Epilepsia最新文献

{"title":"Poststroke seizures and epilepsy increase the risk of dementia among stroke survivors: A population‐based study","authors":"Kuan‐Lin Sung, Miao‐Jen Kuo, Hsin‐Yi Yang, Ching‐Fang Tsai, Sheng‐Feng Sung","doi":"10.1111/epi.18117","DOIUrl":"https://doi.org/10.1111/epi.18117","url":null,"abstract":"ObjectiveWith global aging, the occurrence of stroke and associated outcomes like dementia are on the rise. Seizures and epilepsy are common poststroke complications and have a strong connection to subsequent dementia. This study examines the relationship between poststroke seizures (PSS) or poststroke epilepsy (PSE) and dementia using a national health care database.MethodsWe conducted a retrospective study using data from the Taiwan National Health Insurance Research Database from 2009 to 2020. We identified acute stroke patients from 2010 to 2015, excluding those with pre‐existing neurological conditions. Based on age, sex, stroke severity level, and the year of index stroke, patients with PSS or PSE were matched to those without. The main outcome was incident dementia.ResultsThis study included 62 968 patients with an average age of 63 years, with males accounting for 62.9%. Of them, 60.3% had ischemic strokes, and 39.7% had hemorrhagic strokes. After an average follow‐up period of 5.2 years, dementia developed in 15.9% of patients who had PSS or PSE, as opposed to 8.4% of those without these conditions. A time‐dependent Fine and Gray competing risk analysis showed that PSS and PSE were significantly associated with dementia across all stroke types. Subgroup analyses revealed significantly increased risk of dementia across all age groups (<50, 50–64, and ≥65 years), sexes, and various stroke severity levels. The link between PSS or PSE and dementia was particularly pronounced in men, with a less distinct correlation in women.SignificanceThe risk of incident dementia was higher in patients with PSS or PSE. The potential for therapeutic interventions for seizures and epilepsy to reduce poststroke dementia underscores the importance of seizure screening and treatment in stroke survivors.","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177543","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":"N‐of‐1 trials in epilepsy: A systematic review and lessons paving the way forward","authors":"Victoria M. Defelippe, Eva H. Brilstra, Willem M. Otte, Helen J. Cross, Finbar O'Callaghan, Valentina De Giorgis, Annapurna Poduri, Holger Lerche, Sanjay Sisodiya, Kees P. J. Braun, Floor E. Jansen, Emilio Perucca","doi":"10.1111/epi.18068","DOIUrl":"https://doi.org/10.1111/epi.18068","url":null,"abstract":"ObjectiveDefined as prospective single‐patient crossover studies with repeated paired cycles of active and control intervention, N‐of‐1 trials have gained attention as an option to obtain high‐quality evidence of efficacy, particularly for patients with rare epilepsies in whom conduction of well‐powered randomized controlled trials can be challenging. The objective of this systematic review is to provide an appraisal of the literature on N‐of‐1 trials in individuals with epilepsy.MethodsWe searched PubMed and Embase on January 12, 2024, for studies meeting the following criteria: prospectively planned, within‐patient, multiple‐crossover design in individuals with epilepsy and outcomes related to comorbidities. Information on design, outcome measurements, intervention, and analyses was retrieved. Risk of bias assessment was performed using the Risk of Bias in N‐of‐1 Trials (RoBiNT) scale. We highlighted methodological aspects of the N‐of‐1 trials identified and discuss future recommendations.ResultsFive studies met our inclusion criteria. An additional multiple‐crossover trial that evaluated treatment effects exclusively at group level was also included because of its relevance to N‐of‐1 study methodology. The studies enrolled individuals with focal seizures, absences or cognitive impairement and electrographic discharges. Treatments included established or investigational antiseizure medications, off‐label medications, neurostimulation or lifestyle intervention. Three of the five N‐of‐1 trials reported on individual cases. The studies' strengths were the use of individualized treatment dosages and symptom‐specific patient‐reported outcomes. Limitations were