Comparison of clinical and electrophysiological characteristics between ictal and cardiac asystole encountered during video-EEG monitoring

Aims. Differentiation between syncope secondary to epileptic seizures and cardiac disease in patients displaying transient loss of consciousness associated with convulsive movements is a diagnostic challenge both for neurologists and cardiologists. In such patients, prolonged video-EEG monitoring not only helps in identifying asystole as the cause of syncope, but also in categorizing asystole as primarily cardiac in origin (cardiac asystole) and secondary to epileptic seizures (ictal asystole). We carried out this study to ascertain the prevalence of asystole in an epilepsy monitoring unit, and to contrast the clinical and electrophysiological characteristics between ictal asystole and cardiac asystole. Methods. Through a retrospective search, we identified patients who were shown to have had asystole using a database of patients who underwent prolonged video-EEG monitoring during a 68-month period. We compared the data of 18 consecutive patients; five with ictal asystole and 13 with cardiac asystole, with 121 and 64 events recorded from them, respectively. Results. Of the 10,096 patients who underwent prolonged video-EEG monitoring during the study period, we identified 18 (0.17%) patients with asystole. Cardiac asystole was 2.6 times more frequent than ictal asystole. Older age at onset, heralding symptoms of presyncope, occurrence during wakefulness, and brief duration of the events supported the diagnosis of cardiac asystole. Ictal asystole events were more protracted, and prolonged asystole more frequently occurred in patients with extratemporal seizures compared to temporal lobe seizures. Asystole occurred in only half of the recorded seizures. Conclusions. The accurate categorization of asystole as seizure-related or heart disease-related has huge implications for management strategy and outcome. The necessity of permanent pacemaker implantation is more frequent and urgent in patients with cardiac asystole because of the greater risk of sudden death. Hence, in patients with an ominous diagnosis of cardiac asystole, a thorough cardiac evaluation should surpass neurological evaluation.     

Relation between ictal asystole and cardiac sympathetic dysfunction shown by MIBG‐SPECT

Objective – Tachyarrhythmias are common during epileptic seizures while bradyarrhythmias or asystoles are less frequent. Ictal asystole might be related to epilepsy‐induced cardiac sympathetic denervation. Methods – To evaluate cardiac post‐ganglionic denervation in epilepsy patients with ictal asystoles we assessed I¹²³‐meta‐iodobenzylguanidine (MIBG) as a marker of post‐ganglionic cardiac norepinephrine‐uptake, using single photon emission computed tomography (MIBG‐SPECT). Results – In five of 844 patients with presurgical video‐electroencephalography‐monitoring, we recorded ictal asystoles during nine of 37 seizures. Asystole patients underwent cardiologic examination (Holter‐electrocardiogram, echocardiogram) and cardiac MIBG‐SPECT. We compared cardiac MIBG uptake in the asystole patients to the uptake in 18 temporal lobe epilepsy (TLE) patients without bradyarrhythmias and in 14 controls without cardiac or neurological disease. As the cardiological examinations were unremarkable in all subjects, the heart/mediastinum‐MIBG‐uptake ratios (H/M‐ratios) differed significantly between the three groups (P = 0.004). H/M‐ratios were lower in asystole TLE patients (mean ± SD: 1.58 ± 0.3) than in patients without asystole (1.81 ± 0.18; P = 0.037) or controls (1.96 ± 0.16). Conclusions – Pronounced reduction in cardiac MIBG uptake of asystole patients indicates post‐ganglionic cardiac catecholamine disturbance. Impaired sympathetic cardiac innervation limits adjustment and heart rate modulation, and may increase the risk of asystole and ultimately sudden unexpected death in epilepsy (SUDEP).     

Cardiac Effects of Seizures

Seizures frequently affect the heart rate and rhythm. In most cases, seizure-related cardiac changes are transient and do not appear to cause clinically significant abnormalities for the patient. Great interest in this area of research has been generated because of a possible connection with sudden unexpected death in epilepsy (SUDEP). While there are clear, but rare complications from seizure-related cardiac arrhythmias, such as ictal asystole that causes syncope, the overall risk of seizures on cardiac status and any potential connection between seizures and SUDEP still remain uncertain.     

Ictal asystole in temporal lobe epilepsy before and after pacemaker implantation.

