Significance of T2 lesions in multiple sclerosis: A 13-year longitudinal study
Rudick RA, Lee JC, Simon J, Fisher E;
Commented by , 25 Jul 2006
MRI is central in the diagnosis of multiple sclerosis (MS), visualizing characteristic white matter lesions on T2-weighted images. The T2 lesion load at disease onset may predict disease severity and lesion load is also widely used in clinical trials as a surrogate measure of disease burden. In this context, the validity of T2 measures has been questioned, since several studies have shown a poor relationship between disability and T2 lesion burden. Still, prospective long-term studies have not been performed.
To determine the relation between cerebral MRI-T2 lesions and future disease severity in Relapsing Remitting MS (RRMS).
The study enrolled 30 RRMS patients who were recruited from a randomized, double blind, placebo-controlled interferon-beta trial. Baseline MRI measurements included number of Gd-enhancing lesions, T2 lesion volume and T1 hypointense lesion volume. Disease severity outcomes included EDSS, MSFC and MRI brain parenchymal fraction (BPF).
Magnetization transfer ratio (MTR) in lesions and normal appearing brain tissue (NABT) were only measured at the last visit. Baseline MRI lesions and their change over 2 years were tested for correlation with other study measures at last visit.
EDSS was 2.2 ±0.8 at entry and 4.4 ±1.95 at last visit.
BPF was 0.825 ±0.015 at entry and 0.774 ±0.037 at last visit.
Baseline T2 lesion volume correlated with BPF at last visit (r = -0.66; p < 0.0001), MTR in NABT (r = -0.52; p = 0.004), and lesion MTR (r = -0.76; p < 0.0001).
Change in T2 lesion volume in the first two years correlated with BPF at the last visit (r = -0.40; p = 0.03, NABT MTR (r = -0.44; p = 0.015), lesion MTR (r = - 0.46; 0.018), MSFC (r = - 0.50; 0.005), and PASSAT scores (r =-0.52; p = 0.003).
Age was a significant covariate for clinical, but not MRI-imaging outcomes.
Dr Blinkenberg's comments
The authors demonstrate a strong correlation between T2 lesion load and disease severity 13 years later. T2 lesion burden also correlates strongly with brain tissue loss and brain tissue integrity in the same observation period. Comparing 2 and 13 year data show that correlation between T2 lesion load and clinical measures improves with time, which may explain the "disconnect" between clinical and MRI data reported in previous studies of shorter duration.
The authors hypothesize that a certain pathology threshold must be exceeded, before the relation between pathology and burden of disease become evident. The fact that age is found to be a significant covariate moreover supports this hypothesis. In other words, disease outcome is easier to predict from MRI measures of pathology in older MS patients, since neural redundancy is exhausted.
The results of the study support the use of MRI as a valid surrogate marker of MS pathology in clinical trials. Furthermore, it substantiates the threshold hypothesis explaining fundamental pathological and clinical questions in MS, such as mismatch between MS pathology and disease burden and transition between relapsing remitting and secondary progressive course. It will be interesting to see if future long-term studies using a larger sample size can reproduce these important data.