Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy

=Cerebral Arteriopathy with Subcortical Infarcts and Leukoencephalopathy = Cerebral Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CASIL) is a rare genetic disorder that affects the small blood vessels in the brain, leading to a range of neurological symptoms. This condition is also known as CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy).

Etiology

CASIL is caused by mutations in the NOTCH3 gene, which is located on chromosome 19. The NOTCH3 gene provides instructions for making a protein that is important for the function of vascular smooth muscle cells. Mutations in this gene lead to the accumulation of abnormal protein deposits in the walls of small blood vessels, particularly in the brain.

Clinical Features

The clinical presentation of CASIL can vary widely among affected individuals, but common symptoms include:

• Recurrent strokes or transient ischemic attacks (TIAs)
• Migraine headaches, often with aura
• Cognitive decline and dementia
• Mood disturbances, such as depression
• Seizures

The onset of symptoms typically occurs in adulthood, often between the ages of 30 and 50.

Diagnosis

The diagnosis of CASIL is based on clinical evaluation, family history, and imaging studies. Magnetic resonance imaging (MRI) of the brain often reveals characteristic changes, such as subcortical infarcts and leukoencephalopathy. Genetic testing can confirm the diagnosis by identifying mutations in the NOTCH3 gene.

Pathophysiology

The pathophysiology of CASIL involves the degeneration of vascular smooth muscle cells and the accumulation of granular osmiophilic material (GOM) in the walls of small arteries. This leads to thickening and loss of elasticity in the vessel walls, resulting in reduced blood flow and ischemic damage to the brain.

Management

There is currently no cure for CASIL, and treatment is primarily supportive and symptomatic. Management strategies may include:

• Control of vascular risk factors, such as hypertension and hyperlipidemia
• Antiplatelet therapy to reduce the risk of stroke
• Rehabilitation therapies to address cognitive and physical impairments
• Psychological support for mood disturbances

Prognosis

The prognosis for individuals with CASIL varies depending on the severity of symptoms and the rate of disease progression. While some individuals may experience a relatively mild course, others may develop significant neurological disability over time.

Research Directions

Ongoing research is focused on understanding the molecular mechanisms underlying CASIL and developing targeted therapies. Studies are also exploring the potential role of biomarkers in early diagnosis and disease monitoring.

See Also

• Stroke
• Leukoencephalopathy
• Genetic Disorders
• Joutel, A., et al. (1996). "Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia." Nature.
• Chabriat, H., et al. (2009). "CADASIL." The Lancet Neurology.

NIH genetic and rare disease info

• NIH info on Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy

Cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is a rare disease.