From the Guidelines
The management of CADASIL should focus on counseling on smoking cessation and treatment of hypertension and other vascular risk factors to reduce the risk of incident stroke, as recommended by the 2024 guideline from the American Heart Association/American Stroke Association 1. The treatment of CADASIL involves a multifaceted approach, including:
- Lifestyle modifications such as smoking cessation, blood pressure control, and maintaining healthy cholesterol levels to reduce vascular risk factors
- Antiplatelet therapy, typically aspirin 81-325 mg daily, may be prescribed to prevent ischemic events, though anticoagulants are generally avoided due to the risk of cerebral hemorrhage
- Management of migraine symptoms, which affect many CADASIL patients, with standard migraine treatments like triptans (sumatriptan 50-100 mg as needed), used with caution due to their vasoconstrictive properties
- Depression and mood disorders can be managed with SSRIs such as sertraline (50-200 mg daily) or escitalopram (10-20 mg daily)
- For cognitive decline, acetylcholinesterase inhibitors like donepezil (5-10 mg daily) may provide modest benefits in some patients
- Physical therapy and occupational therapy are important for managing motor symptoms and maintaining independence
- Genetic counseling is essential for patients and families due to the autosomal dominant inheritance pattern, with a 50% chance of passing the condition to offspring
- Regular neurological follow-up with periodic MRI monitoring (typically every 1-2 years) helps track disease progression and adjust management strategies accordingly, as the underlying pathology involves mutations in the NOTCH3 gene, leading to accumulation of the NOTCH3 protein in small blood vessel walls, causing progressive damage to cerebral vasculature 1. Key considerations in the management of CADASIL include:
- The role of vascular risk factor modification, antiplatelet therapy, and calcium channel blockers in stroke prevention in patients with CADASIL is unknown and requires further research 1
- The effectiveness of enzyme replacement therapy (ERT) to reduce the risk of stroke in patients with Fabry disease is not well established 1
- The optimal approach to screening and treatment for brain arteriovenous malformations in individuals with hereditary hemorrhagic telangiectasia (HHT) remains undefined 1
From the Research
Management and Treatment of CADASIL
The management and treatment of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) are primarily focused on alleviating symptoms and preventing further complications. Some key aspects of management include:
- Control of vascular risk factors, although patients with CADASIL are typically free of classical vascular risk factors 2
- Management of migraine with aura, which is a common symptom in CADASIL patients 3, 4
- Monitoring for cognitive decline and dementia, which are common features of the disease 3, 5, 4
- Use of imaging techniques, such as magnetic resonance imaging (MRI), to diagnose and monitor the disease 3, 5, 4, 2
Diagnostic Criteria
Diagnostic criteria for CADASIL have been proposed, based on clinical and imaging parameters 2. These criteria include:
- Presence of migraine with aura
- History of strokes or stroke-like episodes
- Presence of major psychiatric symptoms
- Presence of dementia
- Characteristic findings on cerebral MRI, including diffuse leukoencephalopathy with subcortical infarcts in the basal ganglia and white matter
Current Research and Understanding
Research on CADASIL is ongoing, with studies focused on understanding the pathogenesis of the disease and developing effective treatments 6, 3, 5, 4, 2. The disease is caused by mutations in the Notch3 gene, which encodes a transmembrane receptor protein 3, 4. However, the exact function of Notch3 in adults and the pathogenesis of CADASIL are still unknown 3, 4.