Abstract
Purpose of Review
This review examines the significance of seizures in young athletes and the complex inter-relationship between seizures, epilepsy, and sudden cardiac death.
Recent Findings
A history of seizures may reflect a diagnosis of epilepsy, which should be medically optimized for athletic participation. Epilepsy is associated with sudden unexplained cardiac death (sudden unexplained death in epilepsy, SUDEP), with multiple genetic links identified to define some patients as experiencing a “cardiocerebral channelopathy.” It is also important to consider that a history of seizures may reflect a misdiagnosis of cardiac syncope, requiring careful cardiac evaluation and risk stratification.
Summary
A history of seizures in a young athlete is important to characterize fully and investigate as required. The association of seizures with young sudden cardiac death is still under investigation.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Sudden cardiac death (SCD) occurs in approximately 1 in 60,000 athletes [1]. Many professional sporting bodies conduct screening programs for elite athletes, undertaking a medical and family history, physical examination, and cardiac investigations in order to mitigate the risk of SCD in their athletes. As part of a cardiac history, symptoms such as chest pain, shortness of breath, and syncope are of high priority to identify.
A history of seizures or epilepsy may appear less relevant for cardiac screening purposes; however, 15% of young athletes with sudden unexplained death have a past history of seizures and/or epilepsy [2]. Furthermore, a study of children and young adults with sudden cardiac arrest identified that 24% had a history of syncope or unexplained seizures, with an average of 2.6 seizure episodes over a period of 6 years prior to their life-threatening cardiac arrest [3]. Studies of athletes experiencing unexplained sudden cardiac arrest during exercise have reported a preceding history of syncope or seizure in 55% [4]. The relevance of seizure as a potential cardiac symptom is related to either (i) the possibility of underlying epilepsy with potential for a sudden death event, or (ii) misdiagnosed anoxic seizures indicating the presence of ventricular arrhythmias and an underlying channelopathy (Fig. 1). This review explores the significance of a history of seizures in young athletes, examines potential implications for SCD risk, and provides guidance for the treating practitioner.
Athletes with epilepsy
Epilepsy, defined by a predisposition to unprovoked epileptic seizures, is common and affects approximately 1% of the world or 50 million people [5]. More broadly, it is estimated that up to 10% of people worldwide will have one seizure in their lifetime [6•]. With such high prevalence, there are inevitably a number of athletes with epilepsy, including high-profile Olympians Florence Griffith Joyner, Marion Clignet, and Davis Tarwater.
The participation of people with epilepsy in sporting activity was traditionally restricted, with official guidance from the American Medical Association in 1968, recommending broad-ranging exclusion of people with epilepsy from exercise [6•]. This recommendation was based upon the possibility that physiological changes in exercise (i.e., hyperventilation) might increase seizure frequency, as well concern for risk of injury if seizures occurred during exercise. Following such medical recommendations, it has unfortunately been demonstrated that people with epilepsy are less likely to participate in regular physical activity and are more likely to be overweight or obese than their age-matched peers [7].
More recent research has demonstrated that participation in exercise leads to improved physical and psychosocial well-being for people in epilepsy, as well as reductions in seizure activity [8–11]. The International League Against Epilepsy has now provided guidance recommending regular exercise and sporting activity participation to the highest levels in a range of scenarios [12]. Studies are underway into prescribing exercise as a form of anti-epileptic therapy, representing a comprehensive about-turn in the approach to exercise in epilepsy [6•, 13–16]. The inclusion of athletes with a history of seizures should therefore be expected to increase in future years, and an approach to informed risk assessment is essential.
Impact of epilepsy on the cardiovascular system
When seizures occur, a variety of cardiovascular physiological abnormalities have been documented [17, 18]. Peri-ictal cardiac rhythm abnormalities were first identified by Russell in 1906, who described a case series of patients with peri-ictal asystole, noting that “cardiac arrest does occur in some cases of epilepsy and… such arrest may be far commoner than is suspected [19].”
