Authors: Alexander Leaman, Mary Tremaine, Sandrine Nelson
Background: Seizures have been reported in up to 25% of patients with traumatic brain injury (TBI) and 15.2% of patients with aneurysmal subarachnoid hemorrhage (aSAH). In TBI, seizures within 7 days of injury are associated with increased length of stay, mechanical ventilation, and worse functional outcomes. Neurocritical Care Society Guidelines from 2024 note that seizure prophylaxis may be considered, recommending levetiracetam over phenytoin, for a short duration (≤7 days). Early seizures in aSAH have not been associated with worse outcomes but may cause acute complications, such as increased intracranial pressure and aneurysmal re-rupture. The 2023 aSAH guidelines state that antiseizure medications (ASMs) may be used for seizure prophylaxis in patients with high-risk features for ≤7 days, avoiding phenytoin due to excess morbidity and mortality. Consequently, levetiracetam is commonly used to prevent seizures in both TBI and aSAH, often prescribed as 500 mg twice daily (BID). However, a retrospective study from 2023 found a lower seizure incidence with 750 to 1000 mg BID. Additionally, a prospective study comparing levetiracetam 20 mg/kg loading dose followed by 1000 mg BID to phenytoin found no difference in seizure incidence. This study investigated the incidence of seizures with levetiracetam 500 mg BID compared to 750 to 1000 mg BID in patients with moderate to severe TBI or aSAH with high-risk features for seizures.
Methods: This was a retrospective study of patients admitted to either of two neurosurgical intensive care units (ICUs) in our health system. Patients were at least 18 years of age admitted with TBI or aSAH with high-risk features for seizures and received at least one dose of levetiracetam between January 1, 2023, and September 1, 2025. Patients were excluded for history of seizure disorder or cerebral neoplasm, ASM use prior to admission, death or withdrawal of care within 7 days, hospital admission less than 7 days, seizures on presentation, pregnancy, incarceration, and estimated creatinine clearance less than 30 mL/min. Patients were analyzed in two groups, those receiving levetiracetam 500 mg BID and those receiving levetiracetam 750 to 1000 mg BID. The primary outcome was the incidence of clinical or electrographic seizures within seven days. Secondary outcomes included adverse effects associated with levetiracetam (anemia, leukopenia, thrombocytopenia, or dose reduction or change to another ASM attributed to somnolence or agitation) and evidence of treatment escalation for seizures (increased levetiracetam dose, treatment duration greater than seven days, or addition of another ASM). A power calculation found that 178 patients would be required to find a 10.2% lower seizure incidence with the higher dosing strategy. Baseline characteristics were reported using descriptive statistics, with nominal outcomes analyzed using the Fisher’s exact test.
Results: A total of 79 patients were included, with 47 in the 500 mg BID group and 32 in the 750 to 1000 mg BID group. Baseline weight, serum creatinine, and Glasgow Coma Scale were similar between groups. There was no difference in seizure incidence in the first 7 days between groups, with 7 patients (14.9%) in the 500 mg BID group and 4 patients (12.5%) in the 750 to 1000 mg BID group (p=0.54). There was also no difference in the incidence of adverse effects or treatment escalation between groups.
Conclusions: In this study, the use of levetiracetam 750 to 1000 mg BID did not result in a lower seizure incidence compared to 500 mg BID. Future studies may help to quantify if a true difference exists between these dosing strategies on the incidence of seizures.
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