Barnett and Prineas. Ann Neurol. 2004 Apr;55(4):458-68.
"I am reposting this for those of you have not had time to read all the posts on this blog."
"This study really challenges our understanding of MS; it challenges the dogma!"
The investigators present the pathological findings in 12 patients with RRMS who tragically died during or shortly after the onset of a relapse. Microscopic 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 drive autoimmunity and enter the brain and spinal cord from the peripheral blood. Natalizumab is believed to work by blocking this migration of lymphocytes. 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.
Labels: apoptosis, article of interest, brain stem, Pathology, Prineas, sudden death