The reported prevalence of peri-ictal arrhythmias varies widely, reflective of different methods of ascertainment. A study of patients undergoing simultaneous EEG and ECG monitoring identified an arrhythmia rate of 18% [20], whereas a Russian study of 193 patients with drug-resistant epilepsy and implanted loop recorders reported that 74% of patients experienced arrhythmias [21•]. The most commonly reported peri-ictal arrhythmia is sinus tachycardia, but other peri-ictal transient cardiac abnormalities include sinus bradycardia, asystole, and hypertension [22]. Autonomic abnormalities associated with epilepsy include excessive sympathetic activity, low parasympathetic activity, reduced heart rate variability, high vasomotor tone, and severe dysautonomia [23].
Rates of malignant arrhythmias appear low, with asystole occurring in 0.3–1.0% of patients with epilepsy [24, 25]. The mechanism of high-grade atrioventricular block or asystole in the peri-ictal state has been ascribed to initial stimulation of the limbic cortex activating parasympathetic outflow, with sympathetic activation followed by a profound vagal cardioinhibitory reflex [22]. Isbister et al. noted that “if the primary mechanism is centrally mediated cardiac inhibition, it is not surprising that the majority of seizure-induced brady-arrhythmias are self-resolving, paralleling neurogenic syncope [26].” Dynamic QTc prolongation has also been reported in the peri-ictal state [27], and prolonged QTc interval at baseline is more commonly observed in people with drug-resistant epilepsy on anti-epileptic therapy [17, 28]. Rates of torsades de pointes or ventricular arrhythmias have not, however, been reported at high rates in the peri-ictal setting [18].
In the longer term, the effect of repetitive seizures upon the heart and accompanying arrhythmias contributes to maladaptive changes [29]. People with temporal lobe epilepsy have increased left ventricle stiffness, left ventricle-filling pressures, and left greater atrial volumes compared to controls [30]. Patients with epilepsy have higher rates of myocardial fibrosis, accelerated atherosclerosis, systolic and diastolic dysfunction, and arrhythmias [31]. In more elite athletes, these changes may intersect with exercise-induced cardiovascular adaptations to exercise to either impair athletic performance or provide an enhanced substrate for arrhythmia.
Sudden Unexpected Death in Epilepsy (SUDEP)
Epilepsy is associated with a threefold elevation in the risk of sudden cardiac arrest [32]. Among people with epilepsy, the most common cause of premature mortality is sudden unexpected death in epilepsy, known as SUDEP [33, 34]. Sudden unexpected death, where no cause is found after investigation, occurs at 24 times the rate of the general population [17].
SUDEP is strictly defined according to the criteria established by Nashef et al. as “a sudden, unexpected, witnessed or unwitnessed, nontraumatic, and non-drowning death in people with epilepsy, with or without evidence for a seizure and excluding documented status epilepticus, and in whom post-mortem examination does not reveal a cause of death [35].” To account for case variations, a taxonomy of aligned conditions such as “SUDEP Plus” and “near-SUDEP” has been defined to provide clarity in case definitions [36] (Table 1). Identified risk factors for SUDEP include drug-resistant epilepsy, tonic–clonic seizures, high seizure frequency, nocturnal seizures, antiepileptic drug polytherapy, non-adherence to anti-epileptic therapy, young age of epilepsy onset, intellectual disability, and autonomic dysfunction [17, 37, 38•]. Proposed cardiac-specific risk factors for SUDEP include echocardiographic abnormalities indicating diastolic dysfunction [39, 40••].
The precise nature of SUDEP remains elusive. It is uncertain whether it may represent a subset of unexplained sudden cardiac death, happening to occur more commonly in people with epilepsy, or whether it is a unique entity. The pivotal study to date, the MORTEMUS study, identified that in SUDEP following a convulsive seizure, terminal apnea occurred prior to terminal asystole in all cases. There were no ventricular arrhythmias observed in the cohort of 29 patients [18]. These findings have lent weight to the hypothesis that SUDEP represents a distinct subset of sudden death, in which combined cardiorespiratory failure occurs rather than a primary cardiac arrhythmia.
