We Should Use Magnetic Resonance Imaging to Classify and Monitor the Course of Multiple Sclerosis

Abstract

D ISEASE ACTIVITY IN multiple sclerosis (MS) consists of acute exacerbations that can be either clinical or subclinical (seen on magnetic resonance imaging [MRI]) and incremental increases in disability that can be related to relapses or occur independently of them. In 1996, Lublin and Reingold developed a consensus disease course classification for MS that is now widely used. Persons who demonstrate an acute or subacute clinical exacerbation associated with transient or persistent neurological deficits are assigned into a “relapsing” form while those who accrue disability either without documented exacerbations or superimposed on clinical exacerbations fall into a more “progressive” category. While quite useful, a potential deficiency of this classification is the lack of formally incorporating MRI measures of disease activity. Serial studies of individual patients with MS have clearly shown that the inflammatory lesions of MS occur with considerably greater frequency than is evident clinically. Active inflammation has been detected 5 to 10 times more frequently by conventional MRI and up to 30fold more frequently by using sensitive MRI technology (interferon beta-1b vs glatiramer acetate in MS with triple-dose gadolinium and 3-T MRI end points [D.C., L. J. Wolansky, MD, J. Skurnick, PhD, et al, unpublished data]) than by clinical criteria alone. It has been previously shown that persistent MRI activity (inflammation) may result in axonal loss and irreversible cerebral atrophy. Evidence of axon pathology has also been described within T2 lesions, as has a strong correlation between overall T2 lesion volume, in the first 5 years after diagnosis with clinically isolated syndrome and long-term MS disability. Recently, Fazekas et al suggested that the occurrence of new/enlarging T2 lesions or gadolinium-enhancing lesions supports the idea of insufficient suppression of the inflammatory/demyelinating process. Although the association between MRI activity, using generally available technology, and prognosis is not robust, it is clear that MRI is more sensitive than clinical assessment of disease activity. Indeed, radiographic worsening may prove to be the most sensitive and important laboratory tool currently available for evaluating MS disease course. In contrast to clinical course alone, diagnostic criteria have appropriately evolved to incorporate MRI evidence of disease activity when evidence of clinical relapse is unavailable. The revised McDonald criteria allow MS to be diagnosed when a new lesion is found on an appropriate follow-up MRI. We argue that using this robust tool to monitor the course of MS once diagnosed could also potentially allow for earlier detection of inflammation and ongoing disease activity, even in the absence of clinical symptoms.