Clinical Parkinsonism Related Disorders最新文献_第2页

Differentiating effects of levodopa and subthalamic nucleus deep brain stimulation on motor features in Parkinson disease 左旋多巴和丘脑底核深部脑刺激对帕金森病运动特征的鉴别作用

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-12-16 DOI: 10.1016/j.prdoa.2025.100417

Tiffanie A. Lee , Deepa Ramesh , Mwiza Ushe , Scott A. Norris , Samer D. Tabbal , Joel S. Perlmutter , John R. Younce

Introduction

While deep brain stimulation of the subthalamic nucleus (STN DBS) is traditionally used to treat motor fluctuations in Parkinson disease (PD), recent progress in levodopa delivery systems may offer non-invasive alternatives to surgical options. To gain insight into symptoms more likely to be treated effectively by STN DBS or levodopa, we systematically compared the differential effects of levodopa and STN-DBS on specific parkinsonian motor components.

Methods

We retrospectively analyzed 395 PD patients who received bilateral STN-DBS at Washington University (1999–2020). UPDRS-III was obtained in three conditions: preoperative OFF-medication, preoperative ON-medication, and postoperative ON-DBS/OFF-medication. Exploratory factor analysis identified a consensus structure across conditions. Treatment responses by factor were compared using Wilcoxon rank-sum tests and correlations were assessed with Kendall’s tau.

Results

Both treatments significantly improved all motor features. STN-DBS showed slightly superior efficacy for upper body tremor (mean change: −3.84 vs −3.43, p < 0.001), while levodopa demonstrated much greater effectiveness for axial symptoms (−5.41 vs −2.65, p < 0.001), and slightly greater effectiveness for lower body tremor (−1.25 vs −1.06, p < 0.001), and lower body bradykinesia (−1.18 vs −0.91, p = 0.005). Correlations between treatment responses were weak but statistically significant for rigidity (τ = 0.158), bradykinesia (hand: τ = 0.118; leg: τ = 0.179), and axial symptoms (τ = 0.207).

Conclusion

Levodopa and STN-DBS demonstrate similar but distinct therapeutic profiles across parkinsonian motor domains. However, weak correlations between treatment modalities for all motor features challenge the utility of levodopa responsiveness for DBS candidacy and support individualization of treatment selection based on symptom profile.

虽然丘脑下核深部脑刺激（STN DBS）传统上用于治疗帕金森病（PD）的运动波动，但最近左旋多巴传递系统的进展可能提供非侵入性替代手术选择。为了深入了解STN-DBS或左旋多巴更可能有效治疗的症状，我们系统地比较了左旋多巴和STN-DBS对特定帕金森运动成分的不同影响。方法回顾性分析1999-2020年在华盛顿大学接受双侧STN-DBS治疗的395例PD患者。UPDRS-III是在术前off服药、术前on服药和术后ON-DBS/ off服药三种情况下获得的。探索性因素分析确定了不同条件下的共识结构。采用Wilcoxon秩和检验比较各因素的治疗反应，并采用Kendall 's tau评估相关性。结果两种治疗方法均能显著改善患者的运动功能。STN-DBS对上半身震颤的疗效略好（平均变化：- 3.84 vs - 3.43, p < 0.001），而左旋多巴对轴向症状的疗效更大（- 5.41 vs - 2.65, p < 0.001），对下半身震颤（- 1.25 vs - 1.06, p < 0.001）和下半身运动迟缓（- 1.18 vs - 0.91, p = 0.005）的疗效略好。治疗反应之间的相关性较弱，但在僵硬（τ = 0.158）、运动迟缓（手：τ = 0.118；腿：τ = 0.179）和轴向症状（τ = 0.207）方面具有统计学意义。结论左旋多巴和STN-DBS在帕金森运动域表现出相似但不同的治疗效果。然而，所有运动特征的治疗方式之间的弱相关性挑战了左旋多巴反应性对DBS候选资格的效用，并支持基于症状特征的治疗选择个体化。

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引用次数: 0

Diagnostic analysis of adult neuronal ceroid lipofuscinosis caused by CLN6 gene mutation: a case report. CLN6基因突变致成人神经元样脂褐质病1例诊断分析。

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-08-06 eCollection Date: 2025-01-01 DOI: 10.1016/j.prdoa.2025.100384

Yubo Hu, Haochen Sun, Qin Jiang, Juan Wang, Shugang Zhang, Xingjian Lin

Neuronal ceroid lipofuscinosis is a rare lysosomal storage disorder that is difficult to distinguish from other diseases with similar clinical symptoms in its early stages. This article analyzes and summarizes the diagnostic process of a family affected by adult neuronal ceroid lipofuscinosis caused by CLN6 gene mutation. We collected clinical data from a 48-year-old female patient with neuronal ceroid lipofuscinosis who visited Nanjing Brain Hospital in March 2024. She has presented with corresponding symptoms since 2020. The patient underwent whole exome sequencing (WES) and other examinations. WES showed that both the patient and her elder brother, who exhibited similar symptoms of walking instability, were homozygous for a mutation in the CLN6 gene. This variant (c.856C > T: p.Leu286Phe) has not been previously reported and is classified as a Variant of Uncertain Significance (VUS) based on current American College of Medical Genetics and Genomics/Association for Molecular Pathology(ACMG/AMP) guidelines. Both of the patient's parents displayed normal phenotypes but were found to have heterozygous mutations in the CLN6 gene. Additionally, no nuclear inclusion bodies were found in the patient's skin tissue.

