Transforming Care Across Countries: Lessons from the Integrated Care Networks for Parkinson's Disease Study (iCARE-PD).
改变各国的护理:来自帕金森病综合护理网络研究(iCARE-PD)的经验教训。
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-27
DOI: 10.1002/mds.70110
Deepa Dash,Margherita Fabbri,Joseph Saade,Marlena van Munster,David Pedrosa,Evzen Růžička,Ota Gal,Joaquim J Ferreira,Álvaro Sánchez-Ferro,Timothy Lynch,Carsten Eggers,Aashiyan Singh,David Grimes,Monica Taljaard,Oliver Rascol,Tiago A Mestre,
BACKGROUNDThe optimal design for care delivery in Parkinson's disease (PD) that addresses changing needs of the lived experience is unclear. There is a critical need for care models to be implemented and transferable across diverse healthcare systems with agility.OBJECTIVESWe aimed to evaluate the multinational implementation and impact of a novel pragmatic integrated care delivery program for PD (iCARE-PD).METHODSWe conducted a multinational prospective observational study with a pre-post design (six national PD tertiary centers) of a 4-month integrated care program focused on individualized care plans, enhanced system navigation, and self-care support.PRIMARY OUTCOMESenrollment and program completion rates.SECONDARY OUTCOMEStransnational feasibility of program implementation, processes outcomes, acceptability, and preliminary estimates of health-related outcomes changes.RESULTSBetween May 2021 and February 2023, we enrolled 202 participants ("Newly Diagnosed," n = 43; "Intermediate," n = 54; "Complex Care Needs," n = 105). Median site enrollment rate was 69.6% (range: 21.1-100), and the program completion rate was 96.5%. Overall, there was a positive change in Patient Assessment of Chronic Illness Care + (PACIC+ total score: 0.48; 95% confidence interval [CI]: 0.34, 0.61; P < 0.0001). We found a positive score change in the MDS-UPDRS Part II + III nontremor (4.03; 95% CI: 6.55, 1.52; P = 0.0018) in the "Complex Care Needs" group.CONCLUSIONSThe iCARE-PD model was successfully implemented across a social, cultural, and healthcare system diversity, with high program completion rates and improved care quality perceived by participants living at distinct stages of PD. The findings provide valuable insights about the transferability potential and impact of a pragmatic integrated care model centered in the community, with applicability to other chronic movement disorders. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
求助PDF
{"title":"Transforming Care Across Countries: Lessons from the Integrated Care Networks for Parkinson's Disease Study (iCARE-PD).","authors":"Deepa Dash,Margherita Fabbri,Joseph Saade,Marlena van Munster,David Pedrosa,Evzen Růžička,Ota Gal,Joaquim J Ferreira,Álvaro Sánchez-Ferro,Timothy Lynch,Carsten Eggers,Aashiyan Singh,David Grimes,Monica Taljaard,Oliver Rascol,Tiago A Mestre, ","doi":"10.1002/mds.70110","DOIUrl":"https://doi.org/10.1002/mds.70110","url":null,"abstract":"BACKGROUNDThe optimal design for care delivery in Parkinson's disease (PD) that addresses changing needs of the lived experience is unclear. There is a critical need for care models to be implemented and transferable across diverse healthcare systems with agility.OBJECTIVESWe aimed to evaluate the multinational implementation and impact of a novel pragmatic integrated care delivery program for PD (iCARE-PD).METHODSWe conducted a multinational prospective observational study with a pre-post design (six national PD tertiary centers) of a 4-month integrated care program focused on individualized care plans, enhanced system navigation, and self-care support.PRIMARY OUTCOMESenrollment and program completion rates.SECONDARY OUTCOMEStransnational feasibility of program implementation, processes outcomes, acceptability, and preliminary estimates of health-related outcomes changes.RESULTSBetween May 2021 and February 2023, we enrolled 202 participants (\"Newly Diagnosed,\" n = 43; \"Intermediate,\" n = 54; \"Complex Care Needs,\" n = 105). Median site enrollment rate was 69.6% (range: 21.1-100), and the program completion rate was 96.5%. Overall, there was a positive change in Patient Assessment of Chronic Illness Care + (PACIC+ total score: 0.48; 95% confidence interval [CI]: 0.34, 0.61; P < 0.0001). We found a positive score change in the MDS-UPDRS Part II + III nontremor (4.03; 95% CI: 6.55, 1.52; P = 0.0018) in the \"Complex Care Needs\" group.CONCLUSIONSThe iCARE-PD model was successfully implemented across a social, cultural, and healthcare system diversity, with high program completion rates and improved care quality perceived by participants living at distinct stages of PD. The findings provide valuable insights about the transferability potential and impact of a pragmatic integrated care model centered in the community, with applicability to other chronic movement disorders. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"204 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609914","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
