Worrell, Gregory A.

OBJECTIVETemporal lobectomy is a well-established treatment modality for the management of medically refractory epilepsy in appropriately selected patients. The aim of this study was to assess 30-day morbidity and mortality after temporal lobectomy in cases registered in a national database.METHODSA retrospective cohort analysis was conducted using a multiinstitutional surgical registry compiled between 2006 and 2014. The authors identified patients who underwent anterior temporal lobectomy and/or amygdalohippocampectomy for a primary diagnosis of intractable epilepsy. Univariate and multivariable analyses with regard to patient demographics, comorbidities, operative characteristics, and 30-day outcomes were applied.RESULTSA total of 216 patients were included in the study. The median age was 38 years and 46% of patients were male. The median length of stay was 3 days and the 30-day mortality rate was 1.4%. Fourteen patients (6.5%) developed at least one major complication. Return to the operating room was observed in 7 patients (3.2%). Readmission within 30 days and discharge to a location other than home were available for 2011–2014 (n = 155) and occurred in 11% and 10.3% of patients, respectively. Multivariable regression analysis revealed that increasing age was an independent predictor of discharge disposition other than home and that male sex was a significant risk factor for the development of a major complication. Interestingly, the presence of the attending neurosurgeon and a resident during the procedure was significantly associated with decreased odds of prolonged length of stay (i.e., > 75th percentile [5 days]) and discharge to a location other than home.CONCLUSIONSUsing a multiinstitutional surgical registry, 30-day outcome data after temporal lobectomy for medically intractable epilepsy demonstrates a mortality rate of 1.4%, a major complication rate of 6.5%, and a readmission rate of 11%. Temporal lobectomy is an extremely effective therapy for seizures originating there—however, surgical intervention must be weighed against its morbidity and mortality outcomes.

Summary Objective Technology for localizing epileptogenic brain regions plays a central role in surgical planning. Recent improvements in acquisition and electrode technology have revealed that high‐frequency oscillations ( HFO s) within the 80–500 Hz frequency range provide the neurophysiologist with new information about the extent of the epileptogenic tissue in addition to ictal and interictal lower frequency events. Nevertheless, two decades after their discovery there remain questions about HFO s as biomarkers of epileptogenic brain and there use in clinical practice. Methods In this review, we provide practical, technical guidance for epileptologists and clinical researchers on recording, evaluation, and interpretation of ripples, fast ripples, and very high‐frequency oscillations. Results We emphasize the importance of low noise recording to minimize artifacts. HFO analysis, either visual or with automatic detection methods, of high fidelity recordings can still be challenging because of various artifacts including muscle, movement, and filtering. Magnetoencephalography and intracranial electroencephalography ( iEEG) recordings are subject to the same artifacts. Significance High‐frequency oscillations are promising new biomarkers in epilepsy. This review provides interested researchers and clinicians with a review of current state of the art of recording and identification and potential challenges to clinical translation.

SummaryObjectiveEvaluate the seizure‐reduction response and safety of mesial temporal lobe (MTL) brain‐responsive stimulation in adults with medically intractable partial‐onset seizures of mesial temporal lobe origin.MethodsSubjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain‐responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2–6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events.ResultsThere were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy‐six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow‐up was 6.1 ± (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty‐nine percent of subjects experienced at least one seizure‐free period of 6 months or longer, and 15% experienced at least one seizure‐free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device‐related adverse event was soft tissue implant‐site infection (overall rate, including events categorized as device‐related, uncertain, or not device‐related: 0.03 per implant year, which is not greater than with other neurostimulation devices).SignificanceBrain‐responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

SummaryObjectiveEvaluate the seizure‐reduction response and safety of brain‐responsive stimulation in adults with medically intractable partial‐onset seizures of neocortical origin.MethodsPatients with partial seizures of neocortical origin were identified from prospective clinical trials of a brain‐responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2–6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Additional analyses considered safety and seizure reduction according to lobe and functional area (e.g., eloquent cortex) of seizure onset.ResultsThere were 126 patients with seizures of neocortical onset. The average follow‐up was 6.1 implant years. The median percent seizure reduction was 70% in patients with frontal and parietal seizure onsets, 58% in those with temporal neocortical onsets, and 51% in those with multilobar onsets (last observation carried forward [LOCF] analysis). Twenty‐six percent of patients experienced at least one seizure‐free period of 6 months or longer and 14% experienced at least one seizure‐free period of 1 year or longer. Patients with lesions on magnetic resonance imaging (MRI; 77% reduction, LOCF) and those with normal MRI findings (45% reduction, LOCF) benefitted, although the treatment response was more robust in patients with an MRI lesion (p = 0.02, generalized estimating equation [GEE]). There were no differences in the seizure reduction in patients with and without prior epilepsy surgery or vagus nerve stimulation. Stimulation parameters used for treatment did not cause acute or chronic neurologic deficits, even in eloquent cortical areas. The rates of infection (0.017 per patient implant year) and perioperative hemorrhage (0.8%) were not greater than with other neurostimulation devices.SignificanceBrain‐responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including adults with seizures of neocortical onset, and those with onsets from eloquent cortex.

