Daisuke Ono, Hiroaki Sekiya, Nikhil B Ghayal, Alexia R Maier, Shanu F Roemer, Ryan J Uitti, Irene Litvan, Keith A Josephs, Zbigniew K Wszolek, Dennis W Dickson
{"title":"进行性核上性麻痹的早期亚型和进展：一个数据驱动的脑库研究。","authors":"Daisuke Ono, Hiroaki Sekiya, Nikhil B Ghayal, Alexia R Maier, Shanu F Roemer, Ryan J Uitti, Irene Litvan, Keith A Josephs, Zbigniew K Wszolek, Dennis W Dickson","doi":"10.1101/2025.07.04.25330863","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Progressive supranuclear palsy (PSP) is typically characterized by vertical supranuclear gaze palsy and early falls, referred to as Richardson's syndrome (PSP-RS). Other presentations include postural instability (PSP-PI), parkinsonism (PSP-P), speech/language impairment (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). Differences across the early presentations and in their subsequent progression have yet to be elucidated.</p><p><strong>Objective: </strong>This study aimed to characterize early PSP subtypes and their subsequent progressions using a large postmortem dataset.</p><p><strong>Methods: </strong>An automated pipeline incorporating fine-tuned ChatGPT models was developed. The pipeline collected 195 clinical features with onset information from autopsy-confirmed PSP cases without significant neurodegenerative co-pathologies.</p><p><strong>Results: </strong>A structured clinicopathologic dataset from 588 patients was analyzed. After distilling results with unsupervised clustering, a decision tree model was developed. With five clinical manifestations: frontal presentation, PI, OM, SL, and parkinsonism, this mutually exclusive algorithm identified seven subtypes: PSP-PF (postural and frontal dysfunction), PSP-RS, PSP-PI, PSP-P, PSP-SL, PSP-F, and PSP-OM. PSP-PF, defined by PI and frontal presentation, showed rapid progression, the shortest median disease duration (six years), and high tau burden in cortical and subcortical regions. In PSP-F, frontal presentation preceded other symptoms by four years, and the disease duration was the second longest (nine years) after PSP-P (10 years). PSP-CBS was not identified as an independent subtype.</p><p><strong>Conclusions: </strong>This data-driven study identified a novel, aggressive PSP phenotype characterized by early postural and frontal dysfunction. Early subtyping utilizing the decision tree would help clinicians estimate progression and facilitate early patient recruitment for clinical trials.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12236881/pdf/","citationCount":"0","resultStr":"{\"title\":\"Early Subtypes and Progressions of Progressive Supranuclear Palsy: A Data-Driven Brain Bank Study.\",\"authors\":\"Daisuke Ono, Hiroaki Sekiya, Nikhil B Ghayal, Alexia R Maier, Shanu F Roemer, Ryan J Uitti, Irene Litvan, Keith A Josephs, Zbigniew K Wszolek, Dennis W Dickson\",\"doi\":\"10.1101/2025.07.04.25330863\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Progressive supranuclear palsy (PSP) is typically characterized by vertical supranuclear gaze palsy and early falls, referred to as Richardson's syndrome (PSP-RS). Other presentations include postural instability (PSP-PI), parkinsonism (PSP-P), speech/language impairment (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). Differences across the early presentations and in their subsequent progression have yet to be elucidated.</p><p><strong>Objective: </strong>This study aimed to characterize early PSP subtypes and their subsequent progressions using a large postmortem dataset.</p><p><strong>Methods: </strong>An automated pipeline incorporating fine-tuned ChatGPT models was developed. The pipeline collected 195 clinical features with onset information from autopsy-confirmed PSP cases without significant neurodegenerative co-pathologies.</p><p><strong>Results: </strong>A structured clinicopathologic dataset from 588 patients was analyzed. After distilling results with unsupervised clustering, a decision tree model was developed. With five clinical manifestations: frontal presentation, PI, OM, SL, and parkinsonism, this mutually exclusive algorithm identified seven subtypes: PSP-PF (postural and frontal dysfunction), PSP-RS, PSP-PI, PSP-P, PSP-SL, PSP-F, and PSP-OM. PSP-PF, defined by PI and frontal presentation, showed rapid progression, the shortest median disease duration (six years), and high tau burden in cortical and subcortical regions. In PSP-F, frontal presentation preceded other symptoms by four years, and the disease duration was the second longest (nine years) after PSP-P (10 years). PSP-CBS was not identified as an independent subtype.</p><p><strong>Conclusions: </strong>This data-driven study identified a novel, aggressive PSP phenotype characterized by early postural and frontal dysfunction. 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Early Subtypes and Progressions of Progressive Supranuclear Palsy: A Data-Driven Brain Bank Study.
Background: Progressive supranuclear palsy (PSP) is typically characterized by vertical supranuclear gaze palsy and early falls, referred to as Richardson's syndrome (PSP-RS). Other presentations include postural instability (PSP-PI), parkinsonism (PSP-P), speech/language impairment (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). Differences across the early presentations and in their subsequent progression have yet to be elucidated.
Objective: This study aimed to characterize early PSP subtypes and their subsequent progressions using a large postmortem dataset.
Methods: An automated pipeline incorporating fine-tuned ChatGPT models was developed. The pipeline collected 195 clinical features with onset information from autopsy-confirmed PSP cases without significant neurodegenerative co-pathologies.
Results: A structured clinicopathologic dataset from 588 patients was analyzed. After distilling results with unsupervised clustering, a decision tree model was developed. With five clinical manifestations: frontal presentation, PI, OM, SL, and parkinsonism, this mutually exclusive algorithm identified seven subtypes: PSP-PF (postural and frontal dysfunction), PSP-RS, PSP-PI, PSP-P, PSP-SL, PSP-F, and PSP-OM. PSP-PF, defined by PI and frontal presentation, showed rapid progression, the shortest median disease duration (six years), and high tau burden in cortical and subcortical regions. In PSP-F, frontal presentation preceded other symptoms by four years, and the disease duration was the second longest (nine years) after PSP-P (10 years). PSP-CBS was not identified as an independent subtype.
Conclusions: This data-driven study identified a novel, aggressive PSP phenotype characterized by early postural and frontal dysfunction. Early subtyping utilizing the decision tree would help clinicians estimate progression and facilitate early patient recruitment for clinical trials.
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