David Kernick Exeter Headache Clinic

Two default diagnoses < 50 years Migraine

>50 years Temporal arteritis Systemically unwell Tender artery with allodynia CRP better than ESR Problem with skip lesions

History and examination (Primary care perspective) Headache is in the history Examination In theory: For diagnosis To reassure the patient To keep out of the law courts

History and examination (Primary care perspective) Examination in reality: To keep out of the law courts To reassure the patient For diagnosis BP, Fundoscopy Giles Elrington 3 minute neurol examination

6 month non specific headache Buzzing in ears

What other ocular test?

Pain extra-cranial. Innervation of head

Pain Intracranial - Innervation of dura

Dura stretched, compressed or inflamed CSF – 20 mls/hr, 150 mls capacity

Pain - cervicogenic

45 year old male 3 months continuous background headache generalised Not postural Featureless No medication Family history

IHS Headache classification Primary Secondary Traumatic Vascular Non-vascular (SOL) Substance induced Infection Disturbed homoestasis Facial structures Migraine Tension type Autonomic cephalalgias (cluster)

Headache impact Adults Children Community Primary Care Secondary care 20% have impact 50% visit GP Primary Care 4.4% consultations 3% referred Secondary care 30% of consultations >50% investigated Adults Community 20% have impact 10% visit GP Primary Care 0.6% consultations 25% referred Secondary care ? Children Kernick 2009, Latinovic 2006

University new entrants Kernick 2002 1124 consecutive students Headache that impacted on life 21% 13% > 15 days of the month 45% seen a GP <5% prescribed medications for headache

What do patients have when they present to A and E with headache What do patients have when they present to A and E with headache? Valade 2000 Migraine 55% 80% TTH 25% Cluster 7% Trauma 1.6% Trig Neuralgia 1.6% Sinusitis 1.6% Vascular disorders 1.2% Low Pressure 1.2% Meningitis 0.35% Tumour 0.17% Other Misc < 5%

29 year old male Thunderclap headache CT, LP normal Headache easing after 3 months Has coital headache X 2 in past year GP increased sertraline 4 months ago Heavy cannabis user

Reversible vasoconstriction syndrome

Thunderclap Headache

Cerebral venous sinus thrombosis – any phenotype

Cluster treatment Injectable Sumatriptan Short term steroids Oxygen 100%

Central sensitivity (movement, light, sound, touch) Cluster Migraine Peri-orbital Unilateral. Any part of head Uni or bi-lateral Attack 15 minutes- 2 hours. 4-72 hours Biochronicity - Autonomic features Central sensitivity (movement, light, sound, touch) Active ++ Inactive Aura 30%

Annual Migraine incidence

Some problems Migraine – a complex biopsychosocial disease No clinical markers Mechanisms poorly understood Doesn’t come alone – epilepsy, anxiety, depression, asthma, IBS, fibromyalgia Stigmatised

Implications for gastric stasis and neck pain

Migraine generator – gastric and cervical implications Central and peripheral sensitisation Activation trigeminal nerve Peripheral inflammation Cortical depolarisation and vasoconstriction Classifying headache 2