引用
批量引用
Nuclear Alpha‐Synuclein: Mechanisms and Implications for Synucleinopathies
核α -突触核蛋白:突触核蛋白病的机制和意义
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-26
DOI: 10.1002/mds.70138
Tiago Fleming Outeiro, David J. Koss
Alpha‐synuclein (aSyn), historically studied for its synaptic functions and central role in Lewy body pathology, is emerging as a protein with significant nuclear activities relevant to Parkinson's disease (PD) and related synucleinopathies. Recent advances reveal that aSyn dynamically localizes to neuronal nuclei in both health and disease, where its interactions with chromatin and DNA may contribute to the regulation of genomic stability, DNA damage responses, and cellular aging. Studies using experimental models demonstrate that nuclear aSyn promotes neurodegeneration through transcriptional dysregulation, DNA repair deficits, and cellular senescence, especially when present in phosphorylated or oligomeric forms. The detection of nuclear aSyn in human tissues has proven challenging, but improvements in immunohistochemical and molecular techniques now allow deeper exploration of its physiological and pathological states. Mechanistic studies indicate that aSyn can modulate nuclear import pathways and directly interact with genomic repair machinery, suggesting new avenues for disease modification. As such, nuclear aSyn represents both a promising biomarker for disease stratification and a potential therapeutic target. Integrating mechanistic, biomarker, and translational research on nuclear aSyn may transform our understanding of PD progression and enable precision medicine approaches for early diagnosis and intervention in synucleinopathies. © 2025 International Parkinson and Movement Disorder Society.
求助PDF
{"title":"Nuclear Alpha‐Synuclein: Mechanisms and Implications for Synucleinopathies","authors":"Tiago Fleming Outeiro, David J. Koss","doi":"10.1002/mds.70138","DOIUrl":"https://doi.org/10.1002/mds.70138","url":null,"abstract":"Alpha‐synuclein (aSyn), historically studied for its synaptic functions and central role in Lewy body pathology, is emerging as a protein with significant nuclear activities relevant to Parkinson's disease (PD) and related synucleinopathies. Recent advances reveal that aSyn dynamically localizes to neuronal nuclei in both health and disease, where its interactions with chromatin and DNA may contribute to the regulation of genomic stability, DNA damage responses, and cellular aging. Studies using experimental models demonstrate that nuclear aSyn promotes neurodegeneration through transcriptional dysregulation, DNA repair deficits, and cellular senescence, especially when present in phosphorylated or oligomeric forms. The detection of nuclear aSyn in human tissues has proven challenging, but improvements in immunohistochemical and molecular techniques now allow deeper exploration of its physiological and pathological states. Mechanistic studies indicate that aSyn can modulate nuclear import pathways and directly interact with genomic repair machinery, suggesting new avenues for disease modification. As such, nuclear aSyn represents both a promising biomarker for disease stratification and a potential therapeutic target. Integrating mechanistic, biomarker, and translational research on nuclear aSyn may transform our understanding of PD progression and enable precision medicine approaches for early diagnosis and intervention in synucleinopathies. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"107 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598824","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
引用
批量引用
A Complex FGF14 ( TTC )/( TGC ) Repeat Expansion in Parkinson's Disease
帕金森病中一种复杂的FGF14 (TTC)/(TGC)重复扩增
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-24
DOI: 10.1002/mds.70128
