Refractory Seizures Research Articles

Two novel variants of the STXBP1 and CHRNB2 genes identified in a Chinese boy with refractory seizures and developmental delay.

Autosomal dominant sleep-related hypermotor epilepsy is a rare disease caused by pathogenic variants of CHRNB2, CHRNA4, and CHRNA2 genes, with nocturnal frontal lobe epilepsy as the main symptoms. Syntaxin binding protein 1 (STXBP1) gene mutation can cause developmental and epileptic encephalopathy 4, mainly presenting as a developmental and epileptic encephalopathy. We performed the exome-targeted next-generation sequencing in our patient and identified two heterozygous variants: c.963 + 2T>C of STXBP1 and c.520_527delinsTGCTAC (p.R174Cfs*16) of CHRNB2. Molecular analysis was performed of the variant c.963 + 2T>C. Aberrantly spliced products were observed, proving the pathogenicity of this variant. Refractory seizures and developmental delay could be explained. Although the variant c.520_527delinsTGCTAC could cause the truncation of the proteins, it was ultimately determined to be nonpathogenic. The startle-like responses that occurred occasionally during the night were ultimately determined to be an uncommon phenotype caused by the STXBP1 variant.

Protocol of a prospective multicenter randomized controlled trial of robot-assisted stereotactic lesioning in the treatment of focal drug-resistant epilepsy

BackgroundThis protocol describes the design of a multicenter randomized controlled trial of robot-assisted stereotactic lesioning versus epileptogenic foci resection. Typical causes of focal epilepsy include hippocampal sclerosis and focal cortical dysplasia. These patients usually present with drug resistance and require surgical treatment. Although epileptogenic foci resection is still the most commonly used treatment for such focal epilepsy, there is increasing evidence that epileptogenic focus resection may lead to neurological impairment. The treatment of epilepsy with a robot-assisted stereotactic lesioning mainly includes two new minimally invasive surgical methods: radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT). Seizure-free is less likely to be achieved by these two procedures, but neurologic preservation is better. In this study, we aimed to compare the safety and efficacy of RF-TC, LITT, and epileptogenic foci resection for focal drug-resistant epilepsy.MethodsThis is a multicenter, three-arm, randomized controlled clinical trial. The study will include patients older than 3 years of age with epilepsy who have had medically refractory seizures for at least 2 years and are eligible for surgical treatment with an epileptogenic focus as determined by multidisciplinary evaluation prior to randomization. The primary outcome measure is seizure outcome (quantified by seizure remission rate) at 3-month, 6-month, and 1-year follow-up after treatment. Postoperative neurologic impairment, spectrum distribution change of video electroencephalogram, quality of life, and medical costs will also be assessed as secondary outcomes.Trial registrationChinese Clinical Trials Registry ChiCTR2200060974. Registered on June 14, 2022. The status of the trial is recruiting, and the estimated study completion date is December 31, 2024.

Utilization of the ketogenic diet for adults with status epilepticus

BackgroundThe ketogenic diet (KD) is a high-fat, low-carbohydrate diet with therapeutic potential in refractory seizures, both in outpatient and inpatient settings. Successful implementation of KD involves a multifaceted, interdisciplinary approach to address anticipated challenges. We sought to characterize the utilization of KD among healthcare providers caring for adults with status epilepticus (SE). MethodsWe distributed a web-based survey through professional societies, including the American Academy of Neurology (AAN), Neurocritical Care Society (NCS), American Epilepsy Society (AES), Neuro Anesthesia and Critical Care Society (NACCS), and the Academy of Nutrition and Dietetics (AND), and via research contacts. We asked respondents about practice experience and experience using KD as a treatment for SE. Descriptive statistics and Chi-square tests were used to analyze the results. ResultsOf 156 respondents, 80% of physicians and 18% of non-physicians reported experience with KD for SE. Anticipated difficulty in achieving ketosis (36.3%), lack of expertise (24.2%), and lack of resources (20.9%) were identified as the most important barriers limiting the utilization of KD. The absence of dietitians (37.1%) or pharmacists (25.7%) support was the most important missing resource. Reasons for stopping KD included perceived ineffectiveness (29.1%), difficulty achieving ketosis (24.6%), and side effects (17.3%). Academic centers had more experience with the use of KD and greater EEG monitoring availability and fewer barriers to its implementation. The need for randomized clinical trials supporting efficacy (36.5%) and better practice guidelines for implementation and maintenance of KD (29.6%) were cited most frequently as factors to increase utilization of KD. ConclusionThis study identifies important barriers to the utilization of KD as a treatment for SE despite evidence supporting its efficacy in the appropriate clinical context, namely lack of resources and interdisciplinary support, and lack of established practice guidelines. Our results highlight the need for future research to improve understanding of the efficacy and safety of KD along with better interdisciplinary collaborations to increase its utilization.

Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology.

Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists for most patients. The unmet clinical need requires a more comprehensive understanding of the disease mechanisms and the development of reliable and robust in vivo models that accurately recapitulate human disease. This review aims to summarise and discuss various mouse models harbouring transgenic impairments in genes that regulate mitochondrial function, specifically their neurological phenotype and neuropathological features. Ataxia secondary to cerebellar impairment is one of the most prevalent neurological features of mouse models of mitochondrial dysfunction, consistent with the observation that progressive cerebellar ataxia is a common neurological manifestation in patients with mitochondrial disease. The loss of Purkinje neurons is a shared neuropathological finding in human post-mortem tissues and numerous mouse models. However, none of the existing mouse models recapitulate other devastating neurological phenotypes, such as refractory focal seizures and stroke-like episodes seen in patients. Additionally, we discuss the roles of reactive astrogliosis and microglial reactivity, which may be driving the neuropathology in some of the mouse models of mitochondrial dysfunction, as well as mechanisms through which cellular death may occur, beyond apoptosis, in neurons undergoing mitochondrial bioenergy crisis.

A novel DOCK7 variant as a rare reason for epileptic encephalopathy, cortical blindness, dysmorphic features: A case report and brief review of the literature

Early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615859) is a rare autosomal recessive disorder. It is characterized by refractory seizures, multifocal epileptic activity on electroencephalography, psychomotor development delay, dysmorphic facial features and cortical blindness/visual impairment. DOCK7 is involved in intracellular signaling networks and plays a role in axon formation and neuronal polarization. Function loss of this gene has previously been described in the molecular etiology of EIEE23. Here, we report a boy with a pathogenic novel variant in the DOCK7 gene presenting with, infantile-onset epileptic encephalopathy, severe neurodevelopmental delay, dysmorphic facial features, cortical blindness as well as previously unreported minor dental and extremity anomalies. Few cases with DOCK7 mutations have been reported in the literature. Due to its high genetic heterogeneity and scarcity, it is extremely important to report a novel and specific mutations and their associated clinical phenotypes. Whole exome sequencing revealed a novel pathogenic homozygous frameshift variant which has not been reported (c.5669dup (p.Cys1891ValfsTer2) mutation in the exon 44 of DOCK7).

ID: 208947 Ultrashort Microscopic Magnetic Vagal Stimulation

Electrical stimulation of the cervical vagus nerve is an emerging treatment field for various central nervous system disorders. Invasive electrical Vagus nerve stimulation (VNS) is an FDA-approved add-on treatment to medication for refractory partial-onset seizures in patients 12 years of age and older. However, only approximately 40-50% of patients experience a marked seizure reduction of 50% or more than seizures before treatment [1]. The effects of VNS on neurotransmitter systems, including the noradrenergic system originating from the locus coeruleus and the serotonergic system from the dorsal raphe nucleus, have been reported in experimental settings. The therapeutic effect of VNS in the brain is linked to the stimulation of large diameter afferent fibers. These large myelinated afferent fibers, terminating in the nucleus tractus solitarius in the brainstem, are assumed to deliver the therapeutic effect through further projections into the other brain areas. Non-selective stimulation results in inadvertent activation of efferent fibers that innervate a wide range of peripheral organs resulting in adverse effects [2] with a rare but severe risk of bradyarrhythmia and asystole.

