Movement Disorders最新文献

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Author Response to Comment on “Neuropsychological Tests of Memory, Visuospatial, and Language Function in Parkinson's Disease: Review, Critique, and Recommendations” 作者对“帕金森病中记忆、视觉空间和语言功能的神经心理学测试：回顾、批评和建议”评论的回应

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-16 DOI: 10.1002/mds.70149

Ondrej Bezdicek, Roberta Biundo, Matej Skorvanek, Daniel Weintraub, Gert J. Geurtsen

引用次数: 0

Comment on “Neuropsychological Tests of Memory, Visuospatial, and Language Function in Parkinson's Disease: Review, Critique, and Recommendations” 《帕金森病患者的记忆、视觉空间和语言功能的神经心理学测试：综述、批评和建议》

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-16 DOI: 10.1002/mds.70148

Joshua P. Woller, Alireza Gharabaghi

引用次数: 0

LRRK2 as a Potential Disease‐Modifying Target in Sporadic Parkinson's Disease LRRK2作为散发性帕金森病的潜在疾病修饰靶点

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-13 DOI: 10.1002/mds.70100

Anthony E. Lang, Robert A. Hauser, Lorraine V. Kalia, Bonnie Hersh, Zdenek Berger, Roy Llorens Arenas, Coro Paisan‐Ruiz, Kyle Fraser, Danna Jennings, Jillian H. Kluss, Sarah Huntwork‐Rodriguez, Anastasia G. Henry, J. Timothy Greenamyre

A growing understanding of the role that leucine‐rich repeat kinase 2 (LRRK2) plays in Parkinson's disease (PD) supports continued focus on this enzyme as a therapeutic target for PD. Accumulating evidence suggests that there are phenotypic, neuropathologic, and biological similarities between sporadic PD (sPD) and familial forms in which LRRK2 variants are inherited in an autosomal‐dominant pattern with variable penetrance (LRRK2‐PD). Further, genome‐wide association studies have found specific non‐coding variants that are risk factors for sPD. In this review, we describe the current state of knowledge as it relates to LRRK2's role in sPD, with a focus on comparing the physiology and pathology of sPD with LRRK2‐PD. As in LRRK2‐PD, LRRK2 activity may also be increased in sPD, possibly through interactions between genetics and the environment. Increased activity of LRRK2 and associated endolysosomal dysfunction have been observed in sPD patients, including evidence from postmortem brains of patients with sPD and animal models showing increased LRRK2 activity. Additionally, beneficial effects of LRRK2 inhibitors, such as improved lysosomal function, reduced α‐synuclein accumulation, and amelioration of neurodegeneration, have been demonstrated in animal models of sPD. Therefore, inhibition of LRRK2 kinase activity may be a promising approach to disease modification for sPD and LRRK2‐PD. Ongoing and future clinical studies examining LRRK2 kinase inhibitors will aim to elucidate their clinical efficacy in PD and to assess their potential effects on lysosomal function. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

随着对富含亮氨酸的重复激酶2 （LRRK2）在帕金森病（PD）中所起作用的日益了解，人们继续关注这种酶作为PD的治疗靶点。越来越多的证据表明，散发性PD （sPD）和家族性PD （LRRK2变异以常染色体显性模式遗传，具有可变外显率（LRRK2‐PD））之间存在表型、神经病理学和生物学上的相似性。此外，全基因组关联研究发现特定的非编码变异是sPD的危险因素。在这篇综述中，我们描述了与LRRK2在sPD中的作用相关的知识现状，重点比较了sPD与LRRK2‐PD的生理和病理。与LRRK2‐PD一样，sPD中LRRK2活性也可能增加，这可能是遗传和环境之间的相互作用。在sPD患者中观察到LRRK2活性增加和相关的内溶酶体功能障碍，包括来自sPD患者死后大脑和动物模型的证据显示LRRK2活性增加。此外，LRRK2抑制剂的有益作用，如改善溶酶体功能、减少α‐突触核蛋白积累和改善神经退行性变，已在sPD的动物模型中得到证实。因此，抑制LRRK2激酶活性可能是sPD和LRRK2‐PD疾病修饰的一种有希望的方法。正在进行和未来的临床研究检查LRRK2激酶抑制剂将旨在阐明其在PD中的临床疗效，并评估其对溶酶体功能的潜在影响。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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引用次数: 0

It Is Personal: What People with Parkinson's Disease Say Matters Most for Quality of Life 这是个人的：帕金森病患者说什么对生活质量最重要

