What is CADASIL?

CADASIL stands for Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy. It is a genetic disorder caused by mutations in the NOTCH3 gene. The condition primarily affects the walls of small arteries in the brain, leading to reduced blood flow and damage to deep brain structures.

The Genetic Basis

CADASIL is inherited in an autosomal dominant pattern. This means a person only needs to inherit one copy of the mutated gene from an affected parent to develop the condition. Each child of an affected individual has a 50 percent chance of inheriting the mutation. Genetic testing can confirm the diagnosis by identifying pathogenic variants in the NOTCH3 gene.

Migraine and CADASIL

Migraine with aura is often one of the earliest and most common symptoms of CADASIL. Many affected individuals experience recurrent headaches that may be accompanied by visual disturbances, sensory changes, or speech difficulties. The migraine pattern in CADASIL can sometimes be atypical, with unusually prolonged or severe auras. Recognizing this neurological symptom is important for early investigation, especially when there is a family history of stroke or dementia.

White Matter Changes

White matter refers to the deeper parts of the brain that contain nerve fibers coated with myelin. In CADASIL, progressive damage to small arteries leads to widespread white matter changes that can be seen on brain imaging, particularly MRI. These changes often appear as symmetrical areas of increased signal on certain MRI sequences, commonly affecting the frontal and temporal lobes. Over time, the accumulation of white matter lesions contributes to cognitive decline, gait difficulties, and stroke-like episodes.

Other Clinical Features

Beyond migraine and white matter involvement, CADASIL can cause recurrent subcortical strokes, mood disturbances, apathy, and progressive cognitive impairment. Symptoms typically begin in mid-adulthood, though the age of onset can vary widely. The condition is often underdiagnosed because its early signs may be mistaken for more common neurological disorders.

Diagnosis and Management

Diagnosis is based on clinical history, brain imaging findings, and confirmatory genetic testing. Skin biopsy may also be used to detect characteristic granular osmiophilic material in blood vessel walls. There is currently no cure for CADASIL, so management focuses on controlling symptoms and reducing vascular risk factors. Migraine treatments, antiplatelet therapy, and lifestyle modifications are often discussed with a specialist. Genetic counseling is recommended for families affected by the condition.