Refractory Epilepsy Research Articles

The Efficacy and Cognitive Impact of Perampanel Monotherapy in Patients with Self-Limited Epilepsy with Centrotemporal Spikes: A Retrospective Analysis.

The third generation of antiepileptic medication (ASM) perampanel (PER), is mostly used as an add-on treatment for refractory epilepsy patients, and rarely used as a monotherapy. This study aims to observe the efficacy and assess the cognitive effects of PER monotherapy in patients with self-limited epilepsy with centrotemporal spikes (SeLECTS). Through screening, 86 patients who were first diagnosed with SeLECTS and treated with PER monotherapy were included in this study. All patients were followed up at least 12 months, and Evaluated the efficacy and safety of PER by observing the seizures of patients. At the same time, we used the P300 event-related potential (ERP) component and Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) to evaluate the cognitive changes in children before and after treatment with PER. Ten percent of the children experienced adverse effects, such as dizziness, gait instability, and irritability. The drug retention rate at the last follow-up was 98.83%. Further more, the P300 ERP component and WISC-IV tests were performed no significant difference before and 12 months after PER monotherapy in SeLECTS children. The third-generation of ASM PER monotherapy had a clear effect in children with SeLECTS. A small dose of PER can control seizures well and has no obvious effect on cognitive development.

Analysis of the efficacy and safety of inpatient and outpatient initiation of KD for the treatment of pediatric refractory epilepsy using generalized estimating equations.

To compare the efficacy and safety of inpatient and outpatient initiation ketogenic diet (KD) protocol of pediatric refractory epilepsy. Eligible children with refractory epilepsy were randomly assigned to receive KD with inpatient and outpatient initiation. The generalized estimation equation (GEE) model was used to analyze the longitudinal variables of seizure reduction, ketone body, weight, height, body mass index (BMI), and BMI Z-score at different follow-up times between the two groups. Between January 2013 and December 2021, 78 and 112 patients were assigned to outpatient and inpatient KD initiation groups, respectively. There were no statistical differences between the two groups based on baseline demographics and clinical characteristics (all Ps > 0.05). The GEE model indicated that the rate of reduction of seizures≥50% in the outpatient initiation group was higher than that of the inpatient initiation group (p = 0.049). A negative correlation was observed between the seizure reduction and blood ketone body at 1, 6, and 12 months (all Ps < 0.05). There were no significant differences in height, weight, BMI, and BMI Z-score between the two groups over the 12-month period by the GEE models (all Ps > 0.05). Adverse events were reported by 31 patients (43.05%) in the outpatient KD initiation group and 46 patients (42.20%) in the inpatient KD initiation group, but these differences were not statistically significant (p = 0.909). Our study shows that outpatient KD initiation is a safe and effective treatment for children with refractory epilepsy.

Epileptiform Discharges in Patients with Psychogenic Non-Epileptic Attacks: A Case Series (P1-1.009)

<h3>Objective:</h3> We present a small case series of patients with psychogenic non-epileptic attacks (PNEA), who were misdiagnosed with “refractory epilepsy” based on the presence of epileptiform discharges (EDs), particularly generalized spike-and-wave, on their EEG. This diagnosis was reversed after admission to the epilepsy monitoring unit for spell characterization, where all stereotypical events of interest were captured and were deemed non-epileptic. <h3>Background:</h3> Over the past decade, there was an increased emphasis on the need to correctly diagnose patients with PNEA to avoid unnecessary treatment with anti-seizure drugs and initiate psychotherapy to attain good clinical outcome. Misdiagnosing PNEA with “refractory epilepsy” could be due to misinterpreted EEG as “abnormal with epileptiform discharges” or co-existence of PNEA with EDs in the absence of clinical seizures. Although, PNEA is seen in up to 12% of epilepsy patients, there are rare cases where PNEA only occurs without confirmed epilepsy despite the presence of EDs. <h3>Design/Methods:</h3> We identified seven patients with only PNEA and EDs admitted to Epilepsy Monitoring Unit for “refractory epilepsy” and retrospectively reviewed their records including their EEG. <h3>Results:</h3> None of the stereotypical events captured on video-EEG was associated with ictal EEG correlates. Six had generalized spike-and-wave discharges (GSW) without clinical accompaniments. Of patients who initiated psychotherapy, 60% had ≥ 50% reduction in frequency of PNEA. <h3>Conclusions:</h3> EDs can occur in “PNEA-only” patients and shouldn’t delay PNEA diagnosis or effective psychotherapeutic treatment. <b>Disclosure:</b> Dr. Afify has nothing to disclose. The institution of Dr. Tolchin has received research support from C.G. Swebilius Trust. The institution of Dr. Altalib has received research support from UCB. The institution of Dr. Altalib has received research support from Eisai. The institution of Dr. Altalib has received research support from Sunovian. The institution of Dr. Altalib has received research support from DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aquestive. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Hirsch has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for marinus. Dr. Hirsch has received personal compensation in the range of $0-$499 for serving as a Consultant for Medtronic. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Hirsch has received personal compensation in the range of $0-$499 for serving as a Consultant for Accure. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuropace. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Rafa Laboratories, Ltd. Dr. Hirsch has received publishing royalties from a publication relating to health care. Dr. Hirsch has received publishing royalties from a publication relating to health care. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Neuropace. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Natus. Dr. Hirsch has received personal compensation in the range of $500-$4,999 for serving as a speaker with UCB. Dr. Herlopian has nothing to disclose.

