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
Objective
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.
Methods
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.
Results
The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (rsp = 0.51, p = 0.02). Assay levels were not elevated in CAA-RI patients (n = 6) compared to non-CAA controls (n = 20; p = 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.
Interpretation
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.
{"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
Objective
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.
Methods
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.
Results
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) (p = 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 (p = 0.024).
Interpretations
Our findings underscore the valuable role of tPA levels in distinguishing between stroke subtypes.
{"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
Objectives
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.
Methods
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).
Results
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.
Interpretation
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.
{"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
Objective
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.
Methods
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.
Results
Muscle blood flow was reduced in all patient groups compared to controls, most prominently in BMD patients (p < 0.0001). Echointensity was similarly increased in all patient groups (p < 0.05), while echotexture was reduced only in muscular dystrophy patients (p ≤ 0.002). In BMD, blood flow correlated with echotexture (Pearson r = 0.6098, p = 0.0158) and strength (Spearman r = 0.5471; p = 0.0370). In patients with normal muscle strength, reduced muscle blood flow was evident in all patient groups (p < 0.001), echotexture was reduced in BMD and OMD (p < 0.01), and echointensity was increased in CMT (p < 0.05).
Interpretation
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.
{"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
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.
青少年型亨廷顿氏病（HD）是一种罕见的亚型亨廷顿氏病，症状在18岁之前出现。与成人不同的是，儿童在发病初期会出现行为、精神和认知症状，此外还伴有各种运动障碍。这给诊断和管理带来了独特的挑战。我们在此通过详细的视频记录，描述了七例青少年型 HD 患者的运动障碍谱。我们的发现突出了运动症状之前的早期认知和行为症状。运动障碍的表型多种多样，包括肌张力障碍、帕金森氏症、肌阵挛和舞蹈症，这些发现强调了表现症状的异质性。
{"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
Objective
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.
Methods
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).
Results
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.
Interpretation
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.
{"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
Objective
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.
Methods
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.
Results
The accelerated protocol was safe and feasible in an outpatient setting. Patients in the verum group showed significant improvement (p < 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 (p = 0.009), whereas tremor remained unchanged.
Interpretation
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.
{"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}
Evan Madill, Brian C. Healy, Negar Molazadeh, Mariann Polgar-Turcsanyi, Bonnie I. Glanz, Howard L. Weiner, Tanuja Chitnis
Objective
Glial fibrillary acidic protein (GFAP) is expressed in astrocytes and may be a useful marker of non-active progressive multiple sclerosis (MS). We evaluate serum GFAP (sGFAP) in a large cohort of MS patients to determine if it predicts progression independent of relapse activity (PIRA), future gait aid, and conversion to secondary progressive disease (SPMS).
Methods
Adults with clinically isolated syndrome or any subtype of MS who were listed in the Brigham MS Center Research Database and had at least one sGFAP result were included. All clinic visits following first sample were analyzed for PIRA, future gait aid, and conversion to SPMS. Future cognitive dysfunction and fatigue were evaluated as secondary outcomes.
Results
In total, 741 patients were included (average age: 42.3, average disease duration: 3.7 years, median EDSS: 2, and median follow-up duration: 10.0 years). Of 643 patients (86.8%) without progressive disease at baseline, 15.9% developed SPMS. Among all 741, 50.5% had PIRA and 18.6% developed a gait aid requirement. sGFAP level predicted PIRA, future gait aid, and conversion to SPMS in univariable models (p < 0.001, <0.001, and 0.002). sGFAP remained predictive for PIRA and future gait aid in multivariable models in those younger than 50 (p = 0.048, 0.003). Change in sGFAP level over time was not predictive. There was no association between sGFAP and future fatigue or cognitive dysfunction.
Interpretation
sGFAP helps to predict PIRA, future gait aid, and conversion to SPMS in a large cohort of MS patients. Our data suggest that baseline levels may be more useful than the change over time.
{"title":"Serum glial fibrillary acidic protein predicts disease progression in multiple sclerosis","authors":"Evan Madill, Brian C. Healy, Negar Molazadeh, Mariann Polgar-Turcsanyi, Bonnie I. Glanz, Howard L. Weiner, Tanuja Chitnis","doi":"10.1002/acn3.52187","DOIUrl":"10.1002/acn3.52187","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Glial fibrillary acidic protein (GFAP) is expressed in astrocytes and may be a useful marker of non-active progressive multiple sclerosis (MS). We evaluate serum GFAP (sGFAP) in a large cohort of MS patients to determine if it predicts progression independent of relapse activity (PIRA), future gait aid, and conversion to secondary progressive disease (SPMS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Adults with clinically isolated syndrome or any subtype of MS who were listed in the Brigham MS Center Research Database and had at least one sGFAP result were included. All clinic visits following first sample were analyzed for PIRA, future gait aid, and conversion to SPMS. Future cognitive dysfunction and fatigue were evaluated as secondary outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In total, 741 patients were included (average age: 42.3, average disease duration: 3.7 years, median EDSS: 2, and median follow-up duration: 10.0 years). Of 643 patients (86.8%) without progressive disease at baseline, 15.9% developed SPMS. Among all 741, 50.5% had PIRA and 18.6% developed a gait aid requirement. sGFAP level predicted PIRA, future gait aid, and conversion to SPMS in univariable models (<i>p</i> < 0.001, <0.001, and 0.002). sGFAP remained predictive for PIRA and future gait aid in multivariable models in those younger than 50 (<i>p</i> = 0.048, 0.003). Change in sGFAP level over time was not predictive. There was no association between sGFAP and future fatigue or cognitive dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>sGFAP helps to predict PIRA, future gait aid, and conversion to SPMS in a large cohort of MS patients. Our data suggest that baseline levels may be more useful than the change over time.</p>\u0000 </section>\u0000 </div>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2719-2730"},"PeriodicalIF":4.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52187","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138745","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}
Jeffrey L. Bennett, Sean J. Pittock, Friedemann Paul, Ho Jin Kim, Sarosh R. Irani, Kevin C. O'Connor, Kristina R. Patterson, Michael A. Smith, Michele Gunsior, Nanette Mittereder, William A. Rees, Daniel Cimbora, Bruce A. C. Cree
This post hoc analysis of the randomized, placebo-controlled N-MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B-cell subsets and aquaporin-4 immunoglobulin G (AQP4-lgG) titers and attacks. Among participants receiving placebo, CD20+ and CD27+ B-cell counts were modestly increased from the pre-attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre-attack visit (p = 0.016) and from baseline to attack (p = 0.009). With inebilizumab treatment, B-cell subset counts decreased and did not increase with attacks. No difference in change of AQP4-IgG titers from baseline to time of attack was observed.
这项伊维单抗治疗神经性脊髓炎视网膜频谱紊乱症（NMOSD）的随机安慰剂对照 N-MOmentum 研究（NCT02200770）的事后分析评估了循环 B 细胞亚群和水通道蛋白-4 免疫球蛋白 G (AQP4-lgG) 滴度与发作之间的关系。在接受安慰剂治疗的参与者中，CD20+和CD27+ B细胞计数从发作前到发作期间略有增加；浆细胞/浆细胞基因特征从基线到发作前（p = 0.016）以及从基线到发作期间（p = 0.009）均有所增加。接受伊匹单抗治疗后，B细胞亚群数量减少，且不随发作而增加。从基线到发病时，AQP4-IgG滴度的变化无差异。
{"title":"B cell and aquaporin-4 antibody relationships with neuromyelitis optica spectrum disorder activity","authors":"Jeffrey L. Bennett, Sean J. Pittock, Friedemann Paul, Ho Jin Kim, Sarosh R. Irani, Kevin C. O'Connor, Kristina R. Patterson, Michael A. Smith, Michele Gunsior, Nanette Mittereder, William A. Rees, Daniel Cimbora, Bruce A. C. Cree","doi":"10.1002/acn3.52171","DOIUrl":"10.1002/acn3.52171","url":null,"abstract":"<p>This post hoc analysis of the randomized, placebo-controlled N-MOmentum study (NCT02200770) of inebilizumab in neuromyelitis optica spectrum disorder (NMOSD) evaluated relationships between circulating B-cell subsets and aquaporin-4 immunoglobulin G (AQP4-lgG) titers and attacks. Among participants receiving placebo, CD20<sup>+</sup> and CD27<sup>+</sup> B-cell counts were modestly increased from the pre-attack visit to attack; plasmablast/plasma cell gene signature was increased from baseline to the pre-attack visit (<i>p</i> = 0.016) and from baseline to attack (<i>p</i> = 0.009). With inebilizumab treatment, B-cell subset counts decreased and did not increase with attacks. No difference in change of AQP4-IgG titers from baseline to time of attack was observed.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2792-2798"},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52171","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118503","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}
<div> <section> <h3> Background</h3> <p>Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD.</p> </section> <section> <h3> Methods</h3> <p>Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment.</p> </section> <section> <h3> Results</h3> <p>High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003–2.495; CXCL12: OR, 3.610; 95% CI, 1.011–12.889; IL-1β: OR, 4.500; 95% CI, 1.129–17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538–0.976; MaR1: OR, 0.985; 95% CI, 0.970–0.999; LXA4: OR, 0.849; 95% CI, 0.727–0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (<i>p</i> < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (<i>r</i> = 0.451, <i>p</i> < 0.05).</p> </section> <section> <h3> Conclusion</h3> <p>Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous sy
{"title":"Effects of intravenous pulse methylprednisolone in neuromyelitis optica during the acute phase","authors":"Shengnan Wang, Mengru Xue, Jianglong Wang, Rui Wu, Yanqing Shao, Ke Luo, Jiacheng Liu, Mingqin Zhu","doi":"10.1002/acn3.52188","DOIUrl":"10.1002/acn3.52188","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Neuromyelitis optica spectrum disorder (NMOSD) is an anti-aquaporin 4 (anti-AQP4) autoantibodies-mediated idiopathic inflammatory demyelinating disease of the central nervous system. While intravenous pulse methylprednisolone (IVMP) is the recommended initial treatment option for acute onset NMOSD, its therapeutic mechanism remains unclear. We hypothesized that IVMP would reduce the expression of pro-inflammatory factors and increase the resolution of inflammation in patients with NMOSD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mendelian randomization (MR) analysis was used to screen meaningful inflammatory and resolution factors for inclusion. Three MR methods with inverse variance weighting (IVW) were primarily used to identify positive results. Interleukin (IL)-10, IL-1β, IL-6, C-X-C motif chemokine ligand 12 (CXCL12), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were screened from 41 inflammatory factors, and resolvin D1 (RvD1), maresin 1 (MaR1), and lipoxin A4 (LXA4) were screened from 6 resolution markers for inclusion. Subsequently, 12 patients with NMOSD were enrolled and treated with IVMP. Serum levels of the aforementioned inflammatory and resolution markers were measured by enzyme-linked immunosorbent assay before and after IVMP treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High levels of TRAIL, CXCL12, and IL-1β were associated with an increased risk of NMOSD (TRAIL: odds ratio [OR], 1.582; 95% confidence interval [CI], 1.003–2.495; CXCL12: OR, 3.610; 95% CI, 1.011–12.889; IL-1β: OR, 4.500; 95% CI, 1.129–17.927). High levels of RvD1, MaR1, and LXA4 were associated with a reduced risk of NMOSD (RvD1: OR, 0.725; 95% CI, 0.538–0.976; MaR1: OR, 0.985; 95% CI, 0.970–0.999; LXA4: OR, 0.849; 95% CI, 0.727–0.993). Among patients with NMOSD, serum levels of IL-6, CXCL12, and TRAIL significantly decreased following IVMP treatment, compared with pretreatment levels, while levels of IL-1β, LXA4, and MaR1 significantly increased after IVMP treatment (<i>p</i> < 0.05). A significant positive correlation was observed between CXCL12 levels and Expanded Disability Status Scale (EDSS) scores (<i>r</i> = 0.451, <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Several systemic inflammatory regulators associated with the pathogenesis of NMOSD were identified. The protective roles of LXA4 and MaR1 may be indispensable components of glucocorticoid treatment. Therefore, the use of resolution markers may be a potential strategy for improving central nervous sy","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":"11 10","pages":"2731-2744"},"PeriodicalIF":4.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/acn3.52188","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118505","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}
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