Events of ictal bradycardia or asystole may be of relevance in epilepsy patients presenting with ictal falls, and are a potential contributor to SUDEP. The literature on ictal bradycardia or asystole is anecdotal and consists of case reports and small case series. There are no guidelines for the care of patients with ictal arrhythmias. Insertion of cardiac pacemakers may prevent life-threatening cardiac arrest, syncope and trauma.We report the case of a 41-year-old man who presented with refractory partial seizures resulting in syncope leading to severe head trauma, as the only ictal semiology. During presurgical video-EEG monitoring, two episodes of ictal bradycardia followed by asystole and syncope were recorded. A cardiac pacemaker was implanted. At the nine-month follow-up, the patient reported no overt seizures, syncopes or traumatic falls. Our case demonstrates that implantation of a cardiac pacemaker while continuing AEDs may render a patient free from ictal symptoms and prevent ictal syncope and subsequent trauma. [Published with video sequences].     

Sudden unexpected death in epilepsy: from mechanisms to prevention

PURPOSE OF REVIEW: To discuss the pathophysiology and potential prevention of sudden unexpected death in epilepsy. RECENT FINDINGS: Long-term electrocardiogram monitoring over several months has detected ictal asystole in three out of 20 (15%) patients with refractory epilepsy, suggesting that high-risk ictal arrhythmias occur in a greater proportion of patients with refractory epilepsy than previously thought. In case-control studies, sudden unexpected death in epilepsy was found to be associated with frequent generalized tonic-clonic seizures and greater ictal maximal heart rate, especially during nocturnal attacks. Conversely, supervision at night was associated with a lower risk of occurrence. The impact of epilepsy surgery on the risk of death and sudden unexpected death in epilepsy remains unclear, with comparable long-term survival in an epilepsy surgery cohort compared with a matched population of patients with refractory epilepsy who did not undergo surgery. Previous results may have been partly confounded by the association observed between preoperative decreased heart rate variability and poor postoperative seizure outcome. SUMMARY: Ictal arrhythmias may represent a more prevalent cause of sudden unexpected death in epilepsy than previously thought. No clear recommendations have emerged from the literature regarding the most appropriate therapeutic strategies to prevent the event, apart from the supervision at night of patients with refractory epilepsy.     

Ictal asystole mimicking seizure deterioration in temporal lobe epilepsy

We report on a patient with temporal lobe epilepsy, secondary to a left lateral temporal cavernoma, in whom the change in seizure semiology suggested recurrence of secondary generalized seizures. Anticonvulsive medication previously controlled secondary generalized seizures over a period of years but focal seizures continued at a lower rate. Continuous video‐EEG monitoring revealed ictal asystole associated with myoclonic syncope and falls during focal seizures arising from the left temporal lobe. After implantation of a cardiac pacemaker, no more falls occurred during the focal seizures. In conclusion, recurrence of seizure‐associated falls is typically attributed to recurrence of secondary generalized seizures, however, ictal asystole should be considered in selected epilepsy patients as a differential diagnosis of falls. [Published with video sequence]     

Ictal asystole in a patient with posterior reversible encephalopathy syndrome (PRES) and seizures

We describe a case of ictal asystole in a patient with posterior reversible encephalopathy syndrome (PRES), which has never been described previously. Ictal asystole is rare and has possible serious medical consequences, including syncope, and may be a potential mechanism for sudden unexpected death in epilepsy (SUDEP). Awareness that PRES may be observed with recurrent ictal asystole may aid in the recognition and treatment of seizures in this condition and the prevention of asystole‐associated complications.     

Cardiac asystole associated with epileptic seizures: a case report with simultaneous EEG and ECG.

Cardiac arrhythmias occurring in association with epileptic seizures are a potential source of diagnostic confusion and a possible cause of sudden unexpected death in epilepsy. A case is described in which simultaneous ambulatory electroencephalography and electrocardiography revealed periods of asystole coinciding with epileptic seizures. The aystole appeared to precede obvious changes in the scalp recorded electroencephalogram (EEG), but clinical attacks and EEG seizure activity were not altered by pacemaker correction of the cardiac arrhythmias.     

