The influence of risk factors, biomarkers and care settings on SUDEP counseling.

Although sudden unexpected death in epilepsy (SUDEP) is the most feared epilepsy outcome, there is a dearth of SUDEP counseling provided by neurologists. This may reflect limited time, as well as the lack of guidance on the timing and structure for counseling. We evaluated records from SUDEP cases to examine frequency of inpatient and outpatient SUDEP counseling, and whether counseling practices were influenced by risk factors and biomarkers, such as post-ictal generalized EEG suppression (PGES). We found a striking lack of SUDEP counseling despite modifiable SUDEP risk factors; counseling was limited to outpatients despite many patients having inpatient visits within a year of SUDEP. PGES was inconsistently documented and was never included in counseling. There is an opportunity to greatly improve SUDEP counseling by utilizing inpatient settings and prompting algorithms incorporating risk factors and biomarkers.

Association between postictal EEG suppression, postictal autonomic dysfunction, and sudden unexpected death in epilepsy: Evidence from intracranial EEG.

OBJECTIVE: The association between postictal electroencephalogram (EEG) suppression (PES), autonomic dysfunction, and Sudden Unexpected Death in Epilepsy (SUDEP) remains poorly understood. We compared PES on simultaneous intracranial and scalp-EEG and evaluated the association of PES with postictal heart rate variability (HRV) and SUDEP outcome. METHODS: Convulsive seizures were analyzed in patients with drug-resistant epilepsy at 5 centers. Intracranial PES was quantified using the Hilbert transform. HRV was quantified using root mean square of successive differences of interbeat intervals, low-frequency to high-frequency power ratio, and RR-intervals. RESULTS: There were 64 seizures from 63 patients without SUDEP and 11 seizures from 6 SUDEP patients. PES occurred in 99% and 87% of seizures on intracranial-EEG and scalp-EEG, respectively. Mean PES duration in intracranial and scalp-EEG was similar. Intracranial PES was regional (<90% of channels) in 46% of seizures; scalp PES was generalized in all seizures. Generalized PES showed greater decrease in postictal parasympathetic activity than regional PES. PES duration and extent were similar between patients with and without SUDEP. CONCLUSIONS: Regional intracranial PES can be present despite scalp-EEG demonstrating generalized or no PES. Postictal autonomic dysfunction correlates with the extent of PES. SIGNIFICANCE: Intracranial-EEG demonstrates changes in autonomic regulatory networks not seen on scalp-EEG.

Epilepsy Milestones 2.0: An updated framework for assessing epilepsy fellowships and fellows.

OBJECTIVE: Accreditation Council for Graduate Medical Education (ACGME)-accredited epilepsy fellowships, like other ACGME accredited training programs, use Milestones to establish learning objectives and to evaluate how well trainees are achieving these goals. The ACGME began developing the second iteration of the Milestones 6 years ago, and these are now being adapted to all specialties. Here, we describe the process by which Epilepsy Milestones 2.0 were developed and summarize them. METHODS: A work group of nine board-certified, adult and pediatric epileptologists reviewed Epilepsy Milestones 1.0 and revised them using a modified Delphi approach. RESULTS: The new Milestones share structural changes with all other specialties, including a clearer stepwise progression in professional development and the harmonized Milestones that address competencies common to all medical fields. Much of the epilepsy-specific content remains the same, although a major addition is a set of Milestones focused on reading and interpreting electroencephalograms (EEGs), which the old Milestones lacked. Epilepsy Milestones 2.0 includes a Supplemental Guide to help program directors implement the new Milestones. Together, Epilepsy Milestones 2.0 and the Supplemental Guide recognize advances in epilepsy, including stereo-EEG, neurostimulation, genetics, and safety in epilepsy monitoring units. SIGNIFICANCE: Epilepsy Milestones 2.0 address the shortcomings of the old Milestones and should facilitate the assessment of epilepsy fellowships and fellows by program directors, faculty, and fellows themselves.

Factors Predicting Outcome After Intracranial EEG Evaluation in Patients With Medically Refractory Epilepsy.

