ObjectiveOver recent years, there has been a growing interest in exploring the utility of seizure risk forecasting, particularly how it could improve quality of life for people living with epilepsy. This study reports on user experiences and perspectives of a seizure risk forecaster app, as well as the potential impact on mood and adjustment to epilepsy.MethodsActive app users were asked to complete a survey (baseline and 3-month follow-up) to assess perspectives on the forecast feature as well as mood and adjustment. Post-hoc, nine neutral forecast users (neither agreed nor disagreed it was useful) completed semi-structured interviews, to gain further insight into their perspectives of epilepsy management and seizure forecasting. Non-parametric statistical tests and inductive thematic analyses were used to analyse the quantitative and qualitative data, respectively.ResultsSurveys were completed by 111 users. Responders consisted of “app users” (n = 58), and “app and forecast users” (n = 53). Of the “app and forecast users”, 40 % believed the forecast was accurate enough to be useful in monitoring for seizure risk, and 60 % adopted it for purposes like scheduling activities and helping mental state. Feeling more in control was the most common response to both high and low risk forecasted states. In-depth interviews revealed five broad themes, of which ‘frustrations with lack of direction’ (regarding their current epilepsy management approach), ‘benefits of increased self-knowledge’ and ‘current and anticipated usefulness of forecasting’ were the most common.SignificancePreliminary results suggest that seizure risk forecasting can be a useful tool for people with epilepsy to make lifestyle changes, such as scheduling daily events, and experience greater feelings of control. These improvements may be attributed, at least partly, to the improvements in self-knowledge experienced through forecast use.

A significant challenge of video-electroencephalography (vEEG) in epilepsy diagnosis is timing monitoring sessions to capture epileptiform activity. Given the significant consequences of misdiagnosis or delayed diagnosis, new techniques to improve diagnostic yield of vEEG are needed. In this study, we introduce and validate “pro-ictal EEG scheduling”, a method to schedule vEEG monitoring to coincide with periods of heightened seizure probability as a low-risk approach to enhance the diagnostic yield. A database of long-term ambulatory vEEG monitoring sessions ( n =5038) of adults and children was examined. Data from linked electronic seizure diaries were extracted (minimum 10 self-reported events over 12-months) to generate cycle-based estimates of seizure risk. VEEG monitoring sessions coinciding with periods of estimated high-risk were allocated to the high-risk group (adults n =305, children n =82) and compared to remaining studies (baseline: adults n =3586, children n =1065). Test of Proportions and Risk-Ratios (RR) were used to index differences in proportions and likelihood of capturing outcome measures (abnormal report, confirmed seizure and diary event) during monitoring. The impact of clinical and demographic factors (sex, epilepsy-type, medication) was also explored. During vEEG monitoring, the high-risk group was 25% more likely to have an abnormal vEEG report (190/305:62.3% vs 1790/3586:49.9%, RR=1.25, 95% CI[1.137:1.370], p <0.001), 63% more likely to present with a confirmed seizure (56/305:18.4% vs 424/3586:11.3%, RR=1.63, 95% CI[1.265:2.101], p <0.001) and 42% more likely to report an event (153/305:50.2% vs 1267/3586:35.3%, RR=1.420, 95% CI[1.259:1.602], p <0.001). In children, the high-risk group was 93% more likely to have a confirmed seizure (21/82:25.6% vs 141/1065:13.2%, RR=1.93, 95% CI[1.297:2.885], p= 0.002). Similar effects were observed across clinical and demographic features. This study provides the first large-scale validation of pro-ictal EEG scheduling in improving the yield of vEEG. This innovative approach offers a pragmatic and low-risk strategy to enhance the diagnostic capabilities of vEEG monitoring, significantly impacting epilepsy management.

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.

