Epilepsia Open最新文献

{"title":"Previously defined variants of uncertain significance may play an important role in epilepsy and interactions between certain variants may become pathogenic","authors":"Yara Hussein,&nbsp;Hila Weisblum-Neuman,&nbsp;Bruria Ben Zeev,&nbsp;Shani Stern","doi":"10.1002/epi4.13085","DOIUrl":"10.1002/epi4.13085","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Epilepsy is a chronic neurological disorder related to various etiologies, and the prevalence of active epilepsy is estimated to be between 4 and 10 per 1000 individuals having a significant role in genetic mutations. Next-Generation Sequencing (NGS) panels are utilized for genetic testing, but a substantial proportion of the results remain uncertain and are not considered directly causative of epilepsy. This study aimed to reevaluate pediatric patients diagnosed with epilepsy who underwent genetic investigation using NGS panels, focusing on inconclusive variant findings or multiple variants of uncertain significance (VUSs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A subgroup of pediatric patients aged 0–25 years, diagnosed with epilepsy, who underwent genetic investigation with an NGS epilepsy panel at the Child Neurology Unit, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, between 2018 and 2022 through Invitae, was reevaluated. Patients with inconclusive variant findings or multiple VUSs in their test results were included. Genetic data were analyzed to identify potentially pathogenic variants and frequent genetic combinations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two unrelated potentially pathogenic variants were identified in the SCN9A and QARS1 genes. A frequent genetic combination, RANBP2&amp;RYR3, was also observed among other combinations. The RANBP2 gene consistently co-occurred with RYR3 variants in uncertain results, suggesting potential pathogenicity. Analysis of unaffected parents' data revealed certain combinations inherited from different parents, suggesting specific gene combinations as possible risk factors for the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study highlights the importance of reevaluating genetic data from pediatric epilepsy patients with inconclusive variant findings or multiple VUSs. Identification of potentially pathogenic variants and frequent genetic combinations, such as RANBP2&amp;RYR3, could aid in understanding the genetic basis of epilepsy and identifying potential hotspots.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>We have performed a retrospective analysis on a subpopulation of pediatric patients diagnosed with epilepsy. We found that specific genetic variants were repeatable, indicating their potential pathogenicity to the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2443-2453"},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemical analysis and concentrations of cannabidiol substances used for refractory epilepsy in Chilean patients. An underestimated worldwide risk","authors":"Loreto Ríos-Pohl,&nbsp;Macarena Franco,&nbsp;Daniel Navea,&nbsp;Viviana Venegas,&nbsp;Tomás Cerda","doi":"10.1002/epi4.13081","DOIUrl":"10.1002/epi4.13081","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The purpose of this study is to analyze composition of HMS (homemade CBD), NLS (non-licensed commercial products), and bioequivalent CBD (BES) collected from Chilean patients that voluntary accepted to analyze the “CBD-substance.”&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Samples were collected through an open invitation for different patients to anonymously and free of charge participate in the analysis of CBD oil. The analysis of the active principle was performed using High-Resolution Liquid Chromatography (HPLC).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 35 samples were collected between March 2020 and September 2021, including two BES, six NLS, and 27 HMS products.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;The BES had an average CBD concentration of 89.15 mg/mL and an average THC concentration of 0.015 mg/mL, which complied with the maximum THC levels required by regulatory authorities (&lt;0.2% THC.).&lt;/p&gt;\u0000 \u0000 &lt;p&gt;The NLS (six samples) exhibited significant variability in CBD concentrations, ranging from a maximum of 78.5 mg/mL to a minimum of 0.1 mg/mL, with an average of 25.41 mg/mL. The THC concentrations ranged from 0 mg/mL to 2.43 mg/mL with an average of 0.62 mg/mL.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;The HMS products exhibited even higher variations of CBD concentrations, ranging from 0 to a maximum of 6.6 mg/mL. THC concentrations were even more variable, ranging from 0 mg/mL to 388 mg/mL.