What is the management approach for patients with Fabry disease who have experienced strokes?

Management of Fabry Disease Patients with Stroke

All Fabry disease patients who have experienced stroke or TIA should receive enzyme replacement therapy (ERT) combined with antiplatelet or anticoagulant prophylaxis, as stroke occurs frequently in this population—often before diagnosis and in the absence of other clinical manifestations. 1, 2

Core Treatment Strategy

Enzyme Replacement Therapy (ERT)

• Initiate ERT in all Fabry patients with stroke history, regardless of age, gender, or presence of other organ involvement 1
• Agalsidase beta at 1 mg/kg every other week is the standard dosing regimen 1
• ERT reduces the composite risk of renal, cardiac, cerebrovascular events, or death by 61% when started at earlier stages of disease 1
• Meta-analysis demonstrates stroke recurrence rate of 8.2% with ERT versus 16% without treatment (p=0.03), showing significant benefit for secondary stroke prevention 3
• The American Heart Association/American Stroke Association formally recommends α-galactosidase enzyme replacement therapy for all Fabry patients with ischemic stroke or TIA 1

Antiplatelet/Anticoagulation Therapy

• Prophylaxis with antiplatelet or anticoagulant medication is essential for patients who have had TIA or stroke 1
• Aspirin and clopidogrel are the primary antiplatelet agents recommended 1
• This should be initiated alongside ERT, not as an alternative 1

Critical Clinical Context

Stroke Characteristics in Fabry Disease

• Median age at first stroke is 39 years in males and 45.7 years in females—substantially younger than general population 2
• 50% of males and 38.3% of females experience their first stroke before Fabry disease is even diagnosed 2
• 21% of males and 9% of females have hemorrhagic strokes (not just ischemic), which is higher than typical stroke populations 2
• 70.9% of males and 76.9% of females had no prior renal or cardiac events before their first stroke, making cerebrovascular disease often the presenting manifestation 2
• 30 patients in the Fabry Registry had strokes before age 30 years 2

Adjunctive Cardiovascular Risk Management

• Strict blood pressure control is essential to minimize ongoing cerebrovascular disease 1
• Treat dyslipidemia with statins 1
• ACE inhibitors or ARBs for patients with proteinuria (>300 mg/24 hours) 1
• Smoking cessation is mandatory 1
• Avoid medications that inhibit α-galactosidase A activity: chloroquine, amiodarone, benoquin, or gentamicin 1

Pain Management Considerations

• For neuropathic pain (acroparesthesias), use carbamazepine, gabapentin, or phenytoin 1
• Avoid NSAIDs due to potential adverse effects on renal function 1
• Minimize narcotic analgesics to prevent dependency given the chronic nature of Fabry disease 1

Monitoring After Stroke

Neurological Surveillance

• Comprehensive brain MRI with T1, T2, and FLAIR-weighted sequences at baseline 1
• Magnetic resonance angiography (MRA) to evaluate for cerebral vasculopathy, dolichoectasia of vertebral/basilar arteries 1
• Monitor for white matter lesions which commonly occur in Fabry disease 1, 4

Multi-Organ Assessment

• Annual evaluations must include cardiac and renal monitoring since 60% of males and 25.5% of females develop stage 3-5 chronic kidney disease after stroke 2
• 66.1% of males and 59.5% of females develop left ventricular hypertrophy post-stroke 2
• Echocardiography and electrocardiography at least every 2 years 1
• Annual urinary protein, creatinine clearance, and creatinine-to-albumin ratio 1

Important Caveats

ERT Limitations

• Strokes continue to occur despite ERT, though at reduced rates, emphasizing the need for aggressive adjunctive antiplatelet/anticoagulation therapy 1
• The impact of ERT on stroke prevention remains somewhat unclear with conflicting data—some studies show benefit while others show no difference in stroke rates 1
• Earlier intervention and possibly higher enzyme doses may be needed for optimal stroke prevention 1

Gender Considerations

• Female carriers require the same aggressive treatment approach as males when symptomatic 1
• Females with prior cerebrovascular events or ischemic changes on brain MRI should receive ERT 1
• The frequency of cerebrovascular accidents may be increased in females over age 40 1

Infusion Management

• Initial infusion-associated reactions occur in approximately 57-59% of patients 1
• Manage with slow infusion rates, premedication with acetaminophen and antihistamines 1
• First 6 months of infusions should occur in a medical facility under physician supervision 1