Combined analysis of risk factors for SUDEP

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Hesdorffer DC, Tomson T, Benn E, Sander JW, Nilsson L, Langan Y, Walczak TS, Beghi E, Brodie MJ, Hauser A (2011) Combined analysis of risk factors for SUDEP. Epilepsia 52(6):1150-9

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Abstract: PURPOSE: To pool data from four published case-control studies of sudden unexpected death in epilepsy (SUDEP) with live controls, to increase the power to determine risk factors. METHODS: Case-control studies from the United States, 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. KEY FINDINGS: Of the risk factors that could be analyzed across some or all studies, those that were statistically significant were 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. SIGNIFICANCE: 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.

Keywords: SUDEP, Epilepsy, Case-control study


  • Analysis of SUDEP risk factors from four case-control studies (US, Sweden, Scotland, England). The sample size consisted of 289 cases of SUDEP and 958 controls. Different risk factors were considered, including demographics, seizure etiology, antiepileptic drugs, and comorbidities. Risk factors that were included from all four studies included: gender, age at onset of epilepsy, duration of epilepsy, and age. These risk factors were examined using logistic regression. Results showed that SUDEP patients were more likely to be on polytherapy––in agreement with other studies like Asadi-Pooya AA and Sperling MR, Earnest MP et al., and Bell GS and Sander JW. SUDEP was also found to be more prominent in cases with high frequency of GTCSs. Interestingly, this goes against findings by Hitiris et al. and Vlooswijk et al., who found no correlation between SUDEP and GTCSs.


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