SummaryTwo patients who shared similar presenting clinical features of anterograde and retrograde autobiographical amnesia typical of transient epileptic amnesia (TEA) underwent prolonged video electroencephalogram (VEEG) monitoring and were found to have sleep‐activated epileptiform activity and frequent subclinical bitemporal seizures predominantly during sleep. Case 1 is a 59‐year‐old woman whose presenting complaint was memory impairment. Over 18 months, she had three distinct 8‐h‐long episodes of confusion and disorientation with persistent anterograde and retrograde autobiographical amnesia. VEEG recorded frequent interictal bitemporal sharp waves confined to sleep, and 14 subclinical seizures, also mostly during sleep. Case 2 is a 50‐year‐old woman with known focal epilepsy also presented with memory complaints. Over the course of 1 year, she had two discrete 2‐h‐long episodes of amnesia, with ongoing anterograde and retrograde autobiographical amnesia. VEEG recorded independent bitemporal sharp waves, and 14 subclinical seizures during sleep and drowsiness. Memory impairment improved in both patients with successful treatment of their seizures. Although the etiology of accelerated long‐term forgetting (ALF) and remote memory impairment (RMI) in transient epileptic amnesia (TEA) is unknown, these cases suggest frequent sleep‐related seizures may contribute, and they highlight the importance of video‐EEG monitoring.

Abstract Objective . Automated behavioral state classification can benefit next generation implantable epilepsy devices. In this study we explored the feasibility of automated awake (AW) and slow wave sleep (SWS) classification using wide bandwidth intracranial EEG (iEEG) in patients undergoing evaluation for epilepsy surgery. Approach . Data from seven patients (age 34 ± 12 , 4 women) who underwent intracranial depth electrode implantation for iEEG monitoring were included. Spectral power features (0.1–600 Hz) spanning several frequency bands from a single electrode were used to train and test a support vector machine classifier. Main results . Classification accuracy of 97.8 ± 0.3% (normal tissue) and 89.4 ± 0.8% (epileptic tissue) across seven subjects using multiple spectral power features from a single electrode was achieved. Spectral power features from electrodes placed in normal temporal neocortex were found to be more useful (accuracy 90.8 ± 0.8%) for sleep-wake state classification than electrodes located in normal hippocampus (87.1 ± 1.6%). Spectral power in high frequency band features (Ripple (80–250 Hz), Fast Ripple (250–600 Hz)) showed comparable performance for AW and SWS classification as the best performing Berger bands (Alpha, Beta, low Gamma) with accuracy ⩾90% using a single electrode contact and single spectral feature. Significance . Automated classification of wake and SWS should prove useful for future implantable epilepsy devices with limited computational power, memory, and number of electrodes. Applications include quantifying patient sleep patterns and behavioral state dependent detection, prediction, and electrical stimulation therapies.

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.

SummaryObjectiveLocal field potentials (LFPs) arise from synchronous activation of millions of neurons, producing seemingly consistent waveform shapes and relative synchrony across electrodes. Interictal spikes (IISs) are LFPs associated with epilepsy that are commonly used to guide surgical resection. Recently, changes in neuronal firing patterns observed in the minutes preceding seizure onset were found to be reactivated during postseizure sleep, a process called seizure‐related consolidation (SRC), due to similarities with learning‐related consolidation. Because IISs arise from summed neural activity, we hypothesized that changes in IIS shape and relative synchrony would be observed in the minutes preceding seizure onset and would be reactivated preferentially during postseizure slow‐wave sleep (SWS).MethodsScalp and intracranial recordings were obtained continuously across multiple days from clinical macroelectrodes implanted in patients undergoing treatment for intractable epilepsy. Data from scalp electrodes were used to stage sleep. Data from intracranial electrodes were used to detect IISs using a previously established algorithm. Partial correlations were computed for sleep and wake periods before and after seizures as a function of correlations observed in the minutes preceding seizures. Magnetic resonance imaging (MRI) and computed tomography (CT) scans were co‐registered with electroencephalography (EEG) to determine the location of the seizure‐onset zone (SOZ).ResultsChanges in IIS shape and relative synchrony were observed on a subset of macroelectrodes minutes before seizure onset, and these changes were reactivated preferentially during postseizure SWS. Changes in synchrony were greatest for pairs of electrodes where at least one electrode was located in the SOZ.SignificanceThese data suggest preseizure changes in neural activity and their subsequent reactivation occur across a broad spatiotemporal scale: from single neurons to LFPs, both within and outside the SOZ. The preferential reactivation of seizure‐related changes in IISs during postseizure SWS adds to a growing body of literature suggesting that pathologic neural processes may utilize physiologic mechanisms of synaptic plasticity.