Movement Disorders最新文献

{"title":"α-Synuclein Gene Hypomethylation in LRRK2 Parkinson's Disease Patients.","authors":"Lorena de Mena, Guillem Parés, Alicia Garrido, Daniel F Pilco-Janeta, Manel Fernández, Jesica Pérez, Eduardo Tolosa, Ana Cámara, Francesc Valldeoriola, Mario Ezquerra, María-José Martí, Rubén Fernández-Santiago","doi":"10.1002/mds.30094","DOIUrl":"https://doi.org/10.1002/mds.30094","url":null,"abstract":"<p><strong>Background: </strong>α-Synuclein (SNCA) gene hypomethylation was reported in idiopathic Parkinson's disease (iPD). Based on a high clinical resemblance between iPD and leucine-rich repeat kinase 2 (LRRK2)-driven Parkinson's disease (L2PD), we investigated the epigenetic status of SNCA in an extensive LRRK2 clinical cohort from Spain.</p><p><strong>Methods: </strong>We assessed the methylation levels of 23 CpG sites in the SNCA promoter region using peripheral blood DNA from L2PD patients (n = 151), LRRK2 nonmanifesting carriers (n = 55), iPD patients (n = 115), and healthy control subjects (n = 154) (total: N = 475).</p><p><strong>Results: </strong>Compared with control subjects, we found significant SNCA hypomethylation in 11 of 23 CpGs in L2PD (48%), whereas 22 CpGs (96%) were hypomethylated in iPD. In line with a healthy status, asymptomatic mutation carriers had similar SNCA methylation profiles to control subjects.</p><p><strong>Conclusions: </strong>This study shows for the first time that SNCA hypomethylation occurs in patients with L2PD. Further studies addressing SNCA methylation status in additional worldwide LRRK2 cohorts are warranted. © 2024 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":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876009","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":"Subthalamic γ Oscillation Underlying Rapid Eye Movement Sleep Abnormality in Parkinsonian Patients","authors":"Lingxiao Guan, Huiling Yu, Yue Chen, Chen Gong, Hongwei Hao, Yi Guo, Shujun Xu, Yuhuan Zhang, Xuemei Yuan, Guoping Yin, Jianguo Zhang, Huiling Tan, Luming Li","doi":"10.1002/mds.30091","DOIUrl":"https://doi.org/10.1002/mds.30091","url":null,"abstract":"BackgroundAbnormal rapid eye movement (REM) sleep, including REM sleep behavior disorder (RBD) and reduced REM sleep, is common in Parkinson's disease (PD), highlighting the importance of further study on REM sleep. However, the biomarkers of REM disturbances remain unknown, leading to the lack of REM‐specific neuromodulation interventions.ObjectiveThis study aims to investigate the neurophysiological biomarkers of REM disturbance in parkinsonian patients.MethodsTen PD patients implanted with bilateral subthalamic nucleus‐deep brain stimulation (STN‐DBS) were included in this study, of whom 4 were diagnosed with RBD. Sleep monitoring was conducted 1 month after surgery. Subthalamic local field potentials (LFP) were recorded through sensing‐enabled DBS. The neurophysiological features of subthalamic LFP during phasic and tonic microstates of REM sleep and their correlation with REM sleep fragmentation and RBD were analyzed.ResultsDifferences in subthalamic γ oscillation between phasic and tonic REM correlated positively with the severity of REM sleep fragmentation. Patients with RBD also exhibited stronger γ oscillations during REM sleep compared with non‐RBD patients, and both increased β and γ were found before the onset of RBD episodes. Stimulation changes in simulated γ‐triggered feedback modulation followed more closely with phasic REM density, whereas an opposite trend was found in simulated β‐triggered feedback modulation.ConclusionExcess subthalamic γ oscillations may contribute to REM instability and RBD, suggesting that γ oscillation could serve as a feedback signal for adaptive DBS for REM sleep disorders. © 2024 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":"24 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The First Case of Autosomal Recessive Cerebellar Ataxia with Prominent Paroxysmal Non-kinesigenic Dyskinesia Caused by a Truncating FGF14 Variant in a Turkish Patient.","authors":"Dilşad Türkdoğan, Natalia Smolina, Şeyma Tekgül, Tuğçe Gül, Ahmet Yeşilyurt, Henry Houlden, Stephan Zuchner, Bernard Brais, David Pellerin, Ayşe Nazlı Başak","doi":"10.1002/mds.30087","DOIUrl":"https://doi.org/10.1002/mds.30087","url":null,"abstract":"<p><strong>Background: </strong>ATX-FGF/SCA27A has been exclusively associated with heterozygous variants in the FGF14 gene, presenting with postural tremor, slowly progressive cerebellar ataxia, and psychiatric and behavioral disturbances.