Onset Of Epilepsy Research Articles

Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy.

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a ≈20-µm wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy.

Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. We carried out a multicenter cross-sectional survey of children with epilepsy across China between March2022 and August2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. Overall, 395 epilepsy patients aged 6-18years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Attention-deficit/hyperactivity disorder in children with epilepsy: A systematic review and meta-analysis of prevalence and risk factors.

To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis. Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD. The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment. This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.

Long-term seizure outcome after epilepsy surgery of neuroglial tumors

PurposeNeuroglial tumors are frequently associated with pharmacorefractory epilepsies. However, comprehensive knowledge about long-term outcomes after epilepsy surgery and the main prognostic factors for outcome is still limited. We sought to evaluate long-term outcomes and potential influencing factors in a large cohort of patients who underwent surgery for neuroglial tumors in a single-center setting.MethodsThe study analyzed the outcomes of 107 patients who underwent epilepsy surgery for neuroglial tumors between 2001 and 2020 at the Department of Epileptology, University Hospital Bonn, in Germany. The outcomes were evaluated using Engel classification. Differences in outcome related to potential prognostic factors were examined using the Chi2-test, Fisher’s exact test and sign test. Additionally, stepwise logistic regression analysis was employed to identify independent prognostic factors.ResultsComplete seizure freedom (Engel Class IA) was achieved in 75% of the operated patients at 12 months, and 56% at the last follow-up visit (70.4 ± 6.2 months, median: 40 months). Completeness of resection was a crucial factor for both 12-month follow-up outcomes and the longest available outcomes, whereas lobar tumor localization, histology (ganglioglioma vs. dysembryoplastic neuroepithelial tumor), history of bilateral tonic–clonic seizures prior to surgery, invasive diagnostics, side of surgery (dominant vs. non-dominant hemisphere), age at epilepsy onset, age at surgery, and epilepsy duration did not consistently impact postsurgical outcomes. Among temporal lobe surgeries, patients who underwent lesionectomy and lesionectomy, including hippocampal resection, demonstrated similar outcomes.ConclusionNeuroglial tumors present as excellent surgical substrates in treating structural epilepsy. To achieve an optimal postsurgical outcome, a complete lesion resection should be pursued whenever possible.

Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling

BackgroundHuman patients often experience an episode of serious seizure activity, such as status epilepticus (SE), prior to the onset of temporal lobe epilepsy (TLE), suggesting that SE can trigger the development of epilepsy. Yet, the underlying mechanisms are not fully understood. The low-density lipoprotein receptor related protein (Lrp4), a receptor for proteoglycan-agrin, has been indicated to modulate seizure susceptibility. However, whether agrin-Lrp4 pathway also plays a role in the development of SE-induced TLE is not clear.MethodsLrp4f/f mice were crossed with hGFAP-Cre and Nex-Cre mice to generate brain conditional Lrp4 knockout mice (hGFAP-Lrp4−/−) and pyramidal neuron specific knockout mice (Nex-Lrp4−/−). Lrp4 was specifically knocked down in hippocampal astrocytes by injecting AAV virus carrying hGFAP-Cre into the hippocampus. The effects of agrin-Lrp4 pathway on the development of SE-induced TLE were evaluated on the chronic seizure model generated by injecting kainic acid (KA) into the amygdala. The spontaneous recurrent seizures (SRS) in mice were video monitored.ResultsWe found that Lrp4 deletion from the brain but not from the pyramidal neurons elevated the seizure threshold and reduced SRS numbers, with no change in the stage or duration of SRS. More importantly, knockdown of Lrp4 in the hippocampal astrocytes after SE induction decreased SRS numbers. In accord, direct injection of agrin into the lateral ventricle of control mice but not mice with Lrp4 deletion in hippocampal astrocytes also increased the SRS numbers. These results indicate a promoting effect of agrin-Lrp4 signaling in hippocampal astrocytes on the development of SE-induced TLE. Last, we observed that knockdown of Lrp4 in hippocampal astrocytes increased the extracellular adenosine levels in the hippocampus 2 weeks after SE induction. Blockade of adenosine A1 receptor in the hippocampus by DPCPX after SE induction diminished the effects of Lrp4 on the development of SE-induced TLE.ConclusionThese results demonstrate a promoting role of agrin-Lrp4 signaling in hippocampal astrocytes in the development of SE-induced development of epilepsy through elevating adenosine levels. Targeting agrin-Lrp4 signaling may serve as a potential therapeutic intervention strategy to treat TLE.

