Movement Disorders最新文献

{"title":"Patients with Allan-Herndon-Dudley Syndrome (MCT8 Deficiency) Display Symptoms of Parkinsonism in Childhood and Respond to Levodopa/Carbidopa Treatment","authors":"Nina-Maria Wilpert MD, PhD,&nbsp;Angela L. Hewitt MD, PhD,&nbsp;Roser Pons MD, PhD,&nbsp;Marie-Thérèse Henke MSc,&nbsp;Andrea Dell'Orco MSc,&nbsp;Martin Bauer MSc,&nbsp;Christiane Grolik MD,&nbsp;Stephan Menz,&nbsp;Monika Wahle,&nbsp;Annika Zink PhD,&nbsp;Alessandro Prigione MD, PhD,&nbsp;Christina Reinauer MD,&nbsp;Catharina Lange,&nbsp;Christian Furth MD,&nbsp;Knut Brockmann MD,&nbsp;Sabine Jung-Klawitter MD,&nbsp;Stine Christ MD,&nbsp;Angela M. Kaindl MD,&nbsp;Anna Tietze MD, PhD,&nbsp;Heiko Krude MD,&nbsp;Thomas Opladen MD,&nbsp;Markus Schuelke MD","doi":"10.1002/mds.30152","DOIUrl":"10.1002/mds.30152","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with mutations in the monocarboxylate transporter 8 (MCT8, <i>SLC16A2</i>) suffer from X-linked recessive Allan-Herndon-Dudley syndrome (AHDS), which is characterized by developmental delay and a severe movement disorder. Current trials using thyroid hormone derivatives to overcome the transporter defect have failed to achieve patient-oriented therapeutic goals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Our aim was to define the type of movement disorder in AHDS in an observational cohort study and to investigate the causative role of the dopaminergic system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We present longitudinal clinical data from the DEEPTYPE registry of 11 patients with video documentation, standardized phenotyping, cerebrospinal fluid (CSF) analysis, neuroimaging data, and the treatment response to levodopa/carbidopa supplementation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Children presented with signs of childhood parkinsonism, including hypokinesia, hypomimia, inability to sit or stand, rigidity, dystonia, and autonomic dysfunction. CSF homovanillic acid concentrations were decreased (n = 12), suggesting an isolated dopamine pathway impairment. Seven out of 8 patients responded favorably to <span>l</span>-dopa/carbidopa supplementation and we did not observe any adverse drug reactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>AHDS is associated with childhood parkinsonism, which is linked with biochemical abnormalities of dopamine metabolism. It can be treated with <span>l</span>-dopa/carbidopa supplementation. However, further research is needed to elucidate the exact effect of MCT8 deficiency on dopamine metabolism. © 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 5","pages":"938-949"},"PeriodicalIF":7.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631473","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":"Brain Imaging Phenotypes Associated with Polygenic Risk for Essential Tremor","authors":"Miranda Medeiros, Alexandre Pastor‐Bernier, Houman Azizi, Zoe Schmilovich, Charles‐Etienne Castonguay, Peter Savadjiev, Jean‐Baptiste Poline, Etienne St‐Onge, Fan Zhang, Lauren J. O'Donnell, Ofer Pasternak, Yashar Zeighami, Patrick A. Dion, Alain Dagher, Guy A. Rouleau","doi":"10.1002/mds.30167","DOIUrl":"https://doi.org/10.1002/mds.30167","url":null,"abstract":"Essential tremor (ET) is a common movement disorder with a strong genetic basis. Magnetic resonance imaging (MRI), particularly diffusion‐weighted MRI (dMRI) and T1 MRI, have been used to identify brain abnormalities of ET patients. However, the mechanisms by which genetic risk affects the brain to render individuals vulnerable to ET remain unknown. We aimed to understand how ET manifests by identifying presymptomatic brain vulnerabilities driven by ET genetic risk. We probed the vulnerability of healthy people towards ET by investigating the association of morphometry, and white and grey matter dMRI with ET in polygenic risk scores (PRS) in roughly 30,000 individuals from the UK Biobank (UKB). Our results indicate significant effects of ET‐PRS with mean diffusivity, fractional anisotropy, free water, radial diffusivity, and axial diffusivity in white matter tracts implicated in movement control. We found significant associations between ET‐PRS and grey matter tissue microstructure, including the red nucleus, caudate, putamen, and motor thalamus. ET‐PRS was associated with reduced grey matter volumes in several