Clinical Topics

Sudden Unexplained Death in Epilepsy

Nikesh Ardeshna, MD
Dr. Ardeshna is the Medical Director of Epilepsy Services for the Erlanger Health System in Chattanooga, Tennessee.


 

References

One condition associated with epilepsy that still provokes significant anxiety for patients, physicians, and family members is sudden unexplained death in epilepsy (SUDEP). Although knowledge of SUDEP has increased significantly, a considerable amount remains unknown. The anxiety about SUDEP is so profound that some physicians do not feel comfortable discussing it with their patients with epilepsy. Nevertheless, the issue is real and is a major cause of mortality in these individuals.

The prevalence of SUDEP is one in 1,000 people with epilepsy. In population-based cohorts, the incidence is lower than that in epilepsy clinics. People with epilepsy have a two- to three-times increased risk of death, compared with the general population. The rate of SUDEP in the epilepsy population is 24 times that of the general population. The incidence of SUDEP is lower in children than in adults. It is not clear why risk changes with age, but this change could be related to the cumulative buildup of risk with many years of seizures or with the duration of epilepsy. Overall, most cases of SUDEP are sleep-related and unwitnessed, which adds to the mystery and fear surrounding SUDEP.

Studies have shown that the most important risk factors for SUDEP are frequent generalized tonic–clonic seizures and being on a regimen of multiple antiepileptic drugs (AEDs), or polytherapy. Nocturnal seizures are another risk factor, and some neurologists suggest that night supervision of patients with epilepsy may be protective. Other risk factors that have not necessarily been consistently replicated for SUDEP include male gender, IQ below 70, early onset of epilepsy, and poor compliance with AEDs. Furthermore, a recent study suggests that sleeping in the prone position also may be a risk factor for SUDEP.

The criteria for defining SUDEP include the occurrence of a sudden, unexpected, or unexplained death in a patient with epilepsy. The death does not result from trauma or drowning. It can be witnessed or unwitnessed. Evidence of a recent seizure may be present, but not evidence of status epilepticus. SUDEP is further classified as definite, probable, or possible, primarily based on whether autopsy findings are available. Post-mortem examination does not reveal a cause of death in SUDEP.

The mechanisms causing SUDEP are postulated to be cardiac arrhythmia, respiratory failure, cerebral electrical shutdown, or a combination of these factors. More specifically, pathology may be linked to certain channelopathies or to neurotransmitter dysfunction in the brainstem. SUDEP and sudden infant death syndrome have similar characteristics and mechanisms in common.

Further research into the aforementioned areas such as channelopathies might help identify which patients are at greater risk for SUDEP and how one risk factor interacts with another. Ultimately, this research could lead to the development of an evidence-based algorithm to stratify patients and guide treatment.

Minimizing the risk for and, ideally, preventing SUDEP are two of the most important goals in epilepsy treatment. A multifaceted approach is needed for this goal. The first step is increasing awareness of SUDEP. The second is to reduce the frequency of generalized tonic–clonic seizures, and to employ rational polytherapy with AEDs. Third, continued research is needed particularly into the mechanisms of SUDEP. Most importantly, the risk of SUDEP underscores the need to treat epilepsy aggressively and early with the overriding goal of seizure freedom. Even a single seizure, and not necessarily a generalized tonic–clonic seizure, can increase the risk of SUDEP.

For epilepsy patients of all ages, neurologists should consider all available treatment modalities. In addition, medical practitioners should continually evaluate, re-evaluate, and, if needed, appropriately change the treatment regimen to achieve the goal of seizure freedom while maintaining quality of life. Many new therapeutic options are available. Physicians are encouraged to refer patients with continued seizures to a specialist such as an epileptologist or an epilepsy center.

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