Ventricular asystole during vagus nerve stimulation for epilepsy in humans

Electrical stimulation of the vagus nerve, a recently available option for patients with refractory epilepsy, has demonstrated safety and efficacy. We report four patients with refractory epilepsy who experienced ventricular asystole intraoperatively during initial testing for implantation of the vagus nerve stimulator. Acute intraoperative vagus nerve stimulation may create ventricular asystole in humans. Extracorporeal cervical vagus nerve stimulation testing with continuous EKG monitoring intraoperatively before generator implantation is warranted.     

Ictal asystole—Late manifestation of partial epilepsy and importance of cardiac pacemaker

Ictal asystole (IA) is a life-threatening complication of epilepsy and is a potential mechanism of sudden unexplained death in epilepsy (SUDEP). This entity has been proven by multiple case reports and small case series. The management of the patients with IA is still in early phase of discussion. We report a patient with medically intractable cryptogenic partial epilepsy for 27 years who presented with new onset drop attacks. During the epilepsy monitoring unit stay he was found to have a left fronto-temporal partial onset seizures which triggered brady-arrhythmia followed by asystole for 20 s. A cardiac pacemaker was implanted and the patient was followed for 2 years. He continued to have simple and complex partial seizures but did not have drop attacks anymore. He still occasionally feels the activation of his pacemaker during simple partial phase of his seizures but the characteristic loss of muscle tone never happened again which made him highly satisfied. Our case demonstrates that IA can even happen decades after the onset of epilepsy. Cardiac pacemaker should be considered in all patients with IA as it prevents ictal falls and possibly SUDEP.     

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.     

Cardiac asystole during right frontal lobe seizures: a case report

Abstract The association between partial seizures and cardiac asystole has rarely been reported in the literature. This potentially life-threatening symptom has been observed principally in left-sided epilepsies, in particular during seizures originating in temporal lobe. We describe a case with ictal bradycardia followed by cardiac asystole during right frontal lobe seizures. Video-EEG monitoring recorded two partial seizures with electro-clinical findings suggestive of a right frontal lobe origin, associated with ictal bradycardia followed by prolonged asystole. The brain MRI showed a lesion located in the cingulate gyrus of the right frontal lobe. The patient required a subsequent placement of a pacemaker. In conclusion, cardiac asystole may be a potentially life-threatening symptom during seizures of frontal lobe origin. The right fronto-mesial structures may play a role in autonomic regulation of cardiovascular responses.     

Cardiac asystole during a temporal lobe seizure

The association between temporal lobe seizures and cardiac arrhythmias has been anecdotally reported in the literature. Ictal bradycardia and cardiac asystole are rare, and maybe underestimated. The physiological mechanism is poorly understood. We report a patient with left temporal lobe seizures who developed ictal bradycardia and cardiac asystole during a complex partial seizure and required a subsequent placement of a pacemaker.     

Application of a vagal nerve stimulator in an epilepsy patient with cardiac pacemaker after post‐ictal cardiac arrest

In this case report we present a patient with temporal lobe epilepsy (TLE) showing partial complex seizures and secondary generalization, and treated with several antiepileptic drugs. After two consecutive seizures she had an episode of cardiac arrest followed by AV‐block III which led to the implantation of a cardiac pacemaker. She subsequently received a vagal nerve stimulator because of poor response to epilepsy treatment. Combined treatment with two different electromagnetic stimulators raises the question of safety during surgery which is discussed.     

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].     

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.     

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]     

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.     

Terapia con estimulación del nervio vago en pacientes con epilepsia fármaco-resistente y callosotomía previa

ObjectiveTo analyse the results of vagus nerve stimulation in patients with drug-resistant epilepsy and previous corpus callosotomy.Materials and methodsWe prospectively reviewed data from patients with drug-resistant epilepsy who showed persistence of disabling seizures after undergoing corpus callosotomy, in whom it was not possible to identify an epileptogenic focus and who were subsequently treated with vagus nerve stimulation.Variables analysed included: age, gender, aetiology of epilepsy, frequency and characteristics of the crises and Engel scale classification, before and after vagal stimulator implant. Furthermore, the percentage differences in seizure frequency changes were also calculated.ResultsFour patients were identified: two male and two female. The total seizure frequency had decreased between 20% and 81% after corpus callosotomy in three patients and one of them did not show any favourable response (Engel IVB). Following implantation of the stimulator they became reduced to between 57% and 100% after a mean follow-up period of 8.3 months (range: 3 to 12 months). Generalised seizures decreased between 71.4% and 100%, and focal seizures between 57.7% and 100%.ConclusionsVagus nerve stimulation therapy proved to be an alternative for the reduction of seizure frequency in patients with drug-resistant epilepsy who suffered disabling seizures despite undergoing corpus callosotomy as primary surgery.     

