0840 Migraine update

Research into migraine has shown the condition to be associated with cardiovascular disease and two recent re-analyses have found that migraine with aura appears to be a risk factor for myocardial infarction, coronary revascularisation, angina, and death from ischaemic cardiovascular disease. Interestingly, patent foramen ovale is more common than expected in migraineurs with aura, although closure of the defect may not resolve the problem. There is also familial hemiplegic migraine (FHM), an autosomal dominant disorder associated with attacks of migraine with hemiparesis. FHM1 is due to a missense mutation which codes for a voltage-dependent calcium channel. FHM2 arises from a mutation in the α2 subunit of the Na/K pump. FHM3 is caused by a missense mutation in a neuronal voltage-gated Na+ channel. Functional analysis of the FHM mutations predicts enhanced neuronal excitation which results in excessive firing of neurons and could facilitate cortical spreading depression (CSD) which is probably the basis of the aura and is a short-lasting depolarization wave that moves across the cortex at a rate of 3–5 mm/min. A brief phase of excitation heralds the reaction which is immediately followed by prolonged nerve cell depression synchronously with a dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells and enhanced energy metabolism. Much has been done to challenge and refute the hypothesis that the migraine headache is related to vasodilatation. This obviously questions years of teaching that focused on vasoconstrictors to prevent the headache of migraine, and whereas the triptans were assumed to act by binding to serotonin receptors in cranial blood vessels (causing their constriction) and subsequent inhibition of pro-inflammatory neuropeptide release, evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels, and may decrease the release of several peptides including calcitonin gene-related peptide CGRP. Future therapy is likely to focus on antagonists to CGRP and other agents that interfere with CSD.

Read more:
Lancet 2008; 372: 1369-71
Circulation 2008; 117: 1397-1404
Brain 2008; 10: 2192-2200
Neurology 2008; 70: 1304-12