EEG patterns in Refractory Epilepsy with Focal Cortical Dysplasia and predictors of outcome after surgery (P10-1.003)

<h3>Objective:</h3> To characterize the EEG patterns of type-1 and type-2 FCD with refractory epilepsy, correlate with clinic-radiological features and determine predictors of surgical outcome. <h3>Background:</h3> Focal cortical dysplasia (FCD) is the most common malformation of cortical development (MCD) causing drug refractory epilepsy(DRE) requiring surgical evaluation. Precise characterisation of the FCD and associated epileptogenic zone (EZ) with multimodal evaluation is crucial for surgical success <h3>Design/Methods:</h3> Retrospective analysis data of 188 consecutive patients with FCD operated for DRE and at least two years post-surgery follow-up was analyzed. The clinical features, MRI and interictal and ictal EEG patterns were studied for all patients <h3>Results:</h3> Average age of patients was 17.31±11.26 (2 – 64) years with 48.9% women. Interictal EEG showed regional pattern in 66% of FCD2 patients (p=0.04), while generalised interictal discharges were commonly associated with persistent seizures after surgery (p=0.016). Ictal beta rhythm was significantly associated with FCD2 (p=0.05). Generalised ictal onset was significantly seen in patients with persistent seizures after surgery (p=0.48). MRI showed clear cut FCD in 72.3% patients. At last follow-up 66.0% were seizure free. Patients with FCD type-1 had earlier age at onset (p=0.029) of epilepsy and had multiple seizure patterns (0.034). Patients with FCD type-2 commonly reported aura (p=0.019) and had clear-cut lesion on MRI (p=0.021) and high seizure freedom(p=0.004). Patients with FCD type-1 more often were detected on PET-MRI, underwent multilobar resections and had higher rate of acute postoperative seizures, while complete resection was more frequent in type-2 FCD <h3>Conclusions:</h3> FCD type-1 had early onset of seizures with multiple seizure semiologies, subtle MRI, multi-lobar resection and poor surgical outcome. FCD2 had clear-cut MRI lesion, regional inter-ictal discharges, ictal beta at onset with complete resection at surgery hence favorable post-surgical outcome <b>Disclosure:</b> Dr. Patil has nothing to disclose. Sita Jayalakshmi has nothing to disclose. Dr. Vooturi has nothing to disclose.

An educational intervention to improve the efficacy of responsive neurostimulation scans: a single-center study (P5-1.012)

<h3>Objective:</h3> We aimed to investigate the impact of an educational intervention in improving responsive neurostimulation (RNS) efficacy by motivating patients to undertake regular RNS scans (downloads), allowing for prompt intervention. <h3>Background:</h3> As part of the management of refractory epilepsy with RNS, the recorded data should be regularly retrieved and uploaded to Neuropace for the epileptologist to analyze and make required modifications. <h3>Design/Methods:</h3> Twelve patients with refractory epilepsy undergoing treatment with RNS at our center from January 2021 until May 2022 were included. All patients received an in-person educational session and four weekly reminder emails about data transfer. Data collected included the number of RNS scans 6-months before and 6-months after the session, age, gender, education, intelligence quotient (IQ) scores, verbal comprehension and working memory scores, seizure onset, epilepsy duration, seizure reduction 6-months post-education. <h3>Results:</h3> Total number of downloads 6 months pre and post education were 455 and 411 respectively. An improvement in adherence with downloading data was observed in patients with temporal onset (195 pre, 223 post), 10–15-year duration of epilepsy (9 pre, 39 post) and IQ 80–89 (16 pre, 56 post). Post education scans declined in patients with extremely low to low average working memory (368 pre, 307 post), extra-temporal epilepsy (260 pre, 188 post), seizure duration &gt;15 years (244 pre, 195 post) and IQ 70–79 (228 pre, 166 post). Even though 67% of the patients reported &gt;50% seizure reduction 6 months post education, these patients had fewer scans compared to their pre-education numbers (244 pre, 195 post). <h3>Conclusions:</h3> Our study did not show an improvement in RNS data transfer compliance after re-educating the patients. Further strategies may be needed such as weekly phone calls, text messages and developing smart phone RNS reminder apps. One of the major limitations of this study is small sample size. <b>Disclosure:</b> Dr. Abughanam has nothing to disclose. Dr. Katyal has nothing to disclose. Dr. Gutierrez has nothing to disclose. Dr. Chen has nothing to disclose.

Clinical and Neurophysiological Features of Epilepsy in Pediatric Patients with Vanishing White Matter Disease-A single institute experience and literature review (P12-9.006)

<h3>Objective:</h3> Refractory epilepsy is a common presentation in Vanishing white matter disease (VWMD) patients. However, there is little literature describing the nature and evolution of seizures. We aim to study the electroencephalograpic findings in patients with a genetically confirmed diagnosis of VWMD, and their correlation with MRI progression and clinical status longitudinally. <h3>Background:</h3> Vanishing White Matter Disease (VWMD) is one of the most prevalent leukodystrophies in pediatric patients with unique clinical, pathological, and molecular features. It mostly affects children, but may develop at all ages, from birth to senescence. Incidence in one study is reported to be 1 in 80,000 live births. The molecular basis of the disease has been shown to be due to mutations in subunits of Eukaryotic Translation Initiation Factor 2B (eIF2B) ie eIF2B 1–5. <h3>Design/Methods:</h3> An IRB approved retrospective chart review was conducted at Children’s Medical Center, Dallas TX. The initial search pulled up 42 patients that had an associated diagnosis of leukodystrophy. Four of these 42 patients were found to have a genetically confirmed diagnosis of VWMD. <h3>Results:</h3> In our cohort, there were 3males and 1female. Age of diagnosis ranged between 2–10 years and mutations in EIF2B5 was the most common. The earliest seizure onset was noted at 2 years of age at the time of diagnosis. Patients that presented with intractable seizures were noted to have significant MRI changes. Average time of seizure onset from time of diagnosis was 1.6 years. Our patient that was diagnosed with VWMD at 10 years of age did not go on to develop seizures and his EEG did not have any epileptiform discharges. His MRI did not show significant white matter changes and clinically patient had mild to moderate deficits. <h3>Conclusions:</h3> We observe that there is a wide range of severity of epilepsy in these patients &amp; not all patients with a diagnosis of VWMD go on to develop seizures. <b>Disclosure:</b> Dr. Laheji has nothing to disclose. Dr. Lowden has nothing to disclose.

