High SUDEP Rate in Some Persons with Childhood-Onset Epilepsy

A Commentary by Elson L So, MD
Saturday, January 15, 2011

A landmark study regarding sudden unexpected death in epilepsy (SUDEP) appeared in the New England Journal of Medicine this week. The investigators Dr. Matti Sillanpää of University of Turku, Finland and Dr. Shlomo Shinnar of Albert Einstein College of Medicine, United States prospectively followed a group of 245 children with epilepsy in Turku, for a median period of 40 years. They discovered that the mortality rate during follow-up was surprisingly higher than expected. The mortality rate in the group was 24%, which is about three times higher than expected. Two factors that played a major role in contributing to the mortality were the lack of seizure control during the last five years of the follow-up, and the presence of remote symptomatic cause of epilepsy (i.e. major neurological injury or insult as a cause of epilepsy). Nearly half of the persons who lacked seizure control had died during the follow-up period, compared with only 7% of those whose seizures had been controlled. 37% of those with remote symptomatic cause had died, compared with 12% of those without the cause. Remote symptomatic cause had consistently appeared in previous studies as a major factor associated with increased mortality in persons with epilepsy.

The other surprising finding in this new study is the high SUDEP rate. Over long-term follow-up, about 10% of the whole group had died of SUDEP. Whereas one could conclude with assurance that SUDEP will not happen to 90% of persons with childhood-onset epilepsy, the number of SUDEP cases actually accounted for nearly 40% of all deaths that had occurred in the whole group during the follow-up period. Similarly high numbers had been previously reported in persons with severe epilepsy or medically intractable epilepsy, but it has been widely believed that the rate should be lower in studies that include persons with well-controlled epilepsy, such as with the current population-based study. In any case, we should not fail to grasp the importance of this finding, because if we are able to prevent SUDEP from happening, we could actually be preventing 40% of the deaths in persons with childhood-onset epilepsy. In this light, SUDEP is a major malady with profound implications for public health policy and action.

The strength of this study derives from several features in the design and the conduct of the study. First is that this study is prospective with periodic assessment of the patients and complete ascertainment of their eventual outcome. Nearly all SUDEP studies up to now were retrospective in design. Second is that this study is a population-based study, whereas nearly all SUDEP studies were of select groups of patients with intractable epilepsy. Third is that the follow-up period in this study is long, with half of the patients having been followed for 40 year or longer. Previous studies have capitalized on large numbers of person-years as an advantage of the follow-up, but a large number of person-years often consists of predominantly short follow-up periods in many individual patients. This situation could likely miss SUDEP cases, because long duration of epilepsy had been reported in some studies to be a risk factor for SUDEP. Fourth is that the autopsy rate in this study is desirably high at 70%.

A few issues could be raised by Drs. Sillanpää and Shinnar's study. Are their results applicable to the U.S. population? For now, there is no clearly known demographic or epidemiologic basis to suspect that their results would not be applicable. Epidemiological studies of epilepsy have shown that the incidence, prevalence and distribution of etiologies are comparable among developed countries. Could the inclusion of prevalent epilepsy cases in their cohort increase the mortality rate? Severe epilepsy cases could have been followed longer than well-controlled epilepsy cases (and thus being included more in the prevalent group). The mortality rate of the prevalent cases (9.6 per 1000 person-years) was higher than the incident cases (5.3 per 1000 person-years), but the difference was reported to be not significant. Another question that could be asked is whether the results in this study are applicable to adult-onset epilepsy. We would not know the answer to this question until a similarly well-designed study is conducted in a adult-onset epilepsy population.

The SUDEP rates that I had cited above are those that the authors had qualified as SUDEP based on "alternative definition" by Dr. Lina Nashef. In that definition, SUDEP is not excluded when a seizure had been witnessed to have occurred close to the time of death. Many studies have shown that in the majority of witnessed SUDEP, a seizure had occurred very close to the time of death. Also, there frequently is evidence of tongue bite or urinary incontinence in unwitnessed SUDEP cases.

The cause of SUDEP is still unknown, but Drs. Sillanpää and Shinnar's study reinforces the need to strive for seizure control as one current strategy for reducing SUDEP in persons with epilepsy. Also, the findings in their study further assure persons with well-controlled epilepsy that their SUDEP risk is very low.

Suggested Readings

  • Nashef L, Hindocha N, Makoff A. Risk factors in sudden death in epilepsy (SUDEP): the quest for mechanisms. Epilepsia. 2007 May;48(5):859-71.
  • -Sillanpää M, Shinnar S. Long-term mortality in childhood-onset epilepsy. NEJM. 2010;363:2522-9.
  • So E. What is known about the mechanisms underlying SUDEP? Epilepsia. 2008; 49(Suppl 9):93-8.
  • So E, Bainbridge J, Buchhalter J, Donalty J, Donner E, Finucane A, et al. Special Report: Report of the American Epilepsy Society and the Epilepsy Foundation Joint Task Force on Sudden Unexplained Death in Epilepsy. Epilepsia. 2009;50:917-22.
Authored by: Elson L. So MD on 1/2011

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