Sudden unexpected death in epilepsy and ictal asystole in patients with autoimmune encephalitis: a systematic review.

OBJECTIVE: As autoimmune encephalitis (AE) often involves the mesial temporal structures which are known to be involved in both sudden unexpected death in epilepsy (SUDEP) and ictal asystole (IA), it may represent a good model to study the physiopathology of these phenomena. Herein, we systematically reviewed the occurrence of SUDEP and IA in AE. METHODS: We searched 4 databases (MEDLINE, Scopus, Embase, and Web of Science) for studies published between database inception and December 20, 2022, according to the PRISMA guidelines. We selected articles reporting cases of definite/probable/possible/near-SUDEP or IA in patients with possible/definite AE, or with histopathological signs of AE. RESULTS: Of 230 records assessed, we included 11 cases: 7 SUDEP/near-SUDEP and 4 IA. All patients with IA were female. The median age at AE onset was 30 years (range: 15-65), and the median delay between AE onset and SUDEP was 11 months; 0.9 months for IA. All the patients presented new-onset seizures, and 10/11 also manifested psychiatric, cognitive, or amnesic disorders. In patients with SUDEP, 2/7 were antibody-positive (1 anti-LGI1, 1 anti-GABABR); all IA cases were antibody-positive (3 anti-NMDAR, 1 anti-GAD65). Six patients received steroid bolus, 3 intravenous immunoglobulin, and 3 plasmapheresis. A pacemaker was implanted in 3 patients with IA. The 6 survivors improved after treatment. DISCUSSION: SUDEP and IA can be linked to AE, suggesting a role of the limbic system in their pathogenesis. IA tends to manifest in female patients with temporal lobe seizures early in AE, highlighting the importance of early diagnosis and treatment.

Syncope, Epilepsy and Ictal Asystole: A Case Series and Narrative Review.

IMPORTANCE: Syncope is a common presentation to emergency departments, and cardiac and neurological aetiologies are the predominant causes. Ictal asystole is a rare cardio-neural phenomenon seen in epilepsy syndromes whereby a seizure causes asystole (≥3 s) leading to syncope. OBSERVATIONS: We present three cases of ictal asystole, together with a narrative review of the literature to assess the prevalence of the condition and review the pathophysiology, diagnosis and management. Our review of the literature has shown that ictal asystole is an unlikely contributor to sudden unexplained death in epilepsy (SUDEP). Pacemaker insertion may limit morbidity from trauma related to syncopal episodes but does not impact mortality. CONCLUSIONS AND RELEVANCE: Patients with ictal asystole should be diagnosed with concurrent electroencephalogram-electrocardiograph (EEG-ECG) monitoring, have their anti-epileptic drugs optimised and be considered for epilepsy surgery if feasible. The use of longer term ECG monitoring may be used as a diagnostic aid if ictal asystole is suspected. If there are ongoing syncopal episodes with associated ictal asystole ≥6 seconds, particularly despite medical therapy, a permanent pacemaker may be considered to reduce morbidity. Current guidelines should be updated to reflect the increasing knowledge of this condition.

Epileptic seizures associated with syncope: Ictal bradycardia and ictal asystole.

INTRODUCTION: Heart rate decrease during epileptic seizures is rare and should be considered in patients with unusual or refractory episodes of syncope or in patients with a history suggestive of both epilepsy and syncope. We systematically reviewed the literature to better understand the clinical signs and risk factors of ictal heart rate decreases. MATERIAL AND METHODS: We performed a literature-search on "ictal bradycardia" and "ictal asystole" in Pubmed and added papers from the references and personal archives. Articles relating to animal studies, seizures without ictal decrease of heart rate, cases without simultaneous electroencephalography (EEG) and electrocardiography (ECG), convulsive syncopes, or cases with bradycardia before seizure onset and articles written in other languages than English, Dutch, German, French, or Spanish were excluded. Full texts of the remaining articles were screened for cases of ictal bradycardia or ictal asystole. Cases were selected on the basis of a self-designed quality score. The relationship of RR wave interval of at least 5 s, signs of syncope, and EEG signs of ischemia were analyzed with chi-square test and identifying 95% confidence intervals. RESULTS: Ictal bradycardia and ictal asystole predominantly occurred during focal seizures with loss of awareness (proportion in the combined group of bradycardia and asystole (p1 + 2) = 0.85) in people with mainly left lateralized (p1 + 2 = 0.64; p = 0.001) temporal lobe seizures (p1 + 2 = 0.91). Seizures with ictal asystole typically started with a heart rate decrease. During ictal asystole in the majority of cases, not only the clinical signs of syncope occurred (change of proportion (Δp) = 0.67; 95% CI: 0.48-0.86; p < 0.0001), i.e., interrupting the seizure semiology, but also the characteristic EEG signs of ischemia (Δp = 0.50; 95% CI: 0.26-0.74; p < 0.001). We found a statistically significant relation between signs of syncope and EEG signs of ischemia (Δp = -0.37; 95% CI: (-0.64)-(-0.10); p < 0.01) but not between duration of asystole (5 s) and either signs of syncope (Δp = -0.36; 95% CI: (-0.77)-0.05; p = 0.03) or EEG signs of ischemia (Δp = -0.37; 95% CI: (-1.07)-0.33; p = 0.16). CONCLUSION: In the ictal bradycardia syndrome, signs of syncope disrupt the semiology of ongoing seizures and are associated with EEG signs of brain ischemia and the duration of the cardiac arrhythmia.