Efficacy and Quality of Life Outcome of Combined Epilepsy Surgery with RNS Placement (P5-1.002)

<h3>Objective:</h3> Retrospectively review clinical outcomes in patients treated with resection or Laser interstitial Thermal Therapy (LiTT) immediately (≤ 90 days) after implantation of RNS. <h3>Background:</h3> Surgical resection and LiTT are standard treatments for refractory epilepsy, but these options can be limited by eloquent cortex and seizure multifocality. Previous studies have suggested RNS may be used in conjunction with resective surgery (RNS+R) or LiTT (RNS+LiTT) as a new combination of treatments. Besides seizure control, quality of life and psychiatric symptoms including depression and anxiety are considered as important outcome evaluation after epilepsy surgery. <h3>Design/Methods:</h3> 34 patients that had RNS+R or RNS+LiTT at our center were reviewed and 10 were excluded. The decision of dual procedures was made prior to surgery. Patients received RNS+R had both resective surgery and RNS placement in the same procedure. Patients received RNS+LiTT had several weeks gap between the RNS placement and LiTT due to neurosurgical logistics. Clinical follow-ups were performed at 12, 18, 24, 36 and 48 months for evaluation of seizure frequency. Patient health questionnaire-9 (PHQ-9) is used as a depression assessment. Quality of life in epilepsy questionnaire (QOLIE-31) was used as scoring for evaluation of general quality of life. <h3>Results:</h3> Among the 24 patients that had RNS+R or RNS+LiTT, 22 patients (91.6%) showed improved seizure frequency at the last follow up. Fourteen patients had PHQ-9 evaluation and the average score was 5.85±6.29 (mean±SD), among which nine were between 0–4 (minimal depression), one was between 5–9(mild depression), three were between 10–14(moderate depression), one was 15–19(moderately severe depression) and none was 20–27(severe depression). QOLIE-31 done in eight patients showed average score of 65.61 ± 18.09 (mean±SD) in last follow-up visit. <h3>Conclusions:</h3> Our study showed significant seizure control rate of RNS+R or RNS+LiTT therapy in refractory epilepsy patients. It also suggestive for promising psychiatric outcomes and quality of life scoring after surgery. <b>Disclosure:</b> Dr. Pan has nothing to disclose. Dr. Mirza has nothing to disclose. Dr. Agostini has nothing to disclose. Dr. Alick-Lindstrom has nothing to disclose. Dr. Das has received personal compensation for serving as an employee of Concentra. Dr. Das has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for janicek. The institution of an immediate family member of Dr. Das has received research support from NIH. The institution of Dr. Ding has received research support from National Institute of Aging. The institution of Dr. Ding has received research support from NINDS. Dr. Doyle has nothing to disclose. Dr. Dieppa has nothing to disclose. Dr. Hays has nothing to disclose. Dr. Harvey has received personal compensation for serving as an employee of RSC Diagnostics. The institution of Dr. Harvey has received research support from GW Pharmaceuticals. The institution of Dr. Harvey has received research support from Cerevel Pharmaceuticals. The institution of Dr. Harvey has received research support from UCB Pharmaceuticals. The institution of Bradley Lega has received research support from NIH. irina podkorytova has nothing to disclose. Dr. Zepeda Garcia has nothing to disclose. Dr. Perven has nothing to disclose.

Is there a difference in reduction of seizure frequency between transcutaneous and traditional VNS? (P5-1.009)

<h3>Objective:</h3> Our aim was to compare seizure frequency reduction between traditional and t-VNS <h3>Background:</h3> Transcutaneous vagus nerve stimulation (t-VNS) aims to overcome the disadvantages of surgical implantation of traditional VNS, yet little is known about whether these modalities are equally effective in seizure frequency reduction. <h3>Design/Methods:</h3> We conducted a systematic review following the PRISMA guidelines. Included were clinical and/or randomized trial articles indexed by Embase and Pubmed, with the keywords: “drug-resistant epilepsy” or “refractory epilepsy” and “vagus nerve stimulator”. We performed a meta-analysis, considering treatment success as ≥ 50% of seizure frequency reduction. Statistical analyses were weighted for population size. We performed Mann-Whitney test for between-group and Wilcoxon test for within-group analyses. <h3>Results:</h3> Eighteen studies were included (13 traditional, 5 t-VNS), with a total of 1383 patients, with a mean age of 31.27 ± 8.71 years and median follow-up assessment of 12 months (range, 3.5–36). The median success rate for the traditional and t-VNS groups were 49.2% (range, 28–100) and 28% (range, 0–54), respectively (P &lt; 0.0001), with adherence &gt;70% to t-VNS. High variability was observed within the traditional VNS studies (P=0.002), but not in t-VNS. The most common reported side effects from t-VNS were ear pain, dizziness, and headache while traditional VNS was most associated with cough and dysphonia. <h3>Conclusions:</h3> Although t-VNS presents as a more convenient alternative to its traditionally implanted counterpart, its efficacy seems to be relatively low for refractory epilepsy. Furthermore, t-VNS has been associated with more frequently reported side effects than traditional VNS. <b>Disclosure:</b> Mr. Costa has nothing to disclose. Mr. Dos Santos Silva has nothing to disclose. Henrique Januzzelli has nothing to disclose. Isabella D’Andrea has nothing to disclose.

Selective NKCC1 Inhibitors for the Treatment of Neurodevelopmental and Neurological Disorders with Defective NKCC1/KCC2 expression-ratio (P2-12.003)