Cardiac asystole in epilepsy: clinical and neurophysiologic features

PURPOSE: Cardiac asystole provoked by epileptic seizures is a rare but important complication in epilepsy and is supposed to be relevant to the pathogenesis of sudden unexplained death in epilepsy (SUDEP). We sought to determine the frequency of this complication in a population of patients with medically intractable epilepsy and to analyze the correlation between EEG, electrocardiogram (ECG), and clinical features obtained from long-term video-EEG monitoring. METHODS: Retrospective analysis of the clinical records of hospitalized patients from May 1992 to June 2001 who underwent long-term video-/EEG monitoring. RESULTS: Of a total of 1,244 patients, five patients had cardiac asystole in the course of ictal events. In these patients, 11 asystolic events, between 4 and 60 s long in a total of 19 seizures, were registered. All seizures had a focal origin with simple partial seizures (n = 13), complex partial seizures (n = 4), and secondarily generalized seizures (n = 2). One patient showed the longest asystole ever reported (60 s) because of a seizure. Cardiac asystole occurred in two patients with left-sided temporal lobe epilepsy (TLE) and in three patients with frontal lobe epilepsy (FLE; two left-sided, one bifrontal). Two patients reported previous cardiac disease, but only one had a pathologic ECG by the time of admission. Two patients had a simultaneous central ictal apnea during the asystole. None of the patients had ongoing deficits due to the asystole. CONCLUSIONS: These findings confirm that seizure-induced asystole is a rare complication. The event appeared only in focal epilepsies (frontal and temporal) with a lateralization to the left side. A newly diagnosed or known cardiac disorder could be a risk factor for ictal asystole. Abnormally long postictal periods with altered consciousness might point to reduced cerebral perfusion during the event because of ictal asystole. Central ictal apnea could be a frequent associated phenomenon.     

Management and long-term outcome in patients presenting with ictal asystole or bradycardia

Purpose: Ictal asystole (IA) and ictal bradycardia (IB) are rare autonomic symptoms during epileptic seizures and may be potentially life‐threatening. Guidelines for the care of these patients are missing. The aim of this multicenter study was to evaluate the management and long‐term outcome in patients with IA and IB. Patients and Methods: All patients with IA and IB were included from four epilepsy centers (Bielefeld, Kork, Marburg, and Zürich) from 2002 until 2009. Using a standardized assessment form, clinical data, treatment decisions, and outcomes were extracted from patient charts and simultaneous electroencephalography/electrocardiography (EEG/ECG) recordings. Key Findings: Seizures with IA or IB were identified in 16 patients. In all patients an associated temporal seizure pattern was recorded and in 15 patients, sudden falls, fainting, or trauma was previously reported or recorded during the monitoring. In three patients (18.8%) diagnosis of focal epilepsy was newly established and anticonvulsive treatment was initiated. Two patients with refractory epilepsy underwent epilepsy surgery. In seven patients (43.8%) a cardiac pacemaker was implanted. In 14 of 16 treated patients, seizure freedom (n = 5) or absence of sudden falls, fainting, or trauma (n = 9) could be achieved. Two patients denied epilepsy surgery as well as a pacemaker and continue to have frequent falls and trauma. Significance: Our study demonstrates that epilepsy surgery and antiepileptic drugs may lead to sustained freedom of seizures as well as ictal syncope. In drug‐resistant patients not suitable for epilepsy surgery, implantation of a cardiac pacemaker may prevent sudden falls as well as trauma. Based on our results and previously reported cases we propose a treatment algorithm.     

Blockade of inhibitory neurotransmission evoked seizure-like firing of cardiac parasympathetic neurons in brainstem slices of newborn rats: Implications for sudden deaths in patients of epilepsy

In patients of epilepsy a proportion of unexplained sudden deaths had been attributed to neurogenic arrhythmias. Although some evidence has suggested that epileptogenic activation of the cardiac parasympathetic nerves, which is revealed by ictal bradyarrhythmias or cardiac asystole, might be very critical in causing sudden deaths of patients of epilepsy the firing behavior of cardiac parasympathetic neurons (CPNs) during epileptic attack is not known. In the present study fluorescent tracer was injected into the cardiac sac of newborn rats to retrogradely label the parasympathetic neurons in the nucleus ambiguus (NA). The fluorescence-labeled NA neurons were further examined using whole-cell patch-clamp method in medulla slices with respiratory-like rhythm, and those with an inspiratory-related increase of the mixed inhibitory synaptic activity were identified as CPNs. We have demonstrated that blockade of the GABAergic and the glycinergic receptors in medulla slices evoked intermittent seizure-like firing of CPNs under current-clamp configuration, and evoked intermittent excitatory inward currents (IEICs) under voltage-clamp configuration. These results have given new evidence that CPNs might fire in a seizure-like pattern during epileptic attack, which might be responsible for the neurogenic ictal bradyarrhythmias, cardiac asystole, or even the sudden deaths of patients of epilepsy.     

