New Research Helps to Unravel the Mystery of SUDEP

Photo: Dr. Elizabeth Donner

A highly anticipated study was published online this month in the prestigious medical journal, The Lancet Neurology[1].  Drs. Philippe Ryvlin, Lina Nashef and Torbjörn Tomson, in association with many other physicians and researchers from around the world, reported the results of a large project, known as Mortemus, that was undertaken to shed light on what happens immediately preceding a SUDEP death.

The investigators contacted 160 epilepsy monitoring units in Europe, Israel, Australia and New Zealand, to obtain information on all cardiorespiratory arrests occurring in those units.  An epilepsy monitoring unit, or EMU, is a specialized inpatient hospital unit designed to evaluate and treat seizures.  Typically, people with epilepsy are admitted to an EMU to undergo continuous video electroencephalogram (EEG) monitoring, with the aim to capture seizures on video EEG.  Often this is done to determine if an individual is a candidate for epilepsy surgery or other specialized epilepsy treatments.  People with epilepsy are frequently weaned off their anticonvulsant medications to encourage the occurrence of seizures during the EMU admission.  By collecting data on deaths recorded in EMUs during this intensive monitoring period, the teams hoped to get information on the exact sequence of events preceding SUDEP.

Dr. Ryvlin and colleagues collected data from 147 EMUs, which included 29 cardiorespiratory arrests.  Of the 29 cardiorespiratory arrests, there were 20 deaths and 9 near-deaths, in which the medical team successfully resuscitated the person with epilepsy.  Among the deaths were 16 cases of SUDEP.  Several findings in these 16 cases are consistent with previous reports, including the fact that all deaths occurred at night and all followed a generalized tonic-clonic seizure.  While a death does not need to follow a seizure to meet criteria for SUDEP and there are reported SUDEP deaths occurring with no evidence of a preceding seizure, studies have reported that 50 – 90% of witnessed SUDEP deaths occur following a convulsive seizure.

There were no deaths in children reported in this study, even though the EMUs that were surveyed had a significant number of children admitted.  This is also consistent with previous reports of lower rates of SUDEP in children.  In this study, the absence of any deaths in children may also be related to the closer observation that children receive in an EMU setting.

Ten of the SUDEP deaths occurred during EEG monitoring.  The research team meticulously reviewed the heart, breathing and EEG data and was able to delineate the sequence of events that preceded SUDEP in these 10 cases.  They describe a consistent finding where, following a generalized tonic-clonic seizure, there is a disturbance of heart rate and breathing, coupled with a dramatic flattening of the brain waves on EEG and then slowing of the heart rate and cardiac arrest.  The pattern of brain wave flattening that was noted in this study has also been identified by other investigators of SUDEP and is termed Postictal Generalized EEG Suppression, or PGES.  It has been suggested that the presence of PGES may help to identify those people with a greater risk of SUDEP.

Although PGES tends to occur in cases of SUDEP deaths that follow a seizure, studies show that PGES occurs with between 27 to 82% of generalized seizures, the vast majority of which do not result in death.  The Mortemus study demonstrates that, in all the recorded cases of SUDEP, PGES was accompanied by severe cardiac and breathing abnormalities. Dr. Ryvlin and colleagues suggest that this combination of findings may be secondary to a breakdown in the brain’s control over the basic function of heart rate and breathing.  It is possible that the same brain-mediated mechanism that helps to stop a seizure also affects the brain’s control over heart function and breathing and produces the PGES pattern.

It is important to recognize that people admitted to an EMU do not represent the general population of people with epilepsy and, for that reason, the results of this study cannot be generalized to all people with epilepsy or to all cases of SUDEP.  These findings may be related to the changes in medications that are made during an EMU admission or specific to people being evaluated for epilepsy surgery who are typically admitted to the EMU.  However, the work of this accomplished research team does represent an important step towards a more complete understanding of the underlying mechanism of SUDEP.  As we learn more we get closer to the development of preventative strategies for SUDEP and the ultimate goal of preventing future deaths.

  1. Ryvlin, P et al.  Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study.  Lancet Neurol., 2013 Sep 3; pii:S1474-4422(13)70214-X [Epub ahead of print].

Dr. Elizabeth Donner is a Pediatric Neurologist at the Hospital for Sick Children, Toronto and Associate Professor at the University of Toronto.  She conducts SUDEP research, is implementing a pediatric SUDEP registry and is a co-founder of SUDEP Aware.