<h3>Objective:</h3> The aim of this work was to search for selective NKCC1 inhibitors devoid of undesired diuretic effects as a sustainable therapeutic solution for brain disorders characterized by defective NKCC1/KCC2 expression-ratio. <h3>Background:</h3> Proper intracellular chloride concentration is fundamental for physiological brain development and function. Accordingly, the aberrant expression-ratio of chloride-importer NKCC1 and -exporter KCC2 is implicated in several brain conditions, including drug-resistant epilepsy (e.g. temporal lobe epilepsy (TLE) and Dravet syndrome (DrS)), autism spectrum disorders (ASD) and Down syndrome (DoS). Interestingly, NKCC1 inhibition rescues core symptoms of these disorders in rodent models and/or clinical trials. However, current NKCC1 inhibitors have diuretic effects inhibiting the kidney chloride-transporter NKCC2. This creates critical issues with health concerns, strongly jeopardizing them from becoming a viable therapy for chronic treatment. <h3>Design/Methods:</h3> We performed rational drug design supported by computational methods to develop selective NKCC1 inhibitors, which we tested in several cell-based assays <i>in vitro</i> and in mouse models of neurodevelopmental/neurological disorders. <h3>Results:</h3> Here, we present the discovery of a new class of selective NKCC1 inhibitors. The lead compound IAMA-6, currently in advanced preclinical studies, which rescues social/repetitive behaviours in ASD mice and cognitive deficits in DoS mice, without showing any diuretic or toxic effect. The ongoing investigation of IAMA-6 in two rodent models of drug-resistant epilepsy (TLE and DrS) will provide solid data on the efficacy of our new class of NKCC1 inhibitors in ameliorating core symptoms of neurological conditions representing a highly unmet medical need. <h3>Conclusions:</h3> IAMA-6 represents an effective and solid lead compound to be developed into a clinical candidate. IAMA-6 efficacy in refractory epilepsy will expand our pipeline of therapeutic indications. Finally, the discovery of new classes of selective NKCC1 inhibitors with different properties will further increase the number of candidates to be tested in additional and diverse conditions characterized by NKCC1/KCC2 imbalance. <b>Disclosure:</b> Dr. Savardi has received personal compensation for serving as an employee of Iama Therapeutics. Dr. Savardi has stock in Iama Therapeutics. The institution of Dr. Savardi has received research support from Jerome Lejeune Foundation. Dr. Savardi has received intellectual property interests from a discovery or technology relating to health care. Dr. Borgogno has received personal compensation for serving as an employee of IAMA Therapeutics SRL. Dr. Borgogno has stock in IAMA Therapeutics. Dr. Borgogno has received intellectual property interests from a discovery or technology relating to health care. Dr. De Vivo has received personal compensation in the range of $0-$499 for serving as a Consultant for IAMA. Dr. De Vivo has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for PPP. Dr. De Vivo has stock in IAMA. Dr. De Vivo has received intellectual property interests from a discovery or technology relating to health care. Dr. De Vivo has received publishing royalties from a publication relating to health care. Dr. Cancedda has received personal compensation in the range of $0-$499 for serving as a Consultant for IAMA. Dr. Cancedda has stock in IAMA therapeutics. Dr. Cancedda has received intellectual property interests from a discovery or technology relating to health care. Dr. Cancedda has a non-compensated relationship as a Principal investigator with Istituto Italiano di Tecnologia that is relevant to AAN interests or activities.

High Frequency Stimulation of the Centromedian Thalamic Nucleus to Abort Seizures and Interictal Discharges During Stereoelectroencephalography Evaluation (P5-1.007)

<h3>Objective:</h3> To assess whether high frequency stimulation of the centromedian nucleus of the thalamus can disrupt seizures and/or interictal discharges. <h3>Background:</h3> There is growing evidence that subcortical structures, including the thalamus, are involved in seizure networks in patients with neocortical epilepsy. Responsive neurostimulation of the centromedian nucleus of the thalamus (CMT) has been shown to terminate seizures in case reports of patients with generalized and focal neocortical epilepsy [Burdette, et al. <i>Epilepsy and Behavior</i>, 2020]. However, to our knowledge, no prior reports have demonstrated the utility of stimulating the thalamus during a sEEG evaluation. We present two patients with refractory neocortical epilepsy who underwent sEEG evaluation including an electrode in the CMT. <h3>Design/Methods:</h3> Both patients underwent real-time high frequency stimulation (HFS) at CMT during runs of interictal discharges. Patient 1 was also stimulated during seizures. Stimulation settings for both patients were 50Hz, 0.3msec pulse duration, for 3 seconds. Patient 1 underwent stimulation at 2mA while Patient 2 was 1mA. For patient 1, seizure characteristics before and after stimulation were compared using a student’s t-test (duration) and Fisher exact test (apnea). <h3>Results:</h3> For Patient 1, HFS of the CMT successfully aborted 4 seizures. Compared to 11 seizures prior to stimulation, those with HFS were significantly shorter (9.5 vs. 20.5 seconds, p=0.018). The patient did not develop clinical apnea in any of the 4 seizures aborted with HFS, but did with all of the 11 seizures without stimulation (p=0.001). Stimulation during runs of interictal discharges was inconclusive. In Patient 2, HFS aborted runs of inter-ictal discharges in all 10 attempts. <h3>Conclusions:</h3> These cases demonstrate that stimulation of the CMT during sEEG evaluation can abort electroclinical seizures and potentially interictal discharges. This supports the idea that the CMT is involved in focal neocortical epilepsy networks. Stimulation during sEEG may be useful in predicting efficacy of thalamic neurostimulation. <b>Disclosure:</b> Dr. Nathan has nothing to disclose. Dr. Adney has received research support from NINDS. Joshua M Rosenow, MD, FAANS, FACS has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Boston Scientific Neuromodulation. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Monteris. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Neurelis. Dr. Schuele has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for SK Life Science. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Jazz. Dr. Schuele has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Journal of Clinical Neurophysiology. Dr. Schuele has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Thomas Needham. Dr. Schuele has received research support from National Institute of Health. Dr. Gerard has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Greenwich Pharmaceuticals. The institution of Dr. Gerard has received research support from NIH/NINDS. The institution of Dr. Gerard has received research support from Xenon Pharmaceuticals. The institution of an immediate family member of Dr. Gerard has received research support from NIH. The institution of an immediate family member of Dr. Gerard has received research support from Novo Nordisk. The institution of Dr. Gerard has received research support from Eisai, Inc. (via Stanford University).

A simultaneous intracranial EEG-surface EMG analysis of generalized tonic-clonic seizures (P10-1.004)