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The medical community and patients involved should be aware that Hemp products are not pure and/or innocuous. HMS are likely to have high levels of THC and very low CBD, far away from therapeutic doses of CBD. CBD used in epilepsy should be restricted to licensed products, especially in children where THC toxicity is much more harmful.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The study analyzed three types of CBD (cannabidiol) oils: homemade, non-licensed, and bioequivalent. Homemade and non-licensed products showed nonacceptable variance of CBD and THC concentration (tetrahydrocannabinol), in some cases with 0 mgs of CBD and many beyond THC maximum accepted. The THC is another component found in cannabis and is responsible for the neurotoxic effects. Only bioequivalent products showed concentrations of CBD and THC acceptable for epilepsy treatment, therefore are the only products recommended for suc","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2546-2552"},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to amoxicillin and perampanel in infantile Alexander disease","authors":"Susana Boronat,&nbsp;Eulalia Turon-Viñas,&nbsp;Noel Mac Manus,&nbsp;Asuncion Diaz-Gomez,&nbsp;Mónica Vicente,&nbsp;Victoria Ros-Castelló,&nbsp;Alba Sierra-Marcos","doi":"10.1002/epi4.13077","DOIUrl":"10.1002/epi4.13077","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Type I Alexander disease (AxD) presents with paroxysmal neurodegeneration, refractory epilepsy, and encephalopathy in the first years of life and is associated with a poor prognosis. Although there is no treatment, mild symptomatic improvement has been reported in one case of adult Alexander treated with ceftriaxone, given its interaction with the mutant glial fibrillary acid protein (GFAP) responsible for the disease's pathogenesis. We describe a patient presenting with irritability starting at 2 months of age, initially attributed to gastroesophageal reflux. A ventriculoperitoneal shunt was placed at 3 months of age due to hydrocephalus secondary to aqueduct stenosis detected through an MRI scan, but the irritability persisted. At 5 months, a new brain MRI was performed due to irritability worsening, onset of abnormal ocular movements and seizures. In addition genetic testing was performed. AxD was diagnosed due to the mutation c.716G&gt;A (p.Arg239His) in GFAP. Since irritability had worsened and had not responded to levomepromazine, treatment with amoxicillin (80 mg/kg/day) was attempted to modulate glutamate levels. The patient showed a striking improvement of irritability in 48 h that persisted over the next months. The patient had frequent daily seizures which did not respond to valproate, clonazepam, or phenobarbital. Perampanel, a postsynaptic AMPA receptor antagonist, was added to phenobarbital and he was seizure free for more than 3 months. Drugs modulating glutamate levels in the central nervous system, including β-lactam antibiotics and perampanel, may have an important role in the symptomatic treatment of AxD and other neurodegenerative diseases where glutamatergic excitotoxicity is a pathogenic determinant.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Alexander disease is a rare and serious condition that affects the brain, often leading to neurodegeneration (brain damage), seizures, and other problems in early childhood. The disease is caused by a mutation in a gene called GFAP. There is no cure, and current treatments mainly focus on relieving symptoms. This article discusses the case of a baby who showed signs of irritability and seizures from a young age. The baby was diagnosed with Alexander disease after brain scans and genetic testing. Despite treatment with various drugs, the baby continued to experience seizures and irritability. The doctors decided to try amoxicillin, a common antibiotic, because of its potential to help control the disease by affecting a brain chemical called glutamate. Surprisingly, the baby's irritability improved within 2 days of starting amoxicillin, and the improvement lasted for several months. However, the seizures persisted until another medication, perampanel, was added. This combination contr","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2505-2509"},"PeriodicalIF":2.