related to minimal reporting of baseline characteristics and seizure burden.SignificanceThe trials identified by our search exemplify how the N‐of‐1 design can be applied to assess interventions in individuals with epilepsy‐related disorders. Future N‐of‐1 trials of antiseizure interventions should take into account baseline seizure frequency, should apply statistical models suited to capture seizure frequency changes reliably and make predefined interim assessments. Non‐seizure outcome measures evaluable over short periods should be considered. Tailored N‐of‐1 methodology could pave the way to evidence‐based, treatment selection for patients with rare epilepsies.","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177542","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":"Prediction of epilepsy after stroke: Proposal of a modified SeLECT 2.0 score based on posttreatment stroke outcome.","authors":"Stefano Meletti, Claudia Cuccurullo, Niccolò Orlandi, Giuseppe Borzì, Guido Bigliardi, Stefania Maffei, Cinzia Del Giovane, Riccardo Cuoghi Costantini, Giada Giovannini, Simona Lattanzi","doi":"10.1111/epi.18114","DOIUrl":"https://doi.org/10.1111/epi.18114","url":null,"abstract":"<p><strong>Objective: </strong>The SeLECT 2.0 score is a prognostic model of epilepsy after ischemic stroke. We explored whether replacing the severity of stroke at admission with the severity of stroke after treatment at 72 h from onset could improve the predictive accuracy of the score.</p><p><strong>Methods: </strong>We retrospectively identified consecutive adults with acute first-ever neuroimaging-confirmed ischemic stroke who were admitted to the Stroke Unit of the Ospedale Civile Baggiovara (Modena, Italy) and treated with intravenous thrombolysis and/or endovascular treatment. Study outcome was the occurrence of at least one unprovoked seizure presenting >7 days after stroke.</p><p><strong>Results: </strong>Participants included in the analysis numbered 1094. The median age of the subjects was 74 (interquartile range [IQR] = 64-81) years, and 595 (54.4%) were males. Sixty-five (5.9%) subjects developed unprovoked seizures a median of 10 (IQR = 6-27) months after stroke. The median values of the original and modified SeLECT2.0 scores were 3 (IQR = 2-4) and 2 (IQR = 1-3). The modified SeLECT 2.0 score showed better discrimination for the prediction of poststroke epilepsy at 36, 48, and 60 months after stroke compared to the original score according to the area under time-dependent receiver operating characteristic curves. The modified SeLECT 2.0 score had higher values of Harrell C and Somers D parameters and lower values of Akaike and Bayesian information criteria than the original score. The modified SeLECT 2.0 score produced more accurate risk predictions compared to the SeLECT 2.0 score at all evaluated time points from 12 to 60 months after stroke according to the Net Reclassification Index.</p><p><strong>Significance: </strong>Replacing baseline with posttreatment stroke severity may improve the ability of the SeLECT 2.0 score to predict poststroke epilepsy.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132179","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":"Introduction of the incoming editor-in-chief of Epilepsia","authors":"Fernando Cendes","doi":"10.1111/epi.18084","DOIUrl":"10.1111/epi.18084","url":null,"abstract":"","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105581","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":"Early life seizures and olfactory communication in rats","authors":"Logan J. Bigelow,&nbsp;Emily K. Pope,&nbsp;Jack H. M. Jarvis,&nbsp;Catherine Fiset,&nbsp;Carol Le Maistre-Matthys,&nbsp;Tim A. Benke,&nbsp;Paul B. Bernard","doi":"10.1111/epi.18099","DOIUrl":"10.1111/epi.18099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Early life seizures (ELS) are commonly associated with autism spectrum disorder (ASD); however, the exact role of ELS in the pathology is unknown. Prior studies have demonstrated social deficits, a core feature of ASD, following ELS; consequently, alterations in sensory modalities may contribute to the overall social deficits. Considering the speculated contribution of sensory deficit to social communication, we examined the developmental consequences of early postnatal kainic acid (KA)-induced seizures on