Genetic basis of SUDEP
In the debate regarding the nature of SUDEP, there is also increasing evidence for the counter-argument that SUDEP represents a subset of SCD and is predominantly driven by the same mechanisms [41, 42••, 43]. A range of pathogenic genetic variants has been identified to date with concurrent effects on both the heart and brain, creating a substrate for “cardiocerebral channelopathies” [44] (Table 2).
Cardiac channelopathies such as long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome are conditions in which genetically mediated alterations in cardiac channel structure and function create a substrate for arrhythmias and SCD. A common presenting symptom of the cardiac channelopathies may be episodes of syncope or seizure, and so it is important to be alert to the possibility of a coexistent or primary cardiac channelopathy in people with seizure presentations [45•]. This is particularly the case when therapy with anti-epileptic drugs targeting sodium channel blockade is intended, as such therapy may heighten the risk of malignant cardiac arrhythmia [22].
Specific epilepsy syndromes have an increased SUDEP risk. Dravet syndrome, the prototypic developmental and epileptic encephalopathy, in whom more than 90% have a pathogenic SCN1A variant [46], has a mortality rate of 17% by 20 years of age; more than half of the affected individuals die of SUDEP. Other sodium channel developmental and epileptic encephalopathies also carry an increased SUDEP risk [47].
Exome sequencing in 61 SUDEP patients identified a large number of pathogenic variants implicated in cardiac arrest. Variants known to cause LQTS, a cardiac channelopathy causing SCD, were identified in 7% of cases, with a further 15% of patients having candidate variants in genes believed to predispose to malignant cardiac arrhythmias [33]. The study concluded that “SUDEP in patients with LQTS mutations may be predictable and preventable” [33]. In mice, it has been shown that a point mutation in the most common LQTS gene (KCNQ1) results in an ion channelopathy co-expressed in heart and brain, manifesting as both cardiac arrhythmias and epileptic seizures, with subsequent sudden death captured on both cardiac and cerebral monitoring [48]. Likewise, in patients with genetically verified LQTS but no known history of epilepsy, 71% have abnormal EEG studies, compared to only 13% of control subjects [49].
With regard to the MORTEMUS study findings that death was associated with a centrally mediated alteration of both respiratory and cardiac function, researchers have suggested that people with epilepsy exhibit a higher genetic susceptibility to SCD and are, therefore, more vulnerable to death in the setting of post-ictal hypoxia [50]. Given the rate of cardiogenetic pathogenic variants in people with epilepsy and SUDEP, it is important to consider that many cardiac channelopathies are, in fact, more accurately described as “cardiocerebral channelopathies” [51, 52]. Implications of this research are not limited to reducing SUDEP risk in people with epilepsy by tailoring preventive neurological and cardiac therapy, but findings may also cascade to other family members with critical strategies to reduce the risk of sudden cardiac death in first-degree relatives [53].
“Cardiac” seizures indicating primary arrythmia
Although an increasing amount of research points to a significant overlap between epilepsy and an arrhythmogenic substrate for sudden cardiac death, it is also important to consider the possibility that reported seizures may represent misdiagnosed primary cardiac arrhythmias.
The mechanism by which convulsive movements occur in syncope or cardiac arrest is predominantly believed to be secondary cerebral hypoperfusion causing anoxic seizure activity. In severe cerebral hypoperfusion, electroencephalographic (EEG) monitoring demonstrates a characteristic “slow-flat-slow EEG pattern” in which a generalized short-lasting period of delta waves is followed by flattening of the EEG followed by recurrent delta waves with restoration of cerebral perfusion and then resolution to a normal EEG. Myoclonic jerks, observed in approximately half of these patients, typically appear after the patient has fallen. They result from hypoxia in the telencephalon-inhibiting cortical activity, resulting in unopposed subcortical (brainstem) activity, with the brainstem reticular formation causing sudden contractions [54]. These jerks correlate strongly with the “slow” phase of the EEG and are usually asynchronous and unilateral. Following recovery of the hypoperfusion event, late myoclonic jerks may be seen as cerebral reperfusion is established. These may be associated with characteristic skin flushing as more general perfusion is established [25].