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-13 DOI: 10.1002/mds.70134

Samantha Dorrance, Richa Patel, Glenn T. Stebbins, Jamie Adams, Allison M. Allen, Tara Hastings, Soania Mathur, Onanong Phokaewvarangkul, Gary Rafaloff, Rajasumi Rajalingam, Anette Schrag, Christine Sun, Jennifer Mammen, Connie Marras

Background Little is known about what matters most for quality of life in people with Parkinson's disease and how much it varies between individuals. Objective The goal was to define the relative impact of quality of life determinants in people with Parkinson's disease, including variation across individuals and by disease severity, gender, age, and ethnicity. Methods Sixty‐one factors potentially associated with quality of life in people with Parkinson's disease were identified from the literature and nominated by participants with Parkinson's disease. Forty‐four participants then rated their degree of impact on quality of life from “a lot” to “not at all,” and identified their “top 3 most important” factors. Results At the individual level, determinants of utmost importance varied greatly, with 39 of 61 factors being reported at least once in the “top 3.” There were 17 factors that at least 50% of the sample agreed affected quality of life “a lot,” and only two were symptoms of the disease. Twelve (all positive experiences) retained at least 50% agreement across subgroups defined by disease severity, age, gender and ethnicity. Symptom‐related factors of high importance varied markedly in mild disease subgroup in particular. Conclusions Factors that are not direct consequences of the disease, but may be highly personal and interfere with what one finds meaningful, emerged as highly relevant. Symptoms also greatly impacted quality of life for most individuals, but specific symptoms varied across individuals. Quality of life determinants in people with Parkinson's disease appear highly individualized, and currently used measurement tools with fixed items may not be optimal. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

对于帕金森病患者的生活质量最重要的因素是什么，以及个体之间的差异有多大，我们知之甚少。目的：确定帕金森病患者生活质量决定因素的相对影响，包括个体差异、疾病严重程度、性别、年龄和种族差异。方法从文献中识别出61个可能与帕金森病患者生活质量相关的因素，并由帕金森病患者提出。然后，44名参与者将他们对生活质量的影响程度从“很多”到“根本没有”进行评级，并确定他们“最重要的3个”因素。结果在个体层面上，最重要的决定因素差异很大，61个因素中有39个至少在“前3名”中出现过一次。有17个因素至少有50%的样本同意影响生活质量“很大”，只有两个是疾病的症状。12例（均为积极经历）在按疾病严重程度、年龄、性别和种族定义的亚组中保持至少50%的一致性。在轻度疾病亚组中，高度重要的症状相关因素差异显著。结论：虽然不是疾病的直接后果，但可能是高度个人化的，并且会干扰人们发现有意义的事情，这些因素都是高度相关的。症状也极大地影响了大多数人的生活质量，但具体的症状因人而异。帕金森病患者的生活质量决定因素似乎高度个性化，目前使用的固定项目测量工具可能不是最佳的。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

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引用次数: 0

The Impact of Calcitriol on Frataxin Levels in Friedreich's Ataxia Patients: Insights and Future Directions 骨化三醇对共济失调患者Frataxin水平的影响：见解和未来方向

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-12 DOI: 10.1002/mds.29933

Nie Zhang, Yahui Xu

引用次数: 0

Longitudinal Dynamics of Plasma Neurofilament Light Chain in Hereditary Spastic Paraplegia Type 11 (HSP-SPG11) and Type 15 (HSP-ZFYVE26). 遗传性痉挛性截瘫11型（HSP-SPG11）和15型（HSP-ZFYVE26）血浆神经丝轻链的纵向动力学。

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-09 DOI: 10.1002/mds.70142

Habibah A P Agianda,Julian E Alecu,Amy Tam,Hyo-Min Kim,Joshua Rong,Nicole Battaglia,Kaitlyn Warren,Rebekah Mannix,Nunzio Setola,Melissa Barghigiani,Grace Yoon,Yoshihisa Takiyama,Jangsup Moon,Katerina Bernardi,Kathryn Yang,Luca Schierbaum,Filippo Maria Santorelli,Darius Ebrahimi-Fakhari

