Is migraine a common manifestation of CADASIL-Cons

Abstract

Abstract Headaches and transient neurological symptoms that bear resemblances to clinical manifestations of migraine, especially migraine with aura, are common among patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) or cysteine-altering NOTCH3 genetic variants. However, according to the International Classification of Headache Disorders, Third Edition (ICHD-3), these patients should be diagnosed as headache attributed to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) rather than migraine with or without aura. Although transient focal neurological symptoms are often labeled as migraine aura, these symptoms are often atypical and complicated, and could not easily conform to the criteria for migraine with aura. Besides, the association between migraine and CADASIL could not be supported by population-based genetic studies, and cysteine-altering NOTCH3 genetic variants are not more common among patients with migraine with or without aura compared with non-migraine controls. In addition, the underlying pathophysiology may be different between migraine and CADASIL. Although increased cortical spreading depression (CSD) susceptibility in mice harboring a human pathogenic Notch3 variant is often regarded as supportive evidence for the association, CSD could been seen in conditions other than migraine, such as cerebral ischemia. The role of calcitonin gene-related peptide (CGRP), one of the most important molecules in migraine pathophysiology, in CADASIL patients with migraine-like manifestations is yet to be determined. To sum up, there remain uncertainties whether headache and migraine aura-like manifestations in CADASIL correspond to “ordinary” migraine with or without aura seen in routine clinical practice. Therefore, we are still a number of steps from a firm conclusion about the association between CADASIL and migraine.