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute depletion of complement C3 with cobra venom factor attenuates memory deficits induced by status epilepticus","authors":"Nicole D. Schartz,&nbsp;Yibo Li,&nbsp;Alexandra L. Sommer,&nbsp;Amy L. Brewster","doi":"10.1002/epi4.13030","DOIUrl":"10.1002/epi4.13030","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Status epilepticus (SE) significantly increases the risk for the development of unprovoked seizures, memory loss, and temporal lobe epilepsy. Our prior studies showed that SE increases complement C3 signaling in the hippocampus, which parallels memory deficits. Additionally, C3 knockout (KO) mice were protected against SE-induced memory impairments, suggesting a mechanistic role for C3 in this pathophysiology. In this study, we utilized cobra venom factor (CVF), a structural analog of C3 that results in its depletion, to investigate the protective effects of post-SE C3 ablation on memory deficits that develop during epileptogenesis.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;SE was induced in male rats using the chemoconvulsant pilocarpine. Two weeks later, control (C) and SE rats were treated with either vehicle (V) or CVF. Recognition memory was assessed using the novel object recognition (NOR) test in four groups (C + V, C + CVF, SE + V, and SE + CVF). Immunoblotting was used to measure hippocampal protein levels of C3 along with synaptic, astrocyte, and blood–brain barrier (BBB) stability markers, Psd95, GFAP, and albumin, respectively.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In the NOR test, rats in the C + V and C + CVF groups spent more time exploring the novel object. SE + V rats explored both objects equally, while SE + CVF rats spent significantly more on the novel object, suggesting a rescue of cognitive performance by CVF. While CVF-mediated C3 depletion did not restore normal protein levels of Psd95 or GFAP in hippocampi of SE + CVF rats, CVF treatment attenuated SE-induced extravasation of albumin, suggesting potential rescue of BBB stability.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our findings indicate that acute C3 depletion with CVF can attenuate memory deficits that develop during SE-induced epileptogenesis. This finding further suggests that targeting C3 could hold promise in addressing cognitive comorbidities associated with SE and acquired epilepsy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A long-lasting seizure, known as status epilepticus (SE), can raise the chance of having more seizures in the future and can lead to memory problems. While the exact reasons for these issues are not completely known, it is believed that brain inflammation might be involved. In this study, we show that the activation of the body's immune response, especially a part","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2173-2185"},"PeriodicalIF":2.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of self-stigma in patients with epilepsy: Validation of the self-stigma scale to Spanish (ESSS-S)","authors":"Isabel Manzanares,&nbsp;Izumi Kuramochi,&nbsp;Marta Olivera,&nbsp;María Centeno,&nbsp;Mariam Khawaja,&nbsp;Luis Pintor,&nbsp;Antonio Donaire,&nbsp;María del Mar Carreño,&nbsp;Estefanía Conde-Blanco","doi":"10.1002/epi4.13071","DOIUrl":"10.1002/epi4.13071","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The Epilepsy Self-Stigma Scale (ESSS) has been developed in Japan for patients with epilepsy (PWE). We aimed to validate the scale in Spanish and examine its validity and reliability.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The transcultural adaptation of the ESSS was conducted using translation and back-translation, along with pilot testing and an expert panel review. An online questionnaire was used to assess construct validity, criterion validity, and internal consistency.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;A total of 260 out of 628 participants completed the questionnaires. We found a two-factor structure that explained 61.3% of the total variance: factor 1 “self-perceived discrimination” with a Cronbach's alpha of 0.80, and factor 2 “social isolation” with a Cronbach's alpha of 0.75. The reliability of overall ESSS-S 8-item scores was high (Cronbach's alpha = 0.74). Convergent validity was tested and demonstrated a significant correlation. P.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;Self-perceived discrimination scores were associated with higher anxiety and depression scores (&lt;i&gt;r&lt;/i&gt; = 0.53/0.54; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), lower self-esteem (−0.53; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and lower quality of life (&lt;i&gt;r&lt;/i&gt; = −0.66; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Social isolation scores were associated with higher anxiety and depression scores (&lt;i&gt;r&lt;/i&gt; = 0.41/0.33; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), lower self-esteem (−0.34; &lt;i&gt;p&lt;/i&gt; &lt; 0.001), and lower quality of life (&lt;i&gt;r&lt;/i&gt; = −0.35; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). Temporal reliability was also tested, showing a test–retest ICC of 0.87. The mean self-stigma score in the Spanish population was 17.68 ± 5.45 out of 32 points. Invariance across gender and age groups indicated that there are no systematic response biases by gender or age, so stratified scores could be related to other constructs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The Spanish version of ESSS (ESSS-S) is a valid and reliable tool for the assessment of self-stigma in PWE among Spanish speakers.