Artificial intelligence-enhanced epileptic seizure detection by wearables.

OBJECTIVE: Wrist- or ankle-worn devices are less intrusive than the widely used electroencephalographic (EEG) systems for monitoring epileptic seizures. Using custom-developed deep-learning seizure detection models, we demonstrate the detection of a broad range of seizure types by wearable signals. METHODS: Patients admitted to the epilepsy monitoring unit were enrolled and asked to wear wearable sensors on either wrists or ankles. We collected patients' electrodermal activity, accelerometry (ACC), and photoplethysmography, from which blood volume pulse (BVP) is derived. Board-certified epileptologists determined seizure onset, offset, and types using video and EEG recordings per the International League Against Epilepsy 2017 classification. We applied three neural network models-a convolutional neural network (CNN) and a CNN-long short-term memory (LSTM)-based generalized detection model and an autoencoder-based personalized detection model-to the raw time-series sensor data to detect seizures and utilized performance measures, including sensitivity, false positive rate (the number of false alarms divided by the total number of nonseizure segments), number of false alarms per day, and detection delay. We applied a 10-fold patientwise cross-validation scheme to the multisignal biosensor data and evaluated model performance on 28 seizure types. RESULTS: We analyzed 166 patients (47.6% female, median age = 10.0 years) and 900 seizures (13 254 h of sensor data) for 28 seizure types. With a CNN-LSTM-based seizure detection model, ACC, BVP, and their fusion performed better than chance; ACC and BVP data fusion reached the best detection performance of 83.9% sensitivity and 35.3% false positive rate. Nineteen of 28 seizure types could be detected by at least one data modality with area under receiver operating characteristic curve > .8 performance. SIGNIFICANCE: Results from this in-hospital study contribute to a paradigm shift in epilepsy care that entails noninvasive seizure detection, provides time-sensitive and accurate data on additional clinical seizure types, and proposes a novel combination of an out-of-the-box monitoring algorithm with an individualized person-oriented seizure detection approach.

Development of a Multivariable Seizure Likelihood Assessment Based on Clinical Information and Short Autonomic Activity Recordings for Children With Epilepsy.

BACKGROUND: Predicting seizure likelihood for the following day would enable clinicians to extend or potentially schedule video-electroencephalography (EEG) monitoring when seizure risk is high. Combining standardized clinical data with short-term recordings of wearables to predict seizure likelihood could have high practical relevance as wearable data is easy and fast to collect. As a first step toward seizure forecasting, we classified patients based on whether they had seizures or not during the following recording. METHODS: Pediatric patients admitted to the epilepsy monitoring unit wore a wearable that recorded the heart rate (HR), heart rate variability (HRV), electrodermal activity (EDA), and peripheral body temperature. We utilized short recordings from 9:00 to 9:15 pm and compared mean values between patients with and without impending seizures. In addition, we collected clinical data: age, sex, age at first seizure, generalized slowing, focal slowing, and spikes on EEG, magnetic resonance imaging findings, and antiseizure medication reduction. We used conventional machine learning techniques with cross-validation to classify patients with and without impending seizures. RESULTS: We included 139 patients: 78 had no seizures and 61 had at least one seizure after 9 pm during the concurrent video-EEG and E4 recordings. HR (P < 0.01) and EDA (P < 0.01) were lower and HRV (P = 0.02) was higher for patients with than for patients without impending seizures. The average accuracy of group classification was 66%, and the mean area under the receiver operating characteristics was 0.72. CONCLUSIONS: Short-term wearable recordings in combination with clinical data have great potential as an easy-to-use seizure likelihood assessment tool.

Explainable AI for wearable seizure logging: Impact of data quality, patient age, and antiseizure medication on performance.

