Development and validation of the Unified Multiple System ...

1 Development and validation of the Unified Multiple SystemAtrophy Rating Scale (UMSARS)Gregor K. Wenning, MD, PhD,1*Franc ois Tison, MD,2 Klaus Seppi, MD,1 Cristina Sampaio, MD,3 Anja Diem, MD,1 Farid Yekhlef, MD,2 Imad Ghorayeb, MD,2 Fabienne Ory, MD,4 Monique Galitzky, MD,4 Tommaso Scaravilli, MD,5 Maria Bozi, MD,5 Carlo Colosimo, MD,6 Sid Gilman, MD,7 Clifford W. Shults, MD,8 Niall P. Quinn, MD,5 Olivier Rascol, MD,4 Werner Poewe, MD,1and the Multiple System Atrophy Study Group 1 Department of Neurology, University of Innsbruck, Innsbruck, Austria2 Service de Neurologie, Hopital du Haut-Leveque, Pessac, France3 Faculdade de Medicine de Lisboa, Hospital Santa Maria, Centro de Neurosciencas, Lisboa, Portugal4 Toulouse III University, Laboratoire de Pharmacologie, Faculte de Medecine, Toulouse, France5 University College London, Institute of Neurology, Queen Square, London.

2 United Kingdom6 Dipartimento di Scienze Neurologiche, Universita La Sapienza, Rome, Italy7 Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA8 Department of Neurosciences, University of California San Diego School of Medicine, La Jolla, California, USAA bstract:We aimed to develop and validate a novel ratingscale for Multiple System atrophy ( Unified Multiple SystemAtrophy Rating Scale - UMSARS). The scale comprises thefollowing components: Part I, historical, 12 items; Part II,motor examination, 14 items; Part III, autonomic examination;and Part IV, global disability scale.

3 For validation purposes, 40 MSA patients were assessed in four centers by 4 raters percenter (2 senior and 2 junior raters). The raters applied theUMSARS, as well as a range of other scales, including theUnified Parkinson s Disease Rating Scale (UPDRS) and theInternational Cooperative Ataxia Rating Scale (ICARS). Inter-nal consistency was high for both UMSARS-I (Crohnbach salpha ) and UMSARS-II (Crohnbach s alpha )sections. The interrater reliability of most of the UMSARS-Iand -II items as well as of total UMSARS-I and -II subscoreswas substantial (k (w) ) to excellent (k (w) ).

4 UMSARS-II correlated well with UPDRS-III and ICARS (rs ). Depending on the degree of the patient s disability, com-pletion of the entire UMSARS took 30 to 45 minutes. Based onour findings, the UMSARS appears to be a multidimensional,reliable, and valid scale for semiquantitative clinical assess-ments of MSA patients. 2004 Movement Disorder SocietyKey words: Unified Multiple System Atrophy Rating Scale; validation ; internal consistency; interrater reliabilityMultiple System atrophy (MSA) is a degenerative dis-order of the central and autonomic nervous systemscharacterized by abnormal -synuclein aggregation inoligodendroglia and neurons.

5 Clinically, the cardinal fea-tures include autonomic failure, parkinsonism , cerebellarataxia, and pyramidal signs in any combination. Twomajor motor presentations can be distinguished clini-cally. Parkinsonian features predominate in 80% of pa-tients (MSA-P subtype), whereas cerebellar ataxia pre-dominates in the remaining 20% of patients (MSA-Csubtype).1 MSA is a progressive disorder with earlydisability and shortened life strategies are presently to ad-vances in our understanding of the etiopathogenesis,several possible targets have been identified for multi-center neuroprotective intervention trials in , appropriate trial methodology is lacking.

6 Indeed,Drs. Wenning and Tison contributed equally to this study.*Correspondence to: Dr. Gregor K. Wenning, Department of Neu-rology, University of Innsbruck, A-6020 Innsbruck, : See Acknowledgments for a full list of study 16 January 2004; Revised 9 February 2004; Accepted 17 February 2004 Published online 5 August 2004 in Wiley InterScience ( ). DOI: DisordersVol. 19, No. 12, 2004, pp. 1391 1402 2004 Movement Disorder Society1391clinical rating scales such as the Unified Parkinson sDisease Rating Scale (UPDRS)5or the International Co-operative Ataxia Rating Scale (ICARS)6focus on eitherparkinsonism or ataxia alone and, therefore, may not besufficient to reflect accurately the motor impairment ofMSA patients.

7 Future randomized, controlled trials inMSA will be critically dependent on reliable and validclinical assessment tools to determine the efficacy of agiven intervention. The European MSA Study Group(EMSA-SG) was launched in 1999 to promote concertedtrial activity in MSA across European countries (onlineat ). In March 2001, EMSA-SGconvened a task force with the specific goal of develop-ing and validating a novel Unified MSA Rating Scale(UMSARS). This article introduces the UMSARS, and itgives the methods and results of a multicenter validationstudy of its AND METHODSD evelopment of UMSARSUMSARS was developed using established scales astemplates, including the Hoehn and Yahr Scale (H&Y),the Schwab and England Scale (SES),7the UPDRS, theICARS, and the Composite Autonomic Symptom Scale(COMPASS).

8 8 Previous MSA studies showed that cere-bellar signs can compromise accurate assessment of par-kinsonism by the UPDRS, and conversely, parkinsonismcan obscure the evaluation of cerebellar features duringassessments with the ,10 The scale constructionfollowed a set of principles defined by the EMSA-SGtask force: (1) UMSARS should rate functional impair-ment independent of underlying motor disorder, whichmay be cerebellar or parkinsonian or both; (2) UMSARS items should discriminate five grades of functional im-pairment; (3) Autonomic and urogenital dysfunctionshould be rated historically, except for recording theblood pressure and heart rate change upon standing.

9 (4)A five-point global disability scale analogous to theH&Y scale should be part of UMSARS to capture theprogressive disability of MSA on these principles, the novel UMSARS wasdesigned comprising four parts, including a historicalreview of disease-related impairments (Part I, 12 items),motor examination (Part II, 14 items), autonomic exam-ination (Part III), and global disability scale (Part IV; seeAppendix). A single score using a 0 (no impairment) to4 (severe impairment) scale was generated for each maximum scores are 48 points for UMSARS-I and56 points for UMSARS-II.

10 In contrast to the UPDRS, fora given item of the UMSARS-II that involved limbassessment, only the worst limb was rated in the motorexamination of UMSARSF orty patients with a clinical diagnosis of possible(n 8) or probable (n 32) MSA according to theGilman criteria1were recruited in four EMSA-SG cen-ters. The positive predictive value of the Gilman criteriawas excellent ( 90%) at first neurological visit in arecent validation clinical characteristicsare shown in Table 1. A set of scales and timed tests (seebelow) was applied to the patients, who were maintainedon their regular medication during the patients were evaluated by one senior investigatorwho traveled to the centers ( ).