BACKGROUNDHSP-SPG11 and HSP-ZFYVE26 are autosomal-recessive forms of hereditary spastic paraplegias (HSPs). As therapeutic trials emerge, validated biomarkers are critically needed.OBJECTIVESTo evaluate plasma neurofilament light chain (pNfL) as a biomarker for neurodegeneration and disease progression.METHODSWe analyzed pNfL levels in 57 patients (36 HSP-SPG11, 21 HSP-ZFYVE26) and matched controls using single-molecule array technology. Longitudinal clinical and biomarker data were collected over 5 years.RESULTSBaseline pNfL levels were significantly elevated in patients: 33.85 pg/mL (IQR 25.15-47.38) in HSP-SPG11, 46.70 pg/mL (IQR 29.95-54.84) in HSP-ZFYVE26, and 4.90 pg/mL (IQR 3.48-6.90) in controls (P < 0.001). No significant difference was observed between HSP-SPG11 and HSP-ZFYVE26. In matched pair analysis, pNfL showed inverse correlation with age (ρ = -0.463, P < 0.001). Baseline pNfL did not predict future clinical progression.CONCLUSIONSElevated pNfL reflects early neuroaxonal injury in HSP-SPG11 and HSP-ZFYVE26; however, it could not be used as a surrogate for disease progression. © 2025 International Parkinson and Movement Disorder Society.

背景：dhsp - spg11和HSP-ZFYVE26是遗传性痉挛性截瘫（HSPs）的常染色体隐性形式。随着治疗试验的出现，迫切需要经过验证的生物标志物。目的评价血浆神经丝轻链（pNfL）作为神经变性和疾病进展的生物标志物。方法采用单分子阵列技术分析57例患者（36例HSP-SPG11, 21例HSP-ZFYVE26）和匹配对照组的pNfL水平。纵向临床和生物标志物数据收集超过5年。结果患者pNfL基线水平显著升高：HSP-SPG11组为33.85 pg/mL (IQR 25.15 ~ 47.38)， HSP-ZFYVE26组为46.70 pg/mL (IQR 29.95 ~ 54.84)，对照组为4.90 pg/mL (IQR 3.48 ~ 6.90) （P < 0.001）。HSP-SPG11与HSP-ZFYVE26之间无显著性差异。配对分析中，pNfL与年龄呈负相关（ρ = -0.463, P < 0.001）。基线pNfL不能预测未来的临床进展。结论pNfL升高反映了HSP-SPG11和HSP-ZFYVE26的早期神经轴索损伤；然而，它不能作为疾病进展的替代品。©2025国际帕金森和运动障碍学会。

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引用次数: 0

Oligodendrocyte Inclusion Pathology in Fragile X‐Associated Tremor/Ataxia Syndrome 脆性X相关震颤/共济失调综合征的少突胶质细胞包涵病理

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-06 DOI: 10.1002/mds.70145

Yingratana McLennan, Hassan Aliashrafzadeh, Faith Zirkelbach‐Ngai, Forrest McKenzie, Brett D. Dufour, Lina V. Becerra‐Hernández, Adolfo Sanchez Escobar, Flora Tassone, Paul Hagerman, Randi Hagerman, Veronica Martínez‐Cerdeño

Background Fragile X‐associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder marked by white matter degeneration and intranuclear inclusions. While astrocytic and neuronal inclusions are well‐documented, oligodendrocytes were previously thought to lack such pathology. Objective To demonstrate that oligodendrocytes in the prefrontal cortex of FXTAS patients do harbor intranuclear inclusions, with significantly higher burden in white matter than gray matter. Methods Ubiquitin and p62 immunofluorescence and enzymatic staining were employed to confirm the presence of intranuclear inclusions in oligodendrocytes across multiple brain regions. Results Oligodendrocytes contain inclusions and inclusion burden is correlated with FMR1 CGG repeat length ( ρ = 0.97, P < 0.001) in white matter. Conclusions These findings implicate oligodendrocyte dysfunction in FXTAS pathogenesis which may contribute to demyelination and white matter degeneration. Our data emphasize the need to consider cell type‐specific mechanisms in FXTAS and support future therapeutic efforts aimed at restoring glial proteostasis. © 2025 International Parkinson and Movement Disorder Society.

脆性X相关震颤/共济失调综合征（FXTAS）是一种以白质变性和核内包涵体为特征的神经退行性疾病。虽然星形细胞和神经元包涵体已被充分证明，但少突胶质细胞以前被认为缺乏这种病理。目的探讨FXTAS患者前额叶皮层少突胶质细胞确实存在核内包涵体，其白质负荷明显高于灰质负荷。方法采用泛素、p62免疫荧光和酶促染色方法，证实脑多区少突胶质细胞核内包涵体的存在。结果少突胶质细胞中含有包涵体，包涵体负荷与白质中FMR1 CGG重复长度相关（ρ = 0.97, P < 0.001）。结论少突胶质细胞功能障碍可能参与FXTAS的发病机制，并可能导致脱髓鞘和白质变性。我们的数据强调需要考虑FXTAS的细胞类型特异性机制，并支持未来旨在恢复胶质蛋白平衡的治疗努力。©2025国际帕金森和运动障碍学会。

