Initiating treatment with interferon beta-1a at the time of a first demyelinating event is beneficial for patients with brain lesions on MRI that indicate a high risk of clinically definite multiple sclerosis.

Oxidative stress refers to the cytopathologic consequences of a mismatch between the production of free radicals and the ability of the cell to defend against them. Growing data from experimental models and human brain studies suggest oxidative stress may play an important role in neuronal degeneration in diseases such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. Mitochondrial oxidative metabolism, nitric oxide, phospholipid metabolism, and proteolytic pathways are potential sources of intracellular free radicals. Alterations in free radical defense systems may also contribute to oxidative stress. A net increase in reactive oxygen species can produce damage to lipids, proteins, and DNA and induce necrosis or apoptosis. Elucidating the pathways important in the production of and defense from free radicals may be important in devising new pharmacologic strategies to slow or halt neuronal degeneration.

Objective: To characterize whole-brain atrophy in relapsing-remitting MS (RRMS) patients over an 8-year period. The specific goals of this study were to determine if brain atrophy is related to subsequent disability status and to identify MRI correlates of atrophy progression. Methods: A follow-up study was conducted to reassess patients from a phase III trial of interferon-1a (IFN-1a) 8 years after randomization. Clinical and MRI data from 172 patients followed over 2 years in the original trial were used as baseline data. Follow-up data were obtained on 160 patients, including 134 patients with follow-up MRI examinations. Brain atrophy was estimated by automated calculation of brain parenchymal fraction. The relation between atrophy during the original trial and disability status at follow-up was determined. Correlations were also determined between lesion measurements from the original trial and the brain parenchymal fraction at follow-up. Results: Brain atrophy was correlated with subsequent disability status. Atrophy rate during the original trial was the most significant MRI predictor of disability status at follow-up. Brain atrophy at follow-up was related to lesion volumes measured during the original trial. Conclusions: The relation between atrophy progression and subsequent neurologic disability status suggests that atrophy progression during RRMS is clinically relevant. Therefore, atrophy progression may be a useful marker for disease progression in clinical trials. The relation between lesions and subsequent atrophy indicates that brain atrophy may be related to focal tissue damage at earlier points in time, but important predisposing or other factors contributing to atrophy remain undefined. MRI has fallen short of expectations in terms of providing a surrogate marker in MS. The lack of robust correlations between conventional MRI measures of pathology and clinical measures of disability has been attributed to various shortcomings of both MRI and clinical assessments. At least part of the discrepancy may be due to the use of MRI measurements that include both reversible and irreversible components of MS pathology. Conventional MRI lesion measurements also neglect to account for diffuse abnormalities in normal-appearing tissue in MS. One of the alternative MRI measures that have been proposed to monitor MS progression is the estimation of CNS atrophy. 1-11 In contrast to MRI-visible lesions, CNS atrophy is believed to reflect the net effect of severe and potentially irreversible processes such as demyelination and axonal loss. Measurement of the size of CNS structures may provide an indication of the total amount of tissue damage that has occurred up to a given point in time. New computer-assisted methods have been developed to precisely and reliably quantify tissue loss in MRI, 5-13 and atrophy has been shown to occur even in the early stages of MS. 3,4,6-9 However, previous longitudinal studies in MS 3,6-9,14-16 have not shown very strong or consistent relations between brain atrophy and disability...

IFNbeta-1a demonstrated benefit on MSFC progression, relapses, quality of life, and MRI activity in SPMS.

NAB directed against IFN-beta have in vivo biological consequences in patients with MS. The frequency with which MS patients develop NAB against IFN-beta is significantly greater with IFN-beta-1b therapy compared with IFN-beta-1a therapy. Treatment decisions in MS patients treated with IFN-beta should take into account development of NAB.