Movement Disorders最新文献

{"title":"Self-Reported Motor and Nonmotor Symptoms, Prodromal Parkinson's Disease Probability, and Incident Parkinson's Disease in US Farmers.","authors":"Shengfang Song, Zhehui Luo, Brenda L Plassman, Xuemei Huang, Yaqun Yuan, Srishti Shrestha, Christine G Parks, Jonathan N Hofmann, Laura E Beane Freeman, Dale P Sandler, Honglei Chen","doi":"10.1002/mds.30149","DOIUrl":"https://doi.org/10.1002/mds.30149","url":null,"abstract":"<p><strong>Background: </strong>Few studies have assessed motor and nonmotor symptoms and the prodromal probability of Parkinson's disease (PD) among farming populations.</p><p><strong>Objective: </strong>The aim was to assess self-reported nonmotor and motor symptoms and the prodromal PD probability in relation to incident PD among US farmers.</p><p><strong>Methods: </strong>The study included 16,059 farmers (aged 65.6 ± 10.8 years) from the Agricultural Health Study, with a median of 6.2 years of follow-up. We assessed associations using multivariable logistic regression and presented odds ratios (OR) and 95% confidence intervals (CI).</p><p><strong>Results: </strong>At baseline, the prevalence of individual symptoms ranged from 2.0% for arm/leg tremor to 21.1% for excessive daytime sleepiness. We identified 127 incident PD patients during follow-up. Except for depression, all symptoms were significantly associated with future PD diagnosis, with OR (95% CI) ranging from 1.6 (1.1-2.2) for excessive daytime sleepiness to 3.9 (2.3-6.8) for arm/leg tremor. The prodromal PD probability, calculated based on limited available self-reported prodromal and PD risk markers, was low. Using the Movement Disorder Society's prodromal PD criteria, the median (interquartile range) at baseline was 4.4% (7.2%) for incident PD patients and 2.3% (3.4%) for participants free of PD. Further, it exhibited low sensitivity and positive predictive value in identifying incident PD patients in this farming population.</p><p><strong>Conclusions: </strong>Self-reported prodromal PD symptoms were relatively common in US farmers. They were associated with incident PD diagnosis but had limited values in predicting disease risk. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TBP Repeat Expansion Analysis in Patients Carrying Heterozygous STUB1 Variants.","authors":"Jonathan De Winter, Liedewei Van de Vondel, Kristof Van Schil, Tine Deconinck, Katrien Storm, Karine Geens, Charlotte Sommeling, David Crosiers, Emke Marechal, Willem De Ridder, Peter De Jonghe, Jonathan Baets","doi":"10.1002/mds.30147","DOIUrl":"https://doi.org/10.1002/mds.30147","url":null,"abstract":"<p><strong>Background: </strong>The cooccurrence of intermediate (40-49 CAG/CAA) TBP repeat expansions with STUB1 variants questions the pathogenicity of monoallelic STUB1 variants in cerebellar ataxia.</p><p><strong>Objective: </strong>The objective of this study was to describe the phenotypic spectrum of heterozygous STUB1 variants with or without intermediate TBP repeat expansions.</p><p><strong>Methods: </strong>We determined the presence of TBP repeat expansions and STUB1 variants in six families with cerebellar ataxia.</p><p><strong>Results: </strong>Cooccurrence of both genotypes in one family resulted in cerebellar ataxia, involving cognitive and extrapyramidal complications. Variable degrees of cerebellar ataxia and cognitive impairment were found in four families carrying a heterozygous STUB1 variant and normal TBP alleles. Finally, we report one patient with a mild late-onset cerebellar ataxia carrying an intermediate expanded TBP allele without the presence of a STUB1 variant.