What is the management of chronic cerebral venous thrombosis (CVT) with a falcotentorial dural arteriovenous fistula (AVF) in a patient with a 1298C methylenetetrahydrofolate reductase (MTHFR) homozygous mutation?

Management of Chronic CVT with Falcotentorial Dural AV Fistula and MTHFR 1298C Homozygous Mutation

Primary Treatment Recommendation

Immediate anticoagulation with low-molecular-weight heparin (LMWH) followed by transition to oral anticoagulation for at least 3-6 months is the cornerstone of management, regardless of MTHFR mutation status, with concurrent evaluation for endovascular treatment of the dural arteriovenous fistula. 1, 2

Anticoagulation Protocol

Initial Phase

• Start LMWH immediately (Enoxaparin 1.0 mg/kg twice daily or 1.5 mg/kg once daily, or Dalteparin 200 U/kg once daily) as first-line therapy, even if hemorrhagic transformation is present on imaging 2
• The presence of intracranial hemorrhage related to CVT is not a contraindication to anticoagulation, as the risk of thrombus propagation outweighs bleeding concerns 1, 2
• Continue parenteral anticoagulation for minimum 5 days and until transitioning to oral therapy 2

Transition to Oral Anticoagulation

• Begin oral anticoagulation early while continuing LMWH until therapeutic levels achieved 2
• For vitamin K antagonists (warfarin): target INR 2.0-3.0 (optimal 2.5), continuing LMWH until INR ≥2.0 for at least 24 hours 2
• Direct oral anticoagulants (DOACs) are emerging as safe alternatives to warfarin for CVT management 3

Duration of Anticoagulation

• Minimum 3-6 months for provoked CVT with transient risk factors 1, 2
• Consider 6-12 months or indefinite anticoagulation given the chronic nature of this case with persistent structural abnormality (dural AV fistula) and thrombophilia 1, 2
• The presence of the dural AV fistula represents a persistent provoking factor that may warrant extended anticoagulation until definitive treatment of the fistula 4

MTHFR 1298C Mutation Considerations

Clinical Significance

• The MTHFR 1298C homozygous mutation does NOT alter anticoagulation management decisions 5, 6
• Routine testing for MTHFR mutations has no clinical utility in determining anticoagulation duration or intensity, as treatment decisions are based on clinical presentation rather than genetic status 5
• MTHFR polymorphisms are associated with hyperhomocysteinemia, which correlates with CVT risk but does not change standard anticoagulation protocols 7

Adjunctive Therapy for MTHFR Mutation

• Supplement with folic acid, vitamin B12, and vitamin B6 to reduce homocysteine levels, particularly if hyperhomocysteinemia is documented (>15 µmol/L) 8
• Check baseline homocysteine level, as MTHFR 1298C polymorphism is associated with elevated levels that may serve as a prognostic marker 7

Dural Arteriovenous Fistula Management

Diagnostic Evaluation

• Confirm dAVF characteristics with catheter angiography to assess fistula location, cortical venous drainage pattern, and relationship to thrombosed sinus 4
• The falcotentorial location and association with CVT suggests the fistula may have developed secondary to chronic venous thrombosis (50% of CVT-related dAVFs are diagnosed simultaneously or after CVT diagnosis) 4
• Assess for cortical venous drainage (present in 68% of CVT-related dAVFs), which increases hemorrhage risk and may necessitate more aggressive treatment 4

Treatment Strategy

• Endovascular embolization or surgical treatment of the dAVF should be considered after stabilization on anticoagulation, particularly if cortical venous drainage is present 4
• The decision to treat the dAVF depends on: presence of cortical venous drainage, hemorrhagic presentation, progressive neurological symptoms, and feasibility of safe intervention 4
• Anticoagulation should be continued during and after dAVF treatment until complete obliteration is confirmed and venous drainage normalizes 4

Monitoring and Follow-Up

Acute Phase Monitoring

• Monitor in stroke unit or neurocritical care setting during initial treatment phase 1
• Perform regular neurological assessments to detect clinical deterioration (worsening consciousness, new focal deficits, seizures) 2
• Watch for signs of increased intracranial pressure requiring escalation of care 2

Imaging Follow-Up

• Obtain follow-up MRI/MRV at 3-6 months to assess recanalization of thrombosed sinuses and stability of dAVF 1, 2
• Serial imaging may be needed more frequently if dAVF shows high-risk features or if clinical deterioration occurs 4

Laboratory Monitoring

• Check homocysteine levels at baseline and after supplementation with B vitamins and folate 8, 7
• Monitor INR regularly if on warfarin (target 2.0-3.0) with annual bleeding risk approximately 3% 6
• Consider checking high-sensitivity CRP as it may serve as a prognostic marker in CVT 7

Critical Pitfalls to Avoid

• Do not withhold anticoagulation due to presence of hemorrhagic transformation on imaging, as this is venous congestion-related bleeding that improves with anticoagulation 1, 2
• Do not base anticoagulation duration solely on MTHFR mutation status, as genetic thrombophilia testing does not alter standard CVT management 5, 6
• Do not overlook the dAVF as a persistent risk factor requiring definitive treatment beyond anticoagulation alone 4
• Do not assume the dAVF preceded the CVT, as 56% of CVT-related dAVFs are diagnosed simultaneously and 36% are diagnosed after CVT (median 115 days later) 4
• Do not discontinue anticoagulation prematurely in the setting of an untreated dAVF with cortical venous drainage, as this represents ongoing thrombotic risk 4

Prognosis

• With appropriate anticoagulation, 86% of CVT patients achieve favorable outcomes (modified Rankin Scale 0-2) at 6-12 months 9
• The presence of dAVF does not worsen clinical outcome compared to CVT without dAVF when appropriately managed 4
• Mortality in adequately treated CVT is approximately 2.6%, with most deaths occurring in the acute phase 7, 9