Sudden cardiac arrest and SUDEP: partially overlapping clinical entities

[Part 2: Questions; Lamberts R & Thijs R]

 

 

Seizure-induced cardiac arrhythmia is one of the proposed causes of SUDEP. Sporadic video-EEG recordings in SUDEP suggest that a minority of cases suffers from life-threatening ventricular arrhythmia following an epileptic seizure (Dasheiff et al., 1986; Espinosa et al., 2009). It is, however, difficult to translate these figures to the general community, as these recordings were obtained in a highly selected group of people with severe epilepsy. Interestingly, up to 30% of all cases with a sudden cardiac arrest (SCA) in the general community have a negative postmortem examination, as seen in SUDEP (Puranik et al., 2005). We therefore ascertained in a community-based registry whether epilepsy may carry an increased risk for SCA and if so, whether SCA in epilepsy may partially overlap with SUDEP. We identified 1019 people with ECG-documented ventricular arrhythmia who were resuscitated outside of the hospital and compared those with 2834 controls without ventricular arrhythmia from general practitioners in the same area (Bardai et al., 2012). Documentation of ventricular arrhythmia guaranteed that all cardiac arrests were due to a primary cardiac cause. People with epilepsy were found to have a 3x higher risk of ventricular arrhythmia irrespective of other cardiac risk factors. In a second study, we analyzed whether cases with SCA and epilepsy fulfilled SUDEP criteria and looked for clinical determinants (Lamberts et al., forthcoming). In most people with epilepsy ventricular arrhythmia was not seizure-related and occurred in the context of a definite or presumed cardiovascular cause. In 2 out of 18 cases no such cardiovascular cause was found and a diagnosis of near-SUDEP was established after successful resuscitation. Cases with SCA and epilepsy more frequently appeared to have clinically relevant heart disease and intellectual disability than epilepsy controls. No differences were found between both groups with respect to epilepsy severity.

 

We, thus, found that SCA and SUDEP partially overlap and ventricular arrhythmias are one of the causes of SUDEP not only in ictal recordings of people with severe epilepsy, but also in community-dwelling people with epilepsy. Cardiovascular disease events constitute, however, the predominant cause of SCA in epilepsy. The burden of sudden death in epilepsy is thus not confined to SUDEP. Non-seizure related causes also likely play an important and possibly unrecognized role in the high premature mortality rates in epilepsy. Accordingly, risk of premature death was found to be elevated up to 25 years after the first seizure when most people were seizure-free (Neligan, 2011).

 

Shared genetics, or shared cardiovascular comorbidity are potential explanations for the increased risk of ventricular arrhythmia in people with epilepsy. A single ion channel mutation expressed both in the brain and in the heart may confer a propensity for epilepsy and an innate vulnerability to cardiac arrhythmias. People with epilepsy are known to have a worse cardiovascular risk profile (Gaitatzis et al., 2004; Elliot et al., 2008; CDC, 2010). Epilepsy is associated with an increased prevalence of acquired cardiovascular comorbidity (Gaitatzis et al., 2008; CDC, 2010). When they had cardiovascular comorbidity, people with epilepsy were found to have a higher recurrence of life-threatening cardiac arrhythmias than controls without epilepsy (Janszky et al., 2009; Badheka et al., 2010). We found that two ECG risk markers of SCA, severe QTc-prolongation and early repolarisation pattern (ERP) were more common in people with refractory epilepsy were than in controls without epilepsy (Lamberts et al., 2014). Seizures may additionally increase the QTc-interval (Surges et al., 2010) and thus further augment SCA risk. The association between certain antiepileptic drugs, particularly those with depolarizing or sodium channel blocking properties and SCA remains speculative, as two studies yielded conflicting results (Bardai at al., 2014; Lamberts et al, forthcoming).

