Clinical Parkinsonism Related Disorders最新文献

{"title":"Comprehensive genetic screening of the South African Parkinson's disease study collection using the NeuroBooster array","authors":"Kathryn Step,&nbsp;Lusanda Madula,&nbsp;Nicole Kuznetsov,&nbsp;Elizna Maasdorp,&nbsp;Jonathan Carr,&nbsp;Riaan van Coller,&nbsp;Marlo Möller,&nbsp;Ignacio F. Mata,&nbsp;Soraya Bardien,&nbsp;on behalf of the Global Parkinson's Genetics Program (GP2)","doi":"10.1016/j.prdoa.2026.100508","DOIUrl":"10.1016/j.prdoa.2026.100508","url":null,"abstract":"<div><h3>Introduction</h3><div>Although there have been significant advances in the genetic etiology of Parkinson's disease (PD), most of this research has been conducted in European populations. This study aimed to characterize the genetic landscape of PD in South Africa, whose populations are renowned for their extensive genetic diversity and admixture.</div></div><div><h3>Methods</h3><div>We recruited 689 PD probands across South Africa. These participants were genotyped using the NeuroBooster array in collaboration with the Global Parkinson's Genetics Program (GP2). An in-house computational workflow was used to identify pathogenic missense variants, which were validated using Sanger sequencing. The CNV-Finder pipeline was used to screen for copy number variations (CNVs), which were validated using Multiplex Ligation-dependent Probe Amplification (MLPA). Previously identified pathogenic variants were used as positive controls in our analysis.</div></div><div><h3>Results</h3><div>We identified 16 unique missense variants in 47 individuals, 15 of which were independently confirmed by Sanger sequencing. However, these variants are not considered likely to be associated with PD status. We also identified new homozygous <em>PRKN</em> CNVs in three individuals and a whole-gene <em>SNCA</em> duplication in one individual, all of which were validated by MLPA. In addition, one individual had a CNV in the 5′ untranslated region of <em>SNCA</em>, although its pathogenicity remains unclear. When these findings were combined with our previous results, 3.5% of probands (24 individuals) were found to have a genetic basis for their disease.</div></div><div><h3>Conclusions</h3><div>We conducted the largest pathogenic variant screening to date in this unique and underrepresented population, and our findings highlight the rare contribution of known pathogenic variants. This study underscores the importance of expanding genetic research in African cohorts to improve global understanding of PD etiology.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"15 ","pages":"Article 100508"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149159032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Driving impairment in patients with movement disorders: examining the Baylor driving questionnaire by objective driving assessment","authors":"Abhishek Lenka ,&nbsp;Ruosha Li ,&nbsp;Karim Makhoul ,&nbsp;Alan Gonzalez ,&nbsp;Rory D. Mahabir ,&nbsp;Joseph Jankovic","doi":"10.1016/j.prdoa.2026.100429","DOIUrl":"10.1016/j.prdoa.2026.100429","url":null,"abstract":"<div><h3>Background</h3><div>The development of a screening tool to identify driving impairment in patients with movement disorders is an unmet need.</div></div><div><h3>Objective</h3><div>To validate Baylor Driving Questionnaire for Movement Disorders (BDQMD) by objective driving assessment (ODA).</div></div><div><h3>Methods</h3><div>In this cross-sectional study, 142 patients with various movement disorders completed the 10-item BDQMD and of those, 25 completed ODA using the driver performance analysis system (DPAS).</div></div><div><h3>Results</h3><div>The mean total BDQMD score for the whole cohort was 14.7 ± 5.6 (range 10–47). Patients who underwent ODA had a mean BDQMD score of 12.8 ± 2.9. Four had minimum driving skill, 20 had average, and 1 was highly skilled. Total BDQMD negatively correlated with overall DPAS score (r = -0.45, p = 0.025) and the score reflecting the traffic risk analysis (r = -0.41, p = 0.041).</div></div><div><h3>Conclusion</h3><div>BDQMD total score in this pilot study correlated well with the performance in ODA. Additional validation studies are warranted to explore its potential as a screening tool for driving impairment.