Clinical Features of CADASIL

Area of Science:

• Neurology
• Genetics
• Vascular Biology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disorder.
• Mutations in the Notch3 gene are causative, but disease mechanisms remain unclear.
• Previous studies have focused on Caucasian populations, with limited data on Japanese CADASIL cases.

Purpose of the Study:

• To describe the clinical features of two Japanese CADASIL families with the R141C mutation.
• To investigate potential associations between clinical manifestations and neuroimaging findings.
• To compare clinical characteristics between Japanese and Caucasian CADASIL patients.

Main Methods:

• Clinical assessment of patients from two Japanese families with confirmed R141C Notch3 mutation.
• Magnetic resonance imaging (MRI) to evaluate ischemic lesions.
• Comparison of clinical data with previously reported Caucasian CADASIL cases.

Main Results:

• Mean age of onset was 44.6 years, with recurrent strokes and motor disturbances as primary symptoms.
• Characteristic ischemic lesions were observed in white matter, basal ganglia, temporal lobe, and corpus callosum.
• Japanese patients showed higher frequencies of dementia and pseudobulbar palsy compared to Caucasian counterparts, with less frequent typical migraines.
• Lower nocturnal arterial blood pressure fall was noted in patients, potentially linked to deep white matter lesions.

Conclusions:

• The R141C mutation presents distinct clinical and neuroimaging features in Japanese CADASIL patients.
• Nocturnal hypotension may contribute to deep white matter ischemic lesions in CADASIL.
• Understanding these variations can advance the study of CADASIL and other chronic ischemic brain diseases like leukoaraiosis.