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引用次数: 0

Primary Brain Calcification: An International Consensus on Nomenclature, Diagnosis, Evaluation, and Management 原发性脑钙化：关于命名、诊断、评估和管理的国际共识

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-05 DOI: 10.1002/mds.70140

Wei Luo, Zhidong Cen, Huiberdina Koek, Miryam Carecchio, Isao Hozumi, Wan‐Jin Chen, Amit Batla, Alexander Balck, Francesca Magrinelli, Dehao Yang, Xuewen Cheng, Ana Westenberger, Akiyoshi Kakita, Liam Chen, Christian Lambert, Jing‐Yu Liu, Annika Keller, João Ricardo Mendes de Oliveira, Zhi‐Qi Xiong, Henry Houlden, Kailash P. Bhatia, Christine Klein, Gaël Nicolas

Our understanding of primary brain calcification (PBC) has accelerated with the identification of seven causative genes over the past 13 years, vastly expanding knowledge of the molecular underpinnings of this disorder. Despite this progress, a lack of standardized clinical definitions, variable presentations, and heterogeneous calcification patterns has perpetuated inconsistencies in diagnosis and patient care. To address these challenges, an international expert panel undertook a comprehensive process—combining systematic literature review, virtual and in‐person expert discussions, and iterative Delphi consensus questionnaires—to develop unified recommendations. These consensus guidelines encompass terminology, diagnostic criteria, neuroimaging protocols, clinical evaluation standards, genetic testing approaches, and management strategies. Notably, PBC is recommended as the clinical standard, with new diagnostic criteria, including the use of a computed tomography–based total calcification score and a three‐tiered diagnostic algorithm (possible, probable, definite PBC). A systematic review of 27 symptoms and signs identified 19 as most closely linked with PBC, guiding more focused clinical assessment. Recommendations strongly support comprehensive next‐generation sequencing for genetic testing, favoring whole genome over exome or targeted panels to maximize diagnostic yield. Multidisciplinary management priorities are outlined in four key principles centering on individualized care, symptom relief, genetic counseling, and ongoing monitoring. Widespread adoption of these unified guidelines will facilitate consistent diagnosis, enable comparative international data collection, and lay the groundwork for large‐scale collaborative research—including future randomized controlled trials of symptomatic and disease‐modifying PBC therapies. This consensus fosters clarity and consistency, creating a framework for improved patient care and scientific discovery. © 2025 International Parkinson and Movement Disorder Society.

在过去的13年里，我们对原发性脑钙化（PBC）的理解随着7种致病基因的鉴定而加速，极大地扩展了对这种疾病分子基础的认识。尽管取得了这些进展，但缺乏标准化的临床定义、可变的表现和异质的钙化模式，导致了诊断和患者护理的不一致。为了应对这些挑战，一个国际专家小组进行了一个全面的过程，结合了系统的文献综述，虚拟和面对面的专家讨论，以及迭代的德尔菲共识问卷，以制定统一的建议。这些共识指南包括术语、诊断标准、神经影像学协议、临床评估标准、基因检测方法和管理策略。值得注意的是，PBC被推荐为临床标准，具有新的诊断标准，包括使用基于计算机断层扫描的总钙化评分和三层诊断算法（可能的、可能的、确定的PBC）。对27种症状和体征进行系统回顾，确定了19种与PBC最密切相关的症状和体征，指导更有针对性的临床评估。建议强烈支持全面的下一代基因检测测序，支持全基因组测序，而不是外显子组或靶向组，以最大限度地提高诊断产量。多学科管理的重点概述了四个关键原则，即个体化护理、症状缓解、遗传咨询和持续监测。这些统一指南的广泛采用将促进一致的诊断，使比较国际数据收集成为可能，并为大规模合作研究奠定基础，包括未来对症状性和疾病改变性PBC治疗的随机对照试验。这种共识促进了清晰度和一致性，为改善患者护理和科学发现创造了框架。©2025国际帕金森和运动障碍学会。

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引用次数: 0

Delayed Disease Onset Report in UK Biobank: Implications for Prodromal Studies in Parkinson's Disease 英国生物银行延迟疾病发病报告：对帕金森病前驱研究的启示

