Alcohol for seizure induction in the epilepsy monitoring unit.

RATIONALE: Seizure induction techniques are used in the epilepsy monitoring unit (EMU) to increase diagnostic yield and reduce length of stay. There are insufficient data on the efficacy of alcohol as an induction technique. METHODS: We performed a retrospective cohort study using six years of EMU data at our institution. We compared cases who received alcohol for seizure induction to matched controls who did not. The groups were matched on the following variables: age, reason for admission, length of stay, number of antiseizure medications (ASM) at admission, whether ASMs were tapered during admission, and presence of interictal epileptiform discharges. We used both propensity score and exact matching strategies. We compared the likelihood of epileptic seizures and nonepileptic events in cases versus controls using Kaplan-Meier time-to-event analysis, as well as odds ratios for these outcomes occurring at any time during the admission. RESULTS: We analyzed 256 cases who received alcohol (median dose 2.5 standard drinks) and 256 propensity score-matched controls. Cases who received alcohol were no more likely than controls to have an epileptic seizure (X2(1) = 0.01, p = 0.93) or nonepileptic event (X2(1) = 2.1, p = 0.14) in the first 48 h after alcohol administration. For the admission overall, cases were no more likely to have an epileptic seizure (OR 0.89, 95 % CI 0.61-1.28, p = 0.58), nonepileptic event (OR 0.97, CI 0.62-1.53, p = 1.00), nor require rescue benzodiazepine (OR 0.63, CI 0.35-1.12, p = 0.15). Stratified analyses revealed no increased risk of epileptic seizure in any subgroups. Sensitivity analysis using exact matching showed that results were robust to matching strategy. CONCLUSIONS: Alcohol was not an effective induction technique in the EMU. This finding has implications for counseling patients with epilepsy about the risks of drinking alcohol in moderation in their daily lives.

High-resolution neural recordings improve the accuracy of speech decoding.

Patients suffering from debilitating neurodegenerative diseases often lose the ability to communicate, detrimentally affecting their quality of life. One solution to restore communication is to decode signals directly from the brain to enable neural speech prostheses. However, decoding has been limited by coarse neural recordings which inadequately capture the rich spatio-temporal structure of human brain signals. To resolve this limitation, we performed high-resolution, micro-electrocorticographic (µECoG) neural recordings during intra-operative speech production. We obtained neural signals with 57× higher spatial resolution and 48% higher signal-to-noise ratio compared to macro-ECoG and SEEG. This increased signal quality improved decoding by 35% compared to standard intracranial signals. Accurate decoding was dependent on the high-spatial resolution of the neural interface. Non-linear decoding models designed to utilize enhanced spatio-temporal neural information produced better results than linear techniques. We show that high-density µECoG can enable high-quality speech decoding for future neural speech prostheses.

The seizure severity score: a quantitative tool for comparing seizures and their response to therapy.

Objective.Epilepsy is a neurological disorder characterized by recurrent seizures which vary widely in severity, from clinically silent to prolonged convulsions. Measuring severity is crucial for guiding therapy, particularly when complete control is not possible. Seizure diaries, the current standard for guiding therapy, are insensitive to the duration of events or the propagation of seizure activity across the brain. We present a quantitative seizure severity score that incorporates electroencephalography (EEG) and clinical data and demonstrate how it can guide epilepsy therapies.Approach.We collected intracranial EEG and clinical semiology data from 54 epilepsy patients who had 256 seizures during invasive, in-hospital presurgical evaluation. We applied an absolute slope algorithm to EEG recordings to identify seizing channels. From this data, we developed a seizure severity score that combines seizure duration, spread, and semiology using non-negative matrix factorization. For validation, we assessed its correlation with independent measures of epilepsy burden: seizure types, epilepsy duration, a pharmacokinetic model of medication load, and response to epilepsy surgery. We investigated the association between the seizure severity score and preictal network features.Main results.The seizure severity score augmented clinical classification by objectively delineating seizure duration and spread from recordings in available electrodes. Lower preictal medication loads were associated with higher seizure severity scores (p= 0.018, 97.5% confidence interval = [-1.242, -0.116]) and lower pre-surgical severity was associated with better surgical outcome (p= 0.042). In 85% of patients with multiple seizure types, greater preictal change from baseline was associated with higher severity.Significance.We present a quantitative measure of seizure severity that includes EEG and clinical features, validated on gold standard in-patient recordings. We provide a framework for extending our tool's utility to ambulatory EEG devices, for linking it to seizure semiology measured by wearable sensors, and as a tool to advance data-driven epilepsy care.

Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy.

OBJECTIVE: Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (µECoG) arrays, which provide high spatial resolution over large cortical surface areas. METHODS: We used novel liquid crystal polymer thin-film µECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. RESULTS: We found visually delineable subregions of elevated HFO activity within each µECoG recording. Forty-seven percent of HFOs occurred on single 200-µm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our µECoG recordings. SIGNIFICANCE: These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.

Modeling the Impact of Electrode/Tissue Geometry on Electrical Stimulation in Stereo-EEG.

PURPOSE: Electrical stimulation through depth electrodes is used to map function and seizure onset during stereoelectroencephalography in patients undergoing evaluation for epilepsy surgery. Factors such as electrode design, location, and orientation are expected to impact effects of electrical stimulation. METHODS: We developed a steady-state finite element model of brain tissue including five layers (skull through white matter) and an implanted electrode to explore the impact of electrode design and placement on the activation of brain tissue by electrical stimulation. We calculated electric potentials, current densities, and volume of tissue activated ( Volact ) in response to constant current bipolar stimulation. We modeled two depth electrode designs (3.5- and 4.43-mm intercontact spacing) and varied electrode location and orientation. RESULTS: The electrode with greater intercontact spacing produced 8% to 23% larger Volact (1% to 16% considering only gray matter). Vertical displacement of the electrodes by half intercontact space increased Volact for upward displacement (6% to 83% for all brain tissue or -5% to 96% gray matter only) and decreased Volact (1% to 16% or 24% to 49% gray matter only) for downward displacement. Rotating the electrode in the tissue by 30° to 60° with respect to the vertical axis increased Volact by 30% to 90% (20%-48% gray matter only). CONCLUSIONS: Location and orientation of depth electrodes with respect to surrounding brain tissue have a large impact on the amount of tissue activated during electrical stimulation mapping in stereoelectroencephalography. Electrode design has an impact, although modest for commonly used designs. Individualization of stimulation intensity at each location remains critical, especially for avoiding false-negative results.

Minimum Technical Requirements for Performing Ambulatory EEG.

SUMMARY: Ambulatory EEG (AEEG) devices offer portable, multichannel, digital EEG recording with or without video in the patient's natural environment. The technology applied for AEEG recording is like the technology for routine EEG and inpatient long-term video-EEG monitoring but designed to be compact and wearable. Computer-based AEEG technology is well-suited to digital recording, signal processing, and visual display. However, acquiring interpretable EEG outside of the hospital setting presents its own technical challenges. Published guidelines have established technical standards for performing routine EEG and inpatient video-EEG monitoring, but technical standards for AEEG are lacking. Therefore, this guideline provides minimal technical standards for the performance of AEEG which are essential to ensure the quality of studies for clinical and research practice. We expect these minimum standards to evolve over time with improved performance and advances in the technology.

Intraoperative microseizure detection using a high-density micro-electrocorticography electrode array.

