Movement Disorders最新文献

英文中文

The Race to Salvage Glucocerebrosidase: Understanding Small‐Molecule Therapies for GBA1 ‐Associated Parkinsonism 挽救葡萄糖脑苷酶的竞赛：了解GBA1相关帕金森病的小分子疗法

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-29 DOI: 10.1002/mds.70168

Mark J. Henderson, Tiffany C. Chen, Logan M. Glasstetter, Yu Chen, Juan J. Marugan, Ellen Sidransky

引用次数: 0

Skin Biopsy for Phosphorylated α‐Synuclein in Mild Cognitive Impairment or Dementia Due to Lewy Body Disease in a Convenience Cohort from a Subspecialty Behavioral Neurology Practice 在一个亚专业行为神经病学实践的方便队列中，在路易体病引起的轻度认知障碍或痴呆中磷酸化α‐突触核蛋白的皮肤活检

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-29 DOI: 10.1002/mds.70158

Michael J. Rigby, Hugo Botha, Leland R. Barnard, R. Ross Reichard, Rachel Larsen, Wendy Cogan, Aaron R. Switzer, Vijay K. Ramanan, Bryan J. Neth, Ryan A. Townley, Rodolfo Savica, David T. Jones, Toji Miyagawa, Julie A. Fields, Cynthia Vernon, Zachary A. Trottier, Val J. Lowe, Erik K. St. Louis, David S. Knopman, Ronald C. Petersen, Dennis W. Dickson, Kejal Kantarci, Jonathan Graff‐Radford, Bradley F. Boeve, Stuart J. McCarter

Background Immunohistochemically detected phosphorylated α‐synuclein (p‐α‐syn) in cutaneous nerves has been found in >95% of patients meeting consensus criteria for dementia with Lewy bodies (DLB); however, its performance in prodromal stages (mild cognitive impairment‐Lewy body [MCI‐LB]) and clinical practice is unknown. Objective We evaluated skin biopsy for p‐α‐syn in a convenience cohort of patients with suspected MCI‐LB or DLB in a tertiary care setting. Methods 53 patients underwent commercially available skin biopsy for skin nerve p‐α‐syn as part of a clinical evaluation for suspected MCI‐LB/DLB. Consensus MCI‐LB/DLB criteria blinded to skin biopsy result were applied through retrospective chart review; those not definitively meeting criteria were considered questionable synucleinopathy (QS). Results Median age at skin biopsy was 70 years (range, 43–87 years) with 81% men. 36 patients (68%) had positive skin biopsies. 32/43 (74%) patients meeting clinical consensus criteria for DLB/MCI‐LB had a positive skin biopsy, with higher frequency in MCI‐LB (87%) compared with DLB (60%). 4/10 (40%) QS had positive biopsies. One patient with a positive skin biopsy had no evidence of central nervous system (CNS) α‐syn on autopsy. Conclusions Positive skin biopsy for p‐α‐syn occurs across the spectrum of cognitive presentations of Lewy body disease including prodromal DLB, albeit at a lower frequency in this retrospective review of atypical cases compared with typical clinical presentations. A positive skin biopsy may not reflect CNS synucleinopathy as the etiology for a patient's symptoms in some cases. Longitudinal studies of skin biopsies for p‐α‐syn in suspected MCI‐LB/DLB with autopsy confirmation are needed. © 2025 International Parkinson and Movement Disorder Society.

