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Interferon beta-1a slows progression of brain atrophy in relapsing-remitting
multiple sclerosis predominantly by reducing gray matter atrophy
Robert Zivadinov1*,
Laura Locatelli2,
Diane Cookfair1,
Bhooma Srinivasaraghavan1,
Antonio Bertolotto3,
Maja Ukmar4,
Alessio Bratina2,
Cosimo Maggiore2,
Antonio Bosco2,
Attilio Grop1,
Mauro Catalan2,
Marino Zorzon2
1 Department of Neurology, Buffalo Neuroimaging Analysis Center, The
Jacobs Neurological Institute, University at Buffalo, State University of New
York, Buffalo, NY, USA
2 Department of Clinical Medicine and Neurology, University of Trieste,
Trieste, Italy
3 Centro Riferimento Regionale Sclerosi Multipla (CReSM) and Laboratori
di Neurobiologia Clinica, Ospedale Universitario San Luigi, Orbassano, Italy
4 Department of Clinical, Morphological and Technological Sciences,
University of Trieste, Trieste, Italy
* To whom correspondence should be addressed.
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Abstract |
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Background Brain atrophy, as assessed by magnetic resonance imaging (MRI),
has been correlated with disability in patients with multiple sclerosis (MS). Recent
evidence indicates that both white matter (WM) and gray matter (GM) are subject to
atrophy in patients with MS. Although neurological deficiencies in MS are primarily
due to loss of WM, the clinical significance of GM atrophy has not been fully
explored in MS. Methods We have undertaken a three-year, open-label study,
comparing 26 patients who elected to receive intramuscular interferon beta-1a (IFN
beta-1a) therapy, with 28 patients who elected not to receive therapy. Both groups
had quantitative cranial MRI scans at study entry and after three years, and
standardized clinical assessments every six months. Brain parenchymal fraction
(BPF), GM fraction (GMF), and WM fraction (WMF) percent changes were calculated, and
T2- and T1-lesion volumes (LVs) assessed. Results After three years, mean
percent (%) change in BPF favored the IFN beta-1a treatment group (IFN beta-1a -
1.3% versus the control group - 2.5%, P=0.009), as did the mean
percent change in GMF (+0.2 versus - 1.4%, P=0.014),
and the mean percent change in T1-LV (� - 9.3 versus +91.6%,
P=0.011). At the end of the study, there was a significant
within-patient decrease in BPF for both groups (P=0.02 for the
IFN beta-1a treatment group, and P<0.001 for the control group), a
significant within-patient decrease in WMF for the IFN beta-1a treatment group
(P=0.01), and a significant decrease in GMF for the control
group (P=0.013) when compared with baseline. Conclusion
Over a three-year period, treatment with IFN beta-1a significantly slowed the
progression of whole-brain and GM atrophy, and of T1-hypointense LV accumulation,
when compared with the control group.
Key Words:
atrophy, brain atrophy, gray matter atrophy, interferon beta-1a, magnetic resonance imaging, multiple sclerosis, white matter atrophy
First published on February 9, 2007, doi:10.1177/1352458506070446
Multiple Sclerosis 2007;13:490.
A more recent version of this article appeared on May 1, 2007

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