Multiple Sclerosis is a chronic inflammatory disease, affecting the Central Nervous System and leading to irreversible neurological damage, such as long term functional impairment and disability. It has no cure and the symptoms vary widely, depending on the affected regions, amount of damage, and the ability to activate compensatory mechanisms, which constitutes a challenge to evaluate and predict its course. Additionally, relapsing-remitting patients can evolve its course into a secondary progressive, characterized by a slow progression of disability independent of relapses. With clinical information from Multiple Sclerosis patients, we developed a machine learning exploration framework concerning this disease evolution, more specifically to obtain three predictions: one on conversion to secondary progressive course and two on disease severity with rapid accumulation of disability, concerning the 6th and 10th years of progression. For the first case, the best results were obtained within two years: AUC=$$0.86\pm 0.07$$ 0.86 ± 0.07 , sensitivity=$$0.76\pm 0.14$$ 0.76 ± 0.14 and specificity=$$0.77\pm 0.05$$ 0.77 ± 0.05 ; and for the second, the best results were obtained for the 6th year of progression, also within two years: AUC=$$0.89\pm 0.03$$ 0.89 ± 0.03 , sensitivity=$$0.84\pm 0.11$$ 0.84 ± 0.11 , and specificity=$$0.81\pm 0.05$$ 0.81 ± 0.05 . The Expanded Disability Status Scale value, the majority of functional systems, affected functions during relapses, and age at onset were described as the most predictive features. These results demonstrate the possibility of predicting Multiple Sclerosis progression by using machine learning, which may help to understand this disease’s dynamics and thus, advise physicians on medication intake.

Seizure prediction may improve the quality of life of patients suffering from drug-resistant epilepsy, which accounts for about 30% of the total epileptic patients. The pre-ictal period determination, characterized by a transitional stage between normal brain activity and seizure, is a critical step. Past approaches failed to attain real-world applicability due to lack of generalization capacity. More recently, deep learning techniques may outperform traditional classifiers and handle time dependencies. However, despite the existing efforts for providing interpretable insights, clinicians may not be willing to make high-stake decisions based on them. Furthermore, a disadvantageous aspect of the more usual seizure prediction pipeline is its modularity and significant independence between stages. An alternative could be the construction of a search algorithm that, while considering pipeline stages’ synergy, fine-tunes the selection of a reduced set of features that are widely used in the literature and computationally efficient. With extracranial recordings from 19 patients suffering from temporal-lobe seizures, we developed a patient-specific evolutionary optimization strategy, aiming to generate the optimal set of features for seizure prediction with a logistic regression classifier, which was tested prospectively in a total of 49 seizures and 710 h of continuous recording and performed above chance for 32% of patients, using a surrogate predictor. These results demonstrate the hypothesis of pre-ictal period identification without the loss of interpretability, which may help understanding brain dynamics leading to seizures and improve prediction algorithms.

Seizure prediction might be the solution to tackle the apparent unpredictability of seizures in patients with drug-resistant epilepsy, which comprise about a third of all patients with epilepsy. Designing seizure prediction models involves defining the pre-ictal period, a transition stage between inter-ictal brain activity and the seizure discharge. This period is typically a fixed interval, with some recent studies reporting the evaluation of different patient-specific pre-ictal intervals. Recently, researchers have aimed to determine the pre-ictal period, a transition stage between regular brain activity and a seizure. Authors have been using deep learning models given the ability of such models to automatically perform pre-processing, feature extraction, classification, and handling temporal and spatial dependencies. As these approaches create black-box models, clinicians may not have sufficient trust to use them in high-stake decisions. By considering these problems, we developed an evolutionary seizure prediction model that identifies the best set of features while automatically searching for the pre-ictal period and accounting for patient comfort. This methodology provides patient-specific interpretable insights, which might contribute to a better understanding of seizure generation processes and explain the algorithm’s decisions. We tested our methodology on 238 seizures and 3687 h of continuous data, recorded on scalp recordings from 93 patients with several types of focal and generalised epilepsies. We compared the results with a seizure surrogate predictor and obtained a performance above chance for 32% patients. We also compared our results with a control method based on the standard machine learning pipeline (pre-processing, feature extraction, classifier training, and post-processing), where the control marginally outperformed our approach by validating 35% of the patients. In total, 54 patients performed above chance for at least one method: our methodology or the control one. Of these 54 patients, 21 ($$\approx$$ ≈ 38%) were solely validated by our methodology, while 24 ($$\approx$$ ≈ 44%) were only validated by the control method. These findings may evidence the need for different methodologies concerning different patients.

