Annals of Clinical and Translational Neurology最新文献

{"title":"Stroke-like episodes in patients with adult-onset neuronal intranuclear inclusion disease and patients with late-onset MELAS: A comparative study","authors":"Yuzhi Shi,&nbsp;Gehong Dong,&nbsp;Hua Pan,&nbsp;Hongfei Tai,&nbsp;Yi Zhou,&nbsp;An Wang,&nbsp;Songtao Niu,&nbsp;Bin Chen,&nbsp;Xingao Wang,&nbsp;Zaiqiang Zhang","doi":"10.1002/acn3.52219","DOIUrl":"10.1002/acn3.52219","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To delineate the characteristics of stroke-like episodes (SLEs) in patients with adult-onset neuronal intranuclear inclusion disease (NIID) and to compare these characteristics with those of patients with MELAS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-three adult-onset NIID patients who presented with acute or subacute brain disorders and 13 late-onset MELAS patients were enrolled in the study. Patients with NIID were categorized into the SLEs group and the encephalopathy-like episodes (ELEs) group according to the associated stroke-like lesions (SLLs) findings. Clinical characteristics were compared between the SLEs group and the ELEs group among NIID patients and between NIID patients with SLEs and MELAS patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eleven (47.8%) NIID patients who manifested acute or subacute brain disorders had detectable associated SLLs and were categorized into SLEs group. SLEs patients were more likely to report fever, headache, and seizures instead of sleep disorders than ELEs patients. Four (36.4%) NIID patients with SLEs absence of diagnostic or suggestive NIID imaging features. The clinical manifestations, laboratory test results, and neuroimaging and muscle biopsy histological features of NIID patients with SLEs majorly overlapped with those of late-onset MELAS patients. Older age at the first SLE (OR [95% CI], 1.203 [1.045–1.384]), symptoms of movement disorders on admission (OR [95% CI], 9.625 [1.378–67.246]), and white matter hyperintensity in corpus callosum (OR [95% CI], 16.00 [1.542–166.46]) associated with the NIID diagnosis in patients with SLEs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>NIID patients with SLEs exhibit evident features of mitochondrial disorders. Interventions aimed at mitochondrial dysfunction might be a promising therapeutic approach for treating this disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 12","pages":"3125-3136"},"PeriodicalIF":4.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374733","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":"Evaluating post-thrombectomy effective connectivity changes in anterior circulation stroke","authors":"Jiaona Xu,&nbsp;Weiwei Chen,&nbsp;Guozhong Niu,&nbsp;Yuting Meng,&nbsp;Kefan Qiu,&nbsp;Tongyue Li,&nbsp;Luoyu Wang,&nbsp;Liqing Zhang,&nbsp;Yating Lv,&nbsp;Zhongxiang Ding","doi":"10.1002/acn3.52221","DOIUrl":"10.1002/acn3.52221","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Granger causal analysis (GCA) and amplitude of low-frequency fluctuation (ALFF) are commonly used to evaluate functional alterations in brain disorders. By combining the GCA and ALFF, this study aimed to investigate the effective connectivity (EC) changes in patients with acute ischemic stroke (AIS) and anterior circulation occlusion after mechanical thrombectomy (MT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from 43 AIS patients with anterior circulation occlusion within 1 week post-MT and 37 healthy controls. ALFF and GCA were calculated for each participant. Patients were further divided into groups based on prognosis and perfusion levels. The differences in ALFF and EC were compared between AIS patients and healthy controls and between subgroups of patients. Pearson correlations between EC, ALFF values, and clinical characteristics of patients were calculated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to healthy controls, post-MT, AIS patients exhibited significant ALFF increases in the left precuneus and decreases in the left fusiform gyrus and right caudate. Increased EC from the contralesional lingual gyrus, contralesional putamen, ipsilesional thalamus, and contralesional thalamus to the contralesional caudate was obsrved, while decrease in EC were found for contralesional caudate to the ipsilesional thalamus and medial superior frontal gyrus. EC differences were particularly notable between perfusion groups, with significantly lower EC in the poorly perfused group. EC values were also positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores pre-MT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>In AIS patients, the caudate nucleus was central to the observed EC changes post-MT, characterized by decreased outputs and increased inputs. These changes indicate functional remodeling within the cortico-basal ganglia-thalamic-cortical pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 12","pages":"3152-3162"},"PeriodicalIF":4.