<h3>Objective:</h3> To analyze the neurophysiology of generalized tonic-clonic (GTC) seizures using intracranial-EEG and surface-EMG data. <h3>Background:</h3> The precise mechanism of a GTC seizure is not well understood. A polygraphic analysis with intracranial-EEG (iEEG) and surface-EMG (sEMG) offers a unique opportunity to study this mechanism from a neurophysiological standpoint. <h3>Design/Methods:</h3> We studied two patients with refractory focal epilepsy, admitted to the epilepsy-monitoring unit with iEEG and sEMG. Both patients underwent direct electrical cortical stimulation for cortical mapping. iEEG and EMG signals were recorded using Nihon-Kohden’s JE-120 256-channel amplifier with a sampling rate of 2000Hz. A GTC seizure was provoked in both patients during their respective stimulation sessions. <h3>Results:</h3> The tonic phase demonstrated continuous spike activity in iEEG with highest power in 50–100Hz range. The sEMG activity demonstrated an interference pattern in both agonists and antagonists, consistent with a tetanic contraction with a very similar power spectrum as the iEEG. The clonic phase was characterized by polyspike and slow-wave pattern. The polyspikes and slow-waves were time-locked with synchronized tetanic sEMG bursts and silent-periods in agonists and antagonists, respectively. The polyspikes were superimposed with ~400–600Hz high-frequency oscillations (HFOs). The frequency of the serrations of the motor unit potentials in the sEMG bursts was a subharmonic of the HFOs. The iEEG-sEMG latency was ~17–21ms, consistent with corticospinal conduction. There was a progressive increase of the sEMG burst and silent-period duration during the clonic phase, associated with corresponding increases in the polyspike and slow-wave durations. <h3>Conclusions:</h3> This study shows a very close relationship between iEEG and sEMG activity in a GTC seizure. The very similar power spectra of the iEEG and sEMG activities indicate that a GTC seizure is a direct result of cortical electrical activity varying in a crescendo-decrescendo manner. The transition from tonic to clonic phase is due to the “weakening” of the seizure discharge intensity. <b>Disclosure:</b> Dr. Acar has nothing to disclose. Dr. Ticku has nothing to disclose. Dr. Fotedar has nothing to disclose.

Preclinical Proof-of-concept of a Novel AAV9-microRNA based Targeting of GRIK2 for the Treatment of Temporal Lobe Epilepsy (S44.001)

<h3>Objective:</h3> The objective of this study was to determine if lowering the expression of the Glutamate Ionotropic Receptor Kainate Type Subunit 2 (GRIK2) using RNA interference can be a therapeutic strategy for temporal lobe epilepsy (TLE). <h3>Background:</h3> TLE is the most common form of focal epilepsy characterized by recurrent seizures generated in the hippocampus. Patients with TLE are often resistant to anti-seizure medications. Recurrent mossy fiber sprouting from dentate granule cells (DGCs) is a consistent anatomical hallmark of TLE leading to synaptic reorganization in an aberrant excitatory network. In TLE the DGCs operate via ectopic expression of GluK2/GluK5 receptors. GluK2/GluK5 plays a central role in the generation of seizure activity. <h3>Design/Methods:</h3> We created an AAV9-vector carrying two miRNAs under the control of a neuron-specific promotor targeting GRIK2 (AMT-260). The vector has been tested in a pilocarpine mouse model for TLE and assessed for safety in non-human primates (NHP). Additionally, hippocampal organotypic slices from TLE patients were treated with AMT-260. The efficacy of AMT-260 was measured in the mouse model using electroencephalogram (EEG) and behavior as readouts, and in hippocampal organotypic slices using electrophysiological recordings. The safety and biodistribution of AMT-260 was assessed in NHP after 1 month of treatment. <h3>Results:</h3> AMT-260 showed a dose-dependent decrease in electrical seizures and hyperlocomotion and improved health. A full biological effect was observed at 5.0E+09 vg per hippocampus. Organotypic slices from patients with TLE treated with AMT-260 showed a decrease in the number of electrical seizures. Convection enhanced, MRI guided intrahippocampal delivery in NHP resulted in local high copies of vector and miRNA expression with substantial knockdown of GRIK2, but with no adverse findings and limited peripheral exposure to the vector. <h3>Conclusions:</h3> AMT-260 shows an excellent preclinical and safety profile and will proceed into clinical testing to treat patients with refractory mesial temporal lobe epilepsy. <b>Disclosure:</b> Nick Pearson has nothing to disclose. Dr. Baudouin has received personal compensation for serving as an employee of Uniqure. Dr. Baudouin has stock in Uniqure. Dr. Wartel has received personal compensation for serving as an employee of uniQure biopharma B.V.. Dr. Wartel has stock in uniQure biopharma B.V.. Mr. Keskin has received personal compensation for serving as an employee of uniQure. Mr. Keskin has stock in uniQure. Mr. Keskin has a non-compensated relationship as a Technician with uniQure that is relevant to AAN interests or activities. Dr. Danos has received personal compensation for serving as an employee of REGENXBIO. Dr. Danos has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vor Bio. Dr. Danos has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Coave Therapeutics. Dr. Danos has stock in REGENXBIO. Dr. Danos has stock in Coave Therapeutics. Dr. Danos has stock in Rocket Therapeutics. Dr. Mulle has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Corlieve Therapeutics. Dr. Mulle has stock in Corlieve Therapeutics. Mr. Partouche has nothing to disclose. Dr. CREPEL has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Corlieve Therapeutics. Dr. CREPEL has stock in Corlieve Therapeutics. The institution of Dr. CREPEL has received research support from Corlieve Therapeutics. Dr. CREPEL has received intellectual property interests from a discovery or technology relating to health care. Dr. Borta has received personal compensation for serving as an employee of uniQure. Dr. Borta has stock in uniQure. Dr. Porter has received personal compensation for serving as an employee of Uniqure. Dr. Porter has stock in uniqure. Dr. Porter has stock in roche.

Increased Perirolandic Cortical Excitability May Facilitate Sensory Motor Mapping in Children (P13-1.003)

