Parkinsonism & related disorders最新文献

{"title":"Infantile-onset choreo-dystonia due to a novel homozygous truncating HPCA variant: A first report from India.","authors":"Vikram V Holla, Sandeep Gurram, Sneha D Kamath, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal","doi":"10.1016/j.parkreldis.2025.107329","DOIUrl":"10.1016/j.parkreldis.2025.107329","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107329"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426033","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":"Convention vs. innovation III: The promise of stem cell therapy in Parkinson's disease remains bright (PSG debate 2024).","authors":"Alfonso Fasano, Avery Kundrick, Claire Henchcliffe","doi":"10.1016/j.parkreldis.2025.107849","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107849","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107849"},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972833","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":"Convention vs. innovation I: Skin biopsy for synuclein inclusions should now be used in the clinical setting (PSG debate 2024).","authors":"Drew Kern, Avery Kundrick, Liana S Rosenthal","doi":"10.1016/j.parkreldis.2025.107848","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107848","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107848"},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027387","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":"Combined assessment of blood glucocerebrosidase activity and α-synuclein levels in GBA1 mutation carriers: A novel potential biomarker","authors":"M. Avenali ,&nbsp;S.P. Caminiti ,&nbsp;M. Gegg ,&nbsp;S. Cerri ,&nbsp;P. Mitrotti ,&nbsp;L. Bandirali ,&nbsp;M. Toffoli ,&nbsp;D. Hughes ,&nbsp;C. Cerami ,&nbsp;C. Tassorelli ,&nbsp;E.M. Valente ,&nbsp;A.H.V. Schapira ,&nbsp;F. Blandini","doi":"10.1016/j.parkreldis.2025.107854","DOIUrl":"10.1016/j.parkreldis.2025.107854","url":null,"abstract":"<div><h3>Introduction</h3><div>Heterozygous variants in the <em>GBA1</em> gene encoding the glucocerebrosidase enzyme (GCase) are the most frequent genetic risk factor for Parkinson's Disease (PD). Yet, only a minority of <em>GBA1</em> carriers will eventually develop overt PD, and the mechanisms underlying such reduced penetrance are still largely unexplored.</div><div>Decreased GCase and increased α-synuclein levels are individually considered promising prognostic blood biomarkers for GBA-PD. Here, we aim to assess the combined role of decreased GCase activity and increased α-synuclein levels as a potential biochemical signature of worse outcome in <em>GBA1</em> population.</div></div><div><h3>Methods</h3><div>Ninety-eight subjects (30 GBA-nonPD, 29 GBA-PD and 39 healthy controls) underwent a detailed clinical assessment, as well as measurement of GCase activity and total α-synuclein levels in peripheral blood mononuclear cells (PBMCs). ROC curve analysis and a two-step clustering analysis were performed to classify subjects based on their combined GCase and α-synuclein biochemical profile. Clinical scores were analysed across clusters.</div></div><div><h3>Results</h3><div>ROC curve analysis based on α-synuclein/GCase activity ratio was able to discriminate <em>GBA1</em> positive individuals from healthy controls. We identified two separate biochemical clusters – a benign (high GCase/mid-low α-synuclein) and a malignant (low GCase/high α-synuclein) cluster. All healthy controls belonged to the benign cluster, while 59% of GBA-PD and 47% of GBA-nonPD fell into the malignant cluster. GBA-nonPD within the malignant cluster had greater depressive symptoms, and GBA-PD showed worse cognitive performance.</div></div><div><h3>Conclusions</h3><div>We report for the first time that the combined assessment of blood GCase activity and α-synuclein levels can define two distinctive biochemical clusters able to discriminate GBA-nonPD subjects with greater preclinical non-motor symptoms and GBA-PD patients with a worse cognitive profile. Longitudinal studies are needed to confirm the accuracy of this potential biomarker.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"135 ","pages":"Article 107854"},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918528","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":"Peripheral Immune pattern in a genetic cohort of p.A53T alpha-synuclein carriers","authors":"Christos Koros ,&nbsp;Athina-Maria Simitsi ,&nbsp;Nikolaos Papagiannakis ,&nbsp;Roubina Antonelou ,&nbsp;Anastasia Bougea ,&nbsp;Dimitra Papadimitriou ,&nbsp;Ioanna Pachi ,&nbsp;Ion Beratis ,&nbsp;Dionysia Kontaxopoulou ,&nbsp;Stella Fragkiadaki ,&nbsp;Evangelos Sfikas ,&nbsp;Ioanna Alefanti ,&nbsp;Chrysa Chrysovitsanou ,&nbsp;Efthalia Angelopoulou ,&nbsp;Marianna Bregianni ,&nbsp;Konstantinos Lourentzos ,&nbsp;Vasilios C. Constantinides ,&nbsp;Georgios Velonakis ,&nbsp;Vasilios Prassopoulos ,&nbsp;Anastasios Bonakis ,&nbsp;Leonidas Stefanis","doi":"10.1016/j.parkreldis.2025.107853","DOIUrl":"10.1016/j.parkreldis.2025.107853","url":null,"abstract":"<div><h3>Introduction</h3><div>Previous research has shown that inflammatory immune biomarkers including peripheral white blood cell subpopulations differ between Parkinson's disease (PD) patients and healthy controls (HC), with PD exhibiting higher neutrophil to lymphocyte ratio (NLR). The aim of the present report was to assess the peripheral immune profile in patients or asymptomatic carriers harboring the p.A53T alpha-synuclein (SNCA) mutation.