Xiaosheng Zheng, Zhidong Cen, Xinhui Chen, Fan Zhang, Chenxin Ying, Nan Jin, Peng Liu, Yilin Chen, Haotian Wang, Jiaxiang Li, Joanne Trinh, Joshua Laß, David Pellerin, Matt C. Danzi, Stephan Zuchner, Bernard Brais, Shen‐Yang Lim, Ai Huey Tan, Azlina Ahmad‐Annuar, Dehao Yang, Lebo Wang, Zhiru Lin, Fei Xie, Bo Wang, Sheng Wu, Zhiyuan Ouyang, Piu Chan, Shen Hu, Christine Klein, Hou‐Feng Zheng, Chaodong Wang, Wei Luo
Background Repeat expansions have been reported as genetic causes/risk factors of Parkinson's disease (PD). As a novel repeat expansion locus, the FGF14‐SCA27B (GAA)•(TTC) repeat locus is unexplored in PD. Methods Utilizing genetic sequencing and various polymerase chain reaction (PCR) methodologies, pure and complex repeat expansions in FGF14 were detected in Asian PD patients. Targeted long—read sequencing was performed to investigate the detailed sequence composition of these repeat expansions. Case–control studies were further performed. Results Pure (TTC) ≥250 repeat expansion was detected in 2 of 1190 PD patients (0.17%). Additionally, a more common and complex (TTC)/(TGC) ≥300 repeat expansion was detected as the main expanded genotype in our discovery cluster. Using targeted long‐read sequencing, these complex (TTC)/(TGC) repeat expansions were characterized as (TTC)exp(TGCTTC)exp(TGCTTCTTCTTCTTC)n(TTC)n alleles with four segments (Seg 1–4), and further classified into four genotypic patterns. Pattern 1 was mainly characterized by a (CTC) interruption in the Seg 1‐(TTC)exp. Patterns 2–4 were characterized by different repeat length of Seg 1‐(TTC)exp and Seg 3‐(TGCTTCTTCTTCTTC)n. Case–control analysis revealed a significant enrichment of Pattern 4 (TTC)/(TGC) repeat expansion in PD compared with controls ( P = 0.024, OR: 2.60, 95% CI: 1.07–7.23) in the discovery cluster. This significant association between Pattern 4 (TTC)/(TGC) repeat expansion and PD was confirmed in one of two replication clusters ( P = 0.035, OR: 2.18, 95% CI: 0.95–4.53) and the meta‐analysis across all three clusters ( P = 0.015, OR: 1.75, 95% CI: 1.10–2.79). Interpretation We identified a unique complex (TTC)/(TGC) repeat expansion in FGF14 as a novel genetic risk factor of PD in the Asian population. © 2025 International Parkinson and Movement Disorder Society.
求助PDF
{"title":"A Complex FGF14 ( TTC )/( TGC ) Repeat Expansion in Parkinson's Disease","authors":"Xiaosheng Zheng, Zhidong Cen, Xinhui Chen, Fan Zhang, Chenxin Ying, Nan Jin, Peng Liu, Yilin Chen, Haotian Wang, Jiaxiang Li, Joanne Trinh, Joshua Laß, David Pellerin, Matt C. Danzi, Stephan Zuchner, Bernard Brais, Shen‐Yang Lim, Ai Huey Tan, Azlina Ahmad‐Annuar, Dehao Yang, Lebo Wang, Zhiru Lin, Fei Xie, Bo Wang, Sheng Wu, Zhiyuan Ouyang, Piu Chan, Shen Hu, Christine Klein, Hou‐Feng Zheng, Chaodong Wang, Wei Luo","doi":"10.1002/mds.70128","DOIUrl":"https://doi.org/10.1002/mds.70128","url":null,"abstract":"Background Repeat expansions have been reported as genetic causes/risk factors of Parkinson's disease (PD). As a novel repeat expansion locus, the FGF14‐SCA27B (GAA)•(TTC) repeat locus is unexplored in PD. Methods Utilizing genetic sequencing and various polymerase chain reaction (PCR) methodologies, pure and complex repeat expansions in <jats:italic>FGF14</jats:italic> were detected in Asian PD patients. Targeted long—read sequencing was performed to investigate the detailed sequence composition of these repeat expansions. Case–control studies were further performed. Results Pure (TTC) <jats:sub>≥250</jats:sub> repeat expansion was detected in 2 of 1190 PD patients (0.17%). Additionally, a more common and complex (TTC)/(TGC) <jats:sub>≥300</jats:sub> repeat expansion was detected as the main expanded genotype in our discovery cluster. Using targeted long‐read sequencing, these complex (TTC)/(TGC) repeat expansions were characterized as (TTC)exp(TGCTTC)exp(TGCTTCTTCTTCTTC)n(TTC)n alleles with four segments (Seg 1–4), and further classified into four genotypic patterns. Pattern 1 was mainly characterized by a (CTC) interruption in the Seg 1‐(TTC)exp. Patterns 2–4 were characterized by different repeat length of Seg 1‐(TTC)exp and Seg 3‐(TGCTTCTTCTTCTTC)n. Case–control analysis revealed a significant enrichment of Pattern 4 (TTC)/(TGC) repeat expansion in PD compared with controls ( <jats:italic>P</jats:italic> = 0.024, OR: 2.60, 95% CI: 1.07–7.23) in the discovery cluster. This significant association between Pattern 4 (TTC)/(TGC) repeat expansion and PD was confirmed in one of two replication clusters ( <jats:italic>P</jats:italic> = 0.035, OR: 2.18, 95% CI: 0.95–4.53) and the meta‐analysis across all three clusters ( <jats:italic>P</jats:italic> = 0.015, OR: 1.75, 95% CI: 1.10–2.79). Interpretation We identified a unique complex (TTC)/(TGC) repeat expansion in <jats:italic>FGF14</jats:italic> as a novel genetic risk factor of PD in the Asian population. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"107 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582894","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
