Movement Disorders最新文献

{"title":"Classification and Genotype–Phenotype Relationships of GBA1 Variants: MDSGene Systematic Review","authors":"Malco Rossi MD, PhD,&nbsp;Susen Schaake BSc,&nbsp;Tatiana Usnich MD, PhD,&nbsp;Josephine Boehm,&nbsp;Nina Steffen MD,&nbsp;Nathalie Schell MD,&nbsp;Clara Krüger BSc,&nbsp;Tuğçe Gül-Demirkale PhD,&nbsp;Natascha Bahr,&nbsp;Teresa Kleinz MD,&nbsp;Harutyun Madoev MSc,&nbsp;Björn-Hergen Laabs PhD,&nbsp;Ziv Gan-Or MD, PhD,&nbsp;Roy N. Alcalay MD, MS,&nbsp;Katja Lohmann PhD,&nbsp;Christine Klein MD","doi":"10.1002/mds.30141","DOIUrl":"10.1002/mds.30141","url":null,"abstract":"<p>Depending on zygosity and the specific change, different variants in the <i>GBA1</i> gene can cause Parkinson's disease (PD, PARK-<i>GBA1</i>) 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 <i>GBA1</i> 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 <i>GBA1</i> variant carriers, especially concerning PD. © 2025 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 4","pages":"605-618"},"PeriodicalIF":7.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30141","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":"OA","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 PhD,&nbsp;Isaac Adanyeguh PhD,&nbsp;Benjamin Bender PhD,&nbsp;Sylvia Boesch MD, MSc,&nbsp;Arturo Brunetti MD,&nbsp;Sirio Cocozza MD, PhD,&nbsp;Léo Coutinho MD,&nbsp;Andreas Deistung PhD,&nbsp;Stefano Diciotti PhD,&nbsp;Imis Dogan PhD,&nbsp;Alexandra Durr MD, PhD,&nbsp;Juan Fernandez-Ruiz PhD,&nbsp;Sophia L. Göricke MD,&nbsp;Marina Grisoli MD,&nbsp;Shuo Han PhD,&nbsp;Caterina Mariotti MD,&nbsp;Chiara Marzi PhD,&nbsp;Mario Mascalchi MD, PhD,&nbsp;Fanny Mochel MD, PhD,&nbsp;Wolfgang Nachbauer MD, PhD,&nbsp;Lorenzo Nanetti MD,&nbsp;Anna Nigri PhD,&nbsp;Sergio E. Ono MD, PhD,&nbsp;Chiadi U. Onyike MD,&nbsp;Jerry L. Prince PhD,&nbsp;Kathrin Reetz MD,&nbsp;Sandro Romanzetti PhD,&nbsp;Francesco Saccà MD, PhD,&nbsp;Matthis Synofzik MD,&nbsp;Hélio A. Ghizoni Teive MD, PhD,&nbsp;Sophia I. Thomopoulos BA,&nbsp;Paul M. Thompson PhD,&nbsp;Dagmar Timmann MD,&nbsp;Sarah H. Ying MD,&nbsp;Ian H. Harding PhD,&nbsp;Carlos R. Hernandez-Castillo PhD","doi":"10.1002/mds.30143","DOIUrl":"10.1002/mds.30143","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We undertook a multisite, structural magnetic resonance imaging (MRI) study to comprehensively characterize the neurodegeneration profile of SCA2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Atrophy in SCA2 versus controls was greatest (Cohen's <i>d</i> &gt;2.5) in the cerebellar white matter (WM), middle cerebellar peduncle, pons, and corticospinal tract. Very large effects (<i>d</i> &gt;1.5) were also evident in the superior cerebellar, inferior cerebellar, and cerebral peduncles. In the cerebellar gray matter (GM), large effects (<i>d</i> &gt;0.8) were observed in areas related to both motor coordination and cognitive tasks. Strong correlations (|<i>r</i>| &gt; 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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>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). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 4","pages":"651-661"},"PeriodicalIF":7.4,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30143","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":"OA","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,&nbsp;Véronique Sgambato PhD","doi":"10.1002/mds.30139","DOIUrl":"10.1002/mds.30139","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 3","pages":"443-444"},"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 MD, PhD,&nbsp;Divyani Garg MD, DM,&nbsp;Santiago Perez-Lloret MD, PhD,&nbsp;Norlinah Mohamed Ibrahim MBBCh, MRCP, FRCPE,&nbsp;Onanong Phokaewvarangkul MD, PhD,&nbsp;Jirada Sringean MD, PhD,&nbsp;Vikram Holla MD, DM,&nbsp;Ravi Yadav MD, DM, FRCP,&nbsp;Soaham Desai MD, DM,&nbsp;Pramod Kumar Pal MD, DM, FRCP (Lon)","doi":"10.1002/mds.30142","DOIUrl":"10.1002/mds.30142","url":null,"abstract":"<p>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.