One-third of epilepsy patients suffer from medication-resistant seizures. While surgery to remove epileptogenic tissue helps some patients, 30-70% of patients continue to experience seizures following resection. Surgical outcomes may be improved with more accurate localization of epileptogenic tissue. We have previously developed novel thin-film, subdural electrode arrays with hundreds of microelectrodes over a 100-1000 mm2 area to enable high-resolution mapping of neural activity. Here, we used these high-density arrays to study microscale properties of human epileptiform activity. We performed intraoperative micro-electrocorticographic recordings in nine patients with epilepsy. In addition, we recorded from four patients with movement disorders undergoing deep brain stimulator implantation as non-epileptic controls. A board-certified epileptologist identified microseizures, which resembled electrographic seizures normally observed with clinical macroelectrodes. Recordings in epileptic patients had a significantly higher microseizure rate (2.01 events/min) than recordings in non-epileptic subjects (0.01 events/min; permutation test, P = 0.0068). Using spatial averaging to simulate recordings from larger electrode contacts, we found that the number of detected microseizures decreased rapidly with increasing contact diameter and decreasing contact density. In cases in which microseizures were spatially distributed across multiple channels, the approximate onset region was identified. Our results suggest that micro-electrocorticographic electrode arrays with a high density of contacts and large coverage are essential for capturing microseizures in epilepsy patients and may be beneficial for localizing epileptogenic tissue to plan surgery or target brain stimulation.

Laser ablative treatment of musicogenic epilepsy arising from dominant mesial temporal lobe: illustrative case.

BACKGROUND: Musicogenic epilepsy (ME) is a rare reflex epilepsy in which seizures are triggered by musical stimuli. Prior descriptions of ME have suggested localization to the nondominant temporal lobe, primarily in neocortex. Although resection has been described as a treatment for ME, other surgical modalities, such as laser ablation, may effectively disrupt seizure networks in ME while incurring comparatively lower risks of morbidity. The authors described the use of laser ablation to treat ME arising from the dominant mesial temporal structures. OBSERVATIONS: A 37-year-old woman with a 15-year history of drug-resistant ME was referred for surgical evaluation. Her seizures were triggered by specific musical content and involved behavioral arrest, repetitive swallowing motions, and word incomprehension. Diagnostic studies, including magnetic resonance imaging, single-photon emission computed tomography, magnetoencephalography, Wada testing, and stereoelectroencephalography, indicated seizure onset in the left (dominant) mesial temporal lobe. Laser interstitial thermal therapy was used to ablate the left mesial seizure onset zone. The patient was discharged on postoperative day two. At 18-month follow-up, she was seizure-free with no posttreatment neurological deficits. LESSONS: Laser ablation can be an effective treatment option for well-localized forms of ME, particularly when seizures originate from the dominant mesial temporal lobe.

Seizures detection using multimodal signals: a scoping review.

Introduction. Epileptic seizures are common neurological disorders in the world, impacting 65 million people globally. Around 30% of patients with seizures suffer from refractory epilepsy, where seizures are not controlled by medications. The unpredictability of seizures makes it essential to have a continuous seizure monitoring system outside clinical settings for the purpose of minimizing patients' injuries and providing additional pathways for evaluation and treatment follow-up. Autonomic changes related to seizure events have been extensively studied and attempts made to apply them for seizure detection and prediction tasks. This scoping review aims to depict current research activities associated with the implementation of portable, wearable devices for seizure detection or prediction and inform future direction in continuous seizure tracking in ambulatory settings.Methods. Overall methodology framework includes 5 essential stages: research questions identification, relevant studies identification, selection of studies, data charting and summarizing the findings. A systematic searching strategy guided by systematic reviews and meta-analysis (PRISMA) was implemented to identify relevant records on two databases (PubMed, IEEE).Results. A total of 30 articles were included in our final analysis. Most of the studies were conducted off-line and employed consumer-graded wearable device. ACM is the dominant modality to be used in seizure detection, and widely deployed algorithms entail Support Vector Machine, Random Forest and threshold-based approach. The sensitivity ranged from 33.2% to 100% for single modality with a false alarm rate (FAR) ranging from 0.096 to 14.8 d-1. Multimodality has a sensitivity ranging from 51% to 100% with FAR ranging from 0.12 to 17.7 d-1.Conclusion. The overall performance in seizure detection system based on non-cerebral physiological signals is promising, especially for the detection of motor seizures and seizures accompanied with intense ictal autonomic changes.