引用
批量引用
Pallidal Evoked Resonant Neural Activity as a Candidate Biomarker for Deep Brain Stimulation in Dystonia
白斑诱发共振神经活动作为肌张力障碍深部脑刺激的候选生物标志物
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-22
DOI: 10.1002/mds.70129
Kara A. Johnson, Patricia B. Coutinho, Filipe P. Sarmento, Elizabeth Vo, Joshua K. Wong, Justin D. Hilliard, Kelly D. Foote, Coralie de Hemptinne
Background Deep brain stimulation (DBS) targeted to the globus pallidus (GP) can effectively alleviate dystonia symptoms. However, identifying optimal therapeutic stimulation parameters is challenging due to the manual programming process and the paucity of acute effects of DBS on dystonia symptoms. Objective This study aimed to investigate evoked resonant neural activity (ERNA) in the GP as a potential biomarker to guide DBS contact selection for chronic therapy in patients with dystonia. Methods In n = 8 patients (n = 9 hemispheres) undergoing GP DBS implantation for dystonia, intraoperative local field potential (LFP) recordings were acquired at resting state (30 seconds) and during bursts of high‐frequency stimulation delivered from each DBS contact. ERNA features (amplitude, frequency, and number of peaks) were measured and correlated with dystonia symptom severity, resting‐state LFP spectral power, and postoperative chronic (12‐month) therapeutic stimulation parameters. Results ERNA was consistently elicited by GP DBS but varied in amplitude, frequency, and number of peaks across individuals and stimulating contacts. Higher ERNA amplitudes were associated with stimulation at the GP internus/externus border. ERNA frequency was negatively correlated with cervical dystonia severity ( P < 0.001) and resting‐state alpha (8–12 Hz) power ( P < 0.05). In eight of nine (88.9%) hemispheres, the DBS contact that elicited the maximum ERNA matched the contact empirically selected for chronic therapy by expert clinicians through routine clinical programming. Conclusions Based on its correlation with dystonia symptom severity and therapeutic contact for chronic DBS, ERNA shows promise as an objective candidate biomarker to improve the efficiency and efficacy of DBS for dystonia. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
求助PDF
{"title":"Pallidal Evoked Resonant Neural Activity as a Candidate Biomarker for Deep Brain Stimulation in Dystonia","authors":"Kara A. Johnson, Patricia B. Coutinho, Filipe P. Sarmento, Elizabeth Vo, Joshua K. Wong, Justin D. Hilliard, Kelly D. Foote, Coralie de Hemptinne","doi":"10.1002/mds.70129","DOIUrl":"https://doi.org/10.1002/mds.70129","url":null,"abstract":"Background Deep brain stimulation (DBS) targeted to the globus pallidus (GP) can effectively alleviate dystonia symptoms. However, identifying optimal therapeutic stimulation parameters is challenging due to the manual programming process and the paucity of acute effects of DBS on dystonia symptoms. Objective This study aimed to investigate evoked resonant neural activity (ERNA) in the GP as a potential biomarker to guide DBS contact selection for chronic therapy in patients with dystonia. Methods In n = 8 patients (n = 9 hemispheres) undergoing GP DBS implantation for dystonia, intraoperative local field potential (LFP) recordings were acquired at resting state (30 seconds) and during bursts of high‐frequency stimulation delivered from each DBS contact. ERNA features (amplitude, frequency, and number of peaks) were measured and correlated with dystonia symptom severity, resting‐state LFP spectral power, and postoperative chronic (12‐month) therapeutic stimulation parameters. Results ERNA was consistently elicited by GP DBS but varied in amplitude, frequency, and number of peaks across individuals and stimulating contacts. Higher ERNA amplitudes