Citations

AbstractTemporal lobe epilepsy is the most common form of focal epilepsy and is frequently resistant to antiseizure medication. Non‐invasive biomarkers are crucial when resective epilepsy surgery is considered in order to guide diagnostic work‐up and management. Interictal epileptiform discharges, when concordant with ictal EEG recording and a focal abnormality on functional imaging or anatomic MRI in patients with temporal lobe epilepsy, portend a favorable outcome with resective or ablative surgery. An interictal nonepileptiform feature on EEG believed to have the same localizing potential as epileptiform discharges is temporal intermittent rhythmic delta activity (TIRDA). The precise localization of TIRDA has been a subject of debate, but has been associated with seizures that arise from the temporal region. We report a 64‐year‐old female who underwent unsuccessful right anterior temporal lobectomy for drug‐resistant focal epilepsy, suspected to originate from the right temporal lobe. Subsequent video‐EEG monitoring revealed right, greater than left, TIRDA and interictal epileptiform discharges arising from the temporal regions bilaterally, despite a generous temporal lobectomy demonstrated by brain MRI. Further, using EEG source localization, we identified TIRDA using scalp EEG in sensor space, localized to the ipsilateral orbitofrontal region. We discuss the proposed localization of TIRDA in this case and address the importance of characterizing TIRDA in the presurgical evaluation of patients with epilepsy.

AbstractWith continued advancement in computational technologies, the analysis of electroencephalography (EEG) has shifted from pure visual analysis to a noninvasive computational technique called EEG source imaging (ESI), which involves mathematical modeling of dipolar and distributed sources of a given scalp EEG pattern. ESI is a noninvasive phase I test for presurgical localization of the seizure onset zone in focal epilepsy. It is a relatively inexpensive modality, as it leverages scalp EEG and magnetic resonance imaging (MRI) data already collected typically during presurgical evaluation. With an adequate number of electrodes and combined with patient‐specific MRI‐based head models, ESI has proven to be a valuable and accurate clinical diagnostic tool for localizing the epileptogenic zone. Despite its advantages, however, ESI is routinely used at only a minority of epilepsy centers. This paper reviews the current evidence and practical fundamentals for using ESI of interictal and ictal epileptic activity during the presurgical evaluation of drug‐resistant patients. We identify common errors in processing and interpreting ESI studies, describe the differences in approach needed for localizing interictal and ictal EEG discharges through practical examples, and describe best practices for optimizing the diagnostic information available from these studies.

AbstractTo 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 Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioural inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behaviour and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a handheld device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from nine humans and eight canines with epilepsy, and then implemented prospectively in out-of-sample testing in two pet canines and four humans with drug-resistant epilepsy living in their natural environments. Accurate seizure diaries are needed as the primary clinical outcome measure of epilepsy therapy and to guide brain-stimulation optimization. The brain co-processor system described here enables tracking interictal epileptiform spikes, seizures and correlation with patient behavioural reports. In the future, correlation of spikes and seizures with behaviour will allow more detailed investigation of the clinical impact of spikes and seizures on patients.

Abstract 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 Objective Anterior temporal lobectomy (ATL) is a widely performed and successful intervention for drug‐resistant temporal lobe epilepsy (TLE). However, up to one third of patients experience seizure recurrence within 1 year after ATL. Despite the extensive literature on presurgical electroencephalography (EEG) and magnetic resonance imaging (MRI) abnormalities to prognosticate seizure freedom following ATL, the value of quantitative analysis of visually reviewed normal interictal EEG in such prognostication remains unclear. In this retrospective multicenter study, we investigate whether machine learning analysis of normal interictal scalp EEG studies can inform the prediction of postoperative seizure freedom outcomes in patients who have undergone ATL. Methods We analyzed normal presurgical scalp EEG recordings from 41 Mayo Clinic (MC) and 23 Cleveland Clinic (CC) patients. We used an unbiased automated algorithm to extract eyes closed awake epochs from scalp EEG studies that were free of any epileptiform activity and then extracted spectral EEG features representing (a) spectral power and (b) interhemispheric spectral coherence in frequencies between 1 and 25 Hz across several brain regions. We analyzed the differences between the seizure‐free and non–seizure‐free patients and employed a Naïve Bayes classifier using multiple spectral features to predict surgery outcomes. We trained the classifier using a leave‐one‐patient‐out cross‐validation scheme within the MC data set and then tested using the out‐of‐sample CC data set. Finally, we compared the predictive performance of normal scalp EEG‐derived features against MRI abnormalities. Results We found that several spectral power and coherence features showed significant differences correlated with surgical outcomes and that they were most pronounced in the 10–25 Hz range. The Naïve Bayes classification based on those features predicted 1‐year seizure freedom following ATL with area under the curve (AUC) values of 0.78 and 0.76 for the MC and CC data sets, respectively. Subsequent analyses revealed that (a) interhemispheric spectral coherence features in the 10–25 Hz range provided better predictability than other combinations and (b) normal scalp EEG‐derived features provided superior and potentially distinct predictive value when compared with MRI abnormalities (>10% higher F1 score). Significance These results support that quantitative analysis of even a normal presurgical scalp EEG may help prognosticate seizure freedom following ATL in patients with drug‐resistant TLE. Although the mechanism for this result is not known, the scalp EEG spectral and coherence properties predicting seizure freedom may represent activity arising from the neocortex or the networks responsible for temporal lobe seizure generation within vs outside the margins of an ATL.