在95%符合路易体痴呆（DLB）共识标准的患者中，免疫组织化学检测到皮神经中磷酸化的α‐突触核蛋白（p‐α‐syn）；然而，其在前驱阶段（轻度认知障碍‐路易体[MCI‐LB]）和临床实践中的表现尚不清楚。目的：我们对三级医疗机构中疑似MCI - LB或DLB患者的皮肤活检p - α - syn进行评估。方法53例患者接受了市售皮肤活检，检测皮肤神经p - α - syn，作为疑似MCI - LB/DLB临床评估的一部分。共识MCI‐LB/DLB标准盲法皮肤活检结果通过回顾性图表审查应用；不明确符合标准的被认为是可疑的突触核蛋白病（QS）。结果皮肤活检的中位年龄为70岁（43-87岁），81%为男性。36例（68%）患者皮肤活检阳性。32/43（74%）符合DLB/MCI‐LB临床共识标准的患者皮肤活检阳性，MCI‐LB的频率（87%）高于DLB（60%）。4/10 (40%) QS活检呈阳性。一名皮肤活检阳性的患者尸检时没有中枢神经系统(CNS) α‐syn的证据。结论：p - α - syn皮肤活检阳性发生在路易体病的认知表现中，包括前体DLB，尽管在非典型病例的回顾性回顾中与典型临床表现相比频率较低。在某些情况下，皮肤活检阳性可能不能反映中枢神经系统突触核蛋白病是患者症状的病因。需要对疑似MCI - LB/DLB患者的皮肤活检进行p - α - syn的纵向研究，并进行尸检确认。©2025国际帕金森和运动障碍学会。

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引用次数: 0

A Tribute to Mark Hallett, MD (1943–2025) 致敬马克·哈雷特，医学博士（1943-2025）

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-26 DOI: 10.1002/mds.70155

Joseph Jankovic MD, Günther Deuschl MD

引用次数: 0

Building on European Reference Network for Rare Neurological Diseases (ERN-RND) Experience: Integrating Motor and Non-Motor Assessment in Pediatric Movement Disorders 基于欧洲罕见神经疾病参考网络（ERN - RND）经验：儿科运动障碍的运动和非运动综合评估

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-22 DOI: 10.1002/mds.70166

Maria Eugenia Amato, Juan Darío Ortigoza-Escobar

We read with great interest the Viewpoint by Desjardins et al. highlighting the urgent need for diagnostic-specific and developmentally adapted tools for assessing non-motor symptoms (NMS) in children with movement disorders.1 Their call to move beyond fragmented and non-validated approaches resonates strongly with recent collaborative efforts within the European Reference Network for Rare Neurological Diseases (ERN-RND) Pediatric Issues Working Group.In our recent study, we surveyed 25 experts from 10 European countries to map the real-world use of motor and non-motor rating scales across pediatric movement disorder phenotypes.2 We identified 13 movement disorder-specific motor scales in routine use, complemented by developmental, adaptive, and cognitive measures such as the Bayley Scales, Vineland Adaptive Behavior Scales, and standardized IQ testing. Yet, fewer than half of these tools had been validated for pediatric populations. The variability in their application, particularly in young or cognitively impaired children, revealed similar methodological gaps to those Desjardins et al. now describe for non-motor symptoms. Both studies converge on the same unmet need: a unified and developmentally sensitive assessment framework integrating motor, cognitive, and non-motor dimensions.We fully support the authors' proposal of a modular structure combining a core transdiagnostic component with diagnosis-specific extensions. Our empirical data from ERN-RND centers indicate that such an approach is both feasible and clinically meaningful. In pediatric dystonia or mixed hyperkinetic disorders, for example, we routinely combine the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) with quality-of-life measures such as the Pediatric Quality of Life Inventory (PedsQL) and developmental assessment tools to contextualize motor findings within the child's cognitive and adaptive profile. In addition, disease-specific scales developed within our group—such as those for GNAO1-related disorders3—provide complementary insight beyond motor severity, capturing functional and behavioral fluctuations that significantly influence overall disease burden. This multimodal strategy captures the interplay between motor severity, functional participation, and perceived burden, offering a comprehensive picture of disease impact while remaining practical for longitudinal follow-up.These findings collectively suggest that a unified motor and non-motor framework is achievable. The modular model envisioned by Desjardins et al. could thus build upon the empirical groundwork already established for motor domains within the ERN-RND. Extending this collaboration to include NMS assessment would allow harmonized data collection across Europe and foster consensus on age-banded norms, feasibility thresholds, and minimal clinically important differences—elements es