OBJECTIVE: Objective seizure count estimates are crucial for ambulatory epilepsy management. Wearables have shown promise for the detection of tonic-clonic seizures but may suffer from false alarms and undetected seizures. Seizure signatures recorded by wearables often occur over prolonged periods, including increased levels of electrodermal activity and heart rate long after seizure EEG onset, however, previous detection methods only partially exploited these signatures. Understanding the utility of these prolonged signatures for seizure count estimation and what factors generally determine seizure logging performance, including the role of data quality vs. algorithm performance, is thus crucial for improving wearables-based epilepsy monitoring and determining which patients benefit most from this technology. METHODS: In this retrospective study we examined 76 pediatric epilepsy patients during multiday video-EEG monitoring equipped with a wearable (Empatica E4; records of electrodermal activity, EDA, accelerometry, ACC, heart rate, HR; 1983 h total recording time; 45 tonic-clonic seizures). To log seizures on prolonged data trends, we applied deep learning on continuous overlapping 1-hour segments of multimodal data in a leave-one-subject-out approach. We systematically examined factors influencing logging performance, including patient age, antiseizure medication (ASM) load, seizure type and duration, and data artifacts. To gain insights into algorithm function and feature importance we applied Uniform Manifold Approximation and Projection (UMAP, to represent the separability of learned features) and SHapley Additive exPlanations (SHAP, to represent the most informative data signatures). RESULTS: Performance for tonic-clonic seizure logging increased systematically with patient age (AUC 0.61 for patients 〈 11 years, AUC 0.77 for patients between 11-15 years, AUC 0.85 for patients 〉 15 years). Across all ages, AUC was 0.75 corresponding to a sensitivity of 0.52 and a false alarm rate of 0.28/24 h. Seizures under high ASM load or with shorter duration were detected worse (P=.025, P=.033, respectively). UMAP visualized discriminatory power at the individual patient level, SHAP analyses identified clonic motor activity and peri/postictal increases in HR and EDA as most informative. In contrast, in missed seizures, these features were absent indicating that recording quality but not the algorithm caused the low sensitivity in these patients. SIGNIFICANCE: Our results demonstrate the utility of prolonged, postictal data segments for seizure logging, contribute to algorithm explainability and point to influencing factors, including high ASM dose and short seizure duration. Collectively, these results may help to identify patients who particularly benefit from such technology.

Seizure-related differences in biosignal 24-h modulation patterns.

A seizure likelihood biomarker could improve seizure monitoring and facilitate adjustment of treatments based on seizure risk. Here, we tested differences in patient-specific 24-h-modulation patterns of electrodermal activity (EDA), peripheral body temperature (TEMP), and heart rate (HR) between patients with and without seizures. We enrolled patients who underwent continuous video-EEG monitoring at Boston Children's Hospital to wear a biosensor. We divided patients into two groups: those with no seizures and those with at least one seizure during the recording period. We assessed the 24-h modulation level and amplitude of EDA, TEMP, and HR. We performed machine learning including physiological and clinical variables. Subsequently, we determined classifier performance by cross-validated machine learning. Patients with seizures (n = 49) had lower EDA levels (p = 0.031), EDA amplitudes (p = 0.045), and trended toward lower HR levels (p = 0.060) compared to patients without seizures (n = 68). Averaged cross-validated classification accuracy was 69% (AUC-ROC: 0.75). Our results show the potential to monitor and forecast risk for epileptic seizures based on changes in 24-h patterns in wearable recordings in combination with clinical variables. Such biomarkers might be applicable to inform care, such as treatment or seizure injury risk during specific periods, scheduling diagnostic tests, such as admission to the epilepsy monitoring unit, and potentially other neurological and chronic conditions.

Measuring Real-Time Medication Effects From Electroencephalography.

