Clinical Parkinsonism Related Disorders最新文献_第9页

Retrospective database analysis on the demographics and resource utilization of patients with Parkinson’s disease in Quebec, Canada 加拿大魁北克省帕金森病患者人口统计学和资源利用的回顾性数据库分析

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100300

Véronique Baribeau , Shawn Mohammed , Amnah Awan , Diana Parison , Jean Lachaine

Introduction

Parkinson’s disease (PD) is the most prevalent neurodegenerative movement disorder. Despite its recognized significance, there remains a paucity of recent studies reporting treatment utilization and the economic impact of PD in a real-world setting, especially in Canada. This study aimed to analyze real-world treatment patterns and health care resource utilization (HCRU) of patients with PD in Quebec, Canada.

Methods

This was a retrospective observational study using data between 2010–2019 from the Régie de l’assurance maladie du Québec (RAMQ) databases. Patients with PD were compared to age- and sex-matched controls. Treatment adherence and persistence were measured over 24 months. All-cause and PD-related HCRU and costs were characterized on an annual basis.

Results

Overall, 303 PD patients and 909 age- and sex-matched controls were selected. Adherence rates were high (≥85 %) among all drug classes, but lower with dopamine agonists. Persistence to PD treatment declined over time, with nearly 50 % discontinuation rates at 24 months in all PD drug classes, except the levodopa class (discontinuation rate: 20.4 %). PD patients had a significantly higher total costs per year than the matched control group ($17,405 vs. $6,431), mainly driven by higher inpatient costs.

Conclusion

Many pharmacological options exist for PD patients and, though patients are adherent while on therapy, treatment discontinuation rates are high. This suggests potential long-term challenges in PD management, especially since PD continues to place a substantial burden on the health care system. This study underscores the need for enhanced therapeutic strategies, particularly for patients inadequately controlled with standard therapies.

帕金森病（PD）是最常见的神经退行性运动障碍。尽管其公认的重要性，但最近的研究仍然缺乏报道PD在现实世界中的治疗利用和经济影响，特别是在加拿大。本研究旨在分析加拿大魁北克省PD患者的现实治疗模式和卫生保健资源利用率（HCRU）。方法：本研究是一项回顾性观察性研究，使用了2010-2019年来自quamq数据库的数据。PD患者与年龄和性别匹配的对照组进行比较。治疗依从性和持久性超过24个月。全因和pd相关的HCRU和费用以年度为基础。结果共选择了303例PD患者和909例年龄和性别匹配的对照组。所有药物类别的依从率都很高（≥85%），但多巴胺激动剂的依从率较低。PD治疗的持久性随着时间的推移而下降，在所有PD药物类别中，24个月时停药率接近50%，除了左旋多巴类（停药率：20.4%）。PD患者每年的总费用明显高于对照组（17,405美元对6,431美元），主要是由于住院费用较高。结论PD患者有多种药物选择，虽然患者在治疗期间坚持治疗，但停药率很高。这表明帕金森病管理面临潜在的长期挑战，特别是因为帕金森病继续给卫生保健系统带来沉重的负担。这项研究强调了加强治疗策略的必要性，特别是对标准治疗控制不足的患者。

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引用次数: 0

An unusual presentation of Huntington’s disease-like syndrome in a patient with Xeroderma pigmentosum type F: Case report and review of the literature 色素性干皮病F型患者异常表现亨廷顿病样综合征：病例报告及文献回顾

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100340

Nicolas De Cleene , Federico Carbone , Clancy Cerejo , Marina Peball , Franco Stanzial , Francesco Benedicenti , Renate Lunzer , Klaus Seppi , Beatrice Heim

Background

Xeroderma pigmentosum (XP) is a rare genetic disease in which the Nucleotide Excision Repair (NER) system is affected, resulting in defective DNA-repair. Clinical features are UV-light hypersensitivity with erythema, corneal lesions, and increased risk for skin cancers. Around 20% of affected individuals develop neurological manifestations like movement disorders due to neurodegeneration.

Case

We report a 33-year-old man, presenting with mild choreatic movements of the lower face and limbs, executive dysfunction and mild atactic features. Dermatological changes were seen on sun-exposed skin. Brain MRI revealed global atrophy. Whole exome sequencing and familial segregation analysis revealed two compound heterozygous mutations in the ERCC4 gene, confirming XP-F diagnosis.

