TY - JOUR
T1 - Severity dependent distribution of impairments in PSP and CBS
T2 - Interactive visualizations
AU - The PROPSPERA investigators
AU - 4RNTI-1authors
AU - Tau Restoration on PSP (TAUROS) Investigators
AU - The AL-108-231 Study Group
AU - Brittain, Claire
AU - McCarthy, Andrew
AU - Irizarry, Michael C.
AU - McDermott, Dana
AU - Biglan, Kevin
AU - Höglinger, Günter U.
AU - Lorenzl, Stefan
AU - del Ser, Teodoro
AU - Boxer, Adam L.
AU - Williams, David
AU - Lafontaine, Anne Louise
AU - Marras, Connie
AU - Jog, Mandar
AU - Panisset, Michael
AU - Lang, Anthony
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
AU - Zermansky, Adam
AU - Burn, David
AU - Lees, Andrew
AU - Gozes, Illana
AU - Miller, Bruce L.
AU - Lobach, Iryna V.
AU - Roberson, Erik D.
AU - Honig, Lawrence
AU - Zamrini, Edward
AU - Pahwa, Rajesh
AU - Bordelon, Yvette
AU - Driver-Dunkley, Erika
AU - Lessig, Stephanie
AU - Lew, Mark
AU - Womack, Kyle
AU - Boeve, Brad
AU - Ferrara, Joseph
AU - Hillis, Argyle
AU - Kaufer, Daniel
AU - Kumar, Rajeev
AU - Xie, Tao
AU - Tuite, Paul
N1 - Funding Information:
SL has received research grants from the Bavarian State and the Deutsche Stifterverband. He has received honoraria for presentations from UCB and Abbvie. He has not served as a consultant and has not participated in any Advisory Board during the last year. He has no Intellectual Property Rights, Royalties, Contracts stock ownerships.
Funding Information:
The AL-108-231, TAUROS and PROSPERA clinical trials were conducted and funded by the respective companies. 4RTNI is funded by the NIH ( R01AG038791 ; U54NS092089 ); Eli Lilly funded the analyses for this paper.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/3/1
Y1 - 2019/3/1
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.
AB - 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.
KW - Corticobasal syndrome
KW - Interactive visualizations
KW - PSP rating scale
KW - Predictive models
KW - Progressive supranuclear palsy
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U2 - 10.1016/j.parkreldis.2018.08.025
DO - 10.1016/j.parkreldis.2018.08.025
M3 - Article
C2 - 30201421
AN - SCOPUS:85052968758
SN - 1353-8020
VL - 60
SP - 138
EP - 145
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -