Is prophylactic anti-seizure medication (ASM) indicated for patients with cerebral sinovenous thrombosis (CSVT) at high risk of seizures?

Prophylactic Anti-Seizure Medication for CSVT

Prophylactic anti-seizure medications are NOT routinely indicated for all patients with cerebral sinovenous thrombosis, but should be strongly considered for high-risk patients—specifically those with supratentorial lesions who present with seizures at diagnosis.

Evidence Against Routine Prophylaxis

The general principle from stroke guidelines is clear: prophylactic antiseizure drugs should not be routinely administered to patients with cerebrovascular disease, as they do not consistently prevent seizures and may be associated with worse functional outcomes 1, 2. This recommendation extends to CSVT, where most experts believe primary prophylaxis in the acute phase is not indicated 3.

High-Risk Subgroup Requiring Prophylaxis

However, CSVT differs from other stroke types due to its unique seizure risk profile. The evidence identifies a specific high-risk subgroup that benefits from prophylaxis:

Patients Who Should Receive Prophylaxis:

• Supratentorial lesions PLUS presenting seizures: This combination carries the highest risk of early seizure recurrence (within 2 weeks) 4
• In this subgroup, prophylactic antiseizure drugs dramatically reduce early seizure risk: only 1 of 148 patients (0.7%) on prophylaxis had seizures versus 25 of 47 patients (53%) without prophylaxis (OR=0.006) 4

Risk Factors for Acute Symptomatic Seizures:

Strong predictors requiring heightened vigilance:

• Intracerebral hemorrhage (aOR 4.1) 5
• Supratentorial parenchymal lesions (cerebral edema/infarction, aOR 2.8-3.09) 4, 5
• Cortical vein thrombosis (aOR 2.1-2.31) 4, 5
• Superior sagittal sinus thrombosis (aOR 2.0-2.18) 4, 5, 6
• Focal neurologic deficits (aOR 1.9) 5, 6
• Sulcal subarachnoid hemorrhage (aOR 1.6) 5

Seizure Epidemiology in CSVT

• Acute symptomatic seizures occur in 16-39% of CSVT patients, with most studies reporting 18-34% 4, 3, 7, 5
• Early seizures (within 2 weeks of diagnosis) occur in approximately 7% of patients 4
• Post-CVST epilepsy (unprovoked late seizures after 14 days) develops in 4-16% of patients 3
• Seizure recurrence is common (9.2% in one cohort), particularly in patients with focal deficits, hemorrhagic transformation, or previous acute symptomatic seizures 6

When NOT to Use Prophylaxis

In the absence of presenting seizures, no subgroup has been identified with sufficient risk of post-diagnosis seizures to justify prophylactic treatment 5. Even in patients with cortical vein thrombosis (the highest risk anatomic feature), the positive predictive value for solely post-diagnosis seizures is only 22%, with a negative predictive value of 92% 5.

Medication Selection When Treatment Is Indicated

If prophylaxis or treatment is warranted, levetiracetam is strongly preferred 2:

• Better tolerability with fewer adverse effects 2
• No significant drug interactions with anticoagulation or other neurocritical care medications 2
• No routine serum level monitoring required 2

Avoid phenytoin/fosphenytoin: These agents are associated with excess morbidity and mortality in hemorrhagic stroke, worse cognitive outcomes, and higher adverse effect rates (23%) 2, 8.

Duration of Prophylaxis

If antiseizure medications are initiated for documented seizures or high-risk prophylaxis, treatment should be limited to ≤7 days in the acute/perioperative period unless seizures recur 2. However, given the 9-13% risk of seizure recurrence in CSVT (higher than other stroke types), some patients may require longer treatment 6.

Critical Pitfalls to Avoid

• Do not delay anticoagulation while focusing on seizure management—the thrombosis itself is the primary pathology requiring immediate treatment 4
• Do not use risk scores to justify prophylaxis beyond 7 days without documented seizures, as there is no evidence this prevents late epilepsy 2
• Do not assume early seizures worsen outcomes—prospective studies show acute symptomatic seizures are not independently associated with worse neurological outcomes or mortality in CSVT 5
• Do not withhold anticoagulation due to seizure occurrence, as seizures do not contraindicate necessary anticoagulation therapy 4

Practical Algorithm

1. All CSVT patients: Obtain brain imaging to identify supratentorial lesions, hemorrhage, and thrombosis location 4, 5
2. If presenting seizures + supratentorial lesions: Start levetiracetam prophylaxis for 7 days 4, 2
3. If no presenting seizures: Do not start prophylaxis, regardless of imaging findings 5
4. If seizures occur during hospitalization: Treat acutely and continue levetiracetam for 7 days minimum 2
5. Consider continuous EEG monitoring if altered mental status is disproportionate to imaging findings 2