Parkinsonism & related disorders最新文献

{"title":"Evaluating multivariable clinical prediction models for Parkinson's disease prognosis: A scoping review.","authors":"Lynn Eickholt, Megan Super, Nicholas Fioravante, Shirley Yuan, Whitley W Aamodt","doi":"10.1016/j.parkreldis.2026.109017","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2026.109017","url":null,"abstract":"<p><p>Multivariable clinical prediction models combine two or more patient predictor variables to calculate the probability of a clinical outcome. In persons with Parkinson's disease (PD), clinical prognostic models can be used to predict disease progression or the occurrence of a clinical event. These models can aid in PD prognostication and complement clinical judgment by informing medical decision-making and resource allocation. In this scoping review of the literature from inception through May 2025, we present data from 74 multivariable prognostic models in PD, organized by clinical outcome. We also describe model development, validation, and calibration, if performed, and identify knowledge gaps. By summarizing existing multivariable clinical prognostic models in PD, this review is designed to inform prognostication and foster the development of more accurate, validated prognostic models for use in clinical practice.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"109017"},"PeriodicalIF":4.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149195917","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":"Modeling disease progression among moderate-stage Parkinson's disease patients: A targeted literature review.","authors":"Amy R Mulick, Anna M Groß, Jason Lott, Wei Wei Zhang, Eva-Maria Wicklein, Johannes Lampe, Casper Gøtzsche, Anja Gabriel","doi":"10.1016/j.parkreldis.2026.109018","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2026.109018","url":null,"abstract":"<p><strong>Background: </strong>Predicting disease progression in Parkinson's disease (PD) is challenging, especially for moderate-stage patients already on dopaminergic therapy. Most models focus on early, untreated PD, but progression rates may differ in moderate-stage PD. Better understanding of these trajectories can improve clinical trial design, access to care, and value demonstration for new therapies that target this population.</p><p><strong>Methods: </strong>We conducted a targeted literature review of longitudinal human PD studies in PubMed (inception-December 9, 2024) that quantitatively modeled disease progression, extracting study-, population-, outcome-, and modeling-related details, and qualitatively compared approaches, with an emphasis on moderate-stage PD.</p><p><strong>Results: </strong>Of 1717 records, 30 unique studies were reviewed describing 45 statistical models. Seven of these studies describing twelve models included moderate-stage PD; of those that met quality criteria, one allowed for individual-level trajectory prediction for motor, non-motor, and general disease symptoms, while two supported population-level trajectories for non-motor and general disease symptoms. Progression was assessed using diverse outcomes. Models for longitudinal motor fluctuations were lacking.</p><p><strong>Conclusions: </strong>Few robust models exist for motor symptom progression in moderate-stage PD. The development of such models requires comprehensive, treated patient datasets, long follow-up, and standardized motor outcome measures. Transparently reported, validated models across diverse groups will aid innovative PD therapy development.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"109018"},"PeriodicalIF":4.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216628","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":"The ever-expanding universe of botulinum neurotoxin in movement disorders.","authors":"Raymond L Rosales, Patricia Fleur Andaya, Frances Marie C Tamayo","doi":"10.1016/j.parkreldis.2026.108996","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2026.108996","url":null,"abstract":"<p><p>Botulinum neurotoxin (BoNT) has become a cornerstone in the management of movement disorders since its introduction into neurological practice. Initially established as a first-line therapy for focal dystonias and other hyperkinetic conditions, its efficacy is supported by robust clinical evidence and guideline recommendations. BoNT exerts its therapeutic effects through inhibition of acetylcholine release via cleavage of SNARE proteins, resulting in reversible chemodenervation, with additional evidence supporting modulation of sensory pathways and central motor circuits. This present review intends to summarize the clinical use of BoNT beyond established ones in dystonia and spasticity, as expanding applications accrue. The expanse includes treatment of Parkinson and Non-Parkinson-related movement disorders, hyperexcitability syndromes, autonomic blockade and pain reduction. Emerging utility of BoNT clinical use include the applications at Intensive Care Unit, the pre-emptive use of BoNT during surgeries and the device aided BoNT deliveries. These developments highlight its evolving role as a versatile therapy beyond purely motor control. Despite growing clinical experience, many emerging indications remain supported by limited or heterogeneous evidence. Further studies are needed to define optimal patient selection, dosing strategies, and long-term outcomes. As understanding of disease mechanisms continues to evolve, BoNT is poised to remain at the forefront of personalized and precision-based therapies in movement disorders.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"108996"},"PeriodicalIF":4.