One of the most important studies in the field of MS pathology was published in 2004 describing the hyperacute MS lesion, which has subsequently become known as the Prineas lesion after the senior author of the paper, John Prineas, an MS pathologist based in Sydney, Australia. Professor Prineas has made many several seminal observations in MS and is one of my MS heroes.
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).
The most remarkable observation was that there were very few or no lymphocytes in these lesions. Lymphocytes are the cells that are thought to drive autoimmunity and enter the brain and spinal cord from the peripheral blood.
If these lesions don't have T & B cells in then what is causing the death of the oligodendrocytes?
Prior to this paper it was believed that the first events in new MS lesion formation were orchestrated by lymphocytes. This dogma arose from observations in the animal model of MS called EAE (experimental allergic encephalomyelitis); it is now very clear that MS is not EAE.
The famous 17-hour lesion above, is visible in the critical part of the brain called the medulla; the part of the brain that controls vital functions like breathing. The reduction in myelin in the lesion on the left appears pale, or almost white. Compare this to right side where the normal myelin stains blue. In the high-power picture below we see the myelin producing cells, oligodendrocytes, showing the characteristic signs of programmed cell death or apoptosis. There is a lack of lymphocytes in this area of the lesion.
The study describes the clinical and pathological findings in 12 patients with relapsing and remitting multiple sclerosis, who died during or shortly after the onset of a relapse. Pathological changes not previously associated with the formation of new symptomatic lesions were observed in seven cases, namely, extensive oligodendrocyte apoptosis and microglial activation in myelinated tissue containing few or no lymphocytes or myelin phagocytes. No current laboratory model of multiple sclerosis, in particular, experimental allergic encephalomyelitis, is known with these features, which raises the possibility of some novel process underlying new lesion formation in multiple sclerosis.