Sang-Won Han, Young Ho Park, Paula J Bice, David A. Bennett, SangYun Kim, Andrew J. Saykin, Kwangsik Nho
{"title":"miR-133b as a potential regulator of a synaptic NPTX2 protein in Alzheimer's disease","authors":"Sang-Won Han, Young Ho Park, Paula J Bice, David A. Bennett, SangYun Kim, Andrew J. Saykin, 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}
Nara M. Michaelson, Sandra H. Rúa, Ulrike W. Kaunzner, Melanie Marcille, Iliana Pliska-Bloch, Kimberly Markowitz, Thanh D. Nguyen, Susan A. Gauthier
{"title":"Impact of paramagnetic rim lesions on disability and race in multiple sclerosis: mediation analysis","authors":"Nara M. Michaelson, Sandra H. Rúa, Ulrike W. Kaunzner, Melanie Marcille, Iliana Pliska-Bloch, Kimberly Markowitz, Thanh D. Nguyen, 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> < 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}
Mie Waede, Lasse F. Voss, Christina Kingo, Jesper B. Moeller, Maria L. Elkjaer, Zsolt Illes
{"title":"Longitudinal analysis of peripheral immune cells in patients with multiple sclerosis treated with anti-CD20 therapy","authors":"Mie Waede, Lasse F. Voss, Christina Kingo, Jesper B. Moeller, Maria L. Elkjaer, 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<sup>+</sup> 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<sup>+</sup> T cells and reduced exhaustion markers in both CD4<sup>+</sup> and CD8<sup>+</sup> 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<sup>+</sup> 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}
Emma van den Berg, Rian Roelofs, Lieke Jäkel, Steven M. Greenberg, Andreas Charidimou, Ellis S. van Etten, Delphine Boche, Catharina J. M. Klijn, Floris H. B. M. Schreuder, H. Bea Kuiperij, Marcel M. Verbeek
{"title":"No replicating evidence for anti-amyloid-β autoantibodies in cerebral amyloid angiopathy-related inflammation","authors":"Emma van den Berg, Rian Roelofs, Lieke Jäkel, Steven M. Greenberg, Andreas Charidimou, Ellis S. van Etten, Delphine Boche, Catharina J. M. Klijn, Floris H. B. M. Schreuder, H. Bea Kuiperij, 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><sub>sp</sub> = 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}
Melissa Jauquet, Pierre Gagnepain, Estelle La Porte, Audrey M. Thiebaut, Ambre Rochey, Helene Legros, Baptiste Laine, Marion Berthelot, Valerie Roussel, Joan Montaner, Barbara Casolla, Denis Vivien, Eloise Lemarchand, Richard Macrez, Benoit D. Roussel
{"title":"Endogenous tPA levels: A biomarker for discriminating hemorrhagic stroke from ischemic stroke and stroke mimics","authors":"Melissa Jauquet, Pierre Gagnepain, Estelle La Porte, Audrey M. Thiebaut, Ambre Rochey, Helene Legros, Baptiste Laine, Marion Berthelot, Valerie Roussel, Joan Montaner, Barbara Casolla, Denis Vivien, Eloise Lemarchand, Richard Macrez, 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}
Xavier Caldú, Lee B. Reid, Kerstin Pannek, Jurgen Fripp, Júlia Ballester-Plané, David Leiva, Roslyn N. Boyd, Roser Pueyo, Olga Laporta-Hoyos
{"title":"Tractography of sensorimotor pathways in dyskinetic cerebral palsy: Association with motor function","authors":"Xavier Caldú, Lee B. Reid, Kerstin Pannek, Jurgen Fripp, Júlia Ballester-Plané, David Leiva, Roslyn N. Boyd, Roser Pueyo, Olga Laporta-Hoyos","doi":"10.1002/acn3.52174","DOIUrl":"10.1002/acn3.52174","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Neuroimaging studies of dyskinetic cerebral palsy (CP) are scarce and the neuropathological underpinnings are not fully understood. We delineated the corticospinal tract (CST) and cortico-striatal-thalamocortical (CSTC) pathways with probabilistic tractography to assess their (1) integrity and (2) association with motor functioning in people with dyskinetic CP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Diffusion weighted magnetic resonance images were obtained for 33 individuals with dyskinetic CP and 33 controls. Fractional anisotropy (FA) and mean diffusivity (MD) for the CST and the CSTC pathways were compared between groups. Correlation analyses were performed between tensor metric values and motor function scores of participants with dyskinetic CP as assessed by the Gross Motor Function Classification System (GMFCS), the Bimanual Fine Motor Function (BFMF), and the Manual Ability Classification System (MACS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>White matter integrity in both the CST and the CSTC pathways was reduced in people with dyskinetic CP. The GMFCS, MACS and, less commonly, the BFMF were associated with FA and, particularly, MD in most portions of these pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The present study advances our understanding of the involvement of white matter microstructure in sensorimotor pathways and its relationship with motor impairment in people with dyskinetic CP. Our results are consistent with well-described relationships between upper limb function and white matter integrity in the CST and CSTC pathways in other forms of CP. This knowledge may ultimately help prognosis and therapeutic programmes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2609-2622"},"PeriodicalIF":4.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52174","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202688","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}
