Epilepsia最新文献

{"title":"“Is it a seizure?” Prediction tool for seizure likelihood in children aged 1–24 months admitted for electroencephalographic monitoring of paroxysmal, rhythmic, and repetitive events","authors":"Melisa Carrasco,&nbsp;Theresa Estiphan,&nbsp;Harlan McCaffery,&nbsp;Nancy McNamara","doi":"10.1111/epi.18018","DOIUrl":"10.1111/epi.18018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Paroxysmal, rhythmic, and repetitive events (PRREs) during infancy can be concerning for possible seizures, especially following perinatal brain injuries. The workup for establishing whether a PRRE represents a seizure involves the use of continuous video-electroencephalography (cVEEG) for event characterization. This study aims to determine the diagnostic yield of cVEEG for evaluating events concerning for seizures in children aged 1–24 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a single-center retrospective chart review (January 1, 2019–December 31, 2020) and included all children aged 1–24 months admitted for PRRE capture and characterization using cVEEG. Chart abstraction included demographics, birth and family history, known brain injury, event semiology, duration, and frequency, as well as interictal electroencephalographic (EEG) features. For each of these variables, odds ratios for seizure prediction were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 243 patients were identified for this study. On cVEEG, <i>n</i> = 160 (65.4%) had a target event of concern captured during an initial admission with cVEEG. Whereas <i>n</i> = 41 (25.8%) patients with events captured were confirmed to have seizures, most patients (<i>n</i> = 119) were confirmed to have nonepileptic events. Several variables predicted seizure likelihood during the initial admission with cVEEG, including event duration (&gt;1 min), frequency (occurring ≥3 times per week), and presence of abnormal interictal findings on cVEEG. For patients who did not receive a diagnosis at the time of initial admission with cVEEG, the likelihood of a subsequent epilepsy diagnosis was associated with specific PRRE semiology (motor active or motor passive), longer event duration (&gt;1 min duration), and the presence of interictal abnormal EEG features on initial cVEEG admission. Prediction tools utilizing scoring systems to stratify risk in infants with suspected seizures due to PRREs are included.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Unique patient attributes and PRRE characteristics, as well as the presence of EEG interictal abnormalities, can provide valuable insights for discerning children with a higher likelihood of epilepsy diagnosis following cVEEG admission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160091","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}

{"title":"ArcKR expression modifies synaptic plasticity following epileptic activity: Differential effects with in vitro and in vivo seizure-induction protocols","authors":"Amol Bhandare,&nbsp;Maisy Haley,&nbsp;Vanessa Torrico Anderson,&nbsp;Luana B. Domingos,&nbsp;Marcia Lopes,&nbsp;Sonia A. L. Corrêa,&nbsp;Mark J. Wall","doi":"10.1111/epi.17981","DOIUrl":"10.1111/epi.17981","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Pathological forms of neural activity, such as epileptic seizures, modify the expression pattern of multiple proteins, leading to persistent changes in brain function. One such protein is activity-regulated cytoskeleton-associated protein (Arc), which is critically involved in protein-synthesis–dependent synaptic plasticity underlying learning and memory. In the present study, we have investigated how the expression of ArcKR, a form of Arc in which the ubiquitination sites have been mutated, resulting in slowed Arc degradation, modifies group I metabotropic glutamate receptor–mediated long-term depression (G1-mGluR-LTD) following seizures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used a knock-in mice line that express ArcKR and two hyperexcitation models: an in vitro model, where hippocampal slices were exposed to zero Mg²⁺, 6 mM K⁺; and an in vivo model, where kainic acid was injected unilaterally into the hippocampus. In both models, field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 region of hippocampal slices in response to Schaffer collateral stimulation and G1-mGluR-LTD was induced chemically with the group 1 mGluR agonist DHPG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the in vitro model, ArcKR expression enhanced the effects of seizure activity and increased the magnitude of G1-mGluR LTD, an effect that could be blocked with the mGluR5 antagonist MTEP. In the in vivo model, fEPSPs were significantly smaller in slices from ArcKR mice and were less contaminated by population spikes. In this model, the amount of G1-mGluR-LTD was significantly less in epileptic slices from ArcKR mice as compared to wildtype (WT) mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>We have shown that expression of ArcKR, a form of Arc in which degradation is reduced, significantly modulates the magnitude of G1-mGluR-LTD following epileptic seizures. However, the effect of ArcKR on LTD depends on the epileptic model used, with enhancement of LTD in an in vitro model and a reduction in the kainate mouse model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157524","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":"Socioeconomic differences in use of antiseizure medication in pregnancies with maternal epilepsy: A population-based study from Nordic universal health care systems","authors":"Maarit K. Leinonen,&nbsp;Jannicke Igland,&nbsp;Julie Werenberg Dreier,&nbsp;Silje Alvestad,&nbsp;Jacqueline M. Cohen,&nbsp;Nils Erik Gilhus,&nbsp;Mika Gissler,&nbsp;Yuelian Sun,&nbsp;Torbjörn Tomson,&nbsp;Helga Zoega,&nbsp;Håkon M. Vegrim,&nbsp;Jakob Christensen,&nbsp;Marte-Helene Bjørk","doi":"10.1111/epi.18022","DOIUrl":"10.1111/epi.18022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Research points to disparities in disease burden and access to medical care in epilepsy. We studied the association between socioeconomic status (SES) and antiseizure medication (ASM) use in pregnancies with maternal epilepsy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a cross-sectional study consisting of 21 130 pregnancies with maternal epilepsy identified from Nordic registers during 2006–2017. SES indicators included cohabitation status, migrant background, educational attainment, and household income. Main outcomes were the proportion and patterns of ASM use from 90 days before pregnancy to birth. We applied multiple imputation to handle SES variables with 2%–4% missingness. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) using modified Poisson regression with the highest SES category as reference.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mothers with the highest education and the highest income quintile used ASMs least frequently (56% and 53%, respectively). We observed increased risks of ASM discontinuation prior to or during the first trimester for low SES. The risk estimates varied depending on the SES indicator from aRR = 1.27 for low income (95% CI: 1.03–1.57) to aRR = 1.66 for low education (95% CI: 1.30–2.13). Migrant background was associated with ASM initiation after the first trimester (aRR 2.17; 95% CI 1.88–2.52). Low education was associated with the use of valproate during pregnancy in monotherapy (aRR 1.70; 95% CI 1.29–2.24) and in polytherapy (aRR 2.65; 95% CI 1.66–4.21). Low education was also associated with a 37% to 39% increased risk of switching from one ASM to another depending on the ASM used. For the other SES indicators, aRRs of switching varied from 1.16 (foreign origin; 95% CI 1.08–1.26) to 1.26 (not married or cohabiting; 95% CI 1.17–1.36).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Low SES was associated with riskier patterns of ASM use: discontinuation, late initiation, and switching during pregnancy. These findings may reflect unplanned pregnancies, disparities in access to preconception counseling, and suboptimal care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157538","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}

