6.8.1 Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Description:
An autosomal dominant (with some sporadic cases) small-artery disease of the brain characterized clinically by recurrent small deep infarcts, subcortical dementia, mood disturbances and, in one third of cases, by migraine with aura (which is usually the first symptom of the disease).

Diagnostic criteria:
A. Recurrent attacks of migraine with typical, hemiplegic or prolonged aura, fulfilling criterion C
B. CADASIL has been demonstrated by genetic testing for NOTCH-3 mutations and/or skin biopsy evidence
C. Either or both of the following:

    1. migraine with aura was the earliest clinical manifestation of CADASIL
    2. attacks of migraine with aura improve or cease when other manifestations of CADASIL (eg, ischaemic stroke, mood disturbances and/or cognitive dysfunction) appear and worsen

D. Not better accounted for by another ICHD-3 diagnosis.

Comments:
CADASIL is an autosomal dominant disease, with some sporadic cases, involving the smooth muscle cells in the media of small arteries of the brain. It is due to mutations of the NOTCH-3 gene; the diagnosis is made by screening for NOTCH-3 mutations or by a simple skin biopsy with immunostaining of NOTCH-3 antibodies.

CADASIL is characterized clinically by recurrent small deep infarcts, subcortical dementia, mood disturbances and, in one third of cases, by migraine with aura. In such cases, this is usually the first symptom of the disease, appearing at a mean age of 30 years, some 15 years before ischaemic strokes and 20-30 years before death. Migraine attacks are typical of 1.2 Migraine with aura except for an unusual frequency of prolonged aura.

MRI is always abnormal, with striking white matter changes on T2-weighted images.