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ObjectiveThis study was undertaken to develop a machine learning (ML) model to forecast initial seizure onset in neonatal hypoxic-ischemic encephalopathy (HIE) utilizing clinical and quantitative electroencephalogram (QEEG) features.MethodsWe developed a gradient boosting ML model (Neo-GB) that utilizes clinical features and QEEG to forecast time-dependent seizure risk. Clinical variables included cord blood gas values, Apgar scores, gestational age at birth, postmenstrual age (PMA), postnatal age, and birth weight. QEEG features included statistical moments, spectral power, and recurrence quantification analysis (RQA) features. We trained and evaluated Neo-GB on a University of California, San Francisco (UCSF) neonatal HIE dataset, augmenting training with publicly available neonatal electroencephalogram (EEG) datasets from Cork University and Helsinki University Hospitals. We assessed the performance of Neo-GB at providing dynamic and static forecasts with diagnostic performance metrics and incident/dynamic area under the receiver operating characteristic curve (iAUC) analyses. Model explanations were performed to assess contributions of QEEG features and channels to model predictions.ResultsThe UCSF dataset included 60 neonates with HIE (30 with seizures). In subject-level static forecasting at 30 min after EEG initiation, baseline Neo-GB without time-dependent features had an area under the receiver operating characteristic curve (AUROC) of .76 and Neo-GB with time-dependent features had an AUROC of .89. In time-dependent evaluation of the initial seizure onset within a 24-h seizure occurrence period, dynamic forecast with Neo-GB demonstrated median iAUC = .79 (interquartile range [IQR] .75-.82) and concordance index (C-index) = .82, whereas baseline static forecast at 30 min demonstrated median iAUC = .75 (IQR .72-.76) and C-index = .69. Model explanation analysis revealed that spectral power, PMA, RQA, and cord blood gas values made the strongest contributions in driving Neo-GB predictions. Within the most influential EEG channels, as the preictal period advanced toward eventual seizure, there was an upward trend in broadband spectral power.SignificanceThis study demonstrates an ML model that combines QEEG with clinical features to forecast time-dependent risk of initial seizure onset in neonatal HIE. Spectral power evolution is an early EEG marker of seizure risk in neonatal HIE.

• A simple method allowing intra- & inter-subject seizure prediction days in advance. • Multi-day prediction demonstrated for human/canine, intracranial/subcutaneous EEG. • Cross-patient forecasting benefits patients without waiting for model training. The apparent randomness of seizure occurrence affects greatly the quality of life of persons with epilepsy. Since seizures are often phase-locked to multidien cycles of interictal epileptiform activity, a recent forecasting scheme, exploiting RNS data, is capable of forecasting seizures days in advance. We tested the use of a bandpass filter to capture the universal mid-term dynamics enabling both patient-specific and cross-patient forecasting. In a retrospective study, we explored the feasibility of the scheme on three long-term recordings obtained by the NeuroPace RNS System, the NeuroVista intracranial, and the UNEEG subcutaneous devices, respectively. Better-than-chance forecasting was observed in 15 (83 %) of 18 patients, and in 16 (89 %) patients for daily and hourly forecast, respectively. Meaningful forecast up to 30 days could be achieved in 4 (22 %) patients for hourly forecast frequency. The cross-patient performance decreased only marginally and was patient-wise strongly correlated with the patient-specific one. Comparable performance was obtained for NeuroVista and UNEEG data sets. The feasibility of cross-patient forecasting supports the universal importance of mid-term dynamics for seizure forecasting, demonstrates promising inter-subject-applicability of the scheme on ultra long-term EEG recordings, and highlights its huge potential for clinical use. [ABSTRACT FROM AUTHOR]

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Objective: The aim of this study was to develop a machine learning algorithm using an off‐the‐shelf digital watch, the Samsung watch (SM‐R800), and evaluate its effectiveness for the detection of generalized convulsive seizures (GCS) in persons with epilepsy. Methods: This multisite epilepsy monitoring unit (EMU) phase 2 study included 36 adult patients. Each patient wore a Samsung watch that contained accelerometer, gyroscope, and photoplethysmographic sensors. Sixty‐eight time and frequency domain features were extracted from the sensor data and were used to train a random forest algorithm. A testing framework was developed that would better reflect the EMU setting, consisting of (1) leave‐one‐patient‐out cross‐validation (LOPO CV) on GCS patients, (2) false alarm rate (FAR) testing on nonseizure patients, and (3) "fixed‐and‐frozen" prospective testing on a prospective patient cohort. Balanced accuracy, precision, sensitivity, and FAR were used to quantify the performance of the algorithm. Seizure onsets and offsets were determined by using video‐electroencephalographic (EEG) monitoring. Feature importance was calculated as the mean decrease in Gini impurity during the LOPO CV testing. Results: LOPO CV results showed balanced accuracy of.93 (95% confidence interval [CI] =.8–.98), precision of.68 (95% CI =.46–.85), sensitivity of.87 (95% CI =.62–.96), and FAR of.21/24 h (interquartile range [IQR] = 0–.90). Testing the algorithm on patients without seizure resulted in an FAR of.28/24 h (IQR = 0–.61). During the "fixed‐and‐frozen" prospective testing, two patients had three GCS, which were detected by the algorithm, while generating an FAR of.25/24 h (IQR = 0–.89). Feature importance showed that heart rate‐based features outperformed accelerometer/gyroscope‐based features. Significance: Commercially available wearable digital watches that reliably detect GCS, with minimum false alarm rates, may overcome usage adoption and other limitations of custom‐built devices. Contingent on the outcomes of a prospective phase 3 study, such devices have the potential to provide non‐EEG‐based seizure surveillance and forecasting in the clinical setting. [ABSTRACT FROM AUTHOR]

Wearable devices have attracted significant attention in epilepsy research in recent years for their potential to enhance patient care through improved seizure monitoring and forecasting. This narrative review presents a detailed overview of the current clinical state of the art while addressing how devices that assess autonomic nervous system (ANS) function reflect seizures and central nervous system (CNS) state changes. This includes a description of the interactions between the CNS and the ANS, including physiological and epilepsy‐related changes affecting their dynamics. We first discuss technical aspects of measuring autonomic biosignals and considerations for using ANS sensors in clinical practice. We then review recent seizure detection and seizure forecasting studies, highlighting their performance and capability for seizure detection and forecasting using devices measuring ANS biomarkers. Finally, we address the field's challenges and provide an outlook for future developments. [ABSTRACT FROM AUTHOR]

Objective: Recently, a deep learning artificial intelligence (AI) model forecasted seizure risk using retrospective seizure diaries with higher accuracy than random forecasts. The present study sought to prospectively evaluate the same algorithm. Methods: We recruited a prospective cohort of 46 people with epilepsy; 25 completed sufficient data entry for analysis (median = 5 months). We used the same AI method as in our prior study. Group‐level and individual‐level Brier Skill Scores (BSSs) compared random forecasts and simple moving average forecasts to the AI. Results: The AI had an area under the receiver operating characteristic curve of.82. At the group level, the AI outperformed random forecasting (BSS =.53). At the individual level, AI outperformed random in 28% of cases. At the group and individual level, the moving average outperformed the AI. If pre‐enrollment (nonverified) diaries (with presumed underreporting) were included, the AI significantly outperformed both comparators. Surveys showed most did not mind poor‐quality LOW‐RISK or HIGH‐RISK forecasts, yet 91% wanted access to these forecasts. Significance: The previously developed AI forecasting tool did not outperform a very simple moving average forecasting in this prospective cohort, suggesting that the AI model should be replaced. [ABSTRACT FROM AUTHOR]