Cardiac syncope and even sudden cardiac arrest are, therefore, frequently misdiagnosed as seizures [45•], and differentiation can be challenging [51]. Video analysis of thirty-five episodes of sudden cardiac arrest during sporting events identified that 20% of cases were associated with seizure-like activity [55]. Likewise, a study by Drezner et al. of sudden cardiac arrest in student athletes identified seizure-like movements in 50% of the athletes at the time of their cardiac arrest [56].
Suggestive differentiators between a seizure and a primary arrhythmia may include the number of “jerks” observed (reported to be fewer in syncope than an epileptic seizure) and the timing of onset of convulsions, with convulsions before the onset of unconsciousness favoring a primary seizure event [57] (Fig. 1). An abrupt collapse without warning may also be more indicative of the onset of a ventricular arrhythmia [3]. Tongue biting is rare in arrhythmogenic syncope and predominantly involves the tip rather than the lateral tongue as a consequence of injury rather than tongue biting during convulsions. Urinary incontinence may occur, but fecal incontinence is extremely rare [57]. However, syncopal signs that may cause confusion with a seizure are head turning to one side, oral automatisms, snoring, gasping, sounds, and dystonic posturing—these all reflect predominant brainstem activity during the period of cortical suppression [57]. Pallor may be observed in both conditions as an indicator of generalized hypoperfusion [25].
Syncope that occurs during an athlete’s exercise is an ominous sign suggestive of underlying malignant cardiac disease. In a study of 474 patients with a history of syncope, 33% of those with exercise-induced syncope were ultimately diagnosed with structural cardiac disease placing them at risk of SCD [58]. Video analysis or at least witness descriptions from team members or spectators may be more readily available in the setting of athletes experiencing syncope or seizures during exercise and may provide valuable clues to the challenge of differentiating between a seizure and a primary arrhythmia [59].
Practical implications for the cardiologist or sports physician
For cardiologists and sports physicians evaluating young athletes either as part of pre-participation screening or as a clinical cardiac evaluation, there are clear practice points to emphasize. A history of seizure in a young athlete is concerning and warrants further investigations (Fig. 2). High-risk differential diagnoses include epilepsy with risk of SUDEP or an undiagnosed cardiac channelopathy.
In taking a history, it is important to delineate all features of reported episodes. Episodes occurring during exercise are particularly concerning and warrant a comprehensive cardiac evaluation. Details regarding any prodromal symptoms, color changes, abnormal limb movements, tongue injuries, incontinence and post-episode confusion, drowsiness, and headache should be obtained. The exact timing of abnormal limb movements with respect to loss of consciousness should be clarified as precisely as possible [60]. Video or witness descriptions are critical and should be actively sought. With regard to the patient’s broader medical history, a full medical and medication history should be obtained. A three-generation family pedigree is also valuable to ensure there is no family history of epilepsy, febrile seizures or sudden deaths, cardiac device implantation, or transplantation at under 50 years of age [3].
An electrocardiogram should be performed in all athletes with a history of syncope or seizures [61, 62]. It is reasonable to perform an exercise stress test and echocardiogram to ensure the athlete’s heart is structurally and functionally normal. More advanced investigations such as cardiac MRI, EEG, and cerebral imaging (computed tomography or MRI) should be performed as required according to initial results and degree of concern. If a diagnosis of epilepsy is suspected, a neurologist should be part of the multidisciplinary evaluation team.
If a firm diagnosis of either epilepsy or a channelopathy is made, this is not necessarily a barrier to participation in sports. Participation in sports confers mental and physical benefits, and a blanket ruling on non-participation is unnecessary [63, 64]. Awareness of high-risk features of SUDEP and mitigation of cardiac risk in channelopathies is the mainstay of treatment. Involvement of sports cardiology colleagues at this point is highly valuable to assist in providing informed evaluations and information to the patients and their families.
