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Martin Hardmeier, MD; Stefan Wagenpfeil, PhD; Peter Freitag, MD; Elizabeth Fisher, PhD; Richard A. Rudick, MD; Mariska Kooijmans-Coutinho, MD, PhD; Michel Clanet, MD; Ernst W. Radue, MD; Ludwig Kappos, MD; for the European rIFN -1a in Relapsing MS Dose Comparison Trial Study Group

Arch Neurol. 2003;60:1736-1739.

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.

From the MS MRI Evaluation Centre Basel (Drs Hardmeier, Freitag, Radue, and Kappos), and the Departments of Neurology (Drs Hardmeier and Kappos), and Neuroradiology (Dr Radue), University Hospitals Basel, Basel, Switzerland; Klinikum rechts der Isar, Technical University, Munich, Germany (Dr Wagenpfeil); Cleveland Clinic Foundation, Cleveland, Ohio (Drs Fisher and Rudick); Biogen Inc, Cambridge, Mass (Dr Kooijmans); Hôpital Purpan, Toulouse, France (Dr Clanet). Dr Freitag is currently affiliated with the Department of Radiology, Regionalspital Emmental, Burgdorf, Switzerland. A list of members of the Frequent MRI Subgroup of the European rIFN -1a in Relapsing MS Dose Comparison Trial Study Group is listed in a box.

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