CADASIL is a rare, inherited vascular brain disease. It typically presents with (repetitive) young onset strokes (often lacunar), migraines with aura, psychiatric disorders, and progressive cognitive impairment. Though seizures have been described in up to 15% of cases, it is very rare for patients with CADASIL to present with a seizure as initial manifestation of disease. With an estimated prevalence of 1-9 per 100.000 adults it is an uncommon disease, though presumably some cases have been misinterpreted as multiple sclerosis, Alzheimer’s disease, or other neurodegenerative diseases before the establishment of genetic testing for CADASIL in 2000.

When CADASIL is suspected based on clinical symptoms and MRI findings, the diagnosis can be confirmed by sural nerve biopsy showing characteristic perivascular deposits of granular electron-dense material resembling immunoglobulin deposits when examined through an electron microscope. Genetic testing reveals a missense mutation in the NOTCH3 gene on chromosome 19. It is thought that mutations in this gene cause NOTCH3 protein segment accumulation in blood vessel walls, leading to accumulation of other proteins and loss of function, scarring the blood vessels, leading to progressive vascular disease.

Summary

Clinical history, including family history, is critical for establishing a diagnosis of CADASIL. Characteristic MRI findings are hyperintense white-matter lesions and repetitive stroke lesions. Think of CADASIL in young patients presenting with recurrent stroke, migrains, and progressive cognitive impairment. Genetic testing and/or sural nerve biopsy confirm the diagnosis.