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-05 DOI: 10.1002/mds.70147

Sheida Zolfaghari, Trycia Kouchache, Aline Delva, Sarah Bouhadoun, Mirja Kuhlencord, Amélie Pelletier, Alastair J. Noyce, Sheena Waters, Daniel Belete, Tim Wilkinson, Kathryn Bush, Filip Morys, Andrew Vo, Kristiina Rannikmae, Alain Dagher, Ronald B. Postuma

Background UK Biobank ( UKBB ) provides extensive genetic, imaging, and health data for ~500,000 participants, enabling studies of prodromal phases of diseases like Parkinson's disease ( PD ). However, during analysis, we became concerned about the accuracy of diagnosis timing. Objective To evaluate the accuracy of PD diagnosis timing in UKBB. Methods We examined PD diagnosis timing using hospital, primary care, death records, and self‐reported data. We assessed discrepancies between sources and identified co‐occurring diagnoses recorded on the same date as PD . Results Among 3979 PD cases, 97% of the 786 participants with both self‐reported and electronic health records ( EHRs ) reported their diagnosis earlier than recorded in the EHR , with a typical delay of 5 to 7 years. Multiple codiagnoses were often logged on the same date, suggesting retrospective or batch data entry. Conclusions Substantial delays in PD documentation may misclassify already diagnosed individuals as prodromal. This introduces significant bias into studies of early disease markers and distorts the timing between risk factors and clinical onset. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

UK Biobank （UKBB）为约50万参与者提供了广泛的遗传、成像和健康数据，使帕金森病（PD）等疾病的前驱期研究成为可能。然而，在分析过程中，我们开始关注诊断时间的准确性。目的评价UKBB PD诊断时机的准确性。方法：我们使用医院、初级保健、死亡记录和自我报告的数据来检查PD的诊断时间。我们评估了来源之间的差异，并确定了与PD记录在同一日期的共发生诊断。结果在3979例PD病例中，786名同时使用电子健康记录（EHR）和自我报告的参与者中，97%的人报告他们的诊断早于EHR记录，典型延迟5 - 7年。多次合并诊断通常记录在同一日期，建议回顾性或批量数据输入。结论PD文件的大量延误可能会将已经诊断的个体错误地分类为前驱。这在早期疾病标志物的研究中引入了显著的偏差，并扭曲了危险因素与临床发病之间的时间。©2025作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

{"title":"Delayed Disease Onset Report in UK Biobank: Implications for Prodromal Studies in Parkinson's Disease","authors":"Sheida Zolfaghari, Trycia Kouchache, Aline Delva, Sarah Bouhadoun, Mirja Kuhlencord, Amélie Pelletier, Alastair J. Noyce, Sheena Waters, Daniel Belete, Tim Wilkinson, Kathryn Bush, Filip Morys, Andrew Vo, Kristiina Rannikmae, Alain Dagher, Ronald B. Postuma","doi":"10.1002/mds.70147","DOIUrl":"https://doi.org/10.1002/mds.70147","url":null,"abstract":"Background UK Biobank ( UKBB ) provides extensive genetic, imaging, and health data for ~500,000 participants, enabling studies of prodromal phases of diseases like Parkinson's disease ( PD ). However, during analysis, we became concerned about the accuracy of diagnosis timing. Objective To evaluate the accuracy of PD diagnosis timing in UKBB. Methods We examined PD diagnosis timing using hospital, primary care, death records, and self‐reported data. We assessed discrepancies between sources and identified co‐occurring diagnoses recorded on the same date as PD . Results Among 3979 PD cases, 97% of the 786 participants with both self‐reported and electronic health records ( EHRs ) reported their diagnosis earlier than recorded in the EHR , with a typical delay of 5 to 7 years. Multiple codiagnoses were often logged on the same date, suggesting retrospective or batch data entry. Conclusions Substantial delays in PD documentation may misclassify already diagnosed individuals as prodromal. This introduces significant bias into studies of early disease markers and distorts the timing between risk factors and clinical onset. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"19 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145673609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reply to: Letter to the Editor 回复：给编辑的信

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-05 DOI: 10.1002/mds.70136

Giulia Maria Mattia, Lydia Chougar, Alexandra Foubert‐Samier, Wassilios G. Meissner, Margherita Fabbri, Anne Pavy‐Le Traon, Olivier Rascol, David Grabli, Bertrand Degos, Nadya Pyatigorskaya, Alice Faucher, Marie Vidailhet, Jean‐Christophe Corvol, Stéphane Lehéricy, Patrice Péran

引用次数: 0

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