Risk and cause of death in post-traumatic epilepsy: a register-based retrospective cohort study.

OBJECTIVE: Post-traumatic epilepsy (PTE) is common, but its impact on survival after traumatic brain injury (TBI) of different severity and in different demographic patient groups is unknown. We analyzed the risk of death associated with PTE with adjustment for TBI severity, causes of death, and the contribution of epilepsy as direct or contributing cause of death. METHODS: Register-based, retrospective cohort study. All individuals hospitalized in Sweden for a TBI between 2000 and 2010 without prior seizures were identified in the National Patient Register, with follow-up until 2017. Subsequent epilepsy was identified by ICD-10 codes. Time-dependent Cox proportional hazard ratio (HR) was used to assess hazard of death, with epilepsy as a time-updated covariate. Adjusted analyses for age, gender, injury severity and comorbidities were also performed. Causes of death were analyzed using the Cause of Death Register. RESULTS: Among 111 947 individuals with TBI, subsequent epilepsy diagnosis was associated with a crude HR of 2.3 (95% CI: 2.2-2.4) for death. Stratified analyses showed a HR of 7.8 (95% CI: 6.5-9.4) for death in younger individuals. Epilepsy was a more common underlying cause of death in younger individuals. CONCLUSION: PTE is associated with a higher risk of death and epilepsy seems to contribute to a significant proportion of deaths, especially in younger age groups. Future studies on whether improved epilepsy treatment can reduce mortality are needed.

Potential for improved retention rate by personalized antiseizure medication selection: A register-based analysis.

OBJECTIVE: The first antiseizure medication (ASM) is ineffective or intolerable in 50% of epilepsy cases. Selection between more than 25 available ASMs is guided by epilepsy factors, but also age and comorbidities. Randomized evidence for particular patient subgroups is seldom available. We asked whether register data could be used for retention rate calculations based on demographics, comorbidities, and ASM history, and quantified the potential improvement in retention rates of the first ASM in several large epilepsy cohorts. We also describe retention rates in patients with epilepsy after traumatic brain injury and dementia, patient groups with little available evidence. METHODS: We used medical, demographic, and drug prescription data from epilepsy cohorts from comprehensive Swedish registers, containing 6380 observations. By analyzing 381 840 prescriptions, we studied retention rates of first- and second-line ASMs for patients with epilepsy in multiple sclerosis (MS), brain infection, dementia, traumatic brain injury, or stroke. The rank of retention rates of ASMs was validated by comparison to published randomized control trials. We identified the optimal stratification for each brain disease, and quantified the potential improvement if all patients had received the optimal ASM. RESULTS: Using optimal stratification for each brain disease, the potential improvement in retention rate (percentage points) was MS, 20%; brain infection, 21%; dementia, 14%; trauma, 21%; and stroke, 14%. In epilepsy after trauma, levetiracetam had the highest retention rate at 80% (95% confidence interval [CI] = 65-89), exceeding that of the most commonly prescribed ASM, carbamazepine (p = .04). In epilepsy after dementia, lamotrigine (77%, 95% CI = 68-84) and levetiracetam (74%, 95% CI = 68-79) had higher retention rates than carbamazepine (p = .006 and p = .01, respectively). SIGNIFICANCE: We conclude that personalized ASM selection could improve retention rates and that national registers have potential as big data sources for personalized medicine in epilepsy.

Post-traumatic epilepsy in adults: a nationwide register-based study.

OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of epilepsy. Our aim was to characterise the risk of epilepsy in adults after hospitalisation for TBI. METHODS: Register-based cohort study. All individuals aged 18-100 with a first hospitalisation for TBI in the comprehensive national patient register in Sweden between 2000 and 2010 (n=111 947) and three controls per exposed (n=325 881), matched on age and sex were included. Exposed individuals were categorised according to TBI severity. Kaplan-Meier curves were used to estimate the risk of epilepsy and Cox regression to estimate the hazard in univariate or multivariate regression. RESULTS: The 10-year risk of epilepsy was 12.9% (95% CI 11.7% to 14.1%) for focal cerebral injuries, 8.1% (95% CI 7.5% to 8.7%) for diffuse cerebral injuries, 7.3% (95% CI 6.9% to 7.7%) for extracerebral injuries, 2.8% (95% CI 2.4% to 3.2%) for skull fractures and 2.6% (95% CI 2.4% to 2.8%) for mild TBI. The risk of epilepsy after any TBI was 4.0% (95% CI 3.8% to 4.2%). The corresponding 10-year risk for controls was 0.9% (95% CI 0.9% to 0.9%). The HR increased with a more severe injury, from 3.0 (95% CI 2.8 to 3.2) for mild injury to 16.0 (95% CI 14.5 to 17.5) for focal cerebral injury. Multivariable analyses identified central nervous system (CNS) comorbidities as risk factors, but TBI remained significant also after adjustment for these. Other identified risk factors were male sex, age, mechanical ventilation and seizure during index hospitalisation. CONCLUSION: The risk of post-traumatic epilepsy is considerable, also with adjustments for CNS comorbidities.