Association of outdoor air and noise pollution with unprovoked seizures and new onset epilepsy: A systematic review and meta-analysis.

Research has indicated that certain environmental exposures may increase the risk of unprovoked seizures and new onset epilepsy. This study aimed to synthesize the literature that has estimated the associations between short- and long-term exposure to outdoor air and noise pollution and the risk of unprovoked seizures and new onset epilepsy. We searched Embase, MEDLINE, Scopus, Web of Science, BIOSIS Previews, Latin American and Caribbean Health Sciences Literature, Proquest Dissertations and Theses, conference abstracts, and the gray literature and conducted citation tracing in June 2023. Observational and ecological studies assessing the associations of air and noise pollution with unprovoked seizures or new onset epilepsy were eligible. One reviewer extracted summary data. Using fixed and random effects models, we calculated the pooled risk ratios (RRs) for the studies assessing the associations between short-term exposure to air pollution and unprovoked seizures. Seventeen studies were included, 16 assessing the association of air pollution with seizures and one with epilepsy. Eight studies were pooled quantitatively. Ozone (O3; RR = .99, 95% confidence interval [CI] = .99-.99) and nitrogen dioxide (NO2) exposure adjusted for particulate matter (RR = 1.02, 95% CI = 1.01-1.02) on the same day, and carbon monoxide (CO) exposure 2 days prior (RR = 1.12, 95% CI = 1.02-1.22), were associated with seizure risk. A single study of air pollution and epilepsy did not report a significant association. The risk of bias and heterogeneity across studies was moderate or high. Short-term exposure to O3, NO2, and CO may affect the risk of seizures; however, the effect estimates for O3 and NO2 were minimal. Additional research should continue to explore these and the associations between outdoor air pollution and epilepsy and between noise pollution and seizures and epilepsy.

Familial aggregation of seizure outcomes in four familial epilepsy cohorts.

To assess the possible effects of genetics on seizure outcome by estimating the familial aggregation of three outcome measures: seizure remission, history of ≥4 tonic-clonic seizures, and seizure control for individuals taking antiseizure medication. We analyzed families containing multiple persons with epilepsy in four previously collected retrospective cohorts. Seizure remission was defined as being 5 and 10 years seizure-free at last observation. Total number of tonic-clonic seizures was dichotomized at <4 and ≥4 seizures. Seizure control in patients taking antiseizure medication was defined as no seizures for 1, 2, and 3 years. We used Bayesian generalized linear mixed-effects model (GLMM) to estimate the intraclass correlation coefficient (ICC) of the family-specific random effect, controlling for epilepsy type, age at epilepsy onset, and age at last data collection as fixed effects. We analyzed each cohort separately and performed meta-analysis using GLMMs. The combined cohorts included 3644 individuals with epilepsy from 1463 families. A history of ≥4 tonic-clonic seizures showed strong familial aggregation in three separate cohorts and meta-analysis (ICC .28, 95% confidence interval [CI] .21-.35, Bayes factor 8 × 1016). Meta-analyses did not reveal significant familial aggregation of seizure remission (ICC .08, 95% CI .01-.17, Bayes factor 1.46) or seizure control for individuals taking antiseizure medication (ICC .13, 95% CI 0-.35, Bayes factor 0.94), with heterogeneity among cohorts. A history of ≥4 tonic-clonic seizures aggregated strongly in families, suggesting a genetic influence, whereas seizure remission and seizure control for individuals taking antiseizure medications did not aggregate consistently in families. Different seizure outcomes may have different underlying biology and risk factors. These findings should inform the future molecular genetic studies of seizure outcomes.