olfactory preference and neural markers in the olfactory bulb in both male and female Sprague Dawley rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>KA-induced seizures or saline was administered. Rats were then exposed to a series of biologically relevant scents including male scent, female scent, nest scent, and phenylethylamine during the juvenile period and again during adulthood. Alterations in sensory modalities were expected to be expressed via abnormal preference for certain scents and/or production of abnormal ultrasonic vocalizations in response to scents. The olfactory bulbs were also assessed for the biologically relevant markers glial fibrillary acidic protein (GFAP) and calcium/calmodulin-dependent protein kinase II (CAMKII).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings resulted in no significant differences in olfactory preference following ELS for juveniles or adults compared to controls. Similarly, there were no differences in GFAP expression or the ratio of phosphorylated CAMKII to CAMKII in either olfactory bulb. Interestingly, despite a lack of treatment differences, different scents were shown to elicit different responses in juvenile rats, yet these differences subsided in adulthood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>Overall, the results of this study suggest that olfaction does not contribute to socialization deficit following ELS within the KA model.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105579","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":"Pharmacological management of prolonged seizures in Dravet syndrome including intravenous phenytoin","authors":"Rana Abi Tayeh,&nbsp;Blandine Dozières-Puyravel,&nbsp;Lionel Arnaud,&nbsp;Luigi Titomanlio,&nbsp;Stéphane Dauger,&nbsp;Sophie Höhn,&nbsp;Eric Le Guern,&nbsp;Stéphane Auvin","doi":"10.1111/epi.18101","DOIUrl":"10.1111/epi.18101","url":null,"abstract":"<p>Dravet syndrome (DS) is an infantile onset developmental and epileptic encephalopathy. Sodium channel blockers are known to exacerbate seizures in this syndrome. Due to its high incidence, the management of prolonged seizures is crucial for DS patients. There is still ambiguity regarding the use of intravenous phenytoin for prolonged seizure in DS patients mainly due to the lack of data, raising concern about the safety of it use. We conducted a retrospective study (from January 2009 to January 2020) aiming to assess the management of prolonged seizures in DS with a focus on the use of intravenous phenytoin. Data were collected for patients admitted to our hospital for seizures lasting &gt;5 min. Among 52 identified patients in our database, 23 experienced 59 prolonged seizures managed in our hospital. Only four seizures ceased without rescue medication. Notably, the use of intravenous phenytoin was not associated with discernible adverse effects and was effective in stopping status epilepticus in 71% of cases. This study suggests the safety and efficacy of intravenous phenytoin for prolonged seizure in DS. There is a need for broader investigations of emergency treatments for evidence-based recommendations for the emergency plan of each patient.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105582","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":"Febrile seizures and childhood epilepsy and risk of internalizing and psychotic symptoms","authors":"Sofie J. Nielsen,&nbsp;Bodil H. Bech,&nbsp;Katrine Strandberg-Larsen,&nbsp;Eva Bølling-Ladegaard,&nbsp;Chris Cotsapas,&nbsp;Jakob Christensen,&nbsp;Julie W. Dreier","doi":"10.1111/epi.18095","DOIUrl":"10.1111/epi.18095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess whether children with febrile seizures and/or epilepsy were at increased risk of experiencing internalizing symptoms or psychotic-like experiences at age 11 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cohort study includes 44 819 children from the 11-year follow up of the Danish National Birth Cohort. Information on childhood seizures was retrieved from the Danish National Patient Registry, whereas child psychiatric symptoms were assessed in a web-based questionnaire using the <i>Adolescent Psychotic-like Symptom Screener</i> and <i>the Strength and Difficulties Questionnaire</i>. Adjusted odds ratios (aORs) with corresponding 95% confidence intervals (CIs) for