Parkinsonism & related disorders最新文献

{"title":"Co-stimulating the left vmPFC compensates for apathy after levodopa withdrawal in Parkinson's patients with STN DBS.","authors":"Jip de Bruin,&nbsp;Ki Sueng Choi,&nbsp;Helen S. Mayberg,&nbsp;Joohi Jimenez-Shahed,&nbsp;Christina A. Palmese,&nbsp;Juna Khang,&nbsp;Ha Neul Song,&nbsp;Brian H. Kopell,&nbsp;Martijn Figee","doi":"10.1016/j.parkreldis.2024.107244","DOIUrl":"10.1016/j.parkreldis.2024.107244","url":null,"abstract":"<div><h3>Introduction</h3><div>Subthalamic nucleus deep brain stimulation (STN DBS) improves motor symptoms of Parkinson's disease (PD), but its effect on motivation is controversial. Apathy, the lack of motivation, commonly occurs in PD and is often exacerbated after surgery and its concomitant levodopa reduction. Apathy and reward processing are associated with the ventromedial prefrontal cortex (vmPFC), which standard targeting strategies avoid by targeting the dorsolateral STN. Since apathy can be a levodopa-responsive PD symptom, levodopa withdrawal could unmask apathy without sufficient stimulation of non-motor pathways, similar to the persistence of motor symptoms when motor pathways are underengaged with DBS.</div></div><div><h3>Objective</h3><div>Using an individualized tractography model, maximized left-sided vmPFC engagement following a DBS adjustment improved apathy in a case example. We, therefore, retrospectively investigated the moderating role of stimulation-related left-sided vmPFC connectivity and levodopa reduction on changes in apathy after STN DBS (N = 28).</div></div><div><h3>Methods</h3><div>We measured apathy (Starkstein Apathy Scale) and levodopa dose pre- and post-surgery. Stimulation-related connectivity was quantified using patient-specific diffusion-weighted MRI and probabilistic tractography to test the interaction with levodopa reduction.</div></div><div><h3>Results</h3><div>Effective DBS of the dorsolateral STN included prefrontal non-motor connections. We found a significant interaction between levodopa dose change and STN-connections to the left vmPFC. Apathy severity negatively correlated with stimulation-related connectivity to the left vmPFC in patients with greater levodopa reductions. Apathy change was unrelated to motor pathway connectivity.</div></div><div><h3>Conclusion</h3><div>Insufficient stimulation of the left vmPFC and associated limbic fronto-subthalamic connections combined with high levodopa reduction contributed to DBS-related apathy in PD, which may inspire novel personalized non-motor targeting strategies.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107244"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896682","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":"Vacuolar protein sorting 13 homolog C was associated with motor progression in Parkinson's disease","authors":"Xin Guo ,&nbsp;Bin Teng ,&nbsp;Jianfang Ma","doi":"10.1016/j.parkreldis.2024.107253","DOIUrl":"10.1016/j.parkreldis.2024.107253","url":null,"abstract":"<div><h3>Introduction</h3><div>The SNP rs2414739 of Vacuolar protein sorting 13 homolog C(VPS13C) gene was identified to be linked with Parkinson's Disease (PD).</div></div><div><h3>Objectives</h3><div>Explore the clinical progression feature of PD patients with rs2414739 variant.</div></div><div><h3>Methods</h3><div>Longitudinal data were obtained from the Parkinson's Progression Marker Initiative (PPMI) cohorts. Linear mixed models were used to test the effects of <em>VPS13C</em> with the progression of PD assessed by different scales.</div></div><div><h3>Result</h3><div>A total of 333 patients with PD were included and divided into rs2414739 carriers (n = 138) and noncarriers (n = 195). Patients with PD carrying <em>VPS13C</em> mutation had slower progression, assessed by total scores of MDS-UPDRS (II+III) (β = −1.834, p = 0.000, 95%CI: −2.767, −0.901) than noncarriers. The effect of <em>VPS13C</em> was significant both in the rate of change of UPDRS-II scores (β = −0.284, p = 0.028, 95%CI: −0.537, −0.031) and UPDRS-III scores (β = −0.894, p = 0.009, 95%CI: −1.558, −0.228). We further divided VPS13C carriers into heterozygous and homozygous carriers, and found that the rate of change of UPDRS(II+III) (β = −1.165, p = 0.039, 95%CI: −2.265,−0.062) scores and UPDRS-III scores (β = −9.521, p = 0.041, 95%CI: −18.524,−0.532) were significantly slow in heterozygous VPS13C carriers. There was only 20 homozygous VPS13C carriers, which was too small a sample to perform the analysis.