We have recently been criticised for not covering pathology papers on the blog. Apologies, I agree this is an oversight from our side. None of us are card-carrying pathologists; DrK has the most experience and runs a research group looking at MRI-pathology correlations. Dr Love (who we need to get to do some more writing for us) works in the brain bank at the Free University of Amsterdam and has published extensively on MS pathology. Then we have Mouse Doctor 1 and Mouse Doctor 2 (Thing 1 and Thing 2); they are very good at doing EAE pathology and are also very good at spotting bad research, dodgy data and its over interpretation.
This Barnette-Prineas paper really challenges our understanding of MS and challenges the dogma. They describe the pathological postmortem findings in 12 patients with RRMS who died during or shortly after the onset of a relapse. Changes not previously associated with the formation of new symptomatic lesions were observed in 7 cases, i.e. extensive death of oligodendrocytes (the cells that produce myelin) by a cellular process called programmed cell death or apoptosis*, and the extensive activation of another population of resident inflammatory cells called microglia (tissue scavengers).
What is killing these oligodendrocytes? Could it be a virus? Is the influx of lymphocytes that are seen in older MS lesions a secondary response to the inciting agent? Too many questions and not enough answers. This paper challenged, and continues to challenge, current dogma and raises serious questions about the hypothesis that MS is an autoimmune disease. I for one don’t believe MS is a primary autoimmune disease; I prefer the viral hypothesis and that the inflammation we see in MS is a secondary response to a virus. This paper has been very controversial and the world’s pathologists still can’t agree on the interpretation of the findings. The paper has been criticised by some very eminent pathologists, whereas other have kept a very low profile and not openly expressed an opinion. Why?
* apoptosis /ap·op·to·sis/ (ap″op-to´sis) a pattern of cell death affecting single cells, marked by shrinkage of the cell, condensation of chromatin, and fragmentation of the cell into membrane-bound bodies that are eliminated by phagocytosis. Often used synonymously with programmed cell death. apoptot´ic
Barnett & Prineas. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol. 2004 Apr;55(4):458-68.