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.     

Syncope or seizure? The diagnostic value of synchronous tilt testing and video-EEG monitoring in children with transient loss of consciousness

Syncope and seizure are frequently encountered problems in daily neurology practice, and they also share common findings such as transient loss of consciousness and atonia. Sometimes, it is difficult to make a differentiation between the two entities using only clinical findings. In this study, nineteen patients aged between 5 and 20 years who had recurrent transient loss of consciousness and occasional atonic events were examined with synchronous tilt testing and video-EEG recordings. Eleven patients were initially diagnosed with epilepsy, and they were given antiepileptic drugs. Eight patients displayed neurally mediated syncope during examination. Four of the eight patients had cardioinhibitory syncope type 2B. Three-fourths of the patients with syncope had been initially diagnosed with epilepsy and were prescribed antiepileptic drugs. One patient with cardioinhibitory syncope who had prolonged asystole and frequent attacks needed a cardiac pacemaker. Following implantation, she had no new attacks. Synchronous tilt testing and video-EEG recordings give more information than doing them separately, and they are helpful in the differential diagnosis of syncope and seizure.     

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]     

Synkopen

Syncope occurs in approximately 25% of the population at least once during their lifetime. It therefore represents the most frequent differential diagnosis of an epileptic seizure. Depending on the prognosis and therapy, syncopes can be divided in cardiac syncope, syncope due to orthostatic hypotension and reflex syncope, of which vasovagal (neurocardiogenic) syncope is the most frequent type. Vasovagal syncope typically occurs after prolonged standing, the sight of blood, pain and medical procedures. The pathophysiology is not well understood. Genetic factors play a role as well, mainly following a complex mode of inheritance. Syncope can usually be differentiated from an epileptic seizure based on the medical history. Typical vasovagal triggers, a typical prodrome and pallor suggest syncope, whereas cyanosis, tongue biting and a prolonged postictal state favor an epileptic seizure. In cases of doubt or if cardiac syncope is suspected additional diagnostic tests may be necessary. Due to the increased mortality, patients with cardiac syncope need urgent cardiological treatment. The aim of the treatment of vasovagal syncope is to avoid additional events as this type is not associated with increased mortality. This can be achieved by behavioral changes, e.g. avoiding the trigger situation and lying down or tensing of arm and leg musculature during the prodrome to avoid further reduction of blood pressure. There is only sparse evidence for pharmacotherapeutic options. Cardiac pacemakers mostly have no effect. The implantation of a pacemaker seems to be beneficial only in patients over 40 years old with frequent vasovagal syncope, asystole and negative tilt table test.     

Clustering syncope in a young male with temporal lobe seizures

We report the case of a male aged 2 years 6 months with left temporal lobe epilepsy who presented with ictal bradycardia syndrome leading to asystole. The clinical presentation was remarkable for the occurrence of clustering syncope. A seizure was recorded on a video electroencephalogram- electrocardiogram and analyzed. A cardiac pacemaker was implanted and antiepileptic drug treatment was initiated. We suggest that clustering of syncope is an important feature in the presentation of epilepsy in a young child.     

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).     

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].     

Cardioinhibitory syncope with asystole during nitroglycerin potentiated head up tilt test: prevalence and clinical predictors

Aims

The aim of our study was to evaluate the prevalence and clinical predictors of cardioinhibitory (CI) responses with asystole at the nitroglycerin (NTG)-potentiated head-up tilt test (HUTT) in patients with a history of syncope admitted to a tertiary referral syncope unit.

Methods

We retrospectively evaluated all consecutive patients who underwent NTG-potentiated HUTT for suspected reflex syncope at our institution from March 1 2017 to May 1 2020. The prevalence of HUTT-induced CI syncope was assessed. Univariate and multivariate analyses were performed to test the association of asystolic response to HUTT with a set of clinical covariates.

Results

We enrolled 1285 patients (45 ± 19.1 years; 49.6% male); 368 (28.6%) showed HUTT-induced CI response with asystole. A multivariate analysis revealed that the following factors were independently associated with HUTT-induced CI syncope: male sex (OR 1.48; ConInt 1.14–1.92; P = 0.003), smoking (OR 2.22; ConInt 1.56–3.115; P < 0.001), traumatic syncope (OR: 2.81; ConInt 1.79–4.42; P < 0.001), situational syncope (OR 0.45; ConInt 0.27–0.73; P = 0.002), and the use of diuretics (OR 9.94; ConInt 3.83–25.76; P < 0.001).

Conclusions

The cardioinhibitory syncope with asystole induced by NTG-potentiated HUTT is more frequent than previously reported. The male gender, smoking habit, history of traumatic syncope, and use of diuretics were independent predictors of HUTT-induced CI responses. Conversely, the history of situational syncope seems to reduce this probability.

