1. MIGRAINE Nin Bajaj Neurologist, Nottingham University Hospitals, Clinical Lead Neurology Derby Hospitals NHS Foundation Trust.

2. Migraine Isn’t just headache Aura + headache You can have aura + no headache Headache and no aura Aura with headache

3. Migraine- mechanisms Missense mutations in the gene encoding the 1A subunit of the P/Q type voltage-gated calcium channel are present for 55% of FHM how the FHM mutations influence cellular excitability is obscure mutations in CACNA1A are also associated with the episodic ataxia syndrome EA-2, the spinocerebellar ataxia syndrome SCA-6, and idiopathic generalized epilepsy The second FHM gene to be described was ATP1A2 encoding the α 2 subunit of Na/K ATPase Other allelic conditions include alternating hemiplegia of childhood, basilar type migraine, and migraine without aura 3 rd FHMgene is SCN1A encoding the pore-forming α1 subunit of neuronal voltage-gated sodium channel Nav1.1. Allelic conditions include generalized epilepsy with febrile seizures plus (GEFS) and severe myoclonic epilepsy of infancy Sporadic migraine- often a family history May well be a channelopathy

4. Migraine- mechanisms TMS experiments demonstrate increased cortical excitability in CM and EM Topiramate, a GABA agonist, reduces cortical excitability Brainstem PAG- Electrode stimulation or lesion in PAG can induce migraine; mutation of PAG Ca channels may facilitate trigeminal nociceptive transmission- leading to throbbing facial pain; PET studies show increased PAG, locus caeruleus and dorsal raphe blood flow in a migraine attack; high PAG tissue iron levels in CM may be a surrogate biomarker of increased PAG metabolic activity;

5. Migraine- aura and CSD Leao 1940. Repetitive electrical stimulation of cortex in animal models showed period of electrical inactivity- spreading at 3 mm/min- CSD Speed of propagation of visual (and sendory aura) in migraine same speed Proven by BOLD fMRI in occipital cortex in visual migraine aura

6. Migraine- CSD CSD appears to trigger vasodilatation of meningeal blood vessels This in turn triggers pial nociceptive input to the trigeminal nucleus

7. Migraine- mechanisms and concepts Allodynia in CM Central or peripheral sensitisation Cross over with CPS Cross over with CFS

8. Migraine 5 basic kinds of aura Sensory- tingling, can be painful, can be just at night, can get a dead arm, patchy, variable, frequent, good days and bad days, often cheiro-oral Motor- weakness of a limb or limbs, can be clumsiness (dropping things)

9. Migraine Vertebrobasilar- unsteady, like a boat, mal debarquement, sometimes vertigo, worse on head turning or bending, can cause syncope Migrainous syncope- frequent blackouts, headache occurs before or after, can be prolonged apparent LOC

10. Migraine Visual- the commonest in younger patients, lights, colours, shapes, fortification spectra, scotomata, simple blurring Speech- slurring, reduced verbal fluency, word finding problems

11. Migraine Episodic Migraine and Chronic Migraine Low frequency EM (<10 attacks/month) High frequency EM (10-14 attacks/month) CM- >15 attacks/month CM- stress, stress, stress; poor sleep pattern, pain-killers,triptans, menstrual, weight gain, snoring, depression, age

12. Migraine Work-up MRI- exclude demyelination, vascular aetiology DDx over the years- Acoustic neuroma in vertebrobasilar migraine 2x pituitary tumours 2x MS patients

13. Migraine Treatment strategies EM- triptans, high dose aspirin Offer prophylaxis at 4-5 headache days/month CM- topiramate, zonisamide, amitriptyline, lamotrigine