Objective: Epilepsy is characterized by spontaneous seizures that recur at unexpected times. Nonetheless, using years‐long electroencephalographic (EEG) recordings, we previously found that patient‐reported seizures consistently occur when interictal epileptiform activity (IEA) cyclically builds up over days. This multidien (multiday) interictal–ictal relationship, which is shared across patients, may bear phasic information for forecasting seizures, even if individual patterns of seizure timing are unknown. To test this rigorously in a large retrospective dataset, we pretrained algorithms on data recorded from a group of patients, and forecasted seizures in other, previously unseen patients. Methods: We used retrospective long‐term data from participants (N = 159) in the RNS System clinical trials, including intracranial EEG recordings (icEEG), and from two participants in the UNEEG Medical clinical trial of a subscalp EEG system (sqEEG). Based on IEA detections, we extracted instantaneous multidien phases and trained generalized linear models (GLMs) and recurrent neural networks (RNNs) to forecast the probability of seizure occurrence at a 24‐h horizon. Results: With GLMs and RNNs, seizures could be forecasted above chance in 79% and 81% of previously unseen subjects with a median discrimination of area under the curve (AUC) =.70 and.69 and median Brier skill score (BSS) =.07 and.08. In direct comparison, individualized models had similar median performance (AUC =.67, BSS =.08), but for fewer subjects (60%). Moreover, calibration of pretrained models could be maintained to accommodate different seizure rates across subjects. Significance: Our findings suggest that seizure forecasting based on multidien cycles of IEA can generalize across patients, and may drastically reduce the amount of data needed to issue forecasts for individuals who recently started collecting chronic EEG data. In addition, we show that this generalization is independent of the method used to record seizures (patient‐reported vs. electrographic) or IEA (icEEG vs. sqEEG). [ABSTRACT FROM AUTHOR]

Objective: One of the most disabling aspects of living with chronic epilepsy is the unpredictability of seizures. Cumulative research in the past decades has advanced our understanding of the dynamics of seizure risk. Technological advances have recently made it possible to record pertinent biological signals, including electroencephalogram (EEG), continuously. We aimed to assess whether patient‐specific seizure forecasting is possible using remote, minimally invasive ultra‐long‐term subcutaneous EEG. Methods: We analyzed a two‐center cohort of ultra‐long‐term subcutaneous EEG recordings, including six patients with drug‐resistant focal epilepsy monitored for 46–230 days with median 18 h/day of recorded data, totaling >11 000 h of EEG. Total electrographic seizures identified by visual review ranged from 12 to 36 per patient. Three candidate subject‐specific long short‐term memory network deep learning classifiers were trained offline and pseudoprospectively on preictal (1 h before) and interictal (>1 day from seizures) EEG segments. Performance was assessed relative to a random predictor. Periodicity of the final forecasts was also investigated with autocorrelation. Results: Depending on each architecture, significant forecasting performance was achieved in three to five of six patients, with overall mean area under the receiver operating characteristic curve of.65–.74. Significant forecasts showed sensitivity ranging from 64% to 80% and time in warning from 10.9% to 44.4%. Overall, the output of the forecasts closely followed patient‐specific circadian patterns of seizure occurrence. Significance: This study demonstrates proof‐of‐principle for the possibility of subject‐specific seizure forecasting using a minimally invasive subcutaneous EEG device capable of ultra‐long‐term at‐home recordings. These results are encouraging for the development of a prospective seizure forecasting trial with minimally invasive EEG. [ABSTRACT FROM AUTHOR]

To date, the unpredictability of seizures remains a source of suffering for people with epilepsy, motivating decades of research into methods to forecast seizures. Originally, only few scientists and neurologists ventured into this niche endeavor, which, given the difficulty of the task, soon turned into a long and winding road. Over the past decade, however, our narrow field has seen a major acceleration, with trials of chronic electroencephalographic devices and the subsequent discovery of cyclical patterns in the occurrence of seizures. Now, a burgeoning science of seizure timing is emerging, which in turn informs best forecasting strategies for upcoming clinical trials. Although the finish line might be in view, many challenges remain to make seizure forecasting a reality. This review covers the most recent scientific, technical, and medical developments, discusses methodology in detail, and sets a number of goals for future studies. [ABSTRACT FROM AUTHOR]

This study describes a generalized cross‐patient seizure‐forecasting approach using recurrent neural networks with ultra‐long‐term subcutaneous EEG (sqEEG) recordings. Data from six patients diagnosed with refractory epilepsy and monitored with an sqEEG device were used to develop a generalized algorithm for seizure forecasting using long short‐term memory (LSTM) deep‐learning classifiers. Electrographic seizures were identified by a board‐certified epileptologist. One‐minute data segments were labeled as preictal or interictal based on their relationship to confirmed seizures. Data were separated into training and testing data sets, and to compensate for the unbalanced data ratio in training, noise‐added copies of preictal data segments were generated to expand the training data set. The mean and standard deviation (SD) of the training data were used to normalize all data, preserving the pseudo‐prospective nature of the analysis. Different architecture classifiers were trained and tested using a leave‐one‐patient‐out cross‐validation method, and the area under the receiver‐operating characteristic (ROC) curve (AUC) was used to evaluate the performance classifiers. The importance of each input signal was evaluated using a leave‐one‐signal‐out method with repeated training and testing for each classifier. Cross‐patient classifiers achieved performance significantly better than chance in four of the six patients and an overall mean AUC of 0.602 ± 0.126 (mean ± SD). A time in warning of 37.386% ± 5.006% (mean ± std) and sensitivity of 0.691 ± 0.068 (mean ± std) were observed for patients with better than chance results. Analysis of input channels showed a significant contribution (p <.05) by the Fourier transform of signals channels to overall classifier performance. The relative contribution of input signals varied among patients and architectures, suggesting that the inclusion of all signals contributes to robustness in a cross‐patient classifier. These early results show that it is possible to forecast seizures training with data from different patients using two‐channel ultra‐long‐term sqEEG. [ABSTRACT FROM AUTHOR]

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. 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. 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. Short-term wearable recordings in combination with clinical data have great potential as an easy-to-use seizure likelihood assessment tool. [ABSTRACT FROM AUTHOR]