我们非常感兴趣地阅读了Desjardins等人的观点，强调迫切需要诊断特异性和发展适应的工具来评估运动障碍儿童的非运动症状（NMS）他们呼吁超越碎片化和未经验证的方法，这与欧洲罕见神经疾病参考网络（ERN-RND）儿科问题工作组最近的合作努力产生了强烈共鸣。在我们最近的研究中，我们调查了来自10个欧洲国家的25位专家，绘制了儿童运动障碍表型中运动和非运动评定量表的实际使用情况我们确定了13种常规使用的运动障碍特定运动量表，辅以发展、适应和认知测量，如贝利量表、维尼兰适应行为量表和标准化智商测试。然而，这些工具中只有不到一半用于儿科人群。其应用的可变性，特别是在年幼或认知受损的儿童中，揭示了与Desjardins等人现在描述的非运动症状类似的方法学差距。两项研究都集中在同一个未满足的需求上：一个统一的、发展敏感的评估框架，整合运动、认知和非运动维度。我们完全支持作者提出的模块化结构，将核心跨诊断组件与诊断特定扩展相结合。我们从ERN-RND中心获得的经验数据表明，这种方法既可行又有临床意义。例如，在儿童肌张力障碍或混合性多动障碍中，我们通常将伯克-法恩-马斯登肌张力障碍评定量表（BFMDRS）与生活质量测量（如儿童生活质量量表（PedsQL））和发育评估工具结合起来，将儿童认知和适应状况中的运动发现置于背景中。此外，我们小组开发的疾病特异性量表（如gnao1相关疾病的量表）提供了除运动严重程度之外的补充见解，捕捉了显著影响整体疾病负担的功能和行为波动。这种多模式策略捕获了运动严重程度、功能参与和感知负担之间的相互作用，提供了疾病影响的全面图景，同时对纵向随访仍然实用。这些发现共同表明，统一的运动和非运动框架是可以实现的。因此，Desjardins等人设想的模块化模型可以建立在ERN-RND中已经建立的运动领域的经验基础之上。将这一合作扩展到包括NMS评估，将使整个欧洲的数据收集协调一致，并促进对年龄层规范、可行性阈值和最小临床重要差异的共识，这些都是临床试验和精确护理的基本要素。然而，新的评估系统的建立必须伴随着临床医生的培训机会。由于获得结构化学习材料或认证途径的机会有限，即使是已建立的运动量表也经常未得到充分利用。因此，开发教育资源、研讨会和在线模块应该是一个并行的优先事项，以确保这些工具——无论是运动的、发育的还是非运动的——能够在现实世界的儿科环境中得到一致和自信的应用。我们建议未来的国际倡议-可能加入运动障碍协会的非运动小组和ERN-RND儿科问题工作组-将重点放在共同开发儿科运动障碍评估的核心集上，该核心集整合了运动和非运动领域，结合了照顾者和儿童的观点，并适应发展轨迹。这种整合不仅代表了方法上的进步，而且是朝着以儿童为中心、全面和公平地照顾患有罕见运动障碍的人迈出的切实一步。(1)研究项目：a、构思、b、设计、c、执行；(2)统计分析：A.设计，B.执行，C.回顾与批判；(3)稿件准备：A.初稿撰写，B.定稿编辑。m.e.a: 1B, 1C, 3A, 3B.J.D.O.-E。1b, 1c, 3a, 3b。作者声明没有其他信息需要报告。这项工作没有收到具体的经费。作者声明本研究不存在任何利益冲突。数据共享不适用于本文，因为在当前研究期间没有生成或分析数据集。

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引用次数: 0

Transforming Pediatric Movement Disorders Assessment: From Expert Consensus to Collaborative Approaches 转变儿童运动障碍评估：从专家共识到合作方法

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-22 DOI: 10.1002/mds.70163

Hortensia Gimeno PhD, Clément Desjardins MD, MSc, Christelle Nilles MD, Kathryn J. Peall MD, PhD, Davide Martino MD, PhD, Tamara Pringsheim MD, PhD, Emmanuel Roze MD, PhD

引用次数: 0

Respiratory Function in Friedreich's Ataxia 弗里德赖希共济失调的呼吸功能

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-19 DOI: 10.1002/mds.70162

Celiana Figueiredo Viana, Cristina Saade Jaques, Marcio Luiz Escorcio Bezerra, Orlando Graziani Povoas Barsottini, José Luiz Pedroso