</div></div><div><h3>Conclusion</h3><div><em>VPS13C</em> was associated with slow motor progression in PD patients.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107253"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927046","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":"Glymphatic system in Pantothenase kinase associated neurodegeneration (PKAN)","authors":"Peter Stoeter ,&nbsp;Diones Rivera ,&nbsp;Pedro Roa ,&nbsp;Herwin Speckter ,&nbsp;Cesarina Torres","doi":"10.1016/j.parkreldis.2024.107252","DOIUrl":"10.1016/j.parkreldis.2024.107252","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate if accumulation of iron in the globus pallidus as seen in patients suffering from Pantothenase Kinase Associated Neurodegeneration (PKAN), is related to damage of the cerebral glymphatic system.</div></div><div><h3>Material and methods</h3><div>In a group of 24 patients and an age-matched control group, functionality of the glymphatic system was assessed by the index of Analysis aLong the Perivascular Space (ALPS) from Diffusion Tensor Imaging data and correlated to the values of the T2∗ Times of the globus pallidus and the cerebral white matter measured by a Fast Field Echo sequence.</div></div><div><h3>Results</h3><div>In spite of the important reduction of the T2∗ Time of the globus pallidus, ALPS values of patients and controls were very similar and did not correlate to T2∗Time values in either group.</div></div><div><h3>Conclusion</h3><div>In spite of a prominent accumulation of iron in the globus pallidus of PKAN patients, which is responsible for the “eye-of-the-tiger” sign, our results are not compatible with malfunction of their glymphatic system. Obviously, increased iron content of globus pallidus alone does not necessarily indicate such sort of alteration.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107252"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971901","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":"Late-onset chorea as first manifestation of cerebral amyloid angiopathy","authors":"Daniel López Domínguez ,&nbsp;Berta Alemany Perna ,&nbsp;Gary Álvarez Bravo","doi":"10.1016/j.parkreldis.2024.107225","DOIUrl":"10.1016/j.parkreldis.2024.107225","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107225"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926958","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 α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology","authors":"Alberto J. Espay ,&nbsp;Andrew J. Lees ,&nbsp;Francisco Cardoso ,&nbsp;Steven J. Frucht ,&nbsp;Daniel Erskine ,&nbsp;Ivette M. Sandoval ,&nbsp;Luis Daniel Bernal-Conde ,&nbsp;Andrea Sturchio ,&nbsp;Alberto Imarisio ,&nbsp;Christian Hoffmann ,&nbsp;Kora T. Montemagno ,&nbsp;Dragomir Milovanovic ,&nbsp;Glenda M. Halliday ,&nbsp;Fredric P. Manfredsson","doi":"10.1016/j.parkreldis.2024.107256","DOIUrl":"10.1016/j.parkreldis.2024.107256","url":null,"abstract":"<div><div>The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst (“seed”) to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined. The result is binary: positive, meaning precipitation occurred, and a catalyst is present, or negative, meaning no precipitation, therefore no catalyst. Since protein precipitation via seeding can only occur at a concentration many-fold higher than the human brain, laboratory-elicited seeding does not mean human brain seeding. We suggest that a positive αSyn-SAA reveals the presence of pathological α-synuclein but not the underlying etiology for the precipitation of monomeric α-synuclein into its pathological form. Thus, a positive αSyn-SAA supports a clinical diagnosis of PD but cannot inform disease pathogenesis, ascertain severity, predict the rate of progression, define biology or biological subtypes, or monitor treatment response.