Objective: Previous studies suggested that patients with epilepsy might be able to forecast their own seizures. This study aimed to assess the relationships between premonitory symptoms, perceived seizure risk, and future and recent self‐reported and electroencephalographically (EEG)‐confirmed seizures in ambulatory patients with epilepsy in their natural home environments. Methods: Long‐term e‐surveys were collected from patients with and without concurrent EEG recordings. Information obtained from the e‐surveys included medication adherence, sleep quality, mood, stress, perceived seizure risk, and seizure occurrences preceding the survey. EEG seizures were identified. Univariate and multivariate generalized linear mixed‐effect regression models were used to estimate odds ratios (ORs) for the assessment of the relationships. Results were compared with the seizure forecasting classifiers and device forecasting literature using a mathematical formula converting OR to equivalent area under the curve (AUC). Results: Fifty‐four subjects returned 10 269 e‐survey entries, with four subjects acquiring concurrent EEG recordings. Univariate analysis revealed that increased stress (OR = 2.01, 95% confidence interval [CI] = 1.12–3.61, AUC =.61, p =.02) was associated with increased relative odds of future self‐reported seizures. Multivariate analysis showed that previous self‐reported seizures (OR = 5.37, 95% CI = 3.53–8.16, AUC =.76, p <.001) were most strongly associated with future self‐reported seizures, and high perceived seizure risk (OR = 3.34, 95% CI = 1.87–5.95, AUC =.69, p <.001) remained significant when prior self‐reported seizures were added to the model. No correlation with medication adherence was found. No significant association was found between e‐survey responses and subsequent EEG seizures. Significance: Our results suggest that patients may tend to self‐forecast seizures that occur in sequential groupings and that low mood and increased stress may be the result of previous seizures rather than independent premonitory symptoms. Patients in the small cohort with concurrent EEG showed no ability to self‐predict EEG seizures. The conversion from OR to AUC values facilitates direct comparison of performance between survey and device studies involving survey premonition and forecasting. [ABSTRACT FROM AUTHOR]

Conventional selection of pre-ictal EEG epochs for seizure prediction algorithm training data typically assumes a continuous pre-ictal brain state preceding a seizure. This is carried out by defining a fixed duration, pre-ictal time period before seizures from which pre-ictal training data epochs are uniformly sampled. However, stochastic physiological and pathological fluctuations in EEG data characteristics and underlying brain states suggest that pre-ictal state dynamics may be more complex, and selection of pre-ictal training data segments to reflect this could improve algorithm performance. We propose a semi-supervised technique to select pre-ictal training data most distinguishable from interictal EEG according to pre-specified data characteristics. The proposed method uses hierarchical clustering to identify optimal pre-ictal data epochs. In this paper we compare the performance of a seizure forecasting algorithm with and without hierarchical clustering of pre-ictal periods in chronic iEEG recordings from six canines with naturally occurring epilepsy. Hierarchical clustering of training data improved results for Time In Warning (TIW) (0.18 vs. 0.23) and False Positive Rate (FPR) (0.5 vs. 0.59) when evaluated across all subjects (p

Objective: The factors that influence seizure timing are poorly understood, and seizure unpredictability remains a major cause of disability. Work in chronobiology has shown that cyclical physiological phenomena are ubiquitous, with daily and multiday cycles evident in immune, endocrine, metabolic, neurological, and cardiovascular function. Additionally, work with chronic brain recordings has identified that seizure risk is linked to daily and multiday cycles in brain activity. Here, we provide the first characterization of the relationships between the cyclical modulation of a diverse set of physiological signals, brain activity, and seizure timing. Methods: In this cohort study, 14 subjects underwent chronic ambulatory monitoring with a multimodal wrist‐worn sensor (recording heart rate, accelerometry, electrodermal activity, and temperature) and an implanted responsive neurostimulation system (recording interictal epileptiform abnormalities and electrographic seizures). Wavelet and filter–Hilbert spectral analyses characterized circadian and multiday cycles in brain and wearable recordings. Circular statistics assessed electrographic seizure timing and cycles in physiology. Results: Ten subjects met inclusion criteria. The mean recording duration was 232 days. Seven subjects had reliable electroencephalographic seizure detections (mean = 76 seizures). Multiday cycles were present in all wearable device signals across all subjects. Seizure timing was phase locked to multiday cycles in five (temperature), four (heart rate, phasic electrodermal activity), and three (accelerometry, heart rate variability, tonic electrodermal activity) subjects. Notably, after regression of behavioral covariates from heart rate, six of seven subjects had seizure phase locking to the residual heart rate signal. Significance: Seizure timing is associated with daily and multiday cycles in multiple physiological processes. Chronic multimodal wearable device recordings can situate rare paroxysmal events, like seizures, within a broader chronobiology context of the individual. Wearable devices may advance the understanding of factors that influence seizure risk and enable personalized time‐varying approaches to epilepsy care. [ABSTRACT FROM AUTHOR]

Summary: Background: Seizure risk forecasting could reduce injuries and even deaths in people with epilepsy. There is great interest in using non-invasive wearable devices to generate forecasts of seizure risk. Forecasts based on cycles of epileptic activity, seizure times or heart rate have provided promising forecasting results. This study validates a forecasting method using multimodal cycles recorded from wearable devices. Method: Seizure and heart rate cycles were extracted from 13 participants. The mean period of heart rate data from a smartwatch was 562 days, with a mean of 125 self-reported seizures from a smartphone app. The relationship between seizure onset time and phases of seizure and heart rate cycles was investigated. An additive regression model was used to project heart rate cycles. The results of forecasts using seizure cycles, heart rate cycles, and a combination of both were compared. Forecasting performance was evaluated in 6 of 13 participants in a prospective setting, using long-term data collected after algorithms were developed. Findings: The results showed that the best forecasts achieved a mean area under the receiver-operating characteristic curve (AUC) of 0.73 for 9/13 participants showing performance above chance during retrospective validation. Subject-specific forecasts evaluated with prospective data showed a mean AUC of 0.77 with 4/6 participants showing performance above chance. Interpretation: The results of this study demonstrate that cycles detected from multimodal data can be combined within a single, scalable seizure risk forecasting algorithm to provide robust performance. The presented forecasting method enabled seizure risk to be estimated for an arbitrary future period and could be generalised across a range of data types. In contrast to earlier work, the current study evaluated forecasts prospectively, in subjects blinded to their seizure risk outputs, representing a critical step towards clinical applications. Funding: This study was funded by an Australian Government National Health & Medical Research Council and BioMedTech Horizons grant. The study also received support from the Epilepsy Foundation of America's ‘My Seizure Gauge’ grant.

Introduction: While it is known that poor sleep is a seizure precipitant, this association remains poorly quantified. This study investigated whether seizures are preceded by significant changes in sleep efficiency as measured by a wearable equipped with an electrocardiogram, respiratory bands, and an accelerometer. Methods: Nocturnal recordings from 47 people with epilepsy hospitalized at our epilepsy monitoring unit were analyzed (304 nights). Sleep metrics during nights followed by epileptic seizures (24 h post-awakening) were compared to those of nights which were not. Results: Lower sleep efficiency (percentage of sleep during the night) was found in the nights preceding seizure days (p < 0.05). Each standard deviation decrease in sleep efficiency and increase in wake after sleep onset was respectively associated with a 1.25-fold (95 % CI: 1.05 to 1.42, p < 0.05) and 1.49-fold (95 % CI: 1.17 to 1.92, p < 0.01) increased odds of seizure occurrence the following day. Furthermore, nocturnal seizures were associated with significantly lower sleep efficiency and higher wake after sleep onset (p < 0.05), as well as increased odds of seizure occurrence following wake (OR: 5.86, 95 % CI: 2.99 to 11.77, p < 0.001). Discussion: Findings indicate lower sleep efficiency during nights preceding seizures, suggesting that wearable sensors could be promising tools for sleep- based seizure-day forecasting in people with epilepsy. [ABSTRACT FROM AUTHOR]