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183570","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":"CD8+ T lymphocytes in progressive supranuclear palsy and corticobasal degeneration: Interactions with tau pathology and neuroinflammation","authors":"Paulina Jasak,&nbsp;Aleksandra Wesołowska,&nbsp;Marta Żółtowska,&nbsp;Piotr Alster,&nbsp;Natalia Madetko-Alster","doi":"10.1016/j.parkreldis.2026.108917","DOIUrl":"10.1016/j.parkreldis.2026.108917","url":null,"abstract":"<div><div>Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are primary 4R tauopathies characterized by regionally selective accumulation of hyperphosphorylated tau and progressive neurodegeneration. Accumulating evidence suggests that neuroinflammatory and adaptive immune mechanisms contribute to their pathophysiology, although their precise function remains incompletely understood. This narrative review summarizes the involvement of CD8⁺ T lymphocytes in PSP and CBD, with particular emphasis on their phenotype, spatial distribution, and interactions with glial cells. A comprehensive literature search was conducted to identify relevant human and experimental studies examining central and peripheral immune responses. Existing data indicate that CD8⁺ T-cell infiltration is a consistent feature of PSP, particularly within vulnerable subcortical and brainstem regions such as the substantia nigra, where these cells are in close association with neurons and activated microglia. Their distribution correlates with phosphorylated tau burden and glial activation markers, consistent with coordinated innate–adaptive immune responses. Emerging evidence further suggests that CD8⁺ T cells in tauopathies may adopt non-classical phenotypes, including granzyme K–expressing (GZMK⁺) subsets, which may influence microglial activation rather than exert purely cytotoxic roles. In contrast, evidence in CBD remains limited and is largely derived from broader FTLD-tau cohorts, where CD8⁺ T cells are predominantly associated with cortical tau pathology and glial activation. Overall, CD8⁺ T lymphocytes appear to represent a common component of the neuroinflammatory environment in tauopathies, although their functional role remains context-dependent. Given that current evidence is predominantly correlative and based on post-mortem and experimental studies, further longitudinal and mechanistic investigations are necessary.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"151 ","pages":"Article 108917"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670430","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":"Lesion-induced hemichorea-ballism: A systematic review of 586 cases","authors":"Elina Myller,&nbsp;Vilja Minkkinen,&nbsp;Elizabeth G. Ellis,&nbsp;Daniel T. Corp,&nbsp;Joseph Jankovic,&nbsp;Sanjay Pandey,&nbsp;Juho Joutsa","doi":"10.1016/j.parkreldis.2026.108442","DOIUrl":"10.1016/j.parkreldis.2026.108442","url":null,"abstract":"<div><div>Hemichorea-ballism has historically been linked to lesions involving the subthalamic nucleus (STN). This continues to influence clinical acumen despite several reports describing more heterogenous lesion locations, and the clinical relevance of the lesion locations within hemichorea-ballism is largely unknown. Here, we aimed to conduct the first systematic review of lesion-induced hemichorea-ballism to provide a comprehensive account of the clinical characteristics of this disorder including examination of clinico-radiological correlations.</div><div>Reports of cases with lesion-induced hemichorea-ballism published up until January 2025 were identified by a systematic search. Demographic and clinical data were examined across all cases, and according to lesion locations.</div><div>Of the 586 cases identified, only 24.6 % had lesions intersecting the STN. The majority of cases (83.1 %) had acute symptom-onset within 7 days. Response rate to symptomatic pharmacotherapy was 82.2 %, and 52.8 % of cases remitted. Cases with STN lesions more often showed ballism, had a shorter symptom latency, benefited less often from symptomatic pharmacotherapy, more often underwent functional neurosurgery, and showed a longer delay to remission, compared to cases with non-STN lesions (<em>P</em> &lt; 0.05). Within cases with non-STN lesions, pure cortical lesions were associated with a more favorable prognosis and a shorter delay to remission compared to non-STN lesions involving subcortical structures (<em>P</em> &lt; 0.001).</div><div>Our results show that lesions causing hemichorea-ballism occur in heterogeneous locations, with only 1 in 4 involving the STN. Crucially, lesion locations were associated with the disorder's clinical characteristics and prognosis. These findings provide clinically useful descriptive evidence and may have ramifications for other lesion-induced movement disorders beyond hemichorea-ballism.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"151 ","pages":"Article 108442"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471845","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":"Expert commentary for approach to a case of neuro-gonadal disorder: Perrault syndrome","authors":"Susanne A. Schneider","doi":"10.1016/j.parkreldis.2026.108935","DOIUrl":"10.1016/j.parkreldis.2026.108935","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"151 ","pages":"Article 108935"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796569","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":"Approach to a case of Neuro-Gonadal disorder: Perrault syndrome","authors":"Madathum Kuzhiyil Farsana,&nbsp;Vikram V. Holla,&nbsp;Nitish Kamble,&nbsp;Ravi Yadav,&nbsp;Pramod Kumar Pal","doi":"10.1016/j.parkreldis.2026.108401","DOIUrl":"10.1016/j.parkreldis.2026.108401","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"151 ","pages":"Article 108401"},"PeriodicalIF":4.3,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353103","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":"Subthalamic nucleus beta oscillations and sleep disorders in