Focal Onset Research Articles

Report of three patients with extensive neurocysticercosis in rural southern Tanzania: neurological, serological and neuroradiological findings

BackgroundNeurocysticercosis (NCC) is common in eastern Africa, but disease presentation varies considerably. Most patients have single or few NCC-typical lesions in their brain but some present with a large number of lesions. We present three patients with positive antibody-based serology for Taenia solium cysticercosis screened at the Vwawa district hospital, Mbozi district, southern Tanzania, in whom extensive NCC was confirmed by neuroimaging.Case presentationsPatient 1 was a 55-year-old female from the tribe Malila smallholder farmer who has had four generalized tonic–clonic epileptic seizures over a period of 11 years and one episode of transient left hemiparesis one year before seizure onset. The patient also reported monthly to weekly episodes of severe, progressive, unilateral headache. The computed tomography (CT) scan of the brain showed 25 NCC lesions of which 15 were in the vesicular stage. Patient 2 was a 30-year-old male from tribe Nyha mechanic who reported monthly episodes of moderate to severe, progressive, bilateral headache, but no epileptic seizures. The CT scan showed 63 NCC lesions of which 50 were in the vesicular stage. Patient 3 was a 54-year-old female from the tribe Malila smallholder farmer who suffered from frequent generalized tonic–clonic epileptic seizures with potential signs of focal seizure onset. She also reported weekly to daily episodes of severe, progressive, unilateral headache. The CT scan showed 29 NCC lesions of which 28 were in the vesicular stage.ConclusionsClinical presentation of NCC with multiple brain lesions varies considerably ranging from few epileptic seizures and severe headache to severe epilepsy with frequent epileptic seizures. Individuals with neurological signs/symptoms that may be due to NCC, based for example on epidemiological criteria or serological evidence of cysticercosis, are recommended to undergo neuroimaging before anthelminthic treatment is considered.

Arousal deregulation in the co-shaping of neuropsychological dysfunction in frontal and mesial temporal lobe epilepsy

ObjectiveOur work aims to investigate the role of physiological arousal in the expression of neuropsychological deficits in frontal lobe epilepsy (FLE) and mesial temporal lobe epilepsy (mTLE), by drawing on the Lurian theory of brain function. MethodsFor this study a total of 43 patients with focal onset epilepsy has been taken; twenty-four patients with FLE, 19 patients with mTLE and 26 healthy controls, all matched for age and education. Participants underwent a comprehensive neuropsychological assessment including various cognitive domains, such as attention, episodic memory, speed of information processing, response inhibition and mental flexibility, working memory, verbal fluency (phonological & semantic). ResultsThere were no significant differences between FLE and mTLE patients in terms of neuropsychological performance. However, both FLE and mTLE patients showed significantly worse performance in several cognitive domains than HCs. The results seem to support our hypothesis that aberrant physiological arousal, as reflected in patients’ worse performance in vigilance and attention, response inhibition, and processing speed, along with other disease-specific variables, may co-determine neuropsychological dysfunction and/or impairment in both FLE and mTLE. ConclusionIdentifying a differential arousal-related neuropsychological affection in FLE and mTLE, among the known deleterious effects of the functional deficit zone and other disease-related variables, may further our understanding of the underlying cognitive-pathophysiological mechanisms in focal epilepsy syndromes.

Changes in awake and sleep electroencephalography characteristics after 1-year treatment for childhood and juvenile absence epilepsy

PurposeTo compare electroencephalography (EEG) features of newly diagnosed drug-naive childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) patients and analyze their response to anti-seizure medications (ASMs). MethodEEG characteristics between CAE and JAE patients and responders and non-responders to ASM at baseline and 12 months were compared, and the changes from baseline were analysed. ResultsA total of 62 patients (32 CAE and 30 JAE) were included. Discharges in baseline awake and sleep EEGs and interictal and polyspike discharges in baseline sleep EEGs were more frequent in JAE patients. Although the median discharge densities (discharge containing seconds per minute) were similar in baseline awake and sleep EEGs between the groups, the median was higher in the JAE group at 12 months and decreased significantly in both groups at 12 months compared to the baseline values. Responses to initial ASMs were 94% and 77% in the CAE and JAE groups, respectively. In initial sleep EEGs of non-responders with JAE, focal onset generalized spike and slow wave discharges (GSWDs) were more frequent, and the median ictal and interictal discharge densities were higher. ConclusionJAE patients had more frequent disorganized discharges at baseline in both awake and sleep EEGs and interictal and polyspike discharges in sleep EEGs than those of CAE patients. Improvement in EEG was more pronounced in CAE patients than in JAE patients. Focal-onset GSWDs and higher ictal and interictal discharge densities on baseline EEG were associated with a poor response to initial ASMs in JAE patients.