PURPOSE: Evaluating the effects of antiseizure medication (ASM) on patients with epilepsy remains a slow and challenging process. Quantifiable noninvasive markers that are measurable in real-time and provide objective and useful information could guide clinical decision-making. We examined whether the effect of ASM on patients with epilepsy can be quantitatively measured in real-time from EEGs. METHODS: This retrospective analysis was conducted on 67 patients in the long-term monitoring unit at Boston Children's Hospital. Two 30-second EEG segments were selected from each patient premedication and postmedication weaning for analysis. Nonlinear measures including entropy and recurrence quantitative analysis values were computed for each segment and compared before and after medication weaning. RESULTS: Our study found that ASM effects on the brain were measurable by nonlinear recurrence quantitative analysis on EEGs. Highly significant differences (P < 1e-11) were found in several nonlinear measures within the seizure zone in response to antiseizure medication. Moreover, the size of the medication effect correlated with a patient's seizure frequency, seizure localization, number of medications, and reported seizure frequency reduction on medication. CONCLUSIONS: Our findings show the promise of digital biomarkers to measure medication effects and epileptogenicity.

Identifying Barriers to Care in the Pediatric Acute Seizure Care Pathway.

Objective: We aimed to describe the acute seizure care pathway for pediatric patients and identify barriers encountered by those involved in seizure care management. We also proposed interventions to bridge these care gaps within this pathway. Methods: We constructed a process map that illustrates the acute seizure care pathway for pediatric patients at Boston Children's Hospital (BCH). The map was designed from knowledge gathered from unstructured interviews with experts at BCH, direct observation of patient care management at BCH through a quality improvement implemented seizure diary and from findings through three studies conducted at BCH, including a prospective observational study by the pediatric Status Epilepticus Research Group, a multi-site international consortium. We also reviewed the literature highlighting gaps and strategies in seizure care management. Results: Within the process map, we identified twenty-nine care gaps encountered by caregivers, care teams, residential and educational institutions, and proposed interventions to address these challenges. The process map outlines clinical care of a patient through the following settings: 1) pre-hospitalization setting, defined as residential and educational settings before hospital admission, 2) BCH emergency department and inpatient settings, 3) post-hospitalization setting, defined as residential and educational settings following hospital discharge or clinic visit and 4) follow-up BCH outpatient settings, including neurology, epilepsy, and primary care provider clinics. The acute seizure care pathway for a pediatric patient who presents with seizures exhibits at least twenty-nine challenges in acute seizure care management. Significance: Identification of care barriers in the acute seizure care pathway provides a necessary first step for implementing interventions and strategies in acute seizure care management that could potentially impact patient outcomes.

Wearable device assessments of antiseizure medication effects on diurnal patterns of electrodermal activity, heart rate, and heart rate variability.

Patient-generated health data provide a great opportunity for more detailed ambulatory monitoring and more personalized treatments in many diseases. In epilepsy, robust diagnostics applicable to the ambulatory setting are needed as diagnosis and treatment decisions in current clinical practice are primarily reliant on patient self-reports, which are often inaccurate. Recent work using wearable devices has focused on methods to detect and forecast epileptic seizures. Whether wearable device signals may also contain information about the effect of antiseizure medications (ASMs), which may ultimately help to better monitor their efficacy, has not been evaluated yet. Here we systematically investigated the effect of ASMs on different data modalities (electrodermal activity, EDA, heart rate, HR, and heart rate variability, HRV) simultaneously recorded by a wearable device in 48 patients with epilepsy over several days in the epilepsy long-term monitoring unit at a tertiary hospital. All signals exhibited characteristic diurnal variations. HRV, but not HR or EDA-based metrics, were reduced by ASMs. By assessing multiple signals related to the autonomic nervous system simultaneously, our results provide novel insights into the effects of ASMs on the sympathetic and parasympathetic interplay in the setting of epilepsy and indicate the potential of easy-to-wear wearable devices for monitoring ASM action. Future work using longer data may investigate these metrics on multidien cycles and their utility for detecting seizures, assessing seizure risk, or informing treatment interventions.

Association between semiologic, autonomic, and electrographic seizure characteristics in children with generalized tonic-clonic seizures.

