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  • Title: Atrophy is detectable within a 3-month period in untreated patients with active relapsing remitting multiple sclerosis.
    Author: Hardmeier M, Wagenpfeil S, Freitag P, Fisher E, Rudick RA, Kooijmans-Coutinho M, Clanet M, Radue EW, Kappos L, European rIFN beta-1a in Relapsing MS Dose Comparison Trial Study Group.
    Journal: Arch Neurol; 2003 Dec; 60(12):1736-9. PubMed ID: 14676048.
    Abstract:
    BACKGROUND: Atrophy is recognized as a measure of destructive changes in multiple sclerosis (MS). The time course and pathologic mechanisms of atrophy development are not well understood. Significant atrophy was reported to occur within 9 to 12 months in relapsing remitting MS. OBJECTIVES: To test whether atrophy can be detected over short time intervals, and to evaluate its relationship to inflammation. DESIGN AND METHODS: Prior to randomization to a treatment trial, 138 untreated patients with relapsing remitting MS had 3 magnetic resonance imaging scans within a mean +/- SD follow-up of 76 +/- 20.2 days. Brain parenchymal fraction (BPF), a normalized measure of whole brain volume, the proportion of active (gadolinium-enhancing) scans, and the volume of T1-weighted gadolinium-enhancing and T2-weighted hyperintense lesions were determined at all time points. An annualized atrophy rate was estimated by calculating a regression slope. RESULTS: The median Expanded Disability Status Scale score was 3.5, the mean disease duration was 7.6, and the mean age was 38.5 years. The BPF decreased significantly by -0.229% from scan 1 to scan 3, while the proportion of active scans remained high (65%, 63%, and 67%). The BPF change was only weakly correlated to the volume of T1-weighted gadolinium-enhancing lesions in scan 1 (r = -0.185). The estimated annualized atrophy rate was -1.06% (95% confidence interval, -1.50% to -0.62%). CONCLUSIONS: The annualized atrophy rate found in this study is comparable with rates reported previously. Measurements of BPF allow detection of atrophy over short time intervals in active disease. The short-term relationship of inflammation to atrophy development was weak. Brain parenchymal fraction might be a promising measure in future phase 2 studies of agents, with an expected effect on tissue-destructive pathologic mechanisms of MS.
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