CMSC Recommends Adding MRI to Clinical Classification of MS
The Consortium of Multiple Sclerosis Centers (CMSC) recommends that the Lublin–Reingold clinical classification of multiple sclerosis (MS) be modified to include evidence of new MRI gadolinium-enhancing (Gd+) T1-weighted lesions “and probably unequivocally new or enlarging T2 lesions,” according to a consensus statement published in the Fall 2012 International Journal of MS Care. The group also proposed that Gd+ lesions and possibly unequivocally new or enlarging T2 lesions be recognized as contemporary or prior subclinical relapses, respectively.
No available biomarker is superior to the combination of MRI and clinical criteria for the purpose of disease classification or distinguishing between relapsing and progressive MS, according to the report, which was written by Stuart D. Cook, MD, Professor of Neurosciences at the University of Medicine and Dentistry of New Jersey in Newark, and colleagues. Furthermore, the clinical classification of MS is likely to be revised periodically as experimental quantitative measures are validated and become widely available, the CMSC added.
Questions About the Lublin–Reingold Classification
The Lublin–Reingold clinical classification identifies four types of MS—relapsing-remitting MS, secondary progressive MS, primary progressive MS, and progressive relapsing MS. Over time, neurologists have raised questions about the classification, such as whether progressive relapsing MS is truly a distinct category and whether each of the classification’s categories is heterogeneous.
In addition, neurologists have observed that it is difficult to determine a patient’s transition from relapsing to progressive MS on clinical grounds alone. Others have noted that inter- and intraexaminer variability and limitations in the Expanded Disability Status Scale (EDSS) could hamper the assessment of disease progression. In a 2009 article, Lincoln et al. proposed that MRI be added to the Lublin–Reingold clinical classification of MS.
In March 2010, the CMSC invited 28 MS experts from North America, South America, and Europe to an international consensus conference to examine whether the Lublin–Reingold criteria should be modified and whether adding MRI and other biomarkers to the criteria would improve the understanding and treatment of MS.
The Correlation Between MRI and MS Pathology
During a series of presentations, participants at the meeting analyzed the data regarding the relationship of MRI findings to MS pathology. An overview of biopsy and necropsy studies presented at the conference suggested a strong association between MRI lesions and CNS injury. A review of the literature indicated that when sensitive and frequent MRI studies are performed, “almost all new T2 lesions (95% to 100%) … occur coincidentally with or evolve from Gd+ T1-weighted lesions,” according to the consensus statement. In contrast, “T1 hypointensities or black holes … correlate better with physical disability; tissue injury, including severe demyelination and axonal injury; and brain atrophy.”
Participants also considered the BECOME study, in which patients with early MS or clinically isolated syndrome were randomized to interferon beta-1b or glatiramer acetate. A subset analysis of that study showed that patients with active monthly MRI patterns had a higher relapse rate, greater sustained worsening in the Timed 25-Foot Walk, and more cognitive impairment than those without active MRIs. The observation “reinforces that what we see in clinical practice or during clinical trials using infrequent, less sensitive MRIs represents just a fraction of what is actually occurring in the neuraxis,” according to the consensus statement.
The conference also considered a meta-analysis of 23 randomized, placebo-controlled studies of patients with relapsing-remitting MS. The meta-analysis demonstrated that “the therapeutic response effect on new MRI T2 lesions correlated strongly with the effect of drugs on relapses,” according to the consensus statement. In addition, the meta-analysis showed a significant correlation of MRI response to therapy with effect on disability progression. Based on these and other studies, researchers concluded that “MRI markers satisfy the rigorous Prentice criteria for consideration as a valid surrogate marker in group studies of [relapsing-remitting MS].”
The CMSC did not consider incorporating advanced MRI techniques such as fMRI, multispectral thermal imaging, diffusion tensor imaging, and spectroscopy into the Lublin–Reingold classification, because they are not widely available in clinical practice. These techniques also do not clearly distinguish between MRI subclinical relapses, according to the CMSC.
Cook SD, Dhib-Jalbut S, Dowling P, et al. Consensus statement: Use of magnetic resonance imaging as well as clinical disease activity in the clinical classification of multiple sclerosis and assessment of its course. Int J MS Care. 2012;14(3):105-114.
Lincoln JA, Cadavid D, Pollard J, et al. We should use magnetic resonance imaging to classify and monitor the course of multiple sclerosis. Arch Neurol. 2009;66(3):412-414.