Ictal asystole: a case presentation.

BACKGROUND: Epileptic seizures can lead to cardiac arrhythmias. The arrhythmias may be in the form of tachycardia, bradycardia or asystole. Ictal bradycardia and asystole can lead to sudden unexpected death. CASE PRESENTATION: A case report of a 40-year-old male with complex partial temporal lobe epilepsy. He has coincident attacks of fall and pallor. The patient underwent simultaneous electrocardiogram (ECG) and video electroencephalogram (EEG) monitoring. The slow activity in EEG coincide with the appearance of bradycardia in ECG then cardiac asystole which clinically correspond to the patient syncope. After insertion of a cardiac pacemaker, only complex partial attacks develop with a marked reduction in frequency and no more fall attacks. CONCLUSION: Epileptic seizures can present with cardiac arrhythmias, with ictal asystole leading to sudden unexpected death. Simultaneous EEG and ECG are essential for the diagnosis. A cardiac pacemaker can be lifesaving for patients with ictal arrhythmias.

Long-Term Follow-Up of Ictal Asystole in Temporal Lobe Epilepsy: Is Permanent Pacemaker Therapy Needed?

BACKGROUND: Ictal asystole (IA) is an infrequent complication of temporal lobe epilepsy (TLE), but one that may cause transient loss of consciousness (T-LOC) similar to reflex syncope (particularly the vasovagal faint). Although IA-triggered T-LOC is relatively rare, its recognition is therapeutically important. However, while the need for anti-epileptic drugs (AeDs) is broadly accepted, cardiac pacing in IA is controversial. This study aimed to evaluate the need for cardiac pacing in the follow-up of IA patients being treated with AeDs. METHODS AND RESULTS: Six patients (2 men, mean age of 66 ± 16 years), with documented prolonged asystole on electrocardiogram (ECG) in association with TLE, were followed for an average of 19.7 (range, 2-37) years; a pacemaker had been implanted in 4 of 6 patients, whereas 2 patients underwent long-term ECG monitoring with an implantable loop recorder (ILR). The longest documented IA pause lasted 12.6 ± 6.2 (range: 3.5-20) seconds. All patients were treated with AeDs. During follow-up, after optimization of AeD dosing, none of the patients had T-LOC spells or detected epileptic seizure episodes. During regular device interrogation, there was no evidence of pacing interventions (cumulative ventricular pacing, 0%) in the 4 pacemaker patients, and no symptomatic bradyarrhythmias in the 2 ILR patients. CONCLUSIONS: AeD therapy was effective to prevent IA in this cohort of TLE patients with prior IA. Consequently, pacemaker implantation is not immediately indicated for IA prevention, but should be reserved for those cases in which there is documented failure of AeD therapy.

Ictal bradyarrhythmias and asystole requiring pacemaker implantation: Combined EEG-ECG analysis of 5 cases.

BACKGROUND: Seizures can lead to cardiac arrhythmias by a number of mechanisms including activation/inhibition of cortical autonomic centers, increase in vagal tone through activation of brainstem reflex centers, and respiratory failure. Ictal asystole (IA) is a potential mechanism underlying sudden unexpected death in epilepsy (SUDEP). We analyzed the clinical features of 5 patients who developed IA requiring pacemaker implantation. METHODS: Patients with ictal arrhythmias were identified from the video-telemetry and ambulatory EEG database at Greater Manchester Neurosciences Centre, as well as an independent epilepsy residential care facility. Only those who had IA requiring pacemaker implantation were included in the analysis. A total of 5 patients were identified. RESULTS: Of the 5 patients with IA, 4 were female. All 5 patients had focal epilepsy, and four had temporal lobe epilepsy. Ictal asystole occurred with focal seizures with impairment of awareness. Seizure onset was left-sided in 2 patients, right-sided in one, left-sided onset with switch of lateralization in one, and nonlateralized in one patient. Three patients had hippocampal sclerosis, one of whom had undergone epilepsy surgery, one had traumatic encephalomalacia of the temporal lobe, and one patient had no lesions detected on MRI. Interictal epileptiform activity was more pronounced during sleep in all patients. Asystole occurred in association with sleep-related seizures in 4 of 5 patients. CONCLUSIONS: Ictal asystole (IA) occurred in association with sleep-related seizures in 4 out of 5 cases, predominantly in patients with temporal lobe epilepsy. These findings may be of relevance to SUDEP.