神经性蜡样脂褐质病是一种罕见的溶酶体贮积性疾病，在早期很难与其他具有类似临床症状的疾病区分开来。本文分析总结了一例CLN6基因突变所致成人神经性神经样脂褐质病的诊断过程。我们收集了一名于2024年3月在南京脑科医院就诊的48岁女性神经性脑蜡样脂褐质病患者的临床资料。自2020年以来，她一直出现相应的症状。患者接受了全外显子组测序（WES）和其他检查。WES显示，患者和她的哥哥都表现出类似的行走不稳症状，他们都是CLN6基因突变的纯合子。这种变异（c.856C > T: p.Leu286Phe）以前没有报道过，根据目前美国医学遗传学和基因组学学院/分子病理学协会（ACMG/AMP）的指南，它被归类为不确定意义变异（VUS）。患者的父母都表现出正常的表型，但在CLN6基因中发现了杂合突变。此外，患者皮肤组织中未发现核包涵体。

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引用次数: 0

Beyond the needle: how clinician expertise affects outcomes in the treatment of hemifacial spasm. 针外：临床医生的专业知识如何影响治疗面肌痉挛的结果。

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-08-06 eCollection Date: 2025-01-01 DOI: 10.1016/j.prdoa.2025.100383

Melissa Luque-Llano, Maria Angelica-Coronel, Yulexy T Alvarado-Vanegas, Floralinda García Puello, Laura Arzuza Ortega, Gustavo B Vincos

Background: Hemifacial spasm (HFS) is characterized by abnormal contraction of the muscles innervated by the seventh cranial nerve. It is usually benign and diagnosed clinically. The effectiveness of botulinum toxin (BoNT) for its treatment has been well demonstrated. However, adverse events (AEs) resulting from its administration remain a concern, and some patients express reluctance to be treated by resident physicians, even when under expert supervision.

Objective: To determine the association between the level of expertise of the neurology professional and the presence of AEs following BoNT administration in patients with HFS.

Methods: A cross-sectional descriptive study with an analytical phase conducted at Hospital Occidente de Kennedy (Bogotá, Colombia). Out of 88 medical records reviewed, 73 met all inclusion criteria. Data analysis was performed using SPSS software version 22.

Results: A predominance of female patients was observed, accounting for 74 % of the study population. The mean age of symptom onset was 54.5 ± 12.7 years, with a median symptom duration of 9 years. In most cases, the left side was affected (53.4 %). The average number of botulinum toxin applications per patient was 2.6 during the study period. Adverse events occurred in 12.6 % of cases, primarily mild facial paresis (7.9 %), hematoma (2.6 %), and eyelid ptosis (2.1 %).

Conclusions: The results did not show a statistically significant association between the level of expertise and the occurrence of adverse events. The frequency of observed adverse events was similar between the groups. This suggests that the occurrence of adverse events following BoNT administration was comparable regardless of whether the procedure was performed by a neurologist or a resident under supervision.

背景：面肌痉挛（HFS）以第七脑神经支配的肌肉异常收缩为特征。它通常是良性的，临床诊断。肉毒杆菌毒素（BoNT）对其治疗的有效性已得到很好的证明。然而，其使用引起的不良事件（ae）仍然令人担忧，一些患者表示不愿接受住院医师的治疗，即使在专家监督下。目的：确定神经学专业人员的专业水平与HFS患者BoNT治疗后ae的存在之间的关系。方法：横断面描述性研究与分析阶段进行了医院西肯尼迪（波哥大，哥伦比亚）。在审查的88份医疗记录中，有73份符合所有纳入标准。采用SPSS软件22进行数据分析。结果：以女性患者为主，占研究人群的74%。出现症状的平均年龄为54.5±12.7岁，中位症状持续时间为9年。在大多数病例中，左侧受影响（53.4%）。在研究期间，每位患者平均使用2.6次肉毒杆菌毒素。12.6%的病例发生了不良事件，主要是轻度面部瘫（7.9%）、血肿（2.6%）和眼睑下垂（2.1%）。结论：结果显示专业水平与不良事件发生之间没有统计学上显著的关联。观察到的不良事件的频率在两组之间相似。这表明BoNT给药后不良事件的发生是可比性的，无论手术是由神经科医生还是住院医生监督下进行的。