Objective: Forecasting epileptic seizures can reduce uncertainty for patients and allow preventative actions. While many models can predict the occurrence of seizures from features of the EEG, few models incorporate changes in features over time. Long Short-Term Memory (LSTM) neural networks are a machine learning architecture that can display temporal dynamics due to the recurrent connections. In this paper, we used LSTMs to monitor changes in EEG features over time to improve the accuracy of seizure forecasts and to alter the time window of the forecast. Methods: Long-term intracranial EEG recordings from eight patients from the NeuroVista dataset were used. A Fourier transform of 1-minute segments of EEG was fed into a Convolutional Neural Network (CNN). The outputs from the CNN were input to three different LSTM models at different time intervals: 1 minute, 1 hour and 1 day. The LSTM model outputs were used to predict seizure onset within a time window. The prediction and start of the time window were separated by the same length of time as the window. Window sizes tested included 2, 4, 10, 20 and 40 minutes. Results and Conclusion: Our model forecast seizure onsets well above a random predictor. Compared to other models using the same dataset, our model performed better for some patients and worse for others. Monitoring the change in EEG features over time allowed our model to produce good results over a range of different window sizes, which is an improvement on previous models and raises the possibility of altering the forecast to meet individual patient needs. Furthermore, a window size of 40 minutes provides a potential intervention time of 40 minutes, which is the first time an intervention time of more than 5 minutes have been forecast using long-term EEG recordings.

Objective Emerging evidence has shown that ambient air pollution affects brain health, but little is known about its effect on epileptic seizures. This work aimed to assess the association between daily exposure to ambient air pollution and the risk of epileptic seizures. Methods This study used epileptic seizure data from two independent data sources (NeuroVista and Seer App seizure diary). In the NeuroVista data set, 3273 seizures were recorded using intracranial electroencephalography (iEEG) from 15 participants with refractory focal epilepsy in Australia in 2010-2012. In the seizure diary data set, 3419 self-reported seizures were collected through a mobile application from 34 participants with epilepsy in Australia in 2018-2021. Daily average concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O-3), particulate matter <= 10 mu m in diameter (PM10), and sulfur dioxide (SO2) were retrieved from the Environment Protection Authority (EPA) based on participants' postcodes. A patient-time-stratified case-crossover design with the conditional Poisson regression model was used to determine the associations between air pollutants and epileptic seizures. Results A significant association between CO concentrations and epileptic seizure risks was observed, with an increased seizure risk of 4% (relative risk [RR]: 1.04, 95% confidence interval [CI]: 1.01-1.07) for an interquartile range (IQR) increase of CO concentrations (0.13 parts per million), whereas no significant associations were found for the other four air pollutants in the whole study population. Female participants had a significantly increased risk of seizures when exposed to elevated CO and NO2, with RRs of 1.05 (95% CI: 1.01-1.08) and 1.09 (95% CI: 1.01-1.16), respectively. In addition, a significant association was observed between CO and the risk of subclinical seizures (RR: 1.20, 95% CI: 1.12-1.28). Significance Daily exposure to elevated CO concentrations may be associated with an increased risk of epileptic seizures, especially for subclinical seizures.

Objective Most seizure forecasting algorithms have relied on features specific to electroencephalographic recordings. Environmental and physiological factors, such as weather and sleep, have long been suspected to affect brain activity and seizure occurrence but have not been fully explored as prior information for seizure forecasts in a patient-specific analysis. The study aimed to quantify whether sleep, weather, and temporal factors (time of day, day of week, and lunar phase) can provide predictive prior probabilities that may be used to improve seizure forecasts. Methods This study performed post hoc analysis on data from eight patients with a total of 12.2 years of continuous intracranial electroencephalographic recordings (average = 1.5 years, range = 1.0-2.1 years), originally collected in a prospective trial. Patients also had sleep scoring and location-specific weather data. Histograms of future seizure likelihood were generated for each feature. The predictive utility of individual features was measured using a Bayesian approach to combine different features into an overall forecast of seizure likelihood. Performance of different feature combinations was compared using the area under the receiver operating curve. Performance evaluation was pseudoprospective. Results For the eight patients studied, seizures could be predicted above chance accuracy using sleep (five patients), weather (two patients), and temporal features (six patients). Forecasts using combined features performed significantly better than chance in six patients. For four of these patients, combined forecasts outperformed any individual feature. Significance Environmental and physiological data, including sleep, weather, and temporal features, provide significant predictive information on upcoming seizures. Although forecasts did not perform as well as algorithms that use invasive intracranial electroencephalography, the results were significantly above chance. Complementary signal features derived from an individual's historic seizure records may provide useful prior information to augment traditional seizure detection or forecasting algorithms. Importantly, many predictive features used in this study can be measured noninvasively.

