Abstract
The protagonists are internationally recognized for their expertise in grey matter (GM) disease in multiple sclerosis (MS) (Geurts) and in the development magnetic resonance imaging (MRI) techniques and their application to MS (Filippi and Rocca). The latter argue that both clinical and MRI measures are available to measure GM disease; the problem is that we do not apply them, either in the clinic (cognitive testing) or in the scanner (double inversion recovery techniques and atrophy measures). Geurts summarizes the evidence for GM involvement in MS, and in his last paragraph (in an apposite simile), indicates the future challenge of quantifying its extent and effect.
Does it matter that we cannot/do not measure grey matter disease?
The problem of course is that, in most clinics and hospitals throughout the world (apart from research centres), neurologists do not have access to the clinical or MRI tools to assess GM disease. But does that matter?
Clearly GM disease is important in MS of long duration: GM involvement is prominent in secondary progressive MS, 1 a number of MRI studies have shown that GM atrophy correlates better with disability than white matter lesions at this stage of MS 2 and ‘benign’ patients with GM disease will soon deteriorate. 3
Although GM involvement is present in the early stages of MS (and predicts an increased risk of conversion of the clinically isolated syndrome to MS), 4 it is not a prominent disease feature at this stage. Guerts in discussing the pathogenesis of MS says ‘even the most potent anti- inflammatory drugs . . . .are largely incapable of halting disease progression’ and uses this as evidence against the auto-immune hypothesis. Clinicians would argue that the studies of natalizumab and alemtuzumab have strengthened the auto-immune hypothesis. The CAMMS223 study highlighted the effectiveness of modern monoclonal therapy on atrophy in relapsing–remitting MS; patients in the alemtuzumab arms showed no evidence of atrophy; brain volume increased by 0.9% in the period from 12 to 36 months of treatment and the mean Expanded Disability Status Scale (EDSS) improved by 0.39 over 36 months. 5 In the other arm, patients treated with IFNB-1a showed evidence of atrophy and an increase in mean EDSS score by 0.38. The reason for these outcomes was that this group of highly active patients was treated very early in the course of their illness; therapy was initiated at a median period of 1.3 years from the first relapse. This illustrates that potent monoclonal anti-inflammatory therapies can be effective against atrophy when used early in the disease course.
Making the MRI tools to measure GM disease available in everyday practice will be a challenge; my experience of the double inversion recovery technique in patients undergoing a study of cognition in early MS left me singularly unimpressed by its sensitivity and utility.
Thus, while not denying that GM involvement is important in relation to disability, the evidence that knowing more about it in the early stages of relapsing–remitting MS would alter management in the individual is sparse. The evidence from the CAMMS223 study, that effective anti-inflammatory therapy (initiated for white matter disease) can prevent cerebral atrophy, indicates that perhaps we do not need to know too much about GM disease to make effective treatment decisions.