Movement Disorders最新文献

{"title":"New Insights into Freezing of Gait in Parkinson's Disease from Spectral Dynamic Causal Modeling","authors":"Seira Taniguchi PhD,&nbsp;Yuta Kajiyama MD, PhD,&nbsp;Takanori Kochiyama PhD,&nbsp;Gajanan Revankar MBBS, PhD,&nbsp;Kotaro Ogawa MD, PhD,&nbsp;Emi Shirahata MD,&nbsp;Kana Asai MD,&nbsp;Chizu Saeki MD,&nbsp;Tatsuhiko Ozono MD, PhD,&nbsp;Yasuyoshi Kimura MD, PhD,&nbsp;Kensuke Ikenaka MD, PhD,&nbsp;Nicholas D'Cruz PhD,&nbsp;Moran Gilat PhD,&nbsp;Alice Nieuwboer PhD,&nbsp;Hideki Mochizuki MD, PhD","doi":"10.1002/mds.29988","DOIUrl":"10.1002/mds.29988","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Freezing of gait is one of the most disturbing motor symptoms of Parkinson's disease (PD). However, the effective connectivity between key brain hubs that are associated with the pathophysiological mechanism of freezing of gait remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to identify effective connectivity underlying freezing of gait.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study applied spectral dynamic causal modeling (DCM) of resting-state functional magnetic resonance imaging in dedicated regions of interest determined using a data-driven approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Abnormally increased functional connectivity between the bilateral dorsolateral prefrontal cortex (DLPFC) and the bilateral mesencephalic locomotor region (MLR) was identified in freezers compared with nonfreezers. Subsequently, spectral DCM analysis revealed that increased top-down excitatory effective connectivity from the left DLPFC to bilateral MLR and an independent self-inhibitory connectivity within the left DLPFC in freezers versus nonfreezers (&gt;99% posterior probability) were inversely associated with the severity of freezing of gait. The lateralization of these effective connectivity patterns was not attributable to the initial dopaminergic deficit nor to structural changes in these regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We have identified novel effective connectivity and an independent self-inhibitory connectivity underlying freezing of gait. Our findings imply that modulating the effective connectivity between the left DLPFC and MLR through neurostimulation or other interventions could be a target for reducing freezing of gait in PD. © 2024 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":"39 11","pages":"1982-1992"},"PeriodicalIF":7.4,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29988","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142245602","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":"Genetic Risk Factors in Isolated Dystonia Escape Genome-Wide Association Studies","authors":"Björn-Hergen Laabs PhD,&nbsp;Katja Lohmann PhD,&nbsp;Eva-Juliane Vollstedt MD,&nbsp;Tobias Reinberger PhD,&nbsp;Lisa-Marie Nuxoll MSc,&nbsp;Gamze Kilic-Berkmen PhD,&nbsp;Joel S. Perlmutter MD,&nbsp;Sebastian Loens MD,&nbsp;Carlos Cruchaga PhD,&nbsp;Andre Franke PhD,&nbsp;Valerija Dobricic PhD,&nbsp;Frauke Hinrichs,&nbsp;Anne Grözinger BSc,&nbsp;Eckart Altenmüller MD,&nbsp;Steven Bellows MD,&nbsp;Sylvia Boesch MD, MSc,&nbsp;Susan B. Bressman MD,&nbsp;Kevin R. Duque MD,&nbsp;Alberto J. Espay MD,&nbsp;Andreas Ferbert MD,&nbsp;Jeanne S. Feuerstein MD,&nbsp;Samuel Frank MD,&nbsp;Thomas Gasser MD,&nbsp;Bernhard Haslinger MD,&nbsp;Robert Jech MD, PhD,&nbsp;Frank Kaiser PhD,&nbsp;Christoph Kamm MD,&nbsp;Katja Kollewe MD,&nbsp;Andrea A. Kühn MD,&nbsp;Mark S. LeDoux MD, PhD,&nbsp;Ebba Lohmann MD,&nbsp;Abhimanyu Mahajan MD, MHS,&nbsp;Alexander Münchau MD,&nbsp;Trisha Multhaupt-Buell MS, CGC,&nbsp;Alexander Pantelyat MD,&nbsp;Sarah E. Pirio Richardson MD,&nbsp;Deborah Raymond MS, CGC,&nbsp;Stephen G. Reich MD,&nbsp;Rachel Saunders Pullman MD, MPH, MSc,&nbsp;Barbara Schormair PhD,&nbsp;Nutan Sharma MD, PhD,&nbsp;Azadeh Hamzehei Sichani MA,&nbsp;Kristina Simonyan MD, PhD, DrMed,&nbsp;Jens Volkmann MD,&nbsp;Aparna Wagle Shukla MD,&nbsp;Juliane Winkelmann MD,&nbsp;Laura J. Wright MA,&nbsp;Michael Zech MD,&nbsp;Kirsten E. Zeuner MD,&nbsp;Simone Zittel MD,&nbsp;Meike Kasten MD,&nbsp;Yan V. Sun PhD,&nbsp;Tobias Bäumer MD,&nbsp;Norbert Brüggemann MD,&nbsp;Laurie J. Ozelius PhD,&nbsp;Hyder A. Jinnah MD, PhD,&nbsp;Christine Klein MD,&nbsp;Inke R. König PhD","doi":"10.1002/mds.29968","DOIUrl":"10.1002/mds.29968","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Despite considerable heritability, previous smaller genome-wide association studies (GWASs) have not identified any robust genetic risk factors for isolated