the association between childhood seizures and internalizing symptoms (symptom score ≥8) and psychotic-like experiences (≥2 definite experiences) were obtained using logistic regression models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1620 children with febrile seizures (3.6%), and 311 children with epilepsy (0.7%) were identified. When adjusted for potential confounders, no association between febrile seizures and psychiatric symptoms was observed, and no association was observed between epilepsy and psychotic-like experiences. However, the OR for internalizing symptoms was 1.76 (95% CI: 1.20–2.58) in children with epilepsy compared to children without. This higher risk was evident mainly in boys (OR 2.30, 95% CI 1.37–3.85), children with ≥2 epilepsy-related hospital admissions (OR 2.79, 95% CI 1.81–4.32), and children whose age at first epilepsy-related hospital admission was 0–3 years (OR 2.47, 95% CI 1.45–4.19).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>No association was found between febrile seizures and psychiatric symptoms or epilepsy and psychotic-like experiences at age 11. However, boys with epilepsy were at higher risk of experiencing internalizing symptoms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105580","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":"Utilizing an acute hyperthermia-induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome","authors":"Jeffrey A. Mensah,&nbsp;Kristina Johnson,&nbsp;Tia Freeman,&nbsp;Christopher A. Reilly,&nbsp;Joseph E. Rower,&nbsp;Cameron S. Metcalf,&nbsp;Karen S. Wilcox","doi":"10.1111/epi.18104","DOIUrl":"10.1111/epi.18104","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second-line treatment regimen that combines clobazam and sodium valproate with an add-on drug as a proof-of-principle approach to establish an effective therapeutic regimen in a DS mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the efficacy of add-on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia-induced seizures in <i>Scn1a</i>^{<i>A1783V/WT</i>} mice. Clobazam, N-desmethyl clobazam (an active metabolite of clobazam), sodium valproate, stiripentol, and cannabidiol concentrations were quantified in plasma and brain using liquid chromatography–tandem mass spectrometry for the combinations deemed effective against hyperthermia-induced seizures. The concentration data were used to calculate pharmacokinetic parameters via noncompartmental analysis in Phoenix WinNonLin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia-induced seizures in <i>Scn1a</i>^{<i>A1783V/WT</i>} mice. In <i>Scn1a</i>^<i>WT/WT</i> mice, brain clobazam and N-desmethyl clobazam concentrations were higher in the triple-drug combinations than in the clobazam monotherapy. Stiripentol and cannabidiol brain concentrations were greater in the triple-drug therapy than when given alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug–drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105584","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":"Timing of interventions to control neuronal chloride elevation in a model of neonatal seizures after hippocampal injury.","authors":"Volodymyr I Dzhala, Michelle Mail, Kevin J Staley","doi":"10.1111/epi.18108","DOIUrl":"https://doi.org/10.1111/epi.18108","url":null,"abstract":"<p><strong>Objective: </strong>Following hypoxic-ischemic (HI) brain injury, neuronal cytoplasmic chloride concentration ([Cl^-]_i) increases, potentially contributing to depolarizing γ-aminobutyric acid (GABA) responses, onset of seizures, and the failure of antiepileptic drugs that target inhibitory chloride-permeable GABA_A receptors. Post-HI seizures characteristically begin hours after injury, by which time substantial accumulation of [Cl^-]_i may have already occurred. In immature neurons, a major pathway for Cl^- influx is the reversible Na⁺-K⁺-2Cl^- cotransporter NKCC1.</p><p><strong>Methods: </strong>Spontaneous neuronal network, neuronal [Cl^-]_i, and GABA activity were determined in hippocampal preparations from neonatal Clomeleon and SuperClomeleon/DLX-cre mice to test whether blocking NKCC1 earlier after oxygen-glucose deprivation (OGD) injury would more effectively ameliorate the increase in [Cl^-]_i, ictallike epileptiform discharges (ILDs), and the failure of the GABAergic anticonvulsant phenobarbital.