Clinical and conventional MRI predictors of disability and brain atrophy accumulation in RRMS
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To assess the value of clinical and MRI variables in predicting short-term brain atrophy accumulation and clinical evolution in a large cohort of patients with RRMS, we studied a cohort of 548 patients, previously enrolled as a placebo arm of a 14-month, double-blind trial of oral glatiramer acetate (GA). A logistic regression model with EDSS progression as the dependent variable was built to assess baseline clinical and MRI variables associated with clinical worsening during follow-up. In 466 patients with complete central brain atrophy assessment, another linear regression model with percentage central brain volume change (PCBVC) as the dependent variable was built to assess baseline clinical and MRI variables associated with atrophy development.
A total of 80 patients (15 %) had EDSS progression over the follow-up period. Factors independently predicting the probability to have a clinical progression were lower EDSS (OR = 0.78, 95 % CI = 0.62–0.97 p = 0.02) and higher T2 LL (OR = 1.022, 95 % CI = 1.006–1.038, p = 0.007) at baseline. In the 466 patients with atrophy assessment, PCBVC declined, on average, by –2.0 % (SD = 2.8) (p < 0.001) over the follow-up. The multivariate PCBVC analysis revealed that the PCBVC decrease was independently correlated with higher EDSS (p = 0.03) and T2 LL (p = 0.005) at baseline. The squared correlation coefficients of the composite scores made up of EDSS and T2 LL considered together were able to explain only 3 % of the variance in disability progression and only 4 % of the variance of PCBVC.
In RRMS patients, clinical and conventional MRI findings at baseline only modestly predict shortterm accumulation of brain atrophy and disability. These data confirm the need to develop clinical and MRI measures more sensitive towards the more disabling aspects of the disease.
Key wordsmultiple sclerosis disability conventional MRI brain atrophy disease evolution
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- 3.Belinda SY, Regal J, Soher BJ, Mannon LJ, Grossman RI, Gonen O (2003) Brain metabolite profiles of T1-hypointense lesions in relapsing-remitting multiple sclerosis. AJNR Am J Neuroradiol 24:68–74Google Scholar
- 8.Filippi M, Horsfield MA, Ader HJ, Barkhof F, Bruzzi P, Evans A, Frank JA, Grossman RI, McFarland HF, Molyneux P, Paty DW, Simon J, Tofts PS, Wolinsky JS, Miller DH (1998) Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis. Ann Neurol 43:499–506PubMedCrossRefGoogle Scholar
- 12.Filippi M, Wolinsky JS, Comi G, the CORAL Study Group (2006) Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study. Lancet Neurol 5:213–220PubMedCrossRefGoogle Scholar
- 19.Kappos L, Moeri D, Radue EW, Schoetzau A, Schweikert K, Barkhof F, Miller D, Guttmann CRG, Weiner HL, Gasperini C, Filippi M for the Gadolinium MRI Meta-analysis Group (1999) Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Lancet 353:964–969PubMedCrossRefGoogle Scholar
- 21.Li DK, Paty DW and the UBC MS/MRI Analysis Research group and the PRISMS Study Group (1999) Magnetic resonance imaging results of the PRISMS trial: a randomized, doubleblind, placebo-controlled study of interferon- beta 1a in relapsing-remitting multiple sclerosis. Prevention of Relapses and Disability by Interferonbeta1a Subcutaneously in Multiple Sclerosis. Ann Neurol 46:197–206PubMedCrossRefGoogle Scholar
- 25.Molyneux PD, Kappos L, Polman C, Pozzilli C, Barkhof F, Filippi M, Yousry T, Hahn D, Wagner K, Ghazi M, Beckmann K, Dahlke F, Losseff N, Barker GJ, Thompson AJ, Miller DH for the European Study Group on Interferon Beta-1b in Secondary Progressive MS (2000) The effect of interferon beta 1-b treatment on MRI measures in secondary progressive multiple sclerosis. Brain 123:2256–2263PubMedCrossRefGoogle Scholar
- 26.Molyneux PD, Barker GJ, Barkhof F, Beckmann K, Dahlke F, Filippi M, Ghazi M, Hahn D, MacManus D, Polman C, Pozzilli C, Kappos L, Thompson AJ, Wagner k, Yousry T, Miller DH for the European Study Group on Interferon Beta-1b in Secondary Progressive MS (2001) Clinical-MRI correlations in European trial of interferon-beta 1b in secondary progressive MS. Neurology 57:2191–2197PubMedGoogle Scholar
- 30.Rovaris M, Comi G, Rocca MA, Valsasina P, Ladkani D, Pieri E, Weiss S, Shifroni G, Wolinsky JS, Filippi M, for the European/Canadian Glatiramer Acetate Study Group (2007) Long-term follow-up of patients treated with glatiramer acetate: a multicentre, multinational extension of the European/ Canadian double-blind, placebocontrolled, MRI-monitored trial. Mult Scler 13:502–508PubMedGoogle Scholar
- 37.Simon JH, Jacobs LD, Campion MK, Rudick RA, Cookfair DL, Herndon RM, Richert JR, Salazar AM, Fischer JS, Goodkin DE, Simonian N, Lajaunie M, Miller DE, Wende K, Martens-Davidson A, Kinkel RP, Munschauer FE III, Brownscheidle CM (1999) A longitudinal study of brain atrophy in relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group (MSCRG). Neurology 53:139–148PubMedGoogle Scholar