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Brain Imaging Phenotypes Associated with Polygenic Risk for Essential Tremor
IF 8.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-15 DOI: 10.1002/mds.30167
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
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 (N = 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). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
{"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}
引用次数: 0
Finely Tuned γ Tracks Medication Cycles in Parkinson's Disease: An Ambulatory Brain‐Sense Study
IF 8.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-13 DOI: 10.1002/mds.30160
Aaron Colombo, Elena Bernasconi, Laura Alva, Mario Sousa, Ines Debove, Andreas Nowacki, Camille Serquet, Katrin Petermann, T.A. Khoa Nguyen, Andreia D. Magalhães, Lenard Lachenmayer, Julia Waskönig, Tobias Nef, Michael Schuepbach, Claudio Pollo, Paul Krack, Alberto Averna, Gerd Tinkhauser
BackgroundNovel 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.ObjectivesTo systematically compare the ambulatory neurophysiological dynamics and clinical properties of three candidate biomarkers—low‐frequency, beta (β), and finely tuned γ (FTG) activity.MethodsWe 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 off/on dopaminergic medication and stimulation conditions.ResultsFTG reliably indexed off to on 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 on‐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.ConclusionDespite 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). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
{"title":"Finely Tuned γ Tracks Medication Cycles in Parkinson's Disease: An Ambulatory Brain‐Sense Study","authors":"Aaron Colombo, Elena Bernasconi, Laura Alva, Mario Sousa, Ines Debove, Andreas Nowacki, Camille Serquet, Katrin Petermann, T.A. Khoa Nguyen, Andreia D. Magalhães, Lenard Lachenmayer, Julia Waskönig, Tobias Nef, Michael Schuepbach, Claudio Pollo, Paul Krack, Alberto Averna, Gerd Tinkhauser","doi":"10.1002/mds.30160","DOIUrl":"https://doi.org/10.1002/mds.30160","url":null,"abstract":"BackgroundNovel 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.ObjectivesTo systematically compare the ambulatory neurophysiological dynamics and clinical properties of three candidate biomarkers—low‐frequency, beta (β), and finely tuned γ (FTG) activity.MethodsWe 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 <jats:italic>off</jats:italic>/<jats:italic>on</jats:italic> dopaminergic medication and stimulation conditions.ResultsFTG reliably indexed <jats:italic>off</jats:italic> to <jats:italic>on</jats:italic> 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 <jats:italic>on</jats:italic>‐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.ConclusionDespite 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). <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":"213 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Treatment Efficacy of Theophylline in ADCY5‐Related Dyskinesia: A Retrospective Case Series Study
IF 8.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-13 DOI: 10.1002/mds.30170
Dirk Taenzler, Frank Hause, Andreas Merkenschlager, Andrea Sinz
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). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
{"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}
引用次数: 0
Freezing of Gait During Crawling: The Role of Four-Limb Coordination?
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-10 DOI: 10.1002/mds.30161
Marie-Laure Welter, Jean-Christophe Corvol, Marco Romanato, Brian Lau, Carine Karachi, Jorik Nonnekes, Baastian R Bloem
{"title":"Freezing of Gait During Crawling: The Role of Four-Limb Coordination?","authors":"Marie-Laure Welter, Jean-Christophe Corvol, Marco Romanato, Brian Lau, Carine Karachi, Jorik Nonnekes, Baastian R Bloem","doi":"10.1002/mds.30161","DOIUrl":"https://doi.org/10.1002/mds.30161","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Update on Treatments for Parkinson's Disease Motor Fluctuations - An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review.
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-08 DOI: 10.1002/mds.30162
Rob M A de Bie, Regina Katzenschlager, Bart E K S Swinnen, Marina Peball, Shen-Yang Lim, Tiago A Mestre, Santiago Perez Lloret, Miguel Coelho, Camila Aquino, Ai Huey Tan, Veronica Bruno, Joke M Dijk, Beatrice Heim, Chin-Hsien Lin, Linda Azevedo Kauppila, Irene Litvan, René Spijker, Klaus Seppi, João Costa, Cristina Sampaio, Susan H Fox, Monty A Silverdale

