Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): A retrospective study
French Institute of Health and Medical Research1, University of Cambridge2, Case Western Reserve University3, Columbia University4, University of Bristol5, University of Sydney6, Ghent University7, Harvard University8, University of Copenhagen9, University of Tübingen10, Centre national de la recherche scientifique11, University of Bonn12, University of Göttingen13, Medical University of Vienna14, Umeå University15, University of Liège16, University of Freiburg17, University of California, Davis18, Mayo Clinic19, Anschutz Medical Campus20, Royal Melbourne Hospital21, University of Chicago22, Karolinska Institutet23
TL;DR: Cardiorespiratory data showed a consistent and previously unrecognised pattern whereby rapid breathing developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiore Spiratory dysfunction, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal.
Abstract: Summary Background Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide Methods Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available Findings 147 (92%) of 160 units responded to the survey 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18–50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6–9·2) per 1000 patient-years, with a risk of 1·2 (0·6–2·1) per 10 000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal Interpretation SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest Improved supervision is warranted in epilepsy monitoring units, in particular during night time Funding Commission of European Affairs of the International League Against Epilepsy
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Abstract: ACC
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ACE
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ACS
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AF
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AHA
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Abstract: ACC
: American College of Cardiology
ACE
: angiotensin-converting enzyme
ACS
: acute coronary syndrome
AF
: atrial fibrillation
AGNES
: Arrhythmia Genetics in the Netherlands
AHA
: American Heart Association
AMIOVIRT
: AMIOdarone Versus Implantable cardioverter-defibrillator:
1,513 citations
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TL;DR: Improved understanding of the gradual development of epilepsy, epigenetic determinants, and pharmacogenomics comes the hope for better, disease-modifying, or even curative, pharmacological and non-pharmacological treatment strategies.
762 citations
TL;DR: The lives of most people with epilepsy continue to be adversely affected by gaps in knowledge, diagnosis, treatment, advocacy, education, legislation, and research and Concerted actions to address these challenges are urgently needed.
674 citations
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TL;DR: Sudden unexpected death in epilepsy rates, risk factors, triggers, and proposed mechanisms are reviewed, and potential preventive strategies are critically assessed.
Abstract: Although largely neglected in earlier literature, sudden unexpected death in epilepsy (SUDEP) is the most important epilepsy-related mode of death, and is the leading cause of death in people with chronic uncontrolled epilepsy. Research during the past two to three decades has shown that incidence varies substantially depending on the epilepsy population studied, ranging from 0.09 per 1000 patient-years in newly diagnosed patients to 9 per 1000 patient-years in candidates for epilepsy surgery. Risk profiles have been delineated in case-control studies. These and other studies indicate that SUDEP mainly occurs in the context of a generalised tonic-clonic seizure. However, it remains unclear why a seizure becomes fatal in a person that might have had many similar seizures in the past. Here, we review SUDEP rates, risk factors, triggers, and proposed mechanisms, and critically assess potential preventive strategies. Gaps in knowledge are discussed and ways forward are suggested.
616 citations
TL;DR: A unified SUDEP definition and classification is proposed to resolve current ambiguities and to retrieve cases that would not have been further studied if the previous definitions were used.