{"title":"Global modified-Delphi consensus on comorbidities and prognosis of SCN8A-related epilepsy and/or neurodevelopmental disorders","authors":"Gabrielle Conecker,&nbsp;Maya Y. Xia,&nbsp;JayEtta Hecker,&nbsp;Christelle Achkar,&nbsp;Cristine Cukiert,&nbsp;Seth Devries,&nbsp;Elizabeth Donner,&nbsp;Mark Fitzgerald,&nbsp;Elena Gardella,&nbsp;Michael Hammer,&nbsp;Anaita Hegde,&nbsp;Chunhui Hu,&nbsp;Mitsuhiro Kato,&nbsp;Tian Luo,&nbsp;John M. Schreiber,&nbsp;Yi Wang,&nbsp;Tammy Kooistra,&nbsp;Madeleine Oudin,&nbsp;Kayla Waldrop,&nbsp;J. Tyler Youngquist,&nbsp;Dennis Zhang,&nbsp;Elaine Wirrell,&nbsp;M. Scott Perry","doi":"10.1111/epi.17991","DOIUrl":"10.1111/epi.17991","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to develop consensus on comorbidities (frequency, severity, and prognosis) and overall outcomes in epilepsy, development, and cognition for the five phenotypes of <i>SCN8A</i>-related disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A core panel consisting of 13 clinicians, 1 researcher, and 6 caregivers was formed and split into three workgroups. One group focused on comorbidities and prognosis. All groups performed a literature review and developed questions for use in a modified-Delphi process. Twenty-eight clinicians, one researcher, and 13 caregivers from 16 countries participated in three rounds of the modified-Delphi process. Consensus was defined as follows: strong consensus ≥80% fully agree; moderate consensus ≥80% fully or partially agree, &lt;10% disagree; and modest consensus 67%–79% fully or partially agree, &lt;10% disagree.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Consensus was reached on the presence of 14 comorbidities in patients with Severe Developmental and Epileptic Encephalopathy (Severe DEE) spanning non-seizure neurological disorders and other organ systems; impacts were mostly severe and unlikely to improve or resolve. Across Mild/Moderate Developmental and Epileptic Encephalopathy (Mild/Moderate DEE), Neurodevelopmental Delay with Generalized Epilepsy (NDDwGE), and NDD without Epilepsy (NDDwoE) phenotypes, cognitive and sleep-related comorbidities as well as fine and gross motor delays may be present but are less severe and more likely to improve compared to Severe DEE. There was no consensus on comorbidities in the SeL(F)IE phenotype but strong conesensus that seizures would largely resolve. Seizure freedom is rare in patients with Severe DEE but may occur in some with Mild/Moderate DEE and NDDwGE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Significant comorbidities are present in most phenotypes of <i>SCN8A</i>-related disorders but are most severe and pervasive in the Severe DEE phenotype. We hope that this work will improve recognition, early intervention, and long-term management for patients with these comorbidities and provide the basis for future evidence-based studies on optimal treatments of <i>SCN8A</i>-related disorders. Identifying the prognosis of patients with <i>SCN8A</i>-related disorders will also improve care and quality-of-life for patients and their caregivers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.17991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157530","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}

