Prophylactic Fosphenytoin Reduces Cortical Stimulation Related Complications in Awake Craniotomy Compared to Levetiracetam

Introduction: Awake craniotomy with direct cortical stimulation (DCS) mapping is the gold standard for resection of pathology in eloquent regions. Prophylactic anti-seizure medications (ASMs) are commonly used to prevent intraoperative seizure. Among ASMs, there is a preference for levatiracetam (LEV), due to its low side effect profile. While there are studies which compare the efficacy and outcomes of different ASMs in several neurosurgical patient groups, this has not been done in the setting of DCS during awake craniotomy. We investigated whether a prophylactic dose of IV fosphenytoin (FOS) compared to LEV reduced the risk of intraoperative complications.

Methods: We performed a retrospective analysis of consecutive adult and pediatric awake craniotomy cases from 2018-2024 who received either LEV or FOS at the start of surgery. Data was collected on intraoperative seizures, intraoperative neurologic deficits, mapping failures, and 24-hour neurologic deficits and seizures.

Results: 112 patients met inclusion criteria; 61 (55%) were included in the LEV group and 51 (45%) were included in the FOS group. There was no significant difference in number of recorded or clinical intraoperative seizure between LEV and FOS (p=0.925). The FOS group had a 55.1% lower risk of mapping failure (95% CI -60.3- 87.5; p=0.200), and a 60.1% lower risk of intraoperative neurologic deficit (95% CI -16.1-86.3; p=0.075) relative to LEV. There were significantly fewer 24hr-deficits in the FOS group compared to the LEV group (p=0.012), so that only 4 patients would need to be treated with FOS instead of LEV to prevent one event of 24hr-deficit. When looking at composite outcome (including intraoperative events, mapping failure, and 24-hour deficit), 5 patients would need to be treated with FOS instead of LEV to reduce one composite event.

Conclusion : While the FOS group did not have fewer recorded or clinical intraoperative seizures, there was a lower risk of combined complications. FOS may attenuate focal seizure or epileptic activity from DCS compared to LEV, leading to safer mapping.