Movement Disorders最新文献

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A Complex FGF14 ( TTC )/( TGC ) Repeat Expansion in Parkinson's Disease 帕金森病中一种复杂的FGF14 (TTC)/(TGC)重复扩增

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-11-24 DOI: 10.1002/mds.70128

Xiaosheng Zheng, Zhidong Cen, Xinhui Chen, Fan Zhang, Chenxin Ying, Nan Jin, Peng Liu, Yilin Chen, Haotian Wang, Jiaxiang Li, Joanne Trinh, Joshua Laß, David Pellerin, Matt C. Danzi, Stephan Zuchner, Bernard Brais, Shen‐Yang Lim, Ai Huey Tan, Azlina Ahmad‐Annuar, Dehao Yang, Lebo Wang, Zhiru Lin, Fei Xie, Bo Wang, Sheng Wu, Zhiyuan Ouyang, Piu Chan, Shen Hu, Christine Klein, Hou‐Feng Zheng, Chaodong Wang, Wei Luo

Background Repeat expansions have been reported as genetic causes/risk factors of Parkinson's disease (PD). As a novel repeat expansion locus, the FGF14‐SCA27B (GAA)•(TTC) repeat locus is unexplored in PD. Methods Utilizing genetic sequencing and various polymerase chain reaction (PCR) methodologies, pure and complex repeat expansions in FGF14 were detected in Asian PD patients. Targeted long—read sequencing was performed to investigate the detailed sequence composition of these repeat expansions. Case–control studies were further performed. Results Pure (TTC) ≥250 repeat expansion was detected in 2 of 1190 PD patients (0.17%). Additionally, a more common and complex (TTC)/(TGC) ≥300 repeat expansion was detected as the main expanded genotype in our discovery cluster. Using targeted long‐read sequencing, these complex (TTC)/(TGC) repeat expansions were characterized as (TTC)exp(TGCTTC)exp(TGCTTCTTCTTCTTC)n(TTC)n alleles with four segments (Seg 1–4), and further classified into four genotypic patterns. Pattern 1 was mainly characterized by a (CTC) interruption in the Seg 1‐(TTC)exp. Patterns 2–4 were characterized by different repeat length of Seg 1‐(TTC)exp and Seg 3‐(TGCTTCTTCTTCTTC)n. Case–control analysis revealed a significant enrichment of Pattern 4 (TTC)/(TGC) repeat expansion in PD compared with controls ( P = 0.024, OR: 2.60, 95% CI: 1.07–7.23) in the discovery cluster. This significant association between Pattern 4 (TTC)/(TGC) repeat expansion and PD was confirmed in one of two replication clusters ( P = 0.035, OR: 2.18, 95% CI: 0.95–4.53) and the meta‐analysis across all three clusters ( P = 0.015, OR: 1.75, 95% CI: 1.10–2.79). Interpretation We identified a unique complex (TTC)/(TGC) repeat expansion in FGF14 as a novel genetic risk factor of PD in the Asian population. © 2025 International Parkinson and Movement Disorder Society.

重复扩增被认为是帕金森病（PD）的遗传原因/危险因素。作为一种新的重复扩增位点，FGF14‐SCA27B （GAA）•（TTC）重复扩增位点在PD中尚未被发现。方法利用基因测序和各种聚合酶链反应（PCR）方法检测亚洲PD患者FGF14的纯重复扩增和复杂重复扩增。我们进行了针对性的长读测序，以研究这些重复扩增的详细序列组成。进一步进行了病例对照研究。结果1190例PD患者中2例检测到TTC≥250重复扩增（0.17%）。此外，在我们的发现集群中，检测到更常见和复杂的(TTC)/(TGC)≥300重复扩增作为主要扩增基因型。利用靶向长读测序技术，这些复杂的(TTC)/(TGC)重复扩增序列被表征为（TTC）exp(TGCTTC)exp(tgcttcttcttcttcttc)n(TTC)n等位基因，具有4个片段（Seg 1-4），并进一步分类为4种基因型模式。模式1的主要特征是区段1‐（TTC）exp中的（CTC）中断。模式2-4的特征是Seg 1‐（TTC）exp和Seg 3‐（tgcttcttcttcttcttcttcttcttc）n的重复长度不同。病例-对照分析显示，PD中TTC / TGC重复扩增与对照组相比显著增加（P = 0.024, OR: 2.60, 95% CI: 1.07-7.23）。模式4 (TTC)/(TGC)重复扩增与PD之间的显著关联在两个复制集群中的一个（P = 0.035, OR: 2.18, 95% CI: 0.95-4.53）和所有三个集群的meta分析（P = 0.015, OR: 1.75, 95% CI: 1.10-2.79）中得到证实。我们在FGF14中发现了一个独特的复合物(TTC)/(TGC)重复扩增，作为亚洲人群PD的一个新的遗传危险因素。©2025国际帕金森和运动障碍学会。