were associated with stimulation at the GP internus/externus border. ERNA frequency was negatively correlated with cervical dystonia severity ( <jats:italic>P</jats:italic> < 0.001) and resting‐state alpha (8–12 Hz) power ( <jats:italic>P</jats:italic> < 0.05). In eight of nine (88.9%) hemispheres, the DBS contact that elicited the maximum ERNA matched the contact empirically selected for chronic therapy by expert clinicians through routine clinical programming. Conclusions Based on its correlation with dystonia symptom severity and therapeutic contact for chronic DBS, ERNA shows promise as an objective candidate biomarker to improve the efficiency and efficacy of DBS for dystonia. © 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":"8 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567102","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
引用
批量引用
Propranolol for Tremors in Spinocerebellar Ataxia Type 12: A Randomized Clinical Trial
心得安治疗脊髓小脑性共济失调12型震颤的随机临床试验
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-20
DOI: 10.1002/mds.70115
Prachi Mohapatra, Achal Kumar Srivastava, Divyani Garg, Ayush Agarwal, Divya M. Radhakrishnan, Awadh Kishor Pandit, Pooja Gupta, Sahaj Agrawal, Ashish Datt Upadhyay
求助PDF
{"title":"Propranolol for Tremors in Spinocerebellar Ataxia Type 12: A Randomized Clinical Trial","authors":"Prachi Mohapatra, Achal Kumar Srivastava, Divyani Garg, Ayush Agarwal, Divya M. Radhakrishnan, Awadh Kishor Pandit, Pooja Gupta, Sahaj Agrawal, Ashish Datt Upadhyay","doi":"10.1002/mds.70115","DOIUrl":"https://doi.org/10.1002/mds.70115","url":null,"abstract":"Background Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disorder with prominent upper limb tremors. No trials have evaluated tremor‐targeted therapies in this population. Objectives We evaluated long‐acting propranolol for efficacy and safety in reducing tremors and improving ataxia and quality of life in SCA12. Methods In this single‐center, randomized, double‐blind, placebo‐controlled trial, 60 genetically confirmed SCA12 patients (aged 18–65 years; TETRAS PS [The Essential Tremor Rating Assessment Scale Performance Subscale] upper limb component ≥2) were randomized 1:1 to receive extended‐release propranolol or placebo. Propranolol was escalated by 40 mg/week (placebo by one tablet/week) up to 240 mg/day, limiting side effects or ≥30% reduction in TETRAS PS/ADL (Activities‐of‐Daily‐Living Subscale) + PS. The stable dose was continued for 8 weeks (maintenance phase). Primary outcomes were changes from baseline in TETRAS PS and ADL + PS at maintenance weeks 4 and 8. Secondary outcomes included changes in the Scale for the Assessment and Rating of Ataxia (SARA), RAND 36‐Item Short‐Form Health Survey (SF‐36) domains, and accelerometric tremor parameters. Results Propranolol significantly reduced TETRAS PS (LSM ± SE: −4.4 ± 0.3 at week 4; −4.42 ± 0.4 at week 8) and ADL + PS (−5.5 ± 0.63 at week 4; −5.56 ± 0.62 at week 8; <jats:italic>P</jats:italic> < 0.001 vs. placebo). Significant improvements were also noted in SARA and five of nine SF‐36 domains at both time points. Accelerometry confirmed reductions in tremor peak frequency and power in all positions except rest. Fatigue and headache were the commonest adverse effects, with no discontinuations due to adverse events. Conclusion Propranolol effectively reduced tremors and improved quality of life in SCA12, with good tolerability. © 2025 International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"7 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553749","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
引用
批量引用
Actor or Observer: The Sensorimotor Striatum Shapes Motor Output for Learned but Not Innate Motor Tasks
演员或观察者:感觉运动纹状体决定了习得而非先天运动任务的运动输出
IF 7.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-20
DOI: 10.1002/mds.70137
Christian Espinoza-Vinces MD, Conor Fearon MD, PhD
求助PDF
{"title":"Actor or Observer: The Sensorimotor Striatum Shapes Motor Output for Learned but Not Innate Motor Tasks","authors":"Christian Espinoza-Vinces MD, Conor Fearon MD, PhD","doi":"10.1002/mds.70137","DOIUrl":"10.1002/mds.70137","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 1","pages":"68-69"},"PeriodicalIF":7.6,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553750","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
引用
批量引用
Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.
