Epilepsy as a Contributing Cause of Death Among Malignant Brain Tumour Patients in the United States, 1999-2024: A Multiple-Cause CDC WONDER Joinpoint Analysis with Relevance to the Epilepsy Treatment Gap in Pakistan.

OBJECTIVES

Seizures are among the most disabling neurological manifestations in patients with malignant brain tumours. Pakistan faces a substantial epilepsy treatment gap and lacks integrated neuro-oncology surveillance data. This study aimed to evaluate temporal trends in epilepsy recorded as a contributing cause of death among malignant brain tumour decedents in the United States and to propose a transferable surveillance model for countries with limited epidemiological infrastructure.

METHOD: A retrospective population-based ecological time-trend study was conducted using the CDC WONDER Multiple Cause of Death database from 1999 to 2024. Death certificates listing malignant brain tumours (ICD-10 C71) as the underlying cause and epilepsy or status epilepticus (ICD-10 G40-G41) as contributing causes were included. Annual proportions of malignant brain tumour deaths with epilepsy co-reported were calculated with binomial standard errors. Joinpoint regression was used to estimate Annual Percent Change (APC), Average Annual Percent Change (AAPC), and 95% confidence intervals. Reporting adhered to the STROBE guideline.

RESULTS

The proportion of malignant brain tumour deaths with epilepsy or status epilepticus recorded as a contributing cause increased from 0.26% in 1999 to 1.45% in 2024, representing a 5.5-fold increase. No significant temporal change was observed between 1999 and 2005 (APC -7.36%; non-significant). This was followed by a significant increase between 2005 and 2020 (APC +13.05%; p=0.006), with a continued but non-significant rise from 2020 to 2024 (APC +5.13%). Overall, the average annual increase was significant (AAPC +6.53%; 95% CI 5.42-8.10; p<0.001).

CONCLUSIONS

Epilepsy was increasingly documented as a contributing cause of death among malignant brain tumour decedents in the United States over the 25-year study period, reflecting a persistent seizure burden in neuro-oncology. This reproducible population-based surveillance approach may help characterize epilepsy-related mortality and inform neuro-oncology surveillance strategies in countries lacking comprehensive registries, including Pakistan.