The Evolution of a Migraine Attack – A Review of Recent Evidence

Abstract

A migraine attack is an extraordinarily complex brain event that takes place over hours to days. This review focuses on recent human studies that shed light on the evolution of a migraine attack. It begins with a constellation of premonitory symptoms that are associated with activation of the hypothalamus and may involve the neurotransmitter dopamine. Even in the premonitory phase, patients experience sensitivity to sensory stimuli, indicating that central sensitization is a primary phenomenon. The migraine attack progresses to a phase that in some patients includes aura, which involves changes in cortical function, blood flow, and neurovascular coupling. The aura phase overlaps with the headache phase, which is associated with further changes in blood flow and function of the brainstem, thalamus, hypothalamus, and cortex. Serotonin receptors, nitric oxide, calcitonin gene-related peptide, pituitary adenylate cyclase-activating polypeptide, and prostanoids are demonstrated specific chemical mediators of migraine based on therapeutic and triggered migraine studies. A number of migraine symptoms persist beyond resolution of headache into a postdromal phase, accompanied by persistent blood flow changes in several brain regions. Although these phases of migraine have substantial temporal, neurochemical, and anatomical overlap, each represents an important window onto the pathophysiology of migraine as well as a target for therapeutic intervention. A comprehensive approach to migraine requires an understanding of the entire range of mechanisms and resultant symptoms that occur throughout the evolution of an attack. Key words: headache, positron emission tomography, magnetic resonance imaging, premonitory, aura, postdromeThe understanding of migraine pathophysiology continues to advance rapidly, bringing fresh opportunities for the development of novel acute and preventive therapies. It is convenient to describe the phases of a migraine attack (premonitory, aura, headache, postdrome) relative to the headache phase because headache is the most easily recognizable, stereotyped, and quantifiable feature of an attack. But for a significant number of patients, the other phases of a migraine attack can be more prolonged and even more disabling than headache. Growing evidence indicates that the phases of migraine do not occur in a discrete and linear fashion but rather reflect overlapping chemical, physiological, and anatomical mechanisms.

Reduced insula habituation associated with amplification of trigeminal brainstem input in migraine

“…Specifically, this region has been hypothesized to play an important role as a trigger of migraine attacks, particularly in patients who can sense oncoming attacks from altered arousal and fatigue (38). Moreover, increased excitation (or decreased inhibition) of the hypothalamus (39,40) has been reported to trigger migraine attacks, and significant hypothalamic activation has been observed during migraine episodes and maintained in the postictal state (41). Thus, amplification of sensory stimuli in the hypothalamus may produce alterations of autonomic and other homeostatic functions associated with oncoming attacks.…”

Mimics and chameleons in stroke

“…Typically, migraine aura is spreading rather than apoplectic in onset and there may be a prodromal phase prior to developing aura and headache, with patients reporting symptoms such as tiredness, irritability, nausea, yawning and difficulty concentrating. 17 However, migraine (particularly migraine with aura) itself is associated with a twofold increase in the relative risk of ischaemic stroke when patients with migraine were compared with non-migraineurs. 18 It is also recognised that headache can form part of ischaemic stroke symptomatology with data from an Israeli registry showing that 8.4% of 2001 patients with ischaemic stroke had headache at onset although this proportion was higher at 27% in an Austrian registry.…”

Migraine et contraception

“…La cé phalé e migraineuse serait la consé quence d'une inflammation provoqué e par l'activation des terminaisons nerveuses autour des vaisseaux mé ningé s. Il en ré sulterait une libé ration de neuropeptides vasoactifs comme le calcitonin gene-related peptide (CGRP) et la substance P, une dilatation des vaisseaux mé ningé s, une fuite de plasma dans les tissus environnants, un relargage dans les tissus environnants de substances « algogè nes » (induisant une sensation douloureuse en stimulant les fibres sensitives) et une excitation du nerf trijumeau (dont les fibres conduisent l'influx douloureux) [4]. L'é vé nement à l'origine de l'activation nerveuse produisant l'inflammation initiale reste à identifier : la production locale de nitric oxyde (NO) est une hypothè se en cours de recherche [5].…”

“…L'aura migraineuse correspond, quant à elle, à deux é vé nements neurologiques : la dé pression corticale envahissante, qui correspond à une hyperactivité neuronale fugace suivie d'une inactivation neuronale ; une hypoperfusion cé ré brale consé cutive à cette inactivation neuronale, qui se situe pré fé rentiellement dans les territoires cé ré braux posté rieurs et qui est probablement lié e à une vasoconstriction arté riolaire [4].…”