帕金森病相关的LRRK2和GBA1突变调节对铜绿假单胞菌的外周免疫反应
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-19
DOI: 10.1002/mds.70123
Julian R Mark,Hannah A Staley,Ann M Titus,Julian Agin-Liebes,Alicia Garrido,Laura Hughes,Nicolas Dzamko,Rebecca L Wallings,Malú Gámez Tansey
BACKGROUNDPeripheral disease mechanisms such as immune dysregulation may contribute to Parkinson's disease (PD). To investigate interactions between common PD mutations and immune responses to environmental pathogens, we studied responses to Pseudomonas aeruginosa (P. aeruginosa) in peripheral blood mononuclear cells (PBMCs) from PD patients with leucine-rich repeat kinase 2 (LRRK2) mutations, GBA1 mutations, and idiopathic disease (iPD) relative to neurologically healthy controls (NHC).OBJECTIVESThe goal was to test the hypothesis that LRRK2 and GBA modify the human peripheral immune response to bacteria, specifically P. aeruginosa, based on prior animal studies involving Lrrk2 mutations and microbial pathogens.METHODSPBMCs from LRRK2-PD, GBA-PD, and iPD patients plus age- and sex-matched controls were treated ex vivo with live P. aeruginosa and pharmacological agents that block LRRK2 kinase activity (MLi-2) or enhance glucocerebrosidase (GCase) activation (NCGC00188758) to measure enzymatic activities and cytokine release.RESULTSGBA-PD PBMCs exhibited increased P. aeruginosa-dependent secretion of specific inflammatory cytokines including interleukin-1β. Antigen presentation was increased in LRRK2-PD nonclassical monocytes treated with the GCase activator. Levels of pRab10, a proxy for LRRK2 kinase activity, were increased in GBA-PD classical monocytes relative to NHC and iPD. GCase activator treatment increased pRab10 expression in LRRK2-PD intermediate monocytes. GBA-PD and individual treatments with MLi-2 or GCase activator were associated with reduced P. aeruginosa-dependent LRRK2 protein levels in PBMC subsets.CONCLUSIONSThis work demonstrates that PD-linked mutations in LRRK2 and GBA1 converge on peripheral blood immune cell dysregulation, as evinced by the ability of LRRK2 inhibitors and GCase activators to modulate the ex vivo immune response to bacterial exposure. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
求助PDF
{"title":"Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.","authors":"Julian R Mark,Hannah A Staley,Ann M Titus,Julian Agin-Liebes,Alicia Garrido,Laura Hughes,Nicolas Dzamko,Rebecca L Wallings,Malú Gámez Tansey","doi":"10.1002/mds.70123","DOIUrl":"https://doi.org/10.1002/mds.70123","url":null,"abstract":"BACKGROUNDPeripheral disease mechanisms such as immune dysregulation may contribute to Parkinson's disease (PD). To investigate interactions between common PD mutations and immune responses to environmental pathogens, we studied responses to Pseudomonas aeruginosa (P. aeruginosa) in peripheral blood mononuclear cells (PBMCs) from PD patients with leucine-rich repeat kinase 2 (LRRK2) mutations, GBA1 mutations, and idiopathic disease (iPD) relative to neurologically healthy controls (NHC).OBJECTIVESThe goal was to test the hypothesis that LRRK2 and GBA modify the human peripheral immune response to bacteria, specifically P. aeruginosa, based on prior animal studies involving Lrrk2 mutations and microbial pathogens.METHODSPBMCs from LRRK2-PD, GBA-PD, and iPD patients plus age- and sex-matched controls were treated ex vivo with live P. aeruginosa and pharmacological agents that block LRRK2 kinase activity (MLi-2) or enhance glucocerebrosidase (GCase) activation (NCGC00188758) to measure enzymatic activities and cytokine release.RESULTSGBA-PD PBMCs exhibited increased P. aeruginosa-dependent secretion of specific inflammatory cytokines including interleukin-1β. Antigen presentation was increased in LRRK2-PD nonclassical monocytes treated with the GCase activator. Levels of pRab10, a proxy for LRRK2 kinase activity, were increased in GBA-PD classical monocytes relative to NHC and iPD. GCase activator treatment increased pRab10 expression in LRRK2-PD intermediate monocytes. GBA-PD and individual treatments with MLi-2 or GCase activator were associated with reduced P. aeruginosa-dependent LRRK2 protein levels in PBMC subsets.CONCLUSIONSThis work demonstrates that PD-linked mutations in LRRK2 and GBA1 converge on peripheral blood immune cell dysregulation, as evinced by the ability of LRRK2 inhibitors and GCase activators to modulate the ex vivo immune response to bacterial exposure. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"1 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545179","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
引用
批量引用
Methodological Considerations on the SPAXCOM Scale: A Comment on Di Folco et al.
