Epilepsia最新文献

{"title":"POLR3B is associated with a developmental and epileptic encephalopathy with myoclonic-atonic seizures and ataxia.","authors":"Joseph D Symonds, Kristen L Park, Cyril Mignot, Stewart Macleod, Martin Armstrong, Houman Ashrafian, Geneviève Bernard, Kathleen Brown, Andreas Brunklaus, Mary Callaghan, Georg Classen, Julie S Cohen, Ioana Cutcutache, Jean-Madeleine de Sainte Agathe, David Dyment, Katherine S Elliot, Arnaud Isapof, Shelagh Joss, Boris Keren, Michael Marble, Amy McTague, Matthew Osmond, Matthew Page, Marc Planes, Konrad Platzer, Sylvia Redon, James Reese, Margarita Saenz, Constance Smith-Hicks, Daniel Stobo, Christian Stockhaus, Marie-Laure Vuillaume, Nicole I Wolf, Emma L Wakeling, Grace Yoon, Julian C Knight, Sameer M Zuberi","doi":"10.1111/epi.18115","DOIUrl":"https://doi.org/10.1111/epi.18115","url":null,"abstract":"<p><strong>Objective: </strong>POLR3B encodes the second largest subunit of RNA polymerase III, which is essential for transcription of small non-coding RNAs. Biallelic pathogenic variants in POLR3B are associated with an inherited hypomyelinating leukodystrophy. Recently, de novo heterozygous variants in POLR3B were reported in six individuals with ataxia, spasticity, and demyelinating peripheral neuropathy. Three of these individuals had epileptic seizures. The aim of this article is to precisely define the epilepsy phenotype associated with de novo heterozygous POLR3B variants.</p><p><strong>Methods: </strong>We used online gene-matching tools to identify 13 patients with de novo POLR3B variants. We systematically collected genotype and phenotype data from clinicians using two standardized proformas.</p><p><strong>Results: </strong>All 13 patients had novel POLR3B variants. Twelve of 13 variants were classified as pathogenic or likely pathogenic as per American College of Medical Genetics (ACMG) criteria. Patients presented with generalized myoclonic, myoclonic-atonic, atypical absence, or tonic-clonic seizures between the ages of six months and 4 years. Epilepsy was classified as epilepsy with myoclonic-atonic seizures (EMAtS) in seven patients and \"probable EMAtS\" in two more. Seizures were treatment resistant in all cases. Three patients became seizure-free. All patients had some degree of developmental delay or intellectual disability. In most cases developmental delay was apparent before the onset of seizures. Three of 13 cases were reported to have developmental stagnation or regression in association with seizure onset. Treatments for epilepsy that were reported by clinicians to be effective were: sodium valproate, which was effective in five of nine patients (5/9) who tried it; rufinamide (2/3); and ketogenic diet (2/3). Additional features were ataxia/incoordination (8/13); microcephaly (7/13); peripheral neuropathy (4/13), and spasticity/hypertonia (6/13).</p><p><strong>Significance: </strong>POLR3B is a novel genetic developmental and epileptic encephalopathy (DEE) in which EMAtS is the predominant epilepsy phenotype. Ataxia, neuropathy, and hypertonia may be variously observed in these patients.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical utility of ultra long-term subcutaneous electroencephalographic monitoring in drug-resistant epilepsies: a \"real world\" pilot study.","authors":"Guido Rubboli, Margrete Halvorsen Bø, Kristin Alfstad, Sidsel Armand Larsen, Mads Due Holm Jacobsen, Maria Vlachou, Sigge Weisdorf, Rune Rasmussen, Arild Egge, Oliver Henning, Morten Lossius, Sandor Beniczky","doi":"10.1111/epi.18121","DOIUrl":"https://doi.org/10.1111/epi.18121","url":null,"abstract":"<p><strong>Objective: </strong>This study was undertaken to assess the clinical utility, safety, and tolerability in epilepsy patients of ultra long-term monitoring with a novel subcutaneous electroencephalographic (EEG) device (sqEEG).</p><p><strong>Methods: </strong>Five patients with drug-resistant focal epilepsy were implanted (one patient bilaterally) with sqEEG. In phase 1, we assessed sqEEG sensitivity for seizure recording by recording seizures simultaneously with scalp EEG in the epilepsy monitoring unit (EMU). sqEEG was scored either visually (v-sqEEG) or by using a semiautomatic algorithm (EpiSight; E-sqEEG). In phase 2, the patients were monitored as outpatients for 3-6 months. sqEEG data were analyzed monthly, evaluating concordance of data obtained by v-sqEEG, E-sqEEG, and patients' diaries. v-sqEEG data were used to guide treatment adjustments. sqEEG-related side effects were assessed throughout the study.