BACKGROUND AND OBJECTIVES: The aim of this study was to identify predictors of a resective surgery and subsequent seizure freedom following intracranial EEG (ICEEG) for seizure-onset localization. METHODS: This is a retrospective chart review of 178 consecutive patients with medically refractory epilepsy who underwent ICEEG monitoring from 2002 to 2015. Univariable and multivariable regression analysis identified independent predictors of resection vs other options. Stepwise Akaike information criteria with the aid of clinical consideration were used to select the best multivariable model for predicting resection and outcome. Discrete time survival analysis was used to analyze the factors predicting seizure-free outcome. Cumulative probability of seizure freedom was analyzed using Kaplan-Meier curves and compared between resection and nonresection groups. Additional univariate analysis was performed on 8 select clinical scenarios commonly encountered during epilepsy surgical evaluations. RESULTS: Multivariable analysis identified the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant as independent predictors of resection (p < 0.0001, area under the receiver operating characteristic curve 0.80, 95% CI 0.73-0.87). Focal ICEEG onset and undergoing a resective surgery predicted absolute seizure freedom at the 5-year follow-up. Patients who underwent resective surgery were more likely to be seizure-free at 5 years compared with continued medical treatment or neuromodulation (60% vs 7%; p < 0.0001, hazard ratio 0.16, 95% CI 0.09-0.28). Even patients thought to have unfavorable predictors (nonlesional MRI or extratemporal lobe hypothesis or dominant hemisphere implant) had ≥50% chance of seizure freedom at 5 years if they underwent resection. DISCUSSION: Unfavorable predictors, including having nonlesional extratemporal epilepsy, should not deter a thorough presurgical evaluation, including with invasive recordings in many cases. Resective surgery without functional impairment offers the best chance for sustained seizure freedom and should always be considered first. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of a lesional MRI, presurgical hypothesis suggesting temporal lobe onset, and a nondominant hemisphere implant are independent predictors of resection. Focal ICEEG onset and undergoing resection are independent predictors of 5-year seizure freedom.

Interictal EEG and ECG for SUDEP Risk Assessment: A Retrospective Multicenter Cohort Study.

Objective: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality. Although lots of effort has been made in identifying clinical risk factors for SUDEP in the literature, there are few validated methods to predict individual SUDEP risk. Prolonged postictal EEG suppression (PGES) is a potential SUDEP biomarker, but its occurrence is infrequent and requires epilepsy monitoring unit admission. We use machine learning methods to examine SUDEP risk using interictal EEG and ECG recordings from SUDEP cases and matched living epilepsy controls. Methods: This multicenter, retrospective, cohort study examined interictal EEG and ECG recordings from 30 SUDEP cases and 58 age-matched living epilepsy patient controls. We trained machine learning models with interictal EEG and ECG features to predict the retrospective SUDEP risk for each patient. We assessed cross-validated classification accuracy and the area under the receiver operating characteristic (AUC) curve. Results: The logistic regression (LR) classifier produced the overall best performance, outperforming the support vector machine (SVM), random forest (RF), and convolutional neural network (CNN). Among the 30 patients with SUDEP [14 females; mean age (SD), 31 (8.47) years] and 58 living epilepsy controls [26 females (43%); mean age (SD) 31 (8.5) years], the LR model achieved the median AUC of 0.77 [interquartile range (IQR), 0.73-0.80] in five-fold cross-validation using interictal alpha and low gamma power ratio of the EEG and heart rate variability (HRV) features extracted from the ECG. The LR model achieved the mean AUC of 0.79 in leave-one-center-out prediction. Conclusions: Our results support that machine learning-driven models may quantify SUDEP risk for epilepsy patients, future refinements in our model may help predict individualized SUDEP risk and help clinicians correlate predictive scores with the clinical data. Low-cost and noninvasive interictal biomarkers of SUDEP risk may help clinicians to identify high-risk patients and initiate preventive strategies.

Optimizing the surgical management of MRI-negative epilepsy in the neuromodulation era.