Profile of adult -onset epilepsy in Zagazig university hospitals

BackgroundEpilepsy has many neurobiological consequences. This study aimed to identify the profile of adult patients with new onset epilepsy in our university hospitals as regarding clinical picture, etiology, cerebral imaging and electroencephalogram (EEG) correlation, comorbidities, management, drug therapy and seizure severity and quality of life. We recruited one hundred patients with adult onset epilepsy, and we assessed them clinically, radiologically, and electrophysiologically. We performed Liverpool Seizure Severity Scale (LSSS) to assess seizure severity and the Quality of Life In Epilepsy-10 Questionnaire (QOLIE-10) to assess quality of life of adult patients with new onset epilepsy.ResultsFifty-seven percent of the studied patients were males, and 43.0% were females with mean (± SD) of age was 52.83 (± 17.33), 13.0% of the studied patients had positive family history of epilepsy. 32.0% had focal epilepsy, and 68.0% had generalized epilepsy, 53% of patients had uncontrolled seizures, 49% of patients were on monotherapy, and 51.0% were on polytherapy. The mean (± SD) seizure frequency per month in the studied patients was 4.0 (± 3.15). Imaging abnormalities were found in 88% of studied patients. 43% of the studied patients had abnormal EEG. Post-traumatic epilepsy, focal cortical dysplasia and mesial temporal sclerosis were statistically significant higher in male patients than female patients. Arteriovenous malformations were significantly higher in females. Middle-aged adults’ group had hypertension more than other age groups, older adult age group had atrial fibrillation, coronary heart disease, diabetes mellitus and dyslipidemia more than other age groups. Young adults had migraine more than other age groups. Post-stroke epilepsy was higher in older adult and middle-aged adult groups more than young adult age group. Intracranial neoplasms were higher in older adult age group than other age groups. Patients with moderate, severe, and very severe LSSS score had significantly more frequent uncontrolled seizures, abnormal EEG and higher rate of polytherapy as compared to those with mild LSSS score. Patients with impaired quality of life had more seizure frequency, less seizure control, higher seizure severity, more EEG abnormalities and were mostly treated by AEDs polytherapy than those with average life quality.ConclusionsLevetiracetam was the most preferred drug for treating patients with adult-onset epilepsy (40%), whether used as monotherapy or in combination with other drugs. Seizure severity, and seizure frequency per month strongly impaired patients’ quality of life.

Intravenous Lacosamide Therapy for Pediatric Patients With Cluster Seizures

BackgroundFew studies have investigated intravenous lacosamide use to treat cluster seizures in pediatric patients. Therefore, we aimed to investigate the efficacy and safety of intravenous lacosamide therapy in pediatric patients with cluster seizures. MethodsWe retrospectively evaluated the efficacy and safety of intravenous lacosamide therapy in 25 pediatric patients with cluster seizures at Saitama Children's Medical Center between March 2019 and June 2023. Cluster seizures were defined as a single seizure of less than five minutes duration, repeated three or more times within 12 hours, with recovery of consciousness between seizures. Response was defined as seizure freedom for at least 12 hours after lacosamide infusion. ResultsThe median age at onset of epilepsy was 1.5 (0.0 to 9.8) years. The median seizure frequency was 5 (3 to 20) times per 12 hours. The etiologies were remote (n = 17), acute (n = 4), and progressive (n = 4). The median age at which intravenous lacosamide therapy was administered was 4.2 (0.0 to 11.3) years. The median lacosamide dose was 2.6 (1.3 to 5.2) mg/kg. In total, 12 of 25 patients (48.0%) responded. Among patients treated with intravenous lacosamide as first-line therapy, nine of 17 (52.9%) had complete seizure remission. The frequency of complete seizure remission in patients with remote etiologies was 58.8% (10 of 17); among them, seven of 12 (58.3%) patients with structural abnormalities showed complete seizure remission. No adverse events were observed. ConclusionsIntravenous lacosamide therapy is a potentially useful treatment option for cluster seizures in pediatric patients.

Management of respiratory issues in patients with Rett syndrome: Italian experts' consensus using a Delphi approach.

