Investigation of Migraine-related Intracerebral White Matter Lesions

Abstract

Migraine is defined by the International Headache Society (IHS) as a recurrent primary headache disorder, usually unilateral and pulsatile in nature with moderate to severe pain, with attacks lasting for 4-72 hours, and may associate with aura, nausea, vertigo and autonomic symptoms in adulthood. Migraine is more common in adults (11%, lifetime 15%) than in children/adolescents (7%, lifetime 5%), with a decreasing prevalence (6%, lifetime 8%) in adults over the age of 60 years. In all categories, migraine is more prevalent in women than in men, with 14% vs 6% in adults, 9% vs 7% in children/adolescents and 8% vs 3% in the elderly. The trigemino-vascular system provides an important pain-transmission link between the vascular (dural and cortical) and neuronal (brainstem and thalamus) regions. Since the posterior and lateral regions of the hypothalamus is activated in the early premonitory phase of migraine, it is likely that the hypothalamus is a key organ in the initiation of migraine headache by activation of different brainstem structures. Cortical spreading depression (CSD) starts in the occipital cortex, and it is an appearance of depolarization waves of the neurons and neuroglia that propagate across the gray matter at a velocity of 2–5 mm/min. CSD is a dramatic failure of brain ion homeostasis, efflux of excitatory amino acids (e.g., glutamate) from nerve cells, and increased energy metabolism. CSD is present not just in aura patients, but in aura-free migraineurs, as well. CSD may activate the meningeal nociceptors of trigeminal sensory afferents, resulting in a release of vasoactive neuropeptides (CGRP, SP, NKA, PACAP, VIP). This process leads to the activation of the second-order neurons in the trigeminocervical complex, the third order neurons of the thalamus, and the fourth-order neurons in the sensory cortex (central sensitization). Blood flow is increased in the brainstem nuclei, called “migraine generators” (locus coeruleus, periaqueductal grey matter, raphe nuclei). Cranial parasympathetic fibres are activated in the superior salivatory nucleus in the brainstem. Postganglionic parasympathetic fibres project to the lacrimal, nasal mucosa and salivary glands, and the craniofacial vasculature, and induce lacrimation and rhinorrhoea. The descending pain modulatory pathway activity is decreased, and it may cause more intensive pain.