Body mass index and epilepsy risk: Evidence from cross-sectional and time to event analyses

Epilepsy is a neurological disorder characterized by substantial variability in etiology and clinical presentation. While an association between body mass index (BMI) and epilepsy has been described in clinic-based populations, it remains unclear whether abnormal BMI precedes epilepsy onset or primarily reflects downstream effects of the disease and its treatment.

We performed a retrospective population-based study including over one million adolescents who underwent a uniform medical evaluation prior to mandatory military service. BMI was recorded at the pre-enlistment examination and categorized according to age- and sex-specific percentiles. Epilepsy diagnoses were ascertained from medical documentation reviewed by military physicians and classified using accepted diagnostic criteria. Multivariable logistic regression was used to examine associations between BMI categories and prevalent epilepsy at enlistment, adjusting for sex, socioeconomic status, educational attainment, and cognitive score.

Compared with adolescents in the normal BMI range (5th-84th percentile), those at both extremes of the BMI distribution demonstrated increased epilepsy risk. In multivariable logistic regression adjusted for sex, socioeconomic status, intellectual functioning, and years of education, adolescents below the 5th percentile had higher odds of epilepsy (OR = 1.12, 95% CI 1.01-1.23), as did those in the 85th-94th percentile (OR = 1.09, 95% CI 1.02-1.16) and the ≥95th percentile (OR = 1.10, 95% CI 1.02-1.18). In time-to-event analyses using Cox proportional hazards models, a similar pattern was observed. Compared with the reference group, adolescents below the 5th percentile exhibited a 16% higher hazard of incident epilepsy (HR = 1.16, 95% CI 1.05-1.27), and those in the 85th-94th percentile showed a modestly increased hazard (HR = 1.08, 95% CI 1.01-1.15).

Both low and high BMI in adolescence were associated with a higher prevalence of epilepsy, independent of major sociodemographic variables. These findings support the notion that metabolic and developmental factors may play a role in epilepsy vulnerability and indicate that BMI could provide useful contextual information in population-based assessments.