Ole of Prophylactic Levetiracetam in Central Nervous System Tuberculosis: A Randomized Double-Blind Placebo-Controlled Study

Background: Seizures in central nervous system (CNS) tuberculosis are associated with poor neurological and functional outcomes. Patients with advanced Tuberculosis Medical Research Council (TB-MRC) stage, cortical lesions, hydrocephalus, infarcts, tuberculomas, or epileptiform electroencephalography (EEG) abnormalities represent a high-risk subgroup; however, the role of prophylactic antiseizure medication remains uncertain. Aim: To evaluate the efficacy and safety of prophylactic levetiracetam in preventing first seizure occurrence in high-risk CNS tuberculosis patients. Methods: This randomized, double-blind, placebo-controlled study included patients aged > 12 years with CNS tuberculosis diagnosed within 6 months, without prior seizures or antiseizure medication use. High-risk status was defined by TB-MRC grade II/III, epileptiform EEG abnormalities, or abnormal neuroimaging. Participants were randomized to receive levetiracetam or placebo in addition to standard CNS tuberculosis treatment. Levetiracetam was titrated up to 40 mg/kg/day. The primary outcome was occurrence of first epileptic seizure within 90 days. Secondary outcomes included modified Rankin Scale, Barthel Index, EEG changes, and Side-effect in Antiepileptic Drug Treatment (SIDAED) adverse-effect scores. Results: Of 361 screened patients, 44 were randomized: 23 to levetiracetam and 21 to placebo. The most common exclusions were seizures at presentation in 174/361 patients and prior antiseizure medication use despite no documented seizures in 86/361 patients. During 90-day follow-up, no patient in the levetiracetam arm developed seizures, compared with one patient in the placebo arm. Baseline epileptiform or delta EEG abnormalities were present in nearly half of enrolled patients. At 90 days, EEG abnormalities reduced more clearly in the levetiracetam group, with fewer persistent epileptiform/delta abnormalities than in the placebo group; however, this intergroup difference did not reach statistical significance, likely due to the small sample size. Functional outcomes and SIDAED scores remained comparable between groups. Conclusion: Prophylactic levetiracetam was safe and well tolerated in high-risk CNS tuberculosis patients. It showed a favorable signal for seizure prevention and EEG improvement, warranting confirmation in larger multicentric trials. Publication History Article published online: 15 July 2026 © 2026. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/) Thieme Medical and Scientific Publishers Private Limited A-13A, Graphix Tower 1, 6th floor, Sector 62, Noida 201309, Uttar Pradesh, India