Annals of Clinical and Translational Neurology最新文献

{"title":"Disease progression of spinocerebellar ataxia types 1, 2, 3 and 6 before and after ataxia onset","authors":"Heike Jacobi,&nbsp;Tamara Schaprian,&nbsp;Tanja Schmitz-Hübsch,&nbsp;Matthias Schmid,&nbsp;Thomas Klockgether,&nbsp;the EUROSCA and RISCA Study Groups","doi":"10.1002/acn3.51875","DOIUrl":"10.1002/acn3.51875","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our aim was to study the evolution of ataxia and neurological symptoms before and after ataxia onset in the most common spinocerebellar ataxias (SCAs), SCA1, SCA2, SCA3 and SCA6. We therefore jointly analysed the data of the EUROSCA and RISCA studies, which recruited ataxic and non-ataxic mutation carriers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used mixed effect models to analyse the evolution of Scale for the Rating and Assessment of Ataxia (SARA) scores, SCA Functional Index (SCAFI) and Inventory of Non-Ataxia Signs (INAS) counts. We applied multivariable modelling to identify factors associated with SARA progression. In the time interval 5 years prior to and after ataxia onset, we calculated sensitivity to change ratios (SCS) of SARA, SCAFI and INAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>2740 visits of 677 participants were analysed. All measures showed non-linear progression that was best fitted by linear mixed models with linear, quadratic and cubic time effects. <i>R</i>² values indicating quality of the fit ranged from 0.70 to 0.97. CAG repeat was associated with faster progression in SCA1, SCA2 and SCA3, but not SCA6. 5 years prior to and after ataxia onset, SARA had the highest SCS of all measures with a mean of 1.21 (95% CI: 1.20, 1.21) in SCA1, 0.94 (0.93, 0.94) in SCA2 and 1.23 (1.22, 1.23) in SCA3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Our data have important implications for the understanding of disease progression in SCA1, SCA2, SCA3 and SCA6 across the lifespan. Furthermore, our study provides information for the design of interventional trials, especially in pre-ataxic mutation carriers close to ataxia onset and patients in early disease stages.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1833-1843"},"PeriodicalIF":5.3,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51875","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Neurofilament light chain levels in cerebrospinal fluid as a sensitive biomarker for cerebral adrenoleukodystrophy”","authors":"","doi":"10.1002/acn3.51870","DOIUrl":"https://doi.org/10.1002/acn3.51870","url":null,"abstract":"<p>In the originally published version of the article, the patient labeling in the Results section on page 6 was incorrect and this has been corrected as follows.</p><p>From:</p><p>Cognitive function deteriorated in two patients (patients 20 and 21), while it was preserved in the other two patients (patients 17 and 18).</p><p>To:</p><p>Cognitive function deteriorated in two patients (patients 20 and 21), while it was preserved in the other two patients (patients 18 and 19).</p><p>In the originally published version of the article, there were labeling errors in the Figure 5B.</p><p>We apologize for these errors.</p><p>Kakumoto T, Matsukawa T, Ishiura H, Mori H, Tsuji S, Toda T. Neurofilament light chain levels in cerebrospinal fluid as a sensitive biomarker for cerebral adrenoleukodystrophy. Ann Clin Transl Neurol. 2023. https://doi.org/10.1002/acn3.51818</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 9","pages":"1700"},"PeriodicalIF":5.3,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6932530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pure cerebellar ataxia due to bi-allelic PRDX3 variants including recurring p.Asp202Asn","authors":"Stephanie Efthymiou,&nbsp;Luiz E. Novis,&nbsp;Georgios Koutsis,&nbsp;Chrysoula Koniari,&nbsp;Reza Maroofian,&nbsp;Valentina Turchetti,&nbsp;Georgios Velonakis,&nbsp;Luiz F. Vasconcellos,&nbsp;Salmo Raskin,&nbsp;Varunvenkat M. Srinivasan,&nbsp;Alistair T. Pagnamenta,&nbsp;Yaramanchanahalli B. Arun,&nbsp;Uddhava V. Kinhal,&nbsp;Vykuntaraju K. Gowda,&nbsp;Helio A. G. Teive,&nbsp;Henry Houlden","doi":"10.1002/acn3.51874","DOIUrl":"10.1002/acn3.51874","url":null,"abstract":"<p>Bi-allelic variants in peroxiredoxin 3 (<i>PRDX3</i>) have only recently been associated with autosomal recessive spinocerebellar ataxia characterized by early onset slowly progressive cerebellar ataxia, variably associated with hyperkinetic and hypokinetic features, accompanied by cerebellar atrophy and occasional olivary and brainstem involvement. Herein, we describe a further simplex case carrying a reported <i>PRDX3</i> variant as well as two additional cases with novel variants. We report the first Brazilian patient with SCAR32, replicating the pathogenic status of a known variant. All presented cases from the Brazilian and Indian populations expand the phenotypic spectrum of the disease by displaying prominent neuroradiological findings. SCAR32, although rare, should be included in the differential diagnosis of sporadic or recessive childhood and adolescent-onset pure and complex cerebellar ataxia.