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Photoplethysmography (PPG) as an additional biosignal for a seizure detector has been underutilized so far, which is possibly due to its susceptibility to motion artifacts. We investigated 62 focal seizures from 28 patients with electrocardiography-based evidence of ictal tachycardia (IT). Seizures were divided into subgroups: those without epileptic movements and those with epileptic movements not affecting and affecting the extremities. PPG-based heart rate (HR) derived from a wrist-worn device was calculated for sections with high signal quality, which were identified using spectral entropy. Overall, IT based on PPG was identified in 37 of 62 (60%) seizures (9/19, 7/8, and 21/35 in the three groups, respectively) and could be found prior to the onset of epileptic movements affecting the extremities in 14/21 seizures. In 30/37 seizures, PPG-based IT was in good temporal agreement (

• We investigated heart rate (HR) between epileptic and non-epileptic arousals. • Within 60 s after arousal, HR increased by 86.7% in the epileptic arousals. • Within 60 s after arousal, HR increased by 26.1% in the non-epileptic arousals. • The cutoff value was 48.7%, sensitivity 0.79, and specificity 0.80. • More than 70.1% was only in the epileptic arousals, with 100% specificity. We investigated the difference in heart rate (HR) change between epileptic and non-epileptic arousals in adult patients with epilepsy (PWE). This is a case-control study conducted at the University Hospitals of Cleveland Medical Center. Inclusion criteria are (1) adult (≥18 years old) PWE who had arousal related to a focal aware or impaired awareness automatism seizure with or without focal to bilateral tonic-clonic seizure during an Epilepsy Monitoring Unit (EMU) admission between January 2009 and January 2021 or (2) adult PWE who had a non-epileptic arousal during an EMU admission between July 2020 and January 2021. Outcomes are (1) a percent change in baseline HR within 60 s after arousal and (2) the highest percent change in baseline HR within a 10-s sliding time window within 60 s after arousal. We included 20 non-epileptic arousals from 20 adult PWE and 29 epileptic arousals with seizures from 29 adult PWE. Within 60 s after arousal, HR increased by a median of 86.7% (interquartile range (IQR), 52.7%–121.3%) in the epileptic arousal group compared to a median of 26.1% (12.9%–43.3%) in the non-epileptic arousal group (p < 0.001). The cut-off value was 48.7%. The area under the curve (AUC), sensitivity, and specificity were 0.85, 0.79, and 0.80, respectively. More than 70.1% was only in the epileptic arousals, with 100% specificity. Within 10 s of the greatest change, HR increased by 36.5 (18.7%–48.4%) in the epileptic arousal group compared to 17.7 (10.9%–23.7%) in the non-epileptic arousal group (p < 0.001). The cut-off value was 36.5%. The AUC, sensitivity, and specificity were 0.79, 0.52, and 0.95, respectively. More than 48.1% was only in the epileptic arousals, with 100% specificity. Tachycardia during epileptic arousals was significantly higher and more robust compared to tachycardia during non-epileptic arousals. [ABSTRACT FROM AUTHOR]

Objective Ictal tachycardia (IT) is common and may pave the way towards cardiac conditions with high risk potential. However, the mechanisms of IT remain obscure and therefore difficult to control. For example, whereas IT is associated with a sympathetic surge, it is unclear why the IT effects are not opposed by baroreflex cardiac inhibition during seizures. As the vagus nerves (VN) are main mediators for such baroreflexes, this study was performed to investigate the VN activity in IT. Methods The present experiments were performed in ten pigs where IT seizures were induced by controlled infusion of pentylenetetrazole. The electrocorticogram was recorded using a cranial electrode, the electrocardiogram (ECG) using surface electrodes and the blood pressure (BP) using a catheter inserted in the right carotid artery. The VN activity was recorded from both nerves using cuff electrodes and further analyzed in correlation with the cortical seizures and the associated heart rate (HR), BP and HR variability (HRV) changes. Results The cortical seizures progressed from spike-and-wave (SW) to tonic-clonic (TC) discharges associated with ECG, HR and BP changes proportional with this progression and comparable to the IT effects reported in humans. Those IT effects were accompanied by parasympathetic HRV changes, a 20% VN activation (p = 0.004) before the onset of TC seizures, a suppression of this VN activation during the TC episode and a rebound VN activation by 79% (left VN, p = 0.02) and 57% (right VN, p = 0.03) after the TC offset. Further analysis of an afferent BP-related VN component and a mixed VN component showed normal BP-related afferent input and a suppressed efferent output through both nerves during the TC episode. Conclusions This study indicates a suppressed ictal VN activation and a rebound postictal VN activation, which may account for the absence of baroreflexes during seizures and the postictal cardiac inhibition, respectively. [ABSTRACT FROM AUTHOR]