Objective: To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

{"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, Regina Katzenschlager, Bart E K S Swinnen, Marina Peball, Shen-Yang Lim, Tiago A Mestre, Santiago Perez Lloret, Miguel Coelho, Camila Aquino, Ai Huey Tan, Veronica Bruno, Joke M Dijk, Beatrice Heim, Chin-Hsien Lin, Linda Azevedo Kauppila, Irene Litvan, René Spijker, Klaus Seppi, João Costa, Cristina Sampaio, Susan H Fox, Monty A Silverdale","doi":"10.1002/mds.30162","DOIUrl":"https://doi.org/10.1002/mds.30162","url":null,"abstract":"<p><strong>Objective: </strong>To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).</p><p><strong>Background: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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><p><strong>Conclusions: </strong>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). 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":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells.
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-08 DOI: 10.1002/mds.30150
Hui Wang, Timothy S Chang, Beth A Dombroski, Po-Liang Cheng, Ya-Qin Si, Albert Tucci, Vishakha Patil, Leopoldo Valiente-Banuet, Chong Li, Kurt Farrell, Catriona Mclean, Laura Molina-Porcel, Alex Rajput, Peter Paul De Deyn, Nathalie Le Bastard, Marla Gearing, Laura Donker Kaat, John C Van Swieten, Elise Dopper, Bernardino F Ghetti, Kathy L Newell, Claire Troakes, Justo G de Yébenes, Alberto Rábano-Gutierrez, Tina Meller, Wolfgang H Oertel, Gesine Respondek, Maria Stamelou, Thomas Arzberger, Sigrun Roeber, Ulrich Müller, Franziska Hopfner, Pau Pastor, Alexis Brice, Alexandra Durr, Isabelle Le Ber, Thomas G Beach, Geidy E Serrano, Lili-Naz Hazrati, Irene Litvan, Rosa Rademakers, Owen A Ross, Douglas Galasko, Adam L Boxer, Bruce L Miller, Willian W Seeley, Vivianna M Van Deerlin, Edward B Lee, Charles L White, Huw R Morris, Rohan de Silva, John F Crary, Alison M Goate, Jeffrey S Friedman, Yaroslau Compta, Yuk Yee Leung, Giovanni Coppola, Adam C Naj, Li-San Wang, Clifton Dalgard, Dennis W Dickson, Günter U Höglinger, Jung-Ying Tzeng, Daniel H Geschwind, Gerard D Schellenberg, Wan-Ping Lee

Background: 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).

Objective: To investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.

Methods: 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.

Results: We found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, P = 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 ARL17B, LRRC37A/LRRC37A2, and NSFP1, while down-regulating KANSL1. Single-nucleus RNA-seq of the dorsolateral prefrontal cortex analysis reveals γ duplication primarily up-regulates LRRC37A/LRRC37A2 in neuronal cells.

Conclusions: 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). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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引用次数: 0
Isolated Choreic Manifestations Indicative of Anti-Amphiphysin Antibody-Related Encephalitis in Breast Cancer.
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-05 DOI: 10.1002/mds.30140
Stela Dodaj, Marie Rafiq, Raquel Barbosa, Chloé Bost, Margherita Fabbri, Clémence Leung, Fabrice Bonnevile, Jérémie Pariente, Fabienne Ory-Magne
{"title":"Isolated Choreic Manifestations Indicative of Anti-Amphiphysin Antibody-Related Encephalitis in Breast Cancer.","authors":"Stela Dodaj, Marie Rafiq, Raquel Barbosa, Chloé Bost, Margherita Fabbri, Clémence Leung, Fabrice Bonnevile, Jérémie Pariente, Fabienne Ory-Magne","doi":"10.1002/mds.30140","DOIUrl":"https://doi.org/10.1002/mds.30140","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spinocerebellar Ataxia Progression Measured with the Patient-Reported Outcome Measure of Ataxia.
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-04 DOI: 10.1002/mds.30158
Anna L Burt, Gilbert L'Italien, Susan L Perlman, Liana S Rosenthal, Sheng-Han Kuo, Tetsuo Ashizawa, Theresa Zesiewicz, Cameron Dietiker, Puneet Opal, Antoine Duquette, George R Wilmot, Vikram G Shakkottai, Christopher M Gomez, Sharan R Srinivasan, Henry Paulson, Michael D Geschwind, Sandie Worley, Chiadi U Onyike, Andrew Billnitzer, Amy Ferng, Kristen Matulis, Marie Y Davis, Sub H Subramony, Anoopum Gupta, Christopher D Stephen, Jeremy D Schmahmann

Background: The Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) has been validated cross-sectionally but not longitudinally.

Objective: 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).

Methods: 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 mild, moderate, and severe 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.