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引用次数: 0

Pallidal Evoked Resonant Neural Activity as a Candidate Biomarker for Deep Brain Stimulation in Dystonia 白斑诱发共振神经活动作为肌张力障碍深部脑刺激的候选生物标志物

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-11-22 DOI: 10.1002/mds.70129

Kara A. Johnson, Patricia B. Coutinho, Filipe P. Sarmento, Elizabeth Vo, Joshua K. Wong, Justin D. Hilliard, Kelly D. Foote, Coralie de Hemptinne

Background Deep brain stimulation (DBS) targeted to the globus pallidus (GP) can effectively alleviate dystonia symptoms. However, identifying optimal therapeutic stimulation parameters is challenging due to the manual programming process and the paucity of acute effects of DBS on dystonia symptoms. Objective This study aimed to investigate evoked resonant neural activity (ERNA) in the GP as a potential biomarker to guide DBS contact selection for chronic therapy in patients with dystonia. Methods In n = 8 patients (n = 9 hemispheres) undergoing GP DBS implantation for dystonia, intraoperative local field potential (LFP) recordings were acquired at resting state (30 seconds) and during bursts of high‐frequency stimulation delivered from each DBS contact. ERNA features (amplitude, frequency, and number of peaks) were measured and correlated with dystonia symptom severity, resting‐state LFP spectral power, and postoperative chronic (12‐month) therapeutic stimulation parameters. Results ERNA was consistently elicited by GP DBS but varied in amplitude, frequency, and number of peaks across individuals and stimulating contacts. Higher ERNA amplitudes were associated with stimulation at the GP internus/externus border. ERNA frequency was negatively correlated with cervical dystonia severity ( P < 0.001) and resting‐state alpha (8–12 Hz) power ( P < 0.05). In eight of nine (88.9%) hemispheres, the DBS contact that elicited the maximum ERNA matched the contact empirically selected for chronic therapy by expert clinicians through routine clinical programming. Conclusions Based on its correlation with dystonia symptom severity and therapeutic contact for chronic DBS, ERNA shows promise as an objective candidate biomarker to improve the efficiency and efficacy of DBS for dystonia. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

背景针对苍白球（GP）的深部脑刺激（DBS）可以有效缓解肌张力障碍症状。然而，由于手动编程过程和DBS对肌张力障碍症状的急性影响的缺乏，确定最佳的治疗刺激参数是具有挑战性的。目的探讨GP的诱发共振神经活动（ERNA）作为一种潜在的生物标志物，指导肌张力障碍患者DBS触点选择。方法对8例（9个脑半球）因肌张力障碍而接受GP DBS植入的患者，在静息状态（30秒）和每次DBS接触带来的高频刺激爆发期间，采集术中局部场电位（LFP）记录。测量ERNA特征（振幅、频率和峰数），并与肌张力障碍症状严重程度、静息状态LFP频谱功率和术后慢性（12个月）治疗刺激参数相关。结果GP DBS诱发的ERNA是一致的，但在个体之间和刺激接触时，ERNA的振幅、频率和峰值数量有所不同。较高的ERNA振幅与GP内/外边界的刺激有关。ERNA频率与颈肌张力障碍严重程度（P < 0.001）和静息状态α (8-12 Hz)功率（P < 0.05）呈负相关。在9个半球中的8个（88.9%）中，引发最大ERNA的DBS接触与专家临床医生通过常规临床规划经验选择的慢性治疗接触相匹配。结论基于ERNA与肌张力障碍症状严重程度和慢性DBS治疗接触的相关性，ERNA有望作为一种客观的候选生物标志物，提高DBS治疗肌张力障碍的效率和疗效。©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

Propranolol for Tremors in Spinocerebellar Ataxia Type 12: A Randomized Clinical Trial 心得安治疗脊髓小脑性共济失调12型震颤的随机临床试验

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-11-20 DOI: 10.1002/mds.70115

Prachi Mohapatra, Achal Kumar Srivastava, Divyani Garg, Ayush Agarwal, Divya M. Radhakrishnan, Awadh Kishor Pandit, Pooja Gupta, Sahaj Agrawal, Ashish Datt Upadhyay