Conclusion
A history of seizures in a young athlete is a concerning symptom that requires further investigation. Both epilepsy and cardiac channelopathies causing sudden death appear to be intimately related, and the degree of their entanglement as a “cardiocerebral syndrome” is still being elucidated. Physicians should take a detailed history and appropriate clinical investigations and collaborate in a multidisciplinary manner to best support the athlete’s comprehensive risk profiling and mitigate risk of sudden cardiac death while encouraging ongoing physical activity where safe.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Semsarian C, Sweeting J, Ackerman MJ. Sudden cardiac death in athletes. BMJ : British Med J. 2015;350:h1218.
Marcondes L, Crawford J, Earle N, et al. Long QT molecular autopsy in sudden unexplained death in the young (1–40 years old): lessons learnt from an eight year experience in New Zealand. PLoS ONE. 2018;13:e0196078.
Drezner JA, Fudge J, Harmon KG, Berger S, Campbell RM, Vetter VL. Warning symptoms and family history in children and young adults with sudden cardiac arrest. J Am Board Fam Med. 2012;25:408–15.
Glinge C, Jabbari R, Risgaard B, et al. Symptoms before sudden arrhythmic death syndrome: a nationwide study among the young in Denmark. J Cardiovasc Electrophysiol. 2015;26:761–7.
Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475–82.
• Carter JM, McGrew C. Seizure disorders and exercise/sports participation. Curr Sports Med Rep. 2021;20:26–30. This paper provides a comprehensive overview of the current evidence for participation in sports for people with epilepsy.
Terman SW, Aubert CE, Hill CE, Skvarce J, Burke JF, Mintzer S. Cardiovascular disease risk, awareness, and treatment in people with epilepsy. Epilepsy Behav. 2021;117:107878.
Fountain NB, May AC. Epilepsy and athletics. Clin Sports Med. 2003;22(605–16):x–xi.
Knowles BD, Pleacher MD. Athletes with seizure disorders. Curr Sports Med Rep. 2012;11:16–20.
Manuel C, Feinstein R. Sports participation for young athletes with medical conditions: seizure disorder, infections and single organs. Curr Probl Pediatr Adolesc Health Care. 2018;48:161–71.
Arida RM, Cavalheiro EA, da Silva AC, Scorza FA. Physical activity and epilepsy: proven and predicted benefits. Sports Med. 2008;38:607–15.
Capovilla GKK, Perucca E, Moshe SL, Arida RM. Epilepsy, seizures, physical exercise and sports: a report from the ILAE Task Force on Sports and Epilepsy. Epilepsia. 2016;57:6–12.
Nakken KO, Loyning A, Loyning T, Gloersen G, Larsson PG. Does physical exercise influence the occurrence of epileptiform EEG discharges in children? Epilepsia. 1997;38:279–84.
de Lima C, Vancini RL, Arida RM, et al. Physiological and electroencephalographic responses to acute exhaustive physical exercise in people with juvenile myoclonic epilepsy. Epilepsy Behav. 2011;22:718–22.
Vancini RL, Andrade MS, de Lira CA. Exercise as medicine for people with epilepsy. Scand J Med Sci Sports. 2016;26:856–7.
Zhang CQ, Li HY, Wan Y, Bai XY, Gan L, Sun HB. Effect of different physical activity training methods on epilepsy: a protocol for systematic review and meta-analysis. Medicine (Baltimore). 2022;101.
Barot N, Nei M. Autonomic aspects of sudden unexpected death in epilepsy (SUDEP). Clin Auton Res. 2019;29:151–60.
Ryvlin P, Nashef L, Lhatoo SD, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol. 2013;12:966–77.
Ae R. Cessation of the pulse during the onset of epileptic fits: with remarks on the mechanism of fits. Lancet. 1906;168:152–4.
Kendirli MT, Aparci M, Kendirli N, et al. Diagnostic role of ECG recording simultaneously with EEG testing. Clin EEG Neurosci. 2015;46:214–7.