Equipotency of lacosamide to levetiracetam in new onset focal epilepsy: A randomized controlled trial.

Levetiracetam (LEV) is a well-established broad spectrum antiseizure medication (ASM) effective in focal, generalized, and myoclonic seizures whereas lacosamide (LCM) is a comparatively newer ASM currently approved only as an add-on agent in focal seizures. The aim of the study was to assess the efficacy and the tolerability of oral LCM as monotherapy in adult people with epilepsy (PWE) with new onset focal onset epilepsy compared with those receiving LEV. In this open-label single-center non-inferiority trial, PWE aged between 16 and 65 years suffering from new onset focal seizures, with or without secondary generalization were put on LCM monotherapy or LEV monotherapy. Data regarding demographic characteristics, seizure type and etiology, LCM and LEV daily dose, seizure frequency at baseline and at 6 months of follow-up, and seizure freedom rates were recorded. Thirty-five PWE on LCM (24 males), their mean age: 38.20 ± 16.62 years and 35 PWE on LEV (25 males, mean age: 38.91 ± 17.13 years) were enrolled. The most common type of seizure observed was focal to bilateral tonic-clonic seizure >70% followed by focal impaired awareness seizure and focal awareness seizure. Structural epilepsy was found in 21 among LCM group and 22 of LEV group. In the LCM group, the seizure frequency decreased from 3.33 ± 1.88 to 0.85 ± 1.09 (P = 0.001) at 6 months and from 3.61 ± 3.12 to 0.94 ± 1.24 (P = 0.001) in LEV group, intergroup difference (P = 0.74). At 6-month follow-up period, 78.9% in LCM arm and 87.9% in the LEV arm had experienced a 50% of reduction in seizure frequency while seizure freedom was attained in 43.3% of PWE in both the arms (P = 1). The most common treatment emergent adverse effects in the LCM group were fatiguability, dyspepsia, headache, and dizziness, while in the LEV group; somnolence and behavioral abnormality. Treatment with LCM met the non-inferiority criteria when compared with LEV. Therefore, it might be useful as first-line monotherapy for adults with newly diagnosed focal epilepsy.

ABCB1 Gene Polymorphisms Are Closely Associated With Drug-Resistant Epilepsy: Evidence Based on 377 Subjects in Chinese Pediatric Patients.

P-glycoprotein plays a role in drug resistance of epileptic patients by limiting gastrointestinal absorption and brain access to antiseizure medications. This study aimed to evaluate the association between ABCB1 polymorphisms and drug resistance in epileptic pediatric patients. Three hundred seventy-seven epileptic pediatric patients were treated with antiseizure medications and subsequently divided into the drug-responsive group (n = 256, 68%) and drug-resistant group (n = 121, 32%). The genomic DNA of patients in the different groups was extracted, followed by the determination of the ABCB1 gene polymorphisms using polymerase chain reaction-fluorescence staining in situ hybridization. Drug-resistant patients significantly exhibited a combined generalized and focal onset than drug-responsive patients (χ2 = 12.278, P < 0.001). The TT (χ2 = 5.776, P = 0.016) genotypes of G2677T and CT (χ2 = 6.165, P = 0.013) and TT (χ2 = 11.121, P = 0.001) genotypes of C3435T were significantly more frequent in drug-resistant patients than drug-responsive patients. Similarly, the GT-CT diplotype was significantly more frequent in drug-resistant patients than in drug-responsive patients. Our study findings suggest that the ABCB1 G2677T and C3435T polymorphisms are significantly associated with drug resistance in epileptic patients.

Verification of propagation hypothesis in patients with sporadic hand onset amyotrophic lateral sclerosis.