Migraine: A Featureful Headache Cady, p 206, C1 Par 2 L 1-12 Cady, p 206, C2 Par 2 L 1-4 Premonitory Mood changes Fatigue Cognitive changes Muscle pain Food craving Fully reversible Neurological changes: Visual somatosensory Aura Dull headache Nasal congestion Muscle pain Early Headache Unilateral Throbbing Nausea Photophobia Phonophobia Osmophobia Advanced Headache Fatigue Cognitive changes Muscle pain Postdrome Cady, p 206, C2 Par 3 L 4-6 Cady, p 207, C1 Par 1 L 1-11 Linde, p 71, C2 Par 1 L 4-9 Linde, p 74, C1 Par 3 L 1-15 Key point: Migraine is manifested clinically as a constellation of symptoms that evolve through the various phases of a migraine attack; clinical experience indicates that symptoms typically associated with each phase of an attack often recur during other phases of the attack, resulting in a continuum of symptoms, rather than a succession of distinct phases. CLINICAL PHASES OF MIGRAINE1 A migraine attack can take days to develop and resolve; headache is only 1 of several symptoms associated with migraine.1 Although the symptoms of migraine often overlap, the classic view is to separate an attack into phases.1 The Premonitory Phase1 Seventy percent of patients suffering from migraine with or without aura experience premonitory symptoms.1 Premonitory symptoms are often seen as predictors of the headache attack. 1 Mood alterations, muscle pain, food cravings, cognitive changes, fluid retention, and yawning are common premonitory symptoms.1 Eighty-three percent of subjects with premonitory symptoms could predict over 50% of their attacks.1 The Aura Phase 1 An aura involves focal, reversible neurologic symptoms that often precede the headache.1 Aura symptoms are believed to arise from an electrical disturbance called cortical spreading depression (CSD); it occurs in approximately was 15-32% of migraine attacks.1,2,3 Auras are not always followed by headache pain; such auras are called acephalgic migraine or migraine aura without headache.1 The Headache Phase1 The headache phase is subdivided according to headache pain intensity into an early phase and an advanced phase.1 Early headache: mild pain without the associated symptoms of migraine1 Advanced headache: moderate to severe pain with the associated symptoms of nausea, photophobia, phonophobia, or disability; used to confirm a migraine diagnosis1 Postdrome1 Phase of migraine-associated symptoms beyond the resolution of the headache; often entails significant disability that can last for 1 or 2 days.1 R1, p 206, C1, Par 1, L 1-14 Preheadache Mild Moderate Severe Post headache Time R1, p 206, C1, Par 2, L 1-12 and C2, Par 1, L 1-9 Headache R1, p 206, C2, Par 2, L 1-13 R2, p5, para3, L1-2 R3, p222-3, last para-cont, L11-12 R1, p 206, C2, Par 3, L 1-7 and p 207, C1, Par 1 and Par 2 R1, p 207, C1, Par 3, L 1-4 30 References: Cady R, Schreiber C, Farmer K, Sheftell F. Primary headaches: a convergence hypothesis. Headache. 2002;42(3):204–216 Launer LJ, Terwindt GM, Ferrari MD. The prevalence and characteristics of migraine in a population-based cohort: the GEM study. Neurology. 1999; 53(3): 537—542. 3. Rasmussen BK, Olesen J. Migraine with aura and migraine without aura: an epidemiological study. Cephalalgia.1992;12(4):221-228 .

Migraine Acute treatment Paracetamol, Aspirin, Prokinetic (Domperidone/metochlorpropramide). Triptan Not opiates

30 year old Migraine with aura GP given Sumatriptan 50mg Not effective

Problems Gastric stasis Change formulation (nasal, (wafer), inj) Takes too late or in aura phase Change the Triptan (failure not a class effect) Medication overuse headache

Medication overuse Headache 3% of population Analgesics > 15 days of month Triptans > 10 days of month

Medication overuse headache Withdrawal of all analgesia Increased frequency of headache, associated with increased frequency of analgesia use. Return of episodic headache Daily headache with spikes of more severe pain Headache intensity Migraine attacks Frequent ‘daily’ headaches 35

Migraine with aura taking Sumatriptan 100mg Which cause you concern? On Loestrin 20 Age 69 Past history TIA Started SSRI

Loestin 20 Absolute risk of stroke Bejot 2016

Stroke relative risks Schurks 09 MA 2.2 (1.5-3.0) > MwA 1.2 (0.9-1.7) Female>male: 2.08 (1.13-3.84) > 1.37 (0.09-2.11) Under 45>over 45: 3.65 (2.21-6.04)

Incidence MI/100,000 Cheng-Han 14

Myocardial infact Sacco 2009 Meta analysis 15 studies All migraine RR 1.33 (1.08-1.64) MA (n-1) 1.71 (1.16-2.53)

Possible mechanisms Endothelial dysfunction Platelet dysfunction Mitochondrial dysfunction Patent foramen ovale

