities Sedation Agitation / violent behaviour Usually relieved by sleep

Migraine Variants Ophthalmoplegic Migraine At least 2 attacks with ocular palsy Typically IIIrd nerve with dilated pupil and unilateral eye pain IV and VI palsy (occasional) Ophthalmoplegia – hours to months Differential diagnosis includes Tolosa-Hunt Aneurysm Cavernous sinus / middle cranial fossa lesion Sphenoid sinusitis Lyme, syphilis, coccidiomycosis, HIV Sarcoid, Leukaemia, CNS inflammatory disorder Needs intensive investigation MRI+Gd and MRA DSA LP Bloods

Migraine Variants Hemiplegic Migraine Sporadic or Familial Often starts in childhood Attacks frequently precipitated by minor head injury Change in conscious level often seen (confusion to coma) Differential diagnosis includes Focal seizure Stroke MELAS Homocystinuria FHM Autosomal Dominant with variable penetration Includes episodes with or without motor aura Episodes Days to weeks May include reduced conscious level (confusion to coma), fever, meningism May occur without headache 20% of families have patients who develop fixed cerebellar deficits (linked to Chr 19, eg CACNA1A) Other gene mutations also recognised (eg on Chr 1, ATP1A2 gene mutations)

Migraine Variants Episodic Ataxia type 2 Autosomal dominant Paroxysmal ataxia Provocation: Physical, emotional stress, alcohol, caffeine Interictal nystagmus Responds to acetazolamide Chr 19 (CACNA1A)

Migraine Variants Vertiginous Migraine Vertigo present in approx 1/3 of migraineurs Recurrent vertigo episodes with or without other migraine features, e.g. Prodromal symptoms Nausea Stimulus sensitivity to noise, light, smell Autonomic disturbance, etc.

Migraine Variants Retinal Migraine Not uncommon cause of transient monocular blindness in young adults Recurrent attacks of unilateral visual disturbance / loss with minimal or no headache Gradual enlarging scotoma enlarging to total monocular visual loss ? Due to transient vasospasm of choroidal or retinal arteries Need to exclude vascular (carotid) disease and other ocular conditions

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.     3. I am easily fatigued.     4. Fatigue interferes with my physical functioning.     5. Fatigue causes frequent problems for me.     6. My fatigue prevents sustained physical functioning.     7. Fatigue interferes with carrying out certain duties and responsibilities.     8. Fatigue is among my three most disabling symptoms.     9. Fatigue interferes with my work, family, or social life.

MOH - How much is overuse? Limitations of IHS guidance Dietary caffeine not included as component of overuse in IHS guidance Increased caffeine consumption has been associated with increased risk of developing chronic daily headache1 Literature on detoxification from AAM does not take account of dietary caffeine How much is overuse according to IHS2? Simple analgesics > 15 days per month Triptans or combination analgesics3 > 10 days per month Opioids or ergotamine > 10 days per month ? Depends on individual pharmacogenetics 1 Sholz et al, 1988 2 Mathew et al, 1990, Diamond and Dalessio 1982, Mathew 1990, Saper 1987, Wilkinson 1988, 3 i.e. with caffeine

How much is overuse? All types of analgesic and acute attack medications reported to be associated with MOH Paracetamol, NSAIDS, Opioids All known triptans Ergotamine Rebound headache may occur acutely in single attack stopping AAM = recognised use in first line Rx of status migrainosus: Stop acute attack drugs Rehydration Treatment of nausea and vomiting (+/- later IV steroid, neuroleptic, IV dihydroergotamine) Anecdotally, patients who stop using analgesics or triptans often report shorter attacks of acute migraine following detox

Clinical Features of rebound headache Analgesic rebound headache - No placebo-controlled trials Caffeine rebound headache: stopping low dose caffeine frequently results in withdrawal headache1 Double blind placebo-controlled short-term caffeine withdrawal study N = 64, subjects with low to moderate caffeine intake 32 – placebo; 32 – continued caffeine 50% of those given placebo had headache by day 2 6% of those continuing caffeine had headache by day 2 Nausea, depression, flu-like symptoms common in placebo (detox) group Does not indicate long term consequences of detoxification 1 Silverman et al 1992

Caffeine Overuse Not “proven”, but long recognised to cause headaches, especially on withdrawal Caffeine regarded as acute attack medication Often in combined analgesics Mild headaches (e.g. regarded as TTH) almost always disappear with complete elimination of acute medication and caffeine Caffeine withdrawal - first line for treatment-resistant depression

Caffeine content in drinks 12 oz drink mg Red Bull (8oz) 80 Lucozade 46 Diet coke 46 Dr Pepper 41 Pepsi 38 Diet pepsi 36 Coca cola 34 8 oz drink mg Coffee 70-135 Tea 40-60 Cocoa 14 Decaf coffee 2-3 Horlicks, sprite etc are caffeine free

Walton Centre Audit on Non-headache manifestations of migraine

Retrospective review of 50 consecutive patients at WCNN with chronic migraine

Retrospective review of 50 consecutive patients at WCNN with chronic migraine

Appendix Migraine treatment & preventatives

Approach to successful treatment of chronic migraine The withdrawal: Warn of possible severe worsening for 1-2 weeks Worsening is a good sign and usually heralds reverse to acute migraine Admit for in-patient detoxification if elderly, diabetes, severe triptan or opioid overuse, severe depression and/or suicidal ideation May assist withdrawal with: Fluids (+/- IV) Oral / rectal domperidone up to 120mg per day 5/7 - Naproxen 500mg 8am + 4pm Clonidine (if opiates ++) 5/7 - IM Chlorpromazine @ 10pm IV Dihydroergotamine Steroids Combined pain syndromes: Advise that other pains often eventually improve off painkillers (especially neck and back), due to cessation of central sensitisation Consider other measures for other pains: Back pain – Pilates, Extensor stretch exercises, swimming, pain clinic – epidurals etc Neck Pain – usually improves ++ Arthritis – glucosamine, large joint revision etc.