dystonia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The objective of this study was to perform a large-scale GWAS in a well-characterized, multicenter sample of &gt;6000 individuals to identify genetic risk factors for isolated dystonia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Array-based GWASs were performed on autosomes for 4303 dystonia participants and 2362 healthy control subjects of European ancestry with subgroup analysis based on age at onset, affected body regions, and a newly developed clinical score. Another 736 individuals were used for validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This GWAS identified no common genome-wide significant loci that could be replicated despite sufficient power to detect meaningful effects. Power analyses imply that the effects of individual variants are likely very small.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Moderate single-nucleotide polymorphism–based heritability indicates that common variants do not contribute to isolated dystonia in this cohort. Sequence-based GWASs (eg, by whole-genome sequencing) might help to better understand the genetic basis. © 2024 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":"39 11","pages":"2110-2116"},"PeriodicalIF":7.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29968","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236211","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":"Immediate Effect of Continuous Positive Airway Pressure Therapy on Sleep and Respiration in Patients with Multiple System Atrophy and Sleep-Disordered Breathing","authors":"Giulia Lazzeri MD,&nbsp;Marion Houot MSc,&nbsp;Maxime Patout MD, PhD,&nbsp;Cécile Londner MD,&nbsp;Carole Philippe MD, PhD,&nbsp;Stephane Attard MSc,&nbsp;Teddy Delpy MD,&nbsp;Joanna Ruggeri MSc,&nbsp;Bertrand Degos MD, PhD,&nbsp;Florence Cormier MD,&nbsp;Marie Vidailhet MD,&nbsp;Jean Cristophe Corvol MD, PhD,&nbsp;Isabelle Arnulf MD, PhD,&nbsp;David Grabli MD, PhD,&nbsp;Pauline Dodet MD","doi":"10.1002/mds.29993","DOIUrl":"10.1002/mds.29993","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sleep-disordered breathing (SDB; including stridor and sleep apnea syndromes) is frequent in multiple system atrophy (MSA), but the immediate effect of continuous positive airway pressure (CPAP) therapy is incompletely determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We sought to evaluate the acute effect and safety of CPAP therapy on SDB and sleep architecture, as well as the clinical characteristics of nonresponders to CPAP therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The measures of 63 consecutive patients with MSA who underwent a video-polysomnography during two consecutive nights (a first night in ambient air, a second night with or without CPAP, depending on the presence of SDB and availability of CPAP) in routine care were retrospectively collected. Linear mixed models assessed the two-night change in sleep and respiratory measures, comparing those with and without the CPAP therapy on the second night.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SDB was frequent and mainly associated with the cerebellar phenotype. The introduction of CPAP had immediate benefits, including the normalization of the apnea–hypopnea index and a resolution of stridor in more than two-thirds of the cases, decreased arousal index, and increased rapid eye movement sleep. CPAP therapy was well tolerated, and only two patients had emergent central apneas. Nonresponse to CPAP was generally associated with more severe motor disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CPAP seems a well-tolerated and effective therapy in patients with MSA and SDB in the short term. This treatment shows remarkable immediate benefits by objectively improving both respiratory disturbances and sleep architecture. © 2024 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":"39 11","pages":"2026-2038"},"PeriodicalIF":7.4,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29993","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236843","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":"NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations","authors":"Sara Bandres-Ciga PhD,&nbsp;Faraz Faghri PhD,&nbsp;Elisa Majounie PhD,&nbsp;Mathew J. Koretsky BSc,&nbsp;Jeffrey Kim BSc,&nbsp;Kristin S. Levine MSc,&nbsp;Hampton Leonard MSc,&nbsp;Mary B. Makarious PhD,&nbsp;Hirotaka Iwaki MD,&nbsp;Peter Wild Crea BSc,&nbsp;Dena G. Hernandez PhD,&nbsp;Sampath Arepalli BSc,&nbsp;Kimberley Billingsley PhD,&nbsp;Katja Lohmann PhD,&nbsp;Christine