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Background <p>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 disorder (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). However, differences across the early presentations and their subsequent clinical courses remain to be elucidated.</p> Objective <p>This study aimed to characterize early PSP subtypes and their subsequent progressions using a large postmortem dataset.</p> Methods <p>An automated pipeline incorporating fine-tuned Chat Generative Pretrained Transformer (ChatGPT) was developed. The pipeline collected 195 clinical features with onset information from autopsy-confirmed PSP cases without significant neurodegenerative co-pathologies.</p> Results <p>A structured clinicopathologic dataset from 588 patients was analyzed. The results from unsupervised clustering were distilled into a decision tree model. The 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, based on five clinical manifestations: frontal presentation, postural instability, ocular motor dysfunction, speech/language disorder, and Parkinsonism. PSP-PF 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, with a nine-year disease duration—second longest after PSP-P (10&#xa0;years). PSP-CBS was not identified as an independent subtype.</p> Conclusions <p>This data-driven study identified a novel, aggressive PSP phenotype characterized by early postural and frontal dysfunction. Early subtyping using the decision tree model would help clinicians estimate progression and facilitate early patient recruitment for clinical trials.</p>

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Early subtypes and progressions of progressive supranuclear palsy: a data-driven brain bank study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月17日

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  • 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

摘要

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 disorder (PSP-SL), frontal presentation (PSP-F), ocular motor dysfunction (PSP-OM), and corticobasal syndrome (PSP-CBS). However, differences across the early presentations and their subsequent clinical courses remain 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 Chat Generative Pretrained Transformer (ChatGPT) 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. The results from unsupervised clustering were distilled into a decision tree model. The 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, based on five clinical manifestations: frontal presentation, postural instability, ocular motor dysfunction, speech/language disorder, and Parkinsonism. PSP-PF 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, with a nine-year disease duration—second longest 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 using the decision tree model would help clinicians estimate progression and facilitate early patient recruitment for clinical trials.