cortical and subcortical areas including the cerebellum. Identified anomalies included networks connected to surgical sites effective in ET treatment. Finally, in a secondary analysis, low PRS individuals compared with a small number of patients with ET (<jats:italic>N</jats:italic> = 49) in the UKB revealed many structural differences. Brain structural vulnerabilities in healthy people at risk of developing ET correspond to areas known to be involved in the pathology of ET. High genetic risk of ET seems to disrupt ET brain networks even in the absence of overt symptoms of ET. © 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":"33 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631475","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":"Finely Tuned γ Tracks Medication Cycles in Parkinson's Disease: An Ambulatory Brain-Sense Study","authors":"Aaron Colombo MSc,&nbsp;Elena Bernasconi MSc,&nbsp;Laura Alva MD,&nbsp;Mario Sousa MD,&nbsp;Ines Debove MD,&nbsp;Andreas Nowacki MD,&nbsp;Camille Serquet MSc,&nbsp;Katrin Petermann MSc,&nbsp;T.A. Khoa Nguyen PhD,&nbsp;Andreia D. Magalhães MD, PhD,&nbsp;Lenard Lachenmayer MD,&nbsp;Julia Waskönig MD,&nbsp;Tobias Nef PhD,&nbsp;Michael Schuepbach MD,&nbsp;Claudio Pollo MD,&nbsp;Paul Krack MD, PhD,&nbsp;Alberto Averna PhD,&nbsp;Gerd Tinkhauser MD, PhD","doi":"10.1002/mds.30160","DOIUrl":"10.1002/mds.30160","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Novel commercial brain-sense neurostimulators enable us to contextualize brain activity with symptom and medication states in real-life ambulatory settings in Parkinson's disease (PD). Although various candidate biomarkers have been proposed for adaptive deep brain stimulation (DBS), a comprehensive comparison of their ambulatory profiles is lacking.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To systematically compare the ambulatory neurophysiological dynamics and clinical properties of three candidate biomarkers—low-frequency, beta (β), and finely tuned γ (FTG) activity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We investigated 14 PD patients implanted with the Medtronic Percept PC, who underwent up to two 4-week ambulatory multimodal recording periods on their regular medication and stimulation. Subthalamic nucleus local field potentials (LFPs) of low-frequency, β, and FTG activity were recorded. Additionally, objective motor symptom states, physical activity and heart rate using wearables, as well as medication-intake times, sleep-awake times, and subjective symptom states using diaries were co-registered. LFP dynamics were also compared to high-resolution in-hospital recordings under &lt;i&gt;off&lt;/i&gt;/&lt;i&gt;on&lt;/i&gt; dopaminergic medication and stimulation conditions.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;FTG reliably indexed &lt;i&gt;off&lt;/i&gt; to &lt;i&gt;on&lt;/i&gt; medication states in the ambulatory setting at the group and individual levels, and these spectral dynamics could be anticipated by high-resolution in-hospital recordings. Both FTG and low-frequency correlated with wearable-based dyskinesia scores, whereas diary-based dyskinesia events were only linked to FTG. Importantly, FTG indicated &lt;i&gt;on&lt;/i&gt;-medication states regardless of the presence of dyskinesia and despite potential motion and heart rate artifacts. The 24-hour profile revealed large circadian power shifts that may overdrive medication-intake dynamics.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Despite the limitations of low-temporal resolution recordings, this work provides valuable insights into the real-life dynamics of biomarkers. Specifically, it highlights the utility of FTG as a primary and reliable indicator of medication states for adaptive DBS. © 2025 The Author(s). &lt;i&gt;Movement Disorders&lt;/i&gt; published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 ","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":"881-895"},"PeriodicalIF":7.