</p><p><strong>Objectives: </strong>This study describes the first case of ATX-FGF/SCA27A linked to a biallelic frameshift variant in the FGF14 gene.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was conducted using the Illumina NovaSeq 6000 platform, and the identified variant was confirmed using Sanger sequencing.</p><p><strong>Results: </strong>We report the first case of autosomal recessive FGF14-related cerebellar ataxia caused by a c.75del variant resulting in p.Leu26Serfs*51 truncation of the FGF14 protein. This variant was found in a patient born to consanguineous parents and presented with a complex congenital nonprogressive cerebellar disorder accompanied by neurodevelopmental delay, intellectual disability, and prominent drug-responsive paroxysmal non-kinesigenic dyskinesia. Segregation analysis confirmed that the homozygous variant was inherited from heterozygous parents who developed mild gait ataxia and tremor in their 40s.</p><p><strong>Conclusions: </strong>Biallelic loss-of-function variants in FGF14 are a rare cause of inherited cerebellar ataxia and expand the current genetic spectrum of ATX-FGF14. © 2024 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862710","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":"A Short Progressive Supranuclear Palsy Quality of Life Scale: Data from the PSP-NET","authors":"Arianna Cappiello,&nbsp;Paolo Barone MD, PhD,&nbsp;Marina Picillo MD, PhD,&nbsp;The PSP-NET Study Group.","doi":"10.1002/mds.30052","DOIUrl":"10.1002/mds.30052","url":null,"abstract":"&lt;p&gt;We read with interest the article by Jensen and colleagues who proposed a condensed version of the Progressive Supranuclear Palsy Quality of Life scale (PSP-ShoQoL) as a reliable and practical tool to evaluate quality of life in PSP patients.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The proposed PSP-ShoQoL included 12 items divided into two subscales representing physical (seven items) and mental symptoms (five items) and was administered to 245 patients from the German PSP network. The internal consistency of both total and subscores was high within 0.83 and 0.90. The PSP-ShoQoL significantly correlated with the Progressive Supranuclear Scale-Rating Scale (PSP-RS) and the Geriatric Depression Scale (GDS) but not with the Montreal Cognitive Assessment scale (MoCA). With 12-month follow-up data on a subgroup of 94 patients, the authors showed that the PSP-ShoQoL presented fair sensitivity to change and test–retest reliability.&lt;/p&gt;&lt;p&gt;Herein, we present data on the PSP-ShoQoL on an independent PSP cohort, the Italian PSP-NET supported by Fondazione LIMPE.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; 413 PSP patients performed the same evaluations used by Jensen et al. except for the GDS that was substituted by the Hospital Anxiety and Depression Scale (HADS). Compared with the German cohort, the PSP-NET included older (age: mean ± standard deviation [SD] 71.2 ± 8.1 vs. 69.2 ± 7.4) and more severe patients (PSP-RS: 40.56 ± 16.85 vs. 33.8 ± 13.8) while disease duration was similar (years: 4.44 ± 2.70 vs. 4.1 ± 2.6). Accordingly, PSP-ShoQoL total and subscores were higher within the PSP-NET (PSP-ShoQoL total: 25.33 ± 11.3 vs. 19.27 ± 11.10; PSP-ShoQoL Physical: 18.6 ± 8.2 vs. 13.74 ± 8.25; PSP-ShoQoL Mental: 6.7 ± 5.1 vs. 5.53 ± 4.67). We confirm a fair internal consistency for both the total