Orna Gera, Efrat Shavit-Stein, Taly Amichai, Joab Chapman, Odelia Chorin, Lior Greenbaum, Amir Dori
{"title":"Muscular dystrophy patients show low exercise-induced blood flow in muscles with normal strength","authors":"Orna Gera, Efrat Shavit-Stein, Taly Amichai, Joab Chapman, Odelia Chorin, Lior Greenbaum, Amir Dori","doi":"10.1002/acn3.52194","DOIUrl":"10.1002/acn3.52194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Neuromuscular evaluation increasingly employs muscle ultrasonography to determine muscle thickness, mean grayscale echointensity, and visual semiquantitative echotexture attenuation. However, these measures provide low sensitivity for detection of mild muscle abnormality. Exercise-induced intramuscular blood flow is a physiologic phenomenon, which may be impaired in mildly affected muscles, particularly in dystrophinopathies, and may indicate functional muscle ischemia. We aimed to determine if muscle blood flow is reduced in patients with neuromuscular disorders and preserved muscle strength, and if it correlates with echointensity and digital echotexture measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peak exercise-induced blood flow, echointensity, and echotexture were quantified in the elbow flexor muscles of 15 adult patients with Becker muscular dystrophy (BMD) and 13 patients with other muscular dystrophies (OMD). These were compared to 17 patients with Charcot–Marie–Tooth type 1 (CMT1) neuropathy and 21 healthy adults from a previous study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Muscle blood flow was reduced in all patient groups compared to controls, most prominently in BMD patients (<i>p</i> < 0.0001). Echointensity was similarly increased in all patient groups (<i>p</i> < 0.05), while echotexture was reduced only in muscular dystrophy patients (p ≤ 0.002). In BMD, blood flow correlated with echotexture (Pearson <i>r</i> = 0.6098, <i>p</i> = 0.0158) and strength (Spearman <i>r</i> = 0.5471; <i>p</i> = 0.0370). In patients with normal muscle strength, reduced muscle blood flow was evident in all patient groups (<i>p</i> < 0.001), echotexture was reduced in BMD and OMD (<i>p</i> < 0.01), and echointensity was increased in CMT (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>Muscle blood flow is a sensitive measure to detect abnormality, even in muscles with normal strength. Increased echointensity may indicate a neurogenic disorder when strength is preserved, while low echotexture suggests a dystrophic disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 11","pages":"2866-2876"},"PeriodicalIF":4.4,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202690","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}
Kathryn Yang, Vicente Quiroz, Amy Tam, Rasha Srouji, Ximena Villanueva, Claudia Amarales, Darius Ebrahimi-Fakhari
{"title":"Juvenile-onset Huntington's disease – Spectrum and evolution of presenting movement disorders","authors":"Kathryn Yang, Vicente Quiroz, Amy Tam, Rasha Srouji, Ximena Villanueva, Claudia Amarales, Darius Ebrahimi-Fakhari","doi":"10.1002/acn3.52193","DOIUrl":"10.1002/acn3.52193","url":null,"abstract":"<p>Juvenile-onset Huntington's disease (HD) is a rare subset of HD with symptom-onset before the age of 18. In contrast to the adult population, children present early-on with behavioral, psychiatric, and cognitive symptoms, in addition to a diverse spectrum of movement disorders. This poses a distinct challenge in diagnosis and management. We here describe the spectrum of movement disorders, accompanied with detailed video recordings, in seven cases of juvenile-onset HD. Our findings highlight early cognitive and behavioral symptoms, preceding motor symptoms. The diverse movement disorder phenotypes included dystonia, Parkinsonism, myoclonus, and chorea, findings which underscore the heterogeneity of presenting symptoms.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2805-2810"},"PeriodicalIF":4.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52193","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138744","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}
Chun En Yau, Eric Chi Kiat Ho, Natasha Yixuan Ong, Clifton Joon Keong Loh, Aaron Shengting Mai, Eng-King Tan
{"title":"Innovative technology-based interventions in Parkinson's disease: A systematic review and meta-analysis","authors":"Chun En Yau, Eric Chi Kiat Ho, Natasha Yixuan Ong, Clifton Joon Keong Loh, Aaron Shengting Mai, Eng-King Tan","doi":"10.1002/acn3.52160","DOIUrl":"10.1002/acn3.52160","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Novel technology-based interventions have the potential to improve motor symptoms and gait in Parkinson's disease (PD). Promising treatments include virtual-reality (VR) training, robotic assistance, and biofeedback. Their effectiveness remains unclear, and thus, we conducted a Bayesian network meta-analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched the Medline, Embase, Cochrane CENTRAL, and Clinicaltrials.gov databases until 2 April 2024 and only included randomized controlled trials. Outcomes included changes in UPDRS-III/MDS-UPDRS-III score, stride length, 10-meter walk test (10MWT), timed up-and-go (TUG) test, balance scale scores and quality-of-life (QoL) scores. Results were reported as mean differences (MD) or standardized mean differences (SMD), with 95% credible intervals (95% CrI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Fifty-one randomized controlled trials with 2095 patients were included. For UPDRS (motor outcome), all interventions had similar efficacies. VR intervention was the most effective in improving TUG compared with control (MD: −4.36, 95% CrI: −8.57, −0.35), outperforming robotic, exercise, and proprioceptive interventions. Proprioceptive intervention significantly improved stride length compared to control intervention (MD: 0.11 m, 95% CrI: 0.03, 0.19), outperforming VR, robotic and exercise interventions. Virtual reality improved balance scale scores significantly compared to exercise intervention (SMD: 0.75, 95% CrI: 0.12, 1.39) and control intervention (SMD: 1.42, 95% CrI: 0.06, 2.77). Virtual reality intervention significantly improved QoL scores compared to control intervention (SMD: −0.95, 95% CrI: −1.43, −0.52), outperforming Internet-based interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>VR-based and proprioceptive interventions were the most promising interventions, consistently ranking as the top treatment choices for most outcomes. Their use in clinical practice could be helpful in managing motor symptoms and QoL in PD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2548-2562"},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138743","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}
Marcus Grobe-Einsler, Viktoria Baljasnikowa, Aline Faikus, Tamara Schaprian, Oliver Kaut
{"title":"Cerebellar transcranial magnetic stimulation improves motor function in Parkinson's disease","authors":"Marcus Grobe-Einsler, Viktoria Baljasnikowa, Aline Faikus, Tamara Schaprian, Oliver Kaut","doi":"10.1002/acn3.52183","DOIUrl":"10.1002/acn3.52183","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine whether an accelerated protocol of 48 Hz cerebellar repetitive transcranial magnetic stimulation results in improved motor function in individuals with Parkinson's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this double-blind randomized sham-controlled study, 35 individuals with Parkinson's disease and stable medical treatment were randomized to either sham or verum transcranial magnetic stimulation. The stimulation was applied bilaterally and medial over the cerebellum and comprised a novel accelerated protocol encompassing two sessions per day on 5 consecutive days. Patients were assessed at baseline, on day 5 after the last stimulation and 1 month post intervention. Measurements included dynamic posturography, UPDRS III, 8-Meter walk test, and Timed Up and Go test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The accelerated protocol was safe and feasible in an outpatient setting. Patients in the verum group showed significant improvement (<i>p</i> < 0.001) of motor symptoms as measured in the UPDRS III. Improvement was mainly carried by the domains rigor, bradykinesia, and gait and persisted after 1 month (<i>p</i> = 0.009), whereas tremor remained unchanged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>The effect of a high-dose transcranial magnetic stimulation in patients with Parkinson's disease is encouraging and comparable to other studies using much longer stimulation protocols. This short-term intervention of 5 days facilitates the future application in an outpatient setting. Reduction in hospitalization rates directly benefits patients with motor impairment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2673-2684"},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138742","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}