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study aimed to validate the Epilepsy Self-Stigma Scale (ESSS) for Spanish speakers (ESSS-S). We conducted transcultural adaptation of the scale. ESSS-S showed high reliability and strong validity, correlating with higher anxiety and depression, lower self-esteem, and quality of life. ESSS-S is a reliable and valid tool for assessing self-stigma in Spanish-","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2384-2394"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epilepsy in CHAD: Realities, constraints, and prospects","authors":"Foksouna Sakadi,&nbsp;Madjirabe Ngardidjim Christian,&nbsp;Toure Mohamed Lamine,&nbsp;Kamis Dakisia,&nbsp;Nderbe Melom Christelle,&nbsp;Diponbe Doufene,&nbsp;Lintel Anicet Foksia,&nbsp;Carlos Othon Nguelngar,&nbsp;Anatole Balanmo,&nbsp;Kobada Babing-ne,&nbsp;Desire Nalire,&nbsp;Cisse Amara","doi":"10.1002/epi4.13087","DOIUrl":"10.1002/epi4.13087","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Epilepsy is a significant public health problem. More than 50 million people worldwide live with epilepsy, and over three-quarters of them are in low- and middle-income countries. The situation in Chad regarding people with epilepsy is challenging to assess, starting from the shortage of scientific data, the inadequacy of technical facilities, the lack of human resources, and the inadequacy of government action. The Ministry of Health and Chadian Society of Neurology are looking forward to prioritizing epilepsy as well as improving the living conditions of persons with this disease.</p>\u0000 \u0000 <p>The epilepsy treatment issue is also problematic. Most of the patients are either off treatment or under-medicated. Few antiseizure medications (ASMs) are available, notably carbamazepine, phenobarbital, and valproic acid. Epilepsy remains little-known and does not seem to be a priority for decision-makers. We describe the current situation in Chad, to improve the conditions under which epilepsy is treated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Epilepsies is a chronic brain problem that is common in poorer settings. The daily lives of people with epilepsy are chaotic in Chad. The challenges are numerous, particularly those related to health infrastructures, due to the lack of adequate diagnostic means and the lack of neurologists. The cultural and language challenges, especially since epilepsy is still considered the devil's disease and the name differs according to the dialects. Stigmatization is also frequent and is often responsible for school dropout, refusal, or dismissal from work. Care and prevention are daily challenges that require government action. Social coverage is insufficient and almost absent in rural areas. It is urgent to prioritize epilepsy in future action plans and also to increase awareness of the conditions to overcome these challenges.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2049-2054"},"PeriodicalIF":2.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newer glucose-lowering drugs reduce the risk of late-onset seizure and epilepsy: A meta-analysis","authors":"Udeept Sindhu,&nbsp;Akshay Sharma,&nbsp;Ifrah Zawar,&nbsp;Vineet Punia","doi":"10.1002/epi4.13091","DOIUrl":"10.1002/epi4.13091","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Newer glucose-lowering drugs (GLDs) protect against cerebrovascular, neurodegenerative, and neuroinflammatory pathologies. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) comparing newer GLDs to placebo that assessed long-term cardiovascular and renal outcomes to analyze their potential to prevent late-onset seizures and epilepsy, separately and as a combined outcome. A comprehensive MEDLINE and CENTRAL databases search for DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitor RCTs, which reported adverse effects, including seizures and epilepsy on clinicaltrials.gov, yielded 413 studies. Of them, 27 studies with almost 200 000 patients (mean age 64.9 years, 65.6% males) were included. We calculated relative risk (RR) and odds ratio (OR) using the Mantel–Haenszel method and Peto's method. Patients taking newer GLDs had a 24% lower risk of late-onset seizures and epilepsy, combined, (RR: 0.76, 95% CI: 0.62–0.95) and 22% lower risk of late-onset seizures only (RR = 0.78; 95% CI = 0.60–1.00), compared to patients on placebo. This seizure and epilepsy