Inflammation, Relapse Rate and MRI in MS: Not the Whole Story

Clinical studies have shown that glatiramer acetate and the beta-interferons improve two key measures – relapse rate and MRI. These effects on the relapse rate and the MRI are due, in part, to the effect of these medications on CNS inflammation.

MS has traditionally been considered an autoimmune disorder which results in inflammatory flare-ups in the CNS. So reducing inflammation and producing improvements in the relapse rate and MRI were important advances. However, the "inflammation story" wasn’t the whole story. It was a necessarily simplified version of the MS puzzle and there were several pieces that didn’t fit very well.

For example, traditional anti-inflammatory medications, such as corticosteroids, are often given to people with MS to dampen their immune system hyperresponse and relieve their symptoms. These drugs produce a rapid reduction in CNS inflammation and a corresponding improvement in MS symptoms. However, these anti-inflammatory effects have not been shown to provide long-term benefits. This is because steroids do not appear to have much effect on the underlying disease process in MS.

In a similar vein, the two key measures of treatment success – relapse rate and MRI – have been shown to be imperfect indicators of how well a person will do over the longer term. Someone with frequent relapses might develop little disability. Conversely, people with progressive forms of MS, who typically develop the more severe disabilities seen among people with MS, often have few or no relapses. So relapses alone are not an ideal way to assess disease severity.

Similarly, MRI does not directly measure the most important clinical outcome: disability. It is only a surrogate marker of the disease process. What this means is that while MRI may provide some sense of disease activity, but it isn’t directly measuring the underlying disease process. This is common in medicine because what you’d like to study can’t always be seen directly. When your doctor measures your blood pressure, he/she isn’t actually measuring the extent of heart disease. High blood pressure is only one of many risk factors for cardiovascular disease, so it is a surrogate marker of heart disease. People with high blood pressure may be more likely to have a heart attack, but that doesn’t mean they will. And it doesn’t mean that people with normal blood pressure won’t have a heart attack.

MRI studies have shown that the number and volume of lesions in the CNS are not well-correlated with clinical measures, such as disability. In part, this is because the T2 and T1 lesions that appear on an MRI scan may be caused by many things, such as generalized swelling (edema). Indeed, it has been estimated that inflammatory lesions are ten times more common than actual MS relapses. So T2 and T1 lesions are not a specific marker of MS.