Despite the publication of the 2020 guidelines on how to manage Rett Syndrome (RS), some fundamental topics are still open, in particular respiratory problems. Identification and reinforcement of current recommendations concerning the management of respiratory issues in RS patients. Using a Delphi approach, the leading group reviewed the literature and formulated 14 statements. A multidisciplinary panel of 29 experts were invited to score, for each statement, their agreement on a 1-5 scale. The cut-off level for consensus was 75%, obtained through multiple rounds. The panel agreed that in all RS types, respiratory issues should be faced at an early stage, regardless of epilepsy onset. It is recommended to perform periodically sleep studies in all Congenital Rett Syndrome,and in selected cases with other RS types. Noninvasive ventilationshould be considered in all RS subjects with sleep respiratory disorders and in those with hypotonia associated with hypercapnia. Chest physiotherapy should be performed in all RS patients with difficult management of the accumulation of respiratory secretions, using airway clearance techniques and devices (PEP-mask, AMBU bag, or cough machine), more appropriateand tolerated by the patients. The panel recommended individualized programs for the management of scoliosis, and to consider performing gastrostomyin patients at increased risk of ab ingestis pneumonia. This consensus could support everyday clinical practice on respiratory issues in RS patients, complementary to existing recommendations by regulatory agencies and guidelines.

Low-grade epilepsy-associated tumors: Epilepsy outcome and antiseizure medication discontinuation after lesionectomies as first-line surgical approach in pediatric population.

This study aimed to evaluate epilepsy outcome and antiseizure medication (ASM) discontinuation after lesionectomies as first surgical approach in pediatric population diagnosed with low-grade epilepsy-associated neuroepithelial tumors (LEATs). We conducted a retrospective study. Thirty-six consecutive patients with histological diagnoses of LEATs who underwent surgery between 2018 and 2021 at our institution were included. The clinical and surgical data were retrospectively analyzed. Thirty (83.3%) of 36 patients are free of disabling seizures (Engel class I) and 19 (63,4%) of them are classified as Engel Ia. In 17 (47.2%) patients, ASM could be discontinued. The mean age at surgery was 8.6 years (±4.04) and the mean age at onset of epilepsy was 7.2 years (±3.8), whereas the mean duration of epilepsy in months at the time of surgery was 21.3 months (±23.7). The epileptogenic tumor was in the temporal lobe in 20 (55.5%) patients. Because of seizure persistence, a second or a third surgery was necessary for six patients (16.7%) and four of them had residual lesions (three in temporal and one in extratemporal site). No perioperative complications were recorded, including acute seizures, with a median hospitalization time of 7 days. Shorter epilepsy duration at time of surgery as long as a single ASM was significantly correlated with an Engel class I outcome (p-value = .01 and p-value = .016, respectively). Focal seizure semeiology was associated with an increased probability of antiseizure medication discontinuation (p-value = .042). Our findings confirm that shorter epilepsy disease duration, monotherapy before surgery, and seizure semeiology are determinant factors for a positive seizure outcome and medication discontinuation, also with less invasive surgical approaches such as lesionectomies. However, considering the intrinsic multifactorial epileptogenic nature of LEATs, a tailored surgical approach should be considered to optimize clinical and seizure outcome, especially for lesions located in the temporal lobe.

The relevance of Spearman's g for epilepsy.

Whilst the concept of a general mental factor known as 'g' has been of longstanding interest, for unknown reasons, it has never been interrogated in epilepsy despite the 100+ year empirical history of the neuropsychology of epilepsy. This investigation seeks to identify g within a comprehensive neuropsychological data set and compare participants with temporal lobe epilepsy to controls, characterize the discriminatory power of g compared with domain-specific cognitive metrics, explore the association of g with clinical epilepsy and sociodemographic variables and identify the structural and network properties associated with g in epilepsy. Participants included 110 temporal lobe epilepsy patients and 79 healthy controls between the ages of 19 and 60. Participants underwent neuropsychological assessment, clinical interview and structural and functional imaging. Cognitive data were subjected to factor analysis to identify g and compare the group of patients with control participants. The relative power of g compared with domain-specific tests was interrogated, clinical and sociodemographic variables were examined for their relationship with g, and structural and functional images were assessed using traditional regional volumetrics, cortical surface features and network analytics. Findings indicate (i) significantly (P < 0.005) lower g in patients compared with controls; (ii) g is at least as powerful as individual cognitive domain-specific metrics and other analytic approaches to discriminating patients from control participants; (iii) lower g was associated with earlier age of onset and medication use, greater number of antiseizure medications and longer epilepsy duration (Ps < 0.04); and lower parental and personal education and greater neighbourhood deprivation (Ps < 0.012); and (iv) amongst patients, lower g was linked to decreased total intracranial volume (P = 0.019), age and intracranial volume adjusted total tissue volume (P = 0.019) and age and intracranial volume adjusted total corpus callosum volume (P = 0.012)-particularly posterior, mid-posterior and anterior (Ps < 0.022) regions. Cortical vertex analyses showed lower g to be associated specifically with decreased gyrification in bilateral medial orbitofrontal regions. Network analysis of resting-state data with focus on the participation coefficient showed g to be associated with the superior parietal network. Spearman's g is reduced in patients, has considerable discriminatory power compared with domain-specific metrics and is linked to a multiplex of factors related to brain (size, connectivity and frontoparietal networks), environment (familial and personal education and neighbourhood disadvantage) and disease (epilepsy onset, treatment and duration). Greater attention to contemporary models of human cognition is warranted in order to advance the neuropsychology of epilepsy.