P.069 Is 4 days enough? an investigation into short admissions to the Epilepsy monitoring unit

Background: The Epilepsy Monitoring Unit (EMU) plays a crucial role in a patient’s diagnosis and management for seizures and epilepsy. The duration of stay required to obtain adequate information is not clear, especially in the pediatric population. In this study, we examine whether a one to four day length of stay in the EMU is sufficient to obtain the necessary information. Methods: Retrospective review of 522 admissions (2014-2021). Included any patient admitted to CHEO’s EMU for any length of time. Results: The average admission was 1.75 days with 35.7% of patients requiring repeat EMU visits. Through a binary logistic regression, we show that a previous diagnosis of refractory seizures increases the chance of readmission to the EMU. However, a diagnosis of refractory seizures is also associated with a higher chance of achieving admission goals. While other factors including seizure type, weaning of meds, goals of admission, age, and gender have no influence on likelihood of readmission or achieving admission goals. Conclusions: This study indicates that having a short admission for EMU monitoring is sufficient to capture enough data to achieve admission goals in the pediatric population.

Arginase deficiency-An unheralded cause of developmental epileptic encephalopathy.

Arginase deficiency, which leads to hyperargininaemia is a rare urea cycle disorder caused by a mutation in the ARG1 gene. It is an under-recognized cause of pediatric developmental epileptic encephalopathy, with the key coexistent clinical features being developmental delay or regression and spasticity. Detection of ARG1 gene mutation on genetic testing is the confirmatory diagnostic test. However, elevated levels of plasma arginine and low plasma arginase level can be considered as biochemical markers for diagnosis. We present two cases of arginase deficiency with genetically confirmed ARG1 mutation in one and biochemical confirmation in both. As the spectrum of epilepsy in arginase deficiency has been less explored, we attempted to elucidate the novel electroclinical features and syndromic presentations in these patients. Informed consent was obtained from families of patients. Electroclinical diagnosis was consistent with Lennox Gastaut syndrome (LGS) in the first patient while the second patient had refractory atonic seizures with electrophysiological features consistent with developmental and epileptic encephalopathy. Though primary hyperammonaemia is not a consistent feature, secondary hyperammonaemia in the setting of infectious triggers and drugs like valproate (valproate sensitivity) has been well described as also observed in our patient. In the absence of an overt antecedent in a child with spasticity and seizure disorder, with a progressive course consistent with a developmental epileptic encephalopathy, arginase deficiency merits consideration. Diagnosis often has important therapeutic implications with respect to dietary management and choice of the appropriate antiseizure medications.

Difficulties in the implementation of the ketogenic diet in adult patients with refractory epilepsy

BackgroundKetogenic diet therapies (KDT) are appropriate therapeutic options for pediatric and adult patients with intractable epilepsy. The application of KDT among adult patients with refractory epilepsy is limited compared to children for several reasons, including poor compliance. We present the significant reasons for the lack of adherence to KDT in our adult patients with intractable epilepsy. MethodsThis study was conducted retrospectively in adult patients with drug-resistant epilepsy who wereofferedand accepted toimplementKDT between 2014 and 2021. Demographic and clinical data were collected via electronic health records. The eventual outcome of KDT results was obtained from the consultant dietitian. The prevalence and reasons for the failure to implement KDT were investigated. We also obtained detailed information about patients who successfully applied the KDT. ResultsA total of 33 patients (18F; median age 28) who wereoffered and accepted to implement KDT were included. Baseline seizure frequency was >4 per week in 49%, and more than half of the patients used >3 anti-seizure medications (ASM). Epilepsy types were temporal in 10 (30%), extratemporal in 10 (30%), generalized in 6 (18%), and unclassified in 7 (22%) patients.Only 3 patients (9%) were able to maintain KDT in the long term. One of them (33%) benefited from this therapy.In the remaining 30 patients, the reasons for failure were inability to contact the dietitian in 5, failure to apply KDT for a particular reason in 7, inappropriate blood test results or any medical/surgical comorbidities in 6, improvement in seizure burden due to change in ASM in 5, still insufficient knowledge of KDT in 3, unresponsiveness to diet due to incorrect implementation in 1 and unidentified reasons in 3 patients. ConclusionsA significant percentage of adult patients with refractory seizures failed to use KDTin our study(91%).Strategies to improve compliance and minimize the side effects might increase the number of drug-refractory epilepsy patients who could benefit from this therapy.