</p><p><strong>Conclusions: </strong>Heterozygous STUB1 variants are associated with a milder phenotype and reduced penetrance compared with the cosegregation with intermediate TBP alleles, which causes a fully penetrant complicated form of cerebellar ataxia. © 2025 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Effects of Substantia Nigra and Locus Coeruleus Degeneration on Cognition in Parkinson's Disease.","authors":"Sophie Sun, Victoria Madge, Jelena Djordjevic, Jean-François Gagnon, D Louis Collins, Alain Dagher, Madeleine Sharp","doi":"10.1002/mds.30148","DOIUrl":"https://doi.org/10.1002/mds.30148","url":null,"abstract":"<p><strong>Background: </strong>The substantia nigra (SN) and locus coeruleus (LC) are among the first brain regions to degenerate in Parkinson's disease (PD). This has important implications for early cognitive deficits because these nuclei are sources of ascending neuromodulators (i.e., dopamine and noradrenaline) that support various cognitive functions such as learning, memory, and executive function.</p><p><strong>Objective: </strong>Our aim was to investigate the selective and independent contributions of SN and LC degeneration to cognitive deficits in PD.</p><p><strong>Methods: </strong>We ran a cross-sectional study testing patients with PD and older adults on tasks of positive reinforcement learning, attention/working memory, executive function, and memory to measure cognitive performance in domains thought to be related to dopaminergic and noradrenergic function. Participants also underwent neuromelanin-sensitive magnetic resonance imaging as a measure of degeneration.</p><p><strong>Results: </strong>Reduced SN neuromelanin signal in PD was independently associated with impaired positive reinforcement learning (β = 0.41, 95% confidence interval [CI]: 0.08, 0.74) controlling for changes in the LC. In contrast, reduced LC neuromelanin signal was independently associated with impairments in attention/working memory (β = 0.20, 95% CI [-0.47, -0.10]) and executive function (β = 0.22, 95% CI: -0.57, -0.24), controlling for changes in the SN.</p><p><strong>Conclusions: </strong>These results suggest that SN and LC degeneration may contribute to different cognitive deficits, potentially explaining the heterogeneity that exists in the cognitive manifestations of PD. These results also highlight the potential value of leveraging brain-behavior relationships to develop performance-based measures of cognition that could be used to characterize the phenotypic differences associated with underlying patterns of neurodegeneration. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Memoriam C. Warren Olanow (1941-2024).","authors":"Victor S C Fung, Kailash Bhatia, David J Burn, Christopher G Goetz, Mark Hallett, Joseph Jankovic, Karl Kieburtz, Christine Klein, Jeffrey H Kordower, Anthony E Lang, Marcelo Merello, Matthew B Stern, A Jon Stoessl, Philip D Thompson","doi":"10.1002/mds.30138","DOIUrl":"https://doi.org/10.1002/mds.30138","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143404910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Classification and Genotype-Phenotype Relationships of GBA1 Variants: MDSGene Systematic Review.","authors":"Malco Rossi, Susen Schaake, Tatiana Usnich, Josephine Boehm, Nina Steffen, Nathalie Schell, Clara Krüger, Tuğçe Gül-Demirkale, Natascha Bahr, Teresa Kleinz, Harutyun Madoev, Björn-Hergen Laabs, Ziv Gan-Or, Roy N Alcalay, Katja Lohmann, Christine Klein","doi":"10.1002/mds.30141","DOIUrl":"https://doi.org/10.1002/mds.30141","url":null,"abstract":"<p><p>Depending on zygosity and the specific change, different variants in the GBA1 gene can cause Parkinson's disease (PD, PARK-GBA1) with reduced penetrance, act as genetic risk factors for PD or parkinsonism, and/or lead to Gaucher's disease (GD). This MDSGene systematic literature review covers 27,963 patients carrying GBA1 variants from 1082 publications with 794 variants, including 13,342 patients with PD or other forms of parkinsonism. It provides a comprehensive overview of demographic, clinical, and genetic findings from an ethnically diverse sample originating from 82 countries across five continents. The most frequent pathogenic or likely pathogenic variants were \"N409S\" (aka \"N370S\"; dominating among Jewish and Whites), and \"L483P\" (aka \"L444P\"; dominating among Asians and Hispanics), whereas the most common coding risk variants were \"E365K\" (E326K), and \"T408M\" (T369M) (both common among Whites). A novel finding is that early-onset PD patients were predominantly of Asian ethnicity, whereas late-onset PD patients were mainly of White ethnicity. Motor cardinal