Klein MD, PhD,&nbsp;Steven J. Lubbe PhD,&nbsp;Edwin Jabbari MD, PhD,&nbsp;Paula Saffie-Awad MD,&nbsp;Derek Narendra MD, PhD,&nbsp;Armando Reyes-Palomares PhD,&nbsp;John P. Quinn PhD,&nbsp;Claudia Schulte PhD,&nbsp;Huw R. Morris MD, PhD,&nbsp;Bryan J. Traynor MD, PhD,&nbsp;Sonja W. Scholz MD, PhD,&nbsp;Henry Houlden MD, PhD,&nbsp;John Hardy PhD,&nbsp;Sonya Dumanis PhD,&nbsp;Ekemini Riley PhD,&nbsp;Cornelis Blauwendraat PhD,&nbsp;Andrew Singleton PhD,&nbsp;Mike Nalls PhD,&nbsp;Janina Jeff PhD,&nbsp;Dan Vitale MSc,&nbsp;the Global Parkinson's Genetics Program (GP2) and the Center for Alzheimer's and Related Dementias (CARD)","doi":"10.1002/mds.29902","DOIUrl":"10.1002/mds.29902","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Commercial genome-wide genotyping arrays have historically neglected coverage of genetic variation across populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to create a multi-ancestry genome-wide array that would include a wide range of neuro-specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We developed the Illumina NeuroBooster Array (NBA), a custom high-throughput and cost-effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples. This novel platform includes approximately 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease–related genome-wide association study loci across diverse populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this article, we describe NBA's potential as an efficient means for researchers to assess known and novel disease genetic associations in a multi-ancestry framework. The NBA can identify rare genetic variants and accurately impute more than 15 million common variants across populations. Apart from enabling sample prioritization for further whole-genome sequencing studies, we envisage that NBA will play a pivotal role in recruitment for interventional studies in the precision medicine space.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>From a broader perspective, the NBA serves as a promising means to foster collaborative research endeavors in the field of neurological disorders worldwide. Ultimately, this carefully designed tool is poised to make a substantial contribution to uncovering the genetic etiology underlying these debilitating conditions. © 2024 The Author(s). <i>Movement Disorders</i> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2039-2048"},"PeriodicalIF":7.4,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277687","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":"Unusual Age-Dependent Behavior of Leukocytes Telomere Length in Friedreich's Ataxia","authors":"Daniela Scarabino PhD,&nbsp;Liana Veneziano PhD,&nbsp;Suran Nethisinghe PhD,&nbsp;Elide Mantuano MSc,&nbsp;Alessia Fiore MSc,&nbsp;Giulia Granata MSc,&nbsp;Nita Solanky PhD,&nbsp;Ginevra Zanni MD, PhD,&nbsp;Francesca Cavalcanti MD,&nbsp;Rosa Maria Corbo MD,&nbsp;Paola Giunti MD, PhD","doi":"10.1002/mds.29976","DOIUrl":"10.1002/mds.29976","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by an expanded GAA repeat in the first intron of the <i>FXN</i> gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim of this study was to analyze leukocyte telomeres length (LTL) in FRDA to verify the possible relationships between LTL and disease progression. We investigated LTL in a cohort of FRDA biallelic patients (n = 61), heterozygous (n = 29), and age-matched healthy subjects (n = 87).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>LTL was measured by real-time polymerase chain reaction quantitative analysis (qPCR).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that before 35 years of age, leukocyte telomeres were longer in patients than in controls, whereas the reverse applies in patients above 36 years of age. Interestingly, LTL was greater than controls at any age in heterozygous subjects. This picture mirrors what has been previously observed in vitro in FRDA cultured fibroblasts, showing significantly longer telomeres at early passages because of activation of an alternative lengthening of telomeres (ALT)-like mechanism, but showing accelerated telomere shortening as population doubling increases. GAA1 repeat length is positively correlated with the LTL and negatively correlated with the age at blood sampling. The relationship of LTL with clinical parameters (cardiomyopathy, diabetes, dependence on a wheelchair) was also analyzed. Significantly shorter leukocyte telomeres were associated with the presence of cardiomyopathy, but not with diabetes and the dependence on a wheelchair.