OBJECTIVE: To evaluate the role of intracranial electroencephalography monitoring in diagnosing and directing the appropriate therapy for MRI-negative epilepsy and to present the surgical outcomes of patients following treatment. METHODS: Retrospective chart review between 2015-2021 at a single institution identified 48 patients with no lesion on MRI, who received surgical intervention for their epilepsy. The outcomes assessed were the surgical treatment performed and the International League Against Epilepsy seizure outcomes at 1 year of follow-up. RESULTS: Eleven patients underwent surgery without invasive monitoring, including vagus nerve stimulation (10%), deep brain stimulation (8%), laser interstitial thermal therapy (2%), and callosotomy (2%). The remaining 37 patients received invasive monitoring followed by resection (35%), responsive neurostimulation (21%), and deep brain stimulation (15%) or no treatment (6%). At 1 year postoperatively, 39% were Class 1-2, 36% were Class 3-4 and 24% were Class 5. More patients with Class 1-2 or 3-4 outcomes underwent invasive monitoring (100% and 83% respectively) compared with those with poor outcomes (25%, P < .001). Patients with Class 1-2 outcomes more commonly underwent resection or responsive neurostimulation: 69% and 31%, respectively (P < .001). SIGNIFICANCE: The optimal management of MRI-negative focal epilepsy may involve invasive monitoring followed by resection or responsive neurostimulation in most cases, as these treatments were associated with the best seizure outcomes in our cohort. Unless multifocal onset is clear from the noninvasive evaluation, invasive monitoring is preferred before pursuing deep brain stimulation or vagal nerve stimulation directly.

Management of patients with medically intractable epilepsy and anterior temporal lobe encephaloceles.

OBJECTIVE: Temporal lobe encephaloceles (TLENs) are a significant cause of medically refractory epilepsy, but there is little consensus regarding their workup and treatment. This study characterizes these lesions and their role in seizures and aims to standardize preoperative evaluation and surgical management. METHODS: Patients with TLEN who had undergone resective epilepsy surgery from December 2015 to August 2020 at a single institution were included in the study. Medical records were reviewed for each patient to collect relevant seizure workup information including demographics, radiological findings, surgical data, and neuropsychological evaluation. RESULTS: For patients who presented to the authors' program with suspected medically intractable temporal lobe epilepsy (219 patients), TLEN was considered to be the epileptogenic focus in 5.5%. Ten patients with TLEN had undergone resection and were included in this study. Concordance between ictal scalp electroencephalography (EEG) lateralization and TLEN was found in 9/10 patients (90%), and 4/10 patients (40%) had signs suggestive of idiopathic intracranial hypertension (IIH). Surgical outcome was reported in patients with at least 12 months of follow-up (9/10). Patients with scalp EEG findings concordant with the TLEN side had a good outcome (Engel class I: 7 patients, class II: 1 patient). One patient with discordant EEG findings had a bad outcome (Engel class III). No significant neuropsychological deficits were observed after the surgery. CONCLUSIONS: TLENs are epileptogenic lesions that should be screened for in patients with medically refractory epilepsy who have signs of IIH and no other lesions on MRI. Restricted resection is safe and effective in patients with scalp EEG findings concordant with TLEN.

Depth Electrode Guided Anterior Insulectomy: 2-Dimensional Operative Video.

The insula is well established as an epileptogenic area.1 Insular epilepsy surgery demands precise anatomic knowledge2-4 and tailored removal of the epileptic zone with careful neuromonitoring.5 We present an operative video illustrating an intracranial electroencephalogram (EEG) depth electrode guided anterior insulectomy. We report a 17-yr-old right-handed woman with a 4-yr history of medically refractory epilepsy. The patient reported daily nocturnal ictal vocalization preceded by an indescribable feeling. Preoperative evaluation was suggestive of a right frontal-temporal onset, but the noninvasive results were discordant. She underwent a combined intracranial EEG study with a frontal-parietal grid, with strips and depth electrodes covering the entire right hemisphere. Epileptiform activity was observed in contact 6 of the anterior insula electrode. The patient consented to the procedure and to the publication of her images. A right anterior insulectomy was performed. First, a portion of the frontal operculum was resected and neuronavigation was used for the initial insula localization. However, due to unreliable neuronavigation (ie, brain shift), the medial and anterior borders of the insular resection were guided by the depth electrode reference. The patient was discharged 3 d after surgery with no neurological deficits and remains seizure free. We demonstrate that depth electrode guided insular surgery is a safe and precise technique, leading to an optimal outcome.

Beyond implantation effect? Long-term seizure reduction and freedom following intracranial monitoring without additional surgical interventions.