     

Head-up tilt for triggering and diagnosing syncope

Head-up tilt to 70 degrees lasting for 30 min is a further useful test for studying syncope. In 26.69% of 109 consecutive out-patients referred for loss of consciousness, it induced vasodepressor and/or cardioinhibitory reactions. All symptomatic patients had similar EEG changes and blood pressure fall during symptoms: by contrast, ECG features, due to vagal activation, were different. The pathogenetic mechanism of vasovagal or vasodepressor syncope is an abrupt sympathetic cardiovascular inhibition with more or less marked vagal cardiac activation. This cardiovascular pattern is due to a cardiac reflex in orthostatic syncope or, probably, to a central activation in emotional fainting.     

Vasovagal syncope misdiagnosed as epilepsy for 17 years: prime importance of clinical history.

Distinguishing epilepsy from syncope often can be challenging. We report a case of a 20-year-old patient with presumed refractory epilepsy since the age of 3 years. Although the clinical suspicion of syncope was raised at the age of 9 years, key historic features were not identified, cardiac work-up was not pursued and despite lack of electrographic evidence of epilepsy, he received anticonvulsant treatment. During his presurgical evaluation for "refractory epilepsy", one typical event was captured that was associated with asystole and normal electroencephalogram. The diagnosis of vasodepressor syncope was made and anticonvulsant medication was discontinued. With this case report, we would like to emphasize the importance of a meticulous history and the need to perform continuous video electroencephalographic with simultaneous electrocardiographic recordings in the evaluation of paroxysmal events with atypical presentation. [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 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.     

Adult‐onset photosensitivity: clinical significance and epilepsy syndromes including idiopathic (possibly genetic) photosensitive occipital epilepsy

To evaluate the clinical associations of adult‐onset photosensitivity, we studied the clinical and EEG data of patients who were referred due to a possible first seizure and who had a photoparoxysmal response on their EEG. Patients with clinical evidence of photosensitivity before the age of 20 were excluded. Of a total of 30 patients, four had acute symptomatic seizures, two had vasovagal syncope, and 24 were diagnosed with epilepsy. Nine of the 24 patients had idiopathic (genetic) generalized epilepsies and predominantly generalized photoparoxysmal response, but also rare photically‐induced seizures, while 15 had exclusively, or almost exclusively, reflex photically‐induced occipital seizures with frequent secondary generalization and posterior photoparoxysmal response. Other important differences included a significantly older age at seizure onset and paucity of spontaneous interictal epileptic discharges in patients with photically‐induced occipital seizures; only a quarter of these had occasional occipital spikes, in contrast to the idiopathic (genetic) generalized epilepsy patients with typically generalized epileptic discharges. On the other hand, both groups shared a positive family history of epilepsy, common seizure threshold modulators (such as tiredness and sleep deprivation), normal neurological examination and MRI, a generally benign course, and good response to valproic acid. We demonstrated that photosensitivity can first occur in adult life and manifest, either as idiopathic (possibly genetic) photosensitive occipital epilepsy with secondary generalization or as an EEG, and less often, a clinical/EEG feature of idiopathic (genetic) generalized epilepsies. Identification of idiopathic photosensitive occipital epilepsy fills a diagnostic gap in adult first‐seizure epileptology and is clinically important because of its good response to antiepileptic drug treatment and fair prognosis.     

Tooth‐brushing epilepsy: an SEEG study and surgical treatment

We report a patient with reflex tooth‐brushing‐triggered epilepsy, associated with a post‐central lesion within the right somatosensory face area. Contralateral facial sensory and motor phenomena, associated with contralateral upper limb extension, were present at seizure onset after gingival stimulation, but seizures could also be induced by contact with solid food or liquids. Spontaneous seizures also were recorded. Secondary generalization was infrequent. Stereoelectroencephalography implantation was performed, with seizure recording and cortical/subcortical stimulation for mapping, to identify the precise extent of surgical resection. Complete postoperative control of epilepsy was achieved, accompanied by a mild and transient neurological deficit. [Published with video sequence].     

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.     

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.     

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.     

Complex Partial Seizure Provocation by Vasovagal Syncope: Video-EEG and Intracranial Electrode Documentation

Summary: Vasovagal syncope precipitating an epileptic seizure has only rarely been described. A patient with known intractable complex partial seizures being evaluated for a left anterior temporal lobectomy experienced a typical seizure with mesial temporal onset precipitated by an observed vasovagal episode. This is the first report of a partial epileptic seizure precipitated by vasovagal syncope and the first example of an epileptic seizure induced by syncope in an adult. Video and intracranial depth electrode and subdural grid recordings documented the event.