</p><p><strong>Results: </strong>In phase 1, v-sqEEG detected all seizures recorded in the EMU in all patients, whereas E-sqEEG was as effective in three patients. In the other two patients, E-sqEEG detected only a proportion or none of the seizures, respectively. Sensitivity of E-sqEEG depended on the ictal EEG features. In phase 2, a 100% concordance between E-sqEEG and v-sqEEG in seizure detection was observed for the same three patients as in phase 1. In the other two patients (one implanted bilaterally), effectiveness of E-sqEEG in detecting seizure as compared to v-sqEEG ranged from 0% to 83%. v-sqEEG showed that all patients reported in their diaries fewer seizures than they actually suffered. In four of five patients, v-sqEEG showed that the treatment adjustments had been ineffective or associated with a seizure increment. The only side effect was an infection at the implantation site in one patient.</p><p><strong>Significance: </strong>The sqEEG system could collect reliable information on seizure activity, thus providing clinically relevant information. Sensitivity of EpiSight in detecting seizures varied across patients, depending on the ictal EEG features. sqEEG ultra long-term monitoring was feasible and well tolerated.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of first antiseizure medication with acute health care utilization in a cohort of adults with newly diagnosed epilepsy.","authors":"Leah J Blank, Parul Agarwal, Churl-Su Kwon, Kenneth Boockvar, Nathalie Jetté","doi":"10.1111/epi.18133","DOIUrl":"https://doi.org/10.1111/epi.18133","url":null,"abstract":"<p><strong>Objective: </strong>Epilepsy is primarily treated with antiseizure medications (ASMs). The recommendations for first ASM in newly diagnosed epilepsy are inconsistently followed, and we sought to examine whether nonrecommended first ASM was associated with acute care utilization.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of adults (≥18 years old) with newly diagnosed epilepsy (identified using validated epilepsy/convulsion International Classification of Diseases, Clinical Modification codes) in 2015-2019, sampled from Marketscan's Commercial and Medicare Databases. Exposure of interest was receipt of a non-guideline-recommended ASM, and the primary outcome was acute care utilization (an emergency department visit or hospitalization after the first ASM claim). Descriptive statistics characterized covariates, and multivariable negative binominal regression models were built adjusting for age, sex, Elixhauser Comorbidity Index, comorbid neurologic disease (e.g., stroke), and ASM polypharmacy.</p><p><strong>Results: </strong>Approximately 14 681 people with new epilepsy were prescribed an ASM within 1 year. The three most prescribed medications were levetiracetam (54%, n = 7912), gabapentin (10%, n = 1462), and topiramate (7%, n = 1022). Approximately 4% (n = 648) were prescribed an ASM that should be avoided, and ~74% of people with new epilepsy had an acute care visit during the follow-up period. Mean number of acute care visits during follow-up was 3.34 for \"recommended\" ASMs and 4.42 for ASMs that \"should be avoided.\" Prescription of a recommended/neutral ASM as compared to an ASM that should be avoided was associated with reduced likelihood of acute care utilization (incidence rate ratio [IRR] = .85, 95% confidence interval [CI] = .77-.94). The recommended/neutral category of ASMs was not statistically significantly associated with seizure- or epilepsy-specific acute care utilization (IRR = .93, 95% CI = .79-1.09).</p><p><strong>Significance: </strong>Adults with new epilepsy are frequent users of acute care. There remain a proportion of persons with epilepsy prescribed ASMs that guidelines suggest avoiding, and these ASMs are associated with increased likelihood of emergency department visit or hospitalization. These findings reinforce the importance of optimizing the choice of first ASM in epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of different oral prednisone tapering courses in adult anti-NMDAR encephalitis: A multicenter prospective cohort study.","authors":"Linjun Cai, Gaowei Li, Ammar T Abdulaziz, Xue Gong, Xu Liu, Xueying Kong, Kundian Guo, Aiqing Li, Jinmei Li, Dong Zhou, Zhen Hong","doi":"10.1111/epi.18107","DOIUrl":"https://doi.org/10.1111/epi.18107","url":null,"abstract":"<p><strong>Objective: </strong>In adult anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, corticosteroids are commonly used as first-line treatment. However, the optimal oral prednisone tapering (OPT) following intravenous methylprednisolone pulse therapy remains unclear. We aim to compare the efficacy and safety of different OPT courses in anti-NMDAR encephalitis.