I had an interesting discussion with some like-minded colleagues recently about active and inactive MS. We seemed to agree on what active MS is, be it in the relapsing or progressive phases of MS. However, we couldn’t really agree on what inactive MS is. Take this following case scenario; many said he was inactive, but others felt he had active MS and should have his treatment switched. Would you agree?
When you look at post-mortem studies of people dying with endstage MS they all have active inflammation within their brains. Active inflammation refers to both adaptive (memory responses) and innate (hard-wired) immune responses. MSers at death still have T-cells, B-cells and plasma cells in their brains in addition to astrocyte and microglial activation.
If we extrapolate these pathological findings to life then all MSers have active MS. What is the solution in terms of forming a common nomenclature? Surely MS is a biological disease rather than a clinical disease? If this is the case we need to come up with a biological classification system to describe active and inactive MS.
On reflection, I think we need to get rid of the terms active and inactive and describe what we mean pathologically using metrics. For example,
- This patient has evidence of ongoing focal inflammation (relapses, new and/or enlarging T2 lesions and/or Gd-enhancing lesions and/or raised CSF NFL levels) in the last 12 or 24 months.
- This patient has no evidence of ongoing focal inflammation in the last 24 months but has worsening disability (physical and/or cognitive) and evidence of smouldering MS with increased brain/spinal cord atrophy and/or an increasing T1 black volume.
- This patient has no evidence of ongoing focal inflammation in the last 24 months, is stable clinically (physical and cognitive) and has no evidence of smouldering MS, i.e. no increased brain/spinal cord atrophy and a stable T1 black volume.
I suspect that we will have very few MSers in category 3, simply because with an MS-centric view of the world we are forgetting that MSers are human and will age and will get comorbidities. Therefore, how do we include ageing and comorbidities, which affect these biomarkers, into this classification system? In addition, none of our metrics is black-and-white so there is scope for miss-classification. What is clear that if you take this approach then MS is one, and not two or three, diseases. A person with PPMS with new lesions will be treated in the same way as someone in the relapsing-remitting phase of the disease. Do you have a problem with this?