Identifying patients with epilepsy at high risk of cardiac death: signs,risk factors and initial management of high risk of cardiac death

People with epilepsy have a three‐fold increased risk of dying prematurely, and a significant proportion is due to sudden cardiac death or acute myocardial infarctions. The causes of increased cardiovascular morbidity and mortality in epilepsy are manifold and include acute or remote effects of epileptic seizures, the longstanding epilepsy itself or antiseizure treatments. Seizure‐related cardiac arrhythmias are common and comprise bradyarrhythmia and asystole, atrial fibrillation and ventricular tachycardia. The most frequent clinically relevant seizure‐related arrhythmia is ictal asystole that may require implantation of a cardiac pacemaker, whereas seizure‐related ventricular tachycardias are only rarely reported. Takotsubo cardiomyopathy and myocardial infarction are rare complications and predominantly described in association with tonic‐clonic seizures. Epilepsy‐related cardiac complications include a disturbed cardiac autonomic nervous system and acquired dysfunction of the heart (recently defined as ‘epileptic heart’), probably contributing to the abnormalities of cardiac repolarisation and elevated risk of sudden cardiac death in people with epilepsy. If successful, the use of antiseizure medication prevents seizure‐related cardiac arrhythmias and remote cardiac complications. However, enzyme‐inducing antiseizure medications have a negative impact on cardiovascular risk factors, which may further be aggravated by weight gain linked to specific antiseizure drugs. Given the severe consequences of cardiac risks, the aim of this educational review is to explain the many facets of cardiac complications and their underlying causes, and to enable the reader to recognize and manage these risks with the goal to mitigate the cardiac risks in people with epilepsy. Features of syncope are explained in detail, as syncope of all origins can be mistaken as epileptic seizures in people with or without epilepsy, and ictal syncope (i.e. seizure‐induced syncope) can easily be ignored.     

Ictal asystole in epilepsy patients undergoing inpatient video-EEG monitoring

Ictal asystole (IA) is uncommonly diagnosed and has been implicated as a potential cause of sudden unexpected death in epilepsy. Sudden unexpected death in epilepsy is an increasingly recognizable condition and is more likely to occur in patients with medically intractable epilepsy and those suffering from convulsive epilepsy. We report 2 cases of recent onset of prolonged syncope and unrevealing cardiac work up. The inpatient video-EEG monitoring recorded left temporal ictal discharges followed by IA. Although the role of cardiac pacing is controversial in these patients, both patients had favorable outcome following cardiac pacemaker insertion. This report demonstrates the variability in IA pathophysiology and clinical manifestations. It also advocates that cardiac pacing might have a role in the management of IA.Ictal asystole (IA) is an uncommon event that occurs in 0.1-0.4% of patients experiencing seizures during inpatient video-electroencephalography monitoring (VEEG).1 Ictal asystole is more likely to occur in patients with focal seizures originating from the temporal region.2 It has been implicated as a potential cause for sudden unexpected death in epilepsy patients (SUDEP) that carry an incidence of 0.09-9.3 per 1000 patient-years.1 Although controversial, cardiac pacing has been suggested as a possible preventive measure against IA and SUDEP.3 We report 2 cases of IA encountered at our epilepsy monitoring unit between June 2010 and October 2011, and their clinical outcomes after cardiac pacemaker insertions. These 2 cases highlight the importance in considering IA as a potentially fatal complication of epileptic seizures that might be circumvented by good seizure control, and in some cases cardiac pacing.     

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.     

Newer treatment of epilepsy--brain pacemakers and transcranial magnetic stimulation]

The antiepileptic medication and surgical treatment had brought many patients with epilepsy to be seizure free, however, one third of the patients continue to experience seizures. There has recently been an explosion of research into brain stimulation for treating these intractable epilepsy patients. This is largely due to the success of deep brain stimulation of movement disorders. The intelligent cardiac pacemakers also stimulated the neurosurgeons to utilize the implantable devices. In this paper, brain stimulations with vagus nerve stimulator (VNS), depth electrodes, subdural electrodes, external responsive neuro-stimulator, implantable brain stimulator and transcranial magnetic stimulator are reviewed. The VNS had been approved in Europe and United States for clinical use. The efficacy of the VNS has already proven by the controlled trials. Stimulation of the thalamus, subthalamic nucleus and hippocampus showed some efficacy in a small number of patients, however, large scale traials remains to be undertaken. External responsive neurostimulator has shown efficacy and safety to justify further studies with implantable brain stimulators. The multi-center cooperative study is ongoing in the US to examine the usefulness of the implantable stimulator. Animal studies showed efficacy of the transcranial magnetic stimulation for the treatment and prevention of the seizures and status epilepticus.     