</p><p><strong>Methods: </strong>The CHASE study, a multicenter prospective observational cohort study, enrolled patients with autoimmune encephalitis from October 2011 to March 2023. Patients were grouped based on oral prednisone tapering course: ≤3 months (Group ≤3 month), 3-6 months (Group 3-6 months, including 3 months), and >6 months (Group > 6 months). Kaplan-Meier plots were used to analyze time to relapse and time to total recovery within 2 years.</p><p><strong>Results: </strong>Among 666 screened patients, 171 (median [IQR] age 27 [21.0-36.5] years, 55.0% female) met selection criteria. Responders at 3 months were prevalent in Group ≤3 months (OR 7.251 [95% CI 2.252 to 23.344] and Group 3-6 months (OR, 3.857 [95% CI 1.107 to 13.440] than in Group >6 months. Clinical Assessment Scale for Autoimmune Encephalitis (CASE) scores at 12 months were higher in Group >6 months than in Group ≤3 months and Group 3-6 months (β, -2.329 [95% CI -3.784 to -.875]; β, -2.871 [95% CI -4.490, -1.253]). CASE seizures subscore was higher in Group >6 months than in Group 3-6 months (β, -.452 [95% CI -.788 to -.116]). No significant difference in seizure freedom rates among the groups. Adverse events were higher in Group 3-6 months and Group >6 months than in Group ≤3 months (OR 6.045 [95% CI 2.352 to 15.538]; OR 6.782 [95% CI 1.911 to 24.073]).</p><p><strong>Significance: </strong>Longer oral prednisone courses for adult patients with anti-NMDAR encephalitis did not show superior effects compared to shorter courses in improving modified Rankin Scale (mRS) scores and CASE scores, reducing the risk of relapse within 2 years, or achieving seizure freedom. Instead, extended prednisone courses may lead to more side effects- particularly weight gain. This outcome recommends evaluating the possibility of shortening the duration of oral prednisone after a thorough patient assessment.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus-based recommendations for the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy: A report from the Psychiatric Pediatric Issues Task Force of the International League Against Epilepsy.","authors":"Kette D Valente, Colin Reilly, Rachel M Carvalho, Mary Lou Smith, Marco Mula, Elaine C Wirrell, Jo M Wilmshurst, Nathalie Jetté, Francesco Brigo, Symon M Kariuki, Choong Yi Fong, Yuan-Pang Wang, Guilherme V Polanczyk, Viviane Castanho, Izabel G Demarchi, Stéphane Auvin, Mike Kerr","doi":"10.1111/epi.18116","DOIUrl":"https://doi.org/10.1111/epi.18116","url":null,"abstract":"<p><p>The Psychiatric Pediatric Issues Task Force of the International League Against Epilepsy (ILAE) aimed to develop recommendations for the diagnosis and treatment of anxiety and depression in children and adolescents with epilepsy. The Task Force conducted a systematic review and identified two studies that assessed the accuracy of four screening measures for depression and anxiety symptoms compared with a psychiatric interview. Nine studies met the eligibility criteria for treatment of anxiety and depressive disorders or symptoms. The risk of bias and certainty of evidence were assessed. The evidence generated by this review followed by consensus where evidence was missing generated 47 recommendations. Those with a high level of agreement (≥80%) are summarized. Diagnosis: (1) Universal screening for anxiety and depression is recommended. Closer surveillance is recommended for children after 12 years, at higher risk (e.g., suicide-related behavior), with subthreshold symptoms, and experiencing seizure worsening or therapeutic modifications. (2) Multiple sources of ascertainment and a formal screening are recommended. Clinical interviews are recommended whenever possible. The healthcare provider must always explain that symptom recognition is essential to optimize treatment outcomes and reduce morbidity. (3) Questioning about the relationship between symptoms of anxiety or depression with seizure worsening/control and behavioral adverse effects of antiseizure medications is recommended. Treatment: (1) An individualized treatment plan is recommended. (2) For mild depression, active monitoring must be considered. (3) Referral to a mental health care provider must be considered for moderate to severe depression and anxiety. (4) Clinical care pathways must be developed. (5) Psychosocial interventions must be tailored and age-appropriate. (6) Healthcare providers must monitor children with epilepsy who are prescribed antidepressants, considering symptoms and functioning that may not improve simultaneously. (7) Caregiver education is essential to ensure treatment adherence. (8) A shared-care model involving all healthcare providers is recommended for children and adolescents with epilepsy and mental health