CADASIL

CADASIL is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene, leading to progressive degeneration of vascular smooth muscle cells. Clinically, it manifests with recurrent ischemic strokes, migraine with aura, cognitive decline, and psychiatric symptoms. Pathophysiology involves deposition of granular osmiophilic material in cerebral arterioles, causing vessel wall thickening and white matter lesions. Diagnosis relies on genetic testing, MRI demonstrating subcortical white matter hyperintensities, and sometimes skin biopsy. Management is supportive, focusing on stroke prevention and symptom control; disease progression is chronic and often leads to significant disability.