Complete heart block with ventricular asystole during left vagus nerve stimulation for epilepsy

Vagus nerve stimulation (VNS) is an important therapeutic option for individuals with refractory epilepsy who have failed multiple antiepileptic drugs (AEDs). The intricate relationship of the vagus nerve to cardiac function raises concern that vagal stimulation may affect cardiac rhythm and function. Previous pre- and postmarketing studies have not shown this to be a significant problem, with the incidence of bradyarrhythmias reported to be about 0.1%. We review three cases of ventricular asystole with complete heart block that occurred during intraoperative lead tests. The purpose of these case reports is to identify the specific type of cardiac abnormality associated with vagus nerve stimulation and to identify individuals at risk.     

Bradycardia and asystole during generalised interictal EEG discharges

Few studies have investigated the effects of interictal epileptic discharges on the cardiac autonomic system. This study reports the case of a 37‐year‐old man with refractory generalised epilepsy, who recently reported an increase in frequency of nocturnal tonic‐clonic seizures, not responding to treatment. During the nocturnal video study, in non‐rapid eye movements sleep, we recorded 106 generalised sharp‐ and polyspike‐waves lasting for 3 to 7 seconds, associated with bradycardia and asystole, without behavioural changes and without increase in deltoid muscle activity. The asystole had a duration of between 3 and 8 seconds. In one case, a 7 second asystole was associated with a tonic‐clonic generalised seizure. A 24‐hour electrocardiographic study revealed a bradycardia and a Wenckebach atrioventricular block. Heart rate analysis at the time of the interictal epileptic discharges revealed an abrupt increase in the RR interval, occurring simultaneously with the onset of interictal epileptic discharges and followed by a return to values below baseline value. A cardiac pacemaker was installed with a reduction of asystole length during the interictal epileptic discharges. Our findings indicate, for the first time, the role of interictal generalised discharges in EEG‐related asystole and bradycardia. These data support the hypothesis that some patients with epilepsy may be predisposed to disturbances of the autonomic cardiac system.     

Berardinelli‐Seip syndrome and progressive myoclonus epilepsy

Berardinelli‐Seip syndrome, or congenital generalized lipodystrophy type 2 (CGL2), is characterized by a lack of subcutaneous adipose tissue and precocious metabolic syndrome with insulin resistance, resulting in diabetes, dyslipidaemia, hepatic steatosis, cardiomyopathy, and acanthosis nigricans. Most reported mutations are associated with mild, non‐progressive neurological impairment. We describe the clinical and EEG data of a patient with progressive myoclonus epilepsy (PME), CGL2, and progressive neurological impairment, carrying a homozygous BSCL2 nonsense mutation. The patient had epilepsy onset at the age of two, characterized by monthly generalized tonic‐clonic seizures. By the age of three, he presented with drug‐resistant ongoing myoclonic absence seizures, photosensitivity, progressive neurological degeneration, and moderate cognitive delay. Molecular analysis of the BSCL2 gene yielded a homozygous c.(1076dupC) p.(Glu360*) mutation. Application of a vagus nerve stimulator led to temporary improvement in seizure frequency, general neurological condition, and EEG background activity. Specific BSCL2 mutations may lead to a peculiar CGL2 phenotype characterized by PME and progressive neurodegeneration. Application of a vagus nerve stimulator, rarely used for PMEs, may prove beneficial, if only temporarily, for both seizure frequency and general neurological condition.     

Severe new seizures after initiation of vagus nerve stimulation therapy

Vagus nerve stimulation is considered to be a safe and effective adjunctive therapy for patients with drug-resistant epilepsy. Contrary to some antiepileptic drugs, vagus nerve stimulation is not known to precipitate or aggravate new or preexisting seizures. We describe the emergence of a new type of disabling, recurrent partial seizure immediately after initiation of vagus nerve stimulation in a 51-year-old man with a known history of refractory partial epilepsy. Discontinuation of vagus nerve stimulation therapy and multiple antiepileptic drug interventions were required to abort these unexpected new seizures. We conclude that vagus nerve stimulation may induce paradoxical seizures, similarly to some antiepileptic drugs.     

Management of epilepsy in mentally retarded children using the newer antiepileptic drugs, vagus nerve stimulation, and surgery

Clusters of seizures, prolonged seizures, and status epilepticus occur more frequently in children with multiple disabilities, and chronic seizures are more likely to be refractory to treatment. In many patients, the seizures appear to contribute to the mental retardation. Thus, if the lives of these children are to improve, seizure control is essential. However, medical treatment can interfere with cognition and cause behavioral disturbances, making life very difficult for the child and the child's family. With the introduction of 10 new antiepileptic drugs in the last decade, the treatment of epilepsy in multiply handicapped children has significantly advanced. These new antiepileptic drugs may improve seizure control, medication tolerance, or both. Although the ultimate therapeutic goal is to keep children seizure free and alert, compromises regarding medication choice and dosage are still necessary in many cases. Novel treatment options, such as the vagus nerve stimulator, may decrease seizure frequency without behavioral or cognitive side effects. In carefully selected children with specific epilepsy syndromes, epilepsy surgery can provide partial or complete relief from seizures.