In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is characterized by mid-adult onset of recurrent ischemic stroke, cognitive decline progressing to dementia, a history of migraine with aura, mood disturbance, apathy, and diffuse white matter lesions and subcortical infarcts on neuroimaging.

Diagnosis/testing: The diagnosis of CADASIL is established in a proband either by identification of a heterozygous pathogenic variant in NOTCH3 by molecular genetic testing or, if molecular genetic testing is not definitive, by detection of characteristic findings by electron microscopy and immunohistochemistry of a skin biopsy.

Management: Treatment of manifestations: There is no treatment of proven efficacy for CADASIL. Standard supportive treatment for stroke; the effect of thrombolytic therapy for the treatment of stroke remains unknown. Migraine should be treated symptomatically. Standard treatment for psychiatric disturbance. Supportive care (practical help, emotional support, and counseling) is appropriate for affected individuals and their families.

Prevention of primary manifestations: Antiplatelet therapy may be considered for prevention of stroke/TIA, but efficacy has not been proven. Anticoagulants should be avoided if possible. Control of vascular risk factors (hypertension, diabetes, hypercholesterolemia, smoking). Prophylactic treatment of migraines, depending on the frequency.

Surveillance: Routine evaluation by a neurologist with expertise in CADASIL; consultation with a neuropsychiatrist if symptoms of depression, apathy, or psychiatric manifestations; consultation with other medical specialists (e.g., rehabilitation physician, clinical geneticist, physical therapist, and psychologist) as needed.

Agents to avoid: Thrombolytic therapy (intravenous thrombolysis) and oral anticoagulants probably increase the risk of intracerebral hemorrhage in individuals with CADASIL. These agents should therefore only be used carefully and on a case-by-case basis. Smoking increases the risk of stroke.

Pregnancy management: There may be an increased risk for neurologic events in pregnancy during and shortly after delivery (puerperium); transient neurologic events (migraine with aura) have most commonly been reported.

Genetic counseling: CADASIL is inherited in an autosomal dominant manner. Most affected individuals have an affected parent; de novo pathogenic variants appear to be rare. Each child of an affected person is at a 50% risk of inheriting the pathogenic variant and developing signs of the disease. Prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible if the pathogenic variant in the family is known.

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