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引用次数: 0

The impact of pregabalin and gabapentin on essential tremor: a systematic review and meta-analysis. 普瑞巴林和加巴喷丁对特发性震颤的影响：系统回顾和荟萃分析。

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-07-30 eCollection Date: 2025-01-01 DOI: 10.1016/j.prdoa.2025.100381

Hooman Pourbala, Zhale Nahavandi, Arash Maghsoudlou, Melina Gazerani Farahani, Avin Khallaghi, Sepehr Izadi, Mehrdad Faizi, Mehran Ghaffari, Hadi Esmaily

Introduction: Essential tremor (ET) is a common neurological disorder characterized by involuntary rhythmic oscillations. Emerging evidence suggests that gabapentinoids, including gabapentin and pregabalin, may be effective in managing ET. This study aimed to assess the efficacy of gabapentinoids in treating ET by analyzing data from randomized controlled trials (RCTs).

Methods: A systematic search was conducted across various databases to identify relevant RCTs utilizing gabapentin or pregabalin. Tremor severity was evaluated using the total tremor score (TTS) and accelerometry.

Results: In a between-group meta-analysis of seven RCTs (N = 235), gabapentinoids did not significantly outperform placebo in reducing TTS or its subscales. Accelerometry data suggested a non-significant trend favoring gabapentinoids.However, within-group analyses demonstrated a significant reduction in TTS from baseline with gabapentinoids overall (P = 0.016), an effect driven by gabapentin (P = 0.021) but not pregabalin. No significant within-group improvements were observed for TTS subscales or accelerometry measures post-treatment.

Conclusion: This meta-analysis found no significant advantage of gabapentinoids over placebo in ET. However, within-group analyses demonstrated that gabapentin-but not pregabalin-significantly reduced tremor severity from baseline, suggesting a potential therapeutic signal that warrants further investigation. Larger, standardized trials are needed to identify which patient subgroups, if any, may benefit from gabapentin therapy.

特发性震颤（ET）是一种常见的神经系统疾病，其特征是不自主的节律性振荡。新出现的证据表明，加巴喷丁类药物，包括加巴喷丁和普瑞巴林，可能对ET治疗有效。本研究旨在通过分析随机对照试验（RCTs）的数据来评估加巴喷丁类药物治疗ET的疗效。方法：在不同数据库中进行系统检索，以确定使用加巴喷丁或普瑞巴林的相关随机对照试验。使用总震颤评分（TTS）和加速度计评估震颤严重程度。结果：在7项随机对照试验（N = 235）的组间荟萃分析中，加巴喷丁类在降低TTS或其亚量表方面没有显著优于安慰剂。加速度计数据显示，加巴喷丁类药物没有明显的优势。然而，组内分析显示，加巴喷丁类药物总体上较基线显著降低TTS (P = 0.016)，加巴喷丁（P = 0.021）而普瑞巴林不起作用。治疗后TTS亚量表或加速测量没有观察到组内显著改善。结论：本荟萃分析未发现加巴喷丁类药物在ET治疗中较安慰剂有显著优势。然而，组内分析表明，加巴喷丁（而非普瑞巴林）可显著降低基线震颤严重程度，这表明其潜在的治疗信号值得进一步研究。需要更大规模的标准化试验来确定哪些患者亚组（如果有的话）可以从加巴喷丁治疗中获益。

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引用次数: 0

Nocturnal polyuria is common in Parkinson’s and is associated with orthostatic hypotension 夜间多尿在帕金森症中很常见，并与体位性低血压有关

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100334

Matthew D Smith , Anisha Cullen , Gabriella E Portlock , Marcus J Drake , Yoav Ben-Shlomo , Emily J Henderson

Background

Nocturia is the most common lower urinary tract symptom (LUTS) in Parkinson’s disease (PD) and impacts sleep and subsequent daytime function. Often nocturia in PD is attributed to overactive bladder, however we explored the contribution of the over-production of urine at night, nocturnal polyuria (NP), as another factor.

Objectives

To assess the prevalence and severity of NP in a PD cohort with LUTS and explore associations with autonomic and other patient characteristics.

Methods

Sub-study nested within a trial for LUTS in PD. All participants performed 72-hour bladder diaries. Nocturnal polyuria index (NPi) was calculated from diaries and key associations were explored.

Results

62.6 % of participants had NP based on the NPi33 threshold (producing > 33 % urine at night). Increasing NPi was strongly significantly associated with greater nocturia (OR 1.7 per 5 % NPi unit; 1.5–2.0; P < 0.001). A significant association was observed between NPi and orthostatic hypotension (OR 1.2 per 5 % NPi unit increase; 1.0–1.4; P = 0.03) and reported cardiovascular symptoms (coefficient 0.07; 0.03–0.11; P = 0.002). A marked association was seen with severe NP and orthostatic hypotension (OR 4.9; 1.56–15.57; P = 0.006).

Conclusion

NP is very common in this PD cohort symptomatic for LUTS, and is closely associated with increasing rate of nocturia. NP is linked to cardiovascular symptoms and autonomic dysfunction, particularly blood pressure lability which may be causal or simply reflect advanced disease state.