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142374732","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":"α-Synuclein species in plasma neuron-derived extracellular vesicles as biomarkers for iRBD","authors":"Xuemei Wang,&nbsp;Yuanchu Zheng,&nbsp;Huihui Cai,&nbsp;Wenyi Kou,&nbsp;Chen Yang,&nbsp;Siming Li,&nbsp;Bingxu Zhu,&nbsp;Jiayi Wu,&nbsp;Ning Zhang,&nbsp;Tao Feng,&nbsp;Xiaohong Li,&nbsp;Fulong Xiao,&nbsp;Zhenwei Yu","doi":"10.1002/acn3.52200","DOIUrl":"10.1002/acn3.52200","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Isolated REM sleep behavior disorder (iRBD) is considered as the strongest predictor of Parkinson's disease (PD). Reliable and accurate biomarkers for iRBD detection and the prediction of phenoconversion are in urgent need. This study aimed to investigate whether α-Synuclein (α-Syn) species in plasma neuron-derived extracellular vesicles (NDEVs) could differentiate between iRBD patients and healthy controls (HCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Nanoscale flow cytometry was used to detect α-Syn-containing NDEVs in plasma.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 54 iRBD patients and 53 HCs were recruited. The concentrations of total α-Syn, α-Syn aggregates, and phosphorylated α-Syn at Ser129 (pS129)-containing NDEVs in plasma of iRBD individuals were significantly higher than those in HCs (<i>p</i> &lt; 0.0001 for all). In distinguishing between iRBD and HCs, the area under the receiver operating characteristic (ROC) curve (AUC) for an integrative model incorporating the levels of α-Syn, pS129, and α-Syn aggregate-containing NDEVs in plasma was 0.965. This model achieved a sensitivity of 94.3% and a specificity of 88.9%. In iRBD group, the concentrations of α-Syn aggregate-containing NDEVs exhibited a negative correlation with Sniffin’ Sticks olfactory scores (<i>r</i> = −0.351, <i>p</i> = 0.039). Smokers with iRBD exhibited lower levels of α-Syn aggregates and pS129-containing NDEVs in plasma compared to nonsmokers (<i>p</i>_{α-Syn aggregates} = 0.014; <i>p</i>_pS129 = 0.003).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The current study demonstrated that the levels of total α-Syn, α-Syn aggregates, and pS129-containing NDEVs in the plasma of individuals with iRBD were significantly higher compared to HCs. The levels of α-Syn species-containing NDEVs in plasma may serve as biomarkers for iRBD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2891-2903"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265424","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":"Language abnormalities in Alzheimer's disease indicate reduced informativeness","authors":"Sabereh Bayat,&nbsp;Mahya Sanati,&nbsp;Mehrdad Mohammad-Panahi,&nbsp;Amirhossein Khodadadi,&nbsp;Mahdieh Ghasimi,&nbsp;Sahar Rezaee,&nbsp;Sara Besharat,&nbsp;Zahra Mahboubi-Fooladi,&nbsp;Mostafa Almasi-Dooghaee,&nbsp;Morteza Sanei-Taheri,&nbsp;Bradford C. Dickerson,&nbsp;Neguine Rezaii","doi":"10.1002/acn3.52205","DOIUrl":"10.1002/acn3.52205","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aims to elucidate the cognitive underpinnings of language abnormalities in Alzheimer's Disease (AD) using a computational cross-linguistic approach and ultimately enhance the understanding and diagnostic accuracy of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Computational analyses were conducted on language samples of 156 English and 50 Persian speakers, comprising both AD patients and healthy controls, to extract language indicators of AD. Furthermore, we introduced a machine learning-based metric, Language Informativeness Index (LII), to quantify empty speech.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Despite considerable disparities in surface structures between the two languages, we observed consistency across language indicators of AD in both English and Persian. Notably, indicators of AD in English resulted in a classification accuracy of 90% in classifying AD in Persian. The substantial degree of transferability suggests that the language abnormalities of AD do not tightly link to the surface structures specific to English. Subsequently, we posited that these abnormalities stem from impairments in a more universal aspect of language production: the ability to generate informative messages independent of the language spoken. Consistent with this hypothesis, we found significant correlations between language indicators of AD and empty speech in both English and Persian.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The findings of this study suggest that language impairments in AD arise from a deficit in a universal aspect of message formation rather than from the breakdown of language-specific morphosyntactic structures. Beyond enhancing our understanding of the psycholinguistic deficits of AD, our approach fosters the development of diagnostic tools across various languages, enhancing health equity and biocultural diversity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2946-2957"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265420","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":"Assessment of central vein sign and paramagnetic rim lesions in pediatric multiple sclerosis","authors":"Monica Margoni,&nbsp;Paolo Preziosa,&nbsp;Elisabetta Pagani,&nbsp;Loredana Storelli,&nbsp;Mor Gueye,&nbsp;Lucia Moiola,&nbsp;Massimo Filippi,&nbsp;Maria A. Rocca","doi":"10.1002/acn3.52208","DOIUrl":"10.1002/acn3.52208","url":null,"abstract":"<p>The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"3031-3036"},"PeriodicalIF":4.