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 4","pages":"583-604"},"PeriodicalIF":7.4,"publicationDate":"2025-02-08","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 MD,&nbsp;Anton Forsberg PhD,&nbsp;Per Svenningsson PhD, MD","doi":"10.1002/mds.30144","DOIUrl":"10.1002/mds.30144","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dysregulated leukotriene signaling is proposed to be involved in pathogenesis of Parkinson's disease (PD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>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>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>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). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 4","pages":"739-744"},"PeriodicalIF":7.4,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30144","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor Symptom Variability in Parkinson's Disease: Implications for Personalized Trial Outcomes?","authors":"Jules Janssen Daalen, Maudy van der Heiden, Marjan Meinders, Bart Post","doi":"10.1002/mds.30133","DOIUrl":"https://doi.org/10.1002/mds.30133","url":null,"abstract":"<p><strong>Background: </strong>The Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), Part III, is the gold standard for assessing motor symptoms in Parkinson's disease (PD). However, motor symptoms fluctuate significantly from day to day, potentially limiting the sensitivity of this scale for trials with short duration and crossover designs. This study investigated whether day-to-day variability in motor symptoms exceeds the minimal clinically important difference (MCID) in the MDS-UPDRS, Part III.</p><p><strong>Methods: </strong>Twenty PD participants (Hoehn & Yahr stages 1.5-3) underwent 10 weekly off-medication assessments by one assessor on the same morning. Several determinants of day-to-day variability were explored.</p><p><strong>Results: </strong>Symptom variability often exceeded the MCID for worsening and improvement. Current mental stress and fatigue did not correlate with worse scores, nor did physical activity and sleep quality in the previous week.</p><p><strong>Conclusions: </strong>These findings suggest that day-to-day symptom variability impacts MDS-UPDRS scores in smaller and shorter-duration trials of symptomatic interventions. Continuous monitoring using wearable sensors may offer more accurate and reliable measures for evaluating PD motor symptoms in clinical studies. © 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":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187536","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 MD, PhD","doi":"10.1002/mds.30135","DOIUrl":"10.1002/mds.30135","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 3","pages":"579-580"},"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}

{"title":"Long-Term Outcomes on Pallidal Neurostimulation for Dystonia: A Controlled, Prospective 10-Year Follow-Up.","authors":"Patricia Krause, Philipp Mahlknecht, Inger Marie Skogseid, Frank Steigerwald, Günther Deuschl, Richard Erasmi, Alfons Schnitzler, Tobias Warnecke, Jörg Müller, Werner Poewe, Gerd-Helge Schneider, Jan Vesper, Nils Warneke, Wilhelm Eisner, Thomas Prokop, Jan-Uwe Müller, Jens Volkmann, Andrea A Kühn","doi":"10.1002/mds.30130","DOIUrl":"https://doi.org/10.1002/mds.30130","url":null,"abstract":"<p><strong>Background: </strong>Pallidal neurostimulation is an effective treatment for severe isolated dystonia, but long-term data from clinical trials are lacking.</p><p><strong>Objectives: </strong>To evaluate long-term efficacy and safety of pallidal neurostimulation in patients with isolated generalized or segmental dystonia.</p><p><strong>Methods: </strong>Extension study of the prospective multicenter trial (n = 40; July 2002 to May 2004), all patients received effective stimulation and underwent regular follow-up. The 10-year follow-up (n = 31) included Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability score, Beck Depression Inventory, Beck Anxiety Inventory, and Mattis Dementia Rating Scale. Primary and secondary endpoints compared motor symptoms, disability scores, mood, and cognition changes.