Englot, Dario J.

Abstract Objective There is a need to develop a comprehensive, formalized, and globally applicable epilepsy surgery curriculum in order to help standardize the quality of epilepsy surgery practice in the world. Methods The Epilepsy Surgery Educational Task Force of the ILAE developed a competency‐based epilepsy surgery educational curriculum comprised of four domains: Diagnosis, Counseling, Pre‐surgical Work‐up, and Surgical Techniques. To evaluate this educational curriculum, a survey questionnaire consisting of 11 items was sent out for feedback to ILAE and IESS members. The survey questionnaire asked respondents to rate the degree of importance of each competency on a five‐point scale that ranged from “extremely important” to “not at all important” and provided space for free text comments. All competencies that were rated as “slightly important” or “somewhat important” by more than 10% of responders, as well as all free text feedback comments, were fully reviewed, and the final curriculum was adjusted accordingly. Results One hundred and twenty‐two responses ( n = 122) were submitted by the ILAE and IESS communities. Seventy‐one percent (71.9%) of the responses came from neurosurgeons of varied experience and training levels. Ninety‐four percent (94.4%) of responders stated that they “support a curriculum to determine the competency of neurosurgeons participating in the care of people with epilepsy in my country,” and 94.3% confirmed that they “would be interested in taking or would recommend an ILAE course based on these competencies, that would provide an ILAE certificate of completion.” Relevant changes within the curriculum were made based on feedback. Significance The newly developed ILAE comprehensive epilepsy surgery educational curriculum has a high level of support from neurosurgeons and neurologists around the world and shows potential for broad acceptance and implementation.

Abstract How do brain networks limit seizure activity? In the interictal suppression hypothesis, we recently postulated that high inward connectivity to seizure onset zones (SOZs) from non-involved zones (NIZs) is a sign of broader network suppression. If broad networks appear to be responsible for interictal SOZ suppression, what changes during seizure initiation, spread and termination? For patients with drug-resistant epilepsy, intracranial monitoring offers a view into the electrographic networks that organize around and in response to the SOZ. In this manuscript, we investigate network dynamics in the peri-ictal periods to assess possible mechanisms of seizure suppression and the consequences of this suppression being overwhelmed. Peri-ictal network dynamics were derived from stereo electroencephalography recordings from 75 patients with drug-resistant epilepsy undergoing presurgical evaluation at Vanderbilt University Medical Center. We computed directed connectivity from 5 s windows in the periods between, immediately before, during and after 668 seizures. We aligned connectivity matrices across seizures and patients, then calculated net connectivity changes from the SOZ, propagative zone and NIZ. Across all seizure types, we observed two phases: a rapid increase in directed communication towards the SOZ, followed by a collapse in network connectivity. During the first phase, SOZs could be distinguished from all other regions (one-way ANOVA, P = 8.32 × 10−19–2.22 × 10−7). In the second phase and post-ictal period, SOZ inward connectivity decreased yet remained distinct (one-way ANOVA, P = 2.58 × 10−10–1.66 × 10−2). NIZs appeared to drive increased SOZ connectivity while intra-NIZ connectivity decreased concordantly. Stratifying by seizure subtype, we found that consciousness-impairing seizures decrease inward connectivity from the NIZ earlier than consciousness-sparing seizures (one-way ANOVA, P < 0.01 after false discovery correction). Tracking network reorganization against a surrogate for seizure involvement highlighted a possible antagonism between seizure propagation and the ability of the NIZ to maintain high connectivity to the SOZ. Finally, we found that inclusion of peri-ictal connectivity improved the accuracy of SOZ classification from previous models to a combined area under the curve of 93%. Overall, NIZs appear actively to increase inhibitory signaling towards the SOZ during seizure onset, possibly to thwart seizure activity. Although inhibition appears insufficient to prevent seizure onset, the inability to restrict seizure propagation might contribute to loss of consciousness during larger seizures. Dynamic connectivity patterns uncovered in this work might: (i) facilitate accurate delineation of surgical targets in focal epilepsy; (ii) reveal why interictal suppression of SOZs might be insufficient to prevent all seizures; and (iii) provide insight into mechanisms of loss of consciousness during certain seizures.

