Risk factors in sudden death in epilepsy (SUDEP): The quest for mechanisms

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Nashef L, Hindocha N, and Makoff A (2007) Risk factors in sudden death in epilepsy (SUDEP): The quest for mechanisms. Epilepsia 48:5 859–71.

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Abstract: People with epilepsy may die suddenly and unexpectedly without a structural pathological cause. Most SUDEP cases are likely to be related to seizures. SUDEP incidence varies and is <1:1,000 person-years among prevalent cases in the community and approximately 1:250 person years in specialist centres. Case-control studies identified certain risk factors, some potentially amenable to manipulation, including uncontrolled convulsive seizures and factors relating to treatment and supervision. Both respiratory and cardiac mechanisms are important. The apparent protective effect of lay supervision supports an important role for respiratory factors, in part amenable to intervention by simple measures. Whereas malignant tachyarrhythmias are rare during seizures, sinus bradycardia/arrest, although infrequent, is well documented. Both types of arrhythmias can have a genetic basis. This article reviews SUDEP and explores the potential of coexisting liability to cardiac arrhythmias as a contributory factor, while acknowledging that at present, bridging evidence between cardiac inherited gene determinants and SUDEP is lacking.

Keywords: SUDEP, Cardiac arrhythmia, Sudden death, Long-QT syndrome


  • Review of incidence, risk factors, and possible mechanisms. Most valuable aspect is summary of monogenic mutations that could link epilepsy, SUDEP, and cardiac dysfunction. Summarizes mutations linked to paroxysmal cardiac disorders, noting whether the gene in question is expressed in brain and whether there is any seizure-related phenotype. Also lists a number of monogenic epilepses. Discussion of polygenic nature of paroxysmal cardiac deaths, SIDS, and SUDEP is also informative.


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