夜尿症是帕金森病（PD）中最常见的下尿路症状（LUTS），影响睡眠和随后的白天功能。PD患者夜尿通常归因于膀胱过度活动，但我们探讨了夜间尿量过多的贡献，即夜间多尿（NP），作为另一个因素。目的评估合并LUTS的PD队列中NP的患病率和严重程度，并探讨其与自主神经和其他患者特征的关系。方法在PD患者的LUTS试验中嵌套子研究。所有参与者都记录了72小时膀胱日志。根据日记计算夜间多尿指数（NPi），并探讨其中的关键关联。结果62.6%的参与者根据NPi33阈值(产生>；33%尿在晚上)。NPi的增加与夜尿的增加密切相关(每5% NPi单位OR 1.7；1.5 - -2.0;P & lt;0.001)。观察到NPi与直立性低血压之间存在显著关联(每增加5% NPi单位，OR为1.2；1.0 - -1.4;P = 0.03)和报告的心血管症状(系数0.07；0.03 - -0.11;p = 0.002)。严重NP和直立性低血压有显著相关性(OR 4.9；1.56 - -15.57;p = 0.006)。结论np在有LUTS症状的PD队列中很常见，且与夜尿率增高密切相关。NP与心血管症状和自主神经功能障碍有关，尤其是血压不稳定，这可能是病因，也可能只是反映了疾病的晚期状态。

{"title":"Nocturnal polyuria is common in Parkinson’s and is associated with orthostatic hypotension","authors":"Matthew D Smith , Anisha Cullen , Gabriella E Portlock , Marcus J Drake , Yoav Ben-Shlomo , Emily J Henderson","doi":"10.1016/j.prdoa.2025.100334","DOIUrl":"10.1016/j.prdoa.2025.100334","url":null,"abstract":"<div><h3>Background</h3><div>Nocturia is the most common lower urinary tract symptom (LUTS) in Parkinson’s disease (PD) and impacts sleep and subsequent daytime function. Often nocturia in PD is attributed to overactive bladder, however we explored the contribution of the over-production of urine at night, nocturnal polyuria (NP), as another factor.</div></div><div><h3>Objectives</h3><div>To assess the prevalence and severity of NP in a PD cohort with LUTS and explore associations with autonomic and other patient characteristics.</div></div><div><h3>Methods</h3><div>Sub-study nested within a trial for LUTS in PD. All participants performed 72-hour bladder diaries. Nocturnal polyuria index (NPi) was calculated from diaries and key associations were explored.</div></div><div><h3>Results</h3><div>62.6 % of participants had NP based on the NPi33 threshold (producing > 33 % urine at night). Increasing NPi was strongly significantly associated with greater nocturia (OR 1.7 per 5 % NPi unit; 1.5–2.0; <em>P < 0.001</em>). A significant association was observed between NPi and orthostatic hypotension (OR 1.2 per 5 % NPi unit increase; 1.0–1.4; <em>P = 0.03</em>) and reported cardiovascular symptoms (coefficient 0.07; 0.03–0.11; <em>P = 0.002</em>). A marked association was seen with severe NP and orthostatic hypotension (OR 4.9; 1.56–15.57; <em>P = 0.006</em>).</div></div><div><h3>Conclusion</h3><div>NP is very common in this PD cohort symptomatic for LUTS, and is closely associated with increasing rate of nocturia. NP is linked to cardiovascular symptoms and autonomic dysfunction, particularly blood pressure lability which may be causal or simply reflect advanced disease state.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100334"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Frequency of tremor in people with multiple sclerosis: A systematic review and meta-analysis 多发性硬化症患者震颤频率：一项系统回顾和荟萃分析

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100315

Saeed Vaheb , Danial Dehghani Firouzabadi , Hamed Ghoshouni , Mohammad Yazdan Panah , Vahid Shaygannejad , Omid Mirmosayyeb

Background

Multiple sclerosis (MS) is a chronic neurodegenerative disorder causing various symptoms, including tremors, which significantly affect the quality of life and disability in people with MS (PwMS). Previous studies report a wide range of tremor frequency in PwMS, necessitating a comprehensive review for reliable estimates.

Objectives

This review aimed to elucidate the frequency rate of tremor among PwMS.

Method

A systematic search was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science up to April 27, 2024, to identify studies evaluating various types of tremors in PwMS. The Meta-proportion method implemented in R software version 4.0.0, utilizing a random-effects model, was employed to estimate the pooled frequency rates of tremor, with its 95% confidence interval (CI), among PwMS.