features were similar between PD patients and other forms of parkinsonism, whereas motor complications and non-motor symptoms were more frequently reported in PD patients carrying \"severe\" variants than in those with \"risk\" or \"mild\" variants. Cognitive decline was reported in most patients after surgical treatment, despite achieving a beneficial motor function response. Most GD patients developing PD harbored the \"N409S\" variant, were of Ashkenazi Jewish ethnicity, and showed a positive response to chronic levodopa treatment. With this review, we start to fill the gaps regarding genotype-phenotype correlations in GBA1 variant carriers, especially concerning PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pattern and Stages of Atrophy in Spinocerebellar Ataxia Type 2: Volumetrics from ENIGMA-Ataxia.","authors":"Jason W Robertson, Isaac Adanyeguh, Benjamin Bender, Sylvia Boesch, Arturo Brunetti, Sirio Cocozza, Léo Coutinho, Andreas Deistung, Stefano Diciotti, Imis Dogan, Alexandra Durr, Juan Fernandez-Ruiz, Sophia L Göricke, Marina Grisoli, Shuo Han, Caterina Mariotti, Chiara Marzi, Mario Mascalchi, Fanny Mochel, Wolfgang Nachbauer, Lorenzo Nanetti, Anna Nigri, Sergio E Ono, Chiadi U Onyike, Jerry L Prince, Kathrin Reetz, Sandro Romanzetti, Francesco Saccà, Matthis Synofzik, Hélio A Ghizoni Teive, Sophia I Thomopoulos, Paul M Thompson, Dagmar Timmann, Sarah H Ying, Ian H Harding, Carlos R Hernandez-Castillo","doi":"10.1002/mds.30143","DOIUrl":"https://doi.org/10.1002/mds.30143","url":null,"abstract":"<p><strong>Background: </strong>Spinocerebellar ataxia type 2 (SCA2) is a rare, inherited neurodegenerative disease characterized by progressive deterioration in both motor coordination and cognitive function. Atrophy of the cerebellum, brainstem, and spinal cord are core features of SCA2; however, the evolution and pattern of whole-brain atrophy in SCA2 remain unclear.</p><p><strong>Objective: </strong>We undertook a multisite, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.</p><p><strong>Methods: </strong>Voxel-based morphometry analyses of 110 participants with SCA2 and 128 controls were undertaken to assess groupwise differences in whole-brain volume. Correlations with clinical severity and genotype, and cross-sectional profiling of atrophy patterns at different disease stages, were also performed.</p><p><strong>Results: </strong>Atrophy in SCA2 versus controls was greatest (Cohen's d >2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects (d >1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In the cerebellar gray matter (GM), large effects (d >0.8) were observed in areas related to both motor coordination and cognitive tasks. Strong correlations (|r| > 0.4) between volume and disease severity largely mirrored these groupwise outcomes. Stratification by disease severity exhibited a degeneration pattern beginning in the cerebellar and pontine WM in preclinical subjects; spreading to the cerebellar GM and cerebro-cerebellar/corticospinal WM tracts; and then finally involving the thalamus, striatum, and cortex in severe stages.</p><p><strong>Conclusion: </strong>The magnitude and pattern of brain atrophy evolve over the course of SCA2, with widespread, nonuniform involvement across the brainstem, cerebellar tracts, and cerebellar cortex; and late involvement of the cerebral cortex and striatum. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vivo Positron Emission Tomography Imaging of α-Synuclein: A Major Breakthrough.","authors":"Sirine Hassen, Véronique Sgambato","doi":"10.1002/mds.30139","DOIUrl":"https://doi.org/10.1002/mds.30139","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143381407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement Disorders after Dengue Virus Infection: A Scoping Review","authors":"Elena Cecilia Rosca, Divyani Garg, Santiago Perez‐Lloret, Norlinah Mohamed Ibrahim, Onanong Phokaewvarangkul, Jirada Sringean, Vikram Holla, Ravi Yadav, Soaham Desai, Pramod Kumar Pal","doi":"10.1002/mds.30142","DOIUrl":"https://doi.org/10.1002/mds.30142","url":null,"abstract":"Movement disorders after dengue virus (DENV) infection have