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1910-1916"},"PeriodicalIF":5.3,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51874","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High diagnostic performance of plasma and cerebrospinal fluid beta-synuclein for sporadic Creutzfeldt–Jakob disease","authors":"Samir Abu-Rumeileh,&nbsp;Steffen Halbgebauer,&nbsp;Giuseppe Mario Bentivenga,&nbsp;Lorenzo Barba,&nbsp;Simone Baiardi,&nbsp;Andrea Mastrangelo,&nbsp;Patrick Oeckl,&nbsp;Petra Steinacker,&nbsp;Angela Mammana,&nbsp;Sabina Capellari,&nbsp;Markus Otto,&nbsp;Piero Parchi","doi":"10.1002/acn3.51873","DOIUrl":"10.1002/acn3.51873","url":null,"abstract":"<p>Beta-synuclein is a promising cerebrospinal fluid and blood biomarker of synaptic damage. Here we analysed its accuracy in the discrimination between sporadic Creutzfeldt–Jakob disease (<i>n</i> = 150) and non-prion rapidly progressive dementias (<i>n</i> = 106). In cerebrospinal fluid, beta-synuclein performed better than protein 14-3-3 (AUC 0.95 vs. 0.89) and, to a lesser extent, than total tau (AUC 0.92). Further, the diagnostic value of plasma beta-synuclein (AUC 0.91) outperformed that of plasma tau (AUC 0.79) and neurofilament light chain protein (AUC 0.65) and was comparable to that of cerebrospinal fluid biomarkers. Beta-synuclein might represent the first highly accurate blood biomarker for the diagnosis of sporadic Creutzfeldt–Jakob disease.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1904-1909"},"PeriodicalIF":5.3,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51873","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10014086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D receptor and binding protein genes variants in patients with migraine","authors":"Elena García-Martín,&nbsp;Santiago Navarro-Muñoz,&nbsp;Pedro Ayuso,&nbsp;Christopher Rodríguez,&nbsp;Mercedes Serrador,&nbsp;Hortensia Alonso-Navarro,&nbsp;Marisol Calleja,&nbsp;Silvina Espada-Rubio,&nbsp;Francisco Navacerrada,&nbsp;Laura Turpín-Fenoll,&nbsp;Marta Recio-Bermejo,&nbsp;Rafael García-Ruiz,&nbsp;Jorge Millán-Pascual,&nbsp;José Francisco Plaza-Nieto,&nbsp;Esteban García-Albea,&nbsp;José A.G. Agúndez,&nbsp;Félix Javier Jiménez-Jiménez","doi":"10.1002/acn3.51872","DOIUrl":"10.1002/acn3.51872","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25-hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single-nucleotide variants (SNVs) <i>vitamin D receptor</i> (<i>VDR</i>) gene, <i>VDR</i> rs2228570, and <i>VDR</i> rs731236 have shown an association with migraine risk in a previous case–control association study, while an exome sequencing study identified a rare variant in <i>GC vitamin D binding protein</i> gene. This study aims to look for the association between several common variants in these two genes and the risk for migraine.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We genotyped 290 patients diagnosed with migraine and 300 age-matched controls using specific TaqMan assays for <i>VDR</i> rs2228570, <i>VDR</i> rs731236, <i>VDR</i> rs7975232, <i>VDR</i> rs739837, <i>VDR</i> rs78783628, <i>GC</i> rs7041, and <i>GC</i> rs4588 SNVs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. The <i>VDR</i> rs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In summary, the results of the current study suggest a lack of association between common SNVs in the <i>VDR</i> and <i>GC</i> gene and the risk of developing migraine. The possible relationship between <i>VDR</i> rs731236 and the triggering of migraine episodes with ethanol deserves future studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1824-1832"},"PeriodicalIF":5.3,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51872","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9960667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis","authors":"Bruce A. C. Cree,&nbsp;Rachel Maddux,&nbsp;Amit Bar-Or,&nbsp;Hans-Peter Hartung,&nbsp;Amandeep Kaur,&nbsp;Elizabeth Brown,&nbsp;Yicong Li,&nbsp;Yanhua Hu,&nbsp;James K. Sheffield,&nbsp;Diego Silva,&nbsp;Sarah Harris","doi":"10.1002/acn3.51862","DOIUrl":"10.1002/acn3.51862","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the serologic response, predictors of response, and clinical outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis (RMS) from DAYBREAK.