<h3>Objective:</h3> We are hereby describing a case of refractory pediatric epilepsy where resection of perirolandic seizure foci was performed successfully under neurophysiologic guidance. <h3>Background:</h3> Pediatric neurophysiologic sensory-motor mapping is frequently unsuccessful, due to inability to localize central sulcus (CS) and primary motor cortex (M1). These shortcomings result from poor somatosensory evoked potentials (SSEP) and high M1 depolarization thresholds respectively, both reflections of the immaturity of the central nervous system. <h3>Design/Methods:</h3> Case report <h3>Results:</h3> An 8-year-old boy with developmental delay, debilitating focal epilepsy and epileptic encephalopathy underwent phase 2 video EEG monitoring. The recordings showed seizures with early involvement of several depth electrodes located within the right parieto-frontal regions, and an early motor semiology involving the left arm. The patient underwent neurophysiologically guided resection of the seizure foci under general anesthesia. Pre-resection electrocorticography (ECoG) via a 64 contact grid showed abundant perirolandic epileptiform discharges (ED), maximal postcentrally. Cortical recordings of high amplitude median SSEP and a low depolarization threshold led to successful CS localization and identification of M1, respectively. A subdural strip electrode placed over the precentral gyrus and secured in position, allowed simultaneous ECoG and motor monitoring during the resection of the postcentral foci. Initially, ECoG showed near continuous runs of ED, unchanged by cortical electrical stimulation. Under steady state anesthesia, at a constant propofol infusion rate, this activity decreased in frequency and stopped altogether towards the end stages of the resection, as the M1 threshold increased by 7 mA. Post-resection fronto-parietal ECoG recordings were quiet. Post-operatively, the patient became seizure free, showed cognitive improvement and no motor deficits. <h3>Conclusions:</h3> Increased cortical excitability may lead to successful functional mapping in children. Under steady anesthetic conditions, increases in the M1 threshold during resection of nearby epileptic foci may be an early sign of decrease in the abnormal regional cortical excitability. <b>Disclosure:</b> Dr. Alzahrany has nothing to disclose. Dr. Simon has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Risk Management Foundation of the Harvard Institutions Incorporated. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for MCIC Vermont. Dr. Simon has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Aaronson, Rappaport, Feinstein&amp; Deutch. Dr. Simon has received publishing royalties from a publication relating to health care. Dr. Simon has received personal compensation in the range of $0-$499 for serving as a Speaker with American Clinical Neurophysiology Society . Dr. Simon has a non-compensated relationship as a Speaker with International Society of Intraoperative Neurophysiology that is relevant to AAN interests or activities. Dr. Simon has a non-compensated relationship as a Speaker with Brazilian Congress of Neurology that is relevant to AAN interests or activities.

External Validation of Novel Method of Seizure Onset Zone Localization Based on Neural Resonance (P2-1.006)

<h3>Objective:</h3> We aimed to validate a recently published technique that used neural resonance to localize seizure onset zones (SOZ) with a retrospective dataset collected at an external institution. Further, we critically examined the need for a larger, tailored prospective validation study. <h3>Background:</h3> Accurate localization of the SOZ could improve surgical outcomes in medically refractory epilepsy patients. A recent study successfully used a novel metric of neural resonance to retrospectively identify SOZ regions and predict surgical success. The technique leverages distinct electrophysiological features of evoked responses during single pulse electrode stimulation (SPES) and incorporates them into a dynamical model. We aimed to validate these findings with a retrospective cohort of six patients to assess whether neural resonance predicted surgical outcomes. <h3>Design/Methods:</h3> We collected intracranial electroencephalographic (iEEG) data from six patients that underwent intracranial monitoring, single-pulse electrical stimulation protocol, and resection surgery between June 2020 and May 2021. Four out of six patients were stimulated in both SOZ regions and non-SOZ regions and thus were tested using the logistic regression model trained on the original dataset at the primary study institution. <h3>Results:</h3> Three of the four patients had successful surgical outcomes. Of the four patients tested with the logistic regression model, only one out of four was predicted correctly; the model predicted success for one true success and the failure patient. <h3>Conclusions:</h3> We hypothesize that the non-reproducibility of the original findings are resultant of differences in a research-driven SPES protocol and a clinically driven stimulation protocol. The external validation dataset stimulated a fewer number of sites, used a different clinical EEG and stimulation system, and varied stimulation parameters in a different subspace. However, this work highlights the need for a large, prospective validation dataset that is multi-center and encompasses a wide range of parameters; the gathering of this dataset is currently underway. <b>Disclosure:</b> Mr. Barnagian has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Kang has nothing to disclose. Mark Hays has nothing to disclose. Dr. Gonzalez has nothing to disclose. Dr. Sarma has stock in Neurologic Solutions, Inc.. Dr. Barot has nothing to disclose.

Real-world Outcomes of Cannabidiol For The treatment of Refractory Epilepsy in Pediatric Patients (P13-1.011)

<h3>Objective:</h3> Understand effectiveness of cannabidiol in varied etiologies. <h3>Background:</h3> Cannabidiol(Epidiolex, CBD) is a relatively new antiseizure medication that was FDA approved in 2018 for seizures with Lennox-Gastaut-syndrome(LGS), Dravet-syndrome or tuberous sclerosis. CBD continues to be studied in other epilepsies, particularly genetic epilepsies. <h3>Design/Methods:</h3> We performed a retrospective review of patients prescribed CBD younger than 19 who follow with Children’s Hospital in Omaha, Nebraska. We extracted demographic and clinical information from the medical records. Epilepsy syndromes and etiologies were recorded and classified per the 2017 ILAE guidelines. Records of CBD dose along with start and end of therapy were recorded when available. If discontinued, provider notes were reviewed to determine the reasoning. Given provider variability of notes, we categorized efficacy based on seizure frequency as follows: not improved, mildly improved(&lt;50% reduction), or greatly improved(&gt;50% reduction). The efficacy of CBD therapy was compared between genetic and not genetic etiologies. <h3>Results:</h3> A total of 32 patients were included in the study. Following CBD therapy in patients identified to have genetic etiology of epilepsy, 3 patient(23%)had no improvement, 4(30.7%)had mild improvement, and 6(46.1%)had great improvement (Table 1). In patients without a genetic etiology, 6 patients(31.6%)had no improvement, 1(5.2%)had mild improvement, and 12(63.1%)had great improvement(Table 1). Furthermore, among the non-genetic, 6 patients who did not have any improvement 5(83.3%)were structural and 1(16.7%)was unknown. Among the 12 who had great improvement, 6(50%)were unknown, 5(41.67%)were structural and 1(8.3%)was metabolic. CBD was discontinued in 6(18.8%)of the patients after a mean of 1.3(range 0.4–2.5)years of therapy, with reasons being the medication not being effective(<i>n</i>=2), increased appetite(1), agitation/irritability(1), vomiting(1), and change in diagnosis(1). <h3>Conclusions:</h3> Cannabidiol appears to be effective for the treatment of pediatric patients with both genetic and other etiologies of epilepsy. The majority of patients with non-genetic causes of LGS who did not improve with CBD had a structural etiology for their epilepsy. <b>Disclosure:</b> Dr. Fahad has nothing to disclose. Dr. Cameron has nothing to disclose. Dr. Dennis has nothing to disclose. Dr. Zhou has nothing to disclose. Dr. Rathore has nothing to disclose.

