Papers of the Week

Migraine, the third most common disease worldwide, is a well-known independent risk factor for subclinical focal deep white matter lesions (WML), even in young and otherwise individuals without cardiovascular risk factors. These white matter lesions are more commonly seen in migraine patients with transient neurological symptoms preceding their headaches, the so-called aura, and those with a high attack frequency. Despite their prevalence, the pathophysiology of migraine-related deep white matter hyperintensities remains poorly understood. Characteristic differences in their distribution when compared to common periventricular white matter lesions in the elderly that are related to chronic small vessel ischemic disease suggest a different underlying mechanism. Both ischemic and inflammatory mechanisms have been proposed, as there is increased cerebral vulnerability to ischemia in migraineurs, while there is also evidence for blood-brain-barrier disruption with associated release of pro-inflammatory substances during migraine attacks. An enhanced susceptibility to spreading depolarization, the electrophysiologic event underlying migraine, may be the underlying mechanism to cause repetitive episodes of cerebral hypoperfusion and neuroinflammation during migraine attacks. WML can negatively affect both physical and cognitive function, underscoring the public-health importance of migraine and suggesting that migraine is an important contributor to neurological deficits in the general population.