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618414","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":"Treatment Efficacy of Theophylline in ADCY5‐Related Dyskinesia: A Retrospective Case Series Study","authors":"Dirk Taenzler, Frank Hause, Andreas Merkenschlager, Andrea Sinz","doi":"10.1002/mds.30170","DOIUrl":"https://doi.org/10.1002/mds.30170","url":null,"abstract":"BackgroundADCY5‐related dyskinesia is a rare disorder caused by mutations in the ADCY5 gene resulting in abnormal involuntary movements. Currently, there are no standardized guidelines to treat this condition.ObjectiveThe aim of this study was to evaluate the efficacy of theophylline administration in improving symptoms and quality of life in patients with ADCY5‐related dyskinesia.MethodsA retrospective study was conducted involving 12 patients (aged 2–41 years) with ADCY5‐related dyskinesia. Participants completed a questionnaire about theophylline administration, including dosage, improvement of symptoms, adverse effects, and changes in quality of life. Data were analyzed for reported efficacy and side effects.ResultsTheophylline administration demonstrated substantial efficacy, with 92% (11 of 12) of patients reporting significant improvements in their movement disorders. The average improvement score was 7.0 ± 1.9 (mean ± SD) on a 10‐point scale. Notable improvements included reductions in severity and frequency of episodes, improved gait, more independent mobility, psychosocial well‐being, and quality of sleep. Adverse effects were reported by 6 patients, including dystonia, worsening of speech, headaches, nausea, impaired sleep, and agitation.ConclusionsTheophylline shows substantial promise as a treatment option for ADCY5‐related dyskinesia, improving various aspects of patients' quality of life and movement disorder symptoms. Further research is needed to optimize dosing, to understand long‐term effects, and to explore combinational drug therapies. Despite the small cohort size and the retrospective nature of this study, the results support theophylline administration to decrease dyskinetic movements and enhance overall quality of life in patients. © 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":"18 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618415","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":"Freezing of Gait During Crawling: The Role of Four-Limb Coordination?","authors":"Marie-Laure Welter MD, PhD,&nbsp;Jean-Christophe Corvol MD, PhD,&nbsp;Marco Romanato PhD,&nbsp;Brian Lau PhD,&nbsp;Carine Karachi MD, PhD,&nbsp;Jorik Nonnekes MD, PhD,&nbsp;Baastian R. Bloem MD, PhD","doi":"10.1002/mds.30161","DOIUrl":"10.1002/mds.30161","url":null,"abstract":"&lt;p&gt;Full financial disclosures and author roles may be found in the online version of this article.&lt;/p&gt;&lt;p&gt;Freezing of gait (FOG) is a disabling motor feature of Parkinson's disease (PD) that frequently leads to falls.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Similar motor blocks can also affect the upper limbs, swallowing, or speech.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Many patients can mitigate FOG by using compensatory strategies, such as external cues.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; We describe a unique case of a patient with PD experiencing FOG in all four limbs while crawling.&lt;/p&gt;&lt;p&gt;The patient, a 64-year-old man, had a 26-year history of PD, which began at age 38 with slowness in his right arm. A decade later, he developed FOG, particularly when initiating gait. Sixteen years into his illness, he underwent subthalamic deep brain stimulation (STN-DBS) to manage severe levodopa (&lt;span&gt;l&lt;/span&gt;-dopa)-related motor fluctuations and dyskinesias (&lt;span&gt;l&lt;/span&gt;-dopa equivalent daily dosage of 950 mg/day). &lt;span&gt;l&lt;/span&gt;-dopa provided partial relief of FOG (Unified Parkinson's Disease Rating Scale [UPDRS] item 2.13 &lt;i&gt;off/on&lt;/i&gt; &lt;span&gt;l&lt;/span&gt;-dopa = 2/1) without falls. Postsurgery, his motor symptoms (UPDRS Part III) improved by 45% with STN-DBS alone, with both electrodes accurately placed bilaterally within the STN. FOG showed partial improvement (item 2.13 ON DBS = 1). Over the next 10 years, his FOG progressively worsened (item 2.13 ON DBS = 3), becoming unresponsive to both STN-DBS adjustments and dopaminergic medication, resulting in frequent falls (Video 1, segment 1). He has no dementia (Mattis Dementia Rating Scale = 133). In daily life, he relied on a broom as an external visual cue, stepping over it to initiate walking (Video 1, segment 2). Although this enabled him to take a few steps, FOG quickly recurred. At home, he occasionally resorted to crawling, which initially triggered leg movements but was also impaired by freezing affecting all four limbs (Video 1, segment 3). External visual cues directed at hand movements temporarily alleviated his crawling-related freezing (Video 1, segment 4).