Is the treatment aim of 'maximising the lifelong brain health of every person with MS' realistic?
We know that over many years brain volume loss, or brain atrophy, correlates with poor outcome; i.e. cognitive impairment and physical disability. What this study indicates that we clearly need something additional to an anti-inflammatory to treat MS and prevent end-organ damage. What it is telling me is that we are going to need additional add-on treatments to really make a difference for pwMS. What these add-on treatments turn out to be is speculative. At the moment we talk about add-on neuroprotective, remyelinating and neurorestorative therapies when what we may need are antivirals to suppress EBV and HERVs that are driving the slow burn and gradual loss of brain and spinal cord.
It is clear that unless we normalise brain volume loss in pwMS they will not be able to age normally and nor will be able to 'maximise' their brain health.
One interpretation of this data is that the focal inflammatory lesion, and relapses, are not MS, but are simply the body's response to what is really causing the disease. We need to ask the question what is MS and what is driving this accelerated brain volume loss in the absence of focal inflammation?
Natalizumab continues to make me think about MS and continues to challenge the scientific dogma that MS is simply an organ-specific autoimmune disease. MS is clearly not an organ-specific autoimmune disease; it is a whole lot more complex than that.
For more information please read my recent blog post 'explaining why you get worse despite being NEDA'.
Koskimäki et al. Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment. PLoS One. 2018 Dec 21;13(12):e0209326.
BACKGROUND: Brain volume loss is an important surrogate marker for assessing disability in MS; however, the contribution of gray and white matter to the whole brain volume loss needs further examination in the context of specific MS treatment.
OBJECTIVES: To examine whole and segmented gray, white, thalamic, and corpus callosum volume loss in stable patients receiving natalizumab for 2-5 years.
METHODS: This was a retrospective study of 20 patients undergoing treatment with natalizumab for 24-68 months. Whole brain volume loss was determined with SIENA. Gray and white matter segmentation was done using FAST. Thalamic and corpus callosum volumes were determined using Freesurfer. T1 relaxation values of chronic hypointense lesions (black holes) were determined using a quantitative, in-house developed method to assess lesion evolution.
RESULTS: Over a mean of 36.6 months, median percent brain volume change (PBVC) was -2.0% (IQR 0.99-2.99). There was decline in gray (p = 0.001) but not white matter (p = 0.6), and thalamic (p = 0.01) but not corpus callosum volume (p = 0.09). Gray matter loss correlated with PBVC (Spearman's r = 0.64, p = 0.003) but not white matter (Spearman's r = 0.42, p = 0.07). Age significantly influenced whole brain volume loss (p = 0.010, multivariate regression), but disease duration and baseline T2 lesion volume did not. There was no change in T1 relaxation values of lesions or T2 lesion volume over time. All patients remained clinically stable.
CONCLUSIONS: These results demonstrate that brain volume loss in MS is primarily driven by gray matter changes and may be independent of clinically effective treatment.
CoI: multiple