Abstracts

Rationale: Sudden unexpected death in epilepsy (SUDEP) is the most common condition-related cause of death in chronic epilepsy. Case-control studies using living people with epilepsy as controls have aimed at identifying factors that distinguish the epilepsy patient at risk for SUDEP. Patient demographics, seizure and epilepsy characteristics, comorbidities, and treatment with AEDs have thus to a variable extent been analyzed as risk factors in these studies. Some risk factors, e.g. high frequency of generalized tonic-clonic seizures (GTCS), have been consistently identified. There are also disagreements between the studies and a lack of precision in the risk estimates, which can be attributed to small number of cases in each study. To counteract these limitations, the Epidemiology task force of the International League Against Epilepsy pooled data from the four published case-control studies of sudden unexplained death in epilepsy (SUDEP) with live controls, to increase the power to determine risk factors. Methods: Case-control studies from the US, Sweden, Scotland and England were combined. SUDEP was defined as 1) a history of epilepsy (> 1 epileptic seizure during a period of <5 years); 2) death occurring suddenly; 3) death unexpected (i.e., no life threatening illness); and 4) death remained unexplained after all investigative efforts, including autopsy. Definite SUDEP required all criteria. Logistic regression analyses adjusted for study. Further analysis simultaneously adjusted for study, age at death, gender, and duration of epilepsy. Results: Statistically significant SUDEP risk factors (Table 1) included increased frequency of generalized tonic clonic seizures (GTCS), use of polytherapy, duration of epilepsy, young age at onset, gender, symptomatic etiology, and lamotrigine therapy. Results persisted when epilepsy onset was younger than 16 years and when it was 16 years or older. In univariate analysis, lamotrigine therapy was associated with significantly increased risk for SUDEP among individuals with idiopathic generalized epilepsy. Conclusions: This analysis refines the identification of people with epilepsy that are at particular risk of SUDEP. The emerging profile indicates that people with early onset refractory symptomatic epilepsy with frequent GTCS and antiepileptic drug (AED) polytherapy are at higher risk. The results suggest that reduction of the number of GTCS is a priority, of more importance than reducing the number of AEDs. The role of AEDs and other treatment should be analyzed further in future studies.

Funded by The International League Against Epilepsy