4.7 Article

Axonal metabolic recovery in multiple sclerosis patients treated with interferon β-1b

Journal

JOURNAL OF NEUROLOGY
Volume 248, Issue 11, Pages 979-986

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s004150170052

Keywords

interferon-beta; multiple sclerosis; N-acetylaspartate; axons; magnetic resonance spectroscopy

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Patients with multiple sclerosis (MS) can benefit from treatment with interferon beta -1b. However, the mechanisms of action of this drug are incompletely understood and effects of interferon beta -1b on axonal injury are not known. A measure of axonal injury can be obtained in vivo using magnetic resonance spectroscopy to quantify the resonance intensity of the neuronal marker, N-acetylas-partate (NAA). In a small pilot study, we performed combined magnetic resonance imaging and magnetic resonance spectroscopic imaging on 10 patients with relapsing-remitting MS before and 1 year after starting treatment with subcutaneous interferon beta -1b. Resonance intensities of NAA relative to creatine (Cr) were measured in a large, central brain volume. These measurements were compared with those made in a group of 6 untreated patients selected to have a similar range of scores on the Expanded Disability Status Scale and mean NAA/Cr at baseline. NAA/Cr in the treated group [2.74 (0.16), mean (SD)] showed an increase of 5.5 % 12 months after the start of therapy [2.89 (0.24), p = 0.05], while NAA/Cr in the untreated group decreased, but not significantly [2.76 (0.1) at baseline, 2.65 (0.14) at 12 months,p > 0.1]. NAA/Cr had become significantly higher in the treated group at 12 months than in the untreated group (p = 0.03). Our data suggest that, in addition to losing axons, patients with chronic multiple sclerosis suffer from chronic, sublethal axonal injury that is at least partially reversible with interferon beta -1b therapy.

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