Multiple sclerosis relapses: a multivariable analysis of residual disability determinants Introduction Relapses define the relapsing–remitting (RR) phase of multiple sclerosis (MS); they are the expression of newly formed lesions, characterized by focal inflammation and demyelination. Most relapses are followed by partial or complete recovery; nevertheless, long-term increase of dis- ability after a relapse is frequent (1). Incomplete recovery from the first relapse has been associ- ated with an unfavourable MS course in several studies (2). Previous studies have evaluated the factors influencing recovery after optic neuritis and first demyelinating episodes (3–5); the factors influenc- ing residual disability (RD) after MS relapses have instead been scarcely investigated. Recovery from MS relapses is thought to occur, in a first phase, through the end of the inflammatory process and the removal of noxious factors (nitric oxide, cytokines), and later through redistribution of axonal ion channels, remyelination and cortical reorganization (6). Axonal transection has been demonstrated in MS lesions (7). While the impairment of axonal function due to inflammation and demyelination is partly reversible, the impairment due to axonal transection is irreversible and probably is an important determinant of RD. In this study, we addressed the extent of RD after MS relapses and determined which factors influenced the persistence of RD. Methods We used operational definitions of relapse severity and RD, as there is currently no consensus on how to evaluate these parameters. Definition of RD were modified from a previous study by Lublin (1), and expressed as any increase in the Expanded Acta Neurol Scand 2009: 119: 126–130 DOI: 10.1111/j.1600-0404.2008.01076.x Copyright Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard ACTA NEUROLOGICA SCANDINAVICA Vercellino M, Romagnolo A, Mattioda A, Masera S, Piacentino C, Merola A, Chio` A, Mutani R, Cavalla P. Multiple sclerosis relapses:a multivariable analysis of residual disability determinants. Acta Neurol Scand 2009: 119: 126–130. Ó 2008 The Authors Journal compilation Ó 2008 Blackwell Munksgaard. Background – Recovery from multiple sclerosis (MS) relapses is variable. The factors influencing persistence of residual disability (RD) after a relapse are still to be thoroughly elucidated. Aims of study – To assess RD after MS relapses and to define the factors associated with persistence of RD. Methods – Data were retrospectively collected for all relapses in a population of relapsing–remitting MS patients during 3 years. Relapse severity and RD after 1 year were calculated on Expanded Disability Status Scale basis. A multivariable analysis for factors influencing RD and relapse severity was performed (variables: age, gender, disease duration, oligoclonal bands, relapse severity, monosymptomatic ⁄ polysymptomatic relapse, immunomodulating treatment, incomplete recovery at 1 month). Results – A total of 174 relapses were assessed. RD after 1 year was observed in 54.5% of the relapses. Higher risk of RD was associated with occurrence of a severe relapse (P = 0.024). Incomplete recovery at 1 month was highly predictive of RD at 1 year (P < 0.0001). Risk of a severe relapse was associated with age £ 30 years (P = 0.025) and inversely associated with the use of immunomodulating treatment (P = 0.006). Conclusions – Incomplete recovery at 1 month is a predictor of long- term persistence of RD. Higher relapse severity is associated with higher risk of RD. Risk of severe relapses is lower in patients treated with immunomodulating drugs. M. Vercellino, A. Romagnolo, A. Mattioda, S. Masera, C. Piacentino, A. Merola, A. Chiò, R. Mutani, P. Cavalla Department of Neuroscience, University of Turin, Italy Key words: Disability; multiple sclerosis; multivariable analysis; recovery; relapse; residual disability Paola Cavalla, Department of Neuroscience, University of Turin, Via Cherasco 15 10126, Turin, Italy Tel.: +390116334244 Fax: +390116963487 e-mail: pcavalla@molinette.piemonte.it Accepted for publication May 28, 2008 126