Many epilepsy patients treated with vagus nerve stimulation additionally use an 'on-demand' function, triggering an extra stimulation to terminate a seizure or diminish its severity. Nevertheless, a substantial number of patients are not able to actively trigger stimulations by use of a magnet, due to the absence of an aura or inability for voluntary actions in the early phase of a seizure. To address this need, a novel implantable pulse generator, the AspireSR VNS system, was developed to provide automated ictal stimulation triggered by a seizure-detecting algorithm. We report our experience with three patients in assessing the functionality of ictal stimulation, illustrating the detection system in practice. Detection of ictal tachycardia and variable additional detections of physiological tachycardia depended on the individual seizure-detecting algorithm settings. [ABSTRACT FROM AUTHOR]

Purpose: This study investigates the performance of a cardiac-based seizure detection algorithm (CBSDA) that automatically triggers VNS (NCT01325623).Methods: Thirty-one patients with drug resistant epilepsy were evaluated in an epilepsy monitoring unit (EMU) to assess algorithm performance and near-term clinical benefit. Long-term efficacy and safety were evaluated with combined open and closed-loop VNS.Results: Sixty-six seizures (n=16 patients) were available from the EMU for analysis. In 37 seizures (n=14 patients) a ≥ 20% heart rate increase was found and 11 (n=5 patients) were associated with ictal tachycardia (iTC, 55% or 35 bpm heart rate increase, minimum of 100 bpm). Multiple CBSDA settings achieved a sensitivity of ≥ 80%. False positives ranged from 0.5 to 7.2/h. 27/66 seizures were stimulated within ± 2 min of seizure onset. In 10/17 of these seizures, where triggered VNS overlapped with ongoing seizure activity, seizure activity stopped during stimulation. Physician-scored seizure severity (NHS3-scale) showed significant improvement for complex partial seizures (CPS) at EMU discharge and through 12 months (p<0.05). Patient-scored seizure severity (total SSQ score) showed significant improvement at 3 and 6 months. Quality of life (total QOLIE-31-P score) showed significant improvement at 12 months. The responder rate (≥ 50% reduction in seizure frequency) at 12 months was 29.6% (n=8/27). Safety profiles were comparable to prior VNS trials.Conclusions: The investigated CBSDA has a high sensitivity and an acceptable specificity for triggering VNS. Despite the moderate effects on seizure frequency, combined open- and closed-loop VNS may provide valuable improvements in seizure severity and QOL in refractory epilepsy patients. [ABSTRACT FROM AUTHOR]

Objective Information on the relative timing of electroencephalography ( EEG) seizure onset, ictal tachycardia ( ITC), and first other clinical seizure manifestations is crucial for an understanding of the potential benefit of ITC-detection based closed-loop intervention systems for epilepsy treatment. This study analyzes the temporal relation of ITC, other clinical signs, and seizure onset in relation to intracranial and surface EEG. Methods Seventy-eight seizures with ITC from 13 patients undergoing invasive EEG recordings with simultaneous recordings of electrocardiography ( ECG), intracranial EEG ( iEEG) and surface EEG, and video recordings to determine clinical onset were analyzed. Latencies for ITC were calculated for thresholds of 100 bpm and for a 20% heart rate increase above baseline obtained 60 s prior to seizure onset on iEEG. Patient-based, seizure-based, and seizure origin-based analyses were performed. Results Mean latencies between seizure onset in invasive EEG and the following onset of ITC in the seizure- and patient-based analysis for both thresholds varied between 21.6 and 23.7 s, showing that ITC is an ictal rather a preictal phenomenon. In 10 of 13 patients and in 56 of 78 seizures, at least one of the thresholds for ITC was crossed before any other clinical sign. In the majority of cases, ITC also preceded ictal onset as determined in surface EEG. Latencies to ictal tachycardia were shorter for hippocampal than for extrahippocampal temporal seizure onset. ITC occurred earlier in right than in left temporal seizures. Significance iEEG preceded other seizure manifestations, but ictal tachycardia was an early sign particularly in mesial temporal and in right temporal seizure onset and often preceded not only other clinical manifestations but also first visible patterns in surface EEG. Detection of ictal tachycardia was thus the best noninvasively assessed marker for closed-loop interventions in this multimodally assessed patient group. [ABSTRACT FROM AUTHOR]

Purpose A novel vagus nerve stimulation (VNS) device was recently approved in Europe which rapidly detects increases in heart rates (HR) and applies an additional stimulus if HR-increases exceed a given threshold. The effects of HR-triggered VNS-pulses on seizures were not reported yet under controlled conditions. Here, we quantified the effects of HR-triggered VNS-pulses on the seizure duration in one patient. Methods The novel VNS device was implanted in a 29-year old man with refractory epilepsy. After implantation, the patient underwent video-EEG telemetry for 68 h with no changes in anticonvulsant drugs. On the first day the patient only received sham-stimulation. During the following 46 h HR-related VNS-stimulation was set to 2 mA. Seizure duration was determined based on clinical signs. Results Twelve stereotypical seizures were recorded (six during sham- and six during the active stimulation). The VNS device recognised a total of 139 events as a seizure and correctly identified 11 seizures. The HR-triggered VNS-stimulation significantly reduced the total seizure duration from 33.2 ± 4.8 s to 26.5 ± 5 s and the remaining seizure duration after the onset of the extra-stimulation from 27.8 ± 4.3 s to 16.2 ± 3.2 s. With the given configuration in this patient, sensitivity and specificity of HR-based seizure-detection amounted to 92% and 13.5%, respectively. Conclusions This case illustrates that VNS-stimulation in response to seizure-related HR-increases is able to significantly reduce seizure duration. Despite the limitations of our case, its promising results should prompt larger studies to confirm the clinical benefit of this novel device. [ABSTRACT FROM AUTHOR]