Meningioangiomatosis with Skull Erosion

Meningioangiomatosis (MA) is a rare, poorly studied brain hamartomatous lesion, the etiology of which is not fully elucidated. It typically involves the leptomeninges, extending to the underlying cortex, characterized by small vessel proliferation, perivascular cuffing, and scattered calcifications. Given its close proximity to, or direct involvement of, the cerebral cortex, MA lesions typically manifest in younger patients as recurrent episodes of refractory seizures, comprising approximately 0.6% of operated-on intractable epileptic lesions. Due to the absence of characteristic radiological features, MA lesions constitute a significant radiological challenge, making them easy to miss or misinterpret. Although MA lesions are rarely reported with still-unknown etiology, it is prudent to be aware of these lesions for prompt diagnosis and management to avoid morbidity and mortality associated with delayed diagnosis and treatment. We present a case of a young patient with a first-time seizure caused by a right parieto-occipital MA lesion that was successfully excised via an awake craniotomy, achieving 100% seizure control.

Rare cause of drug-resistant epilepsy due to GABA transaminase deficiency: A case report from India

Gama aminobutyric acid (GABA) transaminase deficiency is an autosomal recessive disorder caused by mutations in the 4-aminobutyrate aminotransferase (ABAT) gene. The disorder is characterised by epileptic encephalopathy, hypersomnoloscnec, movement disorders, and tone changes. Here, we report a 4-year-6-month-old boy child born to non-consanguineous marriage with a normal birth history presented with global developmental delay, refractory seizures, and increased sleep. On examination showed normal anthropometry with mild dysmorphism. Neurological examination showed autistic features and spasticity with brisk deep tendon reflexes. On investigation, electroencephalography showed multifocal epileptiform discharges with secondary generalisation, and magnetic resonance imaging of the brain showed mild hyperintensity of the superior cerebellum. Exome sequencing identified compound heterozygous variants in the ABAT gene and segregates with the condition in the family. The child was treated with antiseizure medications and responded partially. For any child with excessive sleep on the background of epileptic encephalopathy with a movement disorder, a diagnosis of GABA transaminase deficiency has to be considered.

Dyke-Davidoff-Masson Syndrome: A Case Report in a Filipino Male Adolescent

A previously well young Filipino boy presented with prolonged recurrent left focal to bilateral seizure. He was born of a non-consanguineous marriage, home-delivered vaginally, full term with no perinatal complications. He had normal growth and developmental milestones until at the age of 7 months when he developed febrile status epilepticus. Since then, he was left with residual left hemiplegia, dysarthria, cognitive delay and recurrent seizures occurring twice daily. He was poorly compliant on multiple anti-seizure medications. He was able to go to school and do activities of daily living with minimal supervision from his family. Symptoms of refractory seizures, hemiparesis, facial asymmetry, and intellectual disabilities along with brain imaging evidence of cerebral hemi-atrophy with compensatory calvarial thickening and subsequent hyperpneumatization is consistent with Dyke-Davidoff-Masson Syndrome (DDMS). A rare clinico-neuroradiologic condition occurring in fetal or early childhood period as a consequence of chronic brain insult. Diagnosis is established clinically with a characteristic cranial imaging finding. Hemi-spherectomy is the treatment of choice. This case will enlighten our mind as well as aid us in the prompt recognition of this uncommon syndrome with a classic clinico-radiologic presentation. Multidisciplinary intervention is essential, primarily to optimize seizure control as well as provide quality of life.

SZT2 variants associated with partial epilepsy or epileptic encephalopathy and the genotype-phenotype correlation.

Recessive SZT2 variants are reported to be associated with developmental and epileptic encephalopathy 18 (DEE-18) and occasionally neurodevelopment abnormalities (NDD) without seizures. This study aims to explore the phenotypic spectrum of SZT2 and the genotype-phenotype correlation. Trios-based whole-exome sequencing was performed in patients with epilepsy. Previously reported SZT2 mutations were systematically reviewed to analyze the genotype-phenotype correlations. SZT2 variants were identified in six unrelated cases with heterogeneous epilepsy, including one de novo null variant and five pairs of biallelic variants. These variants had no or low frequencies in controls. All missense variants were predicted to alter the hydrogen bonds with surrounding residues and/or protein stability. The three patients with null variants exhibited DEE. The patients with biallelic null mutations presented severe DEE featured by frequent spasms/tonic seizures and diffuse cortical dysplasia/periventricular nodular heterotopia. The three patients with biallelic missense variants presented mild partial epilepsy with favorable outcomes. Analysis of previously reported cases revealed that patients with biallelic null mutations presented significantly higher frequency of refractory seizures and earlier onset age of seizure than those with biallelic non-null mutations or with biallelic mutations containing one null variant. This study suggested that SZT2 variants were potentially associated with partial epilepsy with favorable outcomes without NDD, expanding the phenotypic spectrum of SZT2. The genotype-phenotype correlation helps in understanding the underlying mechanism of phenotypic variation.