Results: 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 moderate patients. Compared with other COAs, PROM-Ataxia captured the most change. Mental features worsened fastest in mild patients, physical in moderate patients, and activities of daily living in severe patients.

Conclusion: 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.

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引用次数: 0
Comparative Study of Focused Ultrasound Unilateral Thalamotomy and Subthalamotomy for Medication‐Refractory Parkinson's Disease Tremor
IF 8.6 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-03 DOI: 10.1002/mds.30159
Steffen Paschen, Elena Natera‐Villalba, José A. Pineda‐Pardo, Marta del Álamo, Rafael Rodríguez‐Rojas, Johannes Hensler, Günther Deuschl, Jose A. Obeso, Ann‐Kristin Helmers, Raúl Martínez‐Fernández
BackgroundUnilateral 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.ObjectiveTo compare the efficacy in parkinsonian tremor control between Vim‐FUS and STN‐FUS.MethodsRetrospective, 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 P < 0.05.ResultsAmong 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, P = 0.48) and tremor severity (5.7 ± 1.5 vs. 5.9 ± 2.5, P = 0.7). While the benefit in tremor was equivalent between the groups at 4 months (P = 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, P = 0.012). In 47.5% (19/40) of STN‐FUS patients tremor was completely abolished versus 8.7% (2/23) in Vim‐FUS patients (P < 0.01). Most adverse events were mild (91%) and resolved by 12 months.ConclusionsSTN‐FUS and Vim‐FUS significantly improved medication‐refractory PD tremor; however, subthalamotomy might have greater and more sustained effect. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
{"title":"Comparative Study of Focused Ultrasound Unilateral Thalamotomy and Subthalamotomy for Medication‐Refractory Parkinson's Disease Tremor","authors":"Steffen Paschen, Elena Natera‐Villalba, José A. Pineda‐Pardo, Marta del Álamo, Rafael Rodríguez‐Rojas, Johannes Hensler, Günther Deuschl, Jose A. Obeso, Ann‐Kristin Helmers, Raúl Martínez‐Fernández","doi":"10.1002/mds.30159","DOIUrl":"https://doi.org/10.1002/mds.30159","url":null,"abstract":"BackgroundUnilateral 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.ObjectiveTo compare the efficacy in parkinsonian tremor control between Vim‐FUS and STN‐FUS.MethodsRetrospective, 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 <jats:italic>P</jats:italic> &lt; 0.05.ResultsAmong 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, <jats:italic>P</jats:italic> = 0.48) and tremor severity (5.7 ± 1.5 vs. 5.9 ± 2.5, <jats:italic>P</jats:italic> = 0.7). While the benefit in tremor was equivalent between the groups at 4 months (<jats:italic>P</jats:italic> = 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, <jats:italic>P</jats:italic> = 0.012). In 47.5% (19/40) of STN‐FUS patients tremor was completely abolished versus 8.7% (2/23) in Vim‐FUS patients (<jats:italic>P</jats:italic> &lt; 0.01). Most adverse events were mild (91%) and resolved by 12 months.ConclusionsSTN‐FUS and Vim‐FUS significantly improved medication‐refractory PD tremor; however, subthalamotomy might have greater and more sustained effect. © 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":"2 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploration of Neurodegenerative Diseases Using Long-Read Sequencing and Optical Genome Mapping Technologies.
IF 7.4 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-03 DOI: 10.1002/mds.30151
Guillaume Cogan, Kensuke Daida, Cornelis Blauwendraat, Kimberley Billingsley, Alexis Brice

Genetic factors play a central role in neurodegenerative disorders. Over the past few decades, significant progress has been made in identifying the causative genes of numerous monogenic disorders, largely due to the widespread adoption of next-generation sequencing (NGS) technologies in both research and clinical settings. However, many likely monogenic disorders still lack an accurate molecular diagnosis, primarily because conventional NGS methods are not effective at detecting structural variants and repeat expansions, both of which are crucial in many neurogenetic diseases. Recently, long-read sequencing (LRS) and optical genome mapping technologies have emerged as powerful tools, offering the ability to capture more complex genetic variations. These technologies have already led to the discovery of novel genes responsible for well-characterized neurodegenerative diseases (ND), enhancing the understanding of the biological underpinning of these conditions. Although currently LRS is mostly used in a research setting, we anticipate broader implementation of these methods in clinical laboratories in the near future. In this review, we explore the contributions of these technologies to ND research and highlight the remaining challenges for future advancements. © 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.

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引用次数: 0
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Movement Disorders
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