Parkinsonism & related disorders最新文献

{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S1353-8020(25)00789-8","DOIUrl":"10.1016/S1353-8020(25)00789-8","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 108048"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219933","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 delphi consensus statement about French practical management of continuous apomorphine infusion in patients with Parkinson's disease and motor fluctuations","authors":"Fabienne Ory Magne ,&nbsp;Sophie Drapier ,&nbsp;Ana-Raquel Marques ,&nbsp;David Maltete ,&nbsp;Frederique Leh ,&nbsp;Cecile Hubsch ,&nbsp;Frederique Fluchere ,&nbsp;Margherita Fabbri ,&nbsp;Angelique Gerdelat ,&nbsp;Solene Frismand ,&nbsp;Gwendoline Dupont ,&nbsp;Cécile Delorme ,&nbsp;Rene Decombe ,&nbsp;Teodor Danaila ,&nbsp;Jarbas Correa Lino ,&nbsp;Olivier Colin ,&nbsp;Cecilia Bonnet ,&nbsp;Alexandre Bonnet ,&nbsp;Sebastien Bailly ,&nbsp;Emmanuel Roze","doi":"10.1016/j.parkreldis.2025.107866","DOIUrl":"10.1016/j.parkreldis.2025.107866","url":null,"abstract":"<div><h3>Background</h3><div>There are currently no consensus guidelines on how to progressively optimize treatment when initiating continuous subcutaneous apomorphine infusion (CSAI) in patients with Parkinson's disease (PwPD).</div></div><div><h3>Aims</h3><div>To provide practical guidelines on CSAI initiation in PwPD with motor fluctuations, with a focus on the target dose of apomorphine over time and subsequent adjustment of oral treatment according to the patient's characteristics.</div></div><div><h3>Methods</h3><div>A panel of French neurologists with extensive experience in treating patients with advanced Parkinson's disease used a modified Delphi approach to generate a knowledge synthesis on CSAI initiation according to patient characteristics.</div></div><div><h3>Results</h3><div>We identified five profiles based on patient characteristics. The target dose of apomorphine over time and the subsequent adjustment of oral therapy were highly dependent on these profiles. The CSAI flow rate varied from a maximum of 3 mg/h for older or more sensitive patients to 6–10 mg/h for younger patients experiencing early fluctuations. In most cases, the preferred approach was to reduce both levodopa and dopamine agonists when increasing CSAI. For optimum efficacy, the total target dose of levodopa equivalent (calculated as the sum of the oral dose and the apomorphine dose) should be greater than or equal to the pre-initiation dose after initiation of CSAI, regardless of patient characteristics.</div></div><div><h3>Conclusion</h3><div>We provide patient-tailored recommendations with precise indications for the adjustment of apomorphine, oral therapy and levodopa equivalent dose over time during CSAI initiation, based on distinct patient profiles.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107866"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142976","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":"Outside Front Cover - Journal name, Cover image, Volume issue details, ISSN, Cover Date, Elsevier Logo and Society Logo if required","authors":"","doi":"10.1016/S1353-8020(25)00784-9","DOIUrl":"10.1016/S1353-8020(25)00784-9","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 108043"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145216597","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":"Apomorphine: past, present and future in Parkinson's disease and beyond","authors":"Manon Auffret","doi":"10.1016/j.parkreldis.2025.107872","DOIUrl":"10.1016/j.parkreldis.2025.107872","url":null,"abstract":"<div><div>The year 2025 marks the 180th anniversary of the first documented synthesis of apomorphine, and the first U.S. Food and Drug Administration (FDA) approval of a subcutaneous apomorphine infusion device for advanced Parkinson's disease (SPN-830). This narrative review therefore aims to examine apomorphine clinical journey, celebrating its turbulent yet founding past, analyzing its current challenges in the treatment of Parkinson's disease (PD) and envisioning its promising future, both in neurological disorders and beyond. Enduring misconceptions and the lack of class 1 evidence for supporting the use of continuous subcutaneous apomorphine infusion (CSAI) in PD have long been thought to have prevented its generalized use. The TOLEDO study, which robustly demonstrated a clinically meaningful reduction in off time (as expected based on decades of clinical experience) has now removed this barrier. Challenges to be addressed moving forward include (1) redefining the place of apomorphine in the PD treatment paradigm (from early use to terminal care), (2) reducing access disparities (availability, cost), (3) improving delivery systems and apomorphine formulations, and (4) expanding clinical use both in and outside of neurological disorders, with already tangible results for atypical Parkinsonian syndromes and disorders of consciousness, and promising perspectives in Alzheimer's disease.