</p><p><strong>Results: </strong>Thirty-one patients (12 female), aged 23-72 years, completed the 10-year study extension. Per protocol analysis showed sustained significant improvement in BFMDRS motor scores at 10 years compared with baseline, without significant change from the 6-month or 5-year follow-up. On average, motor scores decreased by 25.3 ± 5.2 points at 10 years (P < 0.0001; 56% improvement). Individual outcomes varied, with 27 responders (≥25% improvement; mean improvement 65.2 ± 21.4%) and 13 non-responders compared with baseline. Sustained improvements were seen in disability, mood, and anxiety scores. Cognition remained stable.</p><p><strong>Conclusions: </strong>This study presents the longest prospective, multicenter follow-up of pallidal neurostimulation in generalized and segmental dystonia. Two-thirds of patients showed strong and stable long-term improvements of dystonia, confirming sustained efficacy and safety over 10 years in treatment-refractory dystonic patients. However, one-third experienced primary (3/40) or secondary (10/40) treatment failure. Diagnostic advances, including genetic testing, and technological progress in pallidal neurostimulation may help to reduce the non-responder rates in the future. © 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":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187529","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":"Addressing Methodological Variability and Enhancing Efficacy Assessment in Focused Ultrasound Thalamotomy for Parkinson's Tremor","authors":"Yinfang Wu MM,&nbsp;Weixing Xu MM","doi":"10.1002/mds.30136","DOIUrl":"10.1002/mds.30136","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 3","pages":"581-582"},"PeriodicalIF":7.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121878","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":"Evidence of Involvement of the Calcitonin Gene‐Related Peptide in Restless Legs Syndrome","authors":"Maria P. Mogavero, Mojibola Fowowe, Akeem Sanni, Mona Goli, Giuseppe Lanza, Francesca L'Episcopo, Luigi Ferini‐Strambi, Yehia Mechref, Raffaele Ferri","doi":"10.1002/mds.30125","DOIUrl":"https://doi.org/10.1002/mds.30125","url":null,"abstract":"BackgroundRestless legs syndrome (RLS) is a common sensory‐motor disorder characterized by an urge to move the legs, often with unpleasant sensations, particularly during rest. Current treatments include iron supplementation, dopamine agonists, and opioids, but new therapeutic approaches are needed. The dysfunction of the A11 nucleus, which modulates dopaminergic transmission to the spinal cord, is thought to play a role in RLS pathophysiology. Calcitonin gene‐related peptide (CGRP), which is involved in pain modulation, may interact with A11 pathways, suggesting a role in RLS.ObjectivesThis study aimed to assess the involvement of CGRP in RLS by determining if CGRP‐related proteins are overexpressed in RLS patients.MethodsA cross‐sectional study was conducted with 17 drug‐free RLS patients (mean age 55.8 years) and 17 age‐ and gender‐matched controls. Serum samples were analyzed using liquid chromatography‐parallel reaction monitoring‐tandem mass spectrometry (LC‐PRM‐MS/MS) to identify and quantify CGRP‐related proteins. Principal component analysis (PCA) was used to differentiate between groups.ResultsPCA showed clear differentiation between RLS and control groups. Among 13 identified CGRP‐related proteins, 10 were dysregulated in RLS patients: 8 were upregulated, and 2 were downregulated, among them notable proteins such as S100A12, ADM, SRSF6, and ADM2.ConclusionsThis study indicates the significant involvement of CGRP and related proteins in RLS. This suggests these proteins may play roles in various aspects of the disorder. Further research is required to validate these findings and explore their clinical implications, including development of new treatment options that specifically address CGRP pathways. © 2025 The Author(s). <jats:italic>Movement Disorders</jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"45 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056236","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}