INTRODUCTION: Generalized tonic-clonic seizures (GTCS) are associated with elevated electrodermal activity (EDA) and postictal generalized electroencephalographic suppression (PGES), markers that may indicate sudden unexpected death in epilepsy (SUDEP) risk. This study investigated the association of GTCS semiology, EDA, and PGES in children with epilepsy. METHODS: Patients admitted to the Boston Children's Hospital long-term video-EEG monitoring unit wore a sensor that records EDA. We selected patients with at least one GTCS and reviewed video-EEGs for semiology, tonic and clonic phase duration, total clinical seizure duration, electrographic onset, offset, and PGES. We grouped patients into three semiology classes: GTCS 1: bilateral symmetric tonic arm extension, GTCS 2: no specific tonic arm extension or flexion, GTCS 3: unilateral or asymmetrical arm extension, tonic arm flexion or posturing that does not fit into GTCS 1 or 2. We analyzed the correlation between semiology, EDA, and PGES, and measured the area under the curve (AUC) of the ictal EDA (seizure onset to one hour after), subtracting baseline EDA (one-hour seizure-free before seizure onset). Using generalized estimating equation (GEE) and linear regression, we analyzed all seizures and single episodes per patient. RESULTS: We included 30 patients (median age 13.8 ±â€¯3.6 years, 46.7% females) and 53 seizures. With GEE, GTCS 1 was associated with longer PGES duration compared to GTCS 2 (Estimate (ß) = -26.32 s, 95% Confidence Interval (CI): -36.46 to -16.18, p < 0.001), and the presence of PGES was associated with greater EDA change (ß = 429604 µS, 95% CI: 3550.96 to 855657.04, p = 0.048). With single-episode analysis, GTCS 1 had greater EDA change than GTCS 2 ((ß = -601339 µS, 95% CI: -1167016.56 to -35661.44, p = 0.047). EDA increased with PGES presence (ß = 637500 µS, 95% CI: 183571.84 to 1091428.16, p = 0.01) and duration (ß = 16794 µS, 95% CI: 5729.8 to 27858.2, p = 0.006). Patients with GTCS 1 had longer PGES duration compared to GTCS 2 (ß = -30.53 s, 95% CI: -44.6 to -16.46, p < 0.001) and GTCS 3 (ß = -22.07 s, 95% CI: -38.95 to -5.19, p = 0.016). CONCLUSION: In children with epilepsy, PGES correlates with greater ictal EDA. GTCS 1 correlated with longer PGES duration and may indirectly correlate with greater ictal EDA. Our study suggests potential applications in monitoring and preventing SUDEP in these patients.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

Seizure detection using wearable sensors and machine learning: Setting a benchmark.

OBJECTIVE: Tracking seizures is crucial for epilepsy monitoring and treatment evaluation. Current epilepsy care relies on caretaker seizure diaries, but clinical seizure monitoring may miss seizures. Wearable devices may be better tolerated and more suitable for long-term ambulatory monitoring. This study evaluates the seizure detection performance of custom-developed machine learning (ML) algorithms across a broad spectrum of epileptic seizures utilizing wrist- and ankle-worn multisignal biosensors. METHODS: We enrolled patients admitted to the epilepsy monitoring unit and asked them to wear a wearable sensor on either their wrists or ankles. The sensor recorded body temperature, electrodermal activity, accelerometry (ACC), and photoplethysmography, which provides blood volume pulse (BVP). We used electroencephalographic seizure onset and offset as determined by a board-certified epileptologist as a standard comparison. We trained and validated ML for two different algorithms: Algorithm 1, ML methods for developing seizure type-specific detection models for nine individual seizure types; and Algorithm 2, ML methods for building general seizure type-agnostic detection, lumping together all seizure types. RESULTS: We included 94 patients (57.4% female, median age = 9.9 years) and 548 epileptic seizures (11 066 h of sensor data) for a total of 930 seizures and nine seizure types. Algorithm 1 detected eight of nine seizure types better than chance (area under the receiver operating characteristic curve [AUC-ROC] = .648-.976). Algorithm 2 detected all nine seizure types better than chance (AUC-ROC = .642-.995); a fusion of ACC and BVP modalities achieved the best AUC-ROC (.752) when combining all seizure types together. SIGNIFICANCE: Automatic seizure detection using ML from multimodal wearable sensor data is feasible across a broad spectrum of epileptic seizures. Preliminary results show better than chance seizure detection. The next steps include validation of our results in larger datasets, evaluation of the detection utility tool for additional clinical seizure types, and integration of additional clinical information.