Abstract 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.

AbstractBackgroundProgressive dysexecutive syndrome (dAD) is an atypical presentation of early onset Alzheimer’s disease (AD) with increased frontal and parietal region hypometabolism on FDG‐PET imaging compared to classic amnestic AD. We compared electroencephalogram (EEG) and FDG‐PET in dAD patients to determine if there was a correlation between EEG spectral activity and standard uptake value ratios (SUVR) in those regions.MethodFDG‐PET and resting state scalp EEG were obtained on AD‐biomarker confirmed, behavioral neurologist diagnosed cases of dAD (n = 11). We isolated awake‐eyes‐closed segments (mean duration: 113s, median:118s, range: 58‐138s) of each EEG and calculated the relative power of delta, theta, alpha, beta, and gamma bands within a wideband of 0.5‐40 Hz. In bilateral frontal and parietal regions, we averaged select channels across 6 to 14 10‐second windows per subject (fig.1). We evaluated the correlation between relative band powers and SUVRs of the regions by linear regression analysis.ResultThere is a strong negative correlation (R2 = 0.54, p < 0.01) between alpha band relative power and SUVR in bilateral frontal regions (fig 2). Delta band relative power showed a strong positive correlation (R2 = 0.54, p < 0.05) with SUVR in the left frontal region. A positive trend was noted in the delta band in the right frontal region but did not reach statistical significance. Beta band relative power was negatively correlated with frontal region SUVR bilaterally, but only the left side reached statistical significance. These findings remained significant after multiple comparisons correction. No statistically significant correlations were noted in the parietal regions. Exploratory analysis revealed negative correlations between alpha bands and temporal region SUVRs bilaterally.ConclusionIn this small sample of selected individuals with dysexecutive AD, we report a strong correlation between EEG relative spectral power and PET regional SUVR in multiple EEG frequency bands and brain regions. In the bilateral frontal regions, slower delta frequencies and faster alpha and beta frequencies were associated with lower FDG‐PET signal. Future studies are needed to determine if this spectral power pattern and other EEG properties of dAD differ from other clinical dementia phenotypes and its clinical significance.

Abstract EEG source imaging is becoming widely used for the evaluation of medically refractory focal epilepsy. The validity of EEG source imaging has been established in several studies comparing source imaging to the surgical resection cavity and subsequent seizure freedom. We present a cohort of 87 patients and compare EEG source imaging of both ictal and interictal scalp EEG to the seizure onset zone on intracranial EEG. Concordance of EEG source imaging with intracranial EEG was determined on a sublobar level and was quantified by measuring the distance between the source imaging result and the centroid of the active seizure onset zone electrodes. The EEG source imaging results of a subgroup of 26 patients with high density 76-channel EEG were compared with the localization of three experienced epileptologists. Of 87 patients, 95% had at least one analysis concordant with intracranial EEG and 74% had complete concordance. There was a higher rate of complete concordance in temporal lobe epilepsy compared to extratemporal (89.3 and 62.8%, respectively, P = 0.015). Of the total 282 analyses performed on this cohort, higher concordance was also seen in temporal discharges (95%) compared to extratemporal (77%) (P = 0.0012), but no difference was seen comparing high-density EEG with standard (32-channel) EEG. Subgroup analysis of ictal waveforms showed greater concordance for ictal spiking, compared with rhythmic activity, paroxysmal fast activity, or obscured onset. Median distances from the dipole and maximum distributed source to a centroid of seizure onset zone electrodes were 30.0 and 32.5 mm, respectively, and the median distances from dipole and maximum distributed source to nearest seizure onset zone electrode were 22.8 and 21.7, respectively. There were significantly shorter distances in ictal spiking. There were shorter distances in patients with Engel Class 1 outcome from surgical resection compared to patients with worse outcomes. For the subgroup of 26 high-density EEG patients, EEG source localization had a significantly higher concordance (92% versus 65%), sensitivity (57% versus 35%) and positive predictive value (60% versus 36%) compared with epileptologist localization. Our study demonstrates good concordance between ictal and interictal source imaging and intracranial EEG. Temporal lobe discharges have higher concordance rates than extratemporal discharges. Importantly, this study shows that source imaging has greater agreement with intracranial EEG than visual review alone, supporting its role in surgical planning.