Activity in both divisions of the autonomic nervous system (ANS) can increase during seizures and result in tachy- or bradyarrhythmias. We sought to determine the patterns of ANS activity that led to heart rate (HR) changes and whether the character of ANS and HR changes can impact the seizures themselves. Simultaneous recordings of vagus nerve and cervical sympathetic ganglionic or nerve activity, EEG, ECG, and blood pressure were acquired from 16 urethane-anesthetized rats that received systemic kainic acid to induce seizures. After initial continuous seizure activity, discrete seizures were observed in 11/16 rats. Individual seizures were classified based on HR changes as tachycardic (n = 3), bradycardic (n = 17), or one of two more severe categories in which (a) the seizure appeared to be terminated by severe bradyarrhythmia (n = 5) or (b) the animal died (n = 6). Interestingly, even simple bradycardic seizures had episodes of dramatically increased respiratory effort, which we interpret as evidence of airway occlusion based on muscle artifacts in the recordings with transient blood pressure decreases. In the severe outcomes, ANS activity increased during seizures until it caused a drastic HR reduction (>50%), in which case seizure and ANS activity decreased dramatically. Sympathetic activity during this late vulnerable period was important for survival. We conclude that individual seizures produce (a) stereotypical changes in autonomic activity and HR, (b) persistence of sympathetic tone helps to protect against death, and (c) bradycardic seizures may indicate increased risk for seizure-associated obstructive apnea. [ABSTRACT FROM AUTHOR]

Abstract: Panayiotopoulos syndrome (PS) is a common childhood susceptibility to autonomic seizures and status epilepticus. Despite its high prevalence, PS has been a source of significant debate. We present ictal EEG documentation of autonomic seizures and autonomic status epilepticus in six cases of PS and a review of 14 reported cases. Interictal EEGs showed spikes of variable locations that often changed with time. Ictal EEG onsets were also variable, starting from wide anterior or posterior regions usually with theta waves intermixed with small spikes and fast rhythms. Ictal vomiting and other autonomic manifestations, as well as deviation of the eyes, did not appear to relate to any specific region of EEG activation. These data document that PS is a multifocal autonomic epilepsy and support the view that the clinical manifestations are likely to be generated by variable and widely spread epileptogenic foci acting on a temporarily hyperexcitable central autonomic network. [ABSTRACT FROM AUTHOR]

Information contained in the R-R interval series, specific to the pre-ictal period, was sought by applying an unsupervised fuzzy clustering algorithm to the N-dimensional phase space of N consecutive interval durations or the absolute value of duration differences. Data sources were individual, complex partial seizures of temporal-lobe epileptics and generalised seizures of rats rendered epileptic with hyperbaric oxygen. Forecasting success was 86% and 82% (zero false positives in resistant rats), respectively, at times ranging from 10 min to 30 s prior to seizure onset Although certain forecasting clusters predominated in the patient group and different ones predominated in the animal group, forecasting on the whole was seizure-specific. The high prediction sensitivity of this method, which matches that of EEG-based methods, seems promising. It is believed that an on-line version of the algorithm, trained on each patient's peri-ictal ECG, could serve as a basis for a simple seizure alarm system. [ABSTRACT FROM AUTHOR]

• 26.7 % patients showed ≥1 McHugh class improvement after replacement with cardiac-based VNS device. • 50 % patients maintained their McHugh class at last follow up. • 36.7 % Patients showed >50 % seizure reduction after replacement. • 4 patients showed deterioration in behaviour after replacement. This study evaluated the seizure outcomes in children with drug-resistant epilepsy (DRE), having a pre-existing VNS device, after generator replacement with cardiac-based VNS device. This retrospective study enrolled 30 children with DRE from 2 centers with an existing VNS device nearing end-of-service who underwent generator replacement with cardiac-based VNS device and had at least 1 year follow up. Seizure outcomes and adverse effects were studied. The mean age at insertion of cardiac-based VNS device was 15.03 years. 26.7 % patients showed at least one class improvement at last follow up (mean 2.08 years) and half of the patients maintained their McHugh seizure-outcome class. Thirty-six percent of patients had > 50 % seizure reduction at last follow up. Ten patients reported improvement in ictal severity. Most of the patients tolerated the replacement well. Nearly one-third of patients with DRE showed additional improvement after replacement with cardiac based VNS device. Half of the patients maintained their seizure control. [ABSTRACT FROM AUTHOR]

Objectives: The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and long- term clinical outcomes of the device stimulating in all modes., Materials and Methods: The E-37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR(®) in subjects with drug-resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events., Results: Twenty implanted subjects (ages 21-69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3)., Conclusions: The Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements., (© 2015 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.)