{"title":"Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders","authors":"Gabrielle Conecker,&nbsp;Maya Y. Xia,&nbsp;JayEtta Hecker,&nbsp;Christelle Achkar,&nbsp;Cristine Cukiert,&nbsp;Seth Devries,&nbsp;Elizabeth Donner,&nbsp;Mark P. Fitzgerald,&nbsp;Elena Gardella,&nbsp;Michael Hammer,&nbsp;Anaita Hegde,&nbsp;Chunhui Hu,&nbsp;Mitsuhiro Kato,&nbsp;Tian Luo,&nbsp;John M. Schreiber,&nbsp;Yi Wang,&nbsp;Tammy Kooistra,&nbsp;Madeleine Oudin,&nbsp;Kayla Waldrop,&nbsp;J. Tyler Youngquist,&nbsp;Dennis Zhang,&nbsp;Elaine Wirrell,&nbsp;M. Scott Perry","doi":"10.1111/epi.17992","DOIUrl":"10.1111/epi.17992","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to develop consensus for diagnosis/management of <i>SCN8A</i>-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of <i>SCN8A</i>-related disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, &lt;10% disagree; and modest consensus, 67%–79% fully/partially agree, &lt;10% disagree.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Early diagnosis is important for long-term clinical outcomes in <i>SCN8A</i>-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This is the first-ever global consensus for the diagnosis and treatment of <i>SCN8A</i>-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers <i>SCN8A</i> families to advocate for their children.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.17992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157527","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}

{"title":"Population-based study of rare epilepsy incidence in a US urban population","authors":"Kristen Barbour,&nbsp;Niu Tian,&nbsp;Elissa G. Yozawitz,&nbsp;Steven Wolf,&nbsp;Patricia E. McGoldrick,&nbsp;Tristan T. Sands,&nbsp;Aaron Nelson,&nbsp;Natasha Basma,&nbsp;Zachary M. Grinspan","doi":"10.1111/epi.18029","DOIUrl":"10.1111/epi.18029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study was undertaken to estimate incidence of rare epilepsies and compare with literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010–2014). We estimated cumulative incidence and compared with literature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox–Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic–atonic seizures (1 in 34 100), Sturge–Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including <i>PCDH19</i>, <i>CDKL5</i>, Alpers disease, <i>SCN8A</i>, <i>KCNQ2</i>, <i>SCN2A</i>, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097159","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":"Focal cooling: An alternative treatment for drug-resistant epilepsy in a mesial temporal lobe epilepsy primate model—A preliminary study","authors":"Napoleon Torres,&nbsp;Etienne de Montalivet,&nbsp;Quentin Borntrager,&nbsp;Selimen Benahmed,&nbsp;Antoine Legrain,&nbsp;Eleonora Adesso,&nbsp;Nicolas Aubert,&nbsp;Fabien Sauter-Starace,&nbsp;Thomas Costecalde,&nbsp;Felix Martel,&nbsp;David Ratel,&nbsp;Christophe Gaude,&nbsp;Vincent Auboiroux,&nbsp;Brigitte Piallat,&nbsp;Tetiana Aksenova,&nbsp;Jenny Molet,&nbsp;Stephan Chabardes","doi":"10.1111/epi.18012","DOIUrl":"10.1111/epi.18012","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep-seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non-human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two <i>Macaca fascicularis</i> monkeys at three temperatures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hippocampal seizures were observed 40–120 min post-injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097170","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}