The potential role of astroglial GABAA receptors in autoimmune encephalitis associated with GABAA receptor antibodies and seizures.

The γ-aminobutyric acid (GABA) is the main inhibitory transmitter in the central nervous system and GABA receptors mediate the inhibitory synaptic transmission. GABA binding to neuronal GABAA R leads to a rapid hyperpolarization and a higher excitation threshold due to an increase in membrane Cl- permeability. The synaptic GABAA R is mostly composed of two α(1-3), two β, and one γ subunit with the most abundant configuration α1β2γ2. Recently, antibodies (Abs) against α1, β3, and γ2 subunits of GABAA R were detected in a severe form of autoimmune encephalitis with refractory seizures, status epilepticus, and multifocal brain lesions, affecting gray and white matter. Experimental studies confirmed multiple mechanisms and direct functional effects of GABAA R Abs on neurons with decreased GABAergic synaptic transmission and increased neuronal excitability. The expression of GABAA R on astrocytes is well established. However, extensive studies about the effects of autoimmune GABAA R Abs on astrocytic GABAA R are missing. We hypothesize that GABAA R Abs may lead additionally to blocking astrocytic GABAA Rs with impaired Ca2+ homeostasis/spreading, astrocytic Cl- imbalance, dysfunction of astrocyte-mediated gliotransmission (e.g., decreased adenosine levels) and accumulation of excitatory neurotransmission, all this contributing to seizures, variable clinical/MRI presentations, and severity. The most abundant expressed GABAA R subunits in rodent astrocytes are α1, α2, β1, β3, and γ1 localized in both white and gray matter. Data about GABAA R subunits in human astrocytes are even more limited, comprising α2, β1, and γ1. Overlapping binding of GABAA R Abs to neuronal and astroglial receptors is still possible. In vitro and in vivo animal models can be helpful to test the effects of GABAA R Abs on glia. This is from an epileptological point of view relevant because of the increasing evidence, confirming the glial involvement in the pathogenesis of epilepsy. Taken together, autoimmune disorders are complex and multiple mechanisms including glia could contribute to the pathogenesis of GABAA R encephalitis with seizures.

Anti-LGI1 encephalitis with initiating symptom of seizures in children.

Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Case 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.

Refractory Seizures in the Setting of Lupus (P9-5.027)

<h3>Objective:</h3> To present a case of systemic lupus erythematosus (SLE) that manifested as refractory seizures with a positive response to immunosuppressive therapy. <h3>Background:</h3> SLE is a chronic autoimmune disease characterized by the production of autoantibodies resulting in tissue injury across multiple organs; up to 50% of patients develop neurologic involvement, collectively referred to as neuropsychiatric systemic lupus erythematosus. Autoimmune encephalitis remains a rare presentation of SLE. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A previously healthy 22-year-old-female presented with fatigue, worsening cognitive impairment, multiple pre-syncopal episodes that began a few months ago. There was concern for seizures; video-EEG monitoring captured electrographic seizures originating in the right temporal region. Levetiracetam was initiated but focal epileptic seizures in right temporal, frontal regions with secondary generalization continued to occur. Lacosamide and valproic acid were added with some improvement. MRI brain was unremarkable. Given the milieu of the patient’s symptoms, autoimmune encephalitis was suspected. CSF studies showed an elevated opening pressure (30mL), but were negative for Mayo clinic autoimmune encephalitis panel. The patient was started on plasmapheresis concurrently with a 5-day course of IV methylprednisolone with steroid taper. The patient achieved seizure freedom on day 2 of plasmapheresis and day 4 of steroids. A pan-CT scan was essentially unremarkable. Rheumatologic workup revealed low C3, C4, complement levels, positive ANA, and positive double-stranded DNA antibodies, confirming systemic lupus erythematosus. The patient was transitioned to mycophenolic acid. Follow up 8 weeks later showed increased C3, C4 levels while patient was maintained on immunosuppressants and she continued to be seizure free. <h3>Conclusions:</h3> Antibody-mediated diseases can occur anywhere in the body where the immune system is able to gain access to a target antigen. We believe that CNS involvement of lupus may represent an under-recognized entity in the general category of NPSLE with features of autoimmune encephalitis, which include a similar therapeutic response to early plasmapheresis. <b>Disclosure:</b> Dr. Canlas has nothing to disclose. Dr. Kadakia has nothing to disclose. Dr. Shaji has nothing to disclose. Dr. Hosey has nothing to disclose.