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>DAYBREAK (ClinicalTrials.gov-NCT02576717), an open-label extension study of oral ozanimod 0.92 mg, enrolled participants aged 18–55 years with RMS who completed phase 1–3 ozanimod trials. Participants who were fully vaccinated against SARS-CoV-2 with mRNA or non-mRNA vaccines, were unvaccinated, and/or had COVID-19–related adverse events (AEs, with or without vaccination) and postvaccination serum samples were included (<i>n</i> = 288). Spike receptor binding domain (RBD) antibody levels (seroconversion: ≥0.8 U/mL) and serologic evidence of SARS-CoV-2 infection (nucleocapsid IgG: ≥1 U/mL) were assessed (Roche Elecsys/Cobas e411 platform).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In fully vaccinated participants (<i>n</i> = 148), spike RBD antibody seroconversion occurred in 90% (<i>n</i> = 98/109) of those without serologic evidence of prior SARS-CoV-2 exposure (100% [<i>n</i> = 80/80] seroconversion after mRNA vaccination) and in 100% (<i>n</i> = 39/39) of participants with serologic evidence of viral exposure. mRNA vaccination predicted higher spike RBD antibody levels, whereas absolute lymphocyte count (ALC), age, body mass index, and sex did not. COVID-19–related AEs were reported in 10% (<i>n</i> = 15/148) of fully vaccinated participants—all were nonserious and not severe; all participants recovered.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Most ozanimod-treated participants with RMS mounted a serologic response to SARS-CoV-2 vaccination and infection, regardless of participant characteristics or ALC levels. In this analysis, all COVID-19–related AEs post–full vaccination in participants taking ozanimod were nonserious and not severe.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1725-1737"},"PeriodicalIF":5.3,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51862","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10365931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive impairment in pulmonary arterial hypertension","authors":"Sloane Heller,&nbsp;Claudia See,&nbsp;Inderjit Singh,&nbsp;Carolyn A. Fredericks","doi":"10.1002/acn3.51867","DOIUrl":"10.1002/acn3.51867","url":null,"abstract":"<p>Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling with resultant abnormal increase in pulmonary artery pressure and right heart dysfunction. There is evidence that PAH includes cognitive impairment. However, the cognitive impairment syndrome has not been well described, and both the underlying mechanism and the relationship between cardiopulmonary and cognitive dysfunction in PAH are unknown. We performed cognitive evaluations and same day sub-maximum cardiopulmonary exercise testing on adult subjects with PAH. A frontal–subcortical syndrome suggestive of vascular cognitive impairment was found in 26% of subjects and was associated with noninvasive markers of pulmonary vascular remodeling.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1899-1903"},"PeriodicalIF":5.3,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51867","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9956882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A blood biomarker test for brain amyloid impacts the clinical evaluation of cognitive impairment","authors":"Mark Monane,&nbsp;Kim G. Johnson,&nbsp;B. Joy Snider,&nbsp;Raymond S. Turner,&nbsp;Jonathan D. Drake,&nbsp;Demetrius M. Maraganore,&nbsp;James L. Bicksel,&nbsp;Daniel H. Jacobs,&nbsp;Julia L. Ortega,&nbsp;Joni Henderson,&nbsp;Yan Jiang,&nbsp;Shuguang Huang,&nbsp;Justine Coppinger,&nbsp;Ilana Fogelman,&nbsp;Tim West,&nbsp;Joel B. Braunstein","doi":"10.1002/acn3.51863","DOIUrl":"10.1002/acn3.51863","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single-arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (<i>p</i> &lt; 0.0001). Anti-AD drug therapy decreased by 46% in low APS patients (<i>p</i> &lt; 0.0001) and increased by 57% in high APS patients (<i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>These findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1738-1748"},"PeriodicalIF":5.3,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51863","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9950529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical scales in autoimmune encephalitis—A retrospective monocentric cohort study","authors":"Stefan