Electrocardiogram (ECG) recordings, lasting hours before epileptic seizures, have been studied in the search for evidence of the existence of a preictal interval that follows a normal ECG trace and precedes the seizure’s clinical manifestation. The preictal interval has not yet been clinically parametrized. Furthermore, the duration of this interval varies for seizures both among patients and from the same patient. In this study, we performed a heart rate variability (HRV) analysis to investigate the discriminative power of the features of HRV in the identification of the preictal interval. HRV information extracted from the linear time and frequency domains as well as from nonlinear dynamics were analysed. We inspected data from 238 temporal lobe seizures recorded from 41 patients with drug-resistant epilepsy from the EPILEPSIAE database. Unsupervised methods were applied to the HRV feature dataset, thus leading to a new perspective in preictal interval characterization. Distinguishable preictal behaviour was exhibited by 41% of the seizures and 90% of the patients. Half of the preictal intervals were identified in the 40 min before seizure onset. The results demonstrate the potential of applying clustering methods to HRV features to deepen the current understanding of the preictal state.

No abstract

Seizure prediction may be the solution for epileptic patients whose drugs and surgery do not control seizures. Despite 46 years of research, few devices/systems underwent clinical trials and/or are commercialized, where the most recent state‐of‐the‐art approaches, as neural networks models, are not used to their full potential. The latter demonstrates the existence of social barriers to new methodologies due to data bias, patient safety, and legislation compliance. In the form of literature review, we performed a qualitative study to analyze the seizure prediction ecosystem to find these social barriers. With the Grounded Theory, we draw hypotheses from data, while with the Actor‐Network Theory we considered that technology shapes social configurations and interests, being fundamental in healthcare. We obtained a social network that describes the ecosystem and propose research guidelines aiming at clinical acceptance. Our most relevant conclusion is the need for model explainability, but not necessarily intrinsically interpretable models, for the case of seizure prediction. Accordingly, we argue that it is possible to develop robust prediction models, including black‐box systems to some extent, while avoiding data bias, ensuring patient safety, and still complying with legislation, if they can deliver human‐ comprehensible explanations. Due to skepticism and patient safety reasons, many authors advocate the use of transparent models which may limit their performance and potential. Our study highlights a possible path, by using model explainability, on how to overcome these barriers while allowing the use of more computationally robust models.

The development of seizure prediction models is often based on long-term scalp electroencephalograms (EEGs) since they capture brain electrical activity, are non-invasive, and come at a relatively low-cost. However, they suffer from major shortcomings. First, long-term EEG is usually highly contaminated with artefacts. Second, changes in the EEG signal over long intervals, known as concept drift, are often neglected. We evaluate the influence of these problems on deep neural networks using EEG time series and on shallow neural networks using widely-used EEG features. Our patient-specific prediction models were tested in 1577 hours of continuous EEG, containing 91 seizures from 41 patients with temporal lobe epilepsy who were undergoing pre-surgical monitoring. Our results showed that cleaning EEG data, using a previously developed artefact removal method based on deep convolutional neural networks, improved prediction performance. We also found that retraining the models over time reduced false predictions. Furthermore, the results show that although deep neural networks processing EEG time series are less susceptible to false alarms, they may need more data to surpass feature-based methods. These findings highlight the importance of robust data denoising and periodic adaptation of seizure prediction models.

Typical seizure prediction models aim at discriminating interictal brain activity from pre-seizure electrographic patterns. Given the lack of a preictal clinical definition, a fixed interval is widely used to develop these models. Recent studies reporting preictal interval selection among a range of fixed intervals show inter- and intra-patient preictal interval variability, possibly reflecting the heterogeneity of the seizure generation process. Obtaining accurate labels of the preictal interval can be used to train supervised prediction models and, hence, avoid setting a fixed preictal interval for all seizures within the same patient. Unsupervised learning methods hold great promise for exploring preictal alterations on a seizure-specific scale. Multivariate and univariate linear and nonlinear features were extracted from scalp electroencephalography (EEG) signals collected from 41 patients with drug-resistant epilepsy undergoing presurgical monitoring. Nonlinear dimensionality reduction was performed for each group of features and each of the 226 seizures. We applied different clustering methods in searching for preictal clusters located until 2 h before the seizure onset. We identified preictal patterns in 90% of patients and 51% of the visually inspected seizures. The preictal clusters manifested a seizure-specific profile with varying duration (22.9 ± 21.0 min) and starting time before seizure onset (47.6 ± 27.3 min). Searching for preictal patterns on the EEG trace using unsupervised methods showed that it is possible to identify seizure-specific preictal signatures for some patients and some seizures within the same patient.