Incipient CADASIL

Abstract

CEREBRAL autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy caused by mutations in the NOTCH3 gene.¹ Distinctive ultrastructural granular osmiophilic material in the vascular media and degeneration of vascular smooth muscle cells compose the pathological hallmark.^2,3 The clinical diagnosis of CADASIL is considered in patients with otherwise unexplained central nervous system symptoms, extensive white matter changes with or without subcortical infarctions on magnetic resonance imaging (MRI), and a family history of neurological disorders.⁴ The disease presentation and natural history are diverse, but, typically, the diagnosis is made in the fifth decade of life when mutation carriers (MCs) present with recurrent strokelike episodes and/or cognitive decline. Up to 40% of persons diagnosed as having the disease have a history of migraine with aura, with onset in their mid-20s. Psychiatric disturbances can play a role in about a third of affected individuals.⁴