Interestingly, NOTCH3 mutations are responsible for CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), the most common genetic cause of small vessel disease ischemic stroke, often associated with migraine with aura. Here, NOTCH3 is linked to cerebral arteriopathy with subcortical infarcts and leukoencephalopathy.