Sperling, Michael R.

Summary Objective Limited data are available regarding the evolution over time of the rate of sudden unexpected death in epilepsy patients (SUDEP) in drug‐resistant epilepsy. The objective is to analyze a database of 40 443 patients with epilepsy implanted with vagus nerve stimulation (VNS) therapy in the United States (from 1988 to 2012) and assess whether SUDEP rates decrease during the postimplantation follow‐up period. Methods Patient vital status was ascertained using the Centers for Disease Control and Prevention's National Death Index (NDI). An expert panel adjudicated classification of cause of deaths as SUDEP based on NDI data and available narrative descriptions of deaths. We tested the hypothesis that SUDEP rates decrease with time using the Mann‐Kendall nonparametric trend test and by comparing SUDEP rates of the first 2 years of follow‐up (years 1‐2) to longer follow‐up (years 3‐10). Results Our cohort included 277 661 person‐years of follow‐up and 3689 deaths, including 632 SUDEP. Primary analysis demonstrated a significant decrease in age‐adjusted SUDEP rate during follow‐up ( S = −27 P = .008), with rates of 2.47/1000 for years 1‐2 and 1.68/1000 for years 3‐10 (rate ratio 0.68; 95% confidence interval [CI] 0.53‐0.87; P = .002). Sensitivity analyses confirm these findings. Significance Our data suggest that SUDEP risk significantly decreases during long‐term follow‐up of patients with refractory epilepsy receiving VNS Therapy. This finding might reflect several factors, including the natural long‐term dynamic of SUDEP rate, attrition, and the impact of VNS Therapy. The role of each of these factors cannot be confirmed due to the limitations of the study.

Summary Objective A prospective multicenter phase III trial was undertaken to evaluate the performance and tolerability in the epilepsy monitoring unit ( EMU ) of an investigational wearable surface electromyographic ( sEMG ) monitoring system for the detection of generalized tonic–clonic seizures ( GTCSs ). Methods One hundred ninety‐nine patients with a history of GTCSs who were admitted to the EMU in 11 level IV epilepsy centers for clinically indicated video‐electroencephalographic monitoring also received sEMG monitoring with a wearable device that was worn on the arm over the biceps muscle. All recorded sEMG data were processed at a central site using a previously developed detection algorithm. Detected GTCSs were compared to events verified by a majority of three expert reviewers. Results For all subjects, the detection algorithm detected 35 of 46 (76%, 95% confidence interval [CI] = 0.61–0.87) of the GTCSs, with a positive predictive value ( PPV ) of 0.03 and a mean false alarm rate ( FAR ) of 2.52 per 24 h. For data recorded while the device was placed over the midline of the biceps muscle, the system detected 29 of 29 GTCSs (100%, 95% CI = 0.88–1.00), with a detection delay averaging 7.70 s, a PPV of 6.2%, and a mean FAR of 1.44 per 24 h. Mild to moderate adverse events were reported in 28% (55 of 199) of subjects and led to study withdrawal in 9% (17 of 199). These adverse events consisted mostly of skin irritation caused by the electrode patch that resolved without treatment. No serious adverse events were reported. Significance Detection of GTCSs using an sEMG monitoring device on the biceps is feasible. Proper positioning of this device is important for accuracy, and for some patients, minimizing the number of false positives may be challenging.

SummaryObjectivesInterictal epileptiform discharges (IEDs) have been linked to memory impairment, but the spatial and temporal dynamics of this relationship remain elusive. In the present study, we aim to systematically characterize the brain areas and times at which IEDs affect memory.MethodsEighty epilepsy patients participated in a delayed free recall task while undergoing intracranial electroencephalography (EEG) monitoring. We analyzed the locations and timing of IEDs relative to the behavioral data in order to measure their effects on memory.ResultsOverall IED rates did not correlate with task performance across subjects (r = 0.03, p = 0.8). However, at a finer temporal scale, within‐subject memory was negatively affected by IEDs during the encoding and recall periods of the task but not during the rest and distractor periods (p < 0.01, p < 0.001, p = 0.3, and p = 0.8, respectively). The effects of IEDs during encoding and recall were stronger in the left hemisphere than in the right (p < 0.05). Of six brain areas analyzed, IEDs in the inferior‐temporal, medial‐temporal, and parietal areas significantly affected memory (false discovery rate < 0.05).SignificanceThese findings reveal a network of brain areas sensitive to IEDs with key nodes in temporal as well as parietal lobes. They also demonstrate the time‐dependent effects of IEDs in this network on memory.

Summary Objective Epilepsy surgery is the most effective treatment for select patients with drug‐resistant epilepsy. In this article, we aim to provide an accurate understanding of the current epidemiologic characteristics of this intervention, as this knowledge is critical for guiding educational, academic, and resource priorities. Methods We profile the practice of epilepsy surgery between 1991 and 2011 in nine major epilepsy surgery centers in the United States, Germany, and Australia. Clinical, imaging, surgical, and histopathologic data were derived from the surgical databases at various centers. Results Although five of the centers performed their highest number of surgeries for mesial temporal sclerosis ( MTS ) in 1991, and three had their highest number of MTS surgeries in 2001, only one center achieved its peak number of MTS surgeries in 2011. The most productive year for MTS surgeries varied then by center; overall, the nine centers surveyed performed 48% (95% confidence interval [CI] −27.3% to −67.4%) fewer such surgeries in 2011 compared to either 1991 or 2001, whichever was higher. There was a parallel increase in the performance of surgery for nonlesional epilepsy. Further analysis of 5/9 centers showed a yearly increase of 0.6 ± 0.07% in the performance of invasive electroencephalography ( EEG ) without subsequent resections. Overall, although MTS was the main surgical substrate in 1991 and 2001 (proportion of total surgeries in study centers ranging from 33.3% to 70.2%); it occupied only 33.6% of all resections in 2011 in the context of an overall stable total surgical volume. Significance These findings highlight the major aspects of the evolution of epilepsy surgery across the past two decades in a sample of well‐established epilepsy surgery centers, and the critical current challenges of this treatment option in addressing complex epilepsy cases requiring detailed evaluations. Possible causes and implications of these findings are discussed.

Summary Objective Patients with suspected mesial temporal lobe ( MTL ) epilepsy typically undergo inpatient video–electroencephalography ( EEG ) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography ( EC oG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory EC oG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. Methods Ambulatory EC oG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal EC oG activity. EC oG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. Results Eighty‐two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0–376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. Significance About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory EC oG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory EC oG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video‐ EEG monitoring, and can contribute to treatment decisions.