Literature review

An extensive literature review identified sixteen studies reporting patients with confirmed XP as well as chorea as extrapyramidal movement disorder in their clinical phenotype. The clinical phenotyping of these patients was carefully evaluated, listed and analysed. In addition, available genetic data was systematically collected and reviewed.

Conclusion

We describe an XP-patient with a Huntingtońs disease (HD)-like syndrome with discrete cerebellar ataxia. Through reviewing the literature, we identified a total of 41 XP-patients with chorea. Therefore, we suggest testing of NER genes in patients with a HD-like syndrome and negative genetic testing for HD, especially when dermatological changes and atactic features are present.

背景：着色性干皮病（XP）是一种罕见的遗传性疾病，其核苷酸切除修复（NER）系统受到影响，导致dna修复缺陷。临床特征为紫外线过敏伴红斑、角膜病变和皮肤癌风险增加。大约20%的患者会出现神经系统症状，如神经退行性变导致的运动障碍。我们报告一个33岁的男性，表现为轻度的下面部和肢体舞蹈运动，执行功能障碍和轻度的无动作特征。暴露在阳光下的皮肤可见皮肤学变化。脑部MRI显示全身萎缩。全外显子组测序和家族分离分析显示ERCC4基因有两个复合杂合突变，证实了XP-F的诊断。文献综述一项广泛的文献综述确定了16项研究报告了经证实的XP和舞蹈病合并锥体外系运动障碍患者的临床表型。这些患者的临床表型被仔细评估，列出和分析。此外，系统地收集和审查了现有的遗传数据。结论我们描述了一例xp患者与Huntingtońs疾病（HD）样综合征合并离散性小脑性共济失调。通过查阅文献，我们共发现41例xp患者合并舞蹈病。因此，我们建议对患有HD样综合征的患者进行NER基因检测，并对HD进行阴性基因检测，特别是当皮肤变化和无策略特征存在时。

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引用次数: 0

Opicapone improves end-of-dose neuropsychiatric fluctuations in patients with Parkinson’s disease

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100343

Roberta De Fiores , Iolanda Martino , Andrea Quattrone , Basilio Vescio , Gennarina Arabia , Antonio Gambardella , Maurizio Morelli

Introduction

Non-motor fluctuations (NMF) represent one of the main complications that patients with Parkinson’s disease (PD) may experience during long-term levodopa treatment. Opicapone (OPC), a COMT-inhibitor indicated for end-of-dose motor fluctuations (MF), has not been extensively investigated for the management of NMF. We evaluate the efficacy of OPC on end-of-dose neuropsychiatric fluctuations, the most frequent and severe NMF.

Methods

We assessed 15 PD patients who underwent treatment with OPC (PD-OPC) compared to a control group of 15 PD patients (PD-CTRL). All patients had end-of-dose MF and NMF, confirmed by 19-item Wearing-Off Questionnaire (WOQ-19). For each, we identified the first end-of-dose deterioration period through MDS-UPDRS-III administered every 30 min over two consecutive days. On the third day, a comprehensive clinical and neuropsychological battery was administered during this designated period. Subsequently, OPC was prescribed to PD-OPC. After 6 months, patients were re-evaluated using the same baseline assessments during the same end-of-dose period.

Results

At 6-month follow-up, PD-OPC showed significant improvement in the following tests: WOQ-19 (p < 0.001), total MDS-UPDRS and each of its four parts (p < 0.001), NMSS (p < 0.001), executive functions/attention (Weigl’s, p < 0.001; FAS, p < 0.001; FAB, p < 0.001; STROOP, p = 0.001) and mood related-symptoms (BDI-II, HAM-A; both p = 0.001). There was a slightly significant difference in Visual Search (p = 0.018), and no differences in RAVLT-I (p = 0.323), and RAVLT-D (p = 0.155) scores. At follow-up, PD-CTRL showed no significant differences in WOQ-19, motor scales, and neuropsychological tests compared to baseline.

Conclusion

OPC improved end-of-dose fluctuations in anxiety/depression, and executive functions/attention, while memory and visuospatial abilities showed little or no significant changes.