Results

From 3780 studies, 14 studies encompassing 17,458 PwMS (71.5 % female) were included. The mean age was 46.4 years, with a disease duration of 9.3 years and an Expanded Disability Status Scale (EDSS) score of 3.4. The pooled frequency of tremor was 33.32 % (95 % CI: 23.47 % to 44.88 %; I² = 98 %; p-heterogeneity < 0.01). Subgroup analysis by sample size revealed that the pooled frequency of tremor in PwMS was significantly lower (p-value < 0.01) in studies with over 200 participants (22.46, 95 % CI: 15.69 % to 31.08 %, I² = 99 %; p-heterogeneity < 0.01) compared to those with fewer than 200 participants (47.65, 95 % CI: 31.97 % to 63.81 %, I² = 91 %; p-heterogeneity < 0.01)

Conclusion

Tremor is a prevalent complaint in PwMS. These findings highlight the necessity for targeted supportive, therapeutic, and rehabilitative interventions to effectively address this prevalent issue in PwMS.

多发性硬化症（MS）是一种慢性神经退行性疾病，引起包括震颤在内的各种症状，严重影响MS （PwMS）患者的生活质量和残疾。先前的研究报告了PwMS的震颤频率范围很广，需要进行全面的审查以获得可靠的估计。目的了解多发性硬化症患者的震颤频率。方法系统检索截至2024年4月27日的PubMed/MEDLINE、Embase、Scopus、Web of Science等数据库，检索评价不同类型PwMS震颤的研究。采用R软件4.0.0版中实现的Meta-proportion方法，利用随机效应模型，估计PwMS中合并的震颤频率，其95%置信区间（CI）。结果从3780项研究中，纳入了14项研究，共17458例PwMS（71.5 %为女性）。平均年龄46.4 岁，病程9.3 岁，扩展残疾状态量表（EDSS）评分3.4分。合并震颤频率为33.32 %(95 % CI: 23.47 % ~ 44.88 %；I2 = 98 %;p-heterogeneity & lt; 0.01)。按样本量进行的亚组分析显示，在超过200名参与者的研究中，PwMS患者的合并震颤频率显著降低（p值 <； 0.01）(22.46,95 % CI: 15.69 %至31.08 %,I2 = 99 %；p异质性 <； 0.01)与少于200名受试者相比(47.65,95 % CI: 31.97 %至63.81 %,I2 = 91 %；p异质性 <； 0.01)结论震颤是PwMS患者的主要主诉。这些发现强调了有针对性的支持、治疗和康复干预的必要性，以有效地解决这一普遍问题。

{"title":"Frequency of tremor in people with multiple sclerosis: A systematic review and meta-analysis","authors":"Saeed Vaheb , Danial Dehghani Firouzabadi , Hamed Ghoshouni , Mohammad Yazdan Panah , Vahid Shaygannejad , Omid Mirmosayyeb","doi":"10.1016/j.prdoa.2025.100315","DOIUrl":"10.1016/j.prdoa.2025.100315","url":null,"abstract":"<div><h3>Background</h3><div>Multiple sclerosis (MS) is a chronic neurodegenerative disorder causing various symptoms, including tremors, which significantly affect the quality of life and disability in people with MS (PwMS). Previous studies report a wide range of tremor frequency in PwMS, necessitating a comprehensive review for reliable estimates.</div></div><div><h3>Objectives</h3><div>This review aimed to elucidate the frequency rate of tremor among PwMS.</div></div><div><h3>Method</h3><div>A systematic search was conducted in PubMed/MEDLINE, Embase, Scopus, and Web of Science up to April 27, 2024, to identify studies evaluating various types of tremors in PwMS. The Meta-proportion method implemented in R software version 4.0.0, utilizing a random-effects model, was employed to estimate the pooled frequency rates of tremor, with its 95% confidence interval (CI), among PwMS.</div></div><div><h3>Results</h3><div>From 3780 studies, 14 studies encompassing 17,458 PwMS (71.5 % female) were included. The mean age was 46.4 years, with a disease duration of 9.3 years and an Expanded Disability Status Scale (EDSS) score of 3.4. The pooled frequency of tremor was 33.32 % (95 % CI: 23.47 % to 44.88 %; I<sup>2</sup> = 98 %; <em>p</em>-heterogeneity < 0.01). Subgroup analysis by sample size revealed that the pooled frequency of tremor in PwMS was significantly lower (<em>p</em>-value < 0.01) in studies with over 200 participants (22.46, 95 % CI: 15.69 % to 31.08 %, I<sup>2</sup> = 99 %; <em>p</em>-heterogeneity < 0.01) compared to those with fewer than 200 participants (47.65, 95 % CI: 31.97 % to 63.81 %, I<sup>2</sup> = 91 %; <em>p</em>-heterogeneity < 0.01)</div></div><div><h3>Conclusion</h3><div>Tremor is a prevalent complaint in PwMS. These findings highlight the necessity for targeted supportive, therapeutic, and rehabilitative interventions to effectively address this prevalent issue in PwMS.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"12 ","pages":"Article 100315"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of istradefylline on motor and non-motor symptoms in patients with Parkinson’s disease: Subanalysis of the ISTRA ADJUST PD Istradefylline 对帕金森病患者运动和非运动症状的影响：ISTRA ADJUST帕金森病子分析