Patient preferences pertaining to treatment options for drug-resistant focal epilepsy.

OBJECTIVE: To determine patient acceptability of benefit-risk trade-offs in selecting treatment options for drug-resistant mesial temporal lobe epilepsy, including open brain surgery, laser ablation (laser interstitial thermal therapy [LITT]), and continued medications. METHODS: A discrete-choice experiment survey was developed, consisting of 20 versions that were randomly assigned to respondents. Each version had 8 sets of constructed treatment alternatives, representing open brain surgery, LITT, or continued medical management. For each set, respondents indicated the treatment alternative they would choose first. Treatment alternatives were characterized by varying levels of chance of seizure freedom for at least 2 years (20-70%), risk of 30-day mortality (0-10%), and risk of neurological deficits (0-40%). Respondents' choices were analyzed using random-parameters logit models to quantify acceptable benefit-risk trade-offs. Preference heterogeneity was evaluated using latent-class analysis. RESULTS: The survey was administered to 2 cohorts of adult patients with drug-resistant epilepsy: a Duke cohort identified using diagnostic codes (n = 106) and a web-recruited panel with a self-reported physician diagnosis of drug-resistant epilepsy (n = 300). Based on mean preference weights, respondents who indicated a willingness to consider surgical intervention would accept a reduction in chance of seizure freedom from 70% to a minimum-acceptable benefit (MAB) of 23% if they could undergo LITT rather than open brain surgery. For a reduction in 30-day mortality from 1% to 0%, MAB was 52%. For a reduction in risk of long-term deficits from 10% to 0%, MAB was 39%. Latent-class analysis revealed additional choice patterns identifying respondent groups that more strongly favored continuing medications or undergoing surgery. CONCLUSION: Patients who are receptive to surgery would accept significantly lower treatment effectiveness to undergo a minimally invasive procedure relative to open brain surgery. They also were willing to accept lower treatment benefit to reduce risks of mortality or neurological deficits.

Stereotactic EEG Practices: A Survey of United States Tertiary Referral Epilepsy Centers.

PURPOSE: Stereotactic EEG (SEEG) is being increasingly used in the intracranial evaluation of refractory epilepsy in the United States. In this study, the authors describe current practice of SEEG among National Association of Epilepsy Centers tertiary referral (level IV) centers. METHODS: Using the Survey Monkey platform, a survey was sent to all National Association of Epilepsy Centers level IV center directors. RESULTS: Of 192 centers polled, 104 directors completed the survey (54% response rate). Ninety-two percent currently perform SEEG. Of these, 55% of institutions reported that greater than 75% of their invasive electrode cases used SEEG. Stereotactic EEG was commonly used over subdural electrodes in cases of suspected mesial temporal lobe epilepsy (87%), nonlesional frontal lobe epilepsy (79%), insular epilepsy (100%), and individuals with prior epilepsy surgery (74%). Most centers (72%) used single-lead electrocardiogram monitoring concurrently with SEEG, but less than half used continuous pulse oximetry (47%) and only a few used respiratory belts (3%). Other significant intercenter technical variabilities included electrode nomenclature and choice of reference electrode. Patient care protocols varied among centers in patient-to-nurse ratio and allowed patient activity. Half of all centers had personnel who had prior experience in SEEG (50.5%); 20% of centers had adopted SEEG without any formal training. CONCLUSIONS: Stereotactic EEG has become the principal method for intracranial EEG monitoring in the majority of epilepsy surgery centers in the United States. Most report similar indications for use of SEEG, though significant variability exists in the utilization of concurrent cardiopulmonary monitoring as well as several technical and patient care practices. There is significant variability in level of background training in SEEG among practitioners. The study highlights the need for consensus statements and guidelines to benchmark SEEG practice and develop uniform standards in the United States.

Clinical Neurophysiology Fellowship Program Directors Survey on a Standardized Fellowship Match Process: A Call for Action.

PURPOSE: To survey US Clinical Neurophysiology (CNP) fellowship program directors on the nature of CNP and related training programs, current recruitment cycle, and views for a standardized process. METHODS: A 23-question electronic survey was sent to all 93 US Accreditation Council for Graduate Medical Education-accredited CNP fellowship program directors from December 2020 to January 2021. RESULTS: The response rate was 60%. There was great variability in the number of CNP positions and CNP tracks offered. The following tracks were identified: 48% EEG dominant, 26% EMG dominant, 22% split equally between EEG and EMG, and 2% and 1% were neurophysiologic intraoperative monitoring and autonomic dominant, respectively. Of the responding institutions, 43% offered a second year of training options to CNP fellows, mainly in conjunction with Epilepsy fellowship, which was pursued by 25% of CNP fellows. Many programs indicated flexibility in their design between different CNP tracks or between CNP and other related training programs based on the available candidates. The median percentage of CNP fellowship positions filled over the last 5 years was 80%, and there was great variation in the recruitment timeline across institutions. Overall, 86% of program directors favored a universal timeline and 71% favored a formal match for CNP. The respondents were split between an independent CNP match (39%) and joining the initiatives of affiliate societies on a standardized process (61%). CONCLUSIONS: There is significant heterogeneity in the makeup of the CNP fellowship programs and the recruitment process. The majority of CNP program directors are in favor of standardization of the recruitment process.

Electrographic Seizure Detection by Neuroscience Intensive Care Unit Nurses via Bedside Real-Time Quantitative EEG.

OBJECTIVE: Our primary objective was to determine the performance of real-time neuroscience intensive care unit (neuro-ICU) nurse interpretation of quantitative EEG (qEEG) at the bedside for seizure detection. Secondary objectives included determining nurse time to seizure detection and assessing factors that influenced nurse accuracy. METHODS: Nurses caring for neuro-ICU patients undergoing continuous EEG (cEEG) were trained using a 1-hour qEEG panel (rhythmicity spectrogram and amplitude-integrated EEG) bedside display. Nurses' hourly interpretations were compared with post hoc cEEG review by 2 neurophysiologists as the gold standard. Diagnostic performance, time to seizure detection compared with standard of care (SOC), and effects of other factors on nurse accuracy were calculated. RESULTS: A total of 109 patients and 65 nurses were studied. Eight patients had seizures during the study period (7%). Nurse sensitivity and specificity for the detection of seizures were 74% and 92%, respectively. Mean nurse time to seizure detection was significantly shorter than SOC by 132 minutes (Cox proportional hazard ratio 6.96). Inaccurate nurse interpretation was associated with increased hours monitored and presence of brief rhythmic discharges. CONCLUSIONS: This prospective study of real-time nurse interpretation of qEEG for seizure detection in neuro-ICU patients showed clinically adequate sensitivity and specificity. Time to seizure detection was less than that of SOC. TRIAL REGISTRATION INFORMATION: Clinical trial registration number NCT02082873. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that neuro-ICU nurse interpretation of qEEG detects seizures in adults with a sensitivity of 74% and a specificity of 92% compared with traditional cEEG review.

Safety and efficacy of midazolam nasal spray for the treatment of intermittent bouts of increased seizure activity in the epilepsy monitoring unit: A double-blind, randomized, placebo-controlled trial.