非运动波动（NMF）是帕金森病（PD）患者长期左旋多巴治疗期间可能出现的主要并发症之一。Opicapone (OPC)，一种用于治疗剂量末运动波动（MF）的comt抑制剂，尚未被广泛研究用于治疗NMF。我们评估了OPC对最常见和最严重的NMF的剂量末神经精神波动的疗效。方法我们评估了15例接受OPC治疗的PD患者（PD-OPC）与对照组15例PD患者（PD- ctrl）。所有患者均有剂量末MF和NMF，由19项磨损问卷（WOQ-19）证实。对于每一个，我们通过连续两天每30分钟给药的MDS-UPDRS-III确定了第一个剂量末恶化期。在第三天，在指定的时间内进行全面的临床和神经心理学测试。随后给PD-OPC开OPC。6个月后，在相同的给药结束期间，使用相同的基线评估对患者进行重新评估。结果随访6个月后，PD-OPC在以下各项指标均有显著改善：WOQ-19 (p <；0.001)，总MDS-UPDRS及其四个部分(p <；0.001), NMSS (p <；0.001)，执行功能/注意力(Weigl 's, p <；0.001;FAS, p <；0.001;FAB, p <；0.001;STROOP, p = 0.001)和情绪相关症状(BDI-II, HAM-A；p均= 0.001)。两组在视觉搜索（Visual Search）得分上差异有统计学意义（p = 0.018），在RAVLT-I （p = 0.323）和RAVLT-D （p = 0.155）得分上差异无统计学意义。随访时，PD-CTRL在WOQ-19、运动量表和神经心理测试方面与基线相比无显著差异。结论opc改善了焦虑/抑郁和执行功能/注意力的剂量末波动，而记忆和视觉空间能力的变化很少或没有显著变化。

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引用次数: 0

Can Parkinsonism be a solitary manifestation of Wilson’s Disease? 帕金森氏症是威尔逊病的单独表现吗？

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100402

Mehri Salari , Fatemeh Hojjatipour , Kamran Rezaei , Masoud Etemadifar

Wilson’s disease (WD) is a secondary parkinsonian condition that results in multi-organ dysfunction. Accurately diagnosing this disorder as soon as possible is crucial since it is a treatable condition. In order to diagnose WD, a doctor must be aware of the disorder’s early signs and request the following diagnostic tests. These include serum ceruloplasmin levels, 24-hour urinary copper excretion, slit-lamp examination for Kayser-Fleischer rings, liver biopsy, and ATP7B genetic testing when needed. It is mentioned that WD can present with a wide range of manifestations; however, according to our observations of thoroughly analyzing cases and papers concerning WD patients, we conclude that parkinsonism cannot be the only early symptom of WD. Most patients who developed parkinsonian symptoms also showed accompanying features such as dysarthria, dystonia, or behavioral changes. This finding would assist doctors in rolling out WD diagnosis and focusing on other potential diseases. By avoiding unnecessary investigations for WD in cases of isolated, typical parkinsonism, physicians can more effectively allocate resources and explore other more probable differential diagnoses. This situation allows for earlier initiation of appropriate therapy tailored to the correct underlying condition, and the overall financial burden on individuals and health systems would be lessened. Such an approach would also help reduce patient anxiety caused by uncertainty.

威尔逊病（WD）是一种继发性帕金森病，导致多器官功能障碍。尽快准确诊断这种疾病是至关重要的，因为它是一种可治疗的疾病。为了诊断WD，医生必须了解疾病的早期症状，并要求进行以下诊断测试。这些检查包括血清铜蓝蛋白水平、24小时尿铜排泄、开泽-弗莱舍环的裂隙灯检查、肝活检以及必要时的ATP7B基因检测。文中提到，WD可以表现为广泛的表现；然而，根据我们对有关WD患者的病例和论文的深入分析，我们得出结论，帕金森病不可能是WD的唯一早期症状。大多数出现帕金森症状的患者还伴有构音障碍、肌张力障碍或行为改变等特征。这一发现将有助于医生推广WD诊断并关注其他潜在疾病。通过避免在孤立的典型帕金森病例中对WD进行不必要的检查，医生可以更有效地分配资源并探索其他更可能的鉴别诊断。这种情况允许更早地开始针对正确的潜在疾病的适当治疗，并减轻个人和卫生系统的总体经济负担。这种方法也有助于减少病人因不确定性而产生的焦虑。

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引用次数: 0

Effects of the continuous subcutaneous infusion of foslevodopa-foscarbidopa on swallowing in patients with Parkinson’s disease 持续皮下输注foslevodopa-foscarbidopa对帕金森病患者吞咽的影响