If lesions in sporadic amyotrophic lateral sclerosis (ALS) originate from a single focal onset site and spread contiguously by prion-like cell-to-cell propagation at a constant speed, the lesion spread time should be proportional to the anatomical distance. We verify this model in the patients. In 29 sporadic ALS patients with hand onset followed by spread to shoulder and leg, we retrospectively evaluated the inter/intra-regional spread time ratio: time interval of symptoms from hand-to-leg divided by that from hand-to-shoulder. We also obtained the corresponding inter-/intra-regional distance ratios of spinal cord from magnetic resonance imaging of 12 patients, and those of primary motor cortex from coordinates using neuroimaging software. Inter-/intra-regional spread time ratios ranged from 0.29 to 6.00 (median 1.20). Distance ratios ranged from 1.85 to 2.86 in primary motor cortex and from 5.79 to 8.67 in spinal cord. Taken together with clinical manifestations, of 27 patients with the requisite information available, lesion spreading was consistent with the model in primary motor cortex in 4 (14.8%) patients, and in spinal cord in only 1 (3.7%) patient. However, in more patients (12 of 29 patients: 41.4%), the inter-regional spread times in a long anatomical distance of hand-to-leg were shorter than or equal to the intra-regional spread times in a short anatomical distance of hand-to-shoulder. Contiguous cell-to-cell propagation at a constant speed might not play a major role at least in distant lesion spreading of ALS. Several mechanisms can be responsible for progression in ALS.

ID: 208400 Current Trends in Responsive Neurostimulation: A National Inpatient Sample Analysis

Responsive neurostimulation (RNS) has been used to treat adults with medically refractory focal onset epilepsy with 1 to 2 seizure foci since its FDA approval in 2013.1,2 Due to its effectiveness and favorable safety profile, it is utilized for epilepsy in adults and off-label in pediatric populations.3,4 In this study, we analyze current trends in utilization of RNS therapy.

The Association of Sociodemographic Factors, Postictal Symptoms, and Medical History With Seizure Type in Patients With Epilepsy: A Cross-Sectional Study.

Background Approximately 50 million people globally suffer from epilepsy. The prevalence of epilepsy in Saudi Arabia has been reported at 6.5 per 1,000 persons, affecting nearly 1% of the entire population. However, limited data is available in the country regarding the sociodemographic factors affecting epilepsy and its associated postictal symptoms, which may lead to stigmatization and negatively impact patients. Methods A cross-sectional study was conducted at King Abdulaziz University Hospital (KAUH) in a survey format. Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine at King Abdulaziz University. The study population included patients with epilepsy who visited King Abdulaziz University Hospital's outpatient neurology clinics from October 2021 to March 2022. Results The study participants' average age at the time of the first seizure was 16.5 years, with patients experiencing seizures as early as within the first year of life and as late as 70 years of age. Patients who had had their first seizure during the first year of life did not have any schooling (p<0.0001) and had learning difficulties (p<0.00001). Focal onset impaired awareness seizures were significantly associated with motor weakness (p=0.023) and mood alterations (p=0.014), while postictal fear, anxiety or panic, and sleep disruption were statistically significant for focal onset aware seizures (p=0.015 andp=0.050). Conclusion This study highlights the sociodemographic differences between patients in Saudi Arabia and in other areas. It may also point to novel findings regarding the postictal symptoms associated with the various seizure types.

Uso de lacosamida en pacientes pediátricos con epilepsia refractaria como terapia adjunta, revisión sistemática de la literatura

Objetivo: presentar la evidencia publicada hasta el momento acerca de la utilidad de la lacosamida en población pediátrica con epilepsia refractaria.&#x0D; Métodos: se realizaron búsquedas en las bases de datos electrónicas PubMed, Embase, Cochrane y Scielo, encontrando un total de 18 artículos que cumplieron los criterios de búsqueda.&#x0D; Hallazgos principales : lacosamida, uno de los fármacos anticonvulsivantes nuevos, ha sido aprobado como terapia adjunta en epilepsias de inicio focal y epilepsias refractarias en pacientes mayores de 16 años, pero existe creciente evidencia de su eficacia y seguridad en población pediátrica desde los 4 años. Los efectos adversos no difieren en gran medida de los demás anticonvulsivantes y su tasa de éxito es de aproximadamente el 8-40% de control total de crisis. Sin embargo, los estudios no tienen un seguimiento a largo plazo que demuestre que se mantiene este mismo control de crisis en el transcurso del tiempo. Adicionalmente, la lacosamida ofrece mejoría clínica independientemente del control de las crisis en cuanto al patrón motor y comportamental.&#x0D; Conclusiones: Los estudios muestran que la lacosamida es una opción segura indicada para la epilepsia de inicio focal y epilepsia refractaria en la población pediátrica como terapia adjunta, debido a su efectividad en el control de crisis, perfil de seguridad, baja tasa de efectos adversos e interacción con otros medicamentos; no obstante, se requieren estudios con mayor número de pacientes y con seguimientos más prolongados.

Real-world safety and effectiveness of cenobamate in patients with focal onset seizures: Outcomes from an Expanded Access Program.

This study investigated early, real-world outcomes with cenobamate (CNB) in a large series of patients with highly drug-resistant epilepsy within a Spanish Expanded Access Program (EAP). This was a multicenter, retrospective, observational study in 14 hospitals. Inclusion criteria were age ≥18 years, focal seizures, and EAP authorization. Data were sourced from patient clinical records. Primary effectiveness endpoints included reductions (100%, ≥90%, ≥75%, and ≥50%) or worsening in seizure frequency at 3-, 6-, and 12-month visits and at the last visit. Safety endpoints included rates of adverse events (AEs) and AEs leading to discontinuation. The study included 170 patients. At baseline, median epilepsy duration was 26 years and median number of seizures/month was 11.3. The median number of prior antiseizure medications (ASMs) and concomitant ASMs were 12 and 3, respectively. Mean CNB dosages/day were 176 mg, 200 mg, and 250 mg at 3, 6, and 12 months. Retention rates were 98.2%, 94.5%, and 87% at 3, 6, and 12 months. At last available visit, the rate of seizure freedom was 13.3%; ≥90%, ≥75%, and ≥50% responder rates were 27.9%, 45.5%, and 63%, respectively. There was a significant reduction in the number of seizures per month (mean: 44.6%; median: 66.7%) between baseline and the last visit (P < 0.001). Responses were maintained regardless of the number of prior or concomitant ASMs. The number of concomitant ASMs was reduced in 44.7% of patients. The cumulative percentage of patients with AEs and AEs leading to discontinuation were 68.2% and 3.5% at 3 months, 74.1% and 4.1% at 6 months, and 74.1% and 4.1% at 12 months. The most frequent AEs were somnolence and dizziness. In this highly refractory population, CNB showed a high response regardless of prior and concomitant ASMs. AEs were frequent but mostly mild-to-moderate, and few led to discontinuation.

Clinical features and drug-resistance in pediatric epilepsy with co-occurring autism: A retrospective comparative cohort study

ObjectiveWe conducted a retrospective comparative cohort study to determine the phenotypic and real-world management differences in children with epilepsy and co-occurring autism as compared to those without autism. MethodsClinical variables, EEG, brain MRI, genetic results, medical and non-medical treatment were compared between 156 children with both epilepsy and autism, 156 randomly selected and 156 demographically matched children with epilepsy only. Logistic regression analyses were conducted to determine predictors of drug-resistant epilepsy (DRE). ResultsAs compared to the’matched’ cohort, more patients with autism had generalized motor seizures although not statistically significant after Benjamini-Hochberg correction (54.5%, vs 42.3%, p = .0314); they had a lower rate of electroclinical syndromes (12.8%, vs 30.1%, p = .0002). There were more incidental MRI findings but less positive MRI findings to explain their epilepsy in children with autism (26.3%, vs 13.8% and 14.3%, vs 34.2%, respectively; p = .0003). In addition, LEV, LTG, and VPA were the most common ASMs prescribed to children with autism, as opposed to LEV, OXC, and LTG in children without autism. No difference in the major EEG abnormalities was observed. Although the rates of DRE were similar (24.8%, vs 26.6%, p = .7203), we identified two clinical and five electrographic correlates with DRE in children with both epilepsy and autism and a final prediction modeling of DRE that included EEG ictal findings, focal onset seizures, generalized motor seizures, abnormal EEG background, age of epilepsy onset, and history of SE, which were distinct from those in children without autism. SignificanceOur study indicates that detailed seizure history and EEG findings are the most important evaluation and prediction tools for the development of DRE in children with epilepsy and co-occurring autism. Further studies of epilepsy in specific autism subgroups based on their etiology and clinical severity are warranted.

Multisite thalamic recordings to characterize seizure propagation in the human brain.