been increasingly recognized. We aimed to synthesize the clinical and paraclinical characteristics, treatment responses, and outcomes of these neurologic complications. We systematically reviewed PubMed, Embase, Scopus, and LILACS databases up to September 2023 following a published protocol. We identified 73 cases of DENV‐induced movement disorders. Cerebellar ataxia was the most common, followed by parkinsonism, opsoclonus–myoclonus–ataxia syndrome, and dystonia. Movement disorders typically developed within 14 days of DENV infection and were associated with a range of neurological symptoms, including cognitive impairment and psychiatric disturbances. Neuroimaging studies frequently showed abnormalities in the basal ganglia and brainstem. Treatment varied depending on the specific movement disorder and included corticosteroids, intravenous immunoglobulin, and symptomatic medications. Whereas a handful of cases met the criteria for acute encephalitis, many lacked sufficient data to establish a definitive diagnosis. Para‐infectious and postinfectious immune‐mediated movement disorders were also reported. A rare case of chronic progressive panencephalitis due to DENV infection highlights the potential for long‐term neurological consequences. Other DENV‐related complications, such as stroke, pituitary apoplexy, subacute thyroiditis, and metabolic disturbances, can also cause movement disorders. We emphasize the importance of recognizing the diverse neurological manifestations of DENV infection and the need for further research to improve our understanding of the underlying mechanisms and optimize treatment strategies. We propose a more rigorous approach to determining the causality between infection and movement disorder, demanding stronger evidence beyond mere association and advocating for targeted research to fill the existing knowledge gaps. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"26 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Montelukast on Neuroinflammation in Parkinson's Disease: An Open Label Safety and Tolerability Trial with CSF Markers and [¹¹C]PBR28 PET.","authors":"Johan Wallin, Anton Forsberg, Per Svenningsson","doi":"10.1002/mds.30144","DOIUrl":"https://doi.org/10.1002/mds.30144","url":null,"abstract":"<p><strong>Background: </strong>Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD).</p><p><strong>Objective: </strong>The objective was to examine the safety and tolerability of montelukast, a cysteinyl-leukotriene receptor1 and GPR17 antagonist, in patients with PD. Secondary outcomes were target engagement, effects on PD signs/symptoms, and central neuroinflammation.</p><p><strong>Methods: </strong>Fifteen PD patients were recruited to a 12-week open-label trial of 20 mg bi-daily montelukast treatment. Patients underwent ratings with the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), the Montreal Cognitive Assessment (MoCA), Beck's Depression Inventory (BDI), Parkinson's Disease Questionnaire-39 (PDQ-39), [¹¹C]PBR28-PET, and lumbar punctures before and during montelukast treatment.</p><p><strong>Results: </strong>All patients completed the study. Three patients reported loose stool. No serious adverse events related to treatment were reported. MDS-UPDRS-Total scores improved by 6.9 points. Very low levels of montelukast were detected in all cerebrospinal fluid (CSF) samples and resulted in a reduction in inflammation/metabolism markers. [¹¹C]PBR28 binding was lowered in high, but not mixed, affinity binders after montelukast.</p><p><strong>Conclusions: </strong>Montelukast crosses the blood-brain barrier at very low levels and is well tolerated and safe in PD patients. Preliminary effects on neuroinflammation and clinical scores motivate a future randomized controlled trial (RCT) in PD. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143253989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights into the Association of Pesticide Exposure and Parkinson's Disease.","authors":"Bruno Lopes Santos-Lobato","doi":"10.1002/mds.30135","DOIUrl":"https://doi.org/10.1002/mds.30135","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}