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100327

Hiroshi Nagayama , Osamu Kano , Renpei Sengoku , Naotake Yanagisawa , Asako Yoritaka , Keisuke Suzuki , Noriko Nishikawa , Yohei Mukai , Kyoichi Nomura , Norihito Yoshida , Morinobu Seki , Miho Kawabe Matsukawa , Hiroo Terashi , Katsuo Kimura , Jun Tashiro , Shigeki Hirano , Hidetomo Murakami , Hideto Joki , Tsuyoshi Uchiyama , Hideki Shimura , Taku Hatano

Introduction

Parkinson’s disease (PD) presents with diverse motor and non-motor symptoms, some of which do not fully respond to dopamine replacement therapy. To clarify the effects of the adenosine A_2A receptor antagonist istradefylline (IST) on PD symptoms, we conducted a subanalysis of the 37-week ISTRA ADJUST PD randomized controlled trial.

Methods

Patients with PD experiencing wearing-off with levodopa at 300–400 mg/day were randomized 1:1 to receive IST or no IST (control). Levodopa doses were titrated according to clinical severity throughout the study. PD symptoms were assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Parkinson’s Disease Questionnaire-39 (PDQ-39).

Results

The efficacy analyses included 105 patients (IST, n = 52; control, n = 53). Regarding MDS-UPDRS subitems in patients in the IST group, significant improvements (p < 0.05) were observed at week 36 compared with baseline for both motor (e.g., facial expression, rigidity, finger tapping, toe tapping, time spent in the off state, and complexity of motor fluctuation) and non-motor (e.g., daytime sleepiness, fatigue, and doing hobbies and other activities) symptoms. In patients in the control group, significant improvements (p < 0.05) were observed for motor symptoms only. Regarding PDQ-39 subitems in patients in the IST group, significant improvements (p < 0.05) were observed at week 36 compared with baseline in doing up buttons or shoelaces, writing, feeling angry or bitter, and unexpectedly falling asleep during the day.

Conclusion

IST can improve motor and non-motor symptoms and quality of life suggesting that it provides more comprehensive improvement in PD symptoms than increasing the levodopa dose alone.

Clinical trial registration:

Japan Registry of Clinical Trials; study ID: jRCTs031180248.

帕金森病（PD）表现为多种运动和非运动症状，其中一些症状对多巴胺替代治疗不完全有效。为了阐明腺苷A2A受体拮抗剂iststradefylline （IST）对PD症状的影响，我们对为期37周的ISTRA ADJUST PD随机对照试验进行了亚分析。方法左旋多巴剂量为300 ~ 400 mg/d的PD患者，按1:1随机分为IST组和不IST组（对照组）。在整个研究过程中，左旋多巴剂量根据临床严重程度进行滴定。采用运动障碍学会统一帕金森病评定量表（MDS-UPDRS）和帕金森病问卷-39 （PDQ-39）对帕金森病症状进行评估。结果纳入疗效分析105例(IST, n = 52；对照组，n = 53)。IST组患者的MDS-UPDRS分项有显著改善(p <；与基线相比，第36周观察到运动（如面部表情、僵硬、手指敲打、脚趾敲打、处于关闭状态的时间和运动波动的复杂性）和非运动（如白天嗜睡、疲劳、从事爱好和其他活动）症状。在对照组患者中，显著改善(p <；仅在运动症状中观察到0.05)。IST组患者的PDQ-39分项有显著改善(p <；在扣扣子或系鞋带、写作、感到愤怒或痛苦以及白天意外入睡方面，与基线相比，观察到0.05)。结论ist能改善运动和非运动症状及生活质量，提示其对PD症状的改善比单独增加左旋多巴剂量更全面。临床试验注册：日本临床试验注册中心；研究编号：jRCTs031180248。

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引用次数: 0

Impact of pimavanserin on prescribing practices in parkinson disease 匹马万色林对帕金森病处方实践的影响

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100317

Thanh Phuong Pham Nguyen , Vy Le , Daniel Weintraub , Allison W. Willis

Introduction

Parkinson disease psychosis (PDP) is a common complication of PD. Until 2016, the only drugs available to treat PDP in the U.S. were antipsychotics with variable degrees of dopamine-receptor antagonism (DRA) that may worsen PD motor symptoms. We evaluated the impact that pimavanserin, a selective serotonin receptor inverse agonist/antagonist atypical antipsychotic (AAP) with no known DRA, had on PDP treatment practices in a commercially insured population.

Methods

We included adults diagnosed with PD who filled at least one AAP prescription from 2016 to 2022. AAP dispensings were categorized into (1) pimavanserin, (2) clozapine and quetiapine (i.e., PDP-“preferred” mixed receptor antagonist AAPs), and (3) the remaining AAPs (i.e., PDP-“nonpreferred” mixed receptor antagonist AAPs). Trends in quarterly dispensing rates per 1000 persons treated were compared across categories. Secondary analyses focused on the 65+ subpopulations insured by Medicare Advantage programs.