&lt;/p&gt;&lt;p&gt;This is the first report of freezing during crawling in PD, with freezing involving both upper and lower limbs in a quadrupedal position. Crawling, initially adopted as compensatory strategy by the patient, involves diagonal coordination of the forelimbs and hind limbs (trotlike gait) in approximately half of adults.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; This coordination pattern was also evident in our patient (Video 1, segment 5). However, discoordination between all four limbs obstructed his ability to crawl, leading to freezing (segment 5). This observation underscores the importance of coordinated four-limb movement in human locomotion and suggests that dysfunction in this coordination may be a contributing mechanism underlying FOG. In mammals, spinal central pattern generators (CPGs)&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; and ascending proprioceptive signals regulate the rhythmic coordination o","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":"990-991"},"PeriodicalIF":7.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30161","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584086","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":"Update on Treatments for Parkinson's Disease Motor Fluctuations – An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review","authors":"Rob M.A. de Bie MD, PhD,&nbsp;Regina Katzenschlager MD,&nbsp;Bart E.K.S. Swinnen MD, PhD,&nbsp;Marina Peball LLM, PhD,&nbsp;Shen-Yang Lim MD,&nbsp;Tiago A. Mestre MD, PhD,&nbsp;Santiago Perez Lloret MD, PhD,&nbsp;Miguel Coelho MD,&nbsp;Camila Aquino MD, MSc, PhD,&nbsp;Ai Huey Tan MD,&nbsp;Veronica Bruno MD, MPH, FRCPC,&nbsp;Joke M. Dijk MD, PhD,&nbsp;Beatrice Heim MD, PhD,&nbsp;Chin-Hsien Lin MD, PhD,&nbsp;Linda Azevedo Kauppila MD, MSc,&nbsp;Irene Litvan MD,&nbsp;René Spijker MSc,&nbsp;Klaus Seppi MD,&nbsp;João Costa MD, PhD,&nbsp;Cristina Sampaio MD, PhD,&nbsp;Susan H. Fox MD, PhD,&nbsp;Monty A. Silverdale MD, PhD","doi":"10.1002/mds.30162","DOIUrl":"10.1002/mds.30162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane Risk of Bias tool and a modified version of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>On January 1, 2023, a literature search was conducted without date limit in the MEDLINE, Embase, and Cochrane databases using the following search terms: Parkinson disease, levodopa and, for the Embase database, randomized controlled trial (RCT). The inclusion criteria for studies were: patients with PD, on oral levodopa therapy, experiencing motor fluctuations, investigating an intervention that was (commercially) available in at least one country, study design RCT, and with a follow-up duration of at least 3 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 102 studies were included. Levodopa extended release, pramipexole immediate release and extended release, ropinirole immediate release, rotigotine, opicapone, safinamide, and bilateral subthalamic nucleus deep brain stimulation (DBS) were assessed as efficacious, and continuous intestinal levodopa infusion, continuous subcutaneous levodopa, continuous subcutaneous apomorphine, ropinirole prolonged release, ropinirole patch, entacapone, rasagiline, istradefylline, amantadine extended release, zonisamide, bilateral globus pallidus DBS, and pallidotomy were assessed as likely efficacious for the treatment of motor fluctuations in people with PD who are already being treated with levodopa.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There are several treatment options that can improve motor fluctuations in PD. These recommendations will assist physicians and patients in determining which intervention to use. © 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 5","pages":"776-794"},"PeriodicalIF":7.