Copy Number Variant Associated with Familial Epilepsy with Wide Phenotypic Spectrum: A Case Series (P3-1.003)

<h3>Objective:</h3> Not Applicable <h3>Background:</h3> Many patients with familial epilepsy lack identifiable genetic causes. We report a 29-year-old patient with autism and refractory seizures since age 16 years, along with her mother and two sisters who all have epilepsy with varying electroclinical phenotypes. <h3>Design/Methods:</h3> All four family members underwent genetic counseling and pedigree was generated. Three family members (Patient 1, 2 and 4 described below) underwent whole-genome sequencing (WGS). <h3>Results:</h3> WGS of patient, mother, and one sister revealed a 1.1 mb copy number gain of the X chromosome located at position (31,052,355–32,186,379) - including exons 45–79 of the <i>DMD</i> and <i>FTHL17</i> genes. Electroclinical phenotypes are detailed below: <h3>Patient 1 (Proband):</h3> 29-year-old patient with seizure onset at age 16 years and autism. Has multiple refractory seizure types including focal tonic and atonic seizures. Ictal EEG showed left frontocentral onset and diffuse attenuation. Patient is refractory on four anti-seizure medications (ASMs). <h3>Patient 2:</h3> 30-year-old sister with seizure onset since age 14 years. Seizures are bilateral tonic-clonic and focal with impaired awareness. Ictal EEG showed diffuse onset in both types. Patient is refractory on 3 ASMs. <h3>Patient 3:</h3> 32-year-old sister with epilepsy since age 20 years. Seizures are focal with impaired awareness. Ictal EEG showed independent seizures with left temporal and right frontotemporal onset. She is refractory on 2 ASMs. <h3>Patient 4:</h3> 57-year-old mother with seizure onset since age 19 years. Seizures are focal with impaired awareness. Ictal EEG demonstrates right frontoparietal onset. She is well controlled on 2 ASMs. <h3>Conclusions:</h3> We describe an X-linked copy number variant mutation associated with familial epilepsy. Family members have variable electroclinical phenotypes. Role of <i>DMD</i> or <i>FTHL17</i> genes in epileptogenicity is unclear. Emerging data has linked dystrophin to clustering of GABA-a receptors at the post-synaptic membrane, thought to regulate inhibitory input and neuronal activity which warrants further investigation. <b>Disclosure:</b> Dr. Pokharel has nothing to disclose. Dr. Przybycien has nothing to disclose. Karen Krajewski has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Zutshi has nothing to disclose. Dr. Basha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai.

Online CME-Certified Expert Panel Discussion Improves Awareness Among Neurologists Regarding Seizure Freedom in Patients with Epilepsy (P14-2.003)

