Parkinsonism & related disorders最新文献

{"title":"Retinal structural changes in Parkinson's disease: differences in pRNFL thickness between GBA1-associated and idiopathic cases","authors":"Giacomo Portaro ,&nbsp;Michelangelo Giacomelli ,&nbsp;Sara Grisanti ,&nbsp;Lisa Taruffi ,&nbsp;Giulia Di Rauso ,&nbsp;Valentina Fioravanti ,&nbsp;Gaetano Salomone ,&nbsp;Giacomo Argenziano ,&nbsp;Rossella Sabadini ,&nbsp;Giulia Toschi ,&nbsp;Ottavia Iotti ,&nbsp;Isabella Campanini ,&nbsp;Andrea Merlo ,&nbsp;Lorenzo Cavazzuti ,&nbsp;Benedetta Damiano ,&nbsp;Sara Scaltriti ,&nbsp;Augusto Scaglioni ,&nbsp;Jefri J. Paul ,&nbsp;Peter Bauer ,&nbsp;Giuseppe Biagini ,&nbsp;Francesco Cavallieri","doi":"10.1016/j.parkreldis.2025.108134","DOIUrl":"10.1016/j.parkreldis.2025.108134","url":null,"abstract":"<div><h3>Introduction</h3><div>In recent years, retinal structural changes have attracted considerable attention as a potential biomarker of neurodegeneration in Parkinson's disease (PD). Several studies have reported a reduced Retinal Nerve Fiber Layer (pRNFL) thickness in patients with PD compared with age-matched controls. However, potential retinal differences between “idiopathic” PD and GBA1-associated PD (GBA-PD) remain largely unexplored.</div></div><div><h3>Methods</h3><div>In this single-center observational study, we enrolled 59 PD patients: 32 GBA-PD and 27 non-mutated (NM-PD). A comprehensive clinical assessment included MoCA, MDS-UPDRS and Hoehn-Yahr. Spectral-domain OCT measured pRNFL thickness at 3.5, 4.1 and 4.7 mm diameters across six sectors. Statistical analysis assessed intergroup differences and associations with clinical variables.</div></div><div><h3>Results</h3><div>NM-PD exhibited significantly thinner temporal sectors compared to GBA-PD (p &lt; .05, Mann-Whitney <em>U</em> test). In NM-PD, positive correlations emerged between temporal-superior pRNFL and MoCA scores, in line with previous studies, and, more surprisingly, between nasal-inferior sector and MDS-UPDRS part-IV. No robust associations with clinical variables were found in GBA-PD.</div></div><div><h3>Conclusions</h3><div>This study demonstrates differences in retinal thickness between GBA-PD and NM-PD. In particular, a lower pRNFL in NM-PD may be the product of a different pathophysiological mechanism. Moreover, sector-specific retinal thickness showed correlations to cognitive impairment and motor complications in NM-PD. These observations provide novel insights into genotype-specific mechanisms of neurodegeneration in PD and suggest that retinal imaging may offer a window into both cognitive and motor complications. Further longitudinal studies, including healthy controls and expanded retinal layer analyses, are needed to confirm and expand these findings.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108134"},"PeriodicalIF":3.4,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621004","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":"Impact of best practice advisory on reducing contraindicated medications in hospitalized patients with Parkinson's disease","authors":"Zhimin Xu ,&nbsp;Andy Jiang ,&nbsp;Nishitha Bujala ,&nbsp;Ariel Sackonvitz ,&nbsp;Colleen Bond ,&nbsp;Carolin Dohle ,&nbsp;Katherine Amodeo","doi":"10.1016/j.parkreldis.2025.108129","DOIUrl":"10.1016/j.parkreldis.2025.108129","url":null,"abstract":"<div><h3>Background</h3><div>Patients with Parkinson's disease (PD) face heightened risks during hospitalization, including prolonged hospital stay and discharge to higher levels of care. Possible contributing factors include non-adherence to home medication regimens and administration of contraindicated medications.</div></div><div><h3>Objective</h3><div>To evaluate the impact of Best Practice Advisory (BPA), integration into Electronic Medical Records (EMRs) aimed at minimizing the prescription of contraindicated dopamine blocking agents (DBA) in hospitalized PD patients.</div></div><div><h3>Methods</h3><div>This is a single center, retrospective, cohort study comparing frequency of administration of contraindicated medications before and after implementation of a BPA at Westchester Medical Center (WMC) between January 2023 and July 2024. The primary outcome is the prescription of DBA. Secondary outcomes included discharge level of care, and hospital length of stay.