The term 'implantation effect' is used to describe an immediate and transient improvement in seizure frequency following an intracranial study for seizure onset localization. We conducted a retrospective analysis of 190 consecutive patients undergoing intracranial electroencephalogram (EEG) monitoring, of whom 41 had no subsequent resection/ablation/stimulation; 33 had adequate data and follow-up time available for analysis. Analysis of seizure frequency following an intracranial study showed 36% (12/33) responder rate (>50% seizure reduction) at one year, decreasing and stabilizing at 20% from year 4 onwards. In addition, we describe three patients (9%) who had long term seizure freedom of more than five years following electrode implantation alone, two of whom had thalamic depth electrodes. Electrode implantation perhaps leads to a neuromodulatory effect sufficient enough to disrupt epileptogenic networks. Rarely, this may be significant enough to even result in long term seizure freedom, as seen in our three patients.

Realistic driving simulation during generalized epileptiform discharges to identify electroencephalographic features related to motor vehicle safety: Feasibility and pilot study.

OBJECTIVE: Generalized epileptiform discharges (GEDs) can occur during seizures or without obvious clinical accompaniment. Motor vehicle driving risk during apparently subclinical GEDs is uncertain. Our goals were to develop a feasible, realistic test to evaluate driving safety during GEDs, and to begin evaluating electroencephalographic (EEG) features in relation to driving safety. METHODS: Subjects were aged ≥15 years with generalized epilepsy, GEDs on EEG, and no clinical seizures. Using a high-fidelity driving simulator (miniSim) with simultaneous EEG, a red oval visual stimulus was presented every 5 minutes for baseline testing, and with each GED. Participants were instructed to pull over as quickly and safely as possible with each stimulus. We analyzed driving and EEG signals during GEDs. RESULTS: Nine subjects were tested, and five experienced 88 GEDs total with mean duration 2.31 ± 1.89 (SD) seconds. Of these five subjects, three responded appropriately to all stimuli, one failed to respond to 75% of stimuli, and one stopped driving immediately during GEDs. GEDs with no response to stimuli were significantly longer than those with appropriate responses (8.47 ± 3.10 vs 1.85 ± 0.69 seconds, P < .001). Reaction times to stimuli during GEDs were significantly correlated with GED duration (r = 0.30, P = .04). In addition, EEG amplitude was greater for GEDs with no response to stimuli than GEDs with responses, both for overall root mean square voltage amplitude (66.14 µV vs 52.99 µV, P = .02) and for fractional power changes in the frequency range of waves (P < .05) and spikes (P < .001). SIGNIFICANCE: High-fidelity driving simulation is feasible for investigating driving behavior during GEDs. GEDs with longer duration and greater EEG amplitude showed more driving impairment. Future work with a large sample size may ultimately enable classification of GED EEG features to predict individual driving risk.

Comparison of intranasal midazolam versus intravenous lorazepam for seizure termination and prevention of seizure clusters in the adult epilepsy monitoring unit.

OBJECTIVE: The objective of the study was to compare the performance of intravenous (IV) lorazepam (IVL) and intranasal midazolam (INM) for seizure termination and prevention of seizure clusters in adults admitted to the epilepsy monitoring unit (EMU) in whom seizures were captured on continuous video-electroencephalogram. METHODS: Retrospective cohort of consecutive adults (≥18 years) with epilepsy admitted to the EMU at a single tertiary academic center, who experienced epileptic seizures (confirmed electroencephalographically) and required rescue therapy. The study spanned from January 2015 until December 2016, which included one year before and one year after transitioning from IVL to INM as the standard rescue therapy at our institution. RESULTS: A total of 50 subjects received rescue therapy and were included in the analysis. In the first year, out of 216 patients with epilepsy admitted to the EMU, 27 (13%) received IVL; in the second year, 23/217 (11%) received INM. There were no differences in baseline characteristics and markers of epilepsy severity, the median duration of index seizure (1.7 min [interquartile range (IQR): 1.1-2.7] in IVL vs. 2.0 min [IQR: 1.5-2.6] in INM group, p = 0.20), or in the number of subjects requiring repeat benzodiazepine administrations (IVL 8/27 [29.6%] vs. INM 7/23 [30.4%], p = 0.95). There were no differences in the median number of recurrent seizures in 24 h (1 [IQR: 1-3] in IVL vs. 2 [IQR: 1-4] in INM, p = 0.27), occurrence of status epilepticus (IVL 4/27 [14.8%] subjects vs. INM 1/23 [4.3%] subjects, p = 0.36), incidence of seizure clusters (IVL 8/27 [29.6%] subjects vs. INM 7/23 [30.4%] subjects, p = 0.95), need for transfer to an intensive care unit (ICU), or other adverse events. SIGNIFICANCE: In our retrospective study, INM was comparable with IVL for seizure termination and prevention of seizure clusters in the adult EMU. Intranasal midazolam circumvents the need for IV access to be maintained throughout hospitalization and is an attractive alternative to IVL as a rescue therapy in this setting. Ideally, future large, prospective, randomized, and double blind studies are needed to confirm these findings.