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100378

Makito Hirano , Makoto Samukawa , Chiharu Isono , Rino Inada , Yuta Fukumoto , Keisuke Yoshikawa , Hitoshi Namura , Hanami Sakata , Takahiro Hisatomi , Toru Michiura , Hiroto Nakamura , Akira Morita , Genki Hoshino , Kensuke Yamana , Atsushi Terayama , Yuji Higashimoto , Yoshiyuki Mitsui , Yoshitaka Nagai

Background

Dysphagia is a potentially fatal symptom of Parkinson’s disease (PD) and is characterized by frequent silent aspiration, a known risk factor for aspiration pneumonia. A previous study has reported that the dopamine agonist rotigotine (levodopa equivalent dose of 60 mg/day) delivered via transdermal patch improves swallowing function more effectively than oral levodopa (200 mg/day), highlighting the importance of continuous dopaminergic stimulation (CDS) in managing dysphagia. To achieve CDS, patients with advanced PD may require device-assisted therapies (DATs), including levodopa–carbidopa intestinal gel (LCIG), which have significantly improved swallowing function on some measures. In contrast, swallowing function is an important prognostic factor for patients with PD undergoing LCIG. Continuous subcutaneous infusion of foslevodopa/foscarbidopa (CSCI-FF) is a newly developed DAT; however, its effect on swallowing function remains unknown.

Methods

This retrospective open-label evaluator-blinded study included seven patients with PD. Swallowing function was assessed using videofluoroscopic swallow studies (VFSS) conducted before and after initiating CSCI-FF. Evaluations included the Japanese Swallowing Scale, the Dysphagia Outcome and Severity Scale (DOSS), Penetration/Aspiration Scale, oral transit time (OTT), and pharyngeal transit time (PTT).

Results

Following the introduction of CSCI-FF, results of VFSS showed significant improvement in the total score of the Japanese swallowing scale, OTT, and PTT.

Conclusions

This study provides preliminary evidence that CSCI-FF may partially improve swallowing function in patients with advanced PD. Further research with larger cohorts is warranted.

背景：吞咽困难是帕金森病（PD）的一种潜在致命症状，其特征是频繁的无声吸入性，这是吸入性肺炎的已知危险因素。先前的一项研究报道，多巴胺激动剂罗替戈汀（左旋多巴等效剂量为60 mg/天）经透皮贴剂比口服左旋多巴（200 mg/天）更有效地改善吞咽功能，强调了持续多巴胺能刺激（CDS）在治疗吞咽困难中的重要性。为了实现CDS，晚期PD患者可能需要器械辅助治疗（dat），包括左旋多巴-卡比多巴肠凝胶（LCIG），在某些指标上可显著改善吞咽功能。相比之下，吞咽功能是PD患者行LCIG的重要预后因素。连续皮下输注foslevodopa/foscarbidopa （CSCI-FF）是一种新开发的DAT；然而，其对吞咽功能的影响尚不清楚。方法回顾性、开放标签评估盲法研究纳入7例PD患者。在启动CSCI-FF之前和之后，通过视频透视吞咽研究（VFSS）评估吞咽功能。评估包括日本吞咽量表、吞咽困难结局和严重程度量表（DOSS）、渗透/吸入量表、口腔传递时间（OTT）和咽部传递时间（PTT）。结果引入CSCI-FF后，VFSS的日语吞咽量表、OTT、PTT总分均有显著改善。结论本研究提供了CSCI-FF可部分改善晚期PD患者吞咽功能的初步证据。进一步的研究更大的队列是有必要的。

{"title":"Effects of the continuous subcutaneous infusion of foslevodopa-foscarbidopa on swallowing in patients with Parkinson’s disease","authors":"Makito Hirano , Makoto Samukawa , Chiharu Isono , Rino Inada , Yuta Fukumoto , Keisuke Yoshikawa , Hitoshi Namura , Hanami Sakata , Takahiro Hisatomi , Toru Michiura , Hiroto Nakamura , Akira Morita , Genki Hoshino , Kensuke Yamana , Atsushi Terayama , Yuji Higashimoto , Yoshiyuki Mitsui , Yoshitaka Nagai","doi":"10.1016/j.prdoa.2025.100378","DOIUrl":"10.1016/j.prdoa.2025.100378","url":null,"abstract":"<div><h3>Background</h3><div>Dysphagia is a potentially fatal symptom of Parkinson’s disease (PD) and is characterized by frequent silent aspiration, a known risk factor for aspiration pneumonia. A previous study has reported that the dopamine agonist rotigotine (levodopa equivalent dose of 60 mg/day) delivered via transdermal patch improves swallowing function more effectively than oral levodopa (200 mg/day), highlighting the importance of continuous dopaminergic stimulation (CDS) in managing dysphagia. To achieve CDS, patients with advanced PD may require device-assisted therapies (DATs), including levodopa–carbidopa intestinal gel (LCIG), which have significantly improved swallowing function on some measures. In contrast, swallowing function is an important prognostic factor for patients with PD undergoing LCIG. Continuous subcutaneous infusion of foslevodopa/foscarbidopa (CSCI-FF) is a newly developed DAT; however, its effect on swallowing function remains unknown.</div></div><div><h3>Methods</h3><div>This retrospective open-label evaluator-blinded study included seven patients with PD. Swallowing function was assessed using videofluoroscopic swallow studies (VFSS) conducted before and after initiating CSCI-FF. Evaluations included the Japanese Swallowing Scale, the Dysphagia Outcome and Severity Scale (DOSS), Penetration/Aspiration Scale, oral transit time (OTT), and pharyngeal transit time (PTT).</div></div><div><h3>Results</h3><div>Following the introduction of CSCI-FF, results of VFSS showed significant improvement in the total score of the Japanese swallowing scale, OTT, and PTT.</div></div><div><h3>Conclusions</h3><div>This study provides preliminary evidence that CSCI-FF may partially improve swallowing function in patients with advanced PD. Further research with larger cohorts is warranted.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"13 ","pages":"Article 100378"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738776","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

Dystonic tremor in Writer’s cramp Mimicking primary handwriting tremor 书写痉挛中的肌张力异常震颤，模仿原发性书写震颤

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100410

Paulo Cataniag , Cezar Thomas Suratos , Cid Czarina Diesta , Jed Noel Ong

Introduction

Writer’s cramp is a task-specific focal dystonia with peculiarity of occurring only during handwriting. The presence of abnormal posturing and dystonic tremor may exhibit distinctive patterns across individuals, and may closely resemble primary writing tremor, especially when dystonic postures are mild.

Case description

We present a 48-year-old right-handed Filipino businessman who developed a gradually worsening right-hand tremor confined to handwriting over one year, stabilizing after six months. Neurological examination was otherwise normal, but writing tests revealed dystonic wrist extension and shoulder abduction, along with wrist rotational/pronation-supination dystonic tremor during writing. Wavy/oscillating drawing patterns were observed. Diagnosis of writer’s cramp was made, which mimicked primary writing tremor due to overlapping features. Multiple oral medications were ineffective, but ultrasound-guided botulinum toxin injections led to clinical improvements, with better handwriting during faster writing and worse at slower speeds.

Conclusion

This case underscores the complexity of diagnosing and treating task-specific dystonia with tremor. Incorporating tests like line-drawing at different speeds, including vertical and diagonal lines, can enhance evaluation.

作家痉挛是一种任务特异性局灶性肌张力障碍，其特点仅发生在书写过程中。异常体位和肌张力异常震颤可能在个体中表现出不同的模式，并且可能与原发性书写震颤非常相似，特别是当肌张力异常姿势轻微时。病例描述我们报告一位48岁的右利手菲律宾商人，他在一年多的时间里出现了逐渐恶化的右手震颤，局限于书写，六个月后稳定下来。神经学检查其他方面正常，但书写测试显示手腕伸展和肩部外展肌张力障碍，以及书写时手腕旋转/旋前-旋后肌张力障碍震颤。观察到波浪状/振荡的拉丝图案。作者痉挛的诊断，模仿原发书写震颤，由于重叠的特征。多种口服药物无效，但超声引导下的肉毒杆菌毒素注射导致临床改善，书写速度快时字迹更好，书写速度慢时字迹更差。结论本病例强调了任务特异性肌张力障碍伴震颤的诊断和治疗的复杂性。结合不同速度的画线测试，包括垂直线和对角线，可以提高评估。

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引用次数: 0

Effects of dopaminergic medication on upper limb motor function, strength and hand dexterity in people with Parkinson’s disease 多巴胺能药物对帕金森病患者上肢运动功能、力量和手灵活性的影响

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100400

Parisa Alaei , Daryl J. Wile , Jennifer M. Jakobi

Background

Dopaminergic medications improve motor symptoms and hand dexterity in people with Parkinson’s disease (PD). The contribution of altered muscle contractile properties to these functional improvements are not well understood.