OBJECTIVE: Midazolam nasal spray (MDZ-NS) is indicated for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient's usual seizure pattern, in patients 12 years of age and older with epilepsy. This trial evaluated safety and efficacy of MDZ-NS in patients with epilepsy who were admitted to the epilepsy monitoring unit for seizure characterization/presurgical evaluation. METHODS: In this randomized, double-blind, placebo-controlled phase 3 trial (P261-301; NCT01999777), eligible patients with ≥2 seizures in the 6-hour window preceding trial medication administration for whom treatment was appropriate based on investigator's judgment were randomized (1:1) to MDZ-NS 5 mg or placebo. Efficacy outcomes were proportion of patients seizure-free for 6 hours after treatment and time to first seizure within 6 hours. Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs). RESULTS: Sixty-two patients were randomized (MDZ-NS n = 31; placebo n = 31), received trial medication, and completed the trial. A higher proportion of patients on MDZ-NS than placebo were seizure-free for 6 hours following treatment (54.8% vs 38.7%); however, the 16.1% difference was not statistically significant (P = .1972). The Kaplan-Meier curve of time to first seizure showed separation of both groups in favor of MDZ-NS from ~1.5 hours post-dose and throughout the 6-hour Treatment phase. Median time to first seizure was not estimable for MDZ-NS (>50% of patients had no seizure) and 3.9 hours for placebo (P = .1388). TEAEs with MDZ-NS were generally comparable to those with placebo. There were no deaths, serious TEAEs, or discontinuations due to TEAEs. SIGNIFICANCE: Although the observed treatment difference may be clinically meaningful, statistical significance was not demonstrated. Results suggest that MDZ-NS 5 mg may provide improvement over placebo, with efficacy maintained for ≥6 hours post-dose. MDZ-NS was well tolerated in this population.

Spinal cord stimulation and rehabilitation in an individual with chronic complete L1 paraplegia due to a conus medullaris injury: motor and functional outcomes at 18 months.

INTRODUCTION: Epidural electrical stimulation of the conus medullaris has helped facilitate native motor recovery in individuals with complete cervicothoracic spinal cord injuries (SCI). A theorized mechanism of clinical improvement includes supporting central pattern generators intrinsic to the conus medullaris. Because spinal cord stimulators (SCS) are approved for the treatment of neuropathic pain, we were able to test this experimental therapy in a subject with complete L1 paraplegia and neuropathic genital pain due to a traumatic conus injury. CASE PRESENTATION: An otherwise healthy 48-year-old male with chronic complete L1 paraplegia with no zones of partial preservation (ZPP) and intractable neuropathic genital pain presented to our group seeking nonmedical pain relief and any possible help with functional restoration. After extensive evaluation, discussion, and consent, we proceeded with SCS implantation at the conus and an intensive outpatient physical therapy regimen consistent with the recent SCI rehabilitation literature. DISCUSSION: Intraoperatively, no electromyography (EMG) could be elicited with epidural conus stimulation. At 18 months after implantation, his motor ZPPs had advanced from L1 to L5 on the left and from L1 to L3 on the right. Qualitative increases in lower extremity resting state EMG amplitudes were noted, although there was no consistent evidence of voluntary EMG or rhythmic locomotive leg movements. Three validated functional and quality of life (QoL) surveys demonstrated substantial improvements. The modest motor response compared to the literature suggests likely critical differences in the anatomy of such a low injury. However, the change in ZPPs and QoL suggest potential for neuroplasticity even in this patient population.

Barriers and facilitators to implementation of epilepsy self-management programs: a systematic review using qualitative evidence synthesis methods.