prevention benefit was only noted among patients taking GLP-1 receptor agonists. Stroke incidence was comparable between newer GLDs and placebo group. GLP-1 receptor agonists like Semaglutide significantly reduce late-onset seizures and epilepsy, and their anti-epileptogenic potential in older adults needs further exploration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Our analysis 27 clinical trials and nearly 200 000 patients evaluated the potential of newer glucose-lowering drugs (GLDs) to prevent late-onset seizures and epilepsy in older adults. The study found that newer GLDs, especially GLP-1 receptor agonists like Semaglutide, reduced the combined risk of seizures and epilepsy by 24% compared to placebo. These findings suggest that newer GLDs may offer prevention against the development of seizures and epilepsy in older adults. However, further research is needed to confirm their anti-epileptogenic effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2528-2536"},"PeriodicalIF":2.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct visualization of microwires in hybrid depth electrodes using high-resolution photon-counting CT","authors":"Steven Smeijers,&nbsp;Walter Coudyzer,&nbsp;Elina Keirse,&nbsp;Vasiliki Bougou,&nbsp;Thomas Decramer,&nbsp;Tom Theys","doi":"10.1002/epi4.13080","DOIUrl":"10.1002/epi4.13080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Hybrid depth electrodes are increasingly being used for epilepsy monitoring and human neurophysiology research. Microwires extending from the tip of the Behnke-Fried (BF) electrode into (sub)cortical areas allow to isolate single neurons and perform microstimulation. Conventional CT or MRI visualize the entire microwire bundle as an artifact extending from the BF electrode tip with low resolution, without proper identification of individual microwires. We illustrate the first direct visualization method of individual microwires using high-resolution photon-counting CT (PCCT). Coregistration of the PCCT scan with a preoperative MRI can visualize individual wires directly in cortex, which is an advantage as it provides feedback on the accuracy of the implantation method and can guide future implantations. This PCCT technique allows for accurately depicting individual microwires which could be relevant for neuroscientific research through improved visualization and implantation of specific cortical and subcortical brain areas.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Plain Language Summary</h3>\u0000 \u0000 <p>Researchers are using hybrid depth electrodes to study epilepsy and brain activity. These electrodes, called Behnke-Fried (BF) electrodes, have microwires at the tip that can record single neurons and stimulate brain areas. Regular CT or MRI scans do not show the individual microwires clearly. The authors use a new high-resolution photon-counting CT (PCCT) technique, which can show each individual microwire in the brain. By combining PCCT with MRI, the authors can precisely see where the microwires are located. This could improve future implantation surgeries and brain research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2518-2521"},"PeriodicalIF":2.8,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical phenotype and functional influence of GRIN2A variants in epilepsy-aphasia syndrome","authors":"Lu Zhang,&nbsp;Yiran Duan,&nbsp;Rui Ma,&nbsp;Jiaqi Han,&nbsp;Na Pan,&nbsp;Lehong Gao,&nbsp;Yuping Wang","doi":"10.1002/epi4.13057","DOIUrl":"10.1002/epi4.13057","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;N-methyl-D-aspartate receptors are glutamate-gated ion channels that play a crucial role in brain function. Numerous inherited or de novo variants in the &lt;i&gt;GRIN2A&lt;/i&gt; gene, encoding the GluN2A subunit of the receptor, have been identified in patients with epilepsy. In addition, it is worth noting that &lt;i&gt;GRIN2A&lt;/i&gt; variants exhibit a strong correlation with epilepsy-aphasia syndromes, a group of age-dependent epileptic, cognitive, and language disorders with a characteristic electroencephalographic pattern.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Whole exome sequencing was conducted in enrolled patients with epilepsy-aphasia syndromes, and &lt;i&gt;GRIN2A&lt;/i&gt; variants were screened. The conservation of substituted residues, conformational changes of mutant subunits, and in silico predictions of pathogenicity were thoroughly assessed in our study. Functional alterations of the variants were examined using whole-cell voltage-clamp current recordings while the relative surface expression levels of subunit proteins were assessed via immunofluorescence assays. A summary of previously published &lt;i&gt;GRIN2A&lt;/i&gt; missense variants was conducted to investigate the genotypic-phenotypic-functional correlations.