Functional MRI shows persistent activation and hyperoxia in the substantia nigra and red nucleus, implicated in nociception and autonomic dysfunction.10 The increased accumulation of iron in the antinociceptive network of migraineurs may have a role in chronification to CM or may be a physiologic response to repeated activation of nuclei involved in central pain processing.9 In recent years, community-based epidemiologic MRI studies of patients with migraine have helped to elucidate these issues,

particularly those conducted in the Netherlands. In a population-based study in Reykjavik, PD0325901 Iceland, migraineurs (n = 4689; 57% women) were followed from 1967, examined, and interviewed about migraine symptoms 25 to 30 years later (mean age, 51 years; range, 33 to 65 years).11 At about 10 years, participants reporting one or more headaches per month were asked about nausea, unilateral location, photophobia, visual disturbance, and numbness.

Then, between 2002 and 2006, high-resolution, thin-slice (1.5-mm) MRI scans showed infarct-like lesions in 39.3% of men and 24.6% of women. After Tipifarnib molecular weight adjusting for age, sex, and follow-up time, subjects with migraine with aura (n = 361) had an increased risk of late-life infarct-like lesions compared with those not reporting one or more headaches per month (n = 3243; adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Cerebellar lesions were associated with female sex (prevalence of infarcts: 23.0% for women with migraine with aura vs 14.5% for women not reporting headaches [adjusted OR, 1.9; 95% CI, 1.4-2.6] and 19.3% for men with migraine with aura vs 21.3% for men not reporting headaches [adjusted OR, 1.0; 95% CI, 0.6-1.8]; P < .04 for interaction by sex). Migraine without aura and non-migraine headache were not associated with an increased risk of cerebellar infarct-like

lesions, whereas migraine with aura in midlife was associated with late-life prevalence. The release of metallic proteinases during cortical spreading depression (CSD) has been proposed as a cause of blood–brain barrier alterations 上海皓元 in subcortical structures, in turn increasing white matter lesions.3,12,13 White matter lesions may be thought to be manifestations of infarcts. Radiologists may interpret white matter lesions to indicate multiple strokes or multiple sclerosis, but physicians should reassure migraine patients that white matter lesions are a common pathophysiologic feature in CM.3 However, white matter lesions in a migraine patient may rarely indicate underlying CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), or central nervous system vasculitis.