Resting state connectivity in neocortical epilepsy: The epilepsy network as a patient-specific biomarker.

OBJECTIVE: Localization related epilepsy (LRE) is increasingly accepted as a network disorder. To better understand the network specific characteristics of LRE, we defined individual epilepsy networks and compared them across patients. METHODS: The epilepsy network was defined in the slow cortical potential frequency band in 10 patients using intracranial EEG data obtained during interictal periods. Cortical regions were included in the epilepsy network if their connectivity pattern was similar to the connectivity pattern of the seizure onset electrode contact. Patients were subdivided into frontal, temporal, and posterior quadrant cohorts according to the anatomic location of seizure onset. Jaccard similarity was calculated within each cohort to assess for similarity of the epilepsy network between patients within each cohort. RESULTS: All patients exhibited an epilepsy network in the slow cortical potential frequency band. The topographic distribution of this correlated network activity was found to be unique at the single subject level. CONCLUSIONS: The epilepsy network was unique at the single patient level, even between patients with similar seizure onset locations. SIGNIFICANCE: We demonstrated that the epilepsy network is patient-specific. This is in keeping with our current understanding of brain networks and identifies the patient-specific epilepsy network as a possible biomarker in LRE.

Association of Seizure Spread With Surgical Failure in Epilepsy.

Importance: Seizures recur in as many as half of patients who undergo surgery for drug-resistant temporal lobe epilepsy (TLE). Understanding why TLE is resistant to surgery in some patients may reveal insights into epileptogenic networks and direct new therapies to improve outcomes. Objective: To characterize features of surgically refractory TLE. Design, Setting, and Participants: Medical records from a comprehensive epilepsy center were retrospectively reviewed for 131 patients who received a standard anteromedial temporal resection by a single surgeon from January 1, 2000, to December 31, 2015. Thirteen patients were excluded for having less than 1 year of follow-up. Patients at the highest risk for seizure recurrence were identified. Intracranial electroencephalogram (iEEG) analyses generated 3-dimensional seizure spread representations and quantified rapid seizure spread. The final analyses of seizure outcome and follow-up data were performed in June 2017. Main Outcomes and Measures: The Engel class seizure outcome following surgery was evaluated for all patients, defining seizure recurrence as Engel class II or greater. Intracranial recordings of neocortical grids/strips and depth electrodes were analyzed visually for seizure spread. Fast ß power was projected onto reconstructions of patients' brain magnetic resonance imaging scans to visualize spread patterns and was quantified to compare power within vs outside resective margins. Results: Of 118 patients with 1 year of follow-up or more (mean [SD], 6.5 [4.6] years), 66 (55.9%) were women and 52 (44.1%) were men (median age, 39 years [range, 4-66 years]). The cumulative probability of continuous Engel class I seizure freedom since surgery at postoperative year 10 and afterward was 65.6%, with 92% of recurrences in years 1 to 3. Multivariable statistical analyses found that the selection for iEEG study was the most reliable predictor of seizure recurrence, with a mixed-effects model estimating that the Engel score in the iEEG cohort was higher by a mean (SD) of 1.1 (0.33) (P = .001). In patients with iEEG results, rapid seizure spread in less than 10 seconds was associated with recurrence (hazard ratio, 5.99; 95% CI, 1.7-21.1; P < .01). In the first 10 seconds of seizures, fast ß power activity outside the resective margins in the lateral temporal cortex was significantly greater in patients whose seizures recurred compared with patients who were seizure-free (mean [SEM], 137.5% [16.8%] vs 93.4% [4.6%]; P < .05). Conclusions and significance: Rapid seizure spread outside anteromedial temporal resection resective margins plays a significant role in the surgical failure of drug-resistant TLE. Seizure control after epilepsy surgery might be improved by investigating areas of early spread as candidates for resection or neuromodulation.

