Axonal metabolic recovery in multiple sclerosis patients treated with interferon beta-1b.
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-lb 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-acetylaspartate (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-lb. 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-lb therapy.
Narayanan
S
S
Montreal Neurological Institute, Quebec, Canada.
De Stefano
N
N
Francis
G S
GS
Arnaoutelis
R
R
Caramanos
Z
Z
Collins
D L
DL
Pelletier
D
D
Arnason BGW
Antel
J P
JP
Arnold
D L
DL
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D020833:Diffuse Axonal Injury / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology; D012008:Recurrence; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D015415:Biomarkers; D000068576:Interferon beta-1b; D001224:Aspartic Acid; D016899:Interferon-beta; C000179:N-acetylaspartate; D000068556:Interferon beta-1a