Migraine results from episodic changes in central nervous system physiologic function in hyperexcitable brain manifested by abnormal energy metabolism, lowered threshold for phosphene generation, and increased contingent negative variation. Human functional magnetic resonance imaging and magnetoencepholography data strongly suggest that
aura is caused by cortical spreading depression.
REVIEW SUMMARY: Brain hyperexcitability may be caused by low
magnesium levels, mitochondrial abnormalities with abnormal phosphorylation of
adenosine 5'-diphosphate, a dysfunction related to
nitric oxide, or
calcium channelopathy. Low
magnesium can result in opening of
calcium channels, increased intracellular
calcium,
glutamate release, and increased extracellular
potassium, which may in turn trigger cortical spreading depression.
Mitochondrial dysfunction has been suggested by a low
phosphocreatine:Pi ratio and a possible response by
migraine patients to
riboflavin prophylaxis. Nitroglycerine administration results in a delayed
migraine-like
headache in
migraine patients but not in control patients, and a nonspecific
nitric oxide synthase inhibitor aborted
migraine at 2 hours in the majority of tested
migraine patients compared to controls. Many patients with
familial hemiplegic migraine have a missense mutation in the P/Q
calcium channel, so that this form of
migraine, at least, is associated with a demonstrable
calcium channelopathy.
CONCLUSIONS: The generation of
migraine occurs centrally in the brain stem, sometimes preceded by cortical spreading depression and
aura. Activation of the trigeminovascular system stimulates perivascular trigeminal sensory afferent nerves with release of vasoactive
neuropeptides, resulting in vasodilation and transduction of central nociceptive information. There is then a relay of
pain impulses to central second- and third-order neurons and activation of brain stem autonomic nuclei to induce associated symptoms.