Severity dependent distribution of impairments in PSP and CBS: Interactive visualizations.
Corticobasal syndrome
Interactive visualizations
PSP rating scale
Predictive models
Progressive supranuclear palsy
Journal
Parkinsonism & related disorders
ISSN: 1873-5126
Titre abrégé: Parkinsonism Relat Disord
Pays: England
ID NLM: 9513583
Informations de publication
Date de publication:
03 2019
03 2019
Historique:
received:
16
05
2018
revised:
29
08
2018
accepted:
31
08
2018
pubmed:
12
9
2018
medline:
6
5
2020
entrez:
12
9
2018
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 30201421
pii: S1353-8020(18)30384-5
doi: 10.1016/j.parkreldis.2018.08.025
pmc: PMC6399076
mid: NIHMS1002251
pii:
doi:
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
138-145Subventions
Organisme : NIA NIH HHS
ID : R01 AG038791
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG023481
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS092089
Pays : United States
Investigateurs
David Williams
(D)
Anne Louise Lafontaine
(AL)
Connie Marras
(C)
Mandar Jog
(M)
Michael Panisset
(M)
Anthony Lang
(A)
Lesley Parker
(L)
Alistair J Stewart
(AJ)
Jean-Christophe Corvol
(JC)
Jean-Philippe Azulay
(JP)
Philippe Couratier
(P)
Brit Mollenhauer
(B)
Stefan Lorenzl
(S)
Albert Ludolph
(A)
Reiner Benecke
(R)
Gunter Hoglinger
(G)
Axel Lipp
(A)
Heinz Reichmann
(H)
Dirk Woitalla
(D)
Dennis Chan
(D)
Adam Zermansky
(A)
David Burn
(D)
Andrew Lees
(A)
Illana Gozes
(I)
Adam Boxer
(A)
Bruce L Miller
(BL)
Iryna V Lobach
(IV)
Erik Roberson
(E)
Lawrence Honig
(L)
Edward Zamrini
(E)
Rajesh Pahwa
(R)
Yvette Bordelon
(Y)
Erika Driver-Dunkley
(E)
Stephanie Lessig
(S)
Mark Lew
(M)
Kyle Womack
(K)
Brad Boeve
(B)
Joseph Ferrara
(J)
Argyle Hillis
(A)
Daniel Kaufer
(D)
Rajeev Kumar
(R)
Tao Xie
(T)
Steven Gunzler
(S)
Theresa Zesiewicz
(T)
Praveen Dayalu
(P)
Lawrence Golbe
(L)
Murray Grossman
(M)
Joseph Jankovic
(J)
Scott McGinnis
(S)
Anthony Santiago
(A)
Paul Tuite
(P)
Stuart Isaacson
(S)
Julie Leegwater-Kim
(J)
Irene Litvan
(I)
David S Knopman
(DS)
Bruce L Miller
(BL)
Lon S Schneider
(LS)
Rachelle S Doody
(RS)
Lawrence I Golbe
(LI)
Erik D Roberson
(ED)
Mary Koestler
(M)
Clifford R Jack
(CR)
Viviana Van Deerlin
(V)
Christopher Randolph
(C)
Steve Whitaker
(S)
Joe Hirman
(J)
Michael Gold
(M)
Bruce H Morimoto
(BH)
Georg Nuebling G
(G)
Mira Hensler
(M)
Sabine Paul
(S)
Andreas Zwergal
(A)
Hilary W Heuer
(HW)
Maria C Tartaglia
(MC)
Irene Litvan
(I)
Scott M McGinnis
(SM)
Bradford C Dickerson
(BC)
John Kornak
(J)
Norbert Schuff
(N)
Gil D Rabinovici
(GD)
Howard J Rosen
(HJ)
Adam L Boxer
(AL)
J C Gómez
(JC)
B Tijero
(B)
K Berganzo
(K)
J Garc'ıa de Yebenes
(J)
J L Lopez Sendón
(JL)
G Garcia
(G)
E Tolosa
(E)
M T Buongiorno
(MT)
N Bargalló
(N)
J A Burguera
(JA)
I Martinez
(I)
J Ruiz-Mart'ınez
(J)
I Narrativel
(I)
F Vivancos
(F)
I Ybot
(I)
M Aguilar
(M)
P Quilez
(P)
M Boada
(M)
A Lafuente
(A)
I Hernandez
(I)
J J López-Lozano
(JJ)
M Mata
(M)
A Kupsch
(A)
A Lipp
(A)
G Ebersbach
(G)
T Schmidt
(T)
K Hahn
(K)
G Höglinger
(G)
M Höllerhage
(M)
W H Oertel
(WH)
G Respondek
(G)
M Stamelou
(M)
H Reichmann
(H)
M Wolz
(M)
C Schneider
(C)
L Klingelhöfer
(L)
D Berg
(D)
W Maetzler
(W)
K K Srulijes
(KK)
A Ludolph
(A)
J Kassubek
(J)
M Steiger
(M)
K Tyler
(K)
D J Burn
(DJ)
L Morris
(L)
A Lees
(A)
H Ling
(H)
R Hauser
(R)
T McClain
(T)
D Truong
(D)
S Jenkins
(S)
I Litvan
(I)
D Houghton
(D)
J Ferrara
(J)
Y Bordelon
(Y)
A Gratiano
(A)
L Golbe
(L)
M Mark
(M)
R Uitti
(R)
J Ven Gerpen
(J)
Informations de copyright
Copyright © 2018 Elsevier Ltd. All rights reserved.
Références
Mov Disord. 2017 Jun;32(6):853-864
pubmed: 28467028
Brain. 2007 Jun;130(Pt 6):1552-65
pubmed: 17405767
Mov Disord. 2014 Apr;29(4):470-8
pubmed: 24532007
Mov Disord. 2008 May 15;23(7):942-949
pubmed: 18464278
CNS Drugs. 2016 Jul;30(7):629-36
pubmed: 27222018
Neurology. 2013 Jan 29;80(5):496-503
pubmed: 23359374
Neurology. 1988 Jul;38(7):1031-4
pubmed: 3386818
Clin Neurol Neurosurg. 2016 Jul;146:35-9
pubmed: 27136096
Lancet Neurol. 2017 Jul;16(7):552-563
pubmed: 28653647
Neurology. 2003 Mar 25;60(6):917-22
pubmed: 12654953
Semin Neurol. 2014 Apr;34(2):225-34
pubmed: 24963682
Nat Commun. 2015 Jun 16;6:7247
pubmed: 26077951
J Neurol. 2016 Aug;263(8):1565-74
pubmed: 27230855
Neurol Neuroimmunol Neuroinflamm. 2016 Aug 02;3(5):e266
pubmed: 27583276
J Alzheimers Dis. 2016;52(3):1065-80
pubmed: 27079700
Lancet Neurol. 2014 Jul;13(7):676-85
pubmed: 24873720
Brain. 1997 Jan;120 ( Pt 1):65-74
pubmed: 9055798
Neurology. 2016 May 3;86(18):1736-43
pubmed: 27037234