Parkinsonism & related disorders最新文献

{"title":"Differences in progressive supranuclear palsy in patients of Asian ancestry?","authors":"Blas Couto, Maria Carmela Tartaglia, Gabor G. Kovacs, Anthony E. Lang, Ethnic background and distribution of clinical phenotypes in patients with probable progressive supranuclear palsy","doi":"10.1016/j.parkreldis.2024.107179","DOIUrl":"10.1016/j.parkreldis.2024.107179","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"130 ","pages":"Article 107179"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical evaluation of the current landscape of pharmacogenomics in Parkinson's disease - What is missing? A systematic review","authors":"Henry Mauricio Chaparro-Solano ,&nbsp;Maria Rivera Paz ,&nbsp;Saar Anis ,&nbsp;Jennifer K. Hockings ,&nbsp;Avery Kundrick ,&nbsp;Camila C. Piccinin ,&nbsp;Ekhlas Assaedi ,&nbsp;Leila Saadatpour ,&nbsp;Ignacio F. Mata","doi":"10.1016/j.parkreldis.2024.107206","DOIUrl":"10.1016/j.parkreldis.2024.107206","url":null,"abstract":"<div><h3>Introduction</h3><div>The first-line treatment for Parkinson's disease (PD) involves dopamine-replacement therapies; however, significant variability exists in patient responses. Pharmacogenomics has been explored as a potential approach to understanding and predicting treatment outcomes. This review aims to evaluate the current state of knowledge regarding the role of pharmacogenomics in PD, focusing on identifying challenges and proposing future directions.</div></div><div><h3>Methods</h3><div>We conducted a systematic review following PRISMA 2020 guidelines. The PubMed database was searched for original, English-language studies using the R package ‘RISmed.’ Data were extracted and analyzed based on sample size, population origin, evaluated genes and polymorphisms, outcomes, and methodological approaches.</div></div><div><h3>Results</h3><div>Out of 183 identified articles, 76 met the inclusion criteria. The <em>COMT</em>-rs4680 polymorphism was the most frequently studied, and levodopa-related motor complications were the most commonly assessed outcomes. All but two studies employed a candidate gene approach. In 75 % of the studies, the sample size was fewer than 225 individuals. There was a notable underrepresentation of Latino participants, with a lack of studies from Latin American countries other than Brazil. None of the studies produced consistent results across investigations.</div></div><div><h3>Conclusions</h3><div>The variability in patient responses to PD treatments suggests a genetic predisposition. While current research has enhanced our understanding of PD medication metabolism, it has not yet fully elucidated the complex genetic interactions involved in PD pharmacogenomics. Novel approaches, larger and more genetically diverse cohorts, and improved data collection are essential for advancing pharmacogenomics in PD clinical practice.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"130 ","pages":"Article 107206"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease subtypes: Approaches and clinical implications","authors":"Xiao Deng ,&nbsp;Anish Mehta ,&nbsp;Bin Xiao ,&nbsp;K. Ray Chaudhuri ,&nbsp;Eng-King Tan ,&nbsp;Louis CS. Tan","doi":"10.1016/j.parkreldis.2024.107208","DOIUrl":"10.1016/j.parkreldis.2024.107208","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a complex neurodegenerative disorder with significant heterogeneity in disease presentation and progression. Subtype identification remains a top priority in the field of PD clinical research. Several PD subtypes have been identified. Hypothesis-driven subtypes refer to pre-defined subtypes based on specific criteria. Under hypothesis-driven subtypes, motor subtypes are the most common empirical subtype in both research and clinical settings. The concept of the non-motor symptoms (NMS) subtypes is relatively new and less well studied. Mild cognitive impairment (MCI) is one of the more prevalent NMS subtypes of PD. Data-driven subtyping is a hypothesis-free approach, that defines disease phenotypes by comprehensively evaluating multidimensional data. In this review, we summarize the main features for the different PD subtypes: from hypothesis-driven subtypes to data-driven subtypes. NMS and data-driven subtypes are still not yet well understood particularly with regard to biomarker and progression characterization.</div><div>Future PD subtyping based on specific biological makers will enable us to better reflect the underlying pathophysiological underpinnings and enhance our search for specific therapeutic targets. The goal is to develop a simple algorithm to subtype PD patients at an early stage of PD that will enable good prognostication of their disease course, targeted therapies to be delivered, and proactive prevention of complications. Understanding PD subtypes and heterogeneity will also guide future clinical trial design and aid clinicians to better manage PD patients that will enable targeted disease surveillance and personalized treatment. The graphical abstract can be seen below.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"130 ","pages":"Article 107208"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP‐1 receptor agonists for Parkinson's disease: An updated meta-analysis","authors":"Matheus Barros de Albuquerque ,&nbsp;Luiz Eduardo Duarte Borges Nunes ,&nbsp;João Victor de Oliveira Maldonado ,&nbsp;Diogo Grassano Melo Ferreira ,&nbsp;Mateus Macedo Margato ,&nbsp;Lúcio Vilar Rabelo ,&nbsp;Marcelo Moraes Valença ,&nbsp;Lúcia Helena Oliveira Cordeiro","doi":"10.1016/j.parkreldis.2024.107220","DOIUrl":"10.1016/j.parkreldis.2024.107220","url":null,"abstract":"<div><h3>Introduction</h3><div>Treatments for Parkinson's disease (PD) focus on symptom reduction through dopaminergic therapies, without clear evidence of disease-modifying effects. Glucagon-like peptide-1 (GLP-1) receptor agonists may reduce neuroinflammation by decreasing microglia activation in PD. Clinical trials suggest these agents have disease-modifying potential in PD.</div></div><div><h3>Objective</h3><div>Evaluate the efficacy of GLP-1 receptor agonists in PD.</div></div><div><h3>Methods</h3><div>PubMed, Embase and Cochrane Library were searched to identify randomized controlled trials (RCTs) of GLP-1 agonists for PD, up to July 2024. The risk of bias was assessed using the RoB-2 tool, and statistical analysis was performed with RevMan 5.4.1 software.</div></div><div><h3>Results</h3><div>GLP-1 receptor agonists showed a beneficial effect on MDS-UPDRS part III motor scores compared to placebo. Off-medication state, there was a −1.22 point improvement (95%CI -2.46, 0.22; P = 0.05). On-medication state, scores improved by −2.52 points (95%CI -4.02, −1.01; P = 0.001). The global MDS-UPDRS score showed a −3.43-point difference (95%CI -6.48, −0.48; P = 0.02). Cognitive performance, assessed via the Mattis DRS-2, improved by 1.32 points (95%CI 0.16, 2.52; P = 0.03). There were no significant differences in the NMSS (−0,19; 95%IC -3,44, 3,05; P = 0.91), in MADRS (−1,04; 95%IC -2,57, 0,48; P = 0.18), or PDQ-39 (−0,91; 95%IC -2,22, 0,39; P = 0.17).</div></div><div><h3>Conclusion</h3><div>GLP-1 receptor agonists improved motor and cognitive performance in PD, suggesting potential symptomatic benefits. However, further studies are needed to evaluate their long-term effects and their role in disease modification, especially considering ethnic and disease severity variations.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"130 ","pages":"Article 107220"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the neural signatures: Distinct pallidal patterns in dystonia subtypes","authors":"Alexey Sedov ,&nbsp;Indiko Dzhalagoniya ,&nbsp;Ulia Semenova ,&nbsp;Anna Gamaleya ,&nbsp;Alexey Tomskiy ,&nbsp;Hyder A. Jinnah ,&nbsp;Aasef G. Shaikh","doi":"10.1016/j.parkreldis.2024.107207","DOIUrl":"10.1016/j.parkreldis.2024.107207","url":null,"abstract":"<div><h3>Introduction</h3><div>Dystonia manifests as slow twisting movements (pure dystonia) or repetitive, jerky motions (jerky dystonia). Dystonia can coexist with myoclonus (myoclonus dystonia) or tremor (tremor dystonia). Each of these presentations can have distinct etiology, can involve discrete sensorimotor networks, and may have characteristic neurophysiological signature. This study reports distinct neurophysiological signatures corresponding to the phenomenological subcategories and associations of dystonia.