Objective

To compare the treated (ON) and untreated (OFF) states in people with PD to examine effects of dopaminergic medication on hand dexterity, motor symptom severity, muscle twitch properties and maximal voluntary contraction (MVC).

Methods

Sixteen individuals with PD (mean disease duration 6.4 years) completed two sessions: one ON and one OFF dopaminergic medication. Measures included motor symptom severity (MDS-UPDRS III), Grooved Pegboard Test (GPT) time, Purdue Pegboard Test (PPT) peg count, elbow flexion MVC, voluntary activation, and electrically induced twitch properties.

Results

MDS-UPDRS III subscores improved by 27 % ON dopaminergic medication compared to OFF medication, and performance improved on GPT (11 %) and PPT (34 %; p < 0.05). Comparing ON and OFF states, electrically induced contractile properties did not differ, while voluntary elbow flexor MVC increased by 4 %. Normalized MVC was moderately associated with GPT and PPT performance in both ON (GPT: r = –0.48, PPT: r = 0.48) and OFF (GPT: r = –0.61, PPT: r = 0.45) states. Motor symptom severity in the OFF state showed moderate correlations with GPT (r = 0.48) and PPT (r = -0.58), but these associations were not significant in the ON phase (p > 0.05).

Conclusion

Dopaminergic treatment improved motor symptoms, hand dexterity, and strength, without altering electrically induced contractile properties. Improved hand dexterity during treatment appears to be linked to strength gains independent of peripheral muscle changes.

多巴胺能药物可改善帕金森病患者的运动症状和手的灵活性。肌肉收缩特性的改变对这些功能改善的贡献尚不清楚。目的比较PD患者治疗状态（ON）和未治疗状态（OFF），探讨多巴胺能药物对手部灵巧性、运动症状严重程度、肌肉抽搐特性和最大自主收缩（MVC）的影响。方法16例PD患者（平均病程6.4年）完成两次多巴胺能药物治疗：一次开，一次关。测量包括运动症状严重程度（MDS-UPDRS III）、凹槽钉板测试（GPT）时间、普渡钉板测试（PPT）钉数、肘关节屈曲MVC、自主激活和电诱发抽搐特性。结果与关闭多巴胺能药物治疗组相比，使用多巴胺能药物治疗组smds - updrs III评分提高27%，使用多巴胺能药物治疗组GPT（11%）和PPT（34%）评分提高；p < 0.05。比较开状态和关状态，电诱导的收缩特性没有差异，而自愿肘关节屈肌MVC增加了4%。在ON （GPT: r = -0.48, PPT: r = 0.48）和OFF （GPT: r = -0.61, PPT: r = 0.45）状态下，规范化MVC与GPT和PPT表现均有中度相关。OFF状态下运动症状严重程度与GPT （r = 0.48）和PPT （r = -0.58）有中度相关性，但在ON期这些相关性不显著（p > 0.05）。结论多巴胺能改善运动症状、手的灵活性和力量，但不改变电致收缩特性。治疗期间手部灵巧性的改善似乎与外周肌肉变化无关的力量增加有关。

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引用次数: 0

Mesocorticolimbic dopaminergic innervation modulates Levodopa-related improvements in gait in older slow walking Adults: A [11C]PE2I PET study 中皮质边缘多巴胺能神经支配调节老年慢行成人左旋多巴相关的步态改善：一项PE2I PET研究

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100353

N. Paalanen , S. Roytman , M. van Emde Boas , A. Biddix , A. Luker , F. Michalakis , G. Carli , P. Kanel , C. Pongmala , R. Koeppe , L.M. Chahine , C. Rosano , N.I. Bohnen

Purpose

Slow walking in healthy older adults may result from multifactorial deficits involving the muscular, peripheral, and central nervous systems. While mobility depends on these systems, the brain’s neuromodulatory capacity may offer insights for interventions. This open-label imaging study tested whether the dopaminergic system serves as a resilience mechanism for gait in the elderly. Using [¹¹C]PE2I dopamine transporter (DAT) PET, we assessed whether baseline dopaminergic innervation modulates the response to a one-week carbidopa-levodopa regimen in slow-walking older adults without Parkinson’s disease (PD).

Methods

Slow walking older adults without clinical evidence of PD (n = 9) were pre-treated with carbidopa 25 mg one tablet TID for three days, followed by carbidopa-levodopa 25/100 mg starting at one tablet TID for three days and then increased to 1.5 tablets of carbidopa-levodopa 25/100 mg TID daily for four days, as tolerated. [¹¹C]PE2I DAT PET imaging was completed at baseline. Spatiotemporal gait parameters were evaluated at pre-intervention, following carbidopa pre-treatment, and post-intervention.