</div></div><div><h3>Results</h3><div>Two-hundred and eleven charts were reviewed, and patients with confirmed diagnosis of PD or related Parkinsonism, who were prescribed dopaminergic medications at the time of admission were included. After BPA implementation, there was a statistically significant drop in rates of contraindicated prescriptions for psychosis and antiemetics, 33.33 %–2.86 % (p &lt; 0.001) and 11.11 %–0 % (p &lt; 0.001), respectively. There were no significant changes in LOS or discharge to higher levels of care between periods.</div></div><div><h3>Conclusion</h3><div>Implementing a BPA effectively reduced the prescription of contraindicated medications for PD patients. This highlights the value of targeted BPAs in improving PD patient safety and lays the groundwork for further medication quality improvement initiatives aimed at optimizing inpatient care for this vulnerable population.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108129"},"PeriodicalIF":3.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669167","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 gait and balance impairment in cervical dystonia: associated features, functional implications, and the effect of botulinum toxin","authors":"Silvia Galli ,&nbsp;Claudia Ledda ,&nbsp;Silvia Gallo ,&nbsp;Maurizio Zibetti ,&nbsp;Francesco Marenco ,&nbsp;Marcello Campagnoli ,&nbsp;Domiziana Rinaldi ,&nbsp;Morena Giovannelli ,&nbsp;Carlo Alberto Artusi ,&nbsp;Gabriele Imbalzano ,&nbsp;Leonardo Lopiano","doi":"10.1016/j.parkreldis.2025.108130","DOIUrl":"10.1016/j.parkreldis.2025.108130","url":null,"abstract":"<div><h3>Background</h3><div>Cervical dystonia (CD) may affect not only head posture but also gait and balance. The relationship between quantitative gait abnormalities and perceived disability, the contribution of head tremor (HT) and the impact of botulinum toxin (BoNT) on these disturbances remain unclear.</div></div><div><h3>Methods</h3><div>We analyzed gait and balance in twenty-one CD patients (nine with HT) and twenty-two healthy controls (HC) by wearable sensors. Validated scales for CD severity, pain and quality of life (Tsui; TWSTRS-2; CDQ24; CDIP58) were used and CD patients re-evaluated one month after BoNT. Functional impact of gait impairment was assessed by multivariate analyses.</div></div><div><h3>Results</h3><div>Compared with HC, CD patients showed reduced gait speed, cadence, and stride length, longer double-support time, greater stride-length variability (SLV), and increased postural sway (all p &lt; 0.05). SLV was the only gait parameter associated with the CDIP58-Walking subscale (p = 0.003) and remained an independent predictor after age, sex, CD-duration and CD-severity adjustment (p = 0.035). Patients with HT had greater sway than those without tremor after adjusting for disease severity (p = 0.038). All gait and balance parameters were similar after BoNT, except for reduced gait asymmetry. In the HT subgroup, sway improved significantly (p = 0.011).</div></div><div><h3>Conclusions</h3><div>This study confirms subtle gait and balance abnormalities in CD, with SLV emerging as a potential biomarker of functional impairment. HT appears to exacerbate balance dysfunction, while BoNT may partly improve sway in this subgroup. These findings suggest that sensor-based gait analysis may complement clinical evaluation and guide management in CD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108130"},"PeriodicalIF":3.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621003","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":"Phenotypic heterogeneity in P102L Gerstmann-Sträussler-Scheinker disease: A case of spastic paraparesis with ataxia.","authors":"Karla Salinas-Barboza, Juan Manuel Altamirano","doi":"10.1016/j.parkreldis.2025.108131","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.108131","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"108131"},"PeriodicalIF":3.