Arch Neurol. 2003 Dec;60(12):1736-9
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.
MS MRI Evaluation Centre Basel, Basel, Switzerland.
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.