Objectives. People with refractory epilepsy are overwhelmed by the uncertainty of their next seizures. Accurate prediction of future seizures could greatly improve the quality of life for these patients. New evidence suggests that seizure occurrences can have cyclical patterns for some patients. Even though these cyclicalities are not intuitive, they can be identified by machine learning (ML), to identify patients with predictable vs unpredictable seizure patterns. Approach. Self-reported seizure logs of 153 patients from the Human Epilepsy Project with more than three reported seizures (totaling 8337 seizures) were used to obtain inter-seizure interval time-series for training and evaluation of the forecasting models. Two classes of prediction methods were studied: (1) statistical approaches using Bayesian fusion of population-wise and individual-wise seizure patterns; and (2) ML-based algorithms including least squares, least absolute shrinkage and selection operator, support vector machine (SVM) regression, and long short-term memory regression. Leave-one-person-out cross-validation was used for training and evaluation, by training on seizure diaries of all except one subject and testing on the left-out subject. Main results. The leading forecasting models were the SVM regression and a statistical model that combined the median of population-wise seizure time-intervals with a test subject's prior seizure intervals. SVM was able to forecast 50%, 70%, 81%, 84%, and 87% of seizures of unseen subjects within 0, 1, 2, 3 to 4 d of mean absolute forecasting error, respectively. The subject-wise performances show that patients with more frequent seizures were generally better predicted. Significance. ML models can leverage non-random patterns within self-reported seizure diaries to forecast future seizures. While diary-based seizure forecasting alone is only one of many aspects of clinical care of patients with epilepsy, studying the level of predictability across seizures and patients paves the path towards a better understanding of predictable vs unpredictable seizures on individualized and population-wise bases. [ABSTRACT FROM AUTHOR]

Objective : Seizure prediction could greatly improve the quality of life of people suffering from epilepsy. Modern prediction systems leverage artificial intelligence (AI) techniques to automatically analyze neurophysiological data, most commonly the electroencephalogram (EEG), in order to anticipate upcoming epileptic events. However, the performance of these systems is normally assessed using randomized splitting methods, which can suffer from data leakage and thus result in an optimistic evaluation. In this review, we systematically surveyed the available scientific literature looking for research approaches that adopted more stringent assessment methods based on patient-independent testing. Approach : We queried three scientific databases (PubMed, Scopus, and Web of Science), focusing on AI techniques based on non-invasive EEG recorded from human subjects. We first summarize a standardized signal processing pipeline that could be deployed for the development and testing of cross-patient seizure prediction systems. We then analyze the research work that meets our selection criteria. Main results : 21 articles adopted patient-independent validation methods, constituting only 4% of the published work in the entire field of epileptic seizure prediction. Among eligible articles, the most common approach to deal with cross-patient scenarios was based on source domain adaptation techniques, which allow to fine-tune the predictive model on a limited set of data recorded from a set of independent target patients. Significance : Overall, our review indicates that epileptic seizure prediction remains an extremely challenging problem and significant research efforts are still needed to develop automated systems that can be deployed in realistic clinical settings. Our review protocol is based on the preferred reporting items for systematic review and meta-analysis protocols 2020 guidelines for conducting systematic reviews, considering NHLBI and ROBIS tools to mitigate the risk of bias, and it was pre-registered in PROSPERO (registration number: CRD4202452317)., (Creative Commons Attribution license.)

IntroductionWhile it is known that poor sleep is a seizure precipitant, this association remains poorly quantified. This study investigated whether seizures are preceded by significant changes in sleep efficiency as measured by a wearable equipped with an electrocardiogram, respiratory bands, and an accelerometer.MethodsNocturnal recordings from 47 people with epilepsy hospitalized at our epilepsy monitoring unit were analyzed (304 nights). Sleep metrics during nights followed by epileptic seizures (24 h post-awakening) were compared to those of nights which were not.ResultsLower sleep efficiency (percentage of sleep during the night) was found in the nights preceding seizure days (p < 0.05). Each standard deviation decrease in sleep efficiency and increase in wake after sleep onset was respectively associated with a 1.25-fold (95 % CI: 1.05 to 1.42, p < 0.05) and 1.49-fold (95 % CI: 1.17 to 1.92, p < 0.01) increased odds of seizure occurrence the following day. Furthermore, nocturnal seizures were associated with significantly lower sleep efficiency and higher wake after sleep onset (p < 0.05), as well as increased odds of seizure occurrence following wake (OR: 5.86, 95 % CI: 2.99 to 11.77, p < 0.001).DiscussionFindings indicate lower sleep efficiency during nights preceding seizures, suggesting that wearable sensors could be promising tools for sleep-based seizure-day forecasting in people with epilepsy.

Purpose of Review: To review the mutual interactions between sleep and epilepsy, including mechanisms of epileptogenesis, the relationship between sleep apnea and epilepsy, and potential strategies to treat seizures. Recent Findings: Recent studies have highlighted the role of functional network systems underlying epileptiform activation in sleep in several epilepsy syndromes, including absence epilepsy, benign focal childhood epilepsy, and epileptic encephalopathy with spike-wave activation in sleep. Sleep disorders are common in epilepsy, and early recognition and treatment can improve seizure frequency and potentially reduce SUDEP risk. Additionally, epilepsy is associated with cyclical patterns, which has led to new treatment approaches including chronotherapy, seizure monitoring devices, and seizure forecasting. Adenosine kinase and orexin receptor antagonists are also promising new potential drug targets that could be used to treat seizures. Summary: Sleep and epilepsy have a bidirectional relationship that intersects with many aspects of clinical management. In this article, we identify new areas of research involving future therapeutic opportunities in the field of epilepsy. [ABSTRACT FROM AUTHOR]

