Are my myelins under attack?

MS might not be caused by autoimmune attacks to the myelin sheaths. Scientists unlock secrets hidden in the brain bank

By Chris Williams

Multiple Sclerosis (MS) is traditionally known as a disease of myelin deficiency. Nowadays it's considered an autoimmune disease, and its first stage is characterized by a misguided immune system attack on the myelin sheaths that aid transmission of nervous signals in the brain. But, as it turns out, this immune attack may not be the first event after all.

In fact, the immune activity may be nothing more than the mopping up of myelin-producing brain cells that died for a quite different reason, said researcher Dr John W Prineas, of the University of Sydney in Australia. The research, which is the first study of brain tissue from the earliest hours of an MS attack, is published in the February 23 online edition of Annals of Neurology.

Several years ago while Dr Prineas was working at the New Jersey Medical School in Newark, a fellow neuropathologist in Manhattan asked whether Dr Prineas and his colleagues would be interested in examining brain tissue from a 14-year-old girl who died unexpectedly 17 hours into a relapse. Sudden death is a rare occurrence in MS but can happen when lesions develop in parts of the brain that control vital functions such as breathing and blood circulation.

With co-author Dr Michael H Barnett, Dr Prineas began studying the patient's brain and saw something never before observed and recorded in MS -- a lesion in the very first stage of its existence. "This patient proved to be unique in the history of MS in that there was a lesion available for study that was less than a day old," said Dr Prineas.

According to the standard model of MS, when the researchers examined the fresh lesion, they should have found the beginnings of an immune system attack, with severe damage already underway to the myelin in the lesion.

Instead, they noticed that the myelin in the lesion was still intact and there was no evidence that immune system cells had moved into the area. Rather, they observed that oligodendrocyte cells, which produce the myelin, were dying. Myelin is an extension of oligodendrocytes and wraps itself around nearby nerve fibres.

"This encouraged us to re-examine other early MS cases in our brain bank," said Dr Prineas. "Similar lesions, albeit extremely rare, were identified in a number of other early MS cases, which allowed us to conclude that the changes observed probably occur at the onset of any typical new lesion."

Looking at 12 brains of patients who died close to the onset of an attack, they found that seven had lesions that fitted the same pattern -- rather than being attacked, they appeared to have died on their own.

Currently, most MS research is focused on understanding why the immune system attacks myelin. But in the lesions that killed these patients, it seems very possible that the immune system never did any damage at all. The focus may have to shift to understanding why the myelin-producing cells begin to die.

"The important point, at this stage of our investigation, seems to be that we have no laboratory model for this sort of pathology," said Dr Prineas.