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100429"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explore thyself: is it time for metacognition screening in clinical trials?","authors":"Andrew McGarry ,&nbsp;Scott Y.H. Kim ,&nbsp;Peggy Auinger ,&nbsp;Charles Venuto ,&nbsp;John Gaughan","doi":"10.1016/j.prdoa.2026.100424","DOIUrl":"10.1016/j.prdoa.2026.100424","url":null,"abstract":"<div><div>Participant self-report has become increasingly important in the design of clinical trials for Parkinson’s Disease (PD), resonating with the general sense that a person’s account of their experience should be a prime consideration in evaluating the effects of therapeutics. Typical study designs look to minimize the effects of comorbidities like substantial behavioral or cognitive disturbances that are expected to put accurate self-report at risk. However, little attention has been paid to the anticipated or actual ability of otherwise eligible PD study participants to accurately convey their experiences during participation. Metacognition, the ability to identify and reflect on one’s thought processes and output, would seem to be instrumental for the careful evaluation of therapeutics using self-report but is not directly assessed during screening for clinical studies. Evidence suggests metacognition may be impaired in participants expected to be enrolled, suggesting the assessment of metacognitive ability during screening or even study conduct may be a worthwhile evolution in study design. Future directions include modeling performance of participants with a range of metacognitive capabilities to understand its influence on outcomes in both active and placebo groups, and possibly simple tools or tests to assess study candidates at risk for poor metacognitive performance in trials that prioritize self-report.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100424"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The electric brain: approach to suboptimal DBS parameters","authors":"Ananda Carolina Moraes de Falcone ,&nbsp;Carina França ,&nbsp;Thiago Gonçalves Guimarães ,&nbsp;Rubens Gisbert Cury","doi":"10.1016/j.prdoa.2025.100418","DOIUrl":"10.1016/j.prdoa.2025.100418","url":null,"abstract":"<div><div>Deep Brain Stimulation (DBS) has revolutionized Parkinson’s disease treatment, yet post-operative challenges persist, including reversible programming errors caused by insufficient clinician training. Approximately 40 % of suboptimal outcomes referred to tertiary centers stem from correctable programming errors, highlighting the need for standardized approaches <span><span>[1]</span></span>. This article addresses chronic overstimulation syndrome in Subthalamic DBS(STN-DBS), where patients with sustained high-energy stimulation leads poorly tolerated rebound effects when abruptly adjusted. We present a structured, image-guided algorithm combining gradual energy titration with advanced volume of tissue activated (VTA) modeling to optimize therapeutic windows. Three characteristic scenarios are detailed: (1)<!--> <!-->suboptimal lead placement, managed via directional steering to refine stimulation focus; (2)<!--> <!-->excessive stimulation energy, addressed through decremental total electrical energy delivered (TEED) reduction; and (3)<!--> <!-->misplaced leads, requiring systematic deactivation and candidacy assessment for surgical revision. Our tolerance-optimized framework emphasizes spatial precision (leveraging imaging reconstruction) and temporal adaptation (gradual parameter adjustments), offering a paradigm shift for managing chronic DBS complications. While focused on STN-DBS, these principles may extend to other targets facing analogous challenges. The integration of advanced imaging with clinician expertise underscores the dual importance of technology and specialized training in improving DBS outcomes.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100418"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Access to Parkinson's disease treatments in the Middle East: a multi-national survey of availability, affordability, and utilization patterns","authors":"Mehri Salari,&nbsp;Shivam Mittal,&nbsp;Zakiyah Aldaajani,&nbsp;Hanan Khalil,&nbsp;Masoud Etemadifar,&nbsp;Murat Gültekin,&nbsp;Firas Alfwaress,&nbsp;Mudassar Iqbal Arain,&nbsp;Sevim Soleimani","doi":"10.1016/j.prdoa.2026.100482","DOIUrl":"10.1016/j.prdoa.2026.100482","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is an increasing public health challenge in the Middle East, yet regional data on access to therapies and services remain limited. Understanding the gaps in PD treatment availability, affordability, and prescription frequency is necessary for improving care delivery and regional policy development.</div></div><div><h3>Objectives</h3><div>Evaluating the availability, affordability, and utilization of disease-related pharmacological treatments, surgical, device-assisted therapies, and rehabilitative services across multiple Middle Eastern countries.</div></div><div><h3>Methods</h3><div>A cross-sectional, web-based survey was distributed to physicians with expertise in movement disorders across participating countries in the Middle East. The survey assessed three domains of availability, cost, and utilization of key medications, surgical interventions, and specialized PD services.