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107872"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111664","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":"No one size fits all approach with apomorphine initiation","authors":"Christopher Kobylecki ,&nbsp;Richard J.B. Ellis","doi":"10.1016/j.parkreldis.2025.107889","DOIUrl":"10.1016/j.parkreldis.2025.107889","url":null,"abstract":"<div><div>Continuous subcutaneous apomorphine infusion (CSAI) is an important treatment for motor fluctuations in the complex phase of Parkinson's disease (PD). Several barriers to accessing CSAI exist, including perceptions of how treatment initiation should occur. The majority of published work on CSAI initiation reports inpatient admission for this treatment, but restrictions on access to inpatient hospital beds may limit availability. We review here the evidence for different approaches, including published work on outpatient/daycase or home CSAI treatment initiation. Whereas inpatient initiation allows faster titration of CSAI treatment, home initiation has been found to allow effective and safe treatment initiation and offers potential cost savings. Complication rates in all approaches appear comparable, although the overall clinical profile and comorbitidities of patients should be taken into account when deciding on the best method of initiation. A flexible approach to CSAI initiation has potential benefits to people with PD in terms of better access.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107889"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226199","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":"Other clinical uses for apomorphine: Sedation and sleep disorders, withdrawal of oral dopaminergic medication, palliative care, restless legs syndrome, traumatic brain injury, sexual dysfunction","authors":"Marc Vérin MD PhD ,&nbsp;Manon Auffret PharmD PhD","doi":"10.1016/j.parkreldis.2025.107837","DOIUrl":"10.1016/j.parkreldis.2025.107837","url":null,"abstract":"<div><div>Apomorphine is now recognised as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed for patients with advanced Parkinson's disease (PD) with motor fluctuations in Europe, Asia and more recently on the other three continents. In light of its most recent uses and newest challenges, this paper focuses on a number of indications in Parkinson's disease and beyond, which are currently under development or which would benefit from development, given the generally high levels of evidence: sedation and sleep disorders, withdrawal of oral dopaminergic medication, palliative care, restless legs syndrome, traumatic brain injury and sexual dysfunction.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107837"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023479","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 resurrection of apomorphine: A dopamine analogue comparable in potency to L-DOPA","authors":"Andrew J. Lees ,&nbsp;Roongroj Bhidayasiri","doi":"10.1016/j.parkreldis.2025.107923","DOIUrl":"10.1016/j.parkreldis.2025.107923","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107923"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507520","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":"Drooling in Parkinson's disease: A potential clinical marker of disease severity","authors":"Eriko Igami ,&nbsp;Noriko Nishikawa ,&nbsp;Hirotaka Iwaki ,&nbsp;Shin-ichi Ueno ,&nbsp;Haruka Takeshige-Amano ,&nbsp;Wataru Sako ,&nbsp;Taku Hatano ,&nbsp;Nobutaka Hattori","doi":"10.1016/j.parkreldis.2025.108069","DOIUrl":"10.1016/j.parkreldis.2025.108069","url":null,"abstract":"<div><h3>Introduction</h3><div>Drooling is a common but underrecognized non-motor symptom in Parkinson's disease (PD), associated with impaired quality of life and aspiration risk. While often managed as a peripheral issue, it may reflect broader systemic involvement. This study aimed to evaluate the prevalence and clinical significance of drooling in PD, focusing on its relationship with motor, non-motor, cognitive, and autonomic domains.</div></div><div><h3>Methods</h3><div>We conducted a cross-sectional study involving 513 Japanese PD patients. Drooling severity was assessed using Item 2 of the MDS-UPDRS Part II. Motor and non-motor symptoms were evaluated using the MDS-UPDRS Parts I–IV, MMSE, MoCA-J, FAB, PDSS-2, JESS, and PDQ-39. Cardiac sympathetic innervation and dopaminergic integrity were assessed using MIBG myocardial scintigraphy and DaT SPECT, respectively. Multivariable regression analysis was performed with adjustment for age, sex, and disease duration.