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From the Neurology Department (Drs. Roxburgh, Sawcer, and Compston, and A.E. Hensiek), Cambridge University, UK; Auckland City Hospital (Dr. Roxburgh), New Zealand; Max Planck Institute for Psychiatry (Dr. Seaman), Munich, Germany; Division of Neurology (Drs. Masterman and Hillert), NEUROTEC, Karolinska Institute at Huddinge University Hospital, Stockholm, Sweden; EDMUS Coordinating Centre (Drs. Vukusic, Achiti, and Confavreux), Service de Neurologie A, Hôpital Neurologique, Lyon, France; Clinique Neurologique (Drs. Coustans, le Page, and Edan), Centre Hospitalier Universitaire de Rennes, Hôpital de Pontchaillou, France; Northern Ireland Regional Neurology Service (Drs. McDonnell and Hawkins), Royal Victoria Hospital, Belfast; Department of Neurological and Psychiatric Sciences (Drs. Trojano and Liguori), University of Bari, Italy; Department of Neuroscience (Drs. Cocco and Marrosu), Centro Sclerosi, Multipla University of Cagliari, Italy; Clinica Neurologica (Drs. Tesser and Leone), Università del Piemonte Orientale, "A. Avogadro," Novara, Italy; Clinica Neurologica (Drs. Tesser and Leone), Ospedale Maggiore della Carità, Novara, Italy; Institut für Neuroimmunologie (A. Weber and Dr. Zipp), Klinische und Experimentelle Neuroimmunologie, Universitätsklinikum Charité, Neurowissenschaftliches Zentrum, Berlin; Abteilung für Humangenetik (Drs. Miterski and Epplen), Ruhr-Universität Bochum, Germany; Department of Neurology (Drs. Oturai and Soelberg Sørensen), Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Neurology (Dr. Celius), Ullevål University Hospital, Oslo, Norway; Clinical Neuroimmunology Unit (Drs. Téllez Lara and Montalban), Vall D’Hebron, University Hospital, Barcelona, Spain; Multiple Sclerosis Centre (Dr. Villoslada), Department of Neurology, Clinica Universitaria de Navarra, Pamplona, Navarra, Spain; Neuroimmunology Group (Drs. Silva, Marta, and Leite), Department of Neurology, Hospital Geral Santo Antonio, Porto, Portugal; University Hospital Gasthuisberg (Dr. Dubois), University of Leuven, Belgium; The Walter and Eliza Hall Institute of Medical Research (Drs. Rubio, Butzkueven, and Kilpatrick), IG Royal Parade, Parkville, Victoria, Australia; The Cooperative Research Centre for Discovery of Genes for Common Human Diseases (Dr. Kilpatrick), Richmond, Victoria, Australia; Department of Neurology (Drs. Mycko and Selmaj), Medical University of Lodz, Poland; Neurology Department (Drs. Rio and Sá), Hospital de S. Joáo, Porto, Portugal; and Department of Neuropsichiatry (Drs. Salemi and Savettieri), Palermo, Italy.
Address correspondence and reprint requests to Dr. R. Roxburgh, Neurology Dept., Cambridge University, Hills Rd., Cambridge CB2 2QQ, UK; e-mail: richard{at}roxburgh.net.nz
Background: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease.
Methods: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability.
Results: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression.
Conclusion: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 12 issue to find the title link for this article.
*These authors contributed equally to this work.
The Cambridge Multiple Sclerosis Genetics Group and GAMES project were supported by the Wellcome Trust (grant 057097) supplemented by the National Multiple Sclerosis Society of the USA, the Multiple Sclerosis Society of Great Britain and Northern Ireland, and Multiple Sclerosis International Federation. Other groups received financial or clinical assistance from the following: Bari, the Italian Multiple Sclerosis Society; Belfast, MS Society, Action MS and the Royal Group Hospitals Trust; Berlin, the Bundesministerium für Bildung und Forschung and the Ernst Schering Research Foundation; Bochum, Drs. M. Haupts, S. Sindern, and D. Pöhlau, and "Gemeinnützige Hertie-Stiftung" (project no. 1.319.110/02/05); Copenhagen, the Danish Multiple Sclerosis Society; Leuven, Belgian Charcot Foundation, University Hospital Research Council, Leuven; Lyons, Biogen, Schering, Serono and Teva pharmaceutical companies, ARSEP and LFSEP; Stockholm, the Swedish Medical Research Council, the Swedish Association of Neurologically Disabled, Karolinska Institutet, Swedish Brain Foundation and the Swedish Society of Medicine; Tasmania, CRC for Discovery of Genes for Common Human Diseases, the National Multiple Sclerosis Society of the USA, and B. Taylor.
Received November 6, 2003. Accepted in final form December 9, 2004.
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