Neuromodulation of the anterior nuclei of the thalamus (ANT) has shown to be efficacious in a subset of patients with refractory focal epilepsy. One important uncertainty is to what extent thalamic subregions other than the ANT could be recruited more prominently in the propagation of focal onset seizures. We designed the current study to simultaneously monitor the engagement of the ANT, mediodorsal (MD) and pulvinar (PUL) nuclei during seizures in patients who could be candidates for thalamic neuromodulation. We studied 11 patients with clinical manifestations of presumed temporal lobe epilepsy (TLE) undergoing invasive stereo-encephalography (sEEG) monitoring to confirm the source of their seizures. We extended cortical electrodes to reach the ANT, MD and PUL nuclei of the thalamus. More than one thalamic subdivision was simultaneously interrogated in nine patients. We recorded seizures with implanted electrodes across various regions of the brain and documented seizure onset zones (SOZ) in each recorded seizure. We visually identified the first thalamic subregion to be involved in seizure propagation. Additionally, in eight patients, we applied repeated single pulse electrical stimulation in each SOZ and recorded the time and prominence of evoked responses across the implanted thalamic regions. Our approach for multisite thalamic sampling was safe and caused no adverse events. Intracranial EEG recordings confirmed SOZ in medial temporal lobe, insula, orbitofrontal and temporal neocortical sites, highlighting the importance of invasive monitoring for accurate localization of SOZs. In all patients, seizures with the same propagation network and originating from the same SOZ involved the same thalamic subregion, with a stereotyped thalamic EEG signature. Qualitative visual reviews of ictal EEGs were largely consistent with the quantitative analysis of the corticothalamic evoked potentials, and both documented that thalamic nuclei other than ANT could have the earliest participation in seizure propagation. Specifically, pulvinar nuclei were involved earlier and more prominently than ANT in more than half of the patients. However, which specific thalamic subregion first demonstrated ictal activity could not be reliably predicted based on clinical semiology or lobar localization of SOZs. Our findings document the feasibility and safety of bilateral multisite sampling from the human thalamus. This may allow more personalized thalamic targets to be identified for neuromodulation. Future studies are needed to determine if a personalized thalamic neuromodulation leads to greater improvements in clinical outcome.

Antiseizure Drugs

Antiseizure drugs (ASDs) should be selected depending on the drug's efficacy for the seizure types. The seizure types are roughly classified into focal onset and generalized onset (generalized tonic-clonic, absence, and generalized myoclonic) seizures. Due care should be taken when selecting an ASD for patients with comorbidities and women of child-bearing age. If seizures persist after 2 or more trials with an appropriate ASD at optimal doses, the patients should be referred to epileptologists.

Characteristics of febrile seizures with SARS-CoV-2 infection in the Omicron era.

While the pandemic of coronavirus disease 2019 (COVID-19) is ongoing, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been dominant recently. The Omicron variant causes more seizures in pediatric patients compared with previously circulated variants. This study aimed to investigate the incidence and clinical features of febrile seizure (FS) in pediatric patients with COVID-19 during the Omicron era. The medical records of pediatric patients (≤18 years of age) diagnosed with COVID-19, who presented with FS between February 2020 and June 2022, were reviewed retrospectively to analyze clinical characteristics of FS in seven university-affiliated hospitals of Korea. Of 664 pediatric patients with COVID-19 during the study period, 46 during the pre-Omicron period and 589 during the Omicron period were included in the study analysis; 29 patients during the transition period were excluded. Among the included patients, 81 (12.8%) had concomitant FS, and most (76.5%) experienced simple FS. All FS episodes occurred during the Omicron period and none of them during pre-Omicron period (P=0.016). Sixty-five (80.2%) and 16 (19.8%) patients were categorized as FS (patient age ≤60 months) and late-onset FS (patient age >60 months), respectively. Underlying neurologic disease (P=0.013) and focal onset seizure (P=0.012) were more common in the late-onset FS group than in the FS group; however, overall clinical manifestations and outcomes including seizures consistent with characteristics of complex FS and subsequent epilepsy were similar between the two groups. As the COVID-19 pandemic persists, the incidence of FS has increased with the emergence of the Omicron variant. About one-fifth of the patients experiencing FS due to infection by the Omicron variant of SARS-CoV-2 were aged >60 months; however, clinical characteristics and outcomes were favorable. More information and long-term prognoses in patients with FS due to COVID-19 should be acquired.