Results

Dispensing rates varied between 4 and 697/1000 persons treated for pimavanserin, 1434–1821 for preferred, and 394–746 for nonpreferred AAPs. Pimavanserin dispensings surpassed the nonpreferred category after quarter 3 of 2018. However, preferred AAPs, particularly quetiapine, remained the most dispensed category in the sixth year after pimavanserin’s approval. We observed similar trends among Medicare Advantage enrollees.

Conclusion

The availability of pimavanserin was followed by a decline in the use of the most harmful AAPs in persons living with PD. Quetiapine remained the most prescribed AAP. Comparative safety and effectiveness studies are needed to define the relative risks and benefits of treatment options in PDP.

帕金森病精神病（PDP）是帕金森病的常见并发症。直到2016年，美国唯一可用于治疗PDP的药物是具有不同程度多巴胺受体拮抗剂（DRA）的抗精神病药，可能会加重PD运动症状。我们评估了匹马万色林（一种没有已知DRA的选择性5 -羟色胺受体反向激动剂/拮抗剂非典型抗精神病药（AAP））对商业保险人群PDP治疗实践的影响。方法：我们纳入了2016年至2022年期间至少服用过一种AAP处方的PD患者。AAP分配分为(1)匹马万色林，(2)氯氮平和喹硫平（即PDP-“首选”混合受体拮抗剂AAPs），以及(3)剩余的AAPs（即PDP-“非首选”混合受体拮抗剂AAPs）。比较了不同类别每1000人的季度配药率的趋势。二级分析集中在65岁以上的医疗保险优势计划保险人群。结果：匹马万塞林的配药率在4 - 697/1000人之间，首选aap为1434-1821人，非首选aap为394-746人。2018年第三季度之后，皮马万色林超过了非首选类别。然而，在匹马万色林获批后的第六年，首选的aap，尤其是喹硫平，仍然是最畅销的类别。我们在医疗保险优势参保者中观察到类似的趋势。结论随着匹马万色林的普及，PD患者中最有害的AAPs的使用也随之下降。奎硫平仍然是最常用的AAP。需要进行安全性和有效性比较研究，以确定PDP治疗方案的相对风险和益处。

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引用次数: 0

Comparative safety of istradefylline in Parkinson’s disease: A systematic review of randomized controlled trials and real-world studies isstradefylline治疗帕金森病的比较安全性：一项随机对照试验和现实世界研究的系统综述

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100307

Sagari Betté , Joyce Qian , Hannah Cummings , Hiroo Shimoda , Katsumi Shinoda , Ashley Thai , Sarah Batson , Gabrielle Redhead , Alexander Hodkinson , Daniel Truong

Introduction

Istradefylline offers a novel mechanism (adenosine A_2A receptor antagonism) to treat OFF episodes in Parkinson’s disease (PD). It may potentially offer improved tolerability versus other adjuncts, but comparative safety data are lacking.

Methods

A systematic review and Bayesian network meta-analysis (NMA) incorporating RCTs of PD adjuncts until January 10, 2024, was conducted to estimate relative safety. Inconsistency was assessed and heterogeneity evaluated by global I²-statistic and between-study heterogeneity. Incidences of safety outcomes were summarized from RWE identified according to the same criteria.

Results

100 RCTs and 55 RWE publications were identified; 76 RCTs were included in NMAs. Istradefylline demonstrated lower odds of serious AEs (odds ratio [OR] = 0.56; 95 % CrI: 0.32, 0.99), treatment-emergent AEs (0.43; 0.25, 0.73), treatment-related AEs (0.33; 0.19, 0.56), hallucinations (0.25; 0.06, 0.97), and withdrawal due to AEs (0.37; 0.19, 0.68) versus amantadine. Istradefylline showed lower odds of dyskinesia (0.63; 0.41, 0.99) and hypotension (0.19; 0.03, 0.82) versus catechol-O-methyl transferase inhibitors (COMTi), lower odds of nausea (0.58; 0.33, 0.99) versus dopamine agonists (DA), and lower odds of hypotension (0.09; 0.01, 0.52) versus monoamine oxidase-B inhibitors (MAO-Bi). Sensitivity analysis of RCTs published since 2000 found a reduction in odds of dyskinesia and hallucinations for istradefylline versus DA. RWE were heterogeneous but demonstrated lower incidence of certain AEs with istradefylline, specifically dyskinesia (versus MAO-Bi), somnolence (versus DA and COMTi), peripheral edema and hallucinations (versus amantadine), and nausea (versus all comparators).