<h3>Objective:</h3> An online CME-certified activity was developed to educate neurologists on the importance of achieving seizure freedom and clinical data on seizure freedom for anti-seizure medications (ASMs), particularly among patients refractory to treatment. <h3>Background:</h3> The primary goals of epilepsy treatment are to achieve seizure freedom without side effects. However many patients with epilepsy continue to experience seizures and are not offered therapeutic options that may offer greater seizure control. <h3>Design/Methods:</h3> The online CME activity consisted of a 30-minute video discussion between three expert epileptologists. Educational effect was assessed by comparing neurologists’ pre- and post-activity responses to four questions. A paired-samples t-test was used to assess significant differences between pre- and post-assessment responses. Cohen’s <i>d</i> was used to calculate the effect size of the online education. Data were collected between April 6, 2022 and June 29, 2022. <h3>Results:</h3> Among neurologists who participated in the activity, a small educational effect was observed (n=133; <i>d</i>=.34, <i>P</i>&lt;.001). The following areas showed significant (<i>P</i> &lt;.05) pre- vs post-educational improvements: patient-related consequences of uncontrolled seizures and the seizure-freedom rate reported in a clinical trial of an ASM in patients with treatment refractory focal seizures. There was a non-significant pre-vs post educational improvement on a question asking about how to address dosing when a new ASM is added to an existing ASM. Participation in the activity resulted in 32% of neurologists reporting an increase in confidence regarding their ability to optimize the dosing of ASMs to maximize the chance of achieving seizure freedom. <h3>Conclusions:</h3> The results indicated that a CME-certified 30-minute video activity was effective at improving knowledge among neurologists’ regarding seizure freedom in patients with epilepsy. Given the lack of a significant educational effect on ASM dosing, future education should continue to address dosing in the setting of combination ASM therapy. <b>Disclosure:</b> Dr. Finnegan has nothing to disclose. Jovana Lubarda has nothing to disclose. The institution of Dr. Chung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ucb pharma. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SK Life sciences. Dr. Chung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for eisai. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for ucb. Dr. Chung has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for SK Life sciences. Dr. Chung has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for sunovion.

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.

The Utilization of the Ketogenic Diet for Adults with Status Epilepticus (P8-7.003)

<h3>Objective:</h3> To characterize the utilization of ketogenic diet (KD) among healthcare providers caring for adult patients with status epilepticus (SE). <h3>Background:</h3> KD is a high fat, low carbohydrate diet that has been shown to effectively treat refractory seizures, both in the outpatient and inpatient settings. The successful implementation of KD involves a multifaceted, interdisciplinary approach with many potential barriers. <h3>Design/Methods:</h3> 27-question web-based survey (Qualtrics®) targeting healthcare providers who manage adult SE patients in both academic and community-based settings distributed by various neurology and critical care specialties societies. <h3>Results:</h3> Of 156 respondents, 80% of physicians and 18% of non-physicians reported using KD for SE. Achieving ketosis (36.3%), lack of expertise (24.2%), and lack of resources (20.9%) were identified as some of the most important barriers limiting the utilization of KD. Absence of nutrition support (37.1%) and of pharmacy support (25.7%) were the most important missing resources. Reasons for stopping KD were identified as ineffectiveness (29.1%), difficulty achieving ketosis (24.6%) and side-effects (17.3%). The discrepancies are evident when comparing providers in the academic versus non-academic settings. The former has significantly more experience with the use of KD and EEG monitoring availability, and fewer barriers to its implementation. The need for more randomized clinical trials supporting efficacy (36.5%) and increased practical guidelines for implementation and maintenance of KD (29.6%) were mostly cited as factors to increase the utilization of KD for SE. <h3>Conclusions:</h3> We identified multiple target areas to improve the utilization of KD through future research. These include better interdisciplinary collaboration, studies exploring factors affecting the achievement of ketosis and the management of side effects, and large-scale clinical trials examining the efficacy of this treatment. KD represents an underexplored treatment modality which may prove crucial in improving management of SE. <b>Disclosure:</b> Dr. Jacinto Pereira Teixeira has nothing to disclose. Ms. Shannon has nothing to disclose. Dr. Robinson has nothing to disclose. Bakhtawar Ahmad has nothing to disclose. Mr. Katz has nothing to disclose. Guanhong Miao has nothing to disclose. Ms. Seckar has nothing to disclose. Dr. Bruzzone has nothing to disclose. Dr. Busl 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 Society of Critical Care Medicine. The institution of Dr. Busl has received research support from University of Florida Self Insurance Program. The institution of Dr. Busl has received research support from National Institutes of Health. Dr. Busl has a non-compensated relationship as a Board Member with Art in Medicine that is relevant to AAN interests or activities. Dr. Busl has a non-compensated relationship as a Associate Editor with Critical Care Explorations that is relevant to AAN interests or activities. Dr. Busl has a non-compensated relationship as a Editorial Board Member with Neurocritical Care that is relevant to AAN interests or activities. Dr. Cervenka has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Nutricia. Dr. Cervenka has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nestle Health Science/Vitaflo. The institution of Dr. Cervenka has received research support from Nestle Health Science/Vitaflo. Dr. Cervenka has received publishing royalties from a publication relating to health care. Dr. Maciel has received research support from American Heart Association. Dr. Maciel has received research support from National Institute of Health.