Syncope or seizure: that is the question-case report of a young patient with convulsive cardioinhibitory syncope treated with cardioneuroablation.

Background: Differentiation of syncope from seizure is challenging and has therapeutic implications. Cardioinhibitory reflex syncope typically affects young patients where permanent pacing should be avoided whenever possible. Cardioneuroablation may obviate the need for a pacemaker in well-selected patients. Case summary: A previously healthy 24-year-old woman was referred to the emergency department after recurrent episodes of transient loss of consciousness (TLOC). The electrocardiogram (ECG) and the echocardiogram were normal. An electroencephalogram (EEG) showed intermittent, generalized pathological activity. During EEG under photostimulation, the patient developed a short-term TLOC followed by brachial myocloni, while the concurrent ECG registered a progressive bradycardia, which turned into a complete atrioventricular block and sinus arrest with asystole for 14 s. Immediately after, the patient regained consciousness without sequelae. The episode was interpreted as cardioinhibitory convulsive syncope. However, due to the pathological EEG findings, an underlying epilepsy with ictal asystole could not be fully excluded. Therefore, an antiseizure therapy was also started. After discussing the consequences of pacemaker implantation, the patient agreed to undergo a cardioneuroablation and after 72 h without complications, she was discharged home. At 10 months, the patient autonomously discontinued the antiepileptics. The follow-up EEG displayed unspecific activities without clinical correlations. An implantable loop recorder didn't show any relevant bradyarrhythmia. At 1-year follow-up, the patient remained asymptomatic and without syncopal episodes. Discussion: Reflex syncope must be considered in the differential diagnosis of seizures. The cardioneuroablation obviated the need for a pacemaker and allowed for the withdrawal of anticonvulsants, originally started on the premise of seizure.

Ictal Asystole During Focal Seizures Due to Left Occipital Glioneuronal Tumor: A Report of Case Treated With Cardiac Neuromodulation.

Ictal asystole (IA) is a rare but potentially life-threatening complication of focal epilepsy. The sudden onset of loss of consciousness and drop attacks in a patient with chronic epilepsy should suggest the possibility of this complication. Once the diagnosis is established, rapid management should be considered, especially in high-risk cases. The approach does not differ between temporal and extratemporal lobe epilepsies. Strategies can be aimed at preventing the emergence of cortical epileptic activity from the beginning (surgery, antiseizure therapy), neutralizing negative chronotropic effects on the heart (cardiac neuromodulation), or restarting the heart rhythm with a pacemaker. Pacemaker implantation is not a completely complication-free treatment, and living with a device that requires care and follow-up throughout life makes alternative treatment methods more valid for young patients with many years to live or cases that could benefit from surgery. In this article, we present a patient with a left occipital glioneuronal tumor and drug-resistant occipital lobe epilepsy. IA was documented by long-term video EEG monitoring (VEM). During about 2 years of follow-up after a cardiac neuromodulation procedure, there were no drop attacks or asystole with seizures, confirmed by long-term VEM.

The Heart and Seizures: Friends or Enemies?

The heart and seizures are closely linked by an indissoluble relationship that finds its basis in the cerebral limbic circuit whose mechanisms remain largely obscure. The differential diagnosis between seizures and syncopes has always been a cornerstone of the collaboration between cardiologists and neurologists and is renewed as a field of great interest for multidisciplinary collaboration in the era of the diffusion of prolonged telemonitoring units. The occurrence of ictal or post-ictal arrhythmias is currently a cause of great scientific debate with respect to the role and risks that these complications can generate (including sudden unexpected death in epilepsy). Furthermore, the study of epileptic seizures and the arrhythmological complications they cause (during and after seizures) also allows us to unravel the mechanisms that link them. Finally, intercritical arrhythmias may represent great potential in terms of the prevention of cardiological risk in epileptic patients as well as in the possible prediction of the seizures themselves. In this paper, we review the pertaining literature on this subject and propose a scheme of classification of the cases of arrhythmia temporally connected to seizures.