Thalamic neuromodulation outcomes in drug-resistant refractory epilepsy with Deep Brain Stimulation and Responsive Neurostimulation (P5-1.003)

<h3>Objective:</h3> We aim to compare effects of thalamic Deep Brain Stimulator (DBS) and responsive neurostimulator (RNS) device therapy on seizure burden in drug-resistant epilepsy patients. <h3>Background:</h3> Intractable epilepsy unamenable to cortical resection is often treated with a device, either RNS or DBS provides intracranial stimulation. The devices are thought to reduce seizure frequency by reducing synchronization of cortical activity. The RNS provides more localized stimulation while the DBS does this by stimulating the anterior nucleus of the thalamus. At our institution a small number of patients have also undergone thalamic stimulation by using the RNS. <h3>Design/Methods:</h3> We performed retrospective analysis on seizure frequency pre-implant and at most recent follow-up for our cohort, 12 DBS and 6 RNS patients. <h3>Results:</h3> Average age of RNS implantation was 30 years (range 19–41) vs 42 years (range 18–66) for DBS. Thirteen (9 DBS, 4 RNS) of the 18 patients had stereo-EEG (SEEG) evaluation before device placement, SEEG ictal onset was broad or multifocal in all (DBS: 7 – bilateral and 2 – unilateral, RNS: 3 bilateral, 1 unilateral). Three out of five patients who did not have invasive EEG evaluation before device placement had suspected (2) or confirmed (1) genetic etiology, all five had non-localizing, non-lateralizing scalp ictal EEG. The electrodes were placed to the anterior nucleus of thalamus bilaterally in all DBS and four RNS patients, two RNS patients had centromedian nucleus of thalamus sampling. Twelve of our 18 patients (8 out of 12 DBS and 4 out of 6 RNS) were shown to be responders, achieving 50% or greater reduction in seizure frequency. The average follow-up duration for RNS was 22 months (range 3–36), for DBS 13.5 months (range 2–29). <h3>Conclusions:</h3> This analysis demonstrates the potency of thalamic neuromodulation, both RNS and DBS, as therapies capable of seizure relief in wide breadths of epilepsy presentations. <b>Disclosure:</b> Dr. Das has received personal compensation for serving as an employee of Concentra. Dr. Das has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for janicek. The institution of an immediate family member of Dr. Das has received research support from NIH. irina podkorytova has nothing to disclose. Chijindu Iheanacho has nothing to disclose. Dr. Alick-Lindstrom has nothing to disclose. Dr. Agostini has nothing to disclose. Dr. Doyle has nothing to disclose. The institution of Dr. Ding has received research support from National Institute of Aging. The institution of Dr. Ding has received research support from NINDS. Dr. Hays has nothing to disclose. Dr. Perven has nothing to disclose. Dr. Dieppa has nothing to disclose. Dr. Zepeda Garcia has nothing to disclose.

Factors Mediating Public Perceptions of Therapeutic Closed-Loop Brain Implants for Epilepsy and Mood Disorders (P6-9.002)

<h3>Objective:</h3> To examine perceptions of implanted neural devices among groups underserved by prevailing neuropsychiatric treatment approaches. <h3>Background:</h3> “Closed-loop” devices that both sense and modulate brain activity represent a new paradigm for neuropsychiatric treatment. However, neurotechnologists and even neuroethicists are not demographically representative of U.S. society, so the concerns of groups most in need of new paradigms may not be reflected in current neurotechnology development. <h3>Design/Methods:</h3> We fielded a nationally representative survey (n=1047) oversampling non-Hispanic Black (n=214), Hispanic (n=210), and rural Americans (n=219), eliciting treatment preferences in scenarios comparing (1) a therapeutic closed-loop brain implant versus surgical resection for refractory epilepsy, and (2) an investigational closed-loop brain implant versus medications for mood disorders. We asked respondents to rate the importance of differing considerations favoring either the implanted device or traditional treatment. We examined whether such considerations mediate demographic differences in treatment preferences using survey-weighted logistic regression models. <h3>Results:</h3> In both scenarios, non-Hispanic Black Americans were less likely to prefer the implanted neural device than non-Hispanic White Americans (epilepsy OR 0.28, p&lt;0.001; mood OR 0.23, p=0.008); there was no main effect contrasting Hispanic with non-Hispanic White Americans, or contrasting rural with urban/suburban Americans. In the epilepsy scenario the difference between non-Hispanic Black and non-Hispanic White Americans’ treatment preferences was partially mediated by preference for established treatments, concerns about privacy, and concerns about hacking. In the mood scenario the difference between non-Hispanic Black and non-Hispanic White Americans’ treatment preferences was partially mediated by indifference to temporally specific action of a closed-loop device, concerns about changes to core traits, and preference for established treatments. <h3>Conclusions:</h3> Black Americans are less likely than White Americans to prefer closed-loop brain implants to traditional treatment, with specific concerns that may be informed by the history of unethical medical experimentation targeting Black people. <b>Disclosure:</b> Mr. Dada has received personal compensation for serving as an employee of Dreem Health. The institution of Mr. Chen has received research support from the National Institutes of Health (NIH). The institution of Dr. Haeusermann has received research support from the National Institutes of Health (NIH). Ms. Fong has nothing to disclose. Dr. Hamilton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Hamilton has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Highland Instruments. Dr. Hamilton has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology (Journal). The institution of Dr. Hamilton has received research support from NIH. The institution of Dr. Hamilton has received research support from Department of Defense. The institution of Dr. James has received research support from National Institute of Health. The institution of Dr. James has received research support from Society of Family Planning . The institution of Dr. James has received research support from Greenwall Foundation. Prof. Dohan has nothing to disclose. The institution of Dr. Chiong has received research support from the National Institutes of Health. The institution of Dr. Chiong has received research support from the Dana Foundation. Dr. Chiong has received personal compensation in the range of $500-$4,999 for serving as a member, NeuroEthics Working Group with National Institutes of Health.