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637714","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":"Protective or Pathogenic? Kinase activity and the neurodevelopmental origins of G2019S LRRK2-Associated Parkinson's disease","authors":"Emilia M. Gatto ,&nbsp;Alberto J. Espay ,&nbsp;Melisa Espindola ,&nbsp;Gustavo Da Prat ,&nbsp;Marcelo A. Kauffman","doi":"10.1016/j.parkreldis.2025.108133","DOIUrl":"10.1016/j.parkreldis.2025.108133","url":null,"abstract":"<div><div>Mutations in the leucine-rich repeat kinase 2 (<em>LRRK2</em>) gene are the most common monogenic cause of Parkinson's disease (PD), with the p.Gly2019Ser (G2019S) variant being particularly prevalent. The <em>LRRK2</em> gene encodes a large, multi-domain protein (LRRK2) belonging to the Roco family, possessing both kinase and GTPase activities. Because normal LRRK2 function is critical for neuronal development, synaptic plasticity, vesicle trafficking, mitochondrial homeostasis, and neuroinflammatory pathways, pathogenic <em>LRRK2</em> variants likely impair these functions. This is supported by rodent models and induced pluripotent stem cell (iPSC) studies suggesting that G2019S <em>LRRK2</em> variants accelerate neuronal differentiation and disrupt synaptic function early in development, while kinase overactivity (phosphorylation of various substrates) is critical during normal embryonic growth. Contrary to the dominant gain-of-toxic-function hypothesis, these observations support an alternative loss-of-function framework, whereby increased kinase activity may be a compensatory cellular strategy to counteract the loss or alteration of the homeostatic and neurodevelopmental functions associated with G2019S <em>LRRK2</em>. If validated by further studies, including ongoing LRRK2 kinase inhibitor trials, future LRRK2-PD therapeutic strategies may shift from broad kinase inhibition toward individualized modulation of specific LRRK2-mediated impairments, such as vesicle trafficking, mitochondrial integrity, or microglial dysfunction. Such an approach would recognize LRRK2-PD not as a single entity but as a biologically heterogeneous group of PD subtypes.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"143 ","pages":"Article 108133"},"PeriodicalIF":3.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145678406","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":"Identifying the “Sweet Spot” for GPi DBS Programming","authors":"Lubna Jafri ,&nbsp;Jessica Tate ,&nbsp;Mary Ann Thenganatt ,&nbsp;Deepal Shah-Zamora ,&nbsp;Adrian Laxton ,&nbsp;Stephen B. Tatter ,&nbsp;Mustafa S. Siddiqui","doi":"10.1016/j.parkreldis.2025.108132","DOIUrl":"10.1016/j.parkreldis.2025.108132","url":null,"abstract":"<div><h3>Introduction</h3><div>Clinical success of deep brain stimulation (DBS) depends on accurate electrode placement and stimulation within the brain targets. This study aims to explore the optimal stimulation site in the globus pallidus interna (GPi) to address the existing knowledge gap.</div></div><div><h3>Methods</h3><div>A retrospective chart review included Parkinson's disease (PD) patients who underwent GPi DBS between 2020 and 22 at our institution. We used stimulation data at six months post-op to generate a stimulation field model (SFM) for each lead and aggregated to generate volumetric stimulation heatmaps. Primary outcome measure was Clinical Global Impression-Change (CGI-C) scale, determined by response in contralateral tremor, rigidity and bradykinesia, correlated with SFM to generate ideal locations for stimulation in GPi. The secondary outcome measures were difference in pre- and post-DBS Movement Disorders Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS) III scores.</div></div><div><h3>Results</h3><div>Twenty-two PD patients with 36 GPi leads were included. Mean age: 64 ± 8.5 years; 67 % were male. For right GPi leads, 11/16 (69 %) had CGI-C of 1 and 5/16 (31 %) had 2. For left GPi leads, 13/20 (65 %) and 7/20 (35 %) had CGI-C of 1 and 2, respectively. MDS-UPDRS improved from 33.5 to 19.7 (41 %) post-op (p = 0.0003) with significant reduction in levodopa equivalent dosage (p = 0.00043).</div></div><div><h3>Conclusions</h3><div>We identified the “sweet spot” corresponding with CGI-C of 1 in the postero-lateral and mid region of GPi on axial and coronal sequences, respectively. Our findings support the previously reported limited evidence in the literature and can be helpful in image-guided DBS programming in patients with PD.