 

Ictal asystole has also been put forward as a SUDEP mechanism. Ictal asystole appears to be the most common seizure-related arrhythmia with a prevalence of 0.3-0.4% of all people with refractory epilepsy admitted for video-EEG monitoring (Rocamora et al., 2003; Schuele et al., 2007; Lanz et al., 2011). This prevalence may even by higher if people are monitored for a prolonged period of time using implantable loop recorders. Two small studies demonstrated a prevalence of 6-19% with up to 2 years of heart rate recordings (Rugg-Gunn et al., 2004, Nei et al., 2012). It is, however, questionable whether ictal asystole is a SUDEP risk factor. So far, of all 103 reported cases, all but one event were self-limiting (van der Lende et al., forthcoming). In this particular case successful resuscitation was started after 44 seconds of ictal asystole; the episode was classified as near-SUDEP (Lanz et al., 2011). It should be noted, however, that the longest seizure-induced circulatory arrest reported so far (96 seconds) exceeded this duration and was self-limiting (Chalia et al., 2010). Whether an asystolic event is labeled as near-SUDEP or not, will thus critically depend on the action by the observing medical personnel: immediate resuscitation will increase the number of near-SUDEP cases. Given the apparent benign course, it was argued that ictal asystole may parallel the transient cardiac standstill seen in vasovagal syncope (‘fainting’) (Schuele et al., 2008; van Dijk et al., 2014). As long as fatal ictal asystoles are not reported, it remains disputable whether ictal asystole can contribute to SUDEP.

 

In summary, SCA and SUDEP drive the excess of sudden death in epilepsy. SCA and SUDEP are partially overlapping disease entities. Seizure-induced ventricular arrhythmia seems to be a more important cause of SCA in epilepsy than ictal asystole. The increased SCA risk in epilepsy is predominantly explained by cardiovascular comorbidity. Prevention, identification, and adequate treatment of cardiovascular disorders in epilepsy should therefore be an important part of epilepsy management. Particular attention should be given to modifiable risk factors such as smoking, obesity, sedentary lifestyle, high cholesterol and hypertension. This might require a critical review of the epilepsy services. Further studies are needed to improve risk profiling, thus allowing for screening in high risk individuals (e.g. implantable loop recorders) and targeted interventions (e.g. defibrillator). 

 

 

Robert Lamberts, PhD Student, Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, The Netherlands

Roland Thijs, Neurologist, Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede & Leiden University Medical Centre (LUMC), Leiden, The Netherlands

Dec 2014

 

 

How to cite:

Lamberts R & Thijs R. Sudden cardiac arrest and SUDEP: partially overlapping clinical entities. In: Hanna J, Panelli R, Jeffs T, Chapman D, editors. Continuing the global conversation [online]. SUDEP Action, SUDEP Aware & Epilepsy Australia; 2014 [retrieved day/month/year]. Available from: www.sudepglobalconversation.com.

 

 

References

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Badheka A, Rathod A, Kizilbash MA, Lai Z, Mohamad T, Shah A, et al. Epileptic patients who survived sudden cardiac death have increased risk of recurrent arrhythmias and death. J Cardiovasc Med (Hagerstown) 2010;11(11):810-14.

Bardai A, Blom MT, van Noord C, Verhamme KM, Sturkenboom MC, Tan HL. Sudden cardiac death is associated both with epilepsy and with use of antiepileptic medications. Heart 2014, Jul 16. Epub ahead of print.

Bardai A, Lamberts RJ, Blom MT, Spanjaart AM, Berdowski J, van der Staal SR, et al. Epilepsy is a risk factor for sudden cardiac arrest in the general population. PLoS One 2012;7(8):e42749.

Centers for Disease Control & Prevention (CDC) 2010. Comorbidity in adults with epilepsy--United States, 2010. MMWR Morb Mortal Wkly Rep 2013;62(43):849-53.

Chaila E, Bhangu J, Tirupathi S, Delanty N. Ictal bradycardia and asystole associated with intractable epilepsy: a case series. Br J Cardiol 201;17:245-48.

Dasheiff RM, Dickinson LJ. Sudden unexpected death of epileptic patient due to cardiac arrhythmia after seizure. Arch Neurol 1986;43(2):194-96.

Van Dijk JG, Thijs RD, van Zwet E, Tannemaat MR, van Niekerk J, Benditt DG, et al. The semiology of tilt-induced reflex syncope in relation to electroencephalographic changes. Brain. 2014;137:576-85. 

Elliott JO, Moore JL, Lu B. Health status and behavioral risk factors among persons with epilepsy in Ohio based on the 2006 Behavioral Risk Factor Surveillance System. Epilepsy Behav 2008;12(3):434-44.