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, the present study indicates that telomere length analysis in FRDA may be a relevant biomarker for following the stages of the disease. © 2024 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":"39 11","pages":"2058-2066"},"PeriodicalIF":7.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29976","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131386","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":"IRF2BPL-Related Disorder, Causing Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech and Seizures (NEDAMSS) Is Characterized by Pathology Consistent with DRPLA","authors":"Sunita Venkateswaran MD,&nbsp;Jean Michaud MD,&nbsp;Yoko Ito PhD,&nbsp;Michael Geraghty MD, MSc,&nbsp;Evan C. Lewis MD,&nbsp;Benjamin Ellezam MD, PhD,&nbsp;Kym M. Boycott MD, PhD,&nbsp;David A. Dyment MD, PhD,&nbsp;Kristin D. Kernohan PhD,&nbsp;Care4Rare Canada Consortium","doi":"10.1002/mds.29938","DOIUrl":"10.1002/mds.29938","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Childhood neurodegenerative diseases often pose a challenge to clinicians to diagnose because of the degree of genetic heterogeneity and variable presentations. Here, we present a child with progressive neurodegeneration consisting of spasticity, dystonia, and ataxia in which postmortem pathological analysis led to the diagnosis of <i>interferon regulatory factor 2 binding protein like</i> (<i>IRF2BPL</i>)-related disorder.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Detailed postmortem gross and histological examination was conducted, and findings consistent with dentatorubral-pallidoluysian atrophy (DRPLA) and included polyglutamine (polyQ) inclusions. Follow up testing for the CAG repeat expansion at <i>ATN1</i> was non-diagnostic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Subsequent exome sequencing reanalysis of the research exome identified a pathogenic de novo <i>IRF2BPL</i> variant. The <i>IRF2BPL</i> c.562C&gt;T, p.(Arg188Ter) variant, distal to the polyQ repeat tract, results in variable mRNA levels depending on the cell type examined with decreased mRNA in the brain, as well as destabilization of the protein product and corresponding downstream molecular abnormalities in patient derived cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We provide the first detailed pathological description for <i>IRF2BPL</i>-related disorder, termed NEDAMSS (neurodevelopmental disorder with regression, abnormal movements, loss of speech and seizures; Mendelian Inheritance in Man, 618088) and evidence for the inclusion of this condition in the differential diagnosis of spastic-ataxic neurodegenerative conditions, reminiscent of DRPLA. Although the individuals with NEDAMSS do not carry an expansion, the polyQ repeat tract may play a role in the pathological inclusions that would represent a novel disease mechanism for polyQ repeats. © 2024 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2102-2109"},"PeriodicalIF":7.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118570","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":"Rest Tremor in Parkinson's Disease Is Associated with Ipsilateral Striatal Dopamine Transporter Binding","authors":"Kalle J. Niemi MD,&nbsp;Juha Sunikka MD,&nbsp;Hamid Soltanian-Zadeh PhD,&nbsp;Esmaeil Davoodi-Bojd PhD,&nbsp;Arman Rahmim PhD,&nbsp;Valtteri Kaasinen MD, PhD,&nbsp;Juho Joutsa MD, PhD","doi":"10.1002/mds.29997","DOIUrl":"10.1002/mds.29997","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;The cardinal motor symptoms of Parkinson's disease (PD) include rigidity, bradykinesia, and rest tremor. Rigidity and bradykinesia correlate with contralateral nigrostriatal degeneration and striatal dopamine deficit, but association between striatal dopamine function and rest tremor has remained unclear.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objective&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The aim of this study was to investigate the possible link between dopamine function and rest tremor using Parkinson's Progression Markers Initiative dataset, the largest prospective neuroimaging cohort of patients with PD.&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;Clinical, [&lt;sup&gt;123&lt;/sup&gt;I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([&lt;sup&gt;123&lt;/sup&gt;I]FP-CIT) single photon emission computed tomography (SPECT), and structural magnetic resonance imaging data from 354 early PD patients and 166 healthy controls were included in this study. We employed a novel approach allowing nonlinear registration of individual scans accurately to a standard space and voxelwise analyses of the association between motor symptoms and striatal dopamine transporter (DAT) binding.