Antiseizure medication-induced changes in serum ephrin-B2 and their association with treatment response in adults with generalised seizure disorders in Northern India: protocol for a prospective observational cohort study

Introduction Epilepsy affects approximately 65 million people worldwide, and India carries close to one-fifth of the global burden. Although generalised seizures account for a substantial share of new epilepsy diagnoses, approximately one-third of patients do not respond to their first antiseizure medication (ASM). Currently, there is a critical lack of reliable blood biomarkers to predict these treatment outcomes. Ephrin-B2 (encoded by EFNB2) regulates neuronal excitability, neurogenesis and synaptic plasticity via the mTOR and MAPK pathways; Mendelian randomisation evidence indicates that lower serum ephrin-B2 is associated with increased epilepsy risk. Whether ASM therapy raises serum ephrin-B2 and whether this tracks therapeutic response is unknown. Methods and analysis This single-centre, prospective, observational cohort study will enrol 50 adults (18–65 years) with newly diagnosed generalised seizures initiating valproate or levetiracetam monotherapy at clinician discretion. Serum ephrin-B2 will be measured by sandwich enzyme-linked immunosorbent assay (ELISA) at baseline and 24 weeks. The primary outcome is the within-participant change in serum ephrin-B2 to week 24; secondary outcomes are its correlation with the percentage reduction in 28-day seizure frequency and the between-drug difference in ephrin-B2 change. Responders are predefined as achieving ≥50% seizure reduction. Analyses comprise paired t-tests or Wilcoxon signed-rank tests, Pearson/Spearman correlation with regression and receiver operating characteristic analysis of ephrin-B2 as a response biomarker. Ethics and dissemination The study has been approved by the Institutional Ethics Committee, AIIMS Raebareli (IEC 2025-5 IMP-11) and follows ICMR National Ethical Guidelines for Biomedical and Health Research (2017) with written informed consent from all participants. Findings will be disseminated through peer-reviewed publication and conferences.