Macher,&nbsp;Gabriel Bsteh,&nbsp;Romana Höftberger,&nbsp;Thomas Berger,&nbsp;Paulus Rommer,&nbsp;Tobias Zrzavy","doi":"10.1002/acn3.51865","DOIUrl":"10.1002/acn3.51865","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Assessing severity of antibody-mediated encephalitis (AE) or paraneoplastic encephalitis (PE) requires valid and reliable scores to guide treatment decisions and predict outcome both in clinical routine and studies. We aimed to validate the prognostic value of the clinical assessment scale in autoimmune encephalitis (CASE) and the anti-NMDAR-encephalitis one-year functional status (NEOS) score in patients suffering from AE and PE in a large monocentric cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We retrospectively applied the CASE and NEOS score to patients with definite AE and PE treated at a tertiary hospital. Correlations were established between the CASE and NEOS score and the modified Rankin scale (mRs). Multivariable analyses were calculated to identify predictors of outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Thirty-four patients (27 AE, 7 PE) were included. Correlations between mRS and CASE score were strongest in patients with AE compared to PE at all intervals, but in the subgroups (LGI1, NMDAR, GAD, miscellaneous surface antibodies, PE) the correlation was strongest in the interval after baseline. Patients with AE seemed to display better outcomes compared to PE, which was underlined by multivariable analysis. Improvement was mostly observed within 6–12 months after disease onset, after which little or no further improvement was noted with some exception for two patients with anti-NMDARE who recovered substantially even after 12 months of treatment. The NEOS score significantly predicted the outcome at last follow-up in patients with AE with a sensitivity of 79% at a cut-off value of 2 points (AUC 0.79, 95% CI 0.58–0.99, <i>p</i> = 0.04).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The CASE and NEOS score are suitable supplementary tools in addition to the mRS for capturing diverse symptoms, for grading and monitoring symptom severity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1768-1775"},"PeriodicalIF":5.3,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated detection of immune effector cell-associated neurotoxicity syndrome via quantitative EEG","authors":"Christine A. Eckhardt,&nbsp;Haoqi Sun,&nbsp;Preeti Malik,&nbsp;Syed Quadri,&nbsp;Marcos Santana Firme,&nbsp;Daniel K. Jones,&nbsp;Meike van Sleuwen,&nbsp;Aayushee Jain,&nbsp;Ziwei Fan,&nbsp;Jin Jing,&nbsp;Wendong Ge,&nbsp;Husain H. Danish,&nbsp;Caron A. Jacobson,&nbsp;Daniel B. Rubin,&nbsp;Eyal Y. Kimchi,&nbsp;Sydney S. Cash,&nbsp;Matthew J. Frigault,&nbsp;Jong Woo Lee,&nbsp;Jorg Dietrich,&nbsp;M. Brandon Westover","doi":"10.1002/acn3.51866","DOIUrl":"10.1002/acn3.51866","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop an automated, physiologic metric of immune effector cell-associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor-T cell therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor-T cell therapy with a CD19 or B-cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records. Using quantitative EEG features, we developed a machine learning model to detect the presence and severity of neurotoxicity, known as the EEG immune effector cell-associated neurotoxicity syndrome score.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The EEG immune effector cell-associated neurotoxicity syndrome score significantly correlated with the grade of neurotoxicity with a median Spearman's <i>R</i>² of 0.69 (95% CI of 0.59–0.77). The mean area under receiving operator curve was greater than 0.85 for each binary discrimination level. The score also showed significant correlations with maximum ferritin (<i>R</i>² 0.24, <i>p</i> = 0.008), minimum platelets (<i>R</i>² –0.29, <i>p</i> = 0.001), and dexamethasone usage (<i>R</i>² 0.42, <i>p</i> &lt; 0.0001). The score significantly correlated with duration of neurotoxicity (<i>R</i>² 0.31, <i>p</i> &lt; 0.0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The EEG immune effector cell-associated neurotoxicity syndrome score possesses high criterion, construct, and predictive validity, which substantiates its use as a physiologic method to detect the presence and severity of neurotoxicity among patients undergoing chimeric antigen receptor T-cell therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"10 10","pages":"1776-1789"},"PeriodicalIF":5.3,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.51866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}