Problems of diagnosis and clinical manifestations of CADASIL in the practice of a neurologist

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, or CADASIL, is the most common inherited form of cerebral microangiopathy. It is a monogenic disease of small and medium-sized vessels caused by mutations in the NOTCH3 gene on chromosome 19. CADASIL is often misdiagnosed as multiple sclerosis, migraine, or stroke of unknown etiology. Although this disease is rare, its clinical significance and diagnostic shortcomings require increased awareness among healthcare professionals, especially family physicians, who are the first line of care in the healthcare system. Family physicians play a critical role in early detection, differential diagnosis, initial management, and coordination of a multidisciplinary approach to the treatment of patients with this progressive neurodegenerative condition. Methods. A literature review was conducted in the PubMed/MEDLINE, Embase databases from 2000 to 2025. The keywords «CADASIL», «NOTCH3», «familial stroke», «leukoencephalopathy», «primary care» were used. Consensus recommendations and data on phenotypic manifestations characteristic of the medical community were collected. Two clinical cases of the disease from practice are provided. Results. CADASIL manifests itself with a characteristic clinical triad: recurrent subcortical strokes/transient ischemic attacks (starting at 40–50 years of age), migraine with aura (often as the first symptom) and progressive vascular dementia. Typical MRI signs include diffuse leukoencephalopathy and lacunar infarctions, especially pronounced in the anterior pole of the temporal lobes. A family history of strokes or dementia at a young age should raise high suspicion. Management of this condition includes assessment of risk factors and antiplatelet therapy. Conclusions. Physicians play a central role in CADASIL screening. Atypical migraines, strokes at a young age without classic vascular risk factors, and family history are «red flags». Timely referral to a neurologist and genetic testing confirm the diagnosis, allowing for optimized treatment and genetic counseling of the family.

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