Background Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disorder with prominent upper limb tremors. No trials have evaluated tremor‐targeted therapies in this population. Objectives We evaluated long‐acting propranolol for efficacy and safety in reducing tremors and improving ataxia and quality of life in SCA12. Methods In this single‐center, randomized, double‐blind, placebo‐controlled trial, 60 genetically confirmed SCA12 patients (aged 18–65 years; TETRAS PS [The Essential Tremor Rating Assessment Scale Performance Subscale] upper limb component ≥2) were randomized 1:1 to receive extended‐release propranolol or placebo. Propranolol was escalated by 40 mg/week (placebo by one tablet/week) up to 240 mg/day, limiting side effects or ≥30% reduction in TETRAS PS/ADL (Activities‐of‐Daily‐Living Subscale) + PS. The stable dose was continued for 8 weeks (maintenance phase). Primary outcomes were changes from baseline in TETRAS PS and ADL + PS at maintenance weeks 4 and 8. Secondary outcomes included changes in the Scale for the Assessment and Rating of Ataxia (SARA), RAND 36‐Item Short‐Form Health Survey (SF‐36) domains, and accelerometric tremor parameters. Results Propranolol significantly reduced TETRAS PS (LSM ± SE: −4.4 ± 0.3 at week 4; −4.42 ± 0.4 at week 8) and ADL + PS (−5.5 ± 0.63 at week 4; −5.56 ± 0.62 at week 8; P < 0.001 vs. placebo). Significant improvements were also noted in SARA and five of nine SF‐36 domains at both time points. Accelerometry confirmed reductions in tremor peak frequency and power in all positions except rest. Fatigue and headache were the commonest adverse effects, with no discontinuations due to adverse events. Conclusion Propranolol effectively reduced tremors and improved quality of life in SCA12, with good tolerability. © 2025 International Parkinson and Movement Disorder Society.

脊髓小脑性共济失调12型（SCA12）是一种以上肢震颤为主的神经退行性疾病。没有试验评估震颤靶向治疗在这一人群中的效果。目的：我们评估长效心得安在减少震颤、改善心性共济失调和生活质量方面的有效性和安全性。方法在这项单中心、随机、双盲、安慰剂对照试验中，60例基因确诊的SCA12患者（年龄18-65岁；TETRAS PS[特发性震颤等级评定量表表现亚量表]上肢成分≥2）按1:1随机分配，接受缓释心得安或安慰剂治疗。普萘洛尔以40mg /周（安慰剂1片/周）的剂量增加至240mg /天，限制副作用或使TETRAS PS/ADL（活性-日常生活亚量表）+ PS降低≥30%。稳定剂量持续8周（维持期）。主要结局是维持第4周和第8周时TETRAS PS和ADL + PS较基线的变化。次要结局包括失调性运动量表（SARA）、RAND 36项简短健康调查（SF - 36）域和加速震颤参数的变化。结果：普萘洛尔显著降低了TETRAS PS （LSM±SE：第4周为- 4.4±0.3；第8周为- 4.42±0.4）和ADL + PS（第4周为- 5.5±0.63；第8周为- 5.56±0.62；与安慰剂相比P <； 0.001）。在两个时间点，SARA和9个SF - 36结构域中的5个也有显著改善。加速度测量证实，除休息外，所有位置的震颤峰值频率和功率都有所降低。疲劳和头痛是最常见的不良反应，没有因不良事件而停药。结论心得安能有效减轻sc12患者的震颤，改善患者的生活质量，且耐受性好。©2025国际帕金森和运动障碍学会。

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引用次数: 0

Actor or Observer: The Sensorimotor Striatum Shapes Motor Output for Learned but Not Innate Motor Tasks 演员或观察者：感觉运动纹状体决定了习得而非先天运动任务的运动输出

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-11-20 DOI: 10.1002/mds.70137

Christian Espinoza‐Vinces, Conor Fearon

引用次数: 0

Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa. 帕金森病相关的LRRK2和GBA1突变调节对铜绿假单胞菌的外周免疫反应

IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders

Pub Date : 2025-11-19 DOI: 10.1002/mds.70123

Julian R Mark,Hannah A Staley,Ann M Titus,Julian Agin-Liebes,Alicia Garrido,Laura Hughes,Nicolas Dzamko,Rebecca L Wallings,Malú Gámez Tansey