Measuring the effects of sleep on epileptogenicity with multifrequency entropy.

OBJECTIVE: We demonstrate that multifrequency entropy gives insight into the relationship between epileptogenicity and sleep, and forms the basis for an improved measure of medical assessment of sleep impairment in epilepsy patients. METHODS: Multifrequency entropy was computed from electroencephalography measurements taken from 31 children with Benign Epilepsy with Centrotemporal Spikes and 31 non-epileptic controls while awake and during sleep. Values were compared in the epileptic zone and away from the epileptic zone in various sleep stages. RESULTS: We find that (I) in lower frequencies, multifrequency entropy decreases during non-rapid eye movement sleep stages when compared with wakefulness in a general population of pediatric patients, (II) patients with Benign Epilepsy with Centrotemporal Spikes had lower multifrequency entropy across stages of sleep and wakefulness, and (III) the epileptic regions of the brain exhibit lower multifrequency entropy patterns than the rest of the brain in epilepsy patients. CONCLUSIONS: Our results show that multifrequency entropy decreases during sleep, particularly sleep stage 2, confirming, in a pediatric population, an association between sleep, lower multifrequency entropy, and increased likelihood of seizure. SIGNIFICANCE: We observed a correlation between lowered multifrequency entropy and increased epileptogenicity that lays preliminary groundwork for the detection of a digital biomarker for epileptogenicity.

Evaluation and recommendations for effective data visualization for seizure forecasting algorithms.

OBJECTIVE: Seizure forecasting algorithms have become increasingly accurate and may reduce the morbidity and mortality caused by seizure unpredictability. Translating these benefits into meaningful health outcomes for people with epilepsy requires effective data visualization of algorithm outputs. To date, no studies have investigated patient and physician perspectives on effective translation of algorithm outputs into data visualizations through health information technology. MATERIALS AND METHODS: We developed front-end data visualizations as part of a Seizure Forecast Visualization Toolkit. We surveyed 627 people living with epilepsy and caregivers, and 28 epilepsy healthcare providers. Respondents scored each visualization in terms of international standardized software quality criteria for functionality, appropriateness, and usability. RESULTS: People with epilepsy and caregivers ranked hourly radar charts highest for protecting against errors in interpreting forecasts, reducing anxiety from seizure unpredictability, and understanding seizure patterns. Accuracy in interpreting visuals, such as a risk gauge, was dependent on seizure frequency. Visuals showing hourly/daily forecasts were more useful for patients who experienced seizure cycling than those who did not. Hourly line graphs and monthly heat maps were rated highest among clinicians for ease of understanding, anticipated integration into clinical practice, and the likelihood of clinical usage. Epilepsy providers indicated that daily heat maps, daily line graphs, and hourly line graphs were most useful for interpreting seizure diary patterns, assessing therapy impact, and counseling on seizure safety. DISCUSSION: The choice of data visualization impacts the effective translation of seizure forecast algorithms into meaningful health outcomes. CONCLUSION: This effort underlines the importance of incorporating standardized, quantitative methods for assessing the effectiveness of data visualization to translate seizure forecast algorithms into clinical practice.

Twenty-four-hour patterns in electrodermal activity recordings of patients with and without epileptic seizures.

