Seeing blobs on contrast-enhanced MRI and not being able to tie my shoe-laces up is one thing, but figuring out the root cause(s) and mechanism(s) of CLIPPERS is complicated. In fact it is probably far more complicated than I imagine, and I already think it is complicated. One of the most valuable resources for scientists investigating CLIPPERS is access to brain-tissue for direct investigation. Until some suitable animal model displaying CLIPPERS-like features is found, we have to rely on sporadic and sometimes opportunistic access to brain-tissue samples from patients.
I have a couple of reports from such studies in my CLIPPERS folder. These are hard for me, as a layman (and someone who left biology behind a long time ago) to discuss as I am aware of my lack of understanding and cautious about passing it on. Anyway, here goes ....
The first report is from a conference last year (The International Congress of Neuroimmunology). The title nicely summarises the study: "Neuropathological evaluation of four Danish cases of CLIPPERS: Evidence of generalized neuroinflammation but no pre-lymphoma". (Unfortunately the full text does not seem to be publically available, however as a conference paper it was less than half a page of text anyway - a bit mean of the publisher though.) One of the four cases had been autopsied so presumably the whole brain was available for analysis. Perhaps the most interesting finding was that some broader evidence of inflammation was found in brain tissue - "A similar, but less prominent, T-cell infiltration was found in the normal appearing cerebral cortex" - which would not light up in contrast-enhanced MRI i.e. not in visible lesions. Perhaps the most reassuring finding was that "Our study does not suggest that CLIPPERS is a pre-lymphoma condition".
The second report was of a single, quite severe case, of CLIPPERS in an elderly woman who subsequently died of other causes. In their paper "Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): postmortem findings", the authors found less extensive inflammation - "The dura, cortical gray and white matter, ..., were unremarkable." They also remarked that "... our case does show that evolution to lymphoma, even after several years, is not inevitable in CLIPPERS."
So, in these small studies, there are already some interesting agreements and disagreements. It is possible the the variation in CLIPPERS presentation and patients may explain things, or differences in the experimental methods which I have not picked up on. Small steps.
Read other articles in this series at Living With CLIPPERS.
Living With CLIPPERS by Bill Crum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.