Movement Disorders最新文献

Objective: To update evidence-based medicine recommendations for treating motor fluctuations of Parkinson's disease (PD).

Background: The International Parkinson and Movement Disorder Society (MDS) Evidence Based Medicine in Movement Disorders Committee recommendations for the treatments of PD were first published in 2002 and regularly updated. The current review uses a new methodology, including the Cochrane Risk of Bias tool and a modified version of GRADE (Grading of Recommendations, Assessment, Development, and Evaluations).

Methods: On January 1, 2023, a literature search was conducted without date limit in the MEDLINE, Embase, and Cochrane databases using the following search terms: Parkinson disease, levodopa and, for the Embase database, randomized controlled trial (RCT). The inclusion criteria for studies were: patients with PD, on oral levodopa therapy, experiencing motor fluctuations, investigating an intervention that was (commercially) available in at least one country, study design RCT, and with a follow-up duration of at least 3 months.

Results: A total of 102 studies were included. Levodopa extended release, pramipexole immediate release and extended release, ropinirole immediate release, rotigotine, opicapone, safinamide, and bilateral subthalamic nucleus deep brain stimulation (DBS) were assessed as efficacious, and continuous intestinal levodopa infusion, continuous subcutaneous levodopa, continuous subcutaneous apomorphine, ropinirole prolonged release, ropinirole patch, entacapone, rasagiline, istradefylline, amantadine extended release, zonisamide, bilateral globus pallidus DBS, and pallidotomy were assessed as likely efficacious for the treatment of motor fluctuations in people with PD who are already being treated with levodopa.

Conclusions: There are several treatment options that can improve motor fluctuations in PD. These recommendations will assist physicians and patients in determining which intervention to use. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear palsy (PSP).

Objective: To investigate the association between CNVs and structural forms on 17q.21.31 with the risk of PSP.

Methods: Utilizing whole genome sequencing data from 1684 PSP cases and 2392 controls, the three large CNVs (α, β, and γ) and structural forms within 17q21.31 were identified and analyzed for their association with PSP.

Results: We found that the copy number of γ was associated with increased PSP risk (odds ratio [OR] = 1.10, P = 0.0018). From H1β1γ1 (OR = 1.21) and H1β2γ1 (OR = 1.24) to H1β1γ4 (OR = 1.57), structural forms of H1 with additional copies of γ displayed a higher risk for PSP. The frequency of the risk sub-haplotype H1c rises from 1% in individuals with two γ copies to 88% in those with eight copies. Additionally, γ duplication up-regulates expression of ARL17B, LRRC37A/LRRC37A2, and NSFP1, while down-regulating KANSL1. Single-nucleus RNA-seq of the dorsolateral prefrontal cortex analysis reveals γ duplication primarily up-regulates LRRC37A/LRRC37A2 in neuronal cells.

Conclusions: The copy number of γ is associated with the risk of PSP after adjusting for H1/H2, indicating that the complex structure at 17q21.31 is an important consideration when evaluating the genetic risk of PSP. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: The Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) has been validated cross-sectionally but not longitudinally.

Objective: We aimed to validate PROM-Ataxia as a measure of patient experience of disease over time, examine overall and domain-specific progression, and test convergent validity with other clinical outcome assessments (COAs).

Methods: We derived PROM-Ataxia data from 176 patients with spinocerebellar ataxia types 1, 2, 3, 6, 7, 8, or 10 in the Clinical Research Consortium for the Study of Cerebellar Ataxia at baseline and 1 year. We classified patients' ataxia severity stage ("severity") according to the Friedreich's Ataxia Rating Scale Functional Staging into mild, moderate, and severe subgroups. Analyses of the entire cohort and by severity subgroup included internal consistency, sensitivity to disease severity, predictive modeling of score changes, correlations with COAs: Brief Ataxia Rating Scale, Scale for Assessment and Rating of Ataxia, Fatigue Severity Scale, Cerebellar Cognitive Affective Syndrome scale, EuroQol 5-Dimension, and responsiveness to disease progression.

Results: The PROM-Ataxia exhibited high internal consistency and correlated with other COAs. Scores demonstrated sensitivity to disease severity and evolving patient experience. Progression was sigmoidal, with the greatest change in moderate patients. Compared with other COAs, PROM-Ataxia captured the most change. Mental features worsened fastest in mild patients, physical in moderate patients, and activities of daily living in severe patients.

Conclusion: PROM-Ataxia is more sensitive to change than ataxia COAs, captures the evolution of patients' experience of disease over 1 year, and reveals domain-specific progression. Studies of larger cohorts and different ataxia diagnoses over longer periods may provide insights to further enhance clinical care and research. © 2025 International Parkinson and Movement Disorder Society.

Genetic factors play a central role in neurodegenerative disorders. Over the past few decades, significant progress has been made in identifying the causative genes of numerous monogenic disorders, largely due to the widespread adoption of next-generation sequencing (NGS) technologies in both research and clinical settings. However, many likely monogenic disorders still lack an accurate molecular diagnosis, primarily because conventional NGS methods are not effective at detecting structural variants and repeat expansions, both of which are crucial in many neurogenetic diseases. Recently, long-read sequencing (LRS) and optical genome mapping technologies have emerged as powerful tools, offering the ability to capture more complex genetic variations. These technologies have already led to the discovery of novel genes responsible for well-characterized neurodegenerative diseases (ND), enhancing the understanding of the biological underpinning of these conditions. Although currently LRS is mostly used in a research setting, we anticipate broader implementation of these methods in clinical laboratories in the near future. In this review, we explore the contributions of these technologies to ND research and highlight the remaining challenges for future advancements. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.