OBJECTIVE: Daytime and nighttime patterns affect the dynamic modulation of brain and body functions and influence the autonomic nervous system response to seizures. Therefore, we aimed to evaluate 24-hour patterns of electrodermal activity (EDA) in patients with and without seizures. METHODS: We included pediatric patients with (a) seizures (SZ), including focal impaired awareness seizures (FIAS) or generalized tonic-clonic seizures (GTCS), (b) no seizures and normal electroencephalography (NEEG), or (c) no seizures but epileptiform activity in the EEG (EA) during vEEG monitoring. Patients wore a device that continuously recorded EDA and temperature (TEMP). EDA levels, EDA spectral power, and TEMP levels were analyzed. To investigate 24-hour patterns, we performed a nonlinear mixed-effects model analysis. Relative mean pre-ictal (-30 min to seizure onset) and post-ictal (I: 30 min after seizure offset; II: 30 to 60 min after seizure offset) values were compared for SZ subgroups. RESULTS: We included 119 patients (40 SZ, 17 NEEG, 62 EA). EDA level and power group-specific models (SZ, NEEG, EA) (h = 1; P < .01) were superior to the all-patient cohort model. Fifty-nine seizures were analyzed. Pre-ictal EDA values were lower than respective 24-hour modulated SZ group values. Post hoc comparisons following the period-by-seizure type interaction (EDA level: χ2  = 18.50; P < .001, and power: χ2  = 6.73; P = .035) revealed that EDA levels were higher in the post-ictal period I for FIAS and GTCS and in post-ictal period II for GTCS only compared to the pre-ictal period. SIGNIFICANCE: Continuously monitored EDA shows a pattern of change over 24 hours. Curve amplitudes in patients with recorded seizures were lower as compared to patients who did not exhibit seizures during the recording period. Sympathetic skin responses were greater and more prolonged in GTCS compared to FIAS. EDA recordings from wearable devices offer a noninvasive tool to continuously monitor sympathetic activity with potential applications for seizure detection, prediction, and potentially sudden unexpected death in epilepsy (SUDEP) risk estimation.

Machine learning from wristband sensor data for wearable, noninvasive seizure forecasting.

OBJECTIVE: Seizure forecasting may provide patients with timely warnings to adapt their daily activities and help clinicians deliver more objective, personalized treatments. Although recent work has convincingly demonstrated that seizure risk assessment is in principle possible, these early approaches relied largely on complex, often invasive setups including intracranial electrocorticography, implanted devices, and multichannel electroencephalography, and required patient-specific adaptation or learning to perform optimally, all of which limit translation to broad clinical application. To facilitate broader adaptation of seizure forecasting in clinical practice, noninvasive, easily applicable techniques that reliably assess seizure risk without much prior tuning are crucial. Wristbands that continuously record physiological parameters, including electrodermal activity, body temperature, blood volume pulse, and actigraphy, may afford monitoring of autonomous nervous system function and movement relevant for such a task, hence minimizing potential complications associated with invasive monitoring and avoiding stigma associated with bulky external monitoring devices on the head. METHODS: Here, we applied deep learning on multimodal wristband sensor data from 69 patients with epilepsy (total duration > 2311 hours, 452 seizures) to assess its capability to forecast seizures in a statistically significant way. RESULTS: Using a leave-one-subject-out cross-validation approach, we identified better-than-chance predictability in 43% of the patients. Time-matched seizure surrogate data analyses indicated forecasting not to be driven simply by time of day or vigilance state. Prediction performance peaked when all sensor modalities were used, and did not differ between generalized and focal seizure types, but generally increased with the size of the training dataset, indicating potential further improvement with larger datasets in the future. SIGNIFICANCE: Collectively, these results show that statistically significant seizure risk assessments are feasible from easy-to-use, noninvasive wearable devices without the need of patient-specific training or parameter optimization.

Photoplethysmography: A measure for the function of the autonomic nervous system in focal impaired awareness seizures.