{"title":"The changing landscape of electrical stimulation language mapping with subdural electrodes and stereoelectroencephalography for pediatric epilepsy: A literature review and commentary","authors":"Hope M. Reecher,&nbsp;Donald J. Bearden,&nbsp;Jennifer I. Koop,&nbsp;Madison M. Berl,&nbsp;Kristina E. Patrick,&nbsp;Alyssa S. Ailion","doi":"10.1111/epi.18009","DOIUrl":"10.1111/epi.18009","url":null,"abstract":"<p>Electrical stimulation mapping (ESM) is used to locate the brain areas supporting language directly within the human cortex to minimize the risk of functional decline following epilepsy surgery. ESM is completed by utilizing subdural grid or depth electrodes (stereo-electroencephalography [sEEG]) in combination with behavioral evaluation of language. Despite technological advances, there is no standardized method of assessing language during pediatric ESM. To identify current clinical practices for pediatric ESM of language, we surveyed neuropsychologists in the Pediatric Epilepsy Research Consortium. Results indicated that sEEG is used for functional mapping at &gt;80% of participating epilepsy surgery centers (<i>n</i> = 13/16) in the United States. However, &gt;65% of sites did not report a standardized protocol to map language. Survey results indicated a clear need for practice recommendations regarding ESM of language. We then utilized PubMed/Medline and PsychInfo to identify 42 articles that reported on ESM of language, of which 18 met inclusion criteria, which included use of ESM/signal recording to localize language regions in children (&lt;21 years) and a detailed account of the procedure and language measures used, and region-specific language localization outcomes. Articles were grouped based on the language domain assessed, language measures used, and the brain regions involved. Our review revealed the need for evidence-based clinical guidelines for pediatric language paradigms during ESM and a standardized language mapping protocol as well as standardized reporting of brain regions in research. Relevant limitations and future directions are discussed with a focus on considerations for pediatric language mapping.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087226","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":"Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case–control study","authors":"Luke Tait,&nbsp;Lydia E. Staniaszek,&nbsp;Elizabeth Galizia,&nbsp;David Martin-Lopez,&nbsp;Matthew C. Walker,&nbsp;Al Anzari Abdul Azeez,&nbsp;Kay Meiklejohn,&nbsp;David Allen,&nbsp;Chris Price,&nbsp;Sophie Georgiou,&nbsp;Manny Bagary,&nbsp;Sakh Khalsa,&nbsp;Francesco Manfredonia,&nbsp;Phil Tittensor,&nbsp;Charlotte Lawthom,&nbsp;Benjamin B. Howes,&nbsp;Rohit Shankar,&nbsp;John R. Terry,&nbsp;Wessel Woldman","doi":"10.1111/epi.18024","DOIUrl":"10.1111/epi.18024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case–control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (<i>N</i> = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [<i>n</i> = 2], network-based [<i>n</i> = 4], and model-based [<i>n</i> = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080711","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}

{"title":"Sex differences in cholinergic signaling affect functional outcomes for theta–gamma coordination in hippocampal subcircuits following experimental febrile status epilepticus","authors":"Michelle L. Kloc,&nbsp;Gregory L. Holmes,&nbsp;Jeremy M. Barry","doi":"10.1111/epi.18017","DOIUrl":"10.1111/epi.18017","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Sex determines cognitive outcome in animal models of early life seizure, where males exhibit impaired hippocampal-dependent learning and memory compared with females. The physiological underpinnings of this sex effect are unclear. Cholinergic signaling is essential for the generation of hippocampal oscillations, and supplementation of cholinergic precursors prior to status epilepticus in immature male rats prevents subsequent memory deficits. We hypothesized that there are sex differences in acetylcholine circuits and their response to experimental febrile status epilepticus (eFSE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>eFSE was induced in male and female rat pups. We transversed the hippocampus of postnatal day &gt;60 control (CTL) and eFSE rats with a 64-channel laminar silicon probe to assay cholinergic-dependent theta oscillations under urethane anesthesia. Local field potential properties were compared during (1) baseline sensory stimulation, (2) pharmacological stimulation via acetylcholine reuptake blockade, and (3) sensory stimulation after muscarinic acetylcholine receptor block (atropine).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In all groups, a baseline tail pinch could elicit theta oscillations via corticohippocampal synaptic input. Following atropine, a tail pinch response could no longer be elicited in CTL male, CTL female, or eFSE female rats. In contrast, induced slow theta power in eFSE males after atropine was not decreased to spontaneous levels. Analysis of oscillation bandwidths revealed sex differences in acetylcholine modulation of theta frequency and slow gamma frequency and power. This study also identified significant effects of both sex and eFSE on baseline theta–gamma comodulation, indicating a loss of coupling in eFSE males and a potential gain of function in eFSE females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>There are differences in cholinergic modulation of theta and gamma signal coordination between male and female rats. These differences may underlie worse cognitive outcomes in males following eFSE. Promoting the efficacy of muscarinic acetylcholine signaling prior to or following early life seizures could elucidate a mechanism for the temporal discoordination of neural signals within and between hippocampus and neocortex and provide a novel therapeutic approach for improving cognitive outcomes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080715","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}