</div></div><div><h3>Results</h3><div>Thirty-one respondents from nine Middle Eastern countries, including 44% movement-disorder specialists. Medication availability was 65.4%, affordability 68.6%, and prescription 52% across the included countries. Levodopa was nearly universally available (98%), whereas newer dopamine agonists, MAO-B inhibitors, and COMT inhibitors were available inconsistently. Advanced therapies demonstrated disparities; botulinum toxin and deep-brain stimulation were available in high-income countries but not frequently used, while infusion therapies were mostly unavailable. Telemedicine uptake was moderate; genetic testing was cost-restricted. Although general rehabilitation was available, PD-specific services were limited. Affordability constrained equitable care. Qatar had the highest reported prescription frequency of PD medications among the countries.</div></div><div><h3>Conclusions</h3><div>The survey highlights disparities in access to essential PD therapies across the Middle East. Variable availability, costs, and limited specialized services prevent optimal care, urging the need for stronger regional policies, improved insurance coverage, and expanded clinical training to improve equity in PD management.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"15 ","pages":"Article 100482"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148521094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mark Hallett and the renaissance of functional neurological disorder","authors":"Jon Stone","doi":"10.1016/j.prdoa.2026.100464","DOIUrl":"10.1016/j.prdoa.2026.100464","url":null,"abstract":"<div><div>This article traces the contributions of Mark Hallett (1943–2025) to Functional Neurological Disorder (FND) from 2003 to his death. Mark brought his expertise in motor physiology, free will, volition and agency to this neglected but common condition. He raised awareness of our need to understand its pathophysiology, natural history and treatment, and then became a key researcher investigating abnormalities of brain networks found in individuals with the condition, as well as its multifactorial aetiology. He played a pivotal role in organising international meetings and books on functional movement disorder and FND, culminating in his role as the first president of the International FND Society (2019–2022). In 2024, Mark Hallett gave the 2024 American Academy of Neurology Wartenberg lecture, recalling “la lésion dynamique” proposed by Charcot as the pathophysiology of FND in the 19th century. This lecture was emblematic of the renaissance of interest in FND after a long period of neglect and his huge contribution to our understanding of the disorder.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"15 ","pages":"Article 100464"},"PeriodicalIF":2.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13315896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148362788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural covariance network alterations across the spectrum of cognitive status in Parkinson's disease","authors":"Haruto Shibata ,&nbsp;Yuto Uchida ,&nbsp;Keita Sakurai ,&nbsp;Ken Tanaka ,&nbsp;Yuya Kano ,&nbsp;Noriyuki Matsukawa","doi":"10.1016/j.prdoa.2026.100456","DOIUrl":"10.1016/j.prdoa.2026.100456","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson's disease (PD) is a neurodegenerative disorder in which cognitive impairment frequently emerges as the disease progresses. Structural covariance network (SCN) analysis provides a framework for characterizing large-scale brain network organization beyond regional atrophy. This study aimed to assess alterations in SCN topology across the cognitive spectrum of PD.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 16 healthy controls (HC), 20 patients with PD and normal cognition (PD-CN), and 22 patients with PD and mild cognitive impairment (PD-MCI). Cortical thickness–based SCNs were constructed, and graph-theoretical analyses were performed to assess global network metrics, nodal centrality, and modular organization.</div></div><div><h3>Results</h3><div>Using a bootstrap-based area-under-the-curve framework (<em>N</em> = 1000 iterations per group; sparsity 0.15–0.40), a progressive increase in modularity was observed across HC, PD-CN, and PD-MCI (all Bonferroni-corrected <em>p</em> &lt; 0.001), and global efficiency was selectively reduced in PD-MCI. Nodal analyses revealed widespread alterations in betweenness, closeness, and eigenvector centrality, with comparable spatial extents across all three metrics. Community detection using the Louvain algorithm showed progressive reorganization of modular structure, with less distinct intermodular boundaries in PD-CN and more spatially extended modules in PD-MCI.</div></div><div><h3>Conclusions</h3><div>SCN analysis revealed stage-dependent network reorganization in PD, suggesting the utility of network-based approaches for characterizing large-scale brain alterations related to cognitive impairment.