First report of Tunisian patients with CDKL5-related encephalopathy.

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) are associated with a wide spectrum of clinical presentations. Early-onset epileptic encephalopathy (EOEE) is the most recognized phenotype. Here we describe phenotypic features in eight Tunisian patients with CDKL5-related encephalopathy. We included all cases with clinical features consistent with CDKL5-related encephalopathy: infantile epileptic spasm, acquired microcephaly, movement disorders and visual impairment. We collected data about seizure types, electroencephalogram, magnetic resonance imaging, and metabolic analysis. The diagnosis of CDKL5 mutation was made thanks to Sanger sequencing with an ABI PRISM 3100-Avant automated DNA sequencer using a Big Dye Terminator Cycle Sequencing Reaction Kit v1.1. and Next Generation Sequencing (NGS) since the development of a gene panel responsible for DEE within the framework of "Strengthening the Sfax University Expertise for diagnosis and management of epileptic encephalopathies". We collected four boys and four girls aged meanly 6 years old with confirmed mutation on CDKL5 gene. Overall, we identified five de novo CDKL5 mutations including three Frame-shift mutations, one missense mutation, and a splicing variant. The mean age at first seizure onset was 4 months. The first seizure type was infantile epileptic spasm (4/8) followed by tonic (2/8) and myoclonic seizures (2/8). Out of eight cases, four exhibited two stages epileptic course while epilepsy in three other patients progressed on three stages. Regarding development, most cases (6/8) had psychomotor retardation from the start whilst the two others showed psychomotor regression with the onset of seizures. Additional clinical features included visual impairment (7/8), tone abnormalities (7/8), stereotypies (7/8), and acquired microcephaly (6/8). Our present report delineates an unusual phenotype of CDKL5-related encephalopathy with male gender predominance and delayed onset epilepsy. It interestingly described new phenotypic features and uncommon benign developmental profiles in boys, different patterns of CDKL5-epilepsy, neuroimaging findings, and CDKL5 mutational spectrum.

Inhibition of Neuron-Restrictive Silencing Factor (REST/NRSF) Chromatin Binding Attenuates Epileptogenesis.

The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults including trauma, stroke, infections, and long seizures (status epilepticus, SE) increase the nuclear expression and chromatin binding of the neuron-restrictive silencing factor/RE-1 silencing transcription factor (NRSF/REST). REST/NRSF orchestrates major disruption of the expression of key neuronal genes, including ion channels and neurotransmitter receptors, potentially contributing to epileptogenesis. Accordingly, transient interference with REST/NRSF chromatin binding after an epilepsy-provoking SE suppressed spontaneous seizures for the 12 d duration of a prior study. However, whether the onset of epileptogenesis was suppressed or only delayed has remained unresolved. The current experiments determined if transient interference with REST/NRSF chromatin binding prevented epileptogenesis enduringly or, alternatively, slowed epilepsy onset. Epileptogenesis was elicited in adult male rats via systemic kainic acid-induced SE (KA-SE). We then determined if decoy, NRSF-binding-motif oligodeoxynucleotides (NRSE-ODNs), given twice following KA-SE (1) prevented REST/NRSF binding to chromatin, using chromatin immunoprecipitation, or (2) prevented the onset of spontaneous seizures, measured with chronic digital video-electroencephalogram. Blocking NRSF function transiently after KA-SE significantly lengthened the latent period to a first spontaneous seizure. Whereas this intervention did not influence the duration and severity of spontaneous seizures, total seizure number and seizure burden were lower in the NRSE-ODN compared with scrambled-ODN cohorts. Transient interference with REST/NRSF function after KA-SE delays and moderately attenuates insult-related hippocampal epilepsy, but does not abolish it. Thus, the anticonvulsant and antiepileptogenic actions of NRSF are but one of the multifactorial mechanisms generating epilepsy in the adult brain.

