CADASIL

CADASIL is an inherited small-vessel disease caused by NOTCH3 mutations. It damages brain white matter and can cause migraine with aura, recurrent strokes, and cognitive decline.

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NOTCH3: NOTCH3 is a gene encoding a receptor protein expressed mainly in vascular smooth muscle cells and pericytes. CADASIL-causing variants alter this receptor, initiating the vessel-wall changes that define the disease.
Migraine with aura: Migraine with aura is a migraine disorder in which reversible visual, sensory, or language symptoms precede or accompany headache. It often begins early in CADASIL and may precede strokes by years.
Autosomal dominant inheritance: Autosomal dominant inheritance occurs when one altered copy of a gene can cause a trait or disorder. A single pathogenic NOTCH3 variant can cause CADASIL, so the condition may recur across generations.
Vascular cognitive impairment: Vascular cognitive impairment is cognitive decline caused by injury to brain blood vessels and their surrounding tissue. Repeated small-vessel injury in CADASIL can progressively impair processing speed and executive function.
Granular osmiophilic material: Granular osmiophilic material is an electron-dense deposit found around vascular smooth muscle cells in CADASIL. Its presence in small-vessel walls is a distinctive tissue finding linked to abnormal NOTCH3 protein.
Subcortical ischemic vascular disease: Subcortical ischemic vascular disease is brain injury from reduced blood flow in small vessels supplying deep brain structures. CADASIL can cause this pattern of injury, with lacunes and progressive white-matter changes.
Genetic testing: Genetic testing analyzes DNA to identify variants associated with inherited conditions. Finding a pathogenic NOTCH3 variant is the primary way to confirm CADASIL.
Ischemic stroke: An ischemic stroke occurs when blocked blood flow deprives part of the brain of oxygen. CADASIL increases the risk of recurrent ischemic events, often affecting deep brain structures.
Cerebral small-vessel disease: Cerebral small-vessel disease comprises disorders affecting the brain’s arterioles, capillaries, and venules. CADASIL is an inherited cause of this broader group of vessel-related brain injuries.
Anterior temporal pole sign: The anterior temporal pole sign is MRI hyperintensity in the front portions of the temporal lobes. This imaging pattern is particularly suggestive of CADASIL, though its absence does not exclude the disease.