Syncope,seizure-induced bradycardia and asystole: Two cases and review of clinical and pathophysiological features

Episodes of transient loss of consciousness (TLOC) are commonly due to syncope or epileptic seizures. The distinction between both entities on clinical grounds and eyewitness accounts can be challenging and is often hampered by similar clinical features. We briefly summarize syncope-related symptoms and present the case of a female patient who suffered from TLOC episodes due to both reflex syncope and epileptic seizures. Seizure-induced syncope is a rare complication particularly of non-generalized temporal lobe seizures and may be suspected in people with epilepsy who report new semiological features with sudden onset of atonia, TLOC and seizure-related falls. We review epidemiological, clinical and electroencephalographic aspects of seizure-related asystole and syncope and discuss their clinical relevance. The implantation of a cardiac pacemaker appears to efficiently prevent seizure-related falls and consecutive injuries and is an important treatment option if full seizure-control cannot be achieved in these patients. We describe a second case of a patient with refractory temporal lobe epilepsy and seizure-related syncope which ceased after the implantation of a cardiac pacemaker.     

Late onset ictal asystole in refractory epilepsy

Ictal asystole is a cardiac phenomenon associated with epileptic seizures, and may play a role in sudden unexplained death in epilepsy. We present a 17-year-old boy with chronic intractable epilepsy and a vagus nerve stimulator who developed ictal asystole many years after the onset of epilepsy. The asystole was not linked to the vagus nerve stimulator, and ultimately necessitated the placement of a cardiac pacemaker. A cardiac pacemaker and vagus nerve stimulator can be safely used simultaneously after careful testing during placement. The onset of asystolic events many years after the onset of epilepsy suggests that repeated seizures may exert long-term effects on cardiac function.     

Clinical cues for detecting ictal asystole

Objective The occurrence of asystole during an epileptic seizure is the most dramatic manifestation of ictal bradycardia. Recognition of ictal asystole is important as treatment with both antiepileptic drugs and cardiac pacing may be necessary. The purpose of this study was to identify clinical cues to aid in the detection of ictal asystole. Methods We analyzed the clinical and electrophysiologic features of all recorded seizures in consecutive patients diagnosed with ictal bradycardia and asystole on prolonged video-EEG/ECG monitoring over a 14 year period. Results Twenty-nine seizures with ictal bradycardia were identified in 13 patients. Of these, 11 seizures in seven patients were associated with asystole. Bilateral transient limb movements consisting of asymmetric posturing or jerking occurred during eight episodes of ictal asystole, and loss of muscle tone occurred during four. In contrast, neither bilateral limb movement nor loss of muscle tone was observed in any of the non-asystolic seizures, whether ictal bradycardia was present or not. All patients with ictal asystole reported a history of seizure-related falls and brief body and limb jerking. Conclusions The presence of loss of muscle tone or bilateral asymmetric jerky limb movements during a seizure suggests the possibility of ictal asystole. Video-EEG/ECG monitoring should be considered in patients with epilepsy demonstrating these clinical features to determine if ictal asystole is present.     

SCN8A-related developmental and epileptic encephalopathy with ictal asystole requiring cardiac pacemaker implantation

IntroductionSCN8A-related epilepsy has various phenotypes. In particular, patients with developmental and epileptic encephalopathy (DEE) are resistant to antiepileptic drugs and may present with autonomic symptoms, such as marked bradycardia and apnea during seizures, and thus have an increased risk of sudden death. Herein, we report a case of very severe SCN8A-related epilepsy necessitating cardiac pacemaker implantation because of repetitive ictal asystole.Case reportThe patient was a 14-month-old girl. Tremor and generalized tonic seizure occurred after birth. During seizures, bradycardia and perioral cyanosis occurred, and then, after developing tachycardia and apnea, marked bradycardia and generalized cyanosis occurred, which sometimes resulted in ictal asystole requiring cardiopulmonary resuscitation. Her seizures were refractory to antiepileptic drugs. As the seizures requiring resuscitation did not decrease, cardiac pacemaker implantation was performed four months after birth. Exome sequencing revealed a heterozygous de novo variant in SCN8A (NM_014191.3:c.4934T>C,p.(Met1645Thr)). Even though phenytoin was effective, seizures with bradycardia remained approximately once a month, and pacemaker activity was observed.ConclusionsThis is, to our knowledge, the first reported case of SCN8A-related DEE in whom pacemaker implantation was performed. Pacemaker implantation should be considered as a treatment option for critical patients with SCN8A-related DEE as in the present case, because the incidence of sudden unexpected death in epilepsy is reported to be approximately 10% in patients with SCN8A-related DEE.     