Epilepsy surgery in a neonate: Resection of Right Temporal Neocortical Focal Cortical Dysplasia in a Three-Week-Old Infant. (P10-9.003)

<h3>Objective:</h3> n/a <h3>Background:</h3> Epilepsy surgery offers opportunity for seizure remission in patients with focal epilepsy refractory to polytherapy. Traditionally, only small portion of patients with drug resistant epilepsy are referred for surgical consideration. The patients who are referred on average have had epilepsy for two decades or more, leading to seizure related complications. We present our case report of an infant with severe refractory epilepsy, who underwent right temporal neocortical resection for focal cortical dysplasia at day 21 of life <h3>Design/Methods:</h3> Baby born at 38 weeks, on day of life 3 had apneic events associated with movements of her mouth and eye deviation to left. On EEG monitoring showed focal motor seizures originating from right temporal region. MRI Head revealed area of cortical dysplasia in the right middle and inferior temporal gyrus. The seizures were initially controlled but had breakthrough seizures on polytherapy requiring readmission. Risk of ongoing seizures with potential risks of surgery at young age were reviewed by our multidisciplinary team. As resection of the lesion would be curative, parents agreed for the procedure. Patient had the surgery: right sided hippocampal sparing temporal neocortical resection on Day of life 21. Patient was monitored post procedure, there were no seizures, so patient was able to be weaned off phenobarbital and phenytoin. Patient had repeat EEG 3 weeks post procedure for facial twitching and they were not epileptic. In the past year, patient was able to be weaned to Topiramate monotherapy with no further seizures and normal development for age. <h3>Results:</h3> n/a <h3>Conclusions:</h3> We present this case to highlight the use of surgical resection in infants with refractory focal seizures, even within the first month of life. Our patient has had a seizure free first year of life, is now on monotherapy, and her development is normal. <b>Disclosure:</b> Dr. Gangishetti has nothing to disclose. Dr. Ilgarli has nothing to disclose. Mrs. Tadisetty has nothing to disclose. Dr. Mirza has nothing to disclose. Dr. Haghighat has nothing to disclose.

A Potential Systematic Barrier to Community Health Literacy about Epilepsy Surgery: A Preliminary Readability Analysis of Online Health Education Materials in the United States (P6-1.006)

<h3>Objective:</h3> Analyze readability of online health education materials designed to provide epilepsy surgery information to patients. <h3>Background:</h3> Epilepsy surgery is an effective albeit underused treatment for refractory epilepsy. The workup and procedure explanations are complex and further compounded by the cognitive difficulties many people with epilepsy face. A previous United Kingdom study showed poor readability of online resources used for epilepsy surgery. However, there is still much to explore regarding the readability of resources in the United States, and what kinds of sites are associated with better readability. <h3>Design/Methods:</h3> A private browser was used to search Google for the top 100 search results for the terms “epilepsy+surgery”. Scientific papers, insurance pages, pay-wall access sites, and non-text content were excluded. The website text was re-formatted to exclude graphics, contact information, links, and headers. Readability metrics were calculated using an online readability tool (Datayze Readability Analyzer). Analysis was done through R using the Kruskal-Wallis test, and statistical assumptions were assessed. <h3>Results:</h3> Here we present the preliminary analysis of the top 100 items from a Google search yielding 76 websites and 24 exclusions. Websites were categorized as US based organizations or non-US, content from level 4 epilepsy centers, and if the sources were community health websites not associated with academic institutions. The Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL) showed significantly better readability in community health websites (FRE p=.03, FKGL p=.03), non-level 4 epilepsy centers (FRE p=.002, FKGL p=.002), and international websites (FRE p=.02, FKGL =.03). <h3>Conclusions:</h3> Health information source characteristics associated with better readability levels included non-academic centers, non-level 4 epilepsy centers and community health information websites. This analysis suggests that academic centers, especially level 4 epilepsy centers, should consider involving community members, advocacy organizations and non-medical writers in the designing of online epilepsy surgery health education materials. <b>Disclosure:</b> Mr. Seneviratne has nothing to disclose. Ms. Ho has nothing to disclose. Dr. Correa has received personal compensation in the range of $0-$499 for serving as a Consultant for Independent Medical Consultants. Dr. Correa has received personal compensation in the range of $0-$499 for serving as a Consultant for Atheneum Partners. Dr. Correa has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. Dr. Correa has stock in Aidin Inc. Dr. Correa has received research support from Genentech. Dr. Correa has received research support from Psi Upsilon Foundation Inc.

Outcomes of Surgical Resection and VNS in Patients with Medically Refractory Epilepsy and GAD65 Antibody Positivity (S40.004)

<h3>Objective:</h3> To determine effectiveness of vagus nerve stimulator (VNS) and surgical resection in patients with drug-resistant epilepsy associated with glutamic acid decarboxylase 65 (GAD65) antibodies. <h3>Background:</h3> Epilepsy associated with high-titer GAD65 antibodies is often refractory to immunotherapies and antiseizure medications (ASMs), underscoring the need for alternate treatment strategies. <h3>Design/Methods:</h3> We retrospectively identified Mayo Clinic Rochester patients (January 2003 – April 2022) with drug-resistant epilepsy and high serum GAD65-antibody titers (&gt;20 nnmol/L) who underwent surgical resection and/or VNS implantation. A “favorable” surgical outcome was defined as Engel I-II, and a responder to VNS was defined as a &gt;50% reduction in seizure frequency from baseline. <h3>Results:</h3> We identified 15 patients (13 females, 86.7%) who underwent surgical resection (n=7), VNS implantation (n=6), and both (n=2). Patients had failed a median of 5.5 anti-seizure medications. Twelve patients had GAD65 tested in the CSF, all were positive (median titer 3.8). Of the nine patients who underwent surgical intervention (all involving the temporal region), three (33.3%) had a favorable outcome, which was sustained for at least 3.5 years in one, 10 years in another, and the third was lost to follow-up after 1 year. Pathology was available in four patients, only one had evidence of inflammation. Of the 8 patients who underwent VNS implantation, 3 (37.5%) were initially considered a responder, but this was not sustained in two of the three. No clinical factors were statistically associated with favorable surgical or VNS outcomes. <h3>Conclusions:</h3> Temporal surgical resection and VNS are not highly effective in drug-resistant autoimmune-associated epilepsy related to high-titer GAD65 antibodies. Additional therapies are greatly needed for this challenging clinical scenario. <b>Disclosure:</b> Dr. Zhao-Fleming has nothing to disclose. Dr. Britton has received personal compensation in the range of $0-$499 for serving as a Online course with American Clinical Neurophysiology Society. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology . Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Smith has received research support from CURE Epilepsy.