SPAXCOM量表的方法学思考:评Di Folco等。
IF 7.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-18
DOI: 10.1002/mds.70132
Yuesong Shen MB, Meiyu Yang MB, Shuai Fang MB, Tiantian Zhang MCM, Jianjun Ding MB
求助PDF
{"title":"Methodological Considerations on the SPAXCOM Scale: A Comment on Di Folco et al.","authors":"Yuesong Shen MB, Meiyu Yang MB, Shuai Fang MB, Tiantian Zhang MCM, Jianjun Ding MB","doi":"10.1002/mds.70132","DOIUrl":"10.1002/mds.70132","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 1","pages":"288-289"},"PeriodicalIF":7.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535250","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
引用
批量引用
Reply: “Unilateral Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Pallidothalamic Tractotomy in Parkinson's Disease: Promising Results But Uncertain Target”
回复:“单侧磁共振引导聚焦超声(MRgFUS)治疗帕金森病:有希望的结果但不确定的目标”
IF 7.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-18
DOI: 10.1002/mds.70130
Jun Ikezawa MD, PhD, Fusako Yokochi MD, PhD, Toshio Yamaguchi MD, PhD, Keiichi Abe MD, PhD, Tsutomu Kamiyama MD, PhD, Tomoya Kawazoe MD, PhD, Shiro Horisawa MD, Jinichi Sasanuma MD, PhD, Tomokatsu Hori MD, PhD, Hiroki Hori PhD, Toru Kakegawa MD, Ryoichi Okiyama MD, Kazushi Takahashi MD, PhD, Takaomi Taira MD, PhD
求助PDF
{"title":"Reply: “Unilateral Magnetic Resonance-Guided Focused Ultrasound (MRgFUS) Pallidothalamic Tractotomy in Parkinson's Disease: Promising Results But Uncertain Target”","authors":"Jun Ikezawa MD, PhD, Fusako Yokochi MD, PhD, Toshio Yamaguchi MD, PhD, Keiichi Abe MD, PhD, Tsutomu Kamiyama MD, PhD, Tomoya Kawazoe MD, PhD, Shiro Horisawa MD, Jinichi Sasanuma MD, PhD, Tomokatsu Hori MD, PhD, Hiroki Hori PhD, Toru Kakegawa MD, Ryoichi Okiyama MD, Kazushi Takahashi MD, PhD, Takaomi Taira MD, PhD","doi":"10.1002/mds.70130","DOIUrl":"10.1002/mds.70130","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"41 1","pages":"271-272"},"PeriodicalIF":7.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535249","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
引用
批量引用
Correction to “The Digital Frontier in Huntington's Disease: Opportunities for Clinical Trials”
对“亨廷顿舞蹈病的数字前沿:临床试验的机会”的更正
IF 8.6
1区 医学
Q1 CLINICAL NEUROLOGY
Pub Date : 2025-11-18
DOI: 10.1002/mds.70126
求助PDF
{"title":"Correction to “The Digital Frontier in Huntington's Disease: Opportunities for Clinical Trials”","authors":"","doi":"10.1002/mds.70126","DOIUrl":"https://doi.org/10.1002/mds.70126","url":null,"abstract":"","PeriodicalId":213,"journal":{"name":"Movement Disorders","volume":"178 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535248","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
引用
批量引用