[Restlessness and Syncopes in a Patient from a Home for Elderly]. / Eine Frau mit Unruhe und Synkopen im Altersheim.

Restlessness and Syncopes in a Patient from a Home for Elderly Abstract. A broad differential diagnosis should be considered when faced with syncopes. Most common causes are cardiovascular and neurological causes. If there is evidence of epilepsy with sudden loss of tone, look for ictal-triggered arrhythmias. Ictal bradycardias and asystoles are usually benign and self-limiting. In contrast, bradycardias and asystoles in the context of SUDEP are usually fatal and are the result of ictally induced cerebral hypoxemia.

Ictal asystole during long-term video-EEG; semiology, localization, and intervention.

Ictal arrhythmias are disturbances of cardiac conduction that occur during clinical or electrographic seizures. Ictal asystole (IA) is rare, and its incidence can range from 0.3-0.4% in patients with epilepsy who were monitored by video-EEG (van der Lende et al., 2015). We report on ten patients (six males and four females) with an age ranging from 31 to 70 years old) who were monitored in our video-EEG (VEEG) unit over the last eight years. These patients were selected based on the history of documented ictal asystole during inpatient VEEG monitoring). In our series the mean latency from the seizure onset to the onset of ictal asystole was 22 seconds and the mean duration of the IA was 15.8 seconds. During the asystolic phase the seizures may clinically continue or syncopal signs may supervene. In our case series all the patients had either left or right temporal lobe epilepsy, six of which were lesional. We found two patterns of ictal semiology in our series. The first group of patients included five patients who experienced a rapid onset of IA in their seizure and the second group where the latency of ictal asystole was relatively late. All our cohort had a permanent pacemaker following the diagnosis, six of these patients have been event free since placement.

Musicogenic epilepsy with ictal asystole: a video-EEG case report.

Musicogenic seizures and ictal asystole are two rare features mainly encountered in temporal lobe epilepsy. We present the first case of musicogenic epilepsy with ictal asystole in a patient with right temporal lobe epilepsy, confirmed by video-EEG. The pathophysiological mechanism of both conditions remains uncertain. These two features appeared after many years of epilepsy in our patient, and although this association might be coincidental, common mechanisms could be involved, including remodelling of neural connections or seizure propagation to a singular zone. This case also highlights the need for precise electroclinical assessment of seizures that change clinically over time, particularly when falls occur after a certain period of latency, suggesting cardiac consequences of the seizures.

Late-Onset Ictal Asystole and Falls Related to Severe Coronary Artery Stenosis: A Case Report.

Introduction: Ictal asystole (IA) is a rare, underestimated, and life-threatening cause of transient loss of consciousness and fall. Current treatment options for seizures associated with IA usually include cardiac pacemaker implantation. We report, for the first time, a case of IA that is related to coronary stenosis, which was resolved after coronary angioplasty. Case Presentation: A 73-year-old man had a 2-year history of focal seizures with impaired awareness. Three months before our observation, he started to have sudden falls resulting in injury on several occasions. General and neurological examinations, as well as brain MRI, were unremarkable. Interictal electroencephalography (EEG) showed bitemporal spiking. Ictal video-polygraphy revealed a diffuse electrodecrement, followed by a buildup of rhythmic 4-6 Hz sharp activity, which was more evident in the left temporal region. After the seizure onset, the ECG showed sinus bradycardia, followed by sinus arrest that was associated with the patient's fall from the standing position. Afterwards, sinus rhythm returned spontaneously. A diagnosis of IA was made. A comprehensive cardiologic evaluation revealed a sub-occlusive stenosis of the left anterior descending artery. Successful coronary angioplasty resolved IA, levetiracetam was added, and no seizure or fall has occurred in the following 20 months. Moreover, he underwent a 7-day Holter ECG monitoring, and no asystole was depicted. Conclusion: The present case was unique as it shows the potential association between IA and coronary stenosis, also suggesting a possible therapeutic role for coronary angioplasty. It also highlights the importance of carefully investigating epilepsy patients with falls, especially in the elderly, since IA-related falls can be easily misdiagnosed in older age. Thus, if IA is identified, a deeper cardiac evaluation should be considered. As seen in our patient, non-invasive diagnostic examination including routine, prolonged, and exercise ECG, as well as echocardiogram, were readily available and were informative in diagnosing cardiac abnormalities that are amenable to specific treatment.

Low-grade tumour over the left temporal neocortex and ictal asystole: network and surgical implications.