&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;Severity of both rigidity and bradykinesia was negatively associated with contralateral striatal DAT binding (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;FWE&lt;/sub&gt; &lt; 0.05 [FWE, family-wise error corrected]). However, rest tremor amplitude was positively associated with increased ipsilateral DAT binding (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;FWE&lt;/sub&gt; &lt; 0.05). The association between rest tremor and binding remained the same controlling for Hoehn &amp; Yahr stage, Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, bradykinesia–rigidity score, or motor phenotype. The association between rest tremor and binding was independent of bradykinesia-rigidity and replicated using 2-year follow-up data (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;FWE&lt;/sub&gt; &lt; 0.05).&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;In agreement with the existing literature, we did not find a consistent association between rest tremor and contralateral dopamine defect. However, our results demonstrate a link between rest tremor and increased or less decreased ipsilateral DAT binding. Our findings provide novel information about the association between dopaminergic function and parkinsonian rest tremor. © 2024 The Author(s). &lt;i&gt;Movement Disorders&lt;/i&gt; published by Wiley Periodicals LLC on behalf of Internati","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2014-2025"},"PeriodicalIF":7.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29997","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118571","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":"Systematic Review of the Cost of Illness of Parkinson's Disease from a Societal Perspective","authors":"Anke Wijers MD,&nbsp;Anirudhan Ravi MSc,&nbsp;Silvia M.A.A. Evers PhD,&nbsp;Gerrit Tissingh MD, PhD,&nbsp;Ghislaine A.P.G. van Mastrigt PhD","doi":"10.1002/mds.29995","DOIUrl":"10.1002/mds.29995","url":null,"abstract":"<p>Previous reviews on the cost of illness (COI) of Parkinson's disease (PD) have often focused on health-care costs due to PD, underestimating its effects on other sectors. This systematic review determines the COI of PD from a societal perspective. The protocol was registered in PROSPERO (ID: CRD42023428937). Embase, Medline, and EconLit were searched up to October 12, 2023, for studies determining the COI of PD from a societal perspective. From 2812 abstracts, 17 studies were included. The COI of PD averaged €20,911.37 per patient per year, increasing to almost €100,000 in the most severely affected patients. Health-care costs accounted for 46.1% of total costs, followed by productivity loss (37.4%) and costs to patient and family (16.4%). The COI of PD strongly varied between different geographical regions, with costs in North America 3.6 times higher compared to Asia. This study is the first to identify the relative importance of different cost items. Most important were reduced employment, government benefits, informal care, medication, nursing homes, and hospital admission. There was strong variety in the cost items that were included, with 55.2% of cost items measured in fewer than half of articles. Our review shows that PD-COI is high and appears in various cost sectors, with strong variety in the cost items included in different studies. Therefore, a guideline for the measurement of COI in PD should be developed to harmonize this. This article provides a first step toward the development of such a tool by identifying which cost items are most relevant. © 2024 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":"39 11","pages":"1938-1951"},"PeriodicalIF":7.4,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.29995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102712","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":"Skin Tau Quantification as a Novel Biomarker in Huntington's Disease","authors":"Iñigo Ruiz-Barrio MD,&nbsp;Anna Vázquez-Oliver PhD,&nbsp;Arnau Puig-Davi MSc,&nbsp;Elisa Rivas-Asensio BSc,&nbsp;Jesus Perez-Perez MD,&nbsp;Cristina Fernandez-Vizuete BSc,&nbsp;Andrea Horta-Barba PhD,&nbsp;Gonzalo Olmedo-Saura MD,&nbsp;Nil Salvat-Rovira BSc,&nbsp;Frederic Sampedro MD, PhD,&nbsp;Elena Vacchi PhD,&nbsp;Giorgia Melli MD, PhD,&nbsp;Javier Pagonabarraga MD, PhD,&nbsp;Jaime Kulisevsky MD, PhD,&nbsp;Saul Martinez-Horta