• Serdyuk S, Davtyan K, Burd S et al. Cardiac arrhythmias and sudden unexpected death in epilepsy: results of long-term monitoring. Heart Rhythm. 2021;18:221–228. There are few papers directly examining arrhythmias in people with epilepsy. This paper examines results of implantable loop recorder monitoring in 193 patients with drug-resistant epilepsy.
Costagliola G, Orsini A, Coll M, Brugada R, Parisi P, Striano P. The brain-heart interaction in epilepsy: implications for diagnosis, therapy, and SUDEP prevention. Ann Clin Transl Neurol. 2021;8:1557–68.
O’Neal TB, Shrestha S, Singh H, et al. Sudden unexpected death in epilepsy. Neurol Int. 2022;14:600–13.
van der Lende M, Surges R, Sander JW, Thijs RD. Cardiac arrhythmias during or after epileptic seizures. J Neurol Neurosurg Psychiatry. 2016;87:69–74.
Nguyen-Michel VH, Adam C, Dinkelacker V, et al. Characterization of seizure-induced syncopes: EEG, ECG, and clinical features. Epilepsia. 2014;55:146–55.
Isbister JC, Sy RW, Semsarian C. Cardiac arrhythmias in epilepsy: troublemaker, accomplice, or innocent bystander? Heart Rhythm. 2021;18:229–30.
Brotherstone R, Blackhall B, McLellan A. Lengthening of corrected QT during epileptic seizures. Epilepsia. 2010;51:221–32.
Gurses AA, Genc E, Gurses KM, Altiparmak T, Yildirim I, Genc BO. QT interval alterations in epilepsy: a thorough investigation between epilepsy subtypes. J Clin Neurosci. 2022;104:113–7.
Liu Z, Thergarajan P, Antonic-Baker A et al. Cardiac structural and functional abnormalities in epilepsy: a systematic review and meta-analysis. Epilepsia Open. 2023.
Fialho GL, Wolf P, Walz R, Lin K. Increased cardiac stiffness is associated with autonomic dysfunction in patients with temporal lobe epilepsy. Epilepsia. 2018;59:e85–90.
Fialho GL, Wolf P, Walz R, Lin K. Epilepsy and ultra-structural heart changes: the role of catecholaminergic toxicity and myocardial fibrosis. What can we learn from cardiology? Seizure. 2019;71:105–109.
Bardai A, Lamberts RJ, Blom MT, et al. Epilepsy is a risk factor for sudden cardiac arrest in the general population. PLoS ONE. 2012;7:e42749.
Bagnall RD, Crompton DE, Petrovski S, et al. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol. 2016;79:522–34.
Klovgaard M, Lynge TH, Tsiropoulos I, et al. Epilepsy-related mortality in children and young adults in Denmark: a nationwide cohort study. Neurology. 2022;98:e213–24.
Nashef L, So EL, Ryvlin P, Tomson T. Unifying the definitions of sudden unexpected death in epilepsy. Epilepsia. 2012;53:227–33.
Devinsky O, Bundock E, Hesdorffer D, et al. Resolving ambiguities in SUDEP classification. Epilepsia. 2018;59:1220–33.
Lamberts RJ, Thijs RD, Laffan A, Langan Y, Sander JW. Sudden unexpected death in epilepsy: people with nocturnal seizures may be at highest risk. Epilepsia. 2012;53:253–7.
• Thijs RD, Ryvlin P, Surges R. Autonomic manifestations of epilepsy: emerging pathways to sudden death? Nat Rev Neurol. 2021;17:774–788. This review provides an excellent summary of current hypotheses relating to sudden death in epilepsy.
Fialho GL, Pagani AG, Wolf P, Walz R, Lin K. Echocardiographic risk markers of sudden death in patients with temporal lobe epilepsy. Epilepsy Res. 2018;140:192–7.