We describe a patient with focal epilepsy characterized by ictal asystole episodes and low-grade tumour over the left temporal neocortex. Non-invasive pre-surgical evaluation showed an epileptogenic zone extended beyond the low-grade tumour. This extension was confirmed by intraoperative electrocorticography. One-stage surgery with anterior temporal lobe resection was performed. The patient was seizure-free after one year of follow-up. Detailed electroclinical and therapeutic reasoning with hypotheses defining epileptogenic and symptomatogenic networks are discussed.

Focal cortical dysplasia with prolonged ictal asystole, a case report.

INTRODUCTION: Cortical dysplasia carries significant morbidities such as seizures and delayed milestones. Focal cortical dysplasia (FCD) causes refractory epilepsy with various seizure types depending on the location and extent of the dysplasia. FCD in the temporal region and the insular cortex may cause ictal bradycardia (IB) and ictal asystole (IA). Video EEG (VEEG) with simultaneous EKG recording can better diagnose these cardiac abnormalities in FCD. We describe a case of refractory epilepsy. The patient's clinical seizures were usually followed by syncope. VEEG revealed frequent seizures some of which were associated with prolonged ictal asystole. RESULTS: A 15 years old female was admitted to an epilepsy monitoring unit for VEEG. There were widespread fast abnormal discharges known as FREDs with a frequency of 16-20 Hz. She developed numerous habitual seizures and syncope. Some of these were associated with an EKG change in the form of asystole. The cardiac workup was normal. MRI revealed abnormalities in bilateral insular, temporal, and right parietal lobes. CONCLUSION: This case highlights the significance of:●Fast rhythmic epileptiform discharges (FREDs) in cortical dysplasia.●Role of video-EEG monitoring.●Prolonged asystole and the potential role of cardiac intervention in the form of cardiac pacing and cardioneuroablation in decreasing syncope.

Ictal and Interictal Cardiac Manifestations in Epilepsy. A Review of Their Relation With an Altered Central Control of Autonomic Functions and With the Risk of SUDEP.

There is a complex interrelation between epilepsy and cardiac pathology, with both acute and long-term effects of seizures on the regulation of the cardiac rhythm and on the heart functioning. A specific issue is the potential relation between these cardiac manifestations and the risk of Sudden and Unexpected Death in Epilepsy (SUDEP), with unclear respective role of centrally-control ictal changes, long-term epilepsy-related dysregulation of the neurovegetative control and direct effects on the heart function. In the present review, we detailed available data about ictal cardiac changes, along with interictal cardiac manifestations associated with long-term functional and structural alterations of the heart. Pathophysiological mechanisms of these cardiac changes are discussed, with a specific focus on central mechanisms and the investigation of a possible deregulation of the central control of autonomic functions in addition to the role of catecholamine and hypoxemia on heart.

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

INTRODUCTION: SCN8A-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 REPORT: The 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. CONCLUSIONS: This 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.

Ictal Asystole in Drug-Resistant Focal Epilepsy: Two Decades of Experience from an Epilepsy Monitoring Unit.

BACKGROUND: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. Methods: From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R-R interval of ≥3 s during a seizure). Results: IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal (n = 5), temporo-parietal (n = 1) or frontal (n = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. Conclusion: IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure.

Ictal asystole: A condition between neurology and cardiology.

Ictal asystole can appear in patients with focal epilepsy, even in early phases. We present our experience of 7 cases, remarking the electrocardiographic characteristics, the role of apnea, treatment and long-term evolution. Awareness of this entity and collaboration between neurologists and cardiologists are essential for a correct diagnosis and management.

Resolution of ictal bradycardia and asystole following temporal lobectomy: A case report, and review of available cases using pacemakers.

Ictal bradycardia (IB) and ictal asystole (IA) are uncommonly recognized phenomena that increase morbidity in patients with epilepsy by causing syncope and seizure-related falls. These arrhythmias are also suspected to be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We report a case of a 57-year-old male with left temporal lobe epilepsy who experienced both IB and IA. This patient was initially managed with pacemaker implantation, prior to undergoing left temporal lobectomy. Following surgery, the patient had no ongoing IB or IA on his pacemaker recordings, and his seizure control was greatly improved. His pacemaker was removed approximately one year post-operatively and he continued treatment with anti-seizure drugs (ASDs). A literature review of cases of IB and IA that were managed with pacemakers was performed. Pacemaker implantation appears to be quite effective for reducing seizure-related syncope and falls in the setting of IB/IA. Epilepsy surgery also seems to be an effective treatment option for IB/IA, as many patients are able to have their pacemakers removed post-operatively. Further investigations into the pathophysiology of IB and IA and long-term outcomes using different treatment modalities are clearly needed to help formulate treatment guidelines and, potentially, to reduce the occurrence of SUDEP in these patients.