Conclusion

Istradefylline exhibits a favorable safety profile versus other PD adjuncts, as demonstrated by RCTs and RWE.

istradefylline提供了一种新的机制（腺苷A2A受体拮抗剂）来治疗帕金森病（PD）的OFF发作。与其他辅助药物相比，它可能提供更好的耐受性，但缺乏相对安全性的数据。方法采用系统评价和贝叶斯网络荟萃分析（NMA），结合截至2024年1月10日的随机对照试验，评估PD辅助治疗的相对安全性。通过全球i2统计量和研究间异质性评估不一致性和异质性。根据相同的标准，总结了RWE确定的安全结果发生率。结果共纳入rct 100篇，RWE出版物55篇；nma共纳入76项随机对照试验。Istradefylline显示严重ae的发生率较低(优势比[OR] = 0.56；95% CrI: 0.32, 0.99)，治疗发生ae (0.43；0.25, 0.73)，治疗相关ae (0.33；0.19, 0.56)，幻觉(0.25；0.06, 0.97)， ae导致的退出(0.37；0.19, 0.68)对比金刚烷胺。iststradefylline显示运动障碍的几率较低(0.63；0.41, 0.99)和低血压(0.19；0.03, 0.82)与儿茶酚- o -甲基转移酶抑制剂（COMTi）相比，恶心的几率更低(0.58；0.33, 0.99)与多巴胺激动剂（DA）相比，低血压的几率更低(0.09；0.01, 0.52)对比单胺氧化酶- b抑制剂（MAO-Bi）。对2000年以来发表的随机对照试验的敏感性分析发现，与DA相比，司他替林减少了运动障碍和幻觉的几率。RWE是异质性的，但显示出司曲defylline的某些不良事件发生率较低，特别是运动障碍（与MAO-Bi相比）、嗜睡（与DA和COMTi相比）、周围水肿和幻觉（与金刚烷胺相比）和恶心（与所有比较物相比）。结论：rct和RWE表明，与其他PD辅助药物相比，istradefylline具有良好的安全性。

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引用次数: 0

Paroxysmal abdominalgia as a non-motor wearing off phenomenon in Parkinson’s disease. A case series and literature review 阵发性腹痛是帕金森病的一种非运动性磨损现象。个案系列及文献回顾

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100368

Abdalmalik Bin Khunayfir, Stewart A. Factor

Background

Paroxysmal abdominalgia (PxA) is an underrecognized, debilitating form of abdominal pain that manifests during wearing-off (WO) periods in Parkinson’s disease (PD). Despite its profound impact, PxA remains poorly described, complicating diagnosis and management.

Methods

We conducted a retrospective case series of patients with PD and recurrent abdominal pain linked to WO episodes. Demographic, clinical, and detailed pain data were extracted from records. Patients with alternative gastrointestinal (GI) causes were excluded. Data were analyzed descriptively and compared with existing literature.

Results

Five patients (3 males, mean disease duration 14.4 years) met inclusion criteria. PxA was characterized by severe abdominal pain—described as twisting, squeezing, or tightness—that consistently occurred during WO states and frequently led to emergency department visits and repeated GI evaluations which were unremarkable. Symptoms were often associated with anxiety and panic attacks. Standard analgesics and GI therapies were largely ineffective. Extra carbidopa/levodopa doses provided variable relief; apomorphine bolus injections and continuous subcutaneous foslevodopa/foscarbidopa infusion appeared to offer significant benefit in eligible patients. PxA symptoms aligned best with the nociplastic category of the PD Pain Classification System.

Conclusions

PxA is a severe, non-motor complication of PD that likely represents a form of nociplastic pain linked to dopaminergic fluctuations. Increased awareness is needed to reduce misdiagnosis and inappropriate interventions. Further research is required to elucidate underlying mechanisms and guide targeted therapy.

背景：阵发性腹痛（PxA）是帕金森病（PD）患者在磨耗期（WO）表现出的一种未被充分认识的、使人衰弱的腹痛形式。尽管其影响深远，但PxA仍然缺乏描述，使诊断和管理复杂化。方法：我们对PD和复发性腹痛与WO发作相关的患者进行了回顾性研究。从记录中提取人口学、临床和详细的疼痛数据。排除其他胃肠道（GI）原因的患者。对数据进行描述性分析，并与现有文献进行比较。结果5例患者（男性3例，平均病程14.4年）符合纳入标准。PxA的特征是严重的腹痛，描述为扭曲、挤压或紧绷，这在WO状态下一直发生，经常导致急诊室就诊和反复的GI评估，这些都是不显著的。症状通常与焦虑和恐慌发作有关。标准镇痛药和胃肠道治疗基本上无效。额外的卡比多巴/左旋多巴剂量提供不同程度的缓解；阿波啡大剂量注射和持续皮下foslevodopa/foscarbidopa输注在符合条件的患者中似乎提供了显著的益处。PxA症状与PD疼痛分类系统的致害性类别最一致。结论spxa是PD的一种严重的非运动并发症，可能代表了一种与多巴胺能波动相关的伤害性疼痛。需要提高认识，以减少误诊和不当干预。需要进一步的研究来阐明潜在的机制并指导靶向治疗。

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引用次数: 0