title: Disease severity and progression in progressive supranuclear palsy and multiple system atrophy: validation of the NNIPPS--Parkinson Plus Scale.
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.
  
  
  RESULTS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00211224.
authors.affiliation: Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, APHP, UPMC Pharmacologie, Paris 6, UMR 7211, Paris, France.
authors.forename: Christine A M
authors.initials: CA
authors.lastname: Payan
authors.forename: François
authors.initials: F
authors.lastname: Viallet
authors.forename: Bernhard G
authors.initials: BG
authors.lastname: Landwehrmeyer
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bonnet
authors.forename: Michel
authors.initials: M
authors.lastname: Borg
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.forename: Lucette
authors.initials: L
authors.lastname: Lacomblez
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bloch
authors.forename: Marc
authors.initials: M
authors.lastname: Verny
authors.forename: Jacques
authors.initials: J
authors.lastname: Fermanian
authors.forename: Yves
authors.initials: Y
authors.lastname: Agid
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Peter N
authors.initials: PN
authors.lastname: Leigh
authors.forename: Gilbert
authors.initials: G
authors.lastname: Bensimon
mesh_terms: D018450:Disease Progression; D006801:Humans; D019578:Multiple System Atrophy / Q000473:pathology*; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D013494:Supranuclear Palsy, Progressive / Q000473:pathology*