What is MS?
MS is a disease of the central nervous system (CNS). The CNS is the term used to describe the brain and spinal cord. MS is described as an inflammatory demyelinating condition. Taking the inflammatory part first, inflammation can best be thought of by picturing how angry a wound gets when it becomes infected. It may help to recall a cut or abrasion which has become infected. Typically, the wound gets hot, red, swollen and painful. Gaelen, in very early medical writings, first described the findings in inflammation as rubor et calor, tumor et dolor. This means redness and heat, swelling and pain. He added et functio laesa which translates as 'and loss of function'. So the inflamed part stops working as well. These are the typical features of inflammation. At a microscopic level, the immune system sends white cells to the area. These cells secrete messenger chemicals, which cause the inflammatory reaction, and they dispose of bacteria, debris and foreign substances in the wound.
Demyelination refers to the myelin sheath around nerves. Nerve cells in the CNS have many branches, which reach out and travel to other nerve cells, so that they can communicate by transmitting electrical impulses. These branches or axons are like telephone wires connecting phones so that they can 'talk' to each other. They are coated with a form of electrical insulating material called myelin. Myelin is essentially the fatty coating around the axons which results from specialised cells (oligodendrocytes) wrapping themselves around and around the axon, like continuous layers of an onion. This coating is fatty because the membrane or outer coating of every cell is made up largely of fat, so when the cell wraps itself around and around the axon, the multiple layers form a fatty sheath.
The type of fat making up this membrane, and thus how it functions, depends on the type of fats we eat. It is important to recognise as well that the signals which pass down the axons are not really electrical currents, but appear to be because of the rapid movement in and out of the cells of charged particles called ions. These are the minerals we are very familiar with like sodium, potassium, calcium, magnesium and so on, and again, these largely come from the diet. So diet is crucial to nerve conduction. Demyelination occurs when some of this myelin is broken down; inflammatory demyelination means that the myelin is broken down as a consequence of inflammation of the area.
The typical sequence of events then, is that inflammation of a portion of the myelin sheath of a nerve in the CNS is followed by demyelination. This forms the so-called 'lesion' of MS. These lesions were often in the past called plaques, but this is a bit of a misnomer as it implies that something is coating the nerve. In these inflammatory lesions, white cells of the immune system gain access to the myelin sheath, which they usually can't do, because of what is called the 'blood-brain barrier'. Further white cells are probably attracted by some of the chemical messengers released by these initial white cells. The demyelination is followed by some repair and scarring, as usually happens after an episode of inflammation. The functional result is that nerve impulses don't travel along the axon as well as they did before it was injured.
What the person with MS experiences depends on what the nerve connects to. If it is a nerve axon in the spinal cord bringing sensory messages up from the legs, then the person might notice tingling or numbness. If it is carrying motor messages down to the leg muscles, there may be some weakness. If they are nerves inside the brain responsible for say, the sense of balance, it may be impossible to walk without tipping over to one side. Because there is some swelling of the surrounding nervous tissue associated with this process of inflammation, nerve transmission through these nearby axons will also be affected. As the swelling subsides, these nerve cells which aren't seriously injured, but are not functioning because of inflammation and swelling, start to work again. So there is almost always some recovery for this reason alone. Also, some limited repair of damaged nerve cells takes place, with some remyelination, particularly early in the disease, so the symptoms further settle to some degree. There is growing evidence now that remyelination occurs throughout the disease and is considerably more prominent than we have realized to date.1
Thus the area of numbness or tingling is likely to get smaller and the weakness is likely to improve over time, as the lesion heals and scars, and the nerves that are not actually injured but are not working well due to swelling, recover. Recovery though is often incomplete, and people are left with residual symptoms, although less severe than when the attack was at its peak, in the same part of the body. These residual symptoms typically wax and wane depending on numerous factors. Most important of these for most people with MS is the temperature. Nerves conduct less well the warmer they get. So heat tends to make these residual symptoms worse for most people, although for some cold is more of a problem. But dietary factors like the minerals in the diet are also important for day to day nerve conduction. An important point here is that although heat makes the nerves conduct more slowly and the symptoms worse, it is not actually damaging the nerves. So exercising is fine even if it makes symptoms temporarily worse.
Gradually, as more and more of these lesions occur in the CNS, more and more pathways are knocked out. Hence the person notices gradual decline in function. A lot of these lesions occur in 'silent' parts of the brain and so are not noticed. The ones we really notice occur in the spinal cord or in the nerves leading to the eye. Virtually all of these nerve fibres are essential for things like sensation, power, balance, vision and so on. Even a small lesion here is therefore usually noticed. It is a bit like the fact that we can tolerate a few problems in particular programs on a computer (the brain) without noticing too much, but if the cable (spinal cord) connecting to the monitor gets damaged we lose a lot.
A lot of research is now being done on how the CNS attempts to repair these lesions. The nervous system has an amazing capacity not only to regenerate so that impulses can now 'detour' around the damaged lesion, but also in the brain changes occur which involve recruitment of new nerve cells and pathways to compensate for what is missing.2 When there are only a few lesions, the CNS is extremely good at this regeneration and compensation, even if there isn't much remyelination. However, if the process continues, these compensatory mechanisms get overwhelmed and progressive disability occurs. Hence the focus on stabilising the disease early and preventing further damage after initial diagnosis.
- Patani R, Balaratnam M, Vora A, et al. Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathol Appl Neurobiol 2007
- Kerschensteiner M, Bareyre FM, Buddeberg BS, et al. Remodeling of axonal connections contributes to recovery in an animal model of multiple sclerosis. J Exp Med 2004; 200:1027-1038