Introduction Friedreich's ataxia (FA) is a neurodegenerative disorder often accompanied by respiratory dysfunction, but detailed respiratory profiles remain understudied. Objective To evaluate pulmonary parameters and respiratory muscle strength in individuals with FA compared with healthy controls. Methods Sixteen FA patients and 20 age‐matched healthy controls underwent spirometry, maximal inspiratory and expiratory pressure measurements, sniff nasal inspiratory pressure (SNIP), phrenic nerve conduction study, peripheral oxygen saturation (SpO 2 ), and end‐tidal CO2 (ETCO2). Respiratory parameters were analyzed using Student's t ‐test or Mann–Whitney test, and linear or quantile regression adjusted for body mass index and smoking status. Ataxia severity was assessed using the Scale for the Assessment and Rating of Ataxia (SARA). Results FA patients exhibited significantly reduced forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ), alongside decreased maximal respiratory pressures ( P < 0.01). A restrictive ventilatory pattern predominated. Peripheral oxygen saturation was lower in the FA group ( P < 0.01). Conclusions Respiratory impairment appears mostly subclinical, suggesting that FA patients may be vulnerable to pulmonary infections and ventilatory failure. This dysfunction may reflect both neuromuscular weakness and impaired respiratory coordination. Early and regular respiratory assessment, together with preventive and rehabilitative strategies integrated into multidisciplinary care, may improve quality of life and potentially prolong survival in individuals with FA. © 2025 International Parkinson and Movement Disorder Society.

弗里德赖希共济失调（FA）是一种神经退行性疾病，常伴有呼吸功能障碍，但详细的呼吸特征仍未得到充分研究。目的比较FA患者与健康对照者的肺参数和呼吸肌力。方法16例FA患者和20例年龄匹配的健康对照者分别进行肺活量测定、最大吸气和呼气压测量、嗅鼻吸气压（SNIP）、膈神经传导研究、外周氧饱和度（SpO 2）和尾潮CO2 （ETCO2）测定。采用学生t检验或曼-惠特尼检验分析呼吸参数，并根据体重指数和吸烟状况进行线性或分位数回归校正。使用共济失调评定量表（SARA）评估共济失调严重程度。结果FA患者在1 s内用力肺活量（FVC）和用力呼气量（FEV 1）显著降低，最大呼吸压显著降低（P < 0.01）。限制性通气模式占主导地位。FA组外周血氧饱和度较低（P < 0.01）。结论呼吸功能障碍多表现为亚临床，提示FA患者易发生肺部感染和呼吸衰竭。这种功能障碍可能反映神经肌肉无力和呼吸协调受损。早期和定期的呼吸评估，连同预防和康复策略整合到多学科护理中，可以改善FA患者的生活质量，并有可能延长生存期。©2025国际帕金森和运动障碍学会。

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引用次数: 0

Correction to “Development and Validation of a Patient-Reported Outcome Measure of Ataxia” 更正“一种患者报告的共济失调结果测量方法的开发和验证”

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-17 DOI: 10.1002/mds.70157

Schmahmann, JD, Pierce, S, MacMore, J, L'Italien, GJ. 2021; Development and Validation of a Patient-Reported Outcome Measure of Ataxia. Mov Disord 36: 2367–2377. https://doi.org/10.1002/mds.28670

The maximum total score for the Activities of Daily Living (ADLs) section of the Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) should be 68, not 64 as originally published. The maximum PROM-Ataxia Total score remains unchanged at 280.

We apologize for this error.

Schmahmann， JD, Pierce， S, MacMore， J， L'Italien， GJ。2021年;一种由患者报告的共济失调结果测量方法的开发和验证。电影杂志36:2367-2377。https://doi.org/10.1002/mds.28670患者报告的共济失调结果测量（PROM-Ataxia）的日常生活活动（ADLs）部分的最高总分应该是68分，而不是最初公布的64分。prom -共济失调总分保持在280分不变。我们为这个错误道歉。

引用次数: 0

Reversing Autophagy Inhibition Ameliorates Neurodegeneration in Hereditary Spastic Paraplegia Caused by a Degradation‐Resistant SPAST Mutation 逆转自噬抑制可改善由抗降解SPAST突变引起的遗传性痉挛性截瘫的神经退行性变化

