Secondary/Progressive Multiple Sclerosis

We report the findings in 60 patients with Secondary/Progressive Multiple Sclerosis who had monthly Brain MRI studies for 4 months (one baseline and three follow-up scans).

The purpose was to define the short-term MRI natural history in a large cohort with Secondary/Progressive disease and to ascertain its relationship with other clinical and MRI features.

The patients were participating in either a natural history study or the placebo arm or non-treatment phase of a therapeutic trial.

The cohort had clinical features typical of Secondary/Progressive disease: thus, all had moderate or severe locomotor disabilities.

Expanded Disability Status Scale (EDSS), score 3.5-8, with a median disease duration of 12 years. There was equal representation of males and females.

During the 3 months of follow-up there was a total of 362 new enhancing lesions seen in 42 patients, and there were 24 relapses in 20 patients.

There was no correlation between new enhancing lesions and age at study entry, age of disease onset, gender disease duration or EDSS.

But there was a strong correlation with the number of enhancing lesions on the baseline scan (r =0.65, P < 0.0001) and subsequent activity.

There was a non-significant trend for higher numbers of new enhancing lesions in those having relapses during the 3 months of scanning (P = 0.14) or in the preceding 6 months (P = 0.06).

The 34 patients who did not relapse in either period had significantly fewer new active lesions (P = 0.02) than those who relapsed at some stage during the 9 months.

Nevertheless, considerable activity was seen in the Non/Relapsing cohorts: there was a mean of 3.5 (median 2) new enhancing lesions.

In those Not Relapsing during the 3 month study, and 5.5 (median 2) in those Not Relapsing in the previous 6 months.

We conclude that short-term MRI activity is generally high in Secondary/Progressive disease, confirming a useful role for the technique in exploratory trials.

Further work should concentrate on elucidating the mechanisms of Secondary/Progression by longer term follow-up studies of larger cohorts using multiple MRI and clinical measurements.

Background
Magnetic Resonance Imaging is used routinely for diagnosing MS and for objective assessment of the extent of disease as a marker of treatment efficacy in MS clinical trials.

Nevertheless, in many clinical studies only weak correlations have been reported between MRI findings and clinical outcome measures.

Purpose
The purpose of this study is to compare clinical outcome measures (Neurologic Scales) with MRI findings (evaluation of T₂-weighted MRI scans.

Using a semiautomated quantitative technique and with an independent assessment by a Neurologist) in the context of a randomized clinical trial, evaluating the efficacy of Cladribine for treatment in Secondary/Progressive MS.

Methods
Baseline, 6-month, and 12-month scans from 41 Secondary/Progressive MS patients were examined.

And, ranked in terms of lesion burden from the quantitative assessment and independently in terms of severity by neurologic evaluation.

Comparison is made to monthly Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale (SNRS) determinations in these patients with a nonparametric statistical procedure.

Results
Average rank correlations between any of the MRI assessment procedures and either clinical outcome measure were less than 0.15 in absolute magnitude.

The average rank correlation between the two MRI assessment procedures was 0.10.

There is only a weak degree of association between the MRI assessment procedures and the clinical parameters.

Although the study has statistical power in excess of 0.90 to find even a moderate level of association between them.

Conclusions
Disease-related activity in T₂-weighted scans of Secondary/Progressive MS patients is a multidimensional construct.

And, is not summarized adequately solely by quantification of overall lesion burden or by assessment of severity.

Neither method of summarizing information from T₂-weighted scans is strongly related to measures of the clinical course of disease as assessed by the EDSS or SNRS.