AbstractObjectiveEpilepsy is a debilitating disorder affecting more than 50 million people worldwide, and one third of patients continue to have seizures despite maximal medical management. If patients' seizures localize to a discrete brain region, termed a seizure onset zone, resection may be curative. Localization is often confirmed with stereotactic electroencephalography; however, this may require patients to stay in the hospital for weeks to capture spontaneous seizures. Automated localization of seizure onset zones could therefore improve presurgical evaluation and decrease morbidity.MethodsUsing more than 1 000 000 interictal stereotactic electroencephalography segments collected from 78 patients, we performed five‐fold cross‐validation and testing on a multichannel, multiscale, one‐dimensional convolutional neural network to classify seizure onset zones.ResultsAcross held‐out test sets, our models achieved a seizure onset zone classification sensitivity of .702 (95% confidence interval [CI] = .549–.805), specificity of .741 (95% CI = .652–.835), and accuracy of .738 (95% CI = .687–.795), which was significantly better than models trained on random labels. The models performed well across the entire brain, with top five region performance demonstrating accuracies between 70.0% and 88.4%. When split by outcomes, the models performed significantly better on patients with favorable Engel outcomes after resection or who were responsive neurostimulation responders. Finally, SHAP (Shapley Additive Explanation) value analysis on median‐normalized input data assigned consistently high feature importance to interictal spikes and large deflections, whereas similar analyses on histogram‐equalized data revealed differences in feature importance assignments to low‐amplitude segments.SignificanceThis work serves as evidence that deep learning on brief interictal intracranial data can classify seizure onset zones across the brain. Furthermore, our findings corroborate current understandings of interictal epileptiform discharges and may help uncover novel interictal morphologies. Clinical application of our models may reduce dependence on recorded seizures for localization and shorten presurgical evaluation time for drug‐resistant epilepsy patients, reducing patient morbidity and hospital costs.

Abstract Up to 80% of the world's population with epilepsy lives in low and middle‐income countries. Around one‐third of these patients will have drug‐resistant epilepsy, for which epilepsy surgery is an option. Unfortunately, many of these regions, as well as some more developed nations, lack sufficient epilepsy surgery units and trained neurosurgeons. With this in mind, the International League Against Epilepsy (ILAE) formed the Epilepsy Surgery Education Taskforce to address the shortage of further educational opportunities for surgeons and neurologists and to promote the creation of more epilepsy surgery units around the world. In this article, we publish our findings from a web‐based international survey, in which we investigated the global distribution and experience of neurosurgeons who perform epilepsy surgery, their educational paths, and opinions on the further need for epilepsy surgery education, as well as the resources available to them. We report a detailed analysis of the 202 survey replies received from 35 different countries across six continents. The lack of adequate numbers of epilepsy surgery units in the Southern Hemisphere is notable, and the aim of this task force with other ILAE committees, is to improve access to epilepsy surgery for patients and to enhance training for their health care providers.

AbstractObjectiveSummarize the current evidence on efficacy and tolerability of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) through a systematic review and meta‐analysis.MethodsWe followed the Preferred Reporting Items of Systematic reviews and Meta‐Analyses reporting standards and searched Ovid Medline, Ovid Embase, and the Cochrane Central Register of Controlled Trials. We included published randomized controlled trials (RCTs) and their corresponding open‐label extension studies, as well as prospective case series, with ≥20 participants (excluding studies limited to children). Our primary outcome was the mean (or median, when unavailable) percentage decrease in frequency, as compared to baseline, of all epileptic seizures at last follow‐up. Secondary outcomes included the proportion of treatment responders and proportion with seizure freedom.ResultsWe identified 30 eligible studies, six of which were RCTs. At long‐term follow‐up (mean 1.3 years), five observational studies for VNS reported a pooled mean percentage decrease in seizure frequency of 34.7% (95% confidence interval [CI]: −5.1, 74.5). In the open‐label extension studies for RNS, the median seizure reduction was 53%, 66%, and 75% at 2, 5, and 9 years of follow‐up, respectively. For DBS, the median reduction was 56%, 65%, and 75% at 2, 5, and 7 years, respectively. The proportion of individuals with seizure freedom at last follow‐up increased significantly over time for DBS and RNS, whereas a positive trend was observed for VNS. Quality of life was improved in all modalities. The most common complications included hoarseness, and cough and throat pain for VNS and implant site pain, headache, and dysesthesia for DBS and RNS.SignificanceNeurostimulation modalities are an effective treatment option for drug‐resistant epilepsy, with improving outcomes over time and few major complications. Seizure‐reduction rates among the three therapies were similar during the initial blinded phase. Recent long‐term follow‐up studies are encouraging for RNS and DBS but are lacking for VNS.