</p><p><strong>Results: </strong>In vitro, murine intact hippocampi were free of ILDs for 12 h after preparation. Transient OGD resulted in a gradual increase in [Cl^-]_i, depolarizing action of GABA, and facilitation of neuronal network activity. Spontaneous ILDs began 3-5 h after injury. Blocking NKCC1 with 2-10 μmol·L^-1 bumetanide reduced [Cl^-]_i equally well when applied up to 10 h after injury. Whereas phenobarbital or bumetanide applied separately were less effective when applied later after injury, ILDs were successfully suppressed by the combination of phenobarbital and bumetanide regardless of the number of prior ILDs or delay in application.</p><p><strong>Significance: </strong>The present age-specific group studies demonstrate that after OGD, NKCC1 transport activity significantly contributes to progressive [Cl^-]_i accumulation, depolarizing action of GABA, and delayed onset of ILDs. In this neonatal model of neuronal injury and ILDs, earlier treatment with bumetanide alone more efficiently recovered control baseline [Cl^-]_i and depressed epileptiform discharges. However, there was no time dependency to the anti-ictal efficacy of the combination of phenobarbital and bumetanide. These in vitro results suggest that after perinatal injury, early pre-emptive treatment with phenobarbital plus bumetanide would be as efficacious as late treatment after seizures are manifest.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105583","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":"Psychometric evaluation of clinician- and caregiver-reported clinical severity assessments for individuals with CDKL5 deficiency disorder","authors":"Jacinta M. Saldaris,&nbsp;Peter Jacoby,&nbsp;Jenny Downs,&nbsp;Eric D. Marsh,&nbsp;Helen Leonard,&nbsp;Elia Pestana-Knight,&nbsp;Rajsekar Rajaraman,&nbsp;Judith Weisenberg,&nbsp;Bernhard Suter,&nbsp;Heather E. Olson,&nbsp;Dana Price,&nbsp;William Hong,&nbsp;Erin Prange,&nbsp;Tim A. Benke,&nbsp;Scott Demarest","doi":"10.1111/epi.18094","DOIUrl":"10.1111/epi.18094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The CDKL5 Clinical Severity Assessment (CCSA) is a comprehensive, content-validated measurement tool capturing the diverse challenges of cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD), a genetically caused developmental epileptic encephalopathy (DEE). The CCSA is divided into clinician-reported (CCSA-Clinician) and caregiver-reported (CCSA-Caregiver) assessments. The aim of this study was to evaluate the factor structure of these measures through confirmatory factor analysis (CFA) and evaluate their validity and reliability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Participants were recruited from the International CDKL5 Clinical Research Network to take part in an in-clinic CCSA-Clinician evaluation (<i>n</i> = 148) and/or complete the CCSA-Caregiver questionnaire (<i>n</i> = 198). CFA was used to determine domains, and factor loadings and validity were assessed. For the CCSA-Clinician, inter-rater reliability was assessed by nine CDD experienced clinicians via 14 pre-recorded evaluations. Eight clinicians re-viewed and re-scored the videos after 4 weeks to evaluate intra-rater reliability. The CCSA-Caregiver was completed on a second occasion by 34 caregivers after 2–4 weeks to assess test–retest reliability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CFA resulted in three domains for the CCSA-Clinician (motor and movement, communication, vision) and four domains for the CCSA-Caregiver (seizures, behavior, alertness, feeding), with good item loadings across both measures. Structural statistics, internal consistency, discriminant validity, and reliability were satisfactory for both measures, and scores were consistent between known groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Significance</h3>\u0000 \u0000 <p>This study provides strong evidence that the CCSA measures are suitable to assess the clinical severity of individuals with CDD, supporting their use in clinical trials. Further evaluation of responsiveness to change in a longitudinal assessment is planned. Use may also be appropriate in similar DEEs but would require validation in those populations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072301","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}