</div></div><div><h3>Methods</h3><div>We studied 17 dystonia patients undergoing deep brain stimulation surgery. Video-based movement tracking classified them into four phenomenological subcategories: myoclonus dystonia, pure dystonia, jerky dystonia, and tremor dystonia. Microelectrode recordings from the globus pallidus interna (GPi) and externa (GPe) were analyzed to characterize single-neuron activity reflecting underlying physiology.</div></div><div><h3>Results</h3><div>Analysis of 1038 neurons revealed distinct patterns of burst, pause, and tonic activity across subtypes. Myoclonus dystonia had the highest prevalence of burst neurons in the GPi, while tremor dystonia showed a balanced distribution of burst and pause neurons. Myoclonus and pure dystonia had higher firing rates compared to tremor and jerky dystonia. Tremor dystonia showed the most irregular and bursty firing patterns. Overall, myoclonus and tremor dystonia had higher burst rates and lower interburst intervals than pure and jerky dystonia, highlighting distinct neuronal activity patterns across the different dystonia types.</div></div><div><h3>Discussion</h3><div>The differences in pallidal neuron activity across the phenoemenological subtypes and associations of dystonia depict distinct neural mechanisms. These findings offer crucial physiological insights into the diverse phenomenology of different dystonia types.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"130 ","pages":"Article 107207"},"PeriodicalIF":3.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data","authors":"Tania Nikolcheva ,&nbsp;Gennaro Pagano ,&nbsp;Nathalie Pross ,&nbsp;Tanya Simuni ,&nbsp;Kenneth Marek ,&nbsp;Ronald B. Postuma ,&nbsp;Nicola Pavese ,&nbsp;Fabrizio Stocchi ,&nbsp;Klaus Seppi ,&nbsp;Annabelle Monnet ,&nbsp;Nima Shariati ,&nbsp;Benedicte Ricci ,&nbsp;Loes Rutten-Jacobs ,&nbsp;Gesine Respondek ,&nbsp;Thomas Kustermann ,&nbsp;Kirsten I. Taylor ,&nbsp;Dylan Trundell ,&nbsp;Paulo Fontoura ,&nbsp;Rachelle Doody ,&nbsp;Hanno Svoboda ,&nbsp;Azad Bonni","doi":"10.1016/j.parkreldis.2024.107257","DOIUrl":"10.1016/j.parkreldis.2024.107257","url":null,"abstract":"<div><h3>Introduction</h3><div>Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.</div></div><div><h3>Methods</h3><div>PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks. The primary endpoint is time to confirmed motor progression, defined as ≥5 points increase from baseline on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in practically defined OFF-medication state.</div></div><div><h3>Results</h3><div>586 participants were enrolled between May 5th, 2021 and March 22nd, 2023. At baseline, 74.2 % and 25.8 % of participants were receiving levodopa and MAO-Bi, respectively. Mean age was 64.2 years and 63.5 % were male. Mean time from diagnosis was 18.6 months, 85 % of participants were in Hoehn &amp; Yahr (H&amp;Y) Stage 2, and mean MDS-UPDRS Part III score was 24.5. Compared with the PASADENA population, PADOVA participants were older (∼5 years), with longer disease duration (∼8 months), and slightly more advanced based on H&amp;Y stage (10 % more in Stage 2) and MDS-UPDRS Part III (∼3 points more).</div></div><div><h3>Conclusions</h3><div>PADOVA has successfully recruited an early-stage PD population to test the effect of prasinezumab when added to background SOC.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107257"},"PeriodicalIF":3.1,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: Unraveling the neural signatures: Distinct pallidal patterns in dystonia subtypes.","authors":"Yiheng Liu","doi":"10.1016/j.parkreldis.2024.107246","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2024.107246","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107246"},"PeriodicalIF":3.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: TMS-evoked potentials provide novel neurophysiological features of Tourette syndrome","authors":"Yiheng Liu","doi":"10.1016/j.parkreldis.2024.107242","DOIUrl":"10.1016/j.parkreldis.2024.107242","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107242"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurohistopathological findings of the brain parenchyma after long-term deep brain stimulation: Case series and systematic literature review.","authors":"Juan Vivanco-Suarez, Timothy Woodiwiss, Kimberly L Fiock, Marco M Hefti, Ergun Y Uc, Nandakumar S Narayanan, Jeremy D W Greenlee","doi":"10.1016/j.parkreldis.2024.107243","DOIUrl":"10.1016/j.parkreldis.2024.107243","url":null,"abstract":"<p><strong>Introduction: </strong>Efficacy of deep brain stimulation (DBS) is established for several movement and psychiatric disorders. However, the mechanism of action and local tissue changes are incompletely described. We describe neurohistopathological findings of 9 patients who underwent DBS for parkinsonism and performed a systematic literature review on postmortem pathologic reports post-DBS.</p><p><strong>Methods: </strong>We performed a retrospective study of patients who underwent DBS for Parkinsonism between 2000 and 2023 and had postmortem neurohistopathological assessments. Demographics and clinical features were collected. Levodopa equivalent daily dose (LEDD) and total electrical energy delivered (TEED) were calculated. A systematic literature review was conducted.</p><p><strong>Results: </strong>Postmortem assessment of 9 DBS patients was performed (7 Parkinson's disease [PD], 1 Parkinsonism, 1 Multiple System Atrophy with pre-DBS clinical diagnosis of PD). Median age at DBS was 65 years (range, 54-69), 8 were male. Subthalamic nucleus was targeted in 8 patients, globus pallidus in 1. Median DBS duration was 65 months (range, 7-264). Post-DBS LEDD reduction was found in 7/9 patients and TEED increased over time in all cases. There were no DBS-related deaths. Neurohistopathological assessment showed gliosis in 7 patients and activated microglial infiltration in 1. In the literature (between 1977 and 2021), 59 patients with postmortem post-DBS findings were identified: 26 (44 %) PD, 20 (34 %) pain, and 13 (22 %) other conditions.</p><p><strong>Conclusion: </strong>Findings confirm presence of a local tissue reaction (gliosis and activated microglia) around the implanted leads. The effect of local changes on the clinical efficacy of DBS is not established. Further DBS postmortem studies and standardization of tissue processing are needed.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107243"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of biofluid phosphorylated α-synuclein in Parkinson's disease","authors":"Camilla Christina Pedersen ,&nbsp;Jodi Maple-Grødem ,&nbsp;Johannes Lange","doi":"10.1016/j.parkreldis.2024.107240","DOIUrl":"10.1016/j.parkreldis.2024.107240","url":null,"abstract":"<div><h3>Introduction</h3><div>Parkinson's disease (PD) is a progressive neurodegenerative disease, and biomarkers are needed to enhance earlier detection and monitoring. Alpha-synuclein, phosphorylated at serine 129 (pS129-α-syn), is the predominant form of α-syn found in Lewy bodies implicating an involvement in disease pathology. This review aims to systematically evaluate the evidence for pS129-α-syn detection in human biofluid samples of PD utilizing ELISA-based protein detection methods.</div></div><div><h3>Methods</h3><div>A systematic review was conducted following the Preferred Reported Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Electronic searches were performed in PubMed, Web of Science, and Cochrane databases from inception to November 7th, 2024, to identify studies comparing pS129-α-syn in biofluids of PD patients with controls or related neurodegenerative disease. Risk of bias was assessed for each study.</div></div><div><h3>Results</h3><div>Twenty-three publications met the inclusion criteria, with pS129-α-syn detected in cerebrospinal fluid, plasma, red blood cells, serum, and saliva exosomes. Overall, pS129-α-syn levels were elevated in patients with PD compared to controls, and in some studies, correlated with disease severity. There was no consistent pattern when comparing PD patients to those with related neurodegenerative diseases. Significant variability in pS129-α-syn levels and considerable overlap between groups may limit the utility as a biomarker.</div></div><div><h3>Conclusion</h3><div>While pS129-α-syn for PD shows some promise as a diagnostic marker for PD, its differential diagnostic utility remains limited. Further research involving larger cohorts is required. The greatest potential for pS129-α-syn may be as part of a panel with other PD-specific markers, to enhance diagnostic accuracy and prognostic value.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"132 ","pages":"Article 107240"},"PeriodicalIF":3.1,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}