Parkinson's disease: A new perspective on deep brain stimulation regulation mechanisms and circuits.","authors":"Haicheng Huang, Peng Ruan, Yihao Wang, Zhen Liu, Yuyi Wu, Zilu Zhang, Xiaobing Jiang, Peng Fu","doi":"10.1016/j.parkreldis.2026.109001","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2026.109001","url":null,"abstract":"<p><p>Parkinson's disease (PD) is increasingly recognized as a multisystem neurodegenerative disorder that extends far beyond its classical motor manifestations. Among its non-motor symptoms, sleep disturbances are among the most prevalent and disabling clinical features, affecting up to 80% of patients and often preceding the onset of motor symptoms by several years. Recent electrophysiological studies have identified the subthalamic nucleus (STN) as a critical hub linking motor dysfunction to sleep abnormalities. Aberrant synchronization of beta (13-30 Hz) oscillations in STN local field potentials (LFPs) persists across wakefulness and sleep, disrupting normal sleep microarchitecture by suppressing slow-wave activity, impairing sleep spindle generation, and destabilizing sleep-stage transitions. These pathological beta oscillations have therefore emerged as a key electrophysiological hallmark of PD-associated sleep dysfunction. Subthalamic deep brain stimulation (STN-DBS), the current standard surgical treatment for advanced PD, has demonstrated significant benefits beyond motor symptom control. Accumulating evidence suggests that STN-DBS improves sleep through multiple complementary mechanisms, including suppression of pathological beta synchronization, restoration of cortico-basal ganglia-thalamocortical network dynamics, modulation of brainstem arousal circuits and neurotransmitter systems, and alleviation of nocturnal motor symptoms. This review summarizes recent advances in the neuroanatomical, electrophysiological, and circuit-level mechanisms linking STN dysfunction to sleep disorders in PD. We further discuss emerging therapeutic strategies and highlight future directions toward biomarker-guided, individualized treatment. Collectively, this review proposes a mechanistic framework linking STN electrophysiology to sleep regulation and identifies testable hypotheses that may facilitate the development of precision neuromodulation strategies for sleep disorders in Parkinson's disease.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"109001"},"PeriodicalIF":4.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127712","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":"Hope or hype: novel disease-modifying treatments for Huntington disease.","authors":"Surabhi Garg, Tiago A Mestre","doi":"10.1016/j.parkreldis.2026.108998","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2026.108998","url":null,"abstract":"<p><p>Huntington disease research is living a gilded age for experimental disease-modifying therapies (DMTs), unique in the field of neurodegenerative movement disorders. Several studies are evaluating huntingtin-lowering approaches, using a multitude of molecules from antisense oligonucleotides, RNA interference therapies, and small molecule splicing modifiers. In parallel, somatic instability occurring during the life of gene carriers is increasingly recognized as a pathogenic mechanism driving clinical onset and progression, alongside with the established role of the length of a germinal CAG repeat. Recent trials document a consistent reduction of cerebral huntingtin and provide unique hope to researchers, clinicians, and patients of a first disease-modifying therapies in HD. However, a meaningful clinical impact on disease progression remains to be confirmed in phase III studies to support the translation of a first DMT into clinical practice. Dual targeting of both huntingtin and somatic instability is a novel emerging therapeutic concept that provides additional hope for an effective disease modification in Huntington disease in the future.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"108998"},"PeriodicalIF":4.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149113700","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":"Emerging therapies expected to make a difference in Parkinson's disease management.","authors":"Andy Y An, Lorraine V Kalia","doi":"10.1016/j.parkreldis.2026.108962","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2026.108962","url":null,"abstract":"<p><p>Recent advances in Parkinson's disease (PD) therapeutics have generated new opportunities for both symptomatic and disease-modifying treatments. This review discusses four therapeutic approaches that are likely to influence PD management in the coming years: continuous subcutaneous levodopa infusion, cell-based dopamine replacement, immunotherapies targeting α-synuclein, and gene transfer therapies. Subcutaneous levodopa infusion systems have recently demonstrated efficacy in reducing motor fluctuations and represent an important advance toward more physiological dopamine replacement. Stem cell-derived dopaminergic progenitors have revitalized cell replacement research and demonstrated encouraging safety and feasibility in early clinical trials. Although first-generation anti-α-synuclein antibodies have not demonstrated definitive clinical benefit, advances in antibody engineering and biomarker-guided patient selection may help clarify their therapeutic potential. Improvements in viral vector design and delivery are enabling increasingly sophisticated gene-based therapies for both sporadic and genetics forms of PD. Collectively, these advances are expanding therapeutic options and shaping the future management of PD.</p>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"108962"},"PeriodicalIF":4.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977725","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}