OBJECTIVES: Photoplethysmography (PPG) reflects variations of blood perfusion in tissues, which may signify seizure-related autonomic changes. The aim of this study is to assess the variability of PPG signals and their value in detecting peri-ictal changes in patients with focal impaired awareness seizures (FIASs). METHODS: PPG data were recorded using a wearable sensor placed on the wrist or ankle of children with epilepsy admitted for long-term video-electroencephalographic monitoring. We analyzed PPG data in four different periods: seizure-free, preictal, ictal, and postictal. Multiple features were automatically extracted from the PPG signal-frequency, duration, amplitude, increasing and decreasing slopes, smoothness, and area under the curve (AUC)-and were used to identify preictal, ictal, or postictal changes by comparing them with seizure-free periods and with each other using a linear mixed-effects model. RESULTS: We studied PPG in 11 patients (18 FIASs), including seizure-free, preictal, and postictal periods, and a subset of eight patients (12 FIASs) including the ictal period. Compared to the seizure-free period, we found significant changes in PPG (1) during the ictal period across all features; (2) during the preictal period in amplitude, duration, increasing slope, and AUC; and (3) during the postictal period in decreasing slope. SIGNIFICANCE: Specific PPG changes can be seen before, during, and after FIASs. The peri-ictal changes in the PPG features of patients with FIASs suggest potential applications of PPG monitoring for seizure detection.

Autonomic nervous system changes detected with peripheral sensors in the setting of epileptic seizures.

A better understanding of the early detection of seizures is highly desirable as identification of an impending seizure may afford improved treatments, such as antiepileptic drug chronotherapy, or timely warning to patients. While epileptic seizures are known to often manifest also with autonomic nervous system (ANS) changes, it is not clear whether ANS markers, if recorded from a wearable device, are also informative about an impending seizure with statistically significant sensitivity and specificity. Using statistical testing with seizure surrogate data and a unique dataset of continuously recorded multi-day wristband data including electrodermal activity (EDA), temperature (TEMP) and heart rate (HR) from 66 people with epilepsy (9.9 ± 5.8 years; 27 females; 161 seizures) we investigated differences between inter- and preictal periods in terms of mean, variance, and entropy of these signals. We found that signal mean and variance do not differentiate between inter- and preictal periods in a statistically meaningful way. EDA signal entropy was found to be increased prior to seizures in a small subset of patients. Findings may provide novel insights into the pathophysiology of epileptic seizures with respect to ANS function, and, while further validation and investigation of potential causes of the observed changes are needed, indicate that epilepsy-related state changes may be detectable using peripheral wearable devices. Detection of such changes with wearable devices may be more feasible for everyday monitoring than utilizing an electroencephalogram.

Photoplethysmographic evaluation of generalized tonic-clonic seizures.

OBJECTIVE: Photoplethysmography (PPG) is an optical technique measuring variations of blood perfusion in peripheral tissues. We evaluated alterations in PPG signals in relationship to the occurrence of generalized tonic-clonic seizures (GTCSs) in patients with epilepsy to evaluate the feasibility of seizure detection. METHODS: During electroencephalographic (EEG) long-term monitoring, patients wore portable wristband sensor(s) on their wrists or ankles recording PPG signals. We analyzed PPG signals during three time periods, which were defined with respect to seizures detected on EEG: (1) baseline (>30 minutes prior to seizure), (2) preseizure period, and (3) postseizure period. Furthermore, we selected five random control segments during seizure-free periods. PPG features, including frequency, amplitude, duration, slope, smoothness, and area under the curve, were automatically calculated. We used a linear mixed-effect model to evaluate changes in PPG features between different time periods in an attempt to identify signal changes that detect seizures. RESULTS: We prospectively enrolled 174 patients from the epilepsy monitoring unit at Boston Children's Hospital. Twenty-five GTCSs were recorded from 13 patients. Data from the first recorded GTCS of each patient were included in the analysis. We observed an increase in PPG frequency during pre- and postseizure periods that was higher than the changes during seizure-free periods (frequency increase: preseizure = 0.22 Hz, postseizure = 0.58 Hz vs changes during seizure-free period = 0.05 Hz). The PPG slope decreased significantly by 56.71 nW/s during preseizure periods compared to seizure-free periods. Additionally, the smoothness increased significantly by 0.22 nW/s during the postseizure period compared to seizure-free periods. SIGNIFICANCE: Monitoring of PPG signals may assist in the detection of GTCSs in patients with epilepsy. PPG may serve as a promising biomarker for future seizure detection systems and may contribute to future seizure prediction systems.