Anti-seizure efficacy of perampanel in two established rodent models of early-life epilepsy

Early-life seizures can be refractory to conventional antiseizure medications (ASMs) and can also result in chronic epilepsy and long-term behavioral and cognitive deficits. Treatments targeting age-specific mechanisms contributing to epilepsy would be of clinical benefit. One such target is the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subtype of excitatory glutamate receptor, which is upregulated in the developing brain. Perampanel is a non-competitive, selective AMPAR antagonist that is FDA-approved for focal onset seizures (FOS) or primary generalized tonic-clonic seizures (PGTC) in children and adults. However, the efficacy of perampanel treatment in epilepsy patients younger than 4 years has been less documented. We thus tested the efficacy of perampanel in two early-life seizure models: (1) a rat model of hypoxia-induced neonatal seizures and (2) a mouse model of Dravet syndrome with hyperthermia-induced seizures. Pretreatment with perampanel conferred dose-dependent protection against early-life seizures in both experimental models. These findings suggest that AMPAR-mediated hyperexcitability could be involved in the pathophysiology of early-life seizures, which may be amenable to treatment with perampanel.

Effectiveness and Tolerability of Brivaracetam by Number of Lifetime Antiseizure Medications in Adults with Focal Onset Seizures: Pooled Data From Two Real-world Studies (P11-1.010)

<h3>Objective:</h3> Analyze impact of number of lifetime antiseizure medications (ASMs) on effectiveness and tolerability of brivaracetam (BRV) in adults with focal-onset seizures in a real-world clinical setting. <h3>Background:</h3> Increasing number of lifetime ASMs is associated with poorer response to newly administered ASM. <h3>Design/Methods:</h3> Pooled analysis of data from two 12-month, prospective, noninterventional studies (Europe: EP0077/NCT02687711; United States: EP0088) in patients initiating BRV as prescribed by their physician and followed for ≤12 months. Post hoc analysis included patients (≥18 years) with focal-onset seizures and ≥1 lifetime ASM at BRV initiation. Outcomes were assessed by number of lifetime ASMs (ASMs stopped before BRV initiation/ongoing at BRV initiation). <h3>Results:</h3> Of 720 included patients, 14.0%, 22.9%, 16.5%, and 46.5% had 1–2, 3–4, 5–6, and ≥7 lifetime ASMs, respectively. Across ASM subgroups, main reason for BRV initiation was lack of efficacy of current treatment (range: 73.3% [1–2 ASMs] to 89.0% [≥7 ASMs]). In patients with 1–2, 3–4, 5–6, and ≥7 lifetime ASMs, respectively, 12-month BRV retention was 68.3%, 66.1%, 55.5%, and 51.3%; 20.0%, 14.8%, 6.8%, and 2.7% had 12-month seizure freedom since baseline. Patients with 1–2 and 3–4 lifetime ASMs were less likely to discontinue BRV/terminate the study vs those with ≥5 lifetime ASMs. A lower proportion of patients with fewer lifetime ASMs discontinued BRV due to lack of efficacy (range: 1.0% [1–2 ASMs] to 14.9% [≥7 ASMs]) or treatment-emergent adverse events (TEAEs, 5.0% [1–2 ASMs] to 15.2% [≥7 ASMs]). In patients with 1–2, 3–4, 5–6, and ≥7 lifetime ASMs, respectively, TEAEs were reported in 26.7%, 37.0%, 46.2%, and 50.4%; 13.9%, 17.0%, 21.8%, and 30.1% discontinued due to TEAEs. <h3>Conclusions:</h3> Patients with fewer lifetime ASMs upon BRV initiation had numerically higher retention, and numerically lower incidences of TEAEs/discontinuations due to TEAEs. <b>Disclosure:</b> Dr. Martin has received personal compensation for serving as an employee of UCB. Dr. Martin has received stock or an ownership interest from UCB. Dr. Bourikas has nothing to disclose. Mrs. Brock has received personal compensation for serving as an employee of UCB. Dr. Dongre has received personal compensation for serving as an employee of UCB Inc. Dr. Dongre has stock in UCB Inc. Sami Elmoufti has nothing to disclose. Iryna Leunikava has nothing to disclose. Dr. Little has received personal compensation for serving as an employee of UCB. Anne-Liv Schulz has received personal compensation for serving as an employee of UCB. Anne-Liv Schulz has received stock or an ownership interest from UCB.