Sudden unexpected death in people with epilepsy: a pediatric perspective

The possibility of sudden unexpected death in people with epilepsy (SUDEP) is very frightening for parents of a child with epilepsy. The mechanism for SUDEP is unclear but is probably most commonly related to postictal respiratory insufficiency. Occasionally the cause is a cardiac arrhythmia induced by a seizure. Even though children with epilepsy have an increased risk of death, SUDEP is very rare (1-2/10,000 patient-years). Nearly all of the mortality in children with epilepsy is related to the underlying neurologic disorder, not the seizures. Normal children with epilepsy do not have an increased risk of death compared with the general population. There is no current proven strategy to prevent SUDEP, although its rarity precludes systematic trials. Common sense approaches include identifying patients with cardiac arrhythmias as the cause of misdiagnosed epilepsy and vigorous attempts to control resistant seizure disorders.     

Severe cardioinhibitory vasovagal syncope in sleep and supine posture

Severe cardioinhibitory vasovagal syndrome is characterised by syncope accompanied by cardiac asystole which may lead clinically to seizure‐like motor activity. Vasovagal syncope usually occurs in erect posture and is often provoked by emotional or physical triggers. We report two patients who presented with severe cardioinhibitory vasovagal syncope accompanied by cardiac asystole resulting in seizure‐like motor manifestations in sleep and supine posture. Both cases were initially diagnosed as epilepsy and treated with antiepileptic drugs. We discuss the putative mechanisms of this rare condition and its potential for misdiagnosis as epilepsy. [Published with video sequences]     

Autonomic alterations and cardiac changes in epilepsy

Studies with heart rate variability have revealed interictal autonomic alterations in patients with epilepsy. In addition, epilepsy is frequently associated with ictal tachycardia or bradycardia, which sometimes precedes the onset of seizures. Ictal tachycardia is sometimes associated with electrocardiography (ECG) morphologic changes and ictal bradycardia often progresses to asystole. Such cardiac manifestations of seizures have been hypothesized as possible causes for sudden unexplained death in epilepsy (SUPEP). The present review relates to interictal and ictal cardiac manifestations of epilepsy with focus on heart rate, heart rate variability, and ECG changes. Aspects of the supporting mechanisms are discussed and attention is drawn to the interaction between central and peripheral effects, interictal autonomic conditions, ictal autonomic discharges, and administration of antiepileptic drugs in shaping the ictal cardiac changes. Because these interactions are complex and not totally understood, closer surveillance of patients and more experimental work is necessary to elucidate the mechanistic support of autonomic and cardiac changes in epilepsy, and to design better strategies to avoid their undesirable effects. It is also suggested that some of these changes could be used as predictors or markers for the onset of seizures.     

Ictal asystole with convulsive syncope mimicking secondary generalisation: a depth electrode study

Ictal bradycardia is rare and its localising value is debated. Bradyarrhythmias are, however, important because of their potential connection to sudden death and ability to affect clinical seizure manifestations. Cerebral hypoperfusion induces loss of consciousness, at times with myoclonic jerks, whose clinical differentiation from a generalised convulsive seizure may prove difficult.Two invasive and five surface monitored seizures recorded over two years in a 51 year old woman with post-traumatic epilepsy characterised by seizure-triggered asystole were analysed. All seven seizures showed left temporal onset. Both intracranially recorded events started in the left anterior hippocampus/amygdala, spreading to the contralateral hippocampus in 35 and 25 seconds. Within 10 seconds an electrocardiogram showed asystole lasting 21 and 28 seconds, associated with suppression of recorded cerebral electrical activity, except a polyspike suppression pattern remaining in the hippocampi. Clinically, the patient, concomitantly with the cerebral suppression, developed myoclonic twitches of the limbs. A dual chamber cardiac pacemaker was implanted; at 11 months follow up, the patient has experienced only infrequent partial seizures, with none involving falls or shaking.Left temporal lobe seizures produced convulsive syncope initiated by ictal asystole. These observations suggest that intertemporal spread is necessary, though not sufficient, to produce bradycardia and asystole. Furthermore, pacemakers may decrease seizure severity, as well as potentially protect against malignant bradyarrhythmias.