Metabolomics is the laboratory analysis and scientific study of the metabolome—that is, the entire collection of small molecule chemicals in an organism. The metabolome represents the functional state of an organism and provides a multifaceted readout of the aggregate activity of endogenous (cellular) and exogenous (environmental) processes. In this review, we discuss how the integrative and dynamic properties of the metabolome create unique opportunities to study complex pathologies that evolve and oscillate over time, like epilepsy. We explain how the scientific progress and clinical applications of metabolomics remain hampered by biological and technical challenges, and we propose best practices to overcome these challenges so that metabolomics can be used in a rigorous and effective manner to further epilepsy research. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a chronic neurological disorder affecting individuals globally, marked by recurrent and apparently unpredictable seizures that pose significant challenges, including increased mortality, injuries, and diminished quality of life. Despite advancements in treatments, a significant proportion of people with epilepsy continue to experience uncontrolled seizures. The apparent unpredictability of these events has been identified as a major concern for people with epilepsy, highlighting the need for innovative seizure forecasting technologies., Objective: The ATMOSPHERE study aimed to develop and evaluate a digital intervention, using wearable technology and data science, that provides real-time, individualized seizure forecasting for individuals living with epilepsy. This paper reports the protocol for one of the workstreams focusing on the design and testing of a prototype to capture real-time input data needed for predictive modeling. The first aim was to collaboratively design the prototype (work completed). The second aim is to conduct an "in-the-wild" study to assess usability and refine the prototype (planned research)., Methods: This study uses a person-based approach to design and test the usability of a prototype for real-time seizure precipitant data capture. Phase 1 (work completed) involved co-design with individuals living with epilepsy and health care professionals. Sessions explored users' requirements for the prototype, followed by iterative design of low-fidelity, static prototypes. Phase 2 (planned research) will be an "in-the-wild" usability study involving the deployment of a mid-fidelity, functional prototype for 4 weeks, with the collection of mixed methods usability data to assess the prototype's real-world application, feasibility, acceptability, and engagement. This phase involves primary participants (adults diagnosed with epilepsy) and, optionally, their nominated significant other. The usability study will run in 3 rounds of deployment and data collection, aiming to recruit 5 participants per round, with prototype refinement between rounds., Results: The phase-1 co-design study engaged 22 individuals, resulting in the development of a mid-fidelity, functional prototype based on identified requirements, including the tracking of evidence-based and personalized seizure precipitants. The upcoming phase-2 usability study is expected to provide insights into the prototype's real-world usability, identify areas for improvement, and refine the technology for future development. The estimated completion date of phase 2 is the last quarter of 2024., Conclusions: The ATMOSPHERE study aims to make a significant step forward in epilepsy management, focusing on the development of a user-centered, noninvasive wearable device for seizure forecasting. Through a collaborative design process and comprehensive usability testing, this research aims to address the critical need for predictive seizure forecasting technologies, offering a promising approach to improving the lives of individuals with epilepsy. By leveraging predictive analytics and personalized machine learning models, this technology seeks to offer a novel approach to managing epilepsy, potentially improving clinical outcomes, including quality of life, through increased predictability and seizure management., International Registered Report Identifier (irrid): DERR1-10.2196/60129., (©Emily E V Quilter, Samuel Downes, Mairi Therese Deighan, Liz Stuart, Rosie Charles, Phil Tittensor, Leandro Junges, Peter Kissack, Yasser Qureshi, Aravind Kumar Kamaraj, Amberly Brigden. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 19.09.2024.)

Implanted neurostimulation devices are gaining traction as therapeutic options for people with certain forms of drug-resistant focal epilepsy. Some of these devices enable chronic electroencephalography (cEEG), which offers views of the dynamics of brain activity in epilepsy over unprecedented time horizons. This review focuses on clinical insights and basic neuroscience discoveries enabled by analyses of cEEG from an exemplar device, the NeuroPace RNS® System. Applications of RNS cEEG covered here include counting and lateralizing seizures, quantifying medication response, characterizing spells, forecasting seizures, and exploring mechanisms of cognition. Limitations of the RNS System are discussed in the context of next-generation devices in development. The wide temporal lens of cEEG helps capture the dynamism of epilepsy, revealing phenomena that cannot be appreciated with short duration recordings. The RNS System is a vanguard device whose diagnostic utility rivals its therapeutic benefits, but emerging minimally invasive devices, including those with subscalp recording electrodes, promise to be more applicable within a broad population of people with epilepsy. Epileptology is on the precipice of a paradigm shift in which cEEG is a standard part of diagnostic evaluations and clinical management is predicated on quantitative observations integrated over long timescales. [ABSTRACT FROM AUTHOR]

Seizure detection, and more recently seizure forecasting, represent important avenues of clinical development in epilepsy, promoted by progress in wearable devices and mobile health (mHealth), which might help optimizing seizure control and prevention of seizure-related mortality and morbidity in persons with epilepsy. Yet, very long-term continuous monitoring of seizure-sensitive biosignals in the ambulatory setting presents a number of challenges. We herein provide an overview of these challenges and current technological landscape of mHealth devices for seizure detection. Specifically, we display, which types of sensor modalities and analytical methods are available, and give insight into current clinical practice guidelines, main outcomes of clinical validation studies, and discuss how to evaluate device performance at point-of-care facilities. We then address pitfalls which may arise in patient compliance and the need to design solutions adapted to user experience.

Background: Circadian and multiday rhythms are found across many biological systems, including cardiology, endocrinology, neurology, and immunology. In people with epilepsy, epileptic brain activity and seizure occurrence have been found to follow circadian, weekly, and monthly rhythms. Understanding the relationship between these cycles of brain excitability and other physiological systems can provide new insight into the causes of multiday cycles. The brain-heart link has previously been considered in epilepsy research, with potential implications for seizure forecasting, therapy, and mortality (i.e., sudden unexpected death in epilepsy). Methods: We report the results from a non-interventional, observational cohort study, Tracking Seizure Cycles. This study sought to examine multiday cycles of heart rate and seizures in adults with diagnosed uncontrolled epilepsy (N=31) and healthy adult controls (N=15) using wearable smartwatches and mobile seizure diaries over at least four months (M=12.0, SD=5.9; control M=10.6, SD=6.4). Cycles in heart rate were detected using a continuous wavelet transform. Relationships between heart rate cycles and seizure occurrence were measured from the distributions of seizure likelihood with respect to underlying cycle phase. Findings: Heart rate cycles were found in all 46 participants (people with epilepsy and healthy controls), with circadian (N=46), about-weekly (N=25) and about-monthly (N=13) rhythms being the most prevalent. Of the participants with epilepsy, 19 people had at least 20 reported seizures, and 10 of these had seizures significantly phase locked to their multiday heart rate cycles. Interpretation: Heart rate cycles showed similarities to multiday epileptic rhythms and may be comodulated with seizure likelihood. The relationship between heart rate and seizures is relevant for epilepsy therapy, including seizure forecasting, and may also have implications for cardiovascular disease. More broadly, understanding the link between multiday cycles in the heart and brain can shed new light on endogenous physiological rhythms in humans. Funding: This research received funding from the Australian Government National Health and Medical Research Council (investigator grant 1178220), the Australian Government BioMedTech Horizons program, and the Epilepsy Foundation of America's ‘My Seizure Gauge’ grant.

Accurate seizure forecasting is emerging as a near-term possibility due to recent advancements in machine learning and EEG technology improvements. Large-scale data curation and new data element collection through consumer wearables and digital health tools such as longitudinal seizure diary data has uncovered new possibilities for personalized algorithm development that may be used to predict the likelihood of future seizures. The Epilepsy Foundation recognized the unmet need for development in seizure forecasting following a 2016 survey where an overwhelming majority of respondents across all seizure types and frequencies reported that unpredictability of seizures had the strongest impact on their life while living with or caring for someone living with epilepsy. In early 2021, the Epilepsy Foundation conducted an updated survey among those living with epilepsies and/or their caregivers to better understand the use-cases that best suit the needs of our community as seizure forecast research advances. These results will provide researchers with insight into user-acceptance of using a forecasting tool and incorporation into their daily life. Ultimately, this input from people living with epilepsy and caregivers will provide timely feedback on what the community needs are and ensure researchers and companies first and foremost consider these needs in seizure forecasting tools/product development.

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder®), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG.

