Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis

R. Zivadinov, A. T. Reder, M. Filippi, A. Minagar, Olaf Stuve, H. Lassmann, M. K. Racke, M. G. Dwyer, Elliot Frohman, O. Khan

Research output: Contribution to journalReview articlepeer-review

224 Scopus citations


Disease-modifying agents (DMAs), including interferon beta (IFNj3) and glatiramer acetate (GA), are the mainstays of long-term treatment of multiple sclerosis (MS). Other potent antiinflammatory agents like natalizumab and different types of chemotherapeutics are increasingly being used for treatment of MS, particularly in patients with breakthrough disease activity. Brain volume (BV) loss occurs early in the disease process, accelerates over time, and may be only partially affected by DMA therapy. Low-dose, low frequency IFN/3 administered once weekly and GA appear to partially reduce BV decline over the second and third years of treatment. High dose, high frequency IFN/3 demonstrated no clear effect on BV loss during this time period. Current evidence suggests that changes in BV after immunoablation may not be due entirely to the reso-ution of edema but may be related to potential chemotoxicity of high dose cyclophosphamide. Natalizumab reduces the development of BV decline in the second and third years of treatment. IV immunoglobulin showed a positive effect on decelerating BV reduction in relapsing and advanced stages of MS. These differences between DMAs may be explained by the extent of their therapeutic effects on inflammation and on the balance between inhibition or promotion of remy-elination and neuronal repair in the CNS. We described the mechanisms of action by which DMAs nduce accelerated, nontissue-related BV loss (pseudoatrophy) in the short term but, in the long run, may still potentially lead to permanent BV decline. The effects of corticosteroid therapy on changes in BV in patients with MS help clarify the mechanisms through which potent antiinflammatory treatments may prevent, stabilize, or induce BV loss.

Original languageEnglish (US)
Pages (from-to)136-144
Number of pages9
Issue number2
StatePublished - Jul 8 2008

ASJC Scopus subject areas

  • Clinical Neurology


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