score (Cronbach's alpha: 0.87) and subscores (Physical: 0.89; Mental: 0.80). The PSP-ShoQoL correlated significantly with the original PSP-QoL (&lt;i&gt;r&lt;/i&gt; = 0.945, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), the PSP-RS (&lt;i&gt;r&lt;/i&gt; = 0.646, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), the MoCA (−0.340, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), and the HADS (&lt;i&gt;r&lt;/i&gt; = 0.602, &lt;i&gt;P&lt;/i&gt; &lt; 0.001). With 6-month follow-up data available for 80 patients, we revealed a significant increase in both PSP-ShoQoL total score (&lt;i&gt;t&lt;/i&gt; = 5.24, &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and Physical (&lt;i&gt;t&lt;/i&gt; = 5.45, &lt;i&gt;P&lt;/i&gt; &lt; 0.001) and Mental (−2.78, &lt;i&gt;P&lt;/i&gt; &lt; 0.05) subscores. Test–retest reliability was good both for PSP-ShoQoL total score (intraclass correlation coefficient [ICC] = 0.78, &lt;i&gt;P&lt;/i&gt; &lt; 0.001), as well as for its subscales (Physical ICC = 0.80, &lt;i&gt;P&lt;/i&gt; &lt; 0.00; Mental ICC = 0.68, &lt;i&gt;P&lt;/i&gt; &lt; 0.001). Finally, by analyzing the area under the curve (AUC) we identified a value of 34.5 as a discriminating cutoff for a significant impairment of quality of patients' life measured by the PSP-ShoQoL within the PSP-NET (sensibility: 0.97; specificity: 0.15; AUC: 0.93) (Fig. 1).&lt;/p&gt;&lt;p&gt;Jensen and coworkers proposed a brief instrument with fair psychometric properties fo","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 12","pages":"2305-2307"},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851639","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":"Movement Disorders: Volume 39, Number 12, December 2024","authors":"","doi":"10.1002/mds.30088","DOIUrl":"10.1002/mds.30088","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mds.30088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858427","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 Analysis of GCA Repeats in the GLS Gene: Implications for Undiagnosed Ataxia and Spinocerebellar Ataxia 3 in Mainland China.","authors":"Lijing Lei, Linliu Peng, Linlin Wan, Zhao Chen, Chunrong Wang, Huirong Peng, Rong Qiu, Beisha Tang, Hong Jiang","doi":"10.1002/mds.30083","DOIUrl":"https://doi.org/10.1002/mds.30083","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have reported that expanded GCA repeats in the GLS gene can cause glutaminase deficiency with ataxia phenotype. However, to data, no studies have investigated the distribution and role of GCA repeats in the GLS gene of Chinese individuals.</p><p><strong>Objective: </strong>The aim was to investigate the distribution of GCA repeats in Chinese individuals, including undiagnosed ataxia patients for identifying causal factors, healthy controls for determining the normal range, and ATX-ATXN3 (spinocerebellar ataxia type 3, SCA3) patients for exploring genetic modifiers.</p><p><strong>Methods: </strong>We combined whole-genome sequencing (WGS), repeat-primed polymerase chain reaction, capillary electrophoresis (RP-PCR/CE), and ExpansionHunter to screen the GCA repeats in the GLS gene of 349 undiagnosed ataxia individuals, 1505 healthy controls, and 1236 ATX-ATXN3 (SCA3) patients from mainland China.</p><p><strong>Results: </strong>No expanded GCA repeats in the GLS gene were detected across any of the samples. The average number of GCA repeats was 11 (range: 8-31), 12 (range: 6-33), and 11 (range: 6-33) for undiagnosed ataxia patients, healthy controls, and SCA3 patients, respectively. The intermediate repeat size (9 < repeat size ≤ 13) of the nonexpanded GCA allele in the GLS gene was associated with later disease onset in ATX-ATXN3 (SCA3) patients.