disorders. We identified clinical decisions in the management of depression and anxiety that lack solid evidence and provide consensus-based guidance to address the care of children and adolescents with epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying hubness to predict surgical outcomes in epilepsy: Assessing resection-hub alignment in interictal intracranial EEG networks.","authors":"Ruxue Gong, Rebecca W Roth, Kaitlyn Hull, Haris Rashid, William A Vandergrift, Alexandra Parashos, Nishant Sinha, Kathryn A Davis, Leonardo Bonilha, Ezequiel Gleichgerrcht","doi":"10.1111/epi.18128","DOIUrl":"10.1111/epi.18128","url":null,"abstract":"<p><strong>Objective: </strong>Intracranial EEG can identify epilepsy-related networks in patients with focal epilepsy; however, the association between network organization and post-surgical seizure outcomes remains unclear. Hubness serves as a critical metric to assess network organization by identifying brain regions that are highly influential to other regions. In this study, we tested the hypothesis that favorable post-operative seizure outcomes are associated with the surgical removal of interictal network hubs, measured by the novel metric \"Resection-Hub Alignment Degree (RHAD).\"</p><p><strong>Methods: </strong>We analyzed Phase II interictal intracranial EEG from 69 patients with epilepsy who were seizure-free (n = 45) and non-seizure-free (n = 24) 1 year post-operatively. Connectivity matrices were constructed from intracranial EEG recordings using imaginary coherence in various frequency bands, and centrality metrics were applied to identify network hubs. The RHAD metric quantified the congruence between hubs and resected/ablated areas. We used a logistic regression model, incorporating other clinical factors, and evaluated the association of this alignment regarding post-surgical seizure outcomes.</p><p><strong>Results: </strong>There was a significant difference in RHAD in fast gamma (80-200 Hz) interictal network between patients with favorable and unfavorable surgical outcomes (p = .025). This finding remained similar across network definitions (i.e., channel-based or region-based network) and centrality measurements (Eigenvector, Closeness, and PageRank). The alignment between surgically removed areas and other commonly used clinical quantitative measures (seizure-onset zone, irritative zone, high-frequency oscillations zone) did not reveal significant differences in post-operative outcomes. This finding suggests that the hubness measurement may offer better predictive performance and finer-grained network analysis. In addition, the RHAD metric showed explanatory validity both alone (area under the curve [AUC] = .66) and in combination with surgical therapy type (resection vs ablation, AUC = .71).</p><p><strong>Significance: </strong>Our findings underscore the role of network hub surgical removal, measured through the RHAD metric of interictal intracranial EEG high gamma networks, in enhancing our understanding of seizure outcomes in epilepsy surgery.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excess health care use is significantly and persistently reduced following diagnosis of late-onset epilepsy.","authors":"Marta Berglund, Arturo Gonzalez-Izquierdo, Spiros Denaxas, B Cord Lethebe, Tolulope T Sajobi, Jordan D T Engbers, Samuel Wiebe, Colin B Josephson","doi":"10.1111/epi.18105","DOIUrl":"https://doi.org/10.1111/epi.18105","url":null,"abstract":"<p><strong>Objective: </strong>The incidence of late-onset epilepsy (LOE) is rising, and these patients may use an excess of health care resources. This study aimed to measure pre-/post-diagnostic health care use (HCU) for patients with LOE compared to controls.</p><p><strong>Methods: </strong>This was an observational open cohort study covering years 1998-2019 using UK population-based linked primary care (Clinical Practice Research Datalink [CPRD]) and hospital (HES) electronic health records. The participants included patients with incident LOE enrolled in CPRD and 1:10 age-, sex-, and general practice-matched controls. The exposure was incident LOE (diagnosed at age ≥65) using a 5-year washout. The main outcome was all HCU (primary care [PC], accident and emergency [A&E], admitted patient and outpatient care) using inverse proportional weighting to PC use and HCU by setting. An interrupted time-series analysis was used to examine pre-/post-diagnostic HCU between patients with LOE and controls over 4 years either side of diagnosis/matching date. An adjusted mixed-effects negative binomial regression was used for post-diagnosis HCU interactions.