MIGRAINE

Nin BajajNeurologist, Nottingham University Hospitals,Clinical Lead Neurology Derby Hospitals NHS Foundation Trust.

Migraine

• Isn’t just headache

• Aura + headache

• You can have aura + no headache

• Headache and no aura

• Aura with headache

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

• 3rd 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

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;

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

Migraine- CSD

• CSD appears to trigger vasodilatation of meningeal blood vessels

• This in turn triggers pial nociceptive input to the trigeminal nucleus

Migraine- mechanisms and concepts

• Allodynia in CM

• Central or peripheral sensitisation

• Cross over with CPS

• Cross over with CFS

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)

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

Migraine

• Visual- the commonest in younger patients, lights, colours, shapes, fortification spectra, scotomata, simple blurring

• Speech- slurring, reduced verbal fluency, word finding problems

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

Migraine

• Work-up

• MRI- exclude demyelination, vascular aetiology

• DDx over the years-

• Acoustic neuroma in vertebrobasilar migraine

• 2x pituitary tumours

• 2x MS patients

Migraine

• Treatment strategies

• EM- triptans, high dose aspirin

• Offer prophylaxis at 4-5 headache days/month

• CM- topiramate, zonisamide, amitriptyline, lamotrigine