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Abstract
Objective: To assess the time course of brain atrophy and the difference across clinical subtypes in multiple sclerosis (MS).
Methods: The percent brain volume change (PBVC) was computed on existing longitudinal (2 time points) T1-weighted MRI from untreated (trial and nontrial) patients with MS. Patients (n = 963) were classified as clinically isolated syndromes suggestive of MS (CIS, 16%), relapsing-remitting (RR, 60%), secondary progressive (SP, 15%), and primary progressive (9%) MS. The median length of follow-up was 14 months (range 12–68).
Results: There was marked heterogeneity of the annualized PBVC (PBVC/y) across MS subtypes (p = 0.003), with higher PBVC/y in SP than in CIS (p = 0.003). However, this heterogeneity disappeared when data were corrected for the baseline normalized brain volume. When the MS population was divided into trial and nontrial subjects, the heterogeneity of PBVC/y across MS subtypes was present only in the second group, due to the higher PBVC/y values found in trial data in CIS (p = 0.01) and RR (p < 0.001). The estimation of the sample sizes required for demonstrating a reduction of brain atrophy in patients in a placebo-controlled trial showed that this was larger in patients with early MS than in those with the progressive forms of the disease.
Conclusions: This first large study in untreated patients with multiple sclerosis (MS) with different disease subtypes shows that brain atrophy proceeds relentlessly throughout the course of MS, with a rate that seems largely independent of the MS subtype, when adjusting for baseline brain volume.
Glossary
- ANOVA=
- analysis of variance;
- CIS=
- clinically isolated syndrome;
- DMA=
- disease-modifying agent;
- EDSS=
- Expanded Disability Status Scale;
- FSL=
- FMRIB Software Library;
- Gd=
- gadolinium;
- MR=
- magnetic resonance;
- MS=
- multiple sclerosis;
- NBV=
- normalized brain volume;
- PBVC=
- percent brain volume change;
- PP=
- primary progressive;
- RR=
- relapsing-remitting;
- SP=
- secondary progressive.
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