•• Fialho GL, Wolf P, Walz R, Lin K. Left ventricle end-systolic elastance, arterial-effective elastance, and ventricle-arterial coupling in epilepsy. Acta Neurol Scand. 2021;143:34–38. This paper is one of the few that provide direct haemodynamic data from populations with epilepsy.
Lamberts RJ, Blom MT, Wassenaar M, et al. Sudden cardiac arrest in people with epilepsy in the community: circumstances and risk factors. Neurology. 2015;85:212–8.
•• Soh MS, Bagnall RD, Semsarian C, Scheffer IE, Berkovic SF, Reid CA. Rare sudden unexpected death in epilepsy SCN5A variants cause changes in channel function implicating cardiac arrhythmia as a cause of death. Epilepsia. 2022;63:e57–e62. This paper identifies genetic variants in people with epilepsy, positioning SUDEP as potentially being a manifestation of a "cardiocerebral channelopathy".
Soh MS, Bagnall RD, Bennett MF et al. Loss-of-function variants in K(v) 11.1 cardiac channels as a biomarker for SUDEP. Ann Clin Transl Neurol 2021;8:1422–1432.
Bagnall RD, Crompton DE, Semsarian C. Genetic basis of sudden unexpected death in epilepsy. Front Neurol. 2017;8:348.
• Skinner JR, Winbo A, Abrams D, Vohra J, Wilde AA. Channelopathies that lead to sudden cardiac death: clinical and genetic aspects. Heart Lung Circ. 2019;28:22–30. This paper is an excellent summary of cardiac channelopathies and our current understanding.
Cooper MS, McIntosh A, Crompton DE, et al. Mortality in Dravet syndrome. Epilepsy Res. 2016;128:43–7.
Donnan AM, Schneider AL, Russ-Hall S, Churilov L, Scheffer IE. Rates of status epilepticus and sudden unexplained death in epilepsy in people with genetic developmental and epileptic encephalopathies. Neurology. 2023.
Manolis TA, Manolis AA, Melita H, Manolis AS. Sudden unexpected death in epilepsy: the neuro-cardio-respiratory connection. Seizure. 2019;64:65–73.
Haugaa KH, Vestervik TT, Andersson S, et al. Abnormal electroencephalograms in patients with long QT syndrome. Heart Rhythm. 2013;10:1877–83.
Fialho GL, Wolf P, Walz R, Lin K. SUDEP - more attention to the heart? A narrative review on molecular autopsy in epilepsy. Seizure. 2021;87:103–6.
Gonzalez A, Aurlien D, Larsson PG, et al. Seizure-like episodes and EEG abnormalities in patients with long QT syndrome. Seizure. 2018;61:214–20.
Morales-Vidal S, Lichtenberg R, Woods C. Neurologic complications of cardiac disease in athletes. Handb Clin Neurol. 2021;177:269–74.
Bleakley LE, Soh MS, Bagnall RD, et al. Are variants causing cardiac arrhythmia risk factors in sudden unexpected death in epilepsy? Front Neurol. 2020;11:925.
Jackson A, Bower S, Seneviratne U. Semiologic, electroencephalographic and electrocardiographic correlates of seizure-like manifestations caused by cardiac asystole. Seizure. 2015;29:15–9.
Steinskog DM, Solberg EE. Sudden cardiac arrest in sports: a video analysis. Br J Sports Med. 2019;53:1293–8.
Drezner JA, Toresdahl BG, Rao AL, Huszti E, Harmon KG. Outcomes from sudden cardiac arrest in US high schools: a 2-year prospective study from the National Registry for AED Use in Sports. Br J Sports Med. 2013;47:1179–83.
Surges R, Shmuely S, Dietze C, Ryvlin P, Thijs RD. Identifying patients with epilepsy at high risk of cardiac death: signs, risk factors and initial management of high risk of cardiac death. Epileptic Disord. 2021;23:17–39.
Colivicchi F, Ammirati F, Santini M. Epidemiology and prognostic implications of syncope in young competing athletes. Eur Heart J. 2004;25:1749–53.
de Jong JS, Jorstad HT, Thijs RD, Koster RW, Wieling W. How to recognise sudden cardiac arrest on the pitch. Br J Sports Med. 2020;54:1178–80.