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107256"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966271","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":"Comment on “The use of hypoglycemic drugs in Parkinson's disease: An updated meta-analysis of randomized controlled trials”","authors":"Luis Otávio Nogueira,&nbsp;Dayany Leonel Boone","doi":"10.1016/j.parkreldis.2024.107223","DOIUrl":"10.1016/j.parkreldis.2024.107223","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107223"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813935","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":"Authors' reply to “Perfection is the enemy of good - A Letter to the editor on \"Orthostatic hypotension in Parkinson's disease: Sit-to-stand vs. supine-to-stand protocol and clinical correlates”","authors":"Shen-Yang Lim,&nbsp;Kai Bin Lim,&nbsp;Jia Wei Hor,&nbsp;Ai Huey Tan","doi":"10.1016/j.parkreldis.2024.107221","DOIUrl":"10.1016/j.parkreldis.2024.107221","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107221"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847072","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 effect of Amyloid and Tau Co-pathology on disease progression in Lewy body dementia: A systematic review","authors":"Jerry HK. Tan ,&nbsp;Axel AS. Laurell ,&nbsp;Emad Sidhom ,&nbsp;James B. Rowe ,&nbsp;John T. O'Brien","doi":"10.1016/j.parkreldis.2024.107255","DOIUrl":"10.1016/j.parkreldis.2024.107255","url":null,"abstract":"<div><div>Co-morbid Alzheimer's disease (AD) pathology (amyloid-beta and tau) is commonly observed in Lewy body dementia (LBD), and this may affect clinical outcomes. A systematic review of the effect of AD co-pathology on longitudinal clinical outcomes in LBD was conducted. A search of MEDLINE and EMBASE (October 2024) yielded <em>n</em> = 3558 records that were screened by two independent reviewers. Included studies (n = 31) assessed AD co-pathology in LBD by neuropathologic examination (n = 10), positron emission tomography (PET) imaging (n = 7), cerebrospinal fluid (CSF) (n = 8) or plasma biomarkers (n = 6); and reported longitudinal clinical outcomes including cognitive and functional decline, mortality, or treatment response. Most neuropathology, PET and plasma studies reviewed demonstrated poorer prognosis in LBD + compared to LBD-, but discrepant findings were seen among CSF studies. No included study reported better outcomes in LBD+. The risk of bias was assessed with the Quality in Prognosis Studies tool. All studies rated as low risk of bias (<em>n</em> = 12) reported that the presence of AD co-pathology in LBD (LBD+) was associated with accelerated cognitive decline (<em>n</em> = 7/7), accelerated functional decline (<em>n</em> = 3/3), greater mortality (<em>n</em> = 2/2) and poorer response to treatment (<em>n</em> = 1/1). Among these studies, LBD+ was associated with an additional decline of −0.53 to −2.9 MMSE points/year compared to LBD-, while one study reported an adjusted hazard ratio for mortality in LBD + as 3.70. We conclude that AD co-pathology is associated with worse clinical outcomes in LBD whether assessed by greater cognitive decline, increased mortality or greater decline on functional assessment scales.</div></div>","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107255"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915361","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":"The alpha synuclein tug of war: A call for academic civility and open-mindedness","authors":"Hubert H. Fernandez (James and Constance Brown Endowed Chair for Movement Disorders)","doi":"10.1016/j.parkreldis.2025.107261","DOIUrl":"10.1016/j.parkreldis.2025.107261","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107261"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952913","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":"NDUFAF5 variants cause early onset Leigh syndrome","authors":"Breno Kazuo Massuyama,&nbsp;Amanda Monteiro Viagi,&nbsp;Rafael Chaves Claudino de Queiroga,&nbsp;Raphael Pinheiro Camurugy da Hora,&nbsp;Victor Rebelo Procaci,&nbsp;Augusto Bragança Reis Rosa,&nbsp;Thiago Yoshinaga Tonholo Silva,&nbsp;Orlando Graziani Povoas Barsottini,&nbsp;José Luiz Pedroso","doi":"10.1016/j.parkreldis.2024.107227","DOIUrl":"10.1016/j.parkreldis.2024.107227","url":null,"abstract":"","PeriodicalId":19970,"journal":{"name":"Parkinsonism & related disorders","volume":"131 ","pages":"Article 107227"},"PeriodicalIF":3.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829691","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}