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30162","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584087","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":"Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells","authors":"Hui Wang PhD,&nbsp;Timothy S. Chang MD, PhD,&nbsp;Beth A. Dombroski PhD,&nbsp;Po-Liang Cheng PhD,&nbsp;Ya-Qin Si PhD,&nbsp;Albert Tucci PhD,&nbsp;Vishakha Patil MS,&nbsp;Leopoldo Valiente-Banuet,&nbsp;Chong Li MS,&nbsp;Kurt Farrell PhD,&nbsp;Catriona Mclean MD,&nbsp;Laura Molina-Porcel MD, PhD,&nbsp;Alex Rajput MD,&nbsp;Peter Paul De Deyn MD, PhD,&nbsp;Nathalie Le Bastard PhD,&nbsp;Marla Gearing PhD,&nbsp;Laura Donker Kaat MD, PhD,&nbsp;John C. Van Swieten MD, PhD,&nbsp;Elise Dopper MD, PhD,&nbsp;Bernardino F. Ghetti MD,&nbsp;Kathy L. Newell MD,&nbsp;Claire Troakes PhD,&nbsp;Justo G. de Yébenes MD, PhD,&nbsp;Alberto Rábano-Gutierrez MD, PhD,&nbsp;Tina Meller PhD,&nbsp;Wolfgang H. Oertel MD, PhD,&nbsp;Gesine Respondek MD,&nbsp;Maria Stamelou MD,&nbsp;Thomas Arzberger MD,&nbsp;Sigrun Roeber MD,&nbsp;Ulrich Müller MD,&nbsp;Franziska Hopfner MD,&nbsp;Pau Pastor MD, PhD,&nbsp;Alexis Brice MD,&nbsp;Alexandra Durr MD, PhD,&nbsp;Isabelle Le Ber MD, PhD,&nbsp;Thomas G. Beach MD, PhD,&nbsp;Geidy E. Serrano PhD,&nbsp;Lili-Naz Hazrati MD, PhD,&nbsp;Irene Litvan MD,&nbsp;Rosa Rademakers PhD,&nbsp;Owen A. Ross PhD,&nbsp;Douglas Galasko MD,&nbsp;Adam L. Boxer MD, PhD,&nbsp;Bruce L. Miller MD,&nbsp;Willian W. Seeley MD,&nbsp;Vivianna M. Van Deerlin MD, PhD,&nbsp;Edward B. Lee MD, PhD,&nbsp;Charles L. White III MD,&nbsp;Huw R. Morris MD, PhD,&nbsp;Rohan de Silva PhD,&nbsp;John F. Crary MD, PhD,&nbsp;Alison M. Goate PhD,&nbsp;Jeffrey S. Friedman MD, PhD,&nbsp;Yaroslau Compta MD, PhD,&nbsp;Yuk Yee Leung PhD,&nbsp;Giovanni Coppola MD,&nbsp;Adam C. Naj PhD,&nbsp;Li-San Wang PhD,&nbsp;PSP Genetics Study Group,&nbsp;Clifton Dalgard PhD,&nbsp;Dennis W. Dickson MD,&nbsp;Günter U. Höglinger MD,&nbsp;Jung-Ying Tzeng PhD,&nbsp;Daniel H. Geschwind MD, PhD,&nbsp;Gerard D. Schellenberg PhD,&nbsp;Wan-Ping Lee PhD","doi":"10.1002/mds.30150","DOIUrl":"10.1002/mds.30150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing whole genome sequencing data from 1684 PSP cases and 2392 controls, the three large CNVs (α, β, and γ) and structural forms within 17q21.31 were identified and analyzed for their association with PSP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, <i>P</i> = 0.0018). From H1β1γ1 (OR = 1.21) and H1β2γ1 (OR = 1.24) to H1β1γ4 (OR = 1.57), structural forms of H1 with additional copies of γ displayed a higher risk for PSP. The frequency of the risk sub-haplotype H1c rises from 1% in individuals with two γ copies to 88% in those with eight copies. Additionally, γ duplication up-regulates expression of <i>ARL17B</i>, <i>LRRC37A</i>/<i>LRRC37A2</i>, and <i>NSFP1</i>, while down-regulating <i>KANSL1</i>. Single-nucleus RNA-seq of the dorsolateral prefrontal cortex analysis reveals γ duplication primarily up-regulates <i>LRRC37A</i>/<i>LRRC37A2</i> in neuronal cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The copy number of γ is associated with the risk of PSP after adjusting for H1/H2, indicating that the complex structure at 17q21.31 is an important consideration when evaluating the genetic risk of PSP. © 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 5","pages":"950-961"},"PeriodicalIF":7.4,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30150","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584084","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":"Isolated Choreic Manifestations Indicative of Anti-Amphiphysin Antibody-Related Encephalitis in Breast Cancer","authors":"Stela Dodaj,&nbsp;Marie Rafiq,&nbsp;Raquel Barbosa,&nbsp;Chloé Bost,&nbsp;Margherita Fabbri,&nbsp;Clémence Leung,&nbsp;Fabrice Bonnevile,&nbsp;Jérémie Pariente,&nbsp;Fabienne Ory-Magne","doi":"10.1002/mds.30140","DOIUrl":"10.1002/mds.30140","url":null,"abstract":"&lt;p&gt;Over the past two decades, subacute abnormal movements have been increasingly associated with autoimmune or paraneoplastic encephalitis.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Only a few cases, however, have been reported in association with anti-amphiphysin autoantibodies,&lt;span&gt;&lt;sup&gt;2-5&lt;/sup&gt;&lt;/span&gt; and to our knowledge there is only one reported case of choreic movements in an anti-amphiphysin patient.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Similarly, we report here the case of a woman presenting with brachio-facial choreic movements with anti-amphiphysin autoantibody-related encephalitis in the context of breast cancer. This patient made a remarkable recovery following mastectomy, chemotherapy, and treatment with tetrabenazine.