Risk of epilepsy in people with adult-onset hydrocephalus: insights from the UK Biobank

AIM: We aim to determine whether individuals with adult-onset hydrocephalus have an increased risk of incident epilepsy over time. METHODS: We analysed data from the UK Biobank cohort. Diagnoses of "hydrocephalus" and "epilepsy" were identified through ICD-10-coded health records, excluding congenital and secondary cases. The association between these two diseases was investigated using logistic regression (adjusted for age and sex); subsequently, we performed a sampled cohort study to evaluate the hazard ratio (HR) for incident epilepsy in people with adult-onset hydrocephalus using Cox proportional hazards models with a dedicated sensitivity analysis including different sets of covariates such as demographic, lifestyle, vascular, and genetic factors. RESULTS: Our cohort included 483,790 controls, 5,028 individuals with epilepsy, and 320 with adult-onset hydrocephalus. Hydrocephalus and epilepsy were strongly associated (OR: 9.6, 95% CI: 6.4-13.8, p < 0.001). Adjusted Cox models demonstrated a markedly increased risk of incident epilepsy in people with adult-onset hydrocephalus, with HR values ranging from 14.62 (95% CI: 7.91-27.00, p < 0.001) to 23.80 (95% CI: 12.87-44.03, p < 0.001) across models, after adjusting for multiple covariates. Results were also consistent after excluding people with comorbid neurodegenerative dementias such as Alzheimer's disease. CONCLUSIONS: We demonstrated a markedly increased risk of epilepsy in adult-onset hydrocephalus, independent of vascular and neurodegenerative comorbidities and not attributable to shunt-related complications. These findings underscore the importance of increased diagnostic vigilance, as seizures may be under-recognized in this population, and support further research to clarify mechanisms and optimize management strategies.