In the February 2012 issue of the Journal, Epilepsia, there are two studies that address the risk factors of Sudden Unexpected Death in Epilepsy (SUDEP). In the first study, Drs. Hesdorffer and colleagues representing the ILAE Commission on Epidemiology, Subcommission on Mortality, present an analysis of four case-controlled studies of sudden unexpected death in epilepsy (SUDEP). They sought to specifically determine whether it is generalized tonic-clonic seizures or was it a combination of antiepileptic drugs that were actually causing or provided the increased risk towards SUDEP.

The investigators evaluated a number of different medications including carbamazepine, phenytoin, valproic acid and other antiepileptic drugs such as lamotrigine. They looked at the number of seizure drugs that a patient was taking and they assessed separately whether it was the generalized tonic-clonic seizure or whether it was the combination of medications that were contributing to the increased risk of death.

In their analysis, they noted that generalized tonic-clonic seizure frequency, being on more than one seizure medication and the number of seizure medications were associated with an increased risk for SUDEP. An analysis of those individual antiepileptic drugs and the number of antiepileptic drugs adjusting for the frequency of generalized tonic-clonic seizures however revealed no increased risk associated with those seizure drugs when taken either by itself, in combination, or by the number of medications people were taking. Indeed, they found that generalized tonic-clonic seizure frequency remains strongly associated with the increased risk for SUDEP.

The study went on to suggest that none of the antiepileptic drugs considered were associated with increased SUDEP risk. They concluded that their results suggest that prevention of SUDEP must involve increased efforts to stop generalized tonic-clonic seizure frequency in order to avert the occurrence of death.

In an accompanying and separate analysis in the same issue of the journal, Drs. [Laberts] and colleagues and from an international group representing the Netherlands, Ireland and Queen Square in the United Kingdom presented an analysis of sudden unexpected death in epilepsy (SUDEP) and assessing what were the risk factors in their population that led to the increased risk of death. They specifically went to analyze whether their was a higher likelihood for sleep related SUDEP associated with the presence of nighttime or nocturnal seizures and whether the seizure patterns, whether you have seizures only at night vs. both day and night, differed in who was more likely to die.

The investigators examine a group of 154 individuals with epilepsy who died suddenly and after autopsy had confirmation of the definition of SUDEP. They also compared the group to a control group, or 616 people, living with epilepsy who had exclusively either seizures that occurred at day and night or exclusively nocturnal or nighttime seizures.

The investigators found that SUDEP was primarily a sleep related and unwitnessed event. In fact, they found that SUDEP occurred in 58% of cases and it was unwitnessed in 86%. If SUDEP was sleep related, it was more likely to be unwitnessed with an odds ratio of 4.4. Those with sleep related SUDEP were more likely to have a history of nocturnal seizures than those who had non-sleep related SUDEP with an odds ratio of 3.6. Those who died were more likely to have a history of nocturnal seizures than living controls with an odds ratio of 3.9. After correction for previously established SUDEP risk factors, the presence of nocturnal seizures remains significant at 2.6.

The investigators concluded that nocturnal seizures seem to be an independent risk factor for sudden unexpected death in epilepsy. Their findings also underscored the importance of prevention of seizures.

Both studies are important additions to our understanding of the issue of death and epilepsy. Both seem to be stating variations on the same theme that seizures are what cause the death and whatever that can be done to stop seizures is what is going to be necessary to prevent death from this condition. More work is obviously needed but the message is now becoming a little clearer that we must find ways to stop seizures in order to prevent such a terrible and devastating consequence from occurring.

Joseph I. Sirven, MD
Editor-in-Chief, epilepsy.com
Last Reviewed: 3/15/12

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