</p><p><strong>Results: </strong>Of 2 569 874 people ≥65 years of age, 1048 (4%) developed incident LOE. Mean weighted total HCU increased by 32 visits per patient-year (95% confidence interval [95% CI]: 13-50, p = .003) until LOE diagnosis, and then dropped by a mean of 60 visits per patient-year (95% CI: -81 to -40). There was an acute rise and fall over the 1-2 years immediately pre-/post-diagnosis. Incident HCU remained higher for LOE compared to controls post-diagnosis (adjusted incidence rate ratio: 1.72; 95% CI: 1.65-1.70; p < .001), including A&E, outpatient, and admitted care.</p><p><strong>Significance: </strong>Health care use demonstrates an acute on chronic rise over the 4 years before diagnosis of LOE. To what extent the partial reversal of the acute pre-diagnosis rise, and the mediators of the accelerated increase compared to controls are attributed to epilepsy, comorbid and bidirectional disease states, or a combination of both warrants further exploration.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"WONOEP appraisal: Genetic insights into early onset epilepsies.","authors":"Anne Quatraccioni, Silvia Cases-Cunillera, Ganna Balagura, Matthew Coleman, Laura Rossini, James D Mills, Pablo M Casillas-Espinosa, Solomon L Moshé, Raman Sankar, Stéphanie Baulac, Jeffrey L Noebels, Stéphane Auvin, Terence J O'Brien, David C Henshall, Özlem Akman, Aristea S Galanopoulou","doi":"10.1111/epi.18124","DOIUrl":"https://doi.org/10.1111/epi.18124","url":null,"abstract":"<p><p>Early onset epilepsies occur in newborns and infants, and to date, genetic aberrations and variants have been identified in approximately one quarter of all patients. With technological sequencing advances and ongoing research, the genetic diagnostic yield for specific seizure disorders and epilepsies is expected to increase. Genetic variants associated with epilepsy include chromosomal abnormalities and rearrangements of various sizes as well as single gene variants. Among these variants, a distinction can be made between germline and somatic, with the latter being increasingly identified in epilepsies with focal cortical malformations in recent years. The identification of the underlying genetic mechanisms of epilepsy syndromes not only revolutionizes the diagnostic schemes but also leads to a better understanding of the diseases and their interrelationships, ultimately providing new opportunities for therapeutic targeting. At the XVI Workshop on Neurobiology of Epilepsy (WONOEP 2022, Talloires, France, July 2022), various etiologies, research models, and mechanisms of genetic early onset epilepsies were presented and discussed.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo biomarkers of GABAergic function in epileptic rats treated with the GAT-1 inhibitor E2730.","authors":"Idrish Ali, Bianca Jupp, Matthew R Hudson, Brendan Major, Juliana Silva, Glenn R Yamakawa, Pablo M Casillas-Espinosa, Emma Braine, Peravina Thergarajan, Mohammad B Haskali, Lucy Vivash, Robert Brkljaca, Sandy R Shultz, Patrick Kwan, Kazuyuki Fukushima, Pallavi Sachdev, Jocelyn Y Cheng, Richelle Mychasiuk, Nigel C Jones, David K Wright, Terence J OBrien","doi":"10.1111/epi.18119","DOIUrl":"https://doi.org/10.1111/epi.18119","url":null,"abstract":"<p><strong>Objective: </strong>E2730, an uncompetitive γ-aminobutyric acid (GABA) transporter-1 (GAT-1) inhibitor, has potent anti-seizure effects in a rodent model of chronic temporal lobe epilepsy, the kainic acid status epilepticus (KASE) rat model. In this study, we examined purported neuroimaging and physiological surrogate biomarkers of the effect of E2730 on brain GABAergic function.</p><p><strong>Methods: </strong>We conducted a randomized cross-over study, incorporating 1-week treatments with E2730 (100 mg/kg/day subcutaneous infusion) or vehicle in epileptic post-KASE rats. KASE rats underwent serial 9.4 T magnetic resonance spectroscopy (MRS) measuring GABA and other brain metabolites, [¹⁸F]Flumazenil positron emission tomography (PET) quantifying GABA_A receptor availability, quantitative electroencephalography (qEEG) and transcranial magnetic stimulation (TMS)-mediated motor activity, as well as continuous video-EEG recording to measure spontaneous seizures during each treatment. Age-matched, healthy control animals treated with E2730 or vehicle were also studied.</p><p><strong>Results: </strong>E2730 treatment significantly reduced spontaneous seizures, with 8 of 11 animals becoming seizure-free. MRS revealed that E2730-treated animals had significantly reduced taurine levels. [¹⁸F]Flumazenil PET imaging revealed no changes in GABA receptor affinity or density during E2730 treatment. The power of gamma frequency oscillations in the EEG was decreased significantly in the auditory cortex and hippocampus of KASE and control rats during E2730 treatment. Auditory evoked gamma frequency power was enhanced by E2730 treatment in the auditory cortex of KASE and healthy controls, but only in the hippocampus of KASE rats. E2730 did not influence motor evoked potentials triggered by TMS.