Nonlinear Analysis of Visually Normal EEGs to Differentiate Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS).

Childhood epilepsy with centrotemporal spikes, previously known as Benign Epilepsy with Centro-temporal Spikes (BECTS) or Rolandic Epilepsy, is one of the most common forms of focal childhood epilepsy. Despite its prevalence, BECTS is often misdiagnosed or missed entirely. This is in part due to the nocturnal and brief nature of the seizures, making it difficult to identify during a routine electroencephalogram (EEG). Detecting brain activity that is highly associated with BECTS on a brief, awake EEG has the potential to improve diagnostic screening for BECTS and predict clinical outcomes. For this study, 31 patients with BECTS were retrospectively selected from the BCH Epilepsy Center database along with a contrast group of 31 patients in the database who had no form of epilepsy and a normal EEG based on a clinical chart review. Nonlinear features, including multiscale entropy and recurrence quantitative analysis, were computed from 30-second segments of awake EEG signals. Differences were found between these multiscale nonlinear measures in the two groups at all sensor locations, while visual EEG inspection by a board-certified child neurologist did not reveal any distinguishing features. Moreover, a quantitative difference in the nonlinear measures (sample entropy, trapping time and the Lyapunov exponents) was found in the centrotemporal region of the brain, the area associated with a greater tendency to have unprovoked seizures, versus the rest of the brain in the BECTS patients. This difference was not present in the contrast group. As a result, the epileptic zone in the BECTS patients appears to exhibit lower complexity, and these nonlinear measures may potentially serve as a clinical screening tool for BECTS, if replicated in a larger study population.

The onset of pediatric refractory status epilepticus is not distributed uniformly during the day.

PURPOSE: To evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. METHOD: We analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. RESULTS: We analyzed 368 patients (58% males) with a median (p25 - p75) age of 4.2 (1.3-9.7) years. The MESOR was 15.3 (95% CI: 13.9-16.8) and the amplitude was 3.2 (95% CI: 1.1-5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am-12 pm) and trough at night (11 pm-12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am-3 am) with a minimum during the afternoon (2 pm-3 pm) (p = 0.0179). CONCLUSIONS: The distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am-12 pm) and a trough at night (11 pm-12am).

Electroencephalographic Reporting for Refractory Status Epilepticus.

PURPOSE: We aimed to determine whether clinical EEG reports obtained from children in the intensive care unit with refractory status epilepticus could provide data for comparative effectiveness research studies. METHODS: We conducted a retrospective descriptive study to assess the documentation of key variables within clinical continuous EEG monitoring reports based on the American Clinical Neurophysiology Society's standardized EEG terminology for children with refractory status epilepticus from 10 academic centers. Two pediatric electroencephalographers reviewed the EEG reports. We compared reports generated using free text or templates. RESULTS: We reviewed 191 EEG reports. Agreement between the electroencephalographers regarding whether a variable was described in the report ranged from fair to very good. The presence of electrographic seizures (ES) was documented in 46% (87/191) of reports, and these reports documented the time of first ES in 64% (56/87), ES duration in 72% (63/85), and ES frequency in 68% (59/87). Reactivity was documented in 16% (31/191) of reports, and it was more often documented in template than in free-text reports (40% vs. 14%, P = 0.006). Other variables were not differentially reported in template versus free-text reports. CONCLUSIONS: Many key EEG features are not documented consistently in clinical continuous EEG monitoring reports, including ES characteristics and reactivity assessment. Standardization may be needed for clinical EEG reports to provide informative data for large multicenter observational studies.