Payan, Christine A M, Viallet, François, Landwehrmeyer, Bernhard G, Bonnet, Anne-Marie, Borg, Michel, Durif, Franck, Lacomblez, Lucette, Bloch, Frédéric, Verny, Marc, Fermanian, Jacques, Agid, Yves, Ludolph, Albert C, Leigh, Nigel and Bensimon, Gilbert (2011) Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS-Parkinson Plus Scale. PLoS ONE, 6 (8). e22293. ISSN 1932-6203

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Abstract

BACKGROUND

The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study.

METHODS AND FINDINGS

Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar.

CONCLUSIONS

The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA.

TRIAL REGISTRATION

ClinicalTrials.gov NCT00211224.

Item Type:	Article
Schools and Departments:	Brighton and Sussex Medical School > Clinical and Experimental Medicine Brighton and Sussex Medical School > Neuroscience
Subjects:	R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User:	Patricia Butler
Date Deposited:	09 Nov 2012 16:24
Last Modified:	02 Jul 2019 14:03
URI:	http://sro.sussex.ac.uk/id/eprint/42167

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