What is MS ? 

MS is an inflammatory disorder characterised by demyelinating changes affecting multiple white matter tracts within the CNS(many started to believe that the grey matter is also affected from the beginning), with usual onset in young adults; leading to cumulative deficits over time. Currently, the cumulative changes are inevitable and are not yet controlled by the available medications. A lot of research work is on going, and the future for MS sufferers will be much better and more promising.

Is this definition good enough to reflect the real MS as we know it?.

The simplest answer to this question is “NO”. MS is a combination of both inflammatory and degenerative changes likely to happen at the same time, or possibly at very short intervals between the two.

I think we need to pay more attention to this process, as exploring more about it may allow us to understand more about the process of developing MS, and the way to approach its management.

Let us think about it in a practical way. Inflammation is charcterised by four important features:

1. Redness.
2. Tenderness.
3. pain.
4. swelling.

As the lesions are located inside the head or neck, we can’t see the colour of inflammation but in the future we may be able to do so. Currently we can probably see inflammation by the amount of Gadolinium enhancement in or around the demyelinating lesions. what that means?.

Patients who go for MRI test will have Gadolinium injected in the vein before imaging {Because of its paramagnetic properties, solutions of chelated organic gadolinium complexes are used as intravenously administered Gadolinium-based MRI contrast agents in medical magnetic resonance imaging. However, in a small minority of patients with renal failure, at least four such agents have been associated with development of the rare nodular inflammatory disease nephrogenic systemic fibrosis. This is thought to be due to the gadolinium ion itself, since gadolinium(III) carrier molecules associated with the disease differ}, and because of that a kidney function should be done prior to imaging to make sure that the kidney function is fine for this test to be done without leaving any damage behind. It is probably worth mentioning that Gadolinium damage is very rare, and if the kidney function is fine, no damage of any significance would be expected to happen. 

Also, and for the same reason, we can’t be able to appreciate the tenderness of the demyelinating lesion or lesions.

The other point I thought to mention is that brain tissue is painless in most of its structure apart for the meninges, capsules and blood vessel. Lesions are unlikely to cause pain unless they are located in places exerting pressure on those painful structures.

We are left with the “swelling” which is an important factor in the demyelinating process. Swelling can be appreciated on the MRI images by the intensity and the size of the demyalinating lesions which are seen on T2 waited and diffusion images.

Swelling is important in the process of MS immediate progression because it can cause damage to the nerve fibers (axons) via the pressure effect which reduces or stops (depending on the intensity of the swelling) the blood supply to the nerve fiber and that leads to the death of the nerve fiber(degeneration) and for the time being, the dead axons can never recover (regenerate again). Axonal degeneration means “permanent damage”. Hence, it is cumulative.

Therefore, to define MS as inflammatory condition is not enough and it is not fair. New patients with MS usually present themselves to doctors with a first relapse and this is in principle an inflammatory process charcterised by those 4 features as mentioned above. The damage usually starts at about 5 minutes following the acute inflammation, and this means broadly, degeneration started to happen just few minutes after the start of inflammation . A combination of inflammation and degeneration usually takes place at the first presentation of MS to the doctor.  I will come back to this matter later when talking about treatment of MS and the MS complications.

How changes happen in MS?

MS is an autoimmune reaction characterised by the production of auto-antibodies against myelin producing cells in the brain and spinal cord called oligodendrocytes. These autoantibodies are a type of immune reaction resulted from a stimulus (antigen) which for the time being we don’t know what, but we can only guess. I do believe very strongly in the viral theory. I will come back to this subject later when talking about causes of MS.

There are four types of immune reaction it is probably good to mention them here:

1. Anaphylactic (allergic) e.g food allergy.
2. Cytotoxic e.g blood incompatibility reaction.
3. Immune complex i.e Rheumatoid arthritis.
4. Cell mediated (delayed) e.g MS.

Some scientists add another type, and made the immune reactions as five not four. This is called “autoimmune” reaction, and they put Myasthenia gravis as an example to this. I think this type of immune reaction comes under class 4(cell mediated) reaction. Myasthenia gravis is T-cell mediated autoimmune reaction only slightly differ from MS.

Therefor, MS is – as I understand it – a combination of T cell and B cell reaction. It is almost certain that MS is predominantly T cell  reaction, and this is very important.

Let us have a quick visit to learn what happens to the best of my knowledge:

At one time in the patient’s life, an agent ( I believe a virus) has attacked that patient and as it was very selective, it attacked the myelin producing cells in particular. The agent managed to stimulate the T-cells which in turn stimulated B cells, and B cells managed to produce antibodies to kill that agent. Because, the cellular reaction is a late response, B cells can only produce a delayed reaction as a result. Hence, this gives enough time for the attacking virus to leave the body before it is destroyed by the specific anti-antibodies.

Cellular immunity has a long lasting memory,  and antibodies can be produced at any time – likely for the life span of the affected person – responding to any appropriate stimulus. Most of the known stimuli are in the form of chemical stimulants such as interleukins, cytokines, gamma-ferons, and tumour necrosis factor. I am sure many more stimulants are not discovered yet, and their discovery in the future will give many more therapeutic choices.

The first attack produces specific antibodies, and these antibodies are self-produced, hence called auto-antibodies. The production of these antibodies is stimulated by many natural factors leading in principle to excessive stress on the body such as infections, surgery, lack of sleep, depression, excessive radiotherapy, etc.

The auto-antibodies will then attack their producer (oligodendrocytes) and that will produce less myelin sheath, and some of those antibodies would have attacked the produced myelin sheath leading to its damage; a process called demyelination.

Auto-antibodies remain alive and remain idle (remitting status) to be stimulated to get angry and produce more antibodies to destroy more myelin sheath or delays its production (relapsing  status).

These chemicals are so important in the development of relapses in MS and they are important in the management (will come back to them later).