BACKGROUND: Epilepsy affects nearly 50 million people worldwide. Self-management is critical for individuals with epilepsy in order to maintain optimal physical, cognitive, and emotional health. Implementing and adopting a self-management program requires considering many factors at the person, program, and systems levels. We conducted a systematic review of qualitative and mixed-methods studies to identify facilitators and barriers that impact implementation and adoption of self-management programs for adults with epilepsy. METHODS: We used established systematic review methodologies for qualitative and mixed-methods studies. We included studies addressing facilitators (i.e., factors that aided) or barriers (i.e., factors that impeded) to implementation and adoption of self-management interventions for adults with epilepsy. We conducted a narrative thematic synthesis to identify facilitators and barriers. RESULTS: The literature search identified 2700 citations; 13 studies met eligibility criteria. Our synthesis identified five themes that categorize facilitators and barriers to successful implementation epilepsy self-management: (1) relevance, intervention content that facilitates acquisition of self-management skills; (2) personalization, intervention components that account for the individual's social, physical, and environmental characteristics; (3) intervention components, components and dosing of the intervention; (4) technology considerations, considerations that account for individual's use, familiarity with, and ownership of technology; and (5) clinician interventionist, role and preparation of the individual who leads intervention. We identified facilitators in 11 of the 13 studies and barriers in 11 of the 13 studies and classified these by social-ecological level (i.e., patient/caregiver, program, site/system). CONCLUSION: Identification of facilitators and barriers at multiple levels provides insight into disease-specific factors that influence implementation and adoption of self-management programs for individuals with epilepsy. Our findings indicate that involving individuals with epilepsy and their caregivers in intervention development, and then tailoring intervention content during the intervention, can help ensure the content is relevant to intervention participants. Our findings also indicate the role of the clinician (i.e., the individual who provides self-management education) is important to intervention implementation, and key issues with clinicians were identified as barriers and opportunities for improvement. Overall, our findings have practical value for those seeking to implement and adopt self-management interventions for epilepsy and other chronic illnesses. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number is CRD42018098604.

Genomic and clinical predictors of lacosamide response in refractory epilepsies.

OBJECTIVE: Clinical and genetic predictors of response to antiepileptic drugs (AEDs) are largely unknown. We examined predictors of lacosamide response in a real-world clinical setting. METHODS: We tested the association of clinical predictors with treatment response using regression modeling in a cohort of people with refractory epilepsy. Genetic assessment for lacosamide response was conducted via genome-wide association studies and exome studies, comprising 281 candidate genes. RESULTS: Most patients (479/483) were treated with LCM in addition to other AEDs. Our results corroborate previous findings that patients with refractory genetic generalized epilepsy (GGE) may respond to treatment with LCM. No clear clinical predictors were identified. We then compared 73 lacosamide responders, defined as those experiencing greater than 75% seizure reduction or seizure freedom, to 495 nonresponders (<25% seizure reduction). No variants reached the genome-wide significance threshold in our case-control analysis. SIGNIFICANCE: No genetic predictor of lacosamide response was identified. Patients with refractory GGE might benefit from treatment with lacosamide.

Self-management of Epilepsy: A Systematic Review.

Background: Although self-management is recommended for persons with epilepsy, its optimal strategies and effects are uncertain. Purpose: To evaluate the components and efficacy of self-management interventions in the treatment of epilepsy in community-dwelling persons. Data Sources: English-language searches of MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL in April 2018; the MEDLINE search was updated in March 2019. Study Selection: Randomized and nonrandomized comparative studies of self-management interventions for adults with epilepsy. Data Extraction: An investigator assessed study characteristics; intervention details, including 6 components of self-management; and outcomes, which were verified by a second reviewer. Risk of bias (ROB) was assessed independently by 2 investigators. Data Synthesis: 13 randomized and 2 nonrandomized studies (2514 patients) evaluated self-management interventions. Interventions were delivered primarily in group settings, used a median of 4 components, and followed 2 general strategies: 1 based on education and the other on psychosocial therapy. Education-based approaches improved self-management behaviors (standardized mean difference, 0.52 [95% CI, 0.0 to 1.04]), and psychosocial therapy-based approaches improved quality of life (mean difference, 6.64 [CI, 2.51 to 10.77]). Overall, self-management interventions did not reduce seizure rates, but 1 educational intervention decreased a composite of seizures, emergency department visits, and hospitalizations. Limitation: High ROB in most studies, incomplete intervention descriptions, and studies limited to English-language publications. Conclusion: There is limited evidence that self-management strategies modestly improve some patient outcomes that are important to persons with epilepsy. Overall, self-management research in epilepsy is limited by the range of interventions tested, the small number of studies using self-monitoring technology, and uncertainty about components and strategies associated with benefit. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42018098604).