1. Natalizumab use for neuropsychological deficits in relapsing multiple sclerosis K. Edwards, 1,2 W. Goodman, 1 1 MS Center of Northeastern New York (Latham, NY, USA), 2 Harvard Medical School (Boston, MA, USA) Objective Abstract Methods 1.Polman C, O’ Connor P, Havrdova E, Hutchinson M, Kappos L, Miller D, Phillips J. T, Lublin F, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara M, Sandrock A. A randomized, placebo-controlled trial of Natalizumab for Relapsing Multiple Sclerosis. N. Eng. J Med 2006; 354: 899-910 2.Rudick R, Stuart W, Calabresi P, Confavreux C, Galetta S, Radue E, Lublin F, Weinstock-Guttman B, Wynn D, Lynn F, Panzara M, Sandrock A. Natalizumab plus Interferon Beta-1a for Relapsing Multiple Sclerosis. N. Eng J Med 2006;345: 911-23 3.Rao SM, Leo GJ, Bernardin L, Unverzagt F. Cognitive dysfunction in multiple sclerosis. I. Frequency, patterns, and prediction. Neurology. 1991;41:685-691 4.Rovaris M, Riccitelli G, Judica E, Possa F, Caputo D, Ghezzi A, Bertolotto A, Capra R, Falautano M, Mattioli F, Martinelli V, Comi G, Filippi M. Cognitive impairment and structural brain damage in benign multiple sclerosis Neurology 2008;71: 1521-1526 Natalizumab has been shown to reduce the physical disability in MS patients in the Affirm 1 and Sentinel 2 trials. However, the main cause of disability in MS patients is due to neuropsychological (NP) dysfunction. 3 Physical disability in MS does not necessarily correlate with NP disability. A recent study from Milan 4 showed that nearly 1/3 of patients with “benign MS” as based on the EDSS were disabled due to the NP dysfunction. This is a single center, open label, retrospective analysis evaluating change in NP parameters in MS patients before and after 6 or more months of treatment with natalizumab. Subjects were compared to their own baseline activity. Retrospective data from 40 consecutively treated patients were analyzed. The method evaluated each sub-test of a standardized neuropsychological evaluation specific for MS as to a normal or one or more standard deviations from the norm. Each of 9 sub-tests was assigned a value of zero if normal or 0.11 if one standard deviation or more from the norm. If the total score was 0.22 or higher at baseline, the patient was considered “impaired” for NP purposes Natalizumab may stabilize or improve NP function in a significant proportion of MS patients. The improvement of NP status does not appear to be dependent upon improvement in depression and physical disability.This was a small retrospective study. Larger, prospective, controlled studies with NP function as the primary outcome measure need to be pursued. Supported by an unrestricted educational grant from Biogen Idec The primary objective of this retrospective analysis was to evaluate the effect of natalizumab treatment on NP function in patients with relapsing-remitting multiple sclerosis (RRMS) who had a measurable cognitive deficit prior to natalizumab treatment initiation. Conclusions The mean age was 48.5 years with SD of 7.6. Neuropsychological impairment Index at baseline showed a mean of 0.49 with SD of 0.21. The impairment index at follow-up showed a mean of 0.41 with SD of 0.26. Paired sample t-tests demonstrated significant improvement after Natalizumab treatment of p = 0.001. As did the MacNemar’s non-parametric test (p = 0.007) The proportion of patients with an improvement, no change, or worsening was 21 (52.5%), (22.5%), and8 (20%), respectively (p=0.007). Results References * p = 0.001, standard error bars shown Neuropsychological Impairment Improves Over Time With Natalizumab Treatment NP Impairment * Worsening 17.5% Improving 52.5% Unchanged 30% 0 5 10 15 20 25 ImprovingUnchanged Worsening Number of patients improving with Natalizumab treatment Proportion of patients improving at Follow-up visit