Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis.
J Neuroinflammation. 2017; 14(1):171.
BACKGROUND:The diagnosis of multiple sclerosis (MS) is currently based solely on clinical and magnetic resonance imaging features. However, histopathological studies have revealed four different patterns of lesion pathology in patients diagnosed with MS, suggesting that MS may be a pathologically heterogeneous syndrome rather than a single disease entity.
OBJECTIVE:The aim of this study was to investigate whether patients with pattern I MS differ from patients with pattern II or III MS with regard to cerebrospinal fluid (CSF) findings, especially with reference to intrathecal IgG synthesis, which is found in most patients with MS but is frequently missing in MS mimics such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein-IgG-positive encephalomyelitis.
METHODS: Findings from 68 lumbar punctures in patients who underwent brain biopsy as part of their diagnostic work-up and who could be unequivocally classified as having pattern I, pattern II or pattern III MS were analysed retrospectively.
RESULTS: Oligoclonal bands (OCBs) were present in 88.2% of samples from pattern I MS patients but in only 27% of samples from patients with pattern II or pattern III MS (P < 0.00004); moreover, OCBs were present only transiently in some of the latter patients. A polyspecific intrathecal IgG response to measles, rubella and/or varicella zoster virus (so-called MRZ reaction) was previously reported in 60-80% of MS patients, but was absent in all pattern II or III MS patients tested (P < 0.00001 vs. previous cohorts). In contrast, the albumin CSF/serum ratio (QAlb), a marker of blood-CSF barrier function, was more frequently elevated in samples from pattern II and III MS patients (P < 0.002). Accordingly, QAlb values and albumin and total protein levels were higher in pattern II and III MS samples than in pattern I MS samples (P < 0.005, P < 0.009 and P < 0.006, respectively).
CONCLUSIONS: Patients with pattern II or pattern III MS differ significantly from patients with pattern I MS as well as from previous, histologically non-classified MS cohorts with regard to both intrathecal IgG synthesis and blood-CSF barrier function. Our findings strongly corroborate the notion that pattern II and pattern III MS are entities distinct from pattern I MS.
So I first have to explain what a pattern II and pattern III lesion. Following analysis of brain biopsies some pathologists made a suggestion that their were four types of lesion Pattern I-IV. They can be summarised above
However it must be said that through standard analysis of post-mortem tissue it was found that lesions were just type I and II.
The type II is an immune centric demyelinated lesion with antibody in the lesions, the type III lesion is the lesion where the oligodendrocytes are destroyed or damaged but there are few or no immune cells. These are not centred around blood vessels. Some would argue that these are the pre-active lesions that resolve or develop into full blown lesions
In this study they looked in matched CSF and found that 82% in people with type I lesions but only 27% in people with type II and III and people with type II & III had more blood proteins in their CSF. The implications are they there are more than one type of MS. This may be so does it mean that type II and type III are not MS or a different MS?
This is maybe what the pathologists would have us believe. Do they need different treatments?
Maybe it tells us that people with type I lesions have had MS for a bit longer and their disease was not as active as their blood brain barrier isn’t leaking as much because there is less blood proteins in the spinal fluid and no antibody in the lesions because they have stopped leaking. In animals it is very dynamic they leak for a few days and then stop. They have had time for their intrathecal antibody stores to develop, where as those with type II and type III have yet to develop.
Maybe the pathologists will come back in a few years and tell us where these cases clinically definite MS or a mis-diagnosis and how the different people responded to treatment, because if people really have different diseases we have to know this. However that type I and type II lesions are common at post-mortem, would argue that the distinction between type I and type II & III is more of staging thing.
As pathologists can’t seem to agree on anything, we will have to see what others think, but remember based on pathologists…for the longest time they told us MS was a white matter disease until they stopped using luxol fast blue and started staining for myelin with antibodies when it is a grey and white matter disease. You can see this with the naked eye is some brains, so sometimes whilst looking down a microscope to see the trees you can’t see the Wood:-)