Results

Levodopa treatment resulted in improved gait speed (β = 0.69 [0.07, 1.30], p = 0.031), double-support time (β = -0.26 [-0.51, −0.01], p = 0.041), and cadence (β = 0.54 [0.18, 0.89], p = 0.005), but not in turn duration (β = 0.41 [-0.33, 1.14], p = 0.264). These changes were strongly predicted by pre-treatment limbic, subcortical, and neocortical DAT PET uptake, with greater improvements in gait pace observed among individuals with lower DAT availability.

Conclusion

These preliminary findings suggest that the mesocorticolimbic dopaminergic system may be the substrate of a resilience mechanism that can be targeted to manage gait impairments in older adults.

目的：健康老年人行走缓慢可能是由涉及肌肉、外周和中枢神经系统的多因素缺陷所致。虽然活动能力取决于这些系统，但大脑的神经调节能力可能为干预提供见解。这项开放标签成像研究测试了多巴胺能系统是否作为老年人步态的恢复机制。使用[11C]PE2I多巴胺转运体（DAT） PET，我们评估了基线多巴胺能神经支配是否调节无帕金森病（PD）慢行老年人对一周卡比多巴-左旋多巴方案的反应。方法对无PD临床证据的慢行老年人（n = 9）进行卡比多巴25 mg /片剂TID预处理，连续3天，随后加用卡比多巴-左旋多巴25/100 mg /片剂TID，开始剂量为1片，连续3天，然后根据耐受性增加到卡比多巴-左旋多巴25/100 mg /片剂TID，每日1.5片，连续4天。[11C]基线时完成PE2I DAT PET成像。在干预前、卡比多巴预处理后和干预后对时空步态参数进行评估。结果多巴治疗改善了步态速度（β = 0.69 [0.07, 1.30], p = 0.031）、双支撑时间（β = -0.26 [-0.51, - 0.01], p = 0.041）和步频（β = 0.54 [0.18, 0.89], p = 0.005），但对持续时间（β = 0.41 [-0.33, 1.14], p = 0.264）无显著影响。这些变化可以通过治疗前边缘、皮质下和新皮质的DAT PET摄取来预测，在低DAT可用性的个体中观察到更大的步态改善。结论这些初步研究结果表明，中皮质边缘多巴胺能系统可能是恢复机制的基础，可以有针对性地管理老年人步态障碍。

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引用次数: 0

Precision medicine and music therapy for Parkinson’s Disease 帕金森氏症的精准医学和音乐疗法

IF 1.8 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100382

Peng Li-Hua , Lamarana Jallow , Yurong Tan , Ousman Bajinka

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder requiring multidimensional treatment approaches. Recent breakthroughs in precision medicine and growing evidence for music therapy efficacy present new opportunities for comprehensive PD management that addresses both biological mechanisms and quality of life outcomes Objectives: This mini review evaluates the current state of precision medicine and music therapy interventions for PD, with three primary aims: (1) to synthesize evidence for genetic-based treatments and music-based interventions, (2) to identify potential synergies between these approaches, and (3) to highlight critical implementation challenges in clinical practice. Finding: Our analysis revealed that precision medicine approaches, including GBA1-targeted venglustat and LRRK2 kinase inhibitors, show significant promise in clinical trials when guided by genetic profiling. Concurrently, music therapy demonstrates robust clinical benefits, with RAS producing 15–20% improvements in gait parameters and group singing programs enhancing both speech function and psychosocial wellbeing. Emerging technologies, particularly wearable sensors and adaptive AI platforms, are enhancing the precision and personalization of both treatment modalities. However, we identified persistent challenges including the need for standardized biomarkers in precision medicine and more rigorous clinical validation for music therapy protocols. Conclusions: The strategic integration of precision medicine and music therapy offers a novel, patient-centered framework for PD management that simultaneously targets pathological mechanisms and functional outcomes. Future implementation should focus on overcoming accessibility barriers, conducting large-scale longitudinal studies, and developing integrated treatment protocols that combine genetic insights with personalized neuromodulation approaches.