XEN1101, a Novel Potassium Channel Modulator: Interim Data From an Ongoing, Long-Term, Open-Label Extension of a Phase 2b study (X-TOLE) in Adults with Focal Epilepsy (S44.008)

XEN1101, a Novel Potassium Channel Modulator: Interim Data From an Ongoing, Long-Term, Open-Label Extension of a Phase 2b study (X-TOLE) in Adults with Focal Epilepsy (S44.008)

Investigation of changes in MDH enzyme activity in epilepsy

Aims: Epilepsy is one of the most common neurological diseases. It is classified into three groups: focal onset, generalized onset and unclassifiable. A seizure type is difficult to determine. The malate dehydrogenase (MDH) enzyme has a critical role in the excitability of the brain, and it has been reported that recurrent seizures are seen when its regulation is disturbed. We investigated the contribution of MDH enzyme levels as a biomarker to seizure classification. Methods: Our study was conducted prospectively by patients who were admitted to the emergency department of our hospital within a six-month period. Included in the study were 65 patients diagnosed with epilepsy, according to the International League Against Epilepsy (ILAE) classification. The patients were divided into two groups according to seizure type: focal onset and generalized onset. They were compared in terms of enzyme activity. Results: The MDH value was 47.56 ± 38.65 in patients with focal-onset epilepsy and 109.76 ± 128.44 in patients with generalized-onset epilepsy. Conclusion: Our results reveal the potential of MDH as a biomarker that can be used in epilepsy. In addition, the statistically significant difference between focal-onset and generalized-onset epilepsy indicates that it can be a usable biomarker in seizure classification

Reasons for ineligibility for clinical trials of patients with medication-resistant epilepsy.

Selection criteria for clinical trials for medication-resistant epilepsy are used to limit variability and to ensure safety. However, it has become more challenging to recruit subjects for trials. This study investigated the impact of each inclusion and exclusion criterion on medication-resistant epilepsy clinical trial recruitment at a large academic epilepsy center. We retrospectively identified all patients with medication-resistant focal or generalized onset epilepsy who attended an outpatient clinic over a consecutive 3-month period. We assessed each patient's eligibility for trials with commonly required inclusion and exclusion criteria to evaluate the proportion of eligible patients and the most common reasons for exclusion. Among 212 patients with medication-resistant epilepsy, 144 and 28 patients met the criteria for focal or generalized onset epilepsy, respectively. Overall, 9.4% (n = 20) patients were eligible for trials (19 focal onset and one generalized onset). Most patients were excluded from the study due to insufficient seizure frequency (58% of focal onset, 55% of generalized onset). A small proportion of patients with medication-resistant epilepsy were eligible for trials based on common selection criteria. These eligible patients may not be representative of the general population of patients with medication-resistant epilepsy. Insufficient seizure frequency was the most common reason for exclusion.

Post-ictal Rhythmic Thalamic Activity of the Centromedian Nucleus.

Deep brain stimulation of the centromedian nucleus of the thalamus (CMN) to treat drug-resistant epilepsy has been of interest for decades. However, little is known about the electrophysiological activity of the CMN during seizures. We describe a novel CMN EEG finding associated with seizure: post-ictal rhythmic thalamic activity. Five patients with drug-resistant epilepsy of unknown etiology with focal onset seizures underwent stereoelectroencephalography monitoring as part of evaluation for potential resective surgery or neuromodulation. Two patients had previously undergone complete corpus callosotomy and vagus nerve stimulation. A standardized plan for implantation included targets in the bilateral CMN. Each patient had frontal onset seizures, and two patients had additional insular, parietal, or mesial temporal onset seizures. Contacts of CMN were involved synchronously or rapidly after onset in most recorded seizures, particularly those with frontal onset. Focal onset hemiclonic and bilateral tonic-clonic seizures spread to involve cortical contacts with high-amplitude rhythmic spiking followed by abrupt offset with diffuse voltage attenuation. A post-ictal rhythmic 1.5 to 2.5 Hz delta frequency pattern, post-ictal rhythmic thalamic activity, emerged in CMN contacts amid the suppression of background activity in cortical contacts. In the two patients with corpus callosotomy, unilateral seizure spread and ipsilateral post-ictal rhythmic thalamic activity were observed. We observed post-ictal rhythmic thalamic activity in five patients with stereoelectroencephalography monitoring of the CMN with convulsive seizures. This rhythm appears late in ictal evolution and may signal an important role of the CMN in seizure termination. Furthermore, this rhythm may help identify CMN involvement in the epileptic network.