Multiple sclerosis (MS) is a neurodegenerative disease and the most common cause of non-traumatic neurologic disability in young adults. Traditionally, MS has been considered an inflammatory autoimmune disease in which circulating lymphocytes (T-cell and/or B-cells? depends who you talk to...) direct immunological destruction of central nervous system myelin. Most patients go through a relapsing remitting stage in the disease, in which neurologic deficits are eventually restored, presumably through the regenerative process known as remyelination. Then, after repeated immune attacks, permanent disability occurs and the patient moves to a progressive form of the disease. It is now well established that disability is due to axon transection and irreparable damage to neurons. Functional recovery early in the disease could be due to (in addition to remyelination) neural plasticity in the adult brain. After the neural reserve is used up over time, progressive neurologic disability then occurs.
The cause of MS is still unknown. I think there is definitely an immunological component to MS, but whether the immune system is the PRIMARY problem or a SECONDARY aspect of the disease is a hot issue of debate. All current MS therapies are immunomodulatory drugs. Also, acute MS attacks are treated with methylprednisolone, a potent anti-inflammatory drug. However, these drugs are not curative, they are preventative. Some of these drugs have become remarkably efficient at preventing attacks in MS patients. But are these drugs simply masking the real, underlying problem?
Evidence is beginning to emerge that MS may not be a primary immunopathology. In 2004, Prineas and Barnett examined very early MS lesions using histological procedures. In an unusual case, an MS patient died just 17 hours after the beginning of an attack. In these early lesions, researchers found apoptotic oligodendrocytes (the cells which produce central nervous system myelin) without evidence of infiltrating lymphocytes. Is it possible that some insult to oligodendrocytes kicks off the disease, independent of the immune system? And then later on, the immune system becomes sensitized? It could also be possible that the primary insult is to neurons, and oligodendrocyte death and myelin destruction are both indirect effects.
Prineas and Barnett article:
http://onlinelibrary.wiley.com/doi/10.1002/ana.20016/abstract;jsessionid=D01FDD81E1736A59DEC3F3090B6910CC.d03t02
Relevant review article:
http://www.annualreviews.org/doi/abs/10.1146/annurev.neuro.30.051606.094313?url_ver=Z39.88-2003&rfr_dat=cr_pub%3Dpubmed&rfr_id=ori%3Arid%3Acrossref.org&journalCode=neuro
Thank you for this update on MS. I did not realize that there was evidence against the idea of lymphocytes attacking the myelin sheaths. This made me think of the other common ideas around MS, such as the risk factor increases as you move away from the equator. There has been studies coupling epidemiology and genetic testing for many years to show why populations located further from the equator have a higher incidence of MS. So do not worry I looked into this and it still seems to be consensus that Vitamin D, associated with sunshine, has a contributing factor to protect from development and progression of MS. Simon et al., just released a review paper looking at this issue and any new research. Looks like vitamin D levels and genetic abilities to convert vitamin D into its active form are still good indicators to risks for MS.
ReplyDeleteSimon, Kelly C., Munger, Kassandra, & Ascherio, Albertoa.Vitamin D and multiple sclerosis: epidemiology, immunology, and genetics.
Current Opinion in Neurology
Issue: Volume 25(3), June 2012, p 246–251
DOI: 10.1097/WCO.0b013e3283533a7e
The Prineas article was really interesting and made me think. So considering MS mimics are often misdiagnosed as MS (about 10% of all MS diagnoses), I was wondering how sure they were that the case study patient was in fact presenting with MS, and when I read the paper I didn't get a good feel of how they made that distinction, so I looked for any follow up papers to the 2004 paper. They did a review in 2012 about Oligodendrocytes and the early MS lesion (http://onlinelibrary.wiley.com/doi/10.1002/ana.23634/full) and while my initial question wasn't fully addressed they did mention that MS proceed very similarly to neuromyelitis optica (NMO). Both show demyelination as secondary to caspase-3 positive oligodentrocytes. Which raises the question is MS like NMO, an autoimmune disease which oligodendrocyte apoptosis is driven by injury to glial or mesenchymal components? And, for me the next question is what comes first the injury or the immune response?
ReplyDeleteThe idea that something may hurt the oligodendrocytes, and then MS, an autoimmune attack on the brain, follows, sounds to me like the original "something" might be a virus. What's the current thought on that? We'll be talking a lot about this a bit later in the course.
ReplyDelete