What is the best management approach for a patient with Cadasil (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) causing stroke?

Management of CADASIL-Related Stroke

For patients with CADASIL causing stroke, aggressive vascular risk factor modification—particularly smoking cessation and hypertension control—combined with antiplatelet therapy represents the cornerstone of management, as no disease-modifying therapies currently exist. 1

Primary Stroke Prevention Strategy

Vascular Risk Factor Control (Class I Recommendation)

The 2024 AHA/ASA guidelines provide a Class I, Level C-LD recommendation that counseling on smoking cessation and treatment of hypertension and other vascular risk factors are beneficial to reduce incident stroke risk in CADASIL patients 1. This represents the highest level of recommendation despite limited evidence, reflecting the critical importance of these interventions in the absence of disease-specific therapies.

Key modifiable risk factors to aggressively target include: 2

• Hypertension: Requires strict blood pressure control as the arteriopathy already compromises cerebral perfusion
• Smoking: Must be completely eliminated given the underlying small vessel disease
• Other traditional vascular risk factors: Diabetes, hyperlipidemia, physical inactivity

Antiplatelet Therapy

The American Heart Association recommends antiplatelet therapy for stroke prevention in CADASIL patients 2. However, this recommendation requires careful consideration given the hemorrhagic risk profile.

Critical caveat: Anticoagulants should be avoided due to increased hemorrhage risk in CADASIL patients 2. This is particularly important as CADASIL patients can develop cerebral microbleeds and have experienced fatal intracerebral hemorrhages, even on antiplatelet agents 3.

Hemorrhagic Risk Considerations

The decision to use antiplatelet agents must weigh ischemic versus hemorrhagic stroke risk: 3

• CADASIL vasculopathy itself predisposes to both ischemic and hemorrhagic events
• Cerebral microbleeds are common and should be assessed via MRI before initiating antithrombotic therapy
• Fatal intracerebral hemorrhage has been reported in CADASIL patients on aspirin with concurrent hypertension 3
• The combination of CADASIL vasculopathy, cerebral microbleeds, hypertension, and antithrombotic agents creates compounded hemorrhagic risk 3

Practical approach: Before initiating antiplatelet therapy, obtain gradient-echo or susceptibility-weighted MRI sequences to assess for microbleeds and ensure blood pressure is optimally controlled 3.

Symptomatic Management

Migraine Treatment

Standard migraine treatments may be used, but exercise caution with triptans in patients with hemiplegic or basilar migraine, which are common CADASIL manifestations 2. Migraine with aura occurs in approximately one-third of CADASIL patients and may be the first clinical manifestation 4, 5.

Cognitive Decline

Progressive cognitive decline and vascular dementia are inevitable features of CADASIL 4, 6. Management focuses on:

• Optimizing vascular risk factors to slow progression
• Symptomatic treatment of cognitive symptoms
• Psychosocial support for patients and families

Diagnostic Confirmation

CADASIL can be diagnosed before the first stroke occurs: 4

• Characteristic white matter hyperintensities on MRI (particularly in anterior temporal lobes and external capsule) may precede symptoms by over a decade 5
• Skin biopsy showing granular osmiophilic material in dermal arteries is pathognomonic 4
• Genetic testing for NOTCH3 mutations provides definitive diagnosis 4, 5

Common Pitfalls to Avoid

Failure to recognize family history: Inadequate assessment of family history of early-onset stroke or dementia leads to misdiagnosis 2. CADASIL follows autosomal dominant inheritance, so detailed three-generation pedigree analysis is essential 4.

Inadequate vascular risk factor management: The most common and consequential error is insufficient control of hypertension and failure to achieve smoking cessation 2. These are the only proven interventions to modify disease progression.

Inappropriate anticoagulation: Using anticoagulants in CADASIL patients significantly increases hemorrhagic stroke risk 2, 3.

Overlooking microbleeds before antithrombotic therapy: Failing to obtain appropriate MRI sequences to detect cerebral microbleeds before initiating antiplatelet agents 3.

Knowledge Gaps

The 2024 AHA/ASA guidelines explicitly acknowledge that the roles of antiplatelet therapy and calcium channel blockers in stroke prevention in CADASIL patients remain unknown 1. No disease-modifying therapies currently exist, and stroke-specific outcomes from interventions are lacking 1. This underscores why aggressive vascular risk factor modification remains the primary evidence-based intervention.