Gupta A, Menoch M, Levasseur K, Gonzalez IE. Screening pediatric patients in new-onset syncope (SPINS) study. Clin Pediatr (Phila). 2020;59:127–33.
Chahal CAA, Gottwald JA, St Louis EK, et al. QT prolongation in patients with index evaluation for seizure or epilepsy is predictive of all-cause mortality. Heart Rhythm. 2022;19:578–84.
de Sousa JM, Fialho GL, Wolf P, Walz R, Lin K. Determining factors of electrocardiographic abnormalities in patients with epilepsy: a case-control study. Epilepsy Res. 2017;129:106–16.
Sirtbas G, Yalnizoglu D, Livanelioglu A. Comparison of physical fitness, activity, and quality of life of the children with epilepsy and their healthy peers. Epilepsy Res. 2021;178:106795.
van den Bogard F, Hamer HM, Sassen R, Reinsberger C. Sport and physical activity in epilepsy. Dtsch Arztebl Int. 2020;117:1–6.
Funding
Open Access funding enabled and organized by CAUL and its Member Institutions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
Elizabeth D. Paratz reports PhD Scholarships from NHMRC and the National Heart Foundation, and a Senior Research Fellowship from Melbourne University. She is also the Deputy Medical Director for the East Timor Hearts Fund. Ingrid E. Scheffer has served on scientific advisory boards for BioMarin, Chiesi, Eisai, Encoded Therapeutics, Garvan Institute of Medical Research, GlaxoSmithKline, Knopp Biosciences, Nutricia, Rogcon, Takeda Pharmaceuticals, UCB, and Xenon Pharmaceuticals; has received speaker honoraria from GlaxoSmithKline, UCB, BioMarin, Biocodex, Chiesi, Liva Nova, Nutricia, Zuellig Pharma, and Eisai; has received funding for travel from UCB, Biocodex, GlaxoSmithKline, Biomarin, Encoded Therapeutics, National Research Foundation, Singapore and Eisai; has served as an investigator for Anavex Life Sciences, Cerecin Inc., Cerevel Therapeutics, Eisai, Encoded Therapeutics, EpiMinder Inc, Epygenyx, ES-Therapeutics, GW Pharmaceuticals, Marinus Pharmaceuticals, Neurocrine BioSciences, Ovid Therapeutics, Takeda Pharmaceuticals, UCB, Ultragenyx, Xenon Pharmaceuticals, Zogenix and Zynerba Pharmaceuticals; and has consulted for Care Beyond Diagnosis, Epilepsy Consortium, Atheneum Partners, Ovid Therapeutics, UCB, Zynerba Pharmaceuticals, BioMarin, Encoded Therapeutics, and Biohaven Pharmaceuticals; and is a Non-Executive Director of Bellberry Ltd. and a Director of the Australian Academy of Health and Medical Sciences and the Australian Council of Learned Academies Limited. She may accrue future revenue on pending patent WO61/010176 (filed: 2008): Therapeutic Compound; has a patent for SCN1A testing held by Bionomics Inc. and licensed to various diagnostic companies; has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) [PRRT2] 2011904493 and 2012900190 and PCT/AU2012/001321 (TECH ID:2012–009). They also report Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence Grant (GNT2006841) 2020–2024; NHMRC Synergy Grant (GNT2010562) 2022–2026; NHMRC Senior Investigator Fellowship (GNT1172897) 2021–2025; and Einstein Visiting Fellowship (2022–25). Christopher Semsarian reports grants from the National Heart Foundation.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Paratz, E.D., Scheffer, I.E. & Semsarian, C. Is a History of Seizures an Important Risk Factor for Sudden Cardiac Death in Young Athletes?. Curr Treat Options Cardio Med 25, 175–187 (2023). https://doi.org/10.1007/s11936-023-00983-8
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11936-023-00983-8