背景：帕金森病（PD）是一种复杂的神经退行性疾病，需要多方面的治疗方法。精准医学的最新突破和越来越多的证据表明音乐疗法的疗效为全面的PD治疗提供了新的机会，既解决了生物学机制，又解决了生活质量问题。目的：本综述评估了精准医学和音乐疗法干预PD的现状，主要有三个目的：(1)综合基于基因的治疗和基于音乐的干预的证据；(2)确定这些方法之间潜在的协同作用；(3)强调临床实践中关键的实施挑战。研究发现：我们的分析显示，精确医学方法，包括gba1靶向venglustat和LRRK2激酶抑制剂，在基因谱的指导下，在临床试验中显示出显著的前景。同时，音乐疗法显示出强大的临床效益，RAS能使步态参数改善15-20%，团体唱歌项目能增强语言功能和心理健康。新兴技术，特别是可穿戴传感器和自适应人工智能平台，正在提高这两种治疗方式的精确度和个性化。然而，我们发现了持续存在的挑战，包括对精准医学中标准化生物标志物的需求，以及对音乐治疗方案更严格的临床验证。结论：精准医学和音乐治疗的战略整合为PD治疗提供了一种新的、以患者为中心的框架，同时针对病理机制和功能结果。未来的实施应侧重于克服无障碍障碍，进行大规模的纵向研究，并制定综合治疗方案，将遗传见解与个性化神经调节方法相结合。

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引用次数: 0

How to treat orthostatic tremor – Cohort study and systematic review 如何治疗直立性震颤——队列研究和系统评价

IF 1.9 Q3 CLINICAL NEUROLOGY

Clinical Parkinsonism Related Disorders

Pub Date : 2025-01-01 DOI: 10.1016/j.prdoa.2025.100318

W.A. Babeliowsky , M.A. Meulepas , A.W.G. Buijink , R.M.A. de Bie , A.F. van Rootselaar

Introduction

Orthostatic tremor (OT) is a highly disabling condition. Effectiveness of treatments is largely unverified and no treatment guideline exists. The objective of this study is to evaluate the efficacy and adverse effects of treatments used for OT.

Methods

Patients from our online OT-registry were compared to findings from a systematic search in PUBMED. The search included original articles describing clinical features in human primary OT (electromyography peak frequency ≥ 13 Hz), in English or Dutch, and published after 1985. Outcome measures were prescribed treatments and their efficacy (percentage of patients per treatment with a reduction of tremor symptoms) and adverse effects.

Results

A total of 78 primary OT patients in the Netherlands and 613 OT patients from 74 articles, mostly case reports and cohort studies, were included. In the cohort from the Netherlands, perampanel showed both the highest efficacy and adverse effects. In the literature, clonazepam showed the highest efficacy, while data on adverse effects was lacking. Overall, pharmacological treatments were reported often to be insufficient. Bilateral deep brain stimulation (DBS) was reported to be effective in the majority of patients, without a higher prevalence of adverse effects.

Conclusion

Pharmacological treatment is sufficient in some patients, although overall efficacy is limited and often accompanied by adverse effects. Perampanel and clonazepam are first choice treatments. Surgical interventions seem suitable alternatives for medication resistant patients, although this is based on small studies. Future studies should use diagnostic criteria, standardized outcome scales and good study designs, to increase reliability of findings and comparability.

直立性震颤（OT）是一种高度致残的疾病。治疗的有效性在很大程度上未经证实，也没有治疗指南。本研究的目的是评估治疗OT的疗效和不良反应。方法将我们在线ot注册的患者与PUBMED系统搜索的结果进行比较。检索包括1985年以后发表的英文或荷兰文的描述人类原发性OT临床特征（肌电峰值频率≥13 Hz）的原始文章。结果测量是处方治疗及其疗效（每次治疗减少震颤症状的患者百分比）和不良反应。结果共纳入荷兰78例原发性OT患者和来自74篇文章（主要是病例报告和队列研究）的613例OT患者。在来自荷兰的队列中，perampanel显示出最高的疗效和不良反应。文献中氯硝西泮的疗效最高，但缺乏不良反应的数据。总的来说，据报道药物治疗往往是不够的。据报道，双侧深部脑刺激（DBS）对大多数患者有效，没有较高的不良反应发生率。结论部分患者的药物治疗是充分的，但总体疗效有限，并常伴有不良反应。Perampanel和氯硝西泮是首选治疗方法。手术干预似乎是耐药患者的合适选择，尽管这是基于小型研究。未来的研究应使用诊断标准、标准化的结果量表和良好的研究设计，以增加研究结果的可靠性和可比性。

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引用次数: 0