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-17 DOI: 10.1002/mds.70150

Dingyi Zhang, Yang Hu, Jianhe Guo, Dongmei Wu, Yifan Zhang, Lingzi Yang, Yuxi Wang, Nong Xiao, Jinhua Fan, Yanling Dong, Min Zhong, Tongfei Liu

Background Hereditary spastic paraplegias (HSPs) are monogenic neurodegenerative disorders, and SPAST mutations causing spastic paraplegia type 4 (SPG4) represent the most common form of HSP. SPAST mutations elevate SPASTIN protein levels beyond haploinsufficiency, but the mechanisms and downstream consequences are unclear. Methods We identified a de novo SPAST missense variant (p.I344E) in a young Chinese female with SPG4. Wild‐type (WT) and mutant (I344E/K) SPAST constructs were expressed in HEK293 for biochemical and functional assays including cycloheximide chase, ubiquitination analysis, and immunofluorescence. Leveraging somatic cell reprogramming and CRISPR‐based gene editing, we generated patient‐derived induced pluripotent stem cells (iPSCs) and their isogenic controls. Both lines were differentiated into cerebral organoids. Results I344E/K‐SPASTIN exhibited markedly higher steady‐state levels than WT‐SPASTIN owing to impaired ubiquitin‐proteasome‐mediated degradation; the I344E variant showed the greatest accumulation. Mutant SPASTIN mislocalized in cells, displayed diminished microtubule‐severing activity, and elevated acetylated tubulin—phenotypes that were rescued by overexpression of WT‐SPASTIN. In patient cerebral organoids, the I344E mutation led to increased p62/SQSTM1 aggregates, reduced autophagic flux, and enhanced neuronal death. Rapamycin restored autophagy, decreased p62 levels, and reduced cell death. Conclusions Our study provides evidence linking autophagy dysfunction to SPG4 pathogenesis and demonstrates that the I344E mutation acts through a gain‐of‐function mechanism. These findings challenge the prevailing haploinsufficiency model and implicate autophagy modulation as a potential therapeutic strategy for SPG4 and possibly other HSPs. © 2025 International Parkinson and Movement Disorder Society.

遗传性痉挛性截瘫（HSPs）是一种单基因神经退行性疾病，SPAST突变导致痉挛性截瘫4型（SPG4）是最常见的HSP。SPAST突变使SPASTIN蛋白水平升高，超出单倍不足，但机制和下游后果尚不清楚。方法我们在一名患有SPG4的年轻中国女性中鉴定了一种新的SPAST错义变异（p.I344E）。野生型（WT）和突变型（I344E/K） SPAST构建体在HEK293中表达，用于生化和功能分析，包括环己亚胺追踪、泛素化分析和免疫荧光。利用体细胞重编程和基于CRISPR的基因编辑，我们生成了患者来源的诱导多能干细胞（iPSCs）及其等基因对照。两系均分化为脑类器官。结果I344E/K‐SPASTIN稳态水平明显高于WT‐SPASTIN，这是由于泛素蛋白酶体介导的降解受损；I344E型累积量最大。突变型SPASTIN在细胞中定位错误，表现出微管切断活性减弱，乙酰化小管表型升高，这是通过过表达WT - SPASTIN来拯救的。在患者脑类器官中，I344E突变导致p62/SQSTM1聚集增加，自噬通量减少，神经元死亡增加。雷帕霉素恢复自噬，降低p62水平，减少细胞死亡。结论本研究提供了自噬功能障碍与SPG4发病机制联系的证据，并证明I344E突变通过功能增益机制起作用。这些发现挑战了流行的单倍功能不全模型，并暗示自噬调节可能是SPG4和其他热休克蛋白的潜在治疗策略。©2025国际帕金森和运动障碍学会。

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December Infographic 12月信息

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-17 DOI: 10.1002/mds.29863

Prediction of pathological subthalamic nucleus beta burst occurrence in Parkinson's disease

帕金森病病理性丘脑下核β爆发的预测

引用次数: 0

Movement Disorders: Volume 40, Number 12, December 2025 运动障碍：第40卷，第12期，2025年12月

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-12-17 DOI: 10.1002/mds.70154

引用次数: 0

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