Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations

The AL-108-231 Study Group, The PROPSPERA investigators, 4RNTI-1authors, Tau Restoration on PSP (TAUROS) Investigators

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. Objectives: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. Methods: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. Results: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. Conclusion: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.

Original languageEnglish (US)
Pages (from-to)138-145
Number of pages8
JournalParkinsonism and Related Disorders
Volume60
DOIs
StatePublished - Mar 1 2019

Fingerprint

Progressive Supranuclear Palsy
Clinical Trials
Extremities
Tauopathies
Therapeutic Uses
Natural History
Gait
Multicenter Studies
Disease Progression

Keywords

  • Corticobasal syndrome
  • Interactive visualizations
  • Predictive models
  • Progressive supranuclear palsy
  • PSP rating scale

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

The AL-108-231 Study Group, The PROPSPERA investigators, 4RNTI-1authors, & Tau Restoration on PSP (TAUROS) Investigators (2019). Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations. Parkinsonism and Related Disorders, 60, 138-145. https://doi.org/10.1016/j.parkreldis.2018.08.025

Severity dependent distribution of impairments in PSP and CBS : Interactive visualizations. / The AL-108-231 Study Group; The PROPSPERA investigators; 4RNTI-1authors; Tau Restoration on PSP (TAUROS) Investigators.

In: Parkinsonism and Related Disorders, Vol. 60, 01.03.2019, p. 138-145.

Research output: Contribution to journalArticle

The AL-108-231 Study Group, The PROPSPERA investigators, 4RNTI-1authors & Tau Restoration on PSP (TAUROS) Investigators 2019, 'Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations', Parkinsonism and Related Disorders, vol. 60, pp. 138-145. https://doi.org/10.1016/j.parkreldis.2018.08.025
The AL-108-231 Study Group, The PROPSPERA investigators, 4RNTI-1authors, Tau Restoration on PSP (TAUROS) Investigators. Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations. Parkinsonism and Related Disorders. 2019 Mar 1;60:138-145. https://doi.org/10.1016/j.parkreldis.2018.08.025
The AL-108-231 Study Group ; The PROPSPERA investigators ; 4RNTI-1authors ; Tau Restoration on PSP (TAUROS) Investigators. / Severity dependent distribution of impairments in PSP and CBS : Interactive visualizations. In: Parkinsonism and Related Disorders. 2019 ; Vol. 60. pp. 138-145.
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abstract = "Background: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. Objectives: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. Methods: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. Results: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. Conclusion: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.",
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AU - Parker, Lesley

AU - Stewart, Alistair J.

AU - Corvol, Jean Christophe

AU - Azulay, Jean Philippe

AU - Couratier, Philippe

AU - Mollenhauer, Brit

AU - Ludolph, Albert

AU - Benecke, Reiner

AU - Hoglinger, Gunter

AU - Lipp, Axel

AU - Reichmann, Heinz

AU - Woitalla, Dirk

AU - Chan, Dennis

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AU - Boeve, Brad

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AU - Kumar, Rajeev

AU - Xie, Tao

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N2 - Background: Progressive supranuclear palsy (PSP) -Richardson's Syndrome and Corticobasal Syndrome (CBS) are the two classic clinical syndromes associated with underlying four repeat (4R) tau pathology. The PSP Rating Scale is a commonly used assessment in PSP clinical trials; there is an increasing interest in designing combined 4R tauopathy clinical trials involving both CBS and PSP. Objectives: To determine contributions of each domain of the PSP Rating Scale to overall severity and characterize the probable sequence of clinical progression of PSP as compared to CBS. Methods: Multicenter clinical trial and natural history study data were analyzed from 545 patients with PSP and 49 with CBS. Proportional odds models were applied to model normalized cross-sectional PSP Rating Scale, estimating the probability that a patient would experience impairment in each domain using the PSP Rating Scale total score as the index of overall disease severity. Results: The earliest symptom domain to demonstrate impairment in PSP patients was most likely to be Ocular Motor, followed jointly by Gait/Midline and Daily Activities, then Limb Motor and Mentation, and finally Bulbar. For CBS, Limb Motor manifested first and ocular showed less probability of impairment throughout the disease spectrum. An online tool to visualize predicted disease progression was developed to predict relative disability on each subscale per overall disease severity. Conclusion: The PSP Rating Scale captures disease severity in both PSP and CBS. Modelling how domains change in relation to one other at varying disease severities may facilitate detection of therapeutic effects in future clinical trials.

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KW - Corticobasal syndrome

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