</p><p><strong>Conclusions: </strong>Abnormal expansions of GLS GCA repeats are rare in the Chinese population. However, intermediate-length normal GCA repeat sizes may influence the age at onset (AAO) in ATX-ATXN3 (SCA3) patients. © 2024 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851632","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":"Reply to: “A Short Progressive Supranuclear Palsy Quality of Life Scale: Data from the PSP-NET”","authors":"Ida Jensen MD,&nbsp;Sarah Bebermeier PhD,&nbsp;Stephanie Stiel MD,&nbsp;Günter U. Höglinger MD,&nbsp;Martin Klietz MD","doi":"10.1002/mds.30049","DOIUrl":"10.1002/mds.30049","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 12","pages":"2307-2308"},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851648","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":"December Infographic","authors":"","doi":"10.1002/mds.29495","DOIUrl":"10.1002/mds.29495","url":null,"abstract":"<p>\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 A Homozygous Variant in <i>NAA60</i> Is Associated with Primary Familial Brain Calcification</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 12","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/10.1002/mds.29495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858425","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":"FDA Boosts the Progressive Supranuclear Palsy Rating Scale!","authors":"Cristina Sampaio MD, PhD","doi":"10.1002/mds.30040","DOIUrl":"10.1002/mds.30040","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"39 12","pages":"2127-2129"},"PeriodicalIF":7.4,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851645","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":"Association between the Amplification Parameters of the α-Synuclein Seed Amplification Assay and Clinical and Genetic Subtypes of Parkinson's Disease.","authors":"Piergiorgio Grillo, Luis Concha-Marambio, Antonio Pisani, Giulietta Maria Riboldi, Un Jung Kang","doi":"10.1002/mds.30085","DOIUrl":"https://doi.org/10.1002/mds.30085","url":null,"abstract":"<p><strong>Background: </strong>α-Synuclein seed amplification assay on cerebrospinal fluid (CSF-αSyn-SAA) has shown high accuracy for Parkinson's disease (PD) diagnosis. The analysis of CSF-αSyn-SAA parameters may provide useful insight to dissect the heterogeneity of synucleinopathies.</p><p><strong>Objective: </strong>To assess differences in CSF-αSyn-SAA amplification parameters in participants with PD stratified by rapid eye movement (REM) sleep behavior disorder (RBD), dysautonomia, GBA, and LRRK2 variants.</p><p><strong>Methods: </strong>Clinical and CSF-αSyn-SAA data from the Parkinson's Progression Marker Initiative dataset were used. CSF-αSyn-SAA parameters included maximum fluorescence (F_max), time to reach 50% of F_max (T50), time to threshold (TTT), slope, and area under the curve (AUC). Sporadic PD (n = 371) was stratified according to RBD and dysautonomia (DysA) symptoms. Genetic PD included carriers of pathogenic variants of GBA (GBA-PD, n = 52) and LRRK2 (LRRK2-PD, n = 124) gene.</p><p><strong>Results: </strong>CSF-αSyn-SAA was positive in 77% of LRRK2-PD, 92.3% of GBA-PD, and 93.8% of sporadic PD. The LRRK2-PD cohort showed longer T50 and TTT, and smaller AUC than GBA-PD (P = 0.029, P = 0.029, P = 0.016, respectively) and sporadic PD (P = 0.034, P = 0.033, P = 0.014, respectively). In the sporadic cohort, CSF-αSyn-SAA parameters were similar between PD with (n = 157) and without (n = 190) RBD, whereas participants with DysA (n = 193) presented shorter T50 (P = 0.026) and larger AUC (P = 0.029) than those without (n = 150).</p><p><strong>Conclusion: </strong>CSF-αSyn-SAA parameters vary across genetic and non-genetic PD subtypes at the group level. These differences are mostly driven by the presence of LRRK2 variants and DysA. Significant overlaps in the amplification parameter values exist between groups and limit their use at the individual level. Further studies are necessary to understand the mechanisms of CSF-αSyn-SAA parameter differences. © 2024 International Parkinson and Movement Disorder Society.</p>","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845349","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}