Seizure detection, and more recently seizure forecasting, represent important avenues of clinical development in epilepsy, promoted by progress in wearable devices and mobile health (mHealth), which might help optimizing seizure control and prevention of seizure-related mortality and morbidity in persons with epilepsy. Yet, very long-term continuous monitoring of seizure-sensitive biosignals in the ambulatory setting presents a number of challenges. We herein provide an overview of these challenges and current technological landscape of mHealth devices for seizure detection. Specifically, we display, which types of sensor modalities and analytical methods are available, and give insight into current clinical practice guidelines, main outcomes of clinical validation studies, and discuss how to evaluate device performance at point-of-care facilities. We then address pitfalls which may arise in patient compliance and the need to design solutions adapted to user experience. [ABSTRACT FROM AUTHOR]

Accurate seizure forecasting is emerging as a near-term possibility due to recent advancements in machine learning and EEG technology improvements. Large-scale data curation and new data element collection through consumer wearables and digital health tools such as longitudinal seizure diary data has uncovered new possibilities for personalized algorithm development that may be used to predict the likelihood of future seizures. The Epilepsy Foundation recognized the unmet need for development in seizure forecasting following a 2016 survey where an overwhelming majority of respondents across all seizure types and frequencies reported that unpredictability of seizures had the strongest impact on their life while living with or caring for someone living with epilepsy. In early 2021, the Epilepsy Foundation conducted an updated survey among those living with epilepsies and/or their caregivers to better understand the use-cases that best suit the needs of our community as seizure forecast research advances. These results will provide researchers with insight into user-acceptance of using a forecasting tool and incorporation into their daily life. Ultimately, this input from people living with epilepsy and caregivers will provide timely feedback on what the community needs are and ensure researchers and companies first and foremost consider these needs in seizure forecasting tools/product development. [ABSTRACT FROM AUTHOR]

Electroencephalography (EEG) has been used to forecast seizures with varying success. There is an increasing interest to use electrocardiogram (ECG) to help with seizure forecasting. The neural and cardiovascular systems may exhibit critical slowing, which is measured by an increase in variance and autocorrelation of the system, when change from a normal state to an ictal state. To forecast seizures, the variance and autocorrelation of long-term continuous EEG and ECG data from 16 patients were used for analysis. The average period of recordings was 161.9 h, with an average of 9 electrographic seizures in an individual patient. The relationship between seizure onset times and phases of variance and autocorrelation in EEG and ECG data was investigated. The results of forecasting models using critical slowing features, seizure circadian features, and combined critical slowing and circadian features were compared using the receiver-operating characteristic curve. The results demonstrated that the best forecaster was patient-specific and the average area under the curve (AUC) of the best forecaster across patients was 0.68. In 50% of patients, circadian forecasters had the best performance. Critical slowing forecaster performed best in 19% of patients. Combined forecaster achieved the best performance in 31% of patients. The results of this study may help to advance the field of seizure forecasting and lead to the improved quality of life of people who suffer from epilepsy. [ABSTRACT FROM AUTHOR]

Accurate identification of seizure activity, both clinical and subclinical, has important implications in the management of epilepsy. Accurate recognition of seizure activity is essential for diagnostic, management and forecasting purposes, but patient-reported seizures have been shown to be unreliable. Earlier work has revealed accurate capture of electrographic seizures and forecasting is possible with an implantable intracranial device, but less invasive electroencephalography (EEG) recording systems would be optimal. Here, we present preliminary results of seizure detection and forecasting with a minimally invasive sub-scalp device that continuously records EEG. Five participants with refractory epilepsy who experience at least two clinically identifiable seizures monthly have been implanted with sub-scalp devices (Minder®), providing two channels of data from both hemispheres of the brain. Data is continuously captured via a behind-the-ear system, which also powers the device, and transferred wirelessly to a mobile phone, from where it is accessible remotely via cloud storage. EEG recordings from the sub-scalp device were compared to data recorded from a conventional system during a 1-week ambulatory video-EEG monitoring session. Suspect epileptiform activity (EA) was detected using machine learning algorithms and reviewed by trained neurophysiologists. Seizure forecasting was demonstrated retrospectively by utilizing cycles in EA and previous seizure times. The procedures and devices were well-tolerated and no significant complications have been reported. Seizures were accurately identified on the sub-scalp system, as visually confirmed by periods of concurrent conventional scalp EEG recordings. The data acquired also allowed seizure forecasting to be successfully undertaken. The area under the receiver operating characteristic curve (AUC score) achieved (0.88), which is comparable to the best score in recent, state-of-the-art forecasting work using intracranial EEG. [ABSTRACT FROM AUTHOR]

Objective: Ultra long‐term subcutaneous electroencephalography (sqEEG) monitoring is a new modality with great potential for both health and disease, including epileptic seizure detection and forecasting. However, little is known about the long‐term quality and consistency of the sqEEG signal, which is the objective of this study. Methods: The largest multicenter cohort of sqEEG was analyzed, including 14 patients with epilepsy and 12 healthy subjects, implanted with a sqEEG device (24/7 EEG™ SubQ), and recorded from 23 to 230 days (median 42 days), with a median data capture rate of 75% (17.9 hours/day). Median power spectral density plots of each subject were examined for physiological peaks, including at diurnal and nocturnal periods. Long‐term temporal trends in signal impedance and power spectral features were investigated with subject‐specific linear regression models and group‐level linear mixed‐effects models. Results: sqEEG spectrograms showed an approximate 1/f power distribution. Diurnal peaks in the alpha range (8‐13Hz) and nocturnal peaks in the sigma range (12‐16Hz) were seen in the majority of subjects. Signal impedances remained low, and frequency band powers were highly stable throughout the recording periods. Significance: The spectral characteristics of minimally invasive, ultra long‐term sqEEG are similar to scalp EEG, whereas the signal is highly stationary. Our findings reinforce the suitability of this system for chronic implantation on diverse clinical applications, from seizure detection and forecasting to brain‐computer interfaces. [ABSTRACT FROM AUTHOR]

Epilepsy affects about 50 million people worldwide of which one third is refractory to medication. An automated and reliable system that warns of impending seizures would greatly improve patient’s quality of life by overcoming the uncertainty and helplessness due to the unpredicted events. Here we present new seizure prediction results including a performance comparison of different methods. The analysis is based on a new set of intracranial EEG data that has been recorded in our working group during presurgical evaluation. We applied two different methods for seizure prediction and evaluated their performance pseudoprospectively. The comparison of this evaluation with common statistical evaluation reveals possible reasons for overly optimistic estimations of the performance of seizure forecasting systems.

It is a major challenge in clinical epilepsy to diagnose and treat a disease characterized by infrequent seizures based on patient or caregiver reports and limited duration clinical testing. The poor reliability of self-reported seizure diaries for many people with epilepsy is well-established, but these records remain necessary in clinical care and therapeutic studies. A number of wearable devices have emerged, which may be capable of detecting seizures, recording seizure data, and alerting caregivers. Developments in non-invasive wearable sensors to measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), and other signals outside of the traditional clinical environment may be able to identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) and minimally invasive subscalp EEG may allow direct measurement of seizure activity. However, significant network and computational infrastructure is needed for continuous, secure transmission of data. The large volume of data acquired by these devices necessitates computer-assisted review and detection to reduce the burden on human reviewers. Furthermore, user acceptability of such devices must be a paramount consideration to ensure adherence with long-term device use. Such devices can identify tonic–clonic seizures, but identification of other seizure semiologies with non-EEG wearables is an ongoing challenge. Identification of electrographic seizures with subscalp EEG systems has recently been demonstrated over long (>6 month) durations, and this shows promise for accurate, objective seizure records. While the ability to detect and forecast seizures from ambulatory intracranial EEG is established, invasive devices may not be acceptable for many individuals with epilepsy. Recent studies show promising results for probabilistic forecasts of seizure risk from long-term wearable devices and electronic diaries of self-reported seizures. There may also be predictive value in individuals' symptoms, mood, and cognitive performance. However, seizure forecasting requires perpetual use of a device for monitoring, increasing the importance of the system's acceptability to users. Furthermore, long-term studies with concurrent EEG confirmation are lacking currently. This review describes the current evidence and challenges in the use of minimally and non-invasive devices for long-term epilepsy monitoring, the essential components in remote monitoring systems, and explores the feasibility to detect and forecast impending seizures via long-term use of these systems.

