Clinical study
Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis relapses☆

https://doi.org/10.1016/j.jocn.2005.08.012Get rights and content

Abstract

We prospectively investigated the short-term effects of intravenous methyl-prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis (MS) relapse. Ten patients underwent MRI brain studies immediately before and after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased significantly over the 8-week period. The greatest change occurred during IVMP administration. This has implications for MS treatment trials using cerebral atrophy as an endpoint.

Introduction

Pathologic and imaging studies suggest that development of permanent neurologic impairment or disease progression in multiple sclerosis (MS) is associated with progressive brain and spinal cord atrophy. Tissue atrophy has been identified in the early stages of the disease process.1 Atrophy is thought to reflect irreversible axonal loss2 and has been shown to correlate better with clinical disability, as measured by the Expanded Disability Status Score (EDSS),3 than lesion load measurements. As a result, cerebral volume measurement is increasingly being used as a surrogate marker of tissue destruction and disease progression in MS treatment trials. While most treatment trials permit intravenous methylprednisolone (IVMP) administration for the treatment of clinical relapses, the effect on measured cerebral volumes of such treatment has only recently been reported in three retrospective studies.[4], [5], [6] We report the first prospective study addressing this issue.

Section snippets

Methods

We prospectively recruited patients with clinically definite MS, according to the Poser criteria, who were suffering an acute relapse. A relapse was defined as worsening of neurological function for more than 48 h prior to recruitment that, in the opinion of the treating neurologist, required treatment with IVMP. The patients were given IVMP (1 g daily for 3 days). All underwent serial, non-enhanced, MRI brain studies performed within 24 h pre- and post-IVMP, and 4 and 8 weeks later. Clinical

Results

Ten patients were recruited and a total of 40 cerebral MRI studies were evaluated. There were two men and eight women (mean age, 39.4 years; range, 23–59). Mean duration of disease was 6.3 years (range, 1.5–10 years). Eight of the 10 patients were taking a disease-modifying agent (interferon or glatiramer acetate). Four patients had entered the secondary progressive phase of the disease but continued to have relapses. As expected, the EDSS scores improved after treatment in the majority of

Discussion

This prospective pilot study demonstrated that IVMP administration in MS patients experiencing a clinical relapse was associated with a statistically significant reduction in measured cerebral volume over the 8-week study period. The greatest change in cerebral volume occurred during the 3-day period of steroid administration. These findings are consistent with those of Rao et al.5 who retrospectively examined the brain fraction volume (BFV) before and after IVMP in patients with relapsing

Acknowledgement

Caron Chapman is funded by the Schering Multiple Sclerosis Research Fellowship provided by the Melbourne Neuroscience Research Centre, Melbourne University.

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Schering Multiple Sclerosis Research Fellowship provided by the Melbourne Neuroscience Research Centre, Melbourne University. Support from the Neuroscience Foundation, The Royal Melbourne Hospital.

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