LONDON--An ongoing case-control study of sudden unexpected death in epilepsy (SUDEP) has found that 12 of 15 patients with chronic epilepsy whose deaths were witnessed had respiratory distress as well as generalized tonic-clonic seizures. This finding, based on the largest collection of SUDEP cases to date, sheds new light on the phenomenon's proposed mechanisms.

"The accounts of these deaths support the view that both central and obstructive apnea are likely to play important parts in the genesis of SUDEP, with most witnesses stating that the subjects experienced breathing difficulties," reported J. W. Sander and colleagues in the February issue of the Journal of Neurology, Neurosurgery and Psychiatry.[1] "Airway obstruction seemed to be a significant factor in at least two cases."

Although SUDEP is not an uncommon cause of mortality in patients with chronic epilepsy, most deaths are unwitnessed. Of the 135 SUDEP cases identified to date by the investigators, only 15 (11%) were witnessed; nine of these patients had localization-related epilepsy, two had idiopathic generalized epilepsy, and four had epilepsy of undetermined type. Nine were men and six were women; ages ranged from 17 to 47 years. Seven of the patients died in bed, six died elsewhere in the home, and two died outdoors.

In this study, SUDEP was defined as "sudden, unexpected, nontraumatic, and nondrowning death in an individual with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus where postmortem examination does not reveal a cause for death." According to Prof Sander, a consultant neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, London, the rate of postmortem examinations in sudden death cases in the UK exceeds 95%, compared with less than 25% in the US.

Various mechanisms have been proposed for SUDEP, including apnea, which was a frequent finding in a study of ictal cardiorespiratory variables.[2] In addition, in animal models of chemically induced seizures, death is often accompanied by "a precipitous drop in the partial pressure of oxygen [which] occurs along with a concomitant rise in pulmonary artery and left arterial pressures resulting in pulmonary edema," the investigators reported. "This model of SUDEP is consistent with the observation that pulmonary edema, in itself thought insufficient to cause death, is a frequent finding and almost a pathological hallmark for SUDEP." The authors noted that development of apnea during a seizure does not exclude a role for cardiac arrhythmias as a mechanism in SUDEP. Although the mechanism by which epileptic seizures are switched off remains unknown, Prof Sander said there is "circumstantial evidence that this might be driven by the release of endogenous opioids." Up-regulation would thus cause central apnea.

A study of SUDEP cases in the UK soon to be published by Prof Sander's group has found that at least 400 people die each year, "twice as many as we had thought initially. So it might well be that SUDEP is a much wider problem for people with chronic epilepsy than we like to think."

--Debra Hughes

References
1. Langan Y, Nashef L, Sander JW. Sudden unexpected death in epilepsy: a series of witnessed deaths. J Neurol Neurosurg Psychiatry. 2000;68:211-213.
2. Nashef L, Walker F, Allen P, et al. Apnoea and bradycardia during epileptic seizures: relation to sudden death in epilepsy. J Neurol Neurosurg Psychiatry. 1996;60:297-300.

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