Integrating Proteomics and Transcriptomics Reveals the Potential Pathways of Hippocampal Neuron Apoptosis in Dravet Syndrome Model Mice.

An important component contributing to the onset of epilepsy is the death of hippocampal neurons. Several studies have shown that Dravet syndrome model mice: Scn1a KO mice have a high number of apoptotic neurons following seizures, but the precise mechanism underlying this remains unclear. The aim of this research was to elucidate the potential molecular mechanism of neuronal apoptosis in Scn1a KO mice by integrating proteomics and transcriptomics, with the ultimate goal of offering better neuroprotection. We found that apoptotic processes were enriched in both proteomic and transcriptomic GO analyses, and KEGG results also indicated that differential proteins and genes play a role in neurotransmission, the cell cycle, apoptosis, and neuroinflammation. Then, we examined the upstream and downstream KGML interactions of the pathways to determine the relationship between the two omics, and we found that the HIF-1 signaling pathway plays a significant role in the onset and apoptosis of epilepsy. Meanwhile, the expression of the apoptosis-related protein VHL decreased in this pathway, and the expression of p21 was upregulated. Therefore, this study suggests that VHL/HIF-1α/p21 might be involved in the apoptosis of hippocampal neurons in Scn1a KO mice.

Treatment Outcomes and Healthcare Resource Utilization Among People Living with Focal Onset Epilepsy and Deemed to be Drug Resistant in Clinical Practices in the United States (P10-1.007)

Treatment Outcomes and Healthcare Resource Utilization Among People Living with Focal Onset Epilepsy and Deemed to be Drug Resistant in Clinical Practices in the United States (P10-1.007)

476 Middle Cranial Fossa Encephaloceles With Temporal Lobe Epilepsy: An Underdiagnosed Entity

INTRODUCTION: Temporal lobe epilepsy with encephalocele (TLEE) is a lesional epilepsy increasingly recognized as underdiagnosed. Here we report our experience with TLEE-associated epilepsy managed with both traditional ATL with AH compared to a targeted lesionectomy of the encephalocele. METHODS: We used a prospectively maintained database of surgical epilepsy patients to identify all patients with TLEE-associated epilepsy managed over a 13-year interval using ATL with AH, ATL only, or a targeted encephalocele-only lesionectomy. Details regarding epilepsy, neuropsychology, management, complications, and outcomes at the last follow-up were compiled. RESULTS: 793 surgical epilepsy patients were evaluated, with 56 (7.1%) demonstrating TLEE. The average age of epilepsy onset was 31.7 years (range 2-57); the age at the time of surgery was 38.3 years (range 15-69). Twenty-one patients (37.5%) were managed with ATL with AH, 20 (35.7%) with temporal pole resection without AH, and 15 (26.7%) with targeted lesionectomy/LITT of the temporal encephalocele. Forty-seven patients (84%) had good surgical epilepsy outcomes with no significant difference in modality. Targeted lesionectomy demonstrated significantly greater language preservation (p = 0.046) and verbal memory (p = 0.038) when compared to more extensive surgical resections. CONCLUSIONS: TLEE is an overlooked and underreported etiology of epilepsy. In select cases, good surgical epilepsy outcomes can be achieved with targeted lesionectomy of the encephalocele when the epilepsy network is not widespread.

