Electric Shutdown of the Brain: Is it a Cause of SUDEP?

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Wednesday, July 17, 2013

Sudden unexpected death in epilepsy (SUDEP) is the leading epilepsy-related cause of death. Whereas the risk of SUDEP is low if epilepsy is well-controlled, the risk over one year is as high as one in 100 persons with poorly controlled epilepsy.

SUDEP often occurs during sleep, in bed, and as an un-witnessed event. Although seizure-related cardio-respiratory dysfunctions are considered as likely causes of death, the mechanisms of SUDEP remain largely unverified. Data from a recent review of video-EEG-recorded cases of SUDEP revealed that the death is mostly triggered by generalized tonic clonic seizures (GTCS). These GTCS typically cause suppression of brain electrical activity or “electrical shutdown of the brain” (medically termed postictal generalized EEG suppression or PGES for short).

It has been hypothesized that electrical shutdown of the brain causes significant autonomic dysfunction, cardiac arrhythmia, central apnea, and resultant SUDEP. Lhatoo and colleagues compared 10 patients who died of SUDEP with 30 control subjects. They concluded that the duration of PGES was significantly prolonged in SUDEP patients, compared with the control subjects. In fact, the risk of SUDEP increased proportionately with the duration of PGES. However, these findings were not replicated in a subsequent study of 17 SUDEP patients. The discrepancy between these studies may be due to differences in the patients and control subjects used in the studies. A significant limitation in both studies was the lack of respiratory, oxygen and CO2 monitoring in the SUDEP patients. Accordingly, the significance of brain electrical shutdown in the pathophysiology of SUDEP remains controversial. None-the-less, it is noteworthy that PGES is a common EEG pattern in patients following a GTCS. Given that other prior similar seizures in the same person had not been life-threatening, additional intrinsic or extrinsic predisposing factors may be necessary to make one particular but otherwise usual seizure a fatal event.

Recent studies have shown that electrical shutdown of the brain is consistently associated with postictal coma, i.e., unresponsiveness. Could this be an important predisposing factor in SUDEP? Under homeostatic stress, such as hypoxemia (a low amount of oxygen in the blood), postictal coma could prevent patients from awakening and changing body position. Noteworthy too is the fact that SUDEP patients often die in the prone position. Therefore, could partial or complete blockage of the airway contribute to SUDEP? In a well-cited study by Kloster and colleagues, the prone position was observed in 71% (17 of 24) of SUDEP. Strikingly, of the eight video-EEG-recorded cases of SUDEP randomly published over 20 years, seven died in the prone position. Moreover, data in our recent meta-analysis, which was presented at this year’s American Academy of Neurology meeting, showed that the prone position was observed in 68.9% (143 of 205) SUDEP cases where the body position was documented at the time of death. These data demonstrate that there is a strong association between being in the prone position following a GTCS and SUDEP.

Is electrical shutdown of the brain a factor contributing to SUDEP? Despite insufficient evidence, my opinion is probably yes. Clearly, the mechanisms of SUDEP may be multifactorial, including autonomic dysfunction, cardiac arrhythmia, and central apnea. However, emerging data strongly suggest that GTCS can trigger a cascade of multiple factors that predispose a patient to SUDEP. These factors include ictal hypoxemia, PGES (electrical shutdown), postictal coma, and the prone position. A hypoxic and comatose patient who is face-down in a pillow or bed linen is at substantial risk for airway obstruction. The result is positional asphyxia. Accordingly, SUDEP may share mechanisms similar to that of Sudden Infant Death Syndrome (SIDS), and SUDEP is possibly preventable by patients avoiding the prone sleeping position, by arousing and turning the patient following a seizure, and by using anti-suffocation pillows.

Suggested Readings

Devinsky O. Sudden, unexpected death in epilepsy. NEJM.2011;365: 1801-11.

Lhatoo SD, Faulkner HJ, Dembny K, Trippick K, Johnson C, Bird JM. An electroclinical case-control study of sudden unexpected death in epilepsy. Ann Neurol2010;68: 787-96.

Tao JX, Yung I, Lee A, Rose S, Jacobsen J, Ebersole JS. Tonic phase of a generalized convulsive seizure is an independent predictor of postictal generalized EEG suppression. Epilepsia2013;54: 858-65. 

Authored by: James X. Tao MD PhD on 7/2014

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