The importance of early immunotherapy in patients with faciobrachial dystonic seizures.

Faciobrachial dystonic seizures and limbic encephalitis closely associate with antibodies to leucine-rich glioma-inactivated 1 (LGI1). Here, we describe 103 consecutive patients with faciobrachial dystonic seizures and LGI1 antibodies to understand clinical, therapeutic and serological differences between those with and without cognitive impairment, and to determine whether cessation of faciobrachial dystonic seizures can prevent cognitive impairment. The 22/103 patients without cognitive impairment typically had normal brain MRI, EEGs and serum sodium levels (P < 0.0001). Overall, cessation of faciobrachial dystonic seizures with antiepileptic drugs alone occurred in only 9/89 (10%) patients. By contrast, 51% showed cessation of faciobrachial dystonic seizures 30 days after addition of immunotherapy (P < 0.0001), with earlier cessation in cognitively normal patients (P = 0.038). Indeed, expedited immunotherapy (P = 0.031) and normal cognition (P = 0.0014) also predicted reduced disability at 24 months. Furthermore, of 80 patients with faciobrachial dystonic seizures as their initial feature, 56% developed cognitive impairment after 90 days of active faciobrachial dystonic seizures. Whereas only one patient developed cognitive impairment after cessation of faciobrachial dystonic seizures (P < 0.0001). All patients had IgG4-LGI1 antibodies, but those with cognitive impairment had higher proportions of complement-fixing IgG1 antibodies (P = 0.03). Both subclasses caused LGI1-ADAM22 complex internalization, a potential non-inflammatory epileptogenic mechanism. In summary, faciobrachial dystonic seizures show striking time-sensitive responses to immunotherapy, and their cessation can prevent the development of cognitive impairment.awx323media15681705685001.

Using learning analytics to evaluate a video-based lecture series.

BACKGROUND: The video-based lecture (VBL), an important component of the flipped classroom (FC) and massive open online course (MOOC) approaches to medical education, has primarily been evaluated through direct learner feedback. Evaluation may be enhanced through learner analytics (LA) - analysis of quantitative audience usage data generated by video-sharing platforms. METHODS AND RESULTS: We applied LA to an experimental series of ten VBLs on electroencephalography (EEG) interpretation, uploaded to YouTube in the model of a publicly accessible MOOC. Trends in view count; total percentage of video viewed and audience retention (AR) (percentage of viewers watching at a time point compared to the initial total) were examined. The pattern of average AR decline was characterized using regression analysis, revealing a uniform linear decline in viewership for each video, with no evidence of an optimal VBL length. Segments with transient increases in AR corresponded to those focused on core concepts, indicative of content requiring more detailed evaluation. We propose a model for applying LA at four levels: global, series, video, and feedback. DISCUSSION AND CONCLUSIONS: LA may be a useful tool in evaluating a VBL series. Our proposed model combines analytics data and learner self-report for comprehensive evaluation.

Surgical outcome in adolescents with mesial temporal sclerosis: Is it different?

There are extensive studies evaluating mesial temporal sclerosis (MTS) in adults and limited studies in children, with adolescents being included within both patient populations. Our aim was to evaluate predictors of surgical outcome solely in adolescent patients with MRI- and pathology -proven MTS. The Yale Epilepsy Surgery Database was reviewed from 1987 to 2012 for adolescent patients with confirmed MTS on MRI and pathology who underwent temporal lobectomy and had greater than two-year postsurgical follow-up. Clinical and electrographic data were reviewed. Eighteen patients were identified. Eleven patients (61%) were seizure-free. All seven patients (39%) who were not seizure-free free were found to have lateralized ictal onset within one hemisphere involving two or more lobes on scalp EEG (p<0.001). Of the 7 patients who were not seizure-free, 4 had a history of status epilepticus (compared to 1/11 seizure-free patients; p=0.047), and 4 had lateralized hypometabolism involving two or more lobes within a hemisphere seen on PET (compared to 0/8 seizure-free patients; p=0.002). A novel finding in our study was that lateralized (rather than localized) ictal onset on scalp EEG, lateralized hypometabolism on PET, and history of status epilepticus were risk factors for not attaining seizure freedom in adolescents with MTS who underwent temporal lobectomy.

A Video-Based Introductory EEG Curriculum for Neurology Residents and Other EEG Learners.