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265426","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":"miR-133b as a potential regulator of a synaptic NPTX2 protein in Alzheimer's disease","authors":"Sang-Won Han,&nbsp;Young Ho Park,&nbsp;Paula J Bice,&nbsp;David A. Bennett,&nbsp;SangYun Kim,&nbsp;Andrew J. Saykin,&nbsp;Kwangsik Nho","doi":"10.1002/acn3.52175","DOIUrl":"10.1002/acn3.52175","url":null,"abstract":"<p>A synaptic protein, Neuronal Pentraxin 2 (NPTX2), has emerged as a pivotal biomarker for Alzheimer's dementia (AD). We identified candidate miRNAs targeting NPTX2 and performed association and mediation analyses using multi-omics data (N = 702). Among 44 candidate miRNAs, miR-133b was significantly associated with AD and Braak positivity. Higher miR-133b expression was also associated with higher <i>NPTX2</i> gene expression and better cognition. Mediation analysis showed that miR-133b partially influences AD and cognition through the NPTX2 protein. Our integrated approach suggests a potential role of miR-133b in synaptic integrity and offers new insights into AD pathogenesis.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2799-2804"},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52175","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265422","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":"Impact of paramagnetic rim lesions on disability and race in multiple sclerosis: mediation analysis","authors":"Nara M. Michaelson,&nbsp;Sandra H. Rúa,&nbsp;Ulrike W. Kaunzner,&nbsp;Melanie Marcille,&nbsp;Iliana Pliska-Bloch,&nbsp;Kimberly Markowitz,&nbsp;Thanh D. Nguyen,&nbsp;Susan A. Gauthier","doi":"10.1002/acn3.52203","DOIUrl":"10.1002/acn3.52203","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Black American (BA) multiple sclerosis (MS) patients experience greater disability compared to White American (WA) patients. Here, we investigated the role of paramagnetic rim lesions (PRLs), a subset of chronic active lesions, on race-related disability in MS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective observational study comparing BA and WA MS patients. PRLs were identified through Quantitative Susceptibility Mapping (QSM) MRI. A causal mediation analysis explored the impact of PRLs on the relationship between race and disability, as measured by the Expanded Disability Status Scale (EDSS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of PRLs in BA patients with MS was higher at 55% compared to WA patients at 39% (<i>p</i> = 0.022). A higher percentage of PRLs among all white matter lesions was observed with BA (8.01%) patients compared to WA (3.4%) patients (<i>p</i> = 0.003). In a regression analysis, controlling for significant patient-level covariates and income-level demographics, the percentage of PRLs was, on average, 4.61 points higher for BA patients than for WA patients (<i>p</i> = 0.003). In a separate regression analysis, accounting for covariates, BA patients exhibited significantly higher EDSS scores (<i>p</i> &lt; 0.001). Further analysis demonstrated that the percentage of PRLs was a mediator in the association between BA patients and greater disability (<i>p</i> = 0.031). Higher proportion of PRLs in BA population accounted for 14% of the total effect of race on disability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>BA patients exhibit greater disability, in part, due to their higher proportion of PRLs. This study underscores the substantial impact of chronic active lesions on disability outcomes in this specific minority MS patient population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2923-2931"},"PeriodicalIF":4.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265421","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":"Longitudinal analysis of peripheral immune cells in patients with multiple sclerosis treated with anti-CD20 therapy","authors":"Mie Waede,&nbsp;Lasse F. Voss,&nbsp;Christina Kingo,&nbsp;Jesper B. Moeller,&nbsp;Maria L. Elkjaer,&nbsp;Zsolt Illes","doi":"10.1002/acn3.52182","DOIUrl":"10.1002/acn3.52182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Anti-CD20 therapy is a highly effective treatment for multiple sclerosis (MS). In this study, we investigated MS-related changes in peripheral blood mononuclear cell (PBMC) subsets compared to healthy controls and longitudinal changes related to the treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Multicolor spectral flow cytometry analysis was performed on 78 samples to characterize disease- and treatment-related PBMC clusters. Blood samples from MS patients were collected at baseline and up to 8 months post-treatment, with three collection points after treatment initiation. Unsupervised clustering tools and manual gating were applied to identify subclusters of interest and quantify changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>B cells were depleted from the periphery after anti-CD20 treatment as expected, and we observed an isolated acute, transitory drop in the proportion of natural killer (NK) and NKT cells among the main populations of PBMC (<i>P</i> = 0.03, <i>P</i> = 0.004). Major affected PBMC subpopulations were cytotoxic immune cells (NK, NKT, and CD8⁺ T cells), and we observed a higher proportion of cytotoxic cells with reduced brain-homing ability and a higher regulatory function as a long-term anti-CD20-related effect. Additionally, anti-CD20 therapy altered distributions of memory CD8⁺ T cells and reduced exhaustion markers in both CD4⁺ and CD8⁺ T cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The findings of this study elucidate phenotypic clusters of NK and CD8⁺ T cells, which have previously been underexplored in the context of anti-CD20 therapy. Phenotypic modifications towards a more regulatory and controlled phenotype suggest that these subpopulations may play a critical and previously unrecognized role in mediating the therapeutic efficacy of anti-CD20 treatments.