Introduction: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS-EMG) to track... Show moreIntroduction: The lack of reliable biomarkers constrain epilepsy management. We assessed the potential of repeated transcranial magnetic stimulation with electromyography (TMS-EMG) to track dynamical changes in cortical excitability on a within-subject basis. Methods: We recruited people with refractory focal epilepsy who underwent video-EEG monitoring and drug tapering as part of the presurgical evaluation. We performed daily TMS-EMG measurements with additional postictal assessments 1- 6 h following seizures to assess resting motor threshold (rMT), and motor evoked potentials (MEPs) with single- and paired-pulse protocols. Anti-seizure medication (ASM) regimens were recorded for the day before each measurement and expressed in proportion to the dosage before tapering. Additional measurements were performed in healthy controls to evaluate day-to-day rMT variability. Results: We performed 77 (58 baseline, 19 postictal) measurements in 16 people with focal epilepsy and 35 in seven healthy controls. Controls showed minimal day-to-day rMT variation. Withdrawal of ASMs was associated with a lower rMT without affecting MEPs of single- and paired-pulse TMS-EMG paradigms. Postictal measurements following focal to bilateral tonic- clonic seizures demonstrated unaltered rMT and increased short interval intracortical inhibition, while measurements following focal seizures with impaired awareness showed decreased rMT's and reduced short and long interval intracortical inhibition. Conclusion: Serial withinsubject rMT measurements yielded reproducible, stable results in healthy controls. ASM tapering and seizures had distinct effects on TMS-EMG excitability indices in people with epilepsy. Drug tapering decreased rMT, indicating increased overall corticospinal excitability, whereas seizures affected intracortical inhibition with contrasting effects between seizure types. Show less
Introduction In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset... Show moreIntroduction In patients with ictal asystole (IA) both cardioinhibition and vasodepression may contribute to syncopal loss of consciousness. We investigated the temporal relationship between onset of asystole and development of syncope in IA, to estimate the frequency with which pacemaker therapy, by preventing severe bradycardia, may diminish syncope risk. Methods In this retrospective cohort study, we searched video-EEG databases for individuals with focal seizures and IA (asystole >= 3 s preceded by heart rate deceleration) and assessed the durations of asystole and syncope and their temporal relationship. Syncope was evaluated using both video observations (loss of muscle tone) and EEG (generalized slowing/flattening). We assumed that asystole starting <= 3 s before syncope onset, or after syncope began, could not have been the dominant cause. Results We identified 38 seizures with IA from 29 individuals (17 males; median age: 41 years). Syncope occurred in 22/38 seizures with IA and was more frequent in those with longer IA duration (median duration: 20 [range: 5-32] vs. 5 [range: 3-9] s; p < .001) and those with the patient seated vs. supine (79% vs. 46%; p = .049). IA onset always preceded syncope. In 20/22 seizures (91%), IA preceded syncope by >3 s. Thus, in only two instances was vasodepression rather than cardioinhibition the dominant presumptive syncope triggering mechanism. Conclusions In IA, cardioinhibition played an important role in most seizure-induced syncopal events, thereby favoring the potential utility of pacemaker implantation in patients with difficult to suppress IA. Show less
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... Show morePeople 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. Show less
Objectives We ascertained the prevalence of ictal arrhythmias to explain the high rate of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome (DS).Methods We selected cases with clinical... Show moreObjectives We ascertained the prevalence of ictal arrhythmias to explain the high rate of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome (DS).Methods We selected cases with clinical DS, >= 6 years, SCN1A mutation, and >= 1 seizure/week. Home-based ECG recordings were performed for 20 days continuously. Cases were matched for age and sex to two epilepsy controls with no DS and >= 1 major motor seizure during video-EEG. We determined the prevalence of peri-ictal asystole, bradycardia, QTc changes, and effects of convulsive seizures (CS) on heart rate, heart rate variability (HRV), and PR/QRS. Generalized estimating equations were used to account for multiple seizures within subjects, seizure type, and sleep/wakefulness.Results We included 59 cases. Ictal recordings were obtained in 45 cases and compared to 90 controls. We analyzed 547 seizures in DS (300 CS) and 169 in controls (120 CS). No asystole occurred. Postictal bradycardia was more common in controls (n = 11, 6.5%) than cases (n = 4, 0.7%; P = 0.002). Peri-ictal QTc-lengthening (>= 60ms) occurred more frequently in DS (n = 64, 12%) than controls (n = 8, 4.7%, P = 0.048); pathologically prolonged QTc was rare (once in each group). In DS, interictal HRV was lower compared to controls (RMSSD P = 0.029); peri-ictal values did not differ between the groups. Prolonged QRS/PR was rare and more common in controls (QRS: one vs. none; PR: three vs. one).Interpretation We did not identify major arrhythmias in DS which can directly explain high SUDEP rates. Peri-ictal QTc-lengthening was, however, more common in DS. This may reflect unstable repolarization and an increased propensity for arrhythmias. Show less