</p><p><strong>Significance: </strong>This study identified clinically relevant changes in multimodality imaging and functional purported biomarkers of GABAergic activity during E2730 treatment in epileptic and healthy control animals. These biomarkers could be utilized in clinical trials of E2730 and potentially other GABAergic drugs to provide surrogate endpoints, thereby reducing the cost of such trials.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsia – September 2024 announcements","authors":"","doi":"10.1111/epi.18111","DOIUrl":"https://doi.org/10.1111/epi.18111","url":null,"abstract":"&lt;p&gt;\u0000 \u0000 &lt;b&gt;15th European Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;7–11 September 2024&lt;/p&gt;&lt;p&gt;Rome, Italy&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;Cápsula Virtual Sobre Convulsiones Febriles Para América Latina - 2024&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;9–15 September 2024&lt;/p&gt;&lt;p&gt;Online&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ASEPA EEG Part 1 Exam&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;11 September 2024&lt;/p&gt;&lt;p&gt;Jakarta, Indonesia&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;14th International Summer School for Neuropathology and Epilepsy Surgery&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;19–22 September 2024&lt;/p&gt;&lt;p&gt;Erlangen, Germany&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ASEPA SEEG Workshop and DIXI SEEG Course&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;30 October–3 November 2024&lt;/p&gt;&lt;p&gt;Bangkok, Thailand&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;Advanced Pediatric Epilepsy Surgery Course2024&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;7–10 November 2024&lt;/p&gt;&lt;p&gt;Cochin, India&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;7th East Mediterranean Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;14–16 November 2024&lt;/p&gt;&lt;p&gt;Manama, Bahrain&lt;/p&gt;&lt;p&gt;\u0000 &lt;b&gt;2025&lt;/b&gt;\u0000 &lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;14th ILAE School on Pre-Surgical Evaluation for Epilepsy and Epilepsy Surgery&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;20–24 January 2025&lt;/p&gt;&lt;p&gt;Brno, Czech Republic&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;15th Asian &amp; Oceanian Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;20–23 February 2025&lt;/p&gt;&lt;p&gt;New Delhi, India&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;5th African Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;1–31 May 2025&lt;/p&gt;&lt;p&gt;Africa&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;XVIII Workshop on Neurobiology of Epilepsy (WONOEP 2025)&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;25–29 August 2025&lt;/p&gt;&lt;p&gt;Portugal&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;36th International Epilepsy Congress&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;30 August–3 September 2025&lt;/p&gt;&lt;p&gt;Lisbon, Portugal&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;Implementing Epilepsy Surgery in Sub-Saharan Africa&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;3 September 2024&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ADHD in Children with Epilepsy: Screening, diagnosis and management&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;20 September 2024&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ILAE e-Forum: Reducing Epilepsy Related Mortality&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;23 September 2024&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;Psychosocial Factors and Approaches to Care&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;25 September 2024&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;ILAE e-Forum: Optimal Timing For Epilepsy Surgery&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;25 November 2024&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;Localisation en EEG&lt;/b&gt;\u0000 \u0000 &lt;/p&gt;&lt;p&gt;6 September 2024&lt;/p&gt;&lt;p&gt;Rabat, Maroc&lt;/p&gt;&lt;p&gt;\u0000 \u0000 &lt;b&gt;33rd International Congress of Clinical Neurophysiology&lt;/b&gt;\u0000 ","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18111","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}