Espinosa PS, Lee JW, Tedrow UB, Bromfield EB, Dworetzky BA. Sudden unexpected near death in epilepsy: malignant arrhythmia from a partial seizure. Neurology 2009;72(19):1702-3.

Gaitatzis A, Carroll K, Majeed A, Sander JW. The epidemiology of the comorbidity of epilepsy in the general population. Epilepsia 2004;45(12):1613-22.

Janszky I, Hallqvist J, Tomson T, Ahlbom A, Mukamal KJ, Ahnve S. Increased risk and worse prognosis of myocardial infarction in patients with prior hospitalization for epilepsy--the Stockholm Heart Epidemiology Program. Brain 2009;132(Pt 10):2798-804.

Lamberts RJ, Blom MT, Novy J, Belluzzo M, Seldenrijk A, Penninx BW, et al. Increased prevalence of ECG markers for sudden cardiac arrest in refractory epilepsy. J Neurol Neurosurg Psychiatry 2014.

Lamberts RJ, Blom MT, Wassenaar M, Bardai A, Leijten FSS, de Haan GJ, et al. Sudden cardiac arrest in people with epilepsy in the community: circumstances and risk factors. Forthcoming.

Lanz M, Oehl B, Brandt A, Schulze-Bonhage A. Seizure induced cardiac asystole in epilepsy patients undergoing long term video-EEG monitoring. Seizure 2011;20(2):167-72.

Lende van der M, Surges R, Sander JW, Thijs RD. Cardiac arrhythmias during epileptic seizures: a review. Forthcoming.

Nei M, Sperling MR, Mintzer S, Ho RT. Long-term cardiac rhythm and repolarization abnormalities in refractory focal and generalized epilepsy. Epilepsia 2012;53(8):e137-40.

Neligan A, Bell GS, Johnson AL, Goodridge DM, Shorvon SD, Sander JW. The long-term risk of premature mortality in people with epilepsy. Brain 2011;134(Pt 2):388-95.

Puranik R, Chow CK, Duflou JA, Kilborn MJ, McGuire MA. Sudden death in the young. Heart Rhythm 2005;2(12):1277-82.

Rocamora R, Kurthen M, Lickfett L, Von Oertzen J, Elger CE. Cardiac asystole in epilepsy: clinical and neurophysiologic features. Epilepsia 2003;44(2):179-85.

Rugg-Gunn FJ, Simister RJ, Squirrell M, Holdright DR, Duncan JS. Cardiac arrhythmias in focal epilepsy: a prospective long-term study. Lancet 2004;364(9452):2212-19.

Schuele SU, Bermeo AC, Alexopoulos AV, Locatelli ER, Burgess RC, Dinner DS, et al. Video-electrographic and clinical features in patients with ictal asystole. Neurology 2007;69(5):434-41.

Schuele SU, Bermeo AC, Locatelli E, Burgess RC, Luders HO. Ictal asystole: a benign condition? Epilepsia 2008;49(1):168-71.

Surges R, Adjei P, Kallis C, Erhuero J, Scott CA, Bell GS, et al. Pathologic cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden unexpected death in epilepsy: a case-control study. Epilepsia 2010;51(2):233-42.

Please reload

At 5am, on March 28, 2006, my wife and I woke to a loud crash.  Running to our 16 year old son’s room we found him on the floor, wedged between his bed and the nightstand, his lips blue and teeth clenched...

January 16, 2006 is the day that changed our family forever. It was the day we lost our vibrant, caring and precious, nineteen year old, only daughter Kate, and the loving sister of our three sons...

As David had a history of epilepsy, my parents and I imagined he had fallen during a seizure and hit his head, drowning in the running water.  We had no idea that epilepsy can kill directly...

Please reload

continuing the global conversation

Sudden Unexpected Death in Epilepsy

Past Conversations   -   Glossary  -  Bibliography  -  Contact Us  -  Donate

 

©2020

 

 

 

 

 

The editors have endeavoured to publish reliable data and information but cannot assume responsibility for the validity of the materials or the consequences of their use.

 

All rights reserved.  No part of the publication may be reproduced or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without permission of the editors.