Findings of their recent study underscore the potential of epilepsy surgery to modify long-term health trajectories and support the value of early surgical referral and systematic follow-up in optimising outcomes, said a team of British researchers.
Medscape reports that in their study, published online in Epilepsia, they wrote that surgery led to a reduction in premature mortality among adults with drug-resistant focal epilepsy beyond 15 years and gradually normalised their long-term survival to more closely resemble that of the general population.
Older age at surgery, malformations of cortical development (MCD), and poor seizure control were independent predictors of epilepsy-related mortality.
For their study, led by Giorgio Fiore, UCL Queen Square Institute of Neurology, London, the researchers evaluated data of 1 062 adults (mean age at surgery, 36 ± 10 years) who underwent surgery for drug-resistant focal epilepsy at the National Hospital for Neurology and Neurosurgery in London between February 1990 and November 2022.
They assessed postoperative mortality by examining the cumulative incidence, temporal patterns, and causes of death and by comparing observed mortality with population-based expectations.
Key predictors of cause-specific mortality were also evaluated using Fine-Gray and cause-specific hazard models.
Postoperative seizure outcomes were classified annually using the International League Against Epilepsy (ILAE) surgery outcome scale (outcome class [OC], 1-6).
Key takeaways
Epilepsy-related deaths occurred in 36 adults (2.52 per 1 000 person-years), of which 18 deaths (1.26 per 1 000 person-years) were due to epilepsy alone and the remaining 18 were due to underlying neurologic disease (0.7%), suicide (0.7%), and aspiration pneumonia (0.4%).
Epilepsy-related deaths were reported in 25% of adults who were followed up for more than 15 years vs 75% of those who were followed up for 15 years or less (P = .006). Among those who were followed up for more than 15 years, the standardised mortality ratio was 0.65 (95% CI, 0.46-0.89), indicating that long-term survival aligns with that of the general population.
In the Fine-Gray model, older age at surgery (sub-distribution hazard ratio [SHR], 1.04; P = .01), MCD (SHR, 5.2; P = .01), and poor seizure outcomes (OC ≥ 4; SHR, 2.96; P = .04) were independent predictors of epilepsy-related mortality.
In the cause-specific hazard model, older age at surgery (cause-specific hazard ratio [CSHR], 1.05; P = .006), MCD (CSHR, 5.00; P = .017), and poor seizure outcomes (OC ≥ 4; CSHR, 2.90; P = .029) were independently associated with epilepsy-related mortality.
In practice
“The findings underscore the potential of epilepsy surgery to modify long-term health trajectories and support the value of early surgical referral and systematic follow-up in optimizing outcomes,” the authors wrote.
Limitations
The study’s observational design limited the detailed analysis of the association between older age at surgery and an increased risk for epilepsy-related mortality. The ILAE outcome scale was used to classify seizure outcomes, which limited the ability to assess the specific effect of focal to bilateral tonic-clonic seizures on mortality.
This study included only a small number of patients with MCD, restricting conclusion on the pathology-related survival risk.
Study details
Long-term survival after adult epilepsy surgery: Mortality and predictors in a large cohort
Giorgio Fiore, Jane de Tisi, Aidan O'Keeffe, et al.
Published in Epilepsia on 25 July 2025
Abstract
Objective
Long-term survival data in adults undergoing surgery for drug-resistant focal epilepsy remain limited. We examined mortality patterns and predictors in a large cohort followed for over 30 years.
Methods
Adults who underwent epilepsy surgery (1990–2022) were analysed. Prospectively collected clinical, surgical, and outcome data were included. We estimated the cumulative incidence of mortality and standardised mortality ratios (SMRs) for the cohort. Predictors of epilepsy-related and non-epilepsy-related deaths were identified using Fine–Gray and cause-specific hazard models.
Results
A total of 1062 individuals contributed 14 279 person-years of follow-up (median, 13 years). The overall mortality rate was 6.16 per 1000 person-years, with 2.52 per 1000 person-years due to epilepsy-related deaths, including 0.84 per 1000 person-years from sudden unexpected death in epilepsy (SUDEP). Epilepsy-related deaths were more frequent within the first 15 years’ post-surgery (p = 0.006). The overall SMR was 1.12 (95% confidence interval [CI]: 0.90–1.38), and 0.65 (95% CI: 0.46–0.89) among individuals followed for more than 15 years. Independent predictors of epilepsy-related mortality were older age at surgery, cortical malformations, and poor post-operative seizure control (International League Against Epilepsy [ILAE] outcome class ≥4). Non–epilepsy-related mortality was driven primarily by older age at surgery.
Significance
Epilepsy surgery is associated with reduced premature mortality and increasingly normalised long-term survival. Age at surgery, post-operative seizure control, and pathological findings are key determinants of survival, highlighting opportunities to improve surgical outcomes further.
Medscape article – Epilepsy Surgery Shows Long-Term Survival Benefits (Open access)
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