PhD","doi":"10.1002/mds.29989","DOIUrl":"10.1002/mds.29989","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Emerging research implicates tau protein dysregulation in the pathophysiology of Huntington's disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigated skin tau quantification as a potential biomarker for Huntington's disease and its correlation with disease burden outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this cross-sectional study, we measured skin tau levels using enzyme-linked immunosorbent assay in 23 Huntington's disease mutations carriers and eight control subjects, examining group discrimination, correlations with genetic markers, clinical assessments, and neuroimaging data. Brain atrophy was quantified by both volumetric measurements from brain segmentation and a voxel-based morphometry approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings showed elevated skin tau levels in manifest Huntington's disease compared with premanifest and healthy controls. These levels correlated with CAG repeat length, CAG-Age-Product score, composite Unified Huntington's Disease Rating Scale Total Motor Score, cognitive assessments, and disease-related cortical and subcortical volumes, all independent of age and gender. Using skin tau levels in cluster analysis along with genetic and clinical measures led to improved subject stratification, providing enhanced distinction and validity of clusters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study not only confirms the feasibility of skin tau quantification in Huntington's disease but also establishes its potential as a biomarker for enhancing group classification and assessing disease severity across the Huntington's disease spectrum, opening new directions in biomarker research. © 2024 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"2067-2074"},"PeriodicalIF":7.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078666","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":"Glucagon-Like Peptide-1 Receptor Agonists and Risk of Parkinson's Disease in Patients with Type 2 Diabetes: A Population-Based Cohort Study","authors":"Huilin Tang MSc,&nbsp;Ying Lu BA,&nbsp;Michael S. Okun MD,&nbsp;William T. Donahoo MD,&nbsp;Adolfo Ramirez-Zamora MD,&nbsp;Fei Wang PhD,&nbsp;Yu Huang PhD,&nbsp;Melissa Armstrong MD, MSc,&nbsp;Mikael Svensson PhD,&nbsp;Beth A. Virnig PhD, MPH,&nbsp;Steven T. DeKosky MD,&nbsp;Jiang Bian PhD,&nbsp;Jingchuan Guo MD, PhD","doi":"10.1002/mds.29992","DOIUrl":"10.1002/mds.29992","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previous studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may have a disease-modifying effect in the development of Parkinson's disease (PD), but population studies yielded inconsistent results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The aim was to compare the risk of PD associated with GLP-1RAs compared to dipeptidyl peptidase 4 inhibitors (DPP4i) among older adults with type 2 diabetes (T2D).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using U.S. Medicare administrative data from 2016 to 2020, we conducted a population-based cohort study comparing the new use of GLP-1RA with the new use of DPP4i among adults aged ≥66 years with T2D. The primary endpoint was a new diagnosis of PD. A stabilized inverse probability of treatment weighting (sIPTW)–adjusted Cox proportional hazards regression model was employed to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for PD between GLP-1RA and DPP4i users.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study included 89,074 Medicare beneficiaries who initiated either GLP-1RA (n = 30,091) or DPP4i (n = 58,983). The crude incidence rate of PD was lower among GLP-1RA users than DPP4i users (2.85 vs. 3.92 patients per 1000 person-years). An sIPTW-adjusted Cox model showed that GLP-1RA users were associated with a 23% lower risk of PD than DPP4i users (HR, 0.77; 95% CI, 0.63–0.95). Our findings were largely consistent across different subgroup analyses such as sex, race, and molecular structure of GLP-1RA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Among Medicare beneficiaries with T2D, the new use of GLP-1RAs was significantly associated with a decreased risk of PD compared to the new use of DPP4i. © 2024 International Parkinson and Movement Disorder Society.</p>\u0000 </section>\u0000 </div>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 11","pages":"1960-1970"},"PeriodicalIF":7.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071611","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}