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Published on: July 19, 2019
New hypointense lesions on MRI in relapsing-remitting multiple sclerosis patients
1Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif., USA. simone_wagner@med.uni-heidelberg.de
Background:
Preliminary observational studies with multiple sclerosis (MS) patients have reported strong correlations between an increase in hypointense lesion load (black holes) on T1-weighted spin echo images, and an increase in disability.
Objective:
We assessed the relationship of hypointense lesions to the clinical course of disease among 50 relapsing-remitting MS patients in the controlled setting of a randomized clinical trial.
Methods:
Fifty patients with relapsing-remitting disease were enrolled in a randomized double-blind two-arm (cladribine vs. placebo) clinical trial of 1-year duration. All patients had monthly clinical evaluations and MRIs over the course of the trial. Multivariate techniques were used to identify predictors of clinical severity from information on exacerbations, MRIs, baseline clinical parameters, and demographics.
Results:
At baseline, clinical severity is weakly related to counts of black holes, with rank correlations between counts and clinical scores (EDSS and SNRS) of absolute magnitude 0.3. Rates of appearance of new black holes over the course of the trial are higher for patients with more severe disease at baseline (EDSS > or = 4) than for the less severe patients. Changes in clinical severity over the course of the trial are best predicted by baseline neurologic scores and numbers of exacerbations, with black holes adding no further improvement in prediction.
Conclusions:
Numbers of exacerbations seem more critical to short-term clinical outcomes in relapsing-remitting MS, as reflected by patients' clinical scores, rather than black holes. Various imaging methods and MRI indices capture complementary information relating to MS disease processes. The determination of which processes are affected by different drugs should lead to more effective treatment of MS patients.
Insights
In relapsing-remitting multiple sclerosis (MS), exacerbations are more critical to short-term clinical outcomes than black holes. MRI indices capture complementary information for MS treatment.
Area of Science:
- Neurology
- Radiology
- Clinical Trials
Background:
- Observational studies suggest a correlation between T1 hypointense lesions (black holes) and disability in multiple sclerosis (MS).
- Black holes on MRI may indicate irreversible tissue damage and disease progression.
Purpose of the Study:
- To evaluate the relationship between hypointense lesions and the clinical course of relapsing-remitting MS.
- To identify predictors of clinical severity in MS patients within a randomized clinical trial setting.
Main Methods:
- A 1-year randomized, double-blind, placebo-controlled trial involving 50 relapsing-remitting MS patients.
- Monthly clinical evaluations and MRI scans were conducted throughout the trial.
- Multivariate techniques analyzed exacerbations, MRI data, baseline clinical parameters, and demographics to predict clinical severity.
Main Results:
- Baseline clinical severity showed a weak correlation with black hole counts (r=0.3).
- New black holes appeared more frequently in patients with more severe baseline disease (EDSS ≥ 4).
- Clinical severity changes were best predicted by baseline scores and exacerbations; black holes did not improve predictive accuracy.
Conclusions:
- Exacerbations appear more critical than black holes for short-term clinical outcomes in relapsing-remitting MS.
- Different imaging methods and MRI indices provide complementary information on MS disease processes.
- Understanding drug effects on specific MS processes is key to effective treatment.
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