The unpredictability of epileptic seizures exposes people with epilepsy to potential physical harm, restricts day-to-day activities, and impacts mental well-being. Accurate seizure forecasters would reduce the uncertainty associated with seizures but need to be feasible and accessible in the long-term. Wearable devices are perfect candidates to develop non-invasive, accessible forecasts but are yet to be investigated in long-term studies. We hypothesized that machine learning models could utilize heart rate as a biomarker for well-established cycles of seizures and epileptic activity, in addition to other wearable signals, to forecast high and low risk seizure periods. This feasibility study tracked participants' (n = 11) heart rates, sleep, and step counts using wearable smartwatches and seizure occurrence using smartphone seizure diaries for at least 6 months (mean = 14.6 months, SD = 3.8 months). Eligible participants had a diagnosis of refractory epilepsy and reported at least 20 seizures (mean = 135, SD = 123) during the recording period. An ensembled machine learning and neural network model estimated seizure risk either daily or hourly, with retraining occurring on a weekly basis as additional data was collected. Performance was evaluated retrospectively against a rate-matched random forecast using the area under the receiver operating curve. A pseudo-prospective evaluation was also conducted on a held-out dataset. Of the 11 participants, seizures were predicted above chance in all (100%) participants using an hourly forecast and in ten (91%) participants using a daily forecast. The average time spent in high risk (prediction time) before a seizure occurred was 37 min in the hourly forecast and 3 days in the daily forecast. Cyclic features added the most predictive value to the forecasts, particularly circadian and multiday heart rate cycles. Wearable devices can be used to produce patient-specific seizure forecasts, particularly when biomarkers of seizure and epileptic activity cycles are utilized.

The unpredictability of epileptic seizures exposes people with epilepsy to potential physical harm, restricts day-to-day activities, and impacts mental well-being. Accurate seizure forecasters would reduce the uncertainty associated with seizures but need to be feasible and accessible in the long-term. Wearable devices are perfect candidates to develop non-invasive, accessible forecasts but are yet to be investigated in long-term studies. We hypothesized that machine learning models could utilize heart rate as a biomarker for well-established cycles of seizures and epileptic activity, in addition to other wearable signals, to forecast high and low risk seizure periods. This feasibility study tracked participants' (n = 11) heart rates, sleep, and step counts using wearable smartwatches and seizure occurrence using smartphone seizure diaries for at least 6 months (mean = 14.6 months, SD = 3.8 months). Eligible participants had a diagnosis of refractory epilepsy and reported at least 20 seizures (mean = 135, SD = 123) during the recording period. An ensembled machine learning and neural network model estimated seizure risk either daily or hourly, with retraining occurring on a weekly basis as additional data was collected. Performance was evaluated retrospectively against a rate-matched random forecast using the area under the receiver operating curve. A pseudo-prospective evaluation was also conducted on a held-out dataset. Of the 11 participants, seizures were predicted above chance in all (100%) participants using an hourly forecast and in ten (91%) participants using a daily forecast. The average time spent in high risk (prediction time) before a seizure occurred was 37 min in the hourly forecast and 3 days in the daily forecast. Cyclic features added the most predictive value to the forecasts, particularly circadian and multiday heart rate cycles. Wearable devices can be used to produce patient-specific seizure forecasts, particularly when biomarkers of seizure and epileptic activity cycles are utilized. [ABSTRACT FROM AUTHOR]

It is a major challenge in clinical epilepsy to diagnose and treat a disease characterized by infrequent seizures based on patient or caregiver reports and limited duration clinical testing. The poor reliability of self-reported seizure diaries for many people with epilepsy is well-established, but these records remain necessary in clinical care and therapeutic studies. A number of wearable devices have emerged, which may be capable of detecting seizures, recording seizure data, and alerting caregivers. Developments in non-invasive wearable sensors to measure accelerometry, photoplethysmography (PPG), electrodermal activity (EDA), electromyography (EMG), and other signals outside of the traditional clinical environment may be able to identify seizure-related changes. Non-invasive scalp electroencephalography (EEG) and minimally invasive subscalp EEG may allow direct measurement of seizure activity. However, significant network and computational infrastructure is needed for continuous, secure transmission of data. The large volume of data acquired by these devices necessitates computer-assisted review and detection to reduce the burden on human reviewers. Furthermore, user acceptability of such devices must be a paramount consideration to ensure adherence with long-term device use. Such devices can identify tonic–clonic seizures, but identification of other seizure semiologies with non-EEG wearables is an ongoing challenge. Identification of electrographic seizures with subscalp EEG systems has recently been demonstrated over long (>6 month) durations, and this shows promise for accurate, objective seizure records. While the ability to detect and forecast seizures from ambulatory intracranial EEG is established, invasive devices may not be acceptable for many individuals with epilepsy. Recent studies show promising results for probabilistic forecasts of seizure risk from long-term wearable devices and electronic diaries of self-reported seizures. There may also be predictive value in individuals' symptoms, mood, and cognitive performance. However, seizure forecasting requires perpetual use of a device for monitoring, increasing the importance of the system's acceptability to users. Furthermore, long-term studies with concurrent EEG confirmation are lacking currently. This review describes the current evidence and challenges in the use of minimally and non-invasive devices for long-term epilepsy monitoring, the essential components in remote monitoring systems, and explores the feasibility to detect and forecast impending seizures via long-term use of these systems. [ABSTRACT FROM AUTHOR]

Many people with epilepsy are not aware of their seizures or do not have reliable auras. The responsive neurostimulation system (RNS) delivers stimulation triggered by intracranial epileptiform activity. If an epileptiform pattern continues, the RNS repeats stimulation up to five times per event. The RNS can cause acute stimulation‐related symptoms that can be avoided by reducing stimulation. Because each of the five therapies can be programmed independently, it may be possible to program the latter therapies to induce a seizure warning. The goal of this study was to determine what proportion of patients could have tolerable symptoms safely elicited by stimulation, ultimately for the purpose of subjective seizure recognition. Of 18 patients, 12 (67%) had induced symptoms, which were tolerable in 11. Phosphenes were most common. We also present one patient in whom the fifth therapy was set to induce a symptom for early recognition and treatment of clusters of focal impaired awareness seizures, which were previously unrecognized and had led to days of disabling cognitive impairment. This protocol prevented disabling clusters successfully for several years. The findings suggest the RNS can provide a seizure warning, potentially improving safety and quality of life, and leading to prevention of clinical seizures or clusters in select patients. [ABSTRACT FROM AUTHOR]

The article introduces the International Conference on Technology and AnaLysis of Seizures (ICTALS), a conference that brings together experts from various fields to address the problem of epilepsy. The conference focuses on understanding the mechanisms of epilepsy and seizures, developing methods to predict and control seizures, and creating computational models based on neural mechanisms. The 10th edition of ICTALS, called "the tipping point," took place in Bern, Switzerland in 2022. The article also provides summaries of several articles presented at the conference, covering topics such as the relationship between sleep and epilepsy, the theory of seizures begetting seizures, markers of cortical excitability in epilepsy, the cellular origin of focal seizures, stimulation of the epileptic brain, and the current state of seizure forecasting. The article concludes by highlighting the importance of transdisciplinary collaboration in the field of epileptology. [Extracted from the article]

Growing evidence shows the bidirectional interactions between sleep, circadian rhythm, and epilepsy. Comprehending how these interact with each other may help to advance our understanding of the pathophysiology of epilepsy and develop new treatment strategies to improve seizure control by reducing the medication side effects and the risks associated with seizures. In this review, we present the overview of different temporal patterns of interictal epileptiform discharges and epileptic seizures over a period of 24 consecutive hours. Furthermore, we discuss the underlying mechanism of the core-clock gene in periodic seizure occurrences. Finally, we outline the role of circadian patterns of seizures on seizure forecasting models and its implication for chronotherapy in epilepsy.

