EVALUATION OF BENEFICIAL EFFECTS OF LEVETIRACETAM AND CARBAMAZEPINE IN POST STROKE EPILEPSY

Abstract

Post-stroke Epilepsy (PSE) has been identified as a significant clinical condition in stroke survivors affecting outcome, quality of life, and hospital cost. They are clinically underestimated without consensus for prophylaxis and treatment. The PSE were empirically managed with older Anti-Epileptic Drugs (AEDs) like Carbamazepine (CBZ), which is not without issues on side effect, drug-drug interactions, and tolerability. Newer AEDs like levetiracetam (LEV) have better safety and tolerability profiles, however there is limited clinical evidence supporting its use in the treatment and prevention of PSE. This study was therefore designed to identify determinants of PSE and compare prophylactic and therapeutic effects of LEV and CBZ monotherapy. The study was divided into three phases and carried out in three purposively selected tertiary health institutions in South West Nigeria. The first phase involved detailed review of records for socio-demographics, aetiology and medication characteristics of 946 adults, aged ≥1 6, and attending epilepsy clinics for a minimum period of 5 years using convenient sampling method. In the second phase, 346 neuroimage confirmed stroke patients who consented were recruited and followed up for 24 months. Post Stroke Outcome (PSO) such as severity, functional outcome, cognition and epileptiform pattern were assessed using National Institute of Health Stroke Scale (NIHSS), Modified Ranking Scale (MRS), Cognitive Screening Instrument for Dementia (CSID), and Electroencephalography (EEG), respectively. Development of PSE, Mortality Rate (MR) and determinants of PSE were evaluated. Those that developed seizures were randomised into AED groups and followed up for 1 2 months and PSO evaluated. The third phase recruited 240 neuroimage confirmed stroke patients with no prior seizure history and randomly divided into Prophylactic Group (PG) [80 each of LEV and CBZ] and Non-Prophylactic Group (NPG). The Lev (250mg) and CBZ (200mg) were administered twice daily and evaluated for PSO. Data were analysed using descriptive statistics, Chi square, and independent student’s t test at α0.05. The records showed that majority of the patients had idiopathic (60.1 %) and structural epilepsy (24.9%), with stroke being the commonest. Two hundred and ninety-four 294(31 .1 %) were not on AED and 51 5(79.0%) of those on AEDs used CBZ. Twenty-seven percent (27%) developed PSE and identified determinants of PSE were severe stroke (p0.01 0), diabetes mellitus (p0.002), cortical involvement (p0.01 6), insomnia (p0.009) and epileptiform pattern (p0.000). Comparing CBZ with LEV groups among PSE, PSO showed higher MR [21 (45.7%) versus 1 1 (23.9%), p0.029], poor outcome on MRS [28(63.6%) versus 1 7(40.5%), p0.032], severe NIHSS [26(56.5%) versus 1 3(28.3%), p0.006] and impaired cognition on CSID [20(43.5%) versus 1 6(34.8%), p0.08], respectively. In phase 3, 1 7(1 0.6%) of PG [1 0(1 2.8%) CBZ versus LEV 7(8.8%)] compared to 1 7(21 .3%) of NPG developed seizures. There was higher MR [22(1 3.7%) versus 34(42.5%), p0.029], poor outcome on MRS [(47(58.8%) versus 59(36.9%), p0.001 )], and CSID score (53.39±26.1 9 versus 36.37±34.06,vii p0.001 ) in NPG compared with PG. Stroke severity, cortical involvement, epileptiform pattern and background diabetes mellitus were identified as predictors of post stroke epilepsy. Levetiracetam exhibited better therapeutic effect than carbamazepine for prophylaxis and treatment of post stroke epilepsy.