CADASIL

Nancy E Bonthius PharmD (Dr. Bonthius of the University of Iowa has no relevant financial relationships to disclose.)
Daniel J Bonthius MD PhD (Dr. Bonthius of the University of Iowa has no relevant financial relationships to disclose.)
Steven R Levine MD, editor. (Dr. Levine of the SUNY Health Science Center at Brooklyn has received honorariums from Genentech for service on a scientific advisory committee and a research grant from Genentech as a principal investigator.)
Originally released July 28, 1997; last updated March 27, 2017; expires March 27, 2020

This article includes discussion of CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, familial Binswanger disease, familial sclerosing vasculopathy, and hereditary multi-infarct dementia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominant genetic disease that induces recurrent subcortical ischemic strokes and ultimately leads to severe disability and death. In this updated article, the authors discuss advances in the pathogenesis and pathophysiology of this disorder, as well as the differential diagnosis and diagnostic approach to this important genetically-induced cause of stroke.

Key points

 

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetically determined disorder that leads to early transient ischemic attacks and strokes.

 

• Initial symptoms of CADASIL may include migraine headaches or psychiatric disturbance.

 

MRI scan of the brain is always abnormal in symptomatic patients and shows signs of small deep infarcts and leukoencephalopathy.

 

• CADASIL is an autosomal dominant disorder caused by mutation in Notch3 on chromosome 19, and genetic testing is commercially available for this disorder.

 

• Although the disease manifests itself solely as brain dysfunction, the vasculopathy of CADASIL is systemic, thus, providing the opportunity for diagnostic biopsies from skin, muscle, or peripheral nerve.

Historical note and terminology

In 1977, the first reports were published of a hereditary disorder characterized by recurrent subcortical ischemic strokes and stepwise progression of neurologic deficits leading to dementia, pseudobulbar palsy, and severe disability (Sourander and Walinder 1977; Stevens et al 1977). Since then, the disorder has been referred to by several names, including "hereditary multi-infarct dementia" and "familial sclerosing vasculopathy" (Colmant 1980; Sonninen and Savontaus 1987). In the 1990s, the disorder came to be known formally by the awkward, but clinically accurate designation "cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy." It was immediately recognized that a more user-friendly working nomenclature was needed, and the acronym "CADASIL" emerged (Tournier-Lasserve et al 1993; Sabbadini et al 1995). The acronym is now more commonly used (and probably more commonly recognized) than the full name of the disorder. Therefore, as is true of virtually all manuscripts, book chapters, and discussions of this subject, this review will use the acronym throughout its text.

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