Many outstanding studies have reported promising results in seizure forecasting, one of the most challenging predictive data analysis problems. This is mainly because electroencephalogram (EEG) bio-signal intensity is very small, in $\mu \text{V}$ range, and there are significant sensing difficulties given physiological and non-physiological artifacts. Today the process of accurate epileptic seizure identification and data labeling is done by neurologists. The current unpredictability of epileptic seizure activities together with the lack of reliable treatment for patients living with drug resistant forms of epilepsy creates an urgency for research into accurate, sensitive and patient-specific seizure forecasting. Most seizure forecasting algorithms use only labeled data for training purposes. As the seizure data is labeled manually by neurologists, preparing the labeled data is expensive and time consuming, making the best use of the data critical. In this article, we propose an approach that can make use of not only labeled EEG signals but also the unlabeled ones which are more accessible. We use the short-time Fourier transform on 28-s EEG windows as a pre-processing step. A generative adversarial network (GAN) is trained in an unsupervised manner where information of seizure onset is disregarded. The trained Discriminator of the GAN is then used as a feature extractor. Features generated by the feature extractor are classified by two fully-connected layers (can be replaced by any classifier) for the labeled EEG signals. This semi-supervised patient-specific seizure forecasting method achieves an out-of-sample testing area under the operating characteristic curve (AUC) of 77.68%, 75.47% and 65.05% for the CHB-MIT scalp EEG dataset, the Freiburg Hospital intracranial EEG dataset and the EPILEPSIAE dataset, respectively. Unsupervised training without the need for labeling is important because not only it can be performed in real-time during EEG signal recording, but also it does not require feature engineering effort for each patient. To the best of our knowledge, this is the first application of GAN to seizure forecasting.

Whereas, seizure detection provides a means to alert caregivers to seizures when they occur, seizure forecasting aims at reducing uncertainty by quantifying the likelihood of seizures in the future ([1]-[3]). Epilepsy, seizure detection, seizure prediction, seizure forecasting, computational models, machine learning, artificial intelligence Keywords: epilepsy; seizure detection; seizure prediction; seizure forecasting; computational models; machine learning; artificial intelligence EN epilepsy seizure detection seizure prediction seizure forecasting computational models machine learning artificial intelligence 1 3 3 03/21/22 20220316 NES 220316 For the 50 million people with epilepsy worldwide, seizures are seemingly unpredictable events that can be associated with significant morbidity and mortality. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Growing evidence shows the bidirectional interactions between sleep, circadian rhythm, and epilepsy. Comprehending how these interact with each other may help to advance our understanding of the pathophysiology of epilepsy and develop new treatment strategies to improve seizure control by reducing the medication side effects and the risks associated with seizures. In this review, we present the overview of different temporal patterns of interictal epileptiform discharges and epileptic seizures over a period of 24 consecutive hours. Furthermore, we discuss the underlying mechanism of the core-clock gene in periodic seizure occurrences. Finally, we outline the role of circadian patterns of seizures on seizure forecasting models and its implication for chronotherapy in epilepsy. [ABSTRACT FROM AUTHOR]

Objective: Seizure unpredictability is rated as one of the most challenging aspects of living with epilepsy. Seizure likelihood can be influenced by a range of environmental and physiological factors that are difficult to measure and quantify. However, some generalizable patterns have been demonstrated in seizure onset. A majority of people with epilepsy exhibit circadian rhythms in their seizure times, and many also show slower, multiday patterns. Seizure cycles can be measured using a range of recording modalities, including self‐reported electronic seizure diaries. This study aimed to develop personalized forecasts from a mobile seizure diary app. Methods: Forecasts based on circadian and multiday seizure cycles were tested pseudoprospectively using data from 50 app users (mean of 109 seizures per subject). Individuals' strongest cycles were estimated from their reported seizure times and used to derive the likelihood of future seizures. The forecasting approach was validated using self‐reported events and electrographic seizures from the Neurovista dataset, an existing database of long‐term electroencephalography that has been widely used to develop forecasting algorithms. Results: The validation dataset showed that forecasts of seizure likelihood based on self‐reported cycles were predictive of electrographic seizures for approximately half the cohort. Forecasts using only mobile app diaries allowed users to spend an average of 67.1% of their time in a low‐risk state, with 14.8% of their time in a high‐risk warning state. On average, 69.1% of seizures occurred during high‐risk states and 10.5% of seizures occurred in low‐risk states. Significance: Seizure diary apps can provide personalized forecasts of seizure likelihood that are accurate and clinically relevant for electrographic seizures. These results have immediate potential for translation to a prospective seizure forecasting trial using a mobile diary app. It is our hope that seizure forecasting apps will one day give people with epilepsy greater confidence in managing their daily activities. [ABSTRACT FROM AUTHOR]

• A method to predict an epileptic event twenty minutes before its onset using electrocardiogram (ECG) signals. • Adroit integration of maximal overlap wavelet packet transform, homogeneity index, and a K-Nearest Neighbors classifier. • Effectiveness is verified by employing a database provided by the MIT-Beth Israel Hospital (MIT-BIH). • Proposed method effectively predicts an epileptic seizure 20 min prior to its onset with an accuracy of 93.25%. Epilepsy, a complex pathology with various etiological origins, is characterized by producing hyperexcitability in the brain, which can have multiple disruptive symptoms. It impacts about 40 million people worldwide, of which 20 to 30% have chronic and intractable seizures. Each seizure can create hazardous situations for patients resulting from fractures, burns, submersion accidents, and soft-tissue injuries. Therefore, a method capable of predicting a seizure with sufficient window time before its onset is highly desirable because it will allow the patient to locate a safe place or take appropriate precautionary actions. In this article, a novel method is presented through adroit integration of maximal overlap wavelet packet transform, homogeneity index, and a K-Nearest Neighbors classifier to predict an epileptic event twenty minutes before its onset using electrocardiogram (ECG) signals. The method's effectiveness for predicting an epileptic seizure is verified by employing a database provided by the Massachusetts Institute of Technology-Beth Israel Hospital (MIT-BIH), which includes seven patients with ten epileptic seizures. The results show that the proposed method effectively predicts an epileptic seizure 20 min prior to its onset with an accuracy of 93.25%. [ABSTRACT FROM AUTHOR]