BACKGROUNDPeripheral disease mechanisms such as immune dysregulation may contribute to Parkinson's disease (PD). To investigate interactions between common PD mutations and immune responses to environmental pathogens, we studied responses to Pseudomonas aeruginosa (P. aeruginosa) in peripheral blood mononuclear cells (PBMCs) from PD patients with leucine-rich repeat kinase 2 (LRRK2) mutations, GBA1 mutations, and idiopathic disease (iPD) relative to neurologically healthy controls (NHC).OBJECTIVESThe goal was to test the hypothesis that LRRK2 and GBA modify the human peripheral immune response to bacteria, specifically P. aeruginosa, based on prior animal studies involving Lrrk2 mutations and microbial pathogens.METHODSPBMCs from LRRK2-PD, GBA-PD, and iPD patients plus age- and sex-matched controls were treated ex vivo with live P. aeruginosa and pharmacological agents that block LRRK2 kinase activity (MLi-2) or enhance glucocerebrosidase (GCase) activation (NCGC00188758) to measure enzymatic activities and cytokine release.RESULTSGBA-PD PBMCs exhibited increased P. aeruginosa-dependent secretion of specific inflammatory cytokines including interleukin-1β. Antigen presentation was increased in LRRK2-PD nonclassical monocytes treated with the GCase activator. Levels of pRab10, a proxy for LRRK2 kinase activity, were increased in GBA-PD classical monocytes relative to NHC and iPD. GCase activator treatment increased pRab10 expression in LRRK2-PD intermediate monocytes. GBA-PD and individual treatments with MLi-2 or GCase activator were associated with reduced P. aeruginosa-dependent LRRK2 protein levels in PBMC subsets.CONCLUSIONSThis work demonstrates that PD-linked mutations in LRRK2 and GBA1 converge on peripheral blood immune cell dysregulation, as evinced by the ability of LRRK2 inhibitors and GCase activators to modulate the ex vivo immune response to bacterial exposure. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

免疫失调等外周疾病机制可能导致帕金森病（PD）。为了研究常见PD突变与对环境病原体的免疫反应之间的相互作用，我们研究了与神经健康对照（NHC）相比，富亮氨酸重复激酶2 （LRRK2）突变、GBA1突变和特发性疾病（iPD）的PD患者外周血单核细胞（PBMCs）对铜绿假单胞菌（P. aeruginosa）的反应。目的：基于先前涉及LRRK2突变和微生物病原体的动物研究，目的是验证LRRK2和GBA改变人类对细菌（特别是铜绿假单胞菌）的外周免疫反应的假设。方法采用活体铜绿假单胞菌和阻断LRRK2激酶活性（MLi-2）或增强葡萄糖脑苷酶（GCase）活性（NCGC00188758）的药物对LRRK2- pd、GBA-PD和iPD患者的spbmc以及年龄和性别匹配的对照组进行体外治疗，以测量酶活性和细胞因子释放。结果gba - pd PBMCs显示铜绿假单胞菌依赖性特异性炎性细胞因子（包括白细胞介素-1β）分泌增加。GCase激活剂处理的LRRK2-PD非经典单核细胞抗原呈递增加。与NHC和iPD相比，GBA-PD经典单核细胞中的pRab10水平（LRRK2激酶活性的代理因子）升高。GCase激活剂处理增加了LRRK2-PD中间单核细胞中pRab10的表达。GBA-PD和单独使用MLi-2或GCase激活剂治疗与PBMC亚群中铜绿假单胞菌依赖的LRRK2蛋白水平降低相关。结论LRRK2和GBA1与pd相关的突变会聚在外周血免疫细胞失调上，LRRK2抑制剂和GCase激活剂能够调节细菌暴露的体外免疫反应，证明了这一点。©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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Pub Date : 2025-11-18 DOI: 10.1002/mds.70132

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IF 8.6 1区医学 Q1 CLINICAL NEUROLOGY

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Pub Date : 2025-11-18 DOI: 10.1002/mds.70126

引用次数: 0

Unilateral Magnetic Resonance‐Guided Focused Ultrasound (MRgFUS) Pallidothalamic Tractotomy in Parkinson's Disease: Promising Results But Uncertain Target 单侧磁共振引导聚焦超声（MRgFUS）治疗帕金森病：有希望的结果但不确定的目标

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Pub Date : 2025-11-18 DOI: 10.1002/mds.70131

Mickael Aubignat

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Reply to: Utility of Progression Rate Since Symptom Onset in Predicting Subsequent Survival in Progressive Supranuclear Palsy 回复：自症状出现以来的进展率在预测进行性核上性麻痹患者后续生存中的作用

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Movement Disorders

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Andrea Quattrone, Nicolai Franzmeier, Günter U. Höglinger

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