Deferasirox exerts anti-epileptic effects by improving brain iron homeostasis via regulation of ITPRIP

Epilepsy constitutes a global health concern, affecting millions of individuals and approximately one-third of patients exhibit drug resistance. Recent investigations have revealed alterations in cerebral iron content in both epilepsy patients and animal models. However, the extant literature lacks a comprehensive exploration into the ramifications of modulating iron homeostasis as an intervention in epilepsy. This study investigated the impact of deferasirox, a iron ion chelator, on epilepsy. This study unequivocally substantiated the antiepileptic efficacy of deferasirox in a kainic acid-induced epilepsy model. Furthermore, deferasirox administration mitigated seizure susceptibility in a pentylenetetrazol-induced kindling model. Conversely, the augmentation of iron levels through supplementation has emerged as a potential exacerbating factor in the precipitating onset of epilepsy. Intriguingly, our investigation revealed a hitherto unreported discovery: ITPRIP was identified as a pivotal modulator of excitatory synaptic transmission, regulating seizures in response to deferasirox treatment. In summary, our findings indicate that deferasirox exerts its antiepileptic effects through the precise targeting of ITPRIP and amelioration of cerebral iron homeostasis, suggesting that deferasirox is a promising and novel therapeutic avenue for interventions in epilepsy.

THE EFFECT OF GABA-BENZODIAZEPINE RECEPTOR COMPLEX MODULATORS (MPTD-01 AND BS 34-20) ON THE CEREBRAL CORTEX AFTER EXPERIMENTAL BRAIN INJURY

Background. Traumatic brain injury (TBI) is a major medical, social, and public health problem, In the military population the TBI incidence also remains high due to blunt head trauma and blast injuries. Considering the substantial TBI burden on society, including possible postraumatic epilepsy onset and other comorbidities the search for new treatment methods, including drug design with the identification of new molecules, is highly relevant.&#x0D; Aim: The study aimed to evaluate the effect of GABA-benzodiazepine receptor complex modulators (hydrogenated 2,3-benzodiazepines MPTD-01 та BS 34-20) on rat cerebral cortex after traumatic brain injury&#x0D; Materials and methods. The experiment was carried out on male Wistar rats. To obtain traumatic brain injury we used the weight drop model. Based on the received treatment, the Rats were divided into intact, placebo (II), and MPTD-01 (III) and BS 34-20 (IV) groups. The cerebral cortex in the impact zone was harvested for examination. The light microscopy was performed on 3, 7, 14, and 21 days after injury.&#x0D; Results. The observed histological picture of the changes in the cerebral cortex, especially in the II group is similar to those, described by other research papers as mild- to severe traumatic brain injury. The reproduction of the blunt trauma model leads to a series of typical changes that replace each other and can be characterized as alteration, edema, phase of cellular reactions, and repair. Unlike the placebo group, the III and IV experimental groups (GABA-benzodiazepine receptor complex modulators administration) cerebral cortex demonstrated a smoothing of the swelling phase and its reduction, a shift in the time phase of cellular reactions to a later time. In the BS 34-20 group, minimal edema was observed on the 21st day of the experiment.&#x0D; Conclusion. Such morphological changes can be considered a neuroprotective effect, however, to fully characterize the effects of the GABA-benzodiazepine receptor complex modulators, glial reactions and neuron-glial interactions should be investigated.

Early onset absence epilepsy of childhood: Epidemiologic data, treatment and outcome in a sample of 56 patients born between 2000 and 2018

PurposeThe aim of our work is to describe the characteristics of Early Onset Absence Epilepsy (EOAE) and to observe whether specific anamnestic, clinical or electroencephalographic characteristics can influence the drug sensitivity of this pathology. MethodsWe carried out a retrospective study of patients affected by absence epilepsy with onset under four years of age, born between January 1st 2000 and December 31st 2018, who were reffered to the Regional Epilepsy Center of Spedali Civili of Brescia. We then divided the sample into three groups based on the age of onset. ResultsOur sample is composed of 56 patients. Among the children with epilepsy onset under two years of age (11), all were still on therapy after three and six years of follow-up, and 64 % of them required polytherapy. Among patients with epilepsy onset between two and three years of age (24), 87 % were still on therapy after three years of follow-up and 68 % after six years of follow-up; 46 % of these subjects required polytherapy. Among patients with epilepsy onset between three and four years of age (21), 89 % were still on therapy after three years of follow-up and 38 % after six years of follow-up; 38 % of them required polytherapy. ConclusionsWe observe that patients with an earlier epilepsy onset have a worse outcome and a lower drug sensitivity. This may allow to predict in which cases it would be appropriate to maintain antiseizure therapy for a prolonged period.