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Parkinsonism Relat Disord. 2019 Mar;60:138-145. doi: 10.1016/j.parkreldis.2018.08.025. Epub 2018 Sep 4.

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

Collaborators (142)

Williams D8, Lafontaine AL9, Marras C9, Jog M9, Panisset M9, Lang A9, Parker L9, Stewart AJ9, Corvol JC10, Azulay JP10, Couratier P10, Mollenhauer B11, Lorenzl S11, Ludolph A11, Benecke R11, Hoglinger G11, Lipp A11, Reichmann H11, Woitalla D11, Chan D12, Zermansky A12, Burn D12, Lees A12, Gozes I13, Boxer A14, Miller BL14, Lobach IV14, Roberson E14, Honig L14, Zamrini E14, Pahwa R14, Bordelon Y14, Driver-Dunkley E14, Lessig S14, Lew M14, Womack K14, Boeve B14, Ferrara J14, Hillis A14, Kaufer D14, Kumar R14, Xie T14, Gunzler S14, Zesiewicz T14, Dayalu P14, Golbe L14, Grossman M14, Jankovic J14, McGinnis S14, Santiago A14, Tuite P14, Isaacson S14, Leegwater-Kim J14, Litvan I14, Knopman DS14, Miller BL14, Schneider LS14, Doody RS14, Golbe LI14, Roberson ED14, Koestler M14, Jack CR Jr14, Van Deerlin V14, Randolph C14, Whitaker S14, Hirman J14, Gold M14, Morimoto BH14, Nuebling G G, Hensler M, Paul S, Zwergal A, Heuer HW, Tartaglia MC, Litvan I, McGinnis SM, Dickerson BC, Kornak J, Schuff N, Rabinovici GD, Rosen HJ, Boxer AL, Gómez JC15, Tijero B15, Berganzo K15, Garc'ıa de Yebenes J16, Lopez Sendón JL16, Garcia G16, Tolosa E17, Buongiorno MT17, Bargalló N17, Burguera JA18, Martinez I18, Ruiz-Mart'ınez J19, Narrativel I19, Vivancos F20, Ybot I20, Aguilar M21, Quilez P21, Boada M22, Lafuente A22, Hernandez I22, López-Lozano JJ23, Mata M23, Kupsch A24, Lipp A24, Ebersbach G25, Schmidt T25, Hahn K25, Höglinger G26, Höllerhage M26, Oertel WH26, Respondek G26, Stamelou M26, Reichmann H27, Wolz M27, Schneider C27, Klingelhöfer L27, Berg D28, Maetzler W28, Srulijes KK28, Ludolph A29, Kassubek J29, Steiger M30, Tyler K30, Burn DJ31, Morris L31, Lees A32, Ling H32, Hauser R33, McClain T33, Truong D34, Jenkins S34, Litvan I35, Houghton D35, Ferrara J35, Bordelon Y36, Gratiano A36, Golbe L37, Mark M37, Uitti R, Ven Gerpen J.

Author information

1
Eli Lilly and Company, Lilly Research Center, Sunninghill Road, Windlesham, Surrey GU20 6PH, United Kingdom. Electronic address: Claire.Brittain@UCB.com.
2
Eli Lilly and Company, Lilly Research Center, Sunninghill Road, Windlesham, Surrey GU20 6PH, United Kingdom.
3
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA.
4
Memory and Aging Center, Department of Neurology, University of California, 675 Nelson Rising Lane, Suite 193, San Francisco, CA, 94158, USA.
5
Department of Neurology, Technische Universität München, Arcisstraße 2, D-80333, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Feodor-Lynen Str. 17, D-81677, Munich, Germany.
6
Department of Neurology, Hospital Agatharied, Norbert-Kerkel-Platz, 83734, Hausham/Obb, Germany.
7
Neurological Department, Alzheimer Project Research Unit, Fundacion Centro Investigacion Enfermedades Neurologicas, Calle de Valderrebollo, 5, 28031, Madrid, Spain.
8
Australia.
9
Canada.
10
France.
11
Germany.
12
United Kingdom.
13
Israel.
14
United States.
15
Hospital de Cruces, Barakaldo, Spain.
16
Hospital Ramón y Cajal, Madrid, Spain.
17
Hospital Clinic, Barcelona, Spain.
18
Hospital La Fe, Valencia, Spain.
19
Hospital Donostia, San Sebastían, Spain.
20
Hospital La Paz, Madrid, Spain.
21
Hospital Mutua Terrassa, Terrassa, Spain.
22
Fundación ACE, Barcelona, Spain.
23
Hospital Puerta de Hierro, Madrid, Spain.
24
Virchow-Klinikum, Berlin, Germany.
25
Neurologisches Fachkrankenhaus für Bewegungsstörungen, Beelitz, Germany.
26
Universitätsklinikum, Marburg, Germany.
27
Universitätsklinikum, Dresden, Germany.
28
Universitätsklinikum, Tübingen, Germany.
29
Universitütsklinikum, Ulm, Germany.
30
Walton Center, Liverpool, UK.
31
Clinical Ageing Research Unit, Newcastle upon Tyne, UK.
32
Reta Lila Weston Institute, London, UK.
33
University of South Florida, Tampa, FL, USA.
34
The Parkinson's and Movement Disorder Institute, Fountain Valley, CA, USA.
35
Division of Movement Disorders, University of Louisville, Louisville, KY, USA.
36
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
37
Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

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.

KEYWORDS:

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

PMID:
30201421
PMCID:
PMC6399076
[Available on 2020-03-01]
DOI:
10.1016/j.parkreldis.2018.08.025

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