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100456"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148178437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium as a disease-modifying therapy for Parkinson’s disease: mechanisms, preclinical evidence, and clinical prospects","authors":"Jackson T. Boonstra","doi":"10.1016/j.prdoa.2026.100440","DOIUrl":"10.1016/j.prdoa.2026.100440","url":null,"abstract":"<div><div>Parkinson’s disease (PD), the second most common neurodegenerative disorder, involves progressive dopaminergic neuron loss and α-synuclein aggregation. Current treatments, such as levodopa and dopamine agonists, offer symptomatic relief but do not slow neurodegeneration, underscoring the need for disease-modifying therapies. Lithium, a long-used mood stabilizer, shows neuroprotective potential via multiple mechanisms: inhibition of glycogen synthase kinase-3β (GSK-3β), enhancement of autophagy, suppression of neuroinflammation, and reduction of oxidative stress. Evidence from in vitro, animal, and early clinical studies suggests lithium can preserve dopaminergic neurons, improve motor function, and reduce neurodegenerative biomarkers, including serum neurofilament light chain. Preclinical models indicate that low-dose lithium (0.2–0.6 mM serum) improves striatal dopamine integrity, limits microglial activation, and decreases α-synuclein pathology, though study designs show substantial heterogeneity. Preliminary human trials with microdose lithium aspartate hint at slowed PD progression, though robust phase 3 data are lacking. Key challenges include optimizing formulations (<em>e.g.,</em> lithium orotate vs. carbonate), minimizing renal and thyroid risks, and identifying responsive patient subgroups. Comparative evaluation with other experimental therapies, such as glucagon-like peptide-1 agonists and immunotherapies, highlights lithium’s appeal as a cost-effective, repurposed candidate. This review synthesizes molecular and translational evidence, emphasizes research gaps such as long-term safety and standardized dosing, and aims to guide future clinical trial design and therapeutic strategies for PD.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100440"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147850091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chorea-acanthocytosis presenting with epilepsy at onset harboring novel compound heterozygous VPS13A mutations","authors":"Mitsuyoshi Tamura ,&nbsp;Shogo Furukawa ,&nbsp;Masahiro Namiki ,&nbsp;Yukiko Ozawa ,&nbsp;Yuka Urata ,&nbsp;Masayuki Nakamura ,&nbsp;Mitsuru Watanabe ,&nbsp;Hideki Oshima ,&nbsp;Toshiki Obuchi ,&nbsp;Tadashi Ichikawa ,&nbsp;Yuriko Kikkawa","doi":"10.1016/j.prdoa.2026.100433","DOIUrl":"10.1016/j.prdoa.2026.100433","url":null,"abstract":"","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100433"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147515262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Income, employment, and clinical outcomes in Parkinson’s disease","authors":"Melissa N. Pacheco ,&nbsp;Carmen Uribe ,&nbsp;Jaeden Brown ,&nbsp;Jacob D. Jones","doi":"10.1016/j.prdoa.2026.100439","DOIUrl":"10.1016/j.prdoa.2026.100439","url":null,"abstract":"<div><h3>Introduction</h3><div>Socioeconomic factors such as employment status and household income may influence clinical outcomes in Parkinson’s disease, yet their associations with both motor and non-motor symptoms are not well characterized. This study examined whether employment status and income are associated with cognitive complaints, depressive symptoms, health-related quality of life, and motor severity among individuals with Parkinson’s disease.</div></div><div><h3>Methods</h3><div>Data were obtained from FoxInsight, and online longitudinal cohort study. Participants aged 40 years and older with Parkinson’s disease who completed self-report questionnaires were included (n = 29,826). Multilevel models examined associations between employment status and household income with cognitive complaints, depressive symptoms, health-related quality of life, and motor severity across up to three annual assessments.</div></div><div><h3>Results</h3><div>Employment status was significantly associated with all outcomes. Compared with full-time employment, unemployment and retirement were associated with more cognitive complaints, greater depressive symptoms, poorer health-related quality of life, and greater motor severity (all p &lt; 0.05). Part-time employment was generally associated with fewer depressive symptoms and did not significantly differ from full-time employment on several outcomes. Lower household income was significantly associated with greater depressive symptoms, poorer health-related quality of life, and greater motor severity (all p &lt; 0.05), but was not associated with cognitive complaints.</div></div><div><h3>Conclusion</h3><div>Employment status and household income are important social determinants of both motor and non-motor outcomes in Parkinson’s disease. These findings highlight the potential clinical relevance of socioeconomic factors shaping disease experience and emphasize the need for interventions that address economic and occupational vulnerability.</div></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":"14 ","pages":"Article 100439"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147600368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}