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108132"},"PeriodicalIF":3.4,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621002","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":"Effects of Transcranial Pulse Stimulation (TPS) as a potential “add-on” intervention in patients with Parkinson's disease","authors":"Paolo Manganotti ,&nbsp;Marco Liccari ,&nbsp;Tiziana Maria Isabella Lombardo ,&nbsp;Jacopo Della Toffola ,&nbsp;Valentina Cenacchi ,&nbsp;Miloš Ajčević ,&nbsp;Mauro Catalan ,&nbsp;Pierpaolo Busan","doi":"10.1016/j.parkreldis.2025.108128","DOIUrl":"10.1016/j.parkreldis.2025.108128","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108128"},"PeriodicalIF":3.4,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621005","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":"Two homozygous KIF1C variants in a Turkish family presenting with cerebellar dysfunction and spastic paraparesis with MRI findings","authors":"Gullu Tarhan ,&nbsp;Sahinde Fazilet Hiz ,&nbsp;Busra Elif Inanir ,&nbsp;Gulsah Simsir ,&nbsp;Seyma Tekgul ,&nbsp;Ayse Nazlı Basak ,&nbsp;Sebahat Nacar Dogan","doi":"10.1016/j.parkreldis.2025.108127","DOIUrl":"10.1016/j.parkreldis.2025.108127","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108127"},"PeriodicalIF":3.4,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145621006","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":"Levodopa consumption in sleep: A novel parasomnia in Parkinson's disease","authors":"Shreyashi Jha,&nbsp;Mandar S. Jog","doi":"10.1016/j.parkreldis.2025.108122","DOIUrl":"10.1016/j.parkreldis.2025.108122","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108122"},"PeriodicalIF":3.4,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527615","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":"Motor complications and postural abnormalities interplay in Parkinson's disease","authors":"Margherita Fabbri ,&nbsp;Aymeric Lanore ,&nbsp;Nathalie Bertille ,&nbsp;Jean-Christophe Corvol ,&nbsp;Olivier Rascol ,&nbsp;Philippe Remy ,&nbsp;Luc Defebvre ,&nbsp;Chloé Laurencin ,&nbsp;Jean-Philippe Azulay ,&nbsp;Solène Frismand ,&nbsp;Philppe Damier ,&nbsp;Caroline Giordana Reuther ,&nbsp;Melissa Tir ,&nbsp;Claire Thiriez ,&nbsp;Gwendoline Dupont ,&nbsp;Jean-Luc Houeto ,&nbsp;Christian Geny ,&nbsp;Giovanni Castelnovo ,&nbsp;Anne Doe De Maindreville ,&nbsp;Sophie Drapier ,&nbsp;Christine Brefel-Courbon","doi":"10.1016/j.parkreldis.2025.108124","DOIUrl":"10.1016/j.parkreldis.2025.108124","url":null,"abstract":"<div><h3>Background</h3><div>Postural abnormalities (PA) and motor complications (MCs, including motor fluctuations – MFs- and levodopa-induced dyskinesia – LIDs) are hallmark of Parkinson's disease (PD) progression, yet their relationship remains poorly understood.</div></div><div><h3>Objective</h3><div>To investigate the association between PA and MCs, motor symptoms, and non-motor symptoms (NMS) in patients with PD, and to assess whether PA influences the development of MCs over time.</div></div><div><h3>Methods</h3><div>Data of the prospective NS-Park cohort (27 French PD Expert Centers) were analysed. PA was defined by a score ≥2 on item 3.13 of the MDS-UPDRS-III. Associations between PA and MCs, as well as with other motor symptoms and NMS, were assessed using logistic regression models. We used interval censoring survival models to assess the associations between PA at inclusion and the incidence of MCs. Analyses were adjusted for sex, age, disease duration, dopaminergic dose, and disease severity.</div></div><div><h3>Results</h3><div>Among 13,037 included PD patients (58.7 % male, median age at diagnosis 61 years), 724 (5.6 %) presented with PA. Patients with PA had longer disease duration, higher disease severity, and higher dopaminergic treatment. PA exhibited a higher prevalence of troublesome MFs (OR: 5.96; 95 % CI: 4.25–8.32) and LIDs (OR: 2.81; 95 % CI: 1.79–4.30), while associations with milder MCs were inconsistent. However, PA was not significantly associated with the development of MCs during follow-up.</div></div><div><h3>Conclusions</h3><div>PA are associated with more frequent severe MCs, and a higher burden of motor and NMS, making patient care particularly challenging.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"142 ","pages":"Article 108124"},"PeriodicalIF":3.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145574188","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}