BACKGROUND:While the effects of prolonged sleep deprivation (≥24 h) on seizure occurrence has been thoroughly explored, little is known about the effects of day-to-day variations in the duration and quality of sleep on seizure probability. A better understanding of the interaction between sleep and seizures may help to improve seizure management. METHODS:To explore how sleep and epileptic seizures are associated, we analysed continuous intracranial electroencephalography (EEG) recordings collected from 10 patients with refractory focal epilepsy undergoing ordinary life activities between 2010 and 2012 from three clinical centres (Austin Health, The Royal Melbourne Hospital, and St Vincent's Hospital of the Melbourne University Epilepsy Group). A total of 4340 days of sleep-wake data were analysed (average 434 days per patient). EEG data were sleep scored using a semi-automated machine learning approach into wake, stages one, two, and three non-rapid eye movement sleep, and rapid eye movement sleep categories. FINDINGS:Seizure probability changes with day-to-day variations in sleep duration. Logistic regression models revealed that an increase in sleep duration, by 1·66 ± 0·52 h, lowered the odds of seizure by 27% in the following 48 h. Following a seizure, patients slept for longer durations and if a seizure occurred during sleep, then sleep quality was also reduced with increased time spent aroused from sleep and reduced rapid eye movement sleep. INTERPRETATION:Our results suggest that day-to-day deviations from regular sleep duration correlates with changes in seizure probability. Sleeping longer, by 1·66 ± 0·52 h, may offer protective effects for patients with refractory focal epilepsy, reducing seizure risk. Furthermore, the occurrence of a seizure may disrupt sleep patterns by elongating sleep and, if the seizure occurs during sleep, reducing its quality.

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.

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.

SummaryObjectiveWe report on patient‐specific durations of postictal periods in long‐term intracranial electroencephalography (iEEG) recordings. The objective was to investigate the relationship between seizure duration and postictal suppression duration.MethodsLong‐term recording iEEG from 9 patients (>50 seizures recorded) were analyzed. In total, 2310 seizures were recorded during a total of 13.8 years of recording. Postictal suppression duration was calculated as the duration after seizure termination until total signal energy returned to background levels. The relationship between seizure duration and postictal suppression duration was quantified using the correlation coefficient (r). The effects of populations of seizures within patients, on correlations, were also considered. Populations of seizures within patients were distinguished by seizure duration thresholds and k‐means clustering along the dimensions of seizure duration and postictal suppression duration. The effects of bursts of seizures were also considered by defining populations based on interseizure interval (ISI).ResultsSeizure duration accounted for 40% of postictal suppression duration variance, aggregated across all patients and seizures. Seizure duration accounted for more than 25% of the variance in postictal suppression duration in 2 patients and accounted for less than 25% in the remaining 7. In 3 patients, heat maps showed multiple distinct postictal patterns indicating multiple populations of seizures. When accounting for these populations, seizure duration accounted for less than 25% of the variance in postictal duration in all populations. Variance in postictal suppression duration accounted for less than 10% of ISI variance in all patients.SignificanceWe have previously demonstrated that some patients have multiple seizure populations distinguishable by seizure duration. This article shows that different seizure populations have distinct and consistent postictal behaviors. The existence of multiple populations in some patients has implications for seizure management and forecasting, whereas the distinct postictal behaviors may have implications for sudden unexpected death in epilepsy (SUDEP) prediction and prevention.

Background: Seizure prediction can increase independence and allow preventative treatment for patients with epilepsy. We present a proof-of-concept for a seizure prediction system that is accurate, fully automated, patient-specific, and tunable to an individual's needs. Methods: Intracranial electroencephalography (iEEG) data of ten patients obtained from a seizure advisory system were analyzed as part of a pseudoprospective seizure prediction study. First, a deep learning classifier was trained to distinguish between preictal and interictal signals. Second, classifier performance was tested on held-out iEEG data from all patients and benchmarked against the performance of a random predictor. Third, the prediction system was tuned so sensitivity or time in warning could be prioritized by the patient. Finally, a demonstration of the feasibility of deployment of the prediction system onto an ultra-low power neuromorphic chip for autonomous operation on a wearable device is provided. Results: The prediction system achieved mean sensitivity of 69% and mean time in warning of 27%, significantly surpassing an equivalent random predictor for all patients by 42%. Conclusion: This study demonstrates that deep learning in combination with neuromorphic hardware can provide the basis for a wearable, real-time, always-on, patient-specific seizure warning system with low power consumption and reliable long-term performance.