Abstract: Sudden unexpected death in epilepsy (SUDEP) is a category of death in people with epilepsy occurring in the absence of a known structural cause of death and is most likely heterogeneous with regard to mechanisms and circumstances. SUDEP is particularly difficult to investigate in research studies for several reasons, including its relatively low incidence, its unpredictable occurrence often in unwitnessed settings, and its low rate of complete autopsy examinations. Over the past two decades, two complementary definitions have been used in most SUDEP studies, but often with variations. We propose here a unified SUDEP definition and classification to resolve current ambiguities and to retrieve cases that would not have been further studied if the previous definitions were used. The proposed Unified SUDEP Definition and Classification contains, in addition to concepts inherent in the previous definitions, nine main recommendations. (1) The word "unexpected," and not the word "unexplained," should be uniformly used in the term SUDEP. (2) The SUDEP category should be applied when appropriate, whether or not a terminal seizure is known to have occurred. (3) The "Possible SUDEP" category should be used only for cases with competing causes of death, with cases left unclassified when data are insufficient to reasonably permit their classification. (4) Cases that would otherwise fulfill the definition of SUDEP should be designated as "SUDEP Plus" when evidence indicates that a preexisting condition, known before or after autopsy, could have contributed to the death, which otherwise is classified as SUDEP (e.g., coronary insufficiency with no evidence of myocardial infarction or long-QT syndrome with no documented primary ventricular arrhythmia leading to death). (5) To be considered SUDEP, the death should have occurred within 1 h from the onset of a known terminal event. (6) For status epilepticus as an exclusion criterion for SUDEP, the duration of seizure activity should be 30 min or more. (7) A specific category of SUDEP due to asphyxia should not be designated, the distinction being largely impractical on circumstantial or autopsy evidence, with more than one mechanism likely to be contributory in many cases. (8) Death occurring in water but without circumstantial or autopsy evidence of submersion should be classified as "Possible SUDEP." If any evidence of submersion is present, the death should not be classified as SUDEP. (9) A category of "Near-SUDEP" should be agreed to include cases in which cardiorespiratory arrest was reversed by resuscitation efforts with subsequent survival for more than 1 h. Scenarios that demonstrate the basis for each SUDEP category are described. If disagreement exists about which category fits a particular case, we suggest the use of consensus decision by a panel of informed reviewers to adjudicate the classification of the case.
476 citations
TL;DR: To pool data from four published case–control studies of sudden unexpected death in epilepsy with live controls, to increase the power to determine risk factors.
Abstract: Summary
Purpose: To pool data from four published case–control studies of sudden unexpected death in epilepsy (SUDEP) with live controls, to increase the power to determine risk factors.
Methods: Case–control studies from the United States, Sweden, Scotland, and England were combined. SUDEP was defined as (1) a history of epilepsy (>1 epileptic seizure during a period of <5 years); (2) death occurring suddenly; (3) death unexpected (i.e., no life-threatening illness); and (4) death remained unexplained after all investigative efforts, including autopsy. Definite SUDEP required all criteria. Logistic regression analyses adjusted for study. Further analysis simultaneously adjusted for study, age at death, gender, and duration of epilepsy.
Key Findings: Of the risk factors that could be analyzed across some or all studies, those that were statistically significant were increased frequency of generalized tonic–clonic seizures (GTCS), use of polytherapy, duration of epilepsy, young age at onset, gender, symptomatic etiology, and lamotrigine therapy. Results persisted when epilepsy onset was younger than 16 years and when it was 16 years or older. In univariate analysis, lamotrigine therapy was associated with significantly increased risk for SUDEP among individuals with idiopathic generalized epilepsy.
Significance: This analysis refines the identification of people with epilepsy that are at particular risk of SUDEP. The emerging profile indicates that people with early onset refractory symptomatic epilepsy with frequent GTCS and antiepileptic drug (AED) polytherapy are at higher risk. The results suggest that reduction of the number of GTCS is a priority, of more importance than reducing the number of AEDs. The role of AEDs and other treatment should be analyzed further in future studies.
413 citations
TL;DR: Advice to clinicians on ways to minimise the risk of SUDEP is provided, information to pass on to patients, and medicolegal aspects of these deaths are provided.
400 citations
TL;DR: Nocturnal supervision seems to protect against SUDEP, lending support to the view that SUDEP is a seizure-related phenomenon and that control of tonic-clonic seizures is important in its prevention.
Abstract: Objective: To examine the influence of various factors on the risk of sudden unexpected death in epilepsy (SUDEP). Methods: The authors investigated 154 cases in which a postmortem examination was performed. Each case had four controls with epilepsy from the community, matched for age and geographic location. Backward stepwise conditional logistic regression analysis was performed and odds ratios for risk and protection were determined. Results: The risk of SUDEP was increased with a history of generalized tonic-clonic seizures in the previous 3 months (odds ratio [OR]: 13.8, 95% CI: 6.6 to 29.1). The presence of supervision at night was found to be protective (OR: 0.4, 95% CI: 0.2 to 0.8) when a supervising individual shared the same bedroom or when special precautions such as a listening device were employed (OR: 0.1, 95% CI: 0.0 to 0.3). Conclusion: This work lends support to the view that SUDEP is a seizure-related phenomenon and that control of tonic-clonic seizures is important in its prevention. Nocturnal supervision seems to protect against SUDEP.
393 citations