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Demyelinating events in early multiple sclerosis have inherent severity and recovery

From the MS Center, Department of Neurology (E.M.M., M.P., S.D., E.W.), and Department of Epidemiology and Biostatistics (B.G., P.B.), University of California, San Francisco.

Address correspondence and reprint requests to Dr. Ellen M. Mowry, Department of Neurology, Multiple Sclerosis Center, University of California, San Francisco, 350 Parnassus Avenue, Suite 908, San Francisco, CA 94117 ellen.mowry{at}ucsf.edu

Background: It is unclear whether the severity of and recovery from the initial demyelinating event (IDE) are recapitulated in subsequent multiple sclerosis (MS) relapses. We sought to identify the factors associated with relapse severity and recovery and to evaluate whether events have inherent severity or recovery.

Methods: Patients seen at the UCSF MS Clinic within 1 year of disease onset were identified from a prospective database. Ordinal logistic regression was used to analyze predictors of three-level categorizations of event severity and recovery.

Results: We identified 330 patients with MS or clinically isolated syndrome; 152 had a second event and 63 had a third event. Nonwhite and younger patients were at an increased risk of more severe demyelinating events. A severe prior event predicted a substantial increase in the odds of being above any given severity cutoff for a severe subsequent event (for second event severity, odds ratio [OR] = 5.62, 95% confidence interval [CI] [2.39, 13.26], p < 0.0001; for third event severity, OR = 6.74, 95% CI [1.67, 27.18], p = 0.007). Similarly, poor recovery of the IDE predicted poor second event recovery (OR = 5.28, 95% CI [1.95, 14.25], p = 0.001), while fair or poor second event recovery predicted about a 5- or 13-fold increase in the odds of poor third event recovery. A more severe event also predicted a substantial increase in the odds of poor recovery.

Conclusions: Patients with severe presentation and poor recovery at disease onset continue on a similar trajectory with subsequent demyelinating events. Whether genetic or other biologic factors are responsible for this pattern remains to be determined.

Abbreviations: BS/CE = brainstem/cerebellum; CI = confidence interval; CIS = clinically isolated syndrome; DMT = disease-modifying therapy; EDSS = Expanded Disability Status Scale; FS = Functional Systems; IDE = initial demyelinating event; MS = multiple sclerosis; N/A = not applicable; OR = odds ratio; RRMS = relapsing-remitting multiple sclerosis; VA = visual acuity.

Supported by the NMSS (RG-3692A), the Nancy Davis Foundation, a National Multiple Sclerosis Society Sylvia Lawry Fellowship Award, and the Partners MS Center Clinical Fellowship Program. Statistical analysis for this publication was made possible by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131.

Disclosure: Dr. Waubant has received research support from Biogen Idec, Genentech Inc, Pfizer, and Sanofi-Aventis, and honorarium for one educational presentation from Teva and Biogen.

Received August 25, 2008. Accepted in final form November 10, 2008.