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2657-2672"},"PeriodicalIF":4.4,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277496","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":"No replicating evidence for anti-amyloid-β autoantibodies in cerebral amyloid angiopathy-related inflammation","authors":"Emma van den Berg,&nbsp;Rian Roelofs,&nbsp;Lieke Jäkel,&nbsp;Steven M. Greenberg,&nbsp;Andreas Charidimou,&nbsp;Ellis S. van Etten,&nbsp;Delphine Boche,&nbsp;Catharina J. M. Klijn,&nbsp;Floris H. B. M. Schreuder,&nbsp;H. Bea Kuiperij,&nbsp;Marcel M. Verbeek","doi":"10.1002/acn3.52169","DOIUrl":"10.1002/acn3.52169","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Elevated levels of anti-amyloid-β (anti-Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy-related inflammation (CAA-RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA-RI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We replicated the immunoassay to detect CSF anti-Aβ autoantibodies using CSF from CAA-RI patients and non-CAA controls with unrelated disorders and further characterized its performance. Moreover, we conducted a literature review of CAA-RI case reports to investigate neuropathological and CSF evidence of the nature of the inflammatory reaction in CAA-RI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (<i>r</i>_sp = 0.51, <i>p</i> = 0.02). Assay levels were not elevated in CAA-RI patients (<i>n</i> = 6) compared to non-CAA controls (<i>n</i> = 20; <i>p</i> = 0.64). Literature review indicated only occasional presence of B-lymphocytes and plasma cells (i.e., antibody-producing cells), alongside the abundant presence of activated microglial cells, T-cells, and other monocyte lineage cells. CSF analysis did not convincingly indicate intrathecal IgG production.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>We were unable to reproduce the reported elevation of anti-Aβ autoantibody concentration in CSF of CAA-RI patients. Our findings instead support nonspecific detection of IgG levels in CSF by the assay. Reviewed CAA-RI case reports suggested a widespread cerebral inflammatory reaction. In conclusion, our findings do not support anti-Aβ autoantibodies as a diagnostic biomarker for CAA-RI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2563-2571"},"PeriodicalIF":4.4,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265425","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":"Endogenous tPA levels: A biomarker for discriminating hemorrhagic stroke from ischemic stroke and stroke mimics","authors":"Melissa Jauquet,&nbsp;Pierre Gagnepain,&nbsp;Estelle La Porte,&nbsp;Audrey M. Thiebaut,&nbsp;Ambre Rochey,&nbsp;Helene Legros,&nbsp;Baptiste Laine,&nbsp;Marion Berthelot,&nbsp;Valerie Roussel,&nbsp;Joan Montaner,&nbsp;Barbara Casolla,&nbsp;Denis Vivien,&nbsp;Eloise Lemarchand,&nbsp;Richard Macrez,&nbsp;Benoit D. Roussel","doi":"10.1002/acn3.52197","DOIUrl":"10.1002/acn3.52197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Stroke is the leading cause of death and disability. Timely differentiation between ischemic stroke, hemorrhagic stroke, and stroke mimics is critical for tailored treatment and triage. To accelerate the identification of stroke's subtype, we propose to use the levels of circulating tPA as a biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Biostroke is an observational study performed at the Caen Hospital. We quantified tPA levels in 110 patients with ischemic strokes, 30 patients with hemorrhagic strokes, and 67 stroke mimic patients upon their arrival at the emergency. Two logistic regression models were formulated: one with parameters measurable in an ambulance (Model A) and one with parameters measurable at the hospital (Model H). These models were both tested with or without plasma tPA measurements. Our initial assessment involved evaluating the effectiveness of both models in distinguishing between hemorrhagic strokes, ischemic strokes, and stroke mimics within our study cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasmatic tPA levels exhibit significant distinctions between hemorrhagic, ischemic, and mimic stroke patients (1.8; 2.5; 2.4 ng/mL, respectively). The inclusion of tPA in model A significantly enhances the classification accuracy of hemorrhagic patients only, increasing identification from 0.67 (95% CI, 0.59 to 0.75) to 0.78 (95% CI, 0.7 to 0.85) (<i>p</i> = 0.0098). Similarly, in model H, classification accuracy of hemorrhagic patients significantly increased with the addition of tPA, rising from 0.75 (95% CI, 0.67 to 0.83) without tPA to 0.86 (95% CI, 0.81 to 0.91) with tPA (<i>p</i> = 0.024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretations</h3>\u0000 \u0000 <p>Our findings underscore the valuable role of tPA levels in distinguishing between stroke subtypes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2877-2890"},"PeriodicalIF":4.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202689","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}