Epilepsy as a consequence of infantile vitamin B12 deficiency: observations from a prospective cohort study and a review of the literature

Introduction Symptomatic infantile vitamin B12 deficiency has far-reaching neurological consequences for affected children. Development of epilepsy is one such consequence whose incidence and characteristics have been scarcely studied and reported in the literature. Objective To describe the incidence, characteristics, and outcomes of epilepsy in a prospective cohort of children treated for infantile vitamin B12 deficiency and to briefly review the published literature on the topic. Methods A hospital-based prospective cohort study enrolling consecutive children with symptomatic infantile vitamin B12 deficiency was conducted from January 2021 to June 2023 to study the neurological consequences of deficiency. The cohort was followed through March 2026 to determine the incidence of epilepsy during follow-up. Those who developed epilepsy were evaluated for seizure and epilepsy types, neuroimaging and electroencephalography findings, treatment, response to treatment, and outcomes. Multivariable Cox proportional hazards modeling was performed using baseline predictors identified through univariate screening to determine independent associations with epilepsy. Results A total of 141 children with infantile vitamin B12 deficiency were part of the original cohort. Four died, 25 were lost to follow-up. Among the rest of the 112 children, at a median follow-up of 51 months (IQR: 45–55), 31 (28, 95% CI 19–36%) developed epilepsy. In those with epilepsy, the mean age at diagnosis of infantile vitamin B12 deficiency was 12.39 ± 3.9 months, and epilepsy developed after a mean interval of 4.7 ± 3.2 months after treatment. Epileptic spasms were the most common seizure type (15/31, 48.4%), while other forms of epilepsy were observed in 16. Of the 31, at last contact, 21 (68%) had either resolved or well-controlled epilepsy, 8 (26%) had drug-refractory epilepsy, and 2 (6%) died. In the multivariate model, acute-phase seizures were strongly associated with increased epilepsy risk (pooled HR 4.27, 95% CI:1.6–11.5, p = 0.004). Higher follow-up DQ was protective (pooled HR 0.94, 95% CI:0.89–0.99, p = 0.015). There was an early clustering of epilepsy, with all events occurring within 10 months of follow-up. Conclusion Epilepsy is a significant neurological outcome of vitamin B12 deficiency in infants. There is early clustering of epilepsy risk after treatment for deficiency, and acute-phase seizures are the strongest independent predictor of later epilepsy.