INTRODUCTION: It is difficult to provide standardized formal education in EEG because of time limitations and the availability of expert teachers. Video-based miniature lectures are a useful way to standardize the foundational principles of EEG and support learning during EEG/epilepsy rotations. METHODS: A curriculum of 10 EEG teaching videos was developed based on concepts outlined in the Accreditation Council for Graduate Medical Education Neurology Milestones. The videos were short (6-17 minutes) and made available to residents rotating through an EEG/epilepsy rotation in two neurology residency programs. Residents were instructed to review the videos and then apply their newly learned skills during EEG reading sessions. A survey about the process was completed at the end of the year. RESULTS: Twenty-one residents participated in the curriculum, and 15 (71%) responded to the survey. Two-thirds of respondents (10/15) said that they watched all of the videos, and 87% (13/15) watched at least half of the videos. All of the respondents used the videos as introductions to EEG concepts, and approximately half of respondents returned to the videos as a refresher after the rotation was over. Nearly all respondents either agreed or strongly agreed that the curriculum was a useful component of the rotation and helped them to understand difficult concepts. All strongly agreed that they would recommend the curriculum to other residents. DISCUSSION: A video-based approach to EEG teaching could complement existing curricula and ensure that learners have access to foundational miniature lectures when and where they need them.

Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.

OBJECTIVE: Aberrant glutamate and γ-aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. METHODS: Subjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high-performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. RESULTS: Glutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. INTERPRETATION: Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35-45.

Epileptic auras and their role in driving safety in people with epilepsy.

The aim of our study was to evaluate the role of auras in preventing motor vehicle accidents (MVAs) among patients with medically refractory epilepsy. The Multicenter Study of Epilepsy Surgery database was used to perform a case-control study by identifying patients who had seizures while driving that led to MVAs (cases) and those who had seizures while driving without MVAs (controls). We compared presence of reliable auras and other aura-related features between the two groups. Two hundred fifteen of 553 patients reported having seizure(s) while driving; 74 were identified as "controls" and 141 as "cases." The two groups had similar demographic and clinical features. The presence of reliable auras was not different between the two groups (67% in cases vs. 65% in controls; odds ratio [OR] 0.89, 95% confidence interval [CI] 0.49-1.61, p = 0.76). In addition, the groups did not differ in the proportion of patients who reported longer (>1 min) auras (OR 0.7, 95% CI 0.28-1.76, p = 0.47), or who thought that their auras were of sufficient duration to be protective (OR 1.19, 95% CI 0.62-2.00, p = 0.77). Our study questions the long-held belief of a protective role of reliable auras against MVAs in people with epilepsy.

Altered functional connectivity in seizure onset zones revealed by fMRI intrinsic connectivity.

OBJECTIVE: The purpose of this study was to investigate functional connectivity (FC) changes in epileptogenic networks in intractable partial epilepsy obtained from resting-state fMRI by using intrinsic connectivity contrast (ICC), a voxel-based network measure of degree that reflects the number of connections to each voxel. METHODS: We measured differences between intrahemispheric- and interhemispheric-ICC (ICCintra-inter) that could reveal localized connectivity abnormalities in epileptogenic zones while more global network changes would be eliminated when subtracting these values. The ICCintra-inter map was compared with the seizure onset zone (SOZ) based on intracranial EEG (icEEG) recordings in 29 patients with at least 1 year of postsurgical follow-up. Two independent reviewers blindly interpreted the icEEG and fMRI data, and the concordance rates were compared for various clinical factors. RESULTS: Concordance between the icEEG SOZ and ICCintra-inter map was observed in 72.4% (21/29) of the patients, which was higher in patients with good surgical outcome, especially in those patients with temporal lobe epilepsy (TLE) or lateral temporal seizure localization. Concordance was also better in the extratemporal lobe epilepsy than the TLE group. In 85.7% (18/21) of the cases, the ICCintra-inter values were negative in the SOZ, indicating decreased FC within the epileptic hemisphere relative to between hemispheres. CONCLUSIONS: Assessing alterations in FC using fMRI-ICC map can help localize the SOZ, which has potential as a noninvasive presurgical diagnostic tool to improve surgical outcome. In addition, the method reveals that, in focal epilepsy, both intrahemispheric- and interhemispheric-FC may be altered, in the presence of both regional as well as global network abnormalities.