&lt;/p&gt;&lt;p&gt;Anti-amphiphysin antibody-related encephalitis is rare and manifests variable clinical presentations such as stiff person syndrome, sensory ganglionopathy, myelopathy, and cerebellar ataxia.&lt;span&gt;&lt;sup&gt;3, 5, 7, 8&lt;/sup&gt;&lt;/span&gt; Our patient did not experience any other common neurological symptoms classically described in anti-amphiphysin antibody-related encephalitis patients such as limbic encephalitis, limb weakness/numbness, ataxia, sleep disorders, or dysautonomia.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; On the contrary, she presented isolated choreic movements, which have rarely been described previously in anti-amphiphysin antibody-related encephalitis. Due to the atypical phenomenology and clearly unilateral localization of her abnormal movements, we considered the possibility of a paroxystic etiology prompting us to consider continuous focal epilepsy, as is casually observed in anti-amphiphysin antibody-related encephalitis.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; But since no EEG abnormalities and no response to antiepileptic drugs were observed this was ruled out, although the patient's symptoms demonstrably responded to tetrabenazine.&lt;/p&gt;&lt;p&gt;Movement disorders, as a clinical presentation of paraneoplastic neurological syndromes, are rarely seen.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; However, they may be the prominent and common feature in several autoantibody-associated neurological diseases or paraneoplastic neurological syndromes. Paraneoplastic chorea, in particular, typically starts subacutely, progresses rapidly, and involves the four limbs as well as the trunk, head, and neck. They are very rarely confined to only one hemibody (see Table 1). Moreover, it is an extremely rare occurrence of anti-amphiphysin antibody-related encephalitis.&lt;span&gt;&lt;sup&gt;11, 12&lt;/sup&gt;&lt;/span&gt; Thus, this case highlights the importance of considering paraneoplastic origin of an atypical chorea and, notwithstanding the challenges of diagnosing patients with this condition, recognizing and treating the underlying cause is crucial.&lt;/p&gt;&lt;p&gt;(1) Research Project: A. Conception, B. Organization, C. Execution, D. Analysis; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the First Draft, B. Editing of the Final Manuscript.&lt;/p&gt;&lt;p&gt;S.D.: 3A,","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":"986-989"},"PeriodicalIF":7.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555492","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":"Spinocerebellar Ataxia Progression Measured with the Patient-Reported Outcome Measure of Ataxia","authors":"Anna L. Burt AB,&nbsp;Gilbert L'Italien PhD,&nbsp;Susan L. Perlman MD,&nbsp;Liana S. Rosenthal MD, PhD,&nbsp;Sheng-Han Kuo MD,&nbsp;Tetsuo Ashizawa MD,&nbsp;Theresa Zesiewicz MD,&nbsp;Cameron Dietiker MD,&nbsp;Puneet Opal MD, PhD,&nbsp;Antoine Duquette MD,&nbsp;George R. Wilmot MD, PhD,&nbsp;Vikram G. Shakkottai MD, PhD,&nbsp;Christopher M. Gomez MD,&nbsp;Sharan R. Srinivasan MD, PhD,&nbsp;Henry Paulson MD, PhD,&nbsp;Michael D. Geschwind MD, PhD,&nbsp;Sandie Worley MD,&nbsp;Chiadi U. Onyike MD,&nbsp;Andrew Billnitzer MD,&nbsp;Amy Ferng MD,&nbsp;Kristen Matulis DNP,&nbsp;Marie Y. Davis MD, PhD,&nbsp;Sub H. Subramony MD,&nbsp;Anoopum Gupta MD, PhD,&nbsp;Christopher D. Stephen MBChB,&nbsp;Jeremy D. Schmahmann MD","doi":"10.1002/mds.30158","DOIUrl":"10.1002/mds.30158","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) has been validated cross-sectionally but not longitudinally.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to validate PROM-Ataxia as a measure of patient experience of disease over time, examine overall and domain-specific progression, and test convergent validity with other clinical outcome assessments (COAs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We derived PROM-Ataxia data from 176 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, or 10 in the Clinical Research Consortium for the Study of Cerebellar Ataxia at baseline and 1 year. We classified patients' ataxia severity stage (“severity”) according to the Friedreich's Ataxia Rating Scale Functional Staging into <i>mild</i>, <i>moderate</i>, and <i>severe</i> subgroups. Analyses of the entire cohort and by severity subgroup included internal consistency, sensitivity to disease severity, predictive modeling of score changes, correlations with COAs: Brief Ataxia Rating Scale, Scale for Assessment and Rating of Ataxia, Fatigue Severity Scale, Cerebellar Cognitive Affective Syndrome scale, EuroQol 5-Dimension, and responsiveness to disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The PROM-Ataxia exhibited high internal consistency and correlated with other COAs. Scores demonstrated sensitivity to disease severity and evolving patient experience. Progression was sigmoidal, with the greatest change in <i>moderate</i> patients. Compared with other COAs, PROM-Ataxia captured the most change. Mental features worsened fastest in <i>mild</i> patients, physical in <i>moderate</i> patients, and activities of daily living in <i>severe</i> patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>PROM-Ataxia is more sensitive to change than ataxia COAs, captures the evolution of patients' experience of disease over 1 year, and reveals domain-specific progression. Studies of larger cohorts and different ataxia diagnoses over longer periods may provide insights to further enhance clinical care and research. © 2025 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"40 5","pages":"917-927"},"PeriodicalIF":7.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143539594","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":"Comparative Study of Focused Ultrasound Unilateral Thalamotomy and Subthalamotomy for Medication-Refractory Parkinson's Disease Tremor","authors":"Steffen Paschen MD,&nbsp;Elena Natera-Villalba MD,&nbsp;José A. Pineda-Pardo PhD,&nbsp;Marta del Álamo MD,&nbsp;Rafael Rodríguez-Rojas PhD,&nbsp;Johannes Hensler MD,&nbsp;Günther Deuschl PhD,&nbsp;Jose A. Obeso PhD,&nbsp;Ann-Kristin Helmers MD,&nbsp;Raúl Martínez-Fernández PhD","doi":"10.1002/mds.30159","DOIUrl":"10.1002/mds.30159","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Unilateral focused ultrasound ventral intermediate thalamotomy (Vim-FUS) is effective in treating Parkinson's disease (PD) tremor. Ultrasound ablation of the subthalamic nucleus (STN-FUS) has demonstrated efficacy in improving all cardinal motor features of PD, including tremor.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the efficacy in parkinsonian tremor control between Vim-FUS and STN-FUS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Retrospective, two-center study including consecutive PD patients with medication-refractory tremor who underwent unilateral Vim-FUS or STN-FUS between June 2015 and August 2022. Patients scored ≥2 for postural and/or resting tremor on the most affected body side in the off-medication state. The primary outcome was the between-group difference in tremor improvement on the treated side at 12-month follow-up, including a responder's analysis. Data regarding safety, global motor status, and dopaminergic requirements were also collected. Group comparisons used repeated measures ANOVA with Bonferroni correction; statistical significance for <i>P</i> &lt; 0.05.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 175 patients treated at the two sites, 63 were included (23 Vim-FUS, 40 STN-FUS). At baseline, both groups were equivalent in disease duration (6.7 ± 3.8 vs. 6.1 ± 3.4 years, <i>P</i> = 0.48) and tremor severity (5.7 ± 1.5 vs. 5.9 ± 2.5, <i>P</i> = 0.7). While the benefit in tremor was equivalent between the groups at 4 months (<i>P</i> = 0.15), tremor reduction was greater in STN- FUS patients at 12 months (4.4 ± 2.0, 95% CI 3.7–5.0 compared with 2.7 ± 3.7, 95% CI 1.1–4.3 for Vim-FUS, <i>P</i> = 0.012). In 47.5% (19/40) of STN-FUS patients tremor was completely abolished versus 8.7% (2/23) in Vim-FUS patients (<i>P</i> &lt; 0.01). Most adverse events were mild (91%) and resolved by 12 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>STN-FUS and Vim-FUS significantly improved medication-refractory PD tremor; however, subthalamotomy might have greater and more sustained effect. © 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 5","pages":"823-833"},"PeriodicalIF":7.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30159","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538397","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}