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Two missense &lt;i&gt;GRIN2A&lt;/i&gt; variants (c. 2482A &gt;G/p. M828V, c. 2627 T &gt;C/p. I876T) were identified, which are located in the transmembrane helix M4 and C-terminus domain of the GluN2A subunit, respectively. Both variants exhibited reduced current density of NMDARs and surface/total expression levels of GluN2A subunits, while M828V showed a decreased extent of desensitization as well. A further summary of the previously reported &lt;i&gt;GRIN2A&lt;/i&gt; variants demonstrated that more variable phenotypes were observed for variants situated in the C-terminus domain or those with loss-of-function effects.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our study expands the phenotypic and functional range of &lt;i&gt;GRIN2A&lt;/i&gt;-related disorders. In order to optimally establish the domain-function-phenotype correlations in &lt;i&gt;GRIN2A&lt;/i&gt; variants, it is imperative to gather a more extensive set of clinical and functional data.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Plain Language Summary&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;This study has identified two genetic variants of the &lt;i&gt;GRIN2A&lt;/i&gt; gene in patients with epilepsy-aphasia syndrome. We assess the variants' harmfulness through a variety of functional experiments, in","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2306-2318"},"PeriodicalIF":2.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of Vagus nerve stimulation (VNS) on seizure control, cognitive function, and quality of life in individuals with drug-resistant epilepsy: A systematic review article","authors":"Daniel Molla Melese,&nbsp;Abebaye Aragaw,&nbsp;Wondyefraw Mekonen","doi":"10.1002/epi4.13066","DOIUrl":"10.1002/epi4.13066","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the effect of vagus nerve stimulation (VNS) on seizure control, cognitive functions, and quality of life in individuals with drug-resistant epilepsy.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;An extensive search of electronic databases was carried out in order to carry out this systematic review. The databases Google Scholar, Embase, PubMed, and the Cochrane Library were searched first to carryout gray literature. To reduce the quantity of pointless studies in the advanced search, the search is limited to “human studies” and “English language” publications only. Combining keywords and Medical Subject Headings (MeSH) terms like (“Vagus Nerve Stimulation” OR “VNS”) AND (“Epilepsy” OR “Seizure Control”) AND (“Cognitive Function” OR “Quality of Life”). Studies that have been published up to November 30/2023 were included.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The search strategy yielded a total of 392 relevant studies. The mean age of participant's ranges from 11 years to 33 years. The duration of follow-up ranging from 6 to 36 months. Eleven studies were included in the review. The mean≥50% response rate after VNS therapy was 56.94% ranged from 48.90% to 83.00%. Four and three studies provided information about Quality of Life in Epilepsy Inventory (QOLIE-31) and The Liverpool Seizure Severity Scale (LSSS) questionnaires respectively.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Significance&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Epilepsy is a chronic disease characterized by sudden abnormal discharge of brain neurons, which leads to transient brain dysfunction and the presence of spontaneous recurrent seizures. Vagus nerve stimulation has recently been proposed as a potential tool in the treatment of seizure, depressive symptoms, and cognitive impairments. There has been variation in the effects of VNS treatment on seizure control, cognitive functions, and quality of life among patients with drug-resistant epilepsy. So, a comprehensive review of exciting literature is important to see the pooled effect. Previous systematic review and meta-analysis papers were mostly randomized control trial type with specific diseases. The use of a wider variety of study designs than only randomized controlled trials is important. So, we included retrospective and prospective cohort studies in addition to randomized control trials. This enables a more thorough assessment of the connection between quality of life, cognitive function, and vagus nerve stimulation. In addition, the paper looks at a wide range of disease kinds and patterns. We have estab","PeriodicalId":12038,"journal":{"name":"Epilepsia Open","volume":"9 6","pages":"2101-2111"},"PeriodicalIF":2.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11633674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}