Preventative Drugs for Migraine Licensed Unlicensed Beta Blockers* Propranalol (best evidence for use) Timolol, Metoprolol Antiepileptic Drugs (AED) Topiramate*** Others Clonidine (antihistamine and serotonin antagonist) – of no proven efficacy (BNF states “Clonidine is not recommended and may aggravate depression and cause insomnia”) Pizotifen - evidence for effectiveness is poor; adverse effects severely limit use Methysergide*** – considered very effective but concerns about about ergot side effects (retroperitoneal fibrosis etc) Beta Blockers Atenolol (not licensed, but commonly used) Nadolol Tricyclic antidepressants** Amitriptyline (best studied) Dosulepin (commonly used; potentially better tolerated – beware cardiac arrhythmias) Nortryptilline (often better tolerated) Antiepileptic Drugs (AED) Sodium Valproate** Gabapentin (limited evidence of efficacy – 1 study) Zonisamide Neuroleptics Olanzepine amisulpiride Calcium Antagonists Verapamil Flunarizine SSRI’s, Venlafaxine, Levetiracetam, Tizanidine, ACE II antagonists Alternative Butterbur, coenzyme Q10, riboflavin, feverfew * Partial agonists unhelpful; ideal beta blocker is hydrophilic and cardioselective ** Unlicensed, but recommended for use in BNF! *** Hospital Supervision or Specialist Introduction only

First Line Second Line Third Line Refractory cases Alternative agents Nortryptilline / Amitryptilline / Dosulepin Propranalol (Inderal LA) Second Line Epilim Chrono Topiramate Third Line Gabapentin (first line if sleep disorder) Paroxetine Refractory cases Flunarizine Olanzepine Methysergide Botulinum toxin GON Block / GON stimulator Alternative agents Pizotifen Lisinopril, Candesartan Clonidine Lamotrigine, verapamil, carbamazepine Butterbur, coenzyme Q10, riboflavin, feverfew

First Line Second Line Dosulepin Propranalol (Inderal LA) 25mg 7-8pm, increase 25mg each 2/52, aim 1mg/kg or maximum tolerated dose; reduce dose if persistent side effects other than dry mouth Consider ECG Beware, may exacerbate restless legs syndrome and poor sleep and be counterproductive Propranalol (Inderal LA) 80mg, increase 160-240mg Avoid if severe depression Second Line Epilim Chrono 200mg, increase 200mg / week, aim 400-800mg bd + Folic acid and contraception if young female Warn – side effects: weight gain, hair loss, tremor (10%), polycystic ovaries Beware teratogenic++ (learning disabilities etc) Topiramate 25mg, increase each week 25mg, aim 50-150mg bd 20% - cognitive side-effects or reduced speech – must stop Approx 10% - severe mood disorder (depressed / agitated / aggressive / suicidal) must stop Tingling at higher doses (usually settles). Risk of renal calculi, acute glaucoma (if myopic) Drink > 3 Litres per day Occasional hair loss Beware induces POP and COCP Beware teratogenic

Third Line Gabapentin Paroxetine Some evidence of benefit Well tolerated in most Useful if comorbid restless legs my first line if RLS persists after detox 600-1200mg tds Paroxetine SSRI’s not likely to be as useful as tricyclic antidepressants 10mg, increase 20mg after 1 week Warn side-effects (dizzy, nausea, drowsy) typically last only 2/52 May exacerbate poor sleep

Refractory cases Flunarizine Olanzepine Methysergide Off licence calcium antagonist Licensed in some European countries where may be one of first line drugs Anecdotal benefits in prolonged aura and migraine-related dizziness Useful in refractory patients Beware tardive (extrapyramidal) side effects, weight gain and severe depression Olanzepine Very helpful in emergency situations very resistant cases (in specialist clinics only) Short term for important time Beware weight gain, diabetes and tardive movement disorder Methysergide Good anecdotal evidence Useful for refractory cases Safe if <12mg daily dose, drug holidays (1 month off every 5 months) Monitor U+E, FBC, ESR, CXR (6 monthly) and echocardiograms yearly

Alternative agents Pizotifen Lisinopril, Candesartan Clonidine Very poorly tolerated – weight gain and sedation If tolerated, works reasonably Rarely used in headache clinics Lisinopril, Candesartan Small evidence, small effect Clonidine Licensed, but never been studied Lamotrigine, verapamil, carbamazepine Unlikely to work as migraine preventatives Alternative drugs – butterbur, coenzyme Q10, riboflavin, feverfew Small studies, some evidence Lack of systematic safety data Inconsistency of preparations (espec butterbur)

Alternative treatments Greater Occipital Nerve (GON) Blocks Not proven Appear very effective for <3-4/12 in approx 40-50% Useful as stopgap strategy IV Dihydroergotamine Botulinum toxin ? Role in chronic migraine (ineffective in acute migraine) Studies have blinding issues Occipital Nerve Stimulation Experimental Anecdotal benefit in number of primary headache disorders including migraine, cluster headache, SUNCT and hemicrania continua

Migraine Preventatives Reasons for failure Ineffective Acute attack drugs still used Caffeine Not used to high enough dose Aim for “maximum tolerated dose” Used at too high dose Often ineffective if patient persistently sedated Fatigue with migraine distinguished by pre-existing before drug started or absence of fatigue on headache-free day Not used for long enough, i.e. 4 months at top level reached Underlying sleep disorder – RLS, PLM, OSA