Pathophysiology of Multiple Sclerosis (MS)


Klaus Schmierer, MB BS, PhD, FRCP, defines the pathophysiology of multiple sclerosis (MS).

Klaus Schmierer, MB BS, PhD, FRCP: When we’re talking about the pathophysiology of multiple sclerosis [MS], particularly of relapsing and progressive MS, we’re talking about generally an immune-mediated disease that affects the myelin and subsequently the nerve fibers or axons. It’s an inflammatory condition with elements of autoimmunity that leads to damage to these structures in the brain and the spinal cord. Any corner of the central nervous system can be affected by it and that explains the multitude of symptoms that you get with the condition including optic neuritis leading to blurred vision, brain stem syndromes that can lead to double vision or problems with speech, swallowing, and the likes. Cerebellar involvement with ataxia of limbs, [INAUIBLE] walking. The spinal cord, of course, leading to lower limb dysfunction, bladder dysfunction, sexual dysfunction, etc.

Relapsing MS is characterized by episodes of neurological dysfunction with a variable degree of recovery after a new bout of dysfunction. We know that even at the earliest stages of MS; however, there is an undercurrent of progression in the condition. We often speak about MS as relapsing and progressive because this is what very much dominates the phenotype at the beginning versus later stages of the disease. But I think it is very important to realize and recognize that both disease stages have a lot of overlap. When we’re talking about progressive MS, so the later stages, however, there are also elements in the immune system that are probably slightly different compared to the initial stages. And that is related to the way the immune system essentially establishes itself or a separate, literally, immune system in the central nervous system that maintains the damaging activity of the various cell types involved in MS in the brain itself. So we know this, for example, from B and T-cell lymphoid type or follicle type structures that we can find in people with secondary progressive or progressive MS and obviously the presence of oligoclonal bands, which early on suggests there is the evolution of this type of semi-autonomous immune system in the brain early on, then [INAUDIBLE] dominates later on. For example, also we find less gadolinium-enhancing lesions in the later stages of the disease. Also, indication that there’s less blood-brain barrier damage which we find very uncommonly in the earlier phases. That doesn’t mean that there is no new lesion evolution, it’s just less obvious when we look say at MRI [magnetic resonance imaging] scans of disease over time.

When we’re talking about risk factors in multiple sclerosis, we can separate those that lead to the disease as such from those that impact on the disease progression after the actual onset. There is a number of established risk factors and many of you will have heard about the recent research that highlighted something that we knew for decades but is now reiterated and with strong evidence. That a viral infection with EBV, Epstein-Barr Virus, may be a key element in the evolution of multiple sclerosis. There are however a number of other risk factors including smoking, vitamin D level or sunlight exposure, [and] obesity. So particularly adolescent obesity appears to play a significant role. Night work, passive smoking, organic solvent exposure, all these factors appear to contribute to the risk.

Now, this is all in the background of genetic makeup obviously and 1 of the key elements here is being a woman. So in females, you find that disease is 2 to 3 times, or sometimes even more, common than in men. Then there’s another element, the HLA [human leukocyte antigen] typing. So immune typing as it were that plays an important role in the modulation of the risk factors that I just mentioned. In terms of what plays a role for disease progression, there are, again, various factors. I would say the factor that we increasingly and know most about is smoking. Interestingly, there’s now evidence that smoking does contribute to disease progression, but you can also curtail that or stop that by stopping some smoking. There’s good evidence that it is not only a risk factor for developing MS but that is also a modulating factor in the disease course and stopping that will have an impact also on the overall progression.

This transcript has been edited for clarity.

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