</div></div><div><h3>Methods</h3><div>Data regarding 31 p.A53T SNCA PD patients, 9 asymptomatic mutation carriers and 194 HCs were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on peripheral immune blood cells subpopulations and clinical/imaging parameters at baseline.</div></div><div><h3>Results</h3><div>NLR, Absolute Neutrophil cell count and Neutrophils to total Leukocytes ratio were increased in the p.A53T SNCA PD group as compared to HCs [2.77 vs 2.18 (p &lt; 0.001), 4.32 × 10^3 cells/μL vs 3.67 × 10^3 cells/μL (p = 0.001), 65.67 % vs 59.55 % (p &lt; 0.001)]. Differences in NLR were mainly driven by the male patient subgroup. Lymphocytes to total Leukocytes and Monocytes to total Leukocytes ratio were lower in the p.A53T SNCA cohort as compared to HC [(p = 0.001) and (p = 0.002)]. Finally, we observed a positive correlation between the absolute Lymphocyte count and the mean putamen DATSCAN signal. Asymptomatic carriers did not differ statistically from either group.</div></div><div><h3>Discussion</h3><div>Our current study provides evidence of a specific pattern of peripheral immune response in the p.A53T SNCA PD group which aligns well with literature data in idiopathic and GBA-PD. Whether this peripheral immune activation represents a contributing cause or an effect of the neurodegenerative process will require further study.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"135 ","pages":"Article 107853"},"PeriodicalIF":3.1,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907877","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":"Diagnostic work up when suspecting early onset Parkinson disease (EOPD). Recommendations from the MDS EOPD study group","authors":"Raja Mehanna ,&nbsp;Connie Marras ,&nbsp;Jori Fleisher ,&nbsp;Bart Post ,&nbsp;Kishore Raj Kumar ,&nbsp;Alastair Noyce ,&nbsp;Roy Alcalay ,&nbsp;Huw R. Morris ,&nbsp;Taku Hatano ,&nbsp;Mehri Salari ,&nbsp;Katarzyna Smilowska ,&nbsp;Yih Ru Wu ,&nbsp;Baorong Zhang ,&nbsp;Eng-King Tan ,&nbsp;Rodolfo Savica ,&nbsp;EOPD study group","doi":"10.1016/j.parkreldis.2025.107852","DOIUrl":"10.1016/j.parkreldis.2025.107852","url":null,"abstract":"<div><h3>Introduction</h3><div>Early onset Parkinson's disease (EOPD) has been defined as PD with onset of motor symptoms after age 21 but before age 50. While diagnostic criteria are clear, data suggest that clinicians are still uncomfortable making the diagnosis, resulting in multiple investigations and delays in diagnosis and initiation of treatment.</div></div><div><h3>Methods</h3><div>Following the Delphi process, the 15 members of the steering committee of the EOPD study group of the International Parkinson Disease and Movement Disorder Society (MDS) designed and completed a 10 binary or multiple-choice questions survey then met to establish recommendations regarding which investigations are needed for the diagnosis of EOPD.</div></div><div><h3>Results</h3><div>The average age of the 15 respondents (5 females) was 49 years, with 18.2 years average experience in the management of EOPD (range 9–30 years). All geographic sections of the MDS were represented to account for variability of practice. The committee discussed the role of brain MRI, Dopamine transporter (DaT) SPECT scan, laboratory investigation, and genetic testing when suspecting EOPD.</div></div><div><h3>Conclusion</h3><div>If EOPD is suspected on history and examination without any additional findings concerning for secondary or genetic parkinsonism, we recommend limiting investigations to brain MRI and laboratory investigation for Wilson's disease. This may expedite diagnosis and starting the appropriate treatment. Genetic testing is not necessary for diagnosis but can be useful to identify new genetic etiologies which could plausibly be used for trial inclusion.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"135 ","pages":"Article 107852"},"PeriodicalIF":3.1,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887494","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":"Alpha-synuclein in Parkinson's disease: the debate that must go on.","authors":"Tiago F Outeiro","doi":"10.1016/j.parkreldis.2025.107850","DOIUrl":"https://doi.org/10.1016/j.parkreldis.2025.107850","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":" ","pages":"107850"},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010881","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":"KIF5A variant in familial dystonia: A clinicogenetic study of a large Roma kindred","authors":"Jarosław Dulski ,&nbsp;Devesh C. Pant ,&nbsp;Dorota Hoffman-Zacharska ,&nbsp;Magdalena Kwaśniak-Butowska ,&nbsp;Zbigniew K. Wszolek ,&nbsp;Jarosław Sławek","doi":"10.1016/j.parkreldis.2025.107825","DOIUrl":"10.1016/j.parkreldis.2025.107825","url":null,"abstract":"<div><h3>Background</h3><div>Mutations in the <em>KIF5A</em> gene were associated with several neurological diseases, including hereditary spastic paraplegia type 10, Charcot–Marie–Tooth type 2, amyotrophic lateral sclerosis, and neonatal intractable myoclonus. To date, none of the <em>KIF5A</em> variants was linked with dystonia. This study presents the first family with autosomal-dominant dystonia exhibiting incomplete penetrance, potentially linked to a <em>KIF5A</em> variant.