The white matter story

The white matter story Krutz 2004, Swartz 2004, Xie 2018 Nature of lesions unclear (? Microvascular) Increase with age Associated with posterior circulation infarcts (? More vunerable) Female>male Migraine>non-migraine Aura>without aura Related to migraine frequency

Preventative Medications in Migraine Cupboard 1 Propranolol Amitriptyline Topiramate

CGRP monoclonals Eptinezumab Alder IV Erenumab1 AIMOVIG Novartis SC Galcanezumab2 EMAGALITY Lily Fremenezumab3 AJOVY Teva EU Approval 1 =July 18 2= Nov 18 3 = Likely April 19

Chronic Migraine CGRP v Current Therapies

Needles – occipital nerve injection

BOTOX® for Chronic Migraine Needles - Botox BOTOX® for Chronic Migraine UK licence for Chronic Migraine, NICE approved ≥15 days headache of which ≥8 days are migraine Rejected by SMC (2011 and 2013) Starting to be used in patients where most other treatments have failed Mean change in frequency of headache days from baseline (days/28-day period) 52 48 44 40 36 32 28 24 16 12 8 4 Study week 20 56 -2 -4 -6 -8 -10 -12 -14 BOTOX® (n=688) Placebo (n=696) p=0.019 p=0.047 p=0.007 p=0.01 p=0.008 p<0.001 Double-blind phase: BOTOX® vs. placebo Open-label phase: All patients on BOTOX® p=0.011

Transcutaneous vagal nerve stimulation

Supra-orbital nerve stimulator

Exercise headache 35 yr female Migraine 1-2 each year Noticed headache on running Diagnosis?

Exercise headache Migraine 10% Sub arachnoid SOL AC malformation Primary exercise headache

Pressure too low

35 yr male Car shunt one week ago 3 days non specific headache Diagnosis?

Brain injury Direct neuronal damage Secondary damage due to vascular insult Inflammatory response and resolution

Post Traumatic Headache (Post Traumatic syndrome)

Predominant clinical feature Classification Current terms Time to onset Length of symptoms Insult Predominant clinical feature Pathophysiology Traumatic brain injury with immediate effects Acute traumatic brain injury Concussion Immediate Days Single episode of trauma Alterations in consciousness Direct axonal damage Traumatic brain injury with early effects Sub-acute traumatic brain injury Hours to days Weeks to months Headache (IHS < 7 days) Inappropriate inflammatory cascade Traumatic brain injury with late effects Chronic traumatic encephalopathy Years Multiple small traumas. E.g. boxing, heading of the football Cognitive dysfunction Pragmatic classification of traumatic brain injury with associated features

Brain tumour primary or secondary

Tumour diagnosis setting 65

Presentations New onset seizure has the highest positive predictive value of 1-2% Headache most common 23-56% of patients present with headache as their initial symptom

Red Flags Headache with: Abnormal neurological symptoms or signs New seizure Headache with exercise History of cancer elsewhere

Orange Flags Aggregated by Valsalva manoeuvre Headache with significant change in character Awakes from sleep New headache over 50 years Memory loss Personality change If a primary headache diagnosis has not emerged in an isolated headache after 8 weeks

Primary Brain Tumour Population investigated Risk of tumour All consultations with GP for headache 0.09% All consultations with GP where a diagnosis of migraine is made 0.045% All consultations with GP with special interest in headache with headache in intermediate care setting 0.6% All consultations with secondary care neurology with headache Casualty 0.8% 0.17% Primary Brain Tumour Population incidence 10/100,000 per year

Two default diagnoses < 50 years Migraine

>50 years Temporal arteritis Systemically unwell Tender artery with allodynia CRP better than ESR Problem with skip lesions

Primary Brain Tumour Population investigated Risk of tumour All consultations with GP for headache 0.09% All consultations with GP where a diagnosis of migraine is made 0.045% All consultations with GP with special interest in headache with headache in intermediate care setting 0.6% All consultations with secondary care neurology with headache Casualty 0.8% 0.17% Primary Brain Tumour Population incidence 10/100,000 per year