</div></div><div><h3>Results</h3><div>Drooling was observed in 66.5 % of participants, with 28.1 % categorized as severe. Droolers had significantly worse scores in motor and non-motor assessments, poorer sleep quality and quality of life, and greater cognitive deficits. They also exhibited lower heart-to-mediastinum ratios on MIBG and reduced striatal z-scores on DaT SPECT. These associations remained significant after adjustment for covariates.</div></div><div><h3>Conclusion</h3><div>Drooling in PD is linked to broader clinical and imaging abnormalities and may reflect widespread neurodegeneration beyond oropharyngeal dysfunction. These findings support the potential utility of drooling as a clinical marker of disease severity and suggest that it warrants greater attention in both research and clinical practice.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"140 ","pages":"Article 108069"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145221312","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":"Continuous subcutaneous infusion therapies in Parkinson's disease: evidence of efficacy and safety","authors":"Regina Katzenschlager ,&nbsp;Filip Bergquist","doi":"10.1016/j.parkreldis.2025.107905","DOIUrl":"10.1016/j.parkreldis.2025.107905","url":null,"abstract":"<div><div>Continuous dopaminergic drug delivery aims to reduce motor fluctuations in Parkinson's disease (PD). While intestinal levodopa infusions are effecacious, they require gastrojejunal tube insertion. In contrast, subcutaneous (SC) infusions are less invasive. The recent introduction of foslevodopa infusion has renewed interest in SC treatments.</div><div>We review the current evidence for continuous SC infusion of apomorphine and levodopa-based formulations. Apomorphine has been used clinically for decades. The TOLEDO study, the first randomized, placebo-controlled trial of apomorphine infusion, demonstrated significant reductions in OFF time and increases in ON time without troublesome dyskinesia. Long-term open-label studies confirmed sustained benefits and relatively good neuropsychiatric tolerability, with low rates of impulse control disorders, likely due to its dopamine receptor profile. Foslevodopa/foscarbidopa is the first – and currently the only - levodopa-based SC formulation to have been approved; another has data from randomized trials. These showed similar efficacy to apomorphine in reducing OFF time and improving good ON time. Subcutaneous treatments commonly induce skin reactions, and it is not yet known whether long term tolerability differs between foslevodopa and apomorphine. Subcutaneous apomorphine, foslevodopa and levodopa all offer substantial benefits for patients with motor fluctuations. All can be used around the clock, although this use is standard with foslevodopa. Side effect profiles and contraindications differ but they all share the advantage of being easily reversible. While questions around optimal strategies for 24h treatment and long-term adherence and tolerability remain, SC infusions offer meaningful improvements and should be considered earlier, as soon as fluctuations become difficult to manage orally.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107905"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333677","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":"Rethinking the role of continuous dopaminergic stimulation in Parkinson disease therapy","authors":"Peter A. LeWitt","doi":"10.1016/j.parkreldis.2025.107354","DOIUrl":"10.1016/j.parkreldis.2025.107354","url":null,"abstract":"<div><div>This Viewpoint will examine continuous dopaminergic stimulation (CDS), a concept that has long been invoked as the optimal treatment strategy for improving symptomatic control of Parkinson disease (PD) patients experiencing motor fluctuations. The appeal of CDS has always seemed intuitive and is based, in part, on preclinical investigations implicating pulsatile dopaminergic stimulation as causing motor fluctuations and dyskinesia from levodopa (LD) treatment. However, four large-scale randomized controlled clinical trials testing infused drug delivery have demonstrated only partial effectiveness of CDS at reducing daily OFF time. Other clinical trial data has offered evidence that a reduction in OFF time also can be accomplished from targeting sites in motor pathways downstream from the basal ganglia. Neural plasticity and a CNS calcium receptor signaling compound, ophthalmate, may also hold answers to the regulation of OFF time. Finally, insights derived from neural computational modeling of PD motor pathway pharmacology and the involved electrophysiological connections may guide future understanding of motor fluctuations in PD and their management.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"139 ","pages":"Article 107354"},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586642","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}