</div></div><div><h3>Methods</h3><div>Seven family members were recruited between 2017 and 2024. Detailed medical history and neurological examination were conducted for all. Genetic screening, including Sanger sequencing, MLPA analysis of <em>SGCE</em>, and PCR RFLP/<em>Bse</em>RI for the common dystonia <em>TOR1A</em> mutation (c.907-909del), followed by whole exome sequencing, was performed on the proband and one affected relative. The genetic status of the remaining five individuals was assessed with Sanger sequencing.</div></div><div><h3>Results</h3><div>A missense variant in the <em>KIF5A</em> c.118G &gt; A was found in four affected and one asymptomatic individual, while it was absent in two non-affected individuals. The variant is rare in the general population (0.00001 in gnomAD 4.0), affects a highly conserved amino acid, and <em>in silico</em> models (M-CAP) indicates it is pathogenic. It was classified as likely pathogenic per ACMG criteria (PM1, PM2, PP2, PP3).</div></div><div><h3>Conclusions</h3><div>Our study suggests that <em>KIF5A</em> could represent a potential dystonia gene and sheds light on the broader role of motor proteins in human health and disease. This further expands the phenotypes associated with <em>KIF5A</em> and highlights the importance for clinicians to include this variant in their screening panels, as it tends to be underrepresented in current databases.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"135 ","pages":"Article 107825"},"PeriodicalIF":3.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887493","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":"Disease-modifying therapy in GBA1-related Parkinson's disease: the type of variant matters","authors":"Fabiana Colucci ,&nbsp;Emanuele Frattini ,&nbsp;Alessio Di Fonzo ,&nbsp;Roberto Cilia","doi":"10.1016/j.parkreldis.2025.107847","DOIUrl":"10.1016/j.parkreldis.2025.107847","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"135 ","pages":"Article 107847"},"PeriodicalIF":3.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009038","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 Parkinson's disease diagnosis validity on the association with cancer: A systematic review and meta-analysis","authors":"Ayla Mehdiyeva ,&nbsp;Valtteri Kaasinen ,&nbsp;Eetu Heervä ,&nbsp;Jussi O.T. Sipilä","doi":"10.1016/j.parkreldis.2025.107846","DOIUrl":"10.1016/j.parkreldis.2025.107846","url":null,"abstract":"<div><h3>Background</h3><div>Meta-analyses have reported lower cancer incidence in patients with Parkinson's disease (PD) compared to the general population but with considerable data heterogeneity.</div></div><div><h3>Objective</h3><div>To explore how the validity of the PD diagnoses is related to the association with cancer.</div></div><div><h3>Methods</h3><div>We conducted a systematic review and meta-analysis in which studies were stratified into groups based on the diagnostic validity of Parkinson's disease. Studies investigating mortality data and those examining cancer risk within certain genetic subgroups of PD were excluded.</div></div><div><h3>Results</h3><div>Thirty-four articles encompassing 533,102 patients with PD from 11 countries met the inclusion criteria. Stratified analyses revealed no association between PD and overall cancer risk preceding or following the PD diagnosis in studies using validated PD data. Studies utilizing less robust PD identification methods, the majority of which were cohort studies, demonstrated a neutral or decreased cancer risk among PD patients. In the studies with the most rigorous PD validation organ-specific analyses showed an increased risk of cutaneous melanoma but no decreased risk in any type of cancer. The positive association between PD and melanoma was more pronounced in the studies with more robust PD diagnosis validity.</div></div><div><h3>Conclusions</h3><div>The reported associations between PD and cancer are substantially influenced by the quality of PD data. Future investigations should concentrate on organ-specific cancers, instead of pooling cancers together, and use only PD cohorts with validated diagnosis.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"135 ","pages":"Article 107846"},"PeriodicalIF":3.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038510","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}