What is MS?

MS is an organ-specific autoimmune disease.

Organ-specific means that the MS as a disease is limited to one organ, the central nervous system (CNS). The CNS constitutes the brain, spinal cord and optic nerves.

Autoimmune simply means that the immune system, which primary role is to fight infections and cancers, goes awry and attacks its self. The self in the case of MS is the CNS. Please be aware that every organ in the body has it own specific autoimmune disease; for example:

    1. Joints = rheumatoid arthritis
    2. Skin = psoriasis
    3. Insulin producing cells of the pancreas = type 1 diabetes
    4. Intestines = inflammatory bowel disease
    5. Kidneys = autoimmune nephritis (interstitial or glomerular nephritis)

Cause of MS: At present the exact cause of MS is not known.

MS is a complex disease that occurs due to the interaction of the environment with inherited or genetic factors.

Some of the main environmental factors are:

    1. Low vitamin D levels or a lack of sunshine
    2. Smoking
    3. Epstein-Barr virus (EBV), the virus that causes infectious mononucleosis or glandular fever
    4. Obesity, particularly in adolescence

What we don't know is how these genetic and environmental factors interact to cause MS. Although there are many genetic variants that predispose one to getting MS it is still only a minority of people who have these variants that get the disease. Similarly, only a minority of people who are exposed to the environmental risk factors get the disease.

Mechanisms that underlie the common manifestations of MS

MS is characterised by inflammatory lesions that come and go.

Relapses

The clinical manifestations of MS depend on where these inflammatory lesions occur. If for example the lesion involves the (1) the optic nerve it will cause reduced, or loss of, vision, (2) the brain stem double vision, vertigo or unsteadiness of gait, (3) the spinal cord loss of feeling, limb weakness or bladder and bowel problems.

A new MS lesion in a site that is eloquent will cause symptoms and neurological signs that need to last for at least a day to be called an attack or relapse. If the lesion occurs in a site not associated with overt symptoms this is often referred to as a sub-clinical, or asymptomatic, relapse. Sub-clinical relapses can be detected using magnetic resonance imaging (MRI). It is said that for every clinical attack there are 10 or more sub-clinical attacks (new MRI lesions).

At the site of MS lesions damage occurs. The inflammation strips the myelin covering the nerve processes and may cut through axons. Axons are the nerve processes that transmit electrical impulses or signals. When the axons are stripped of their myelin sheath, and/or are cut, they can't transmit electrical signals and this causes loss of function, which manifests with specific symptoms.

Intermittent symptoms

Surviving axons that pass through the lesion are able to recover function, by synthesising and distributing ion channels across the demyelinated segment or by being remyelinated. Both these process are not perfect. For example, the new sodium channels may not function normally and fire spontaneously. The spontaneous firing of axons may cause positive symptoms, for example pins and needles, pain or spasms. The new myelin is typically thinner and shorter than normal and is temperature, fatigue and stretch sensitive.

Stretch: Lhermitte's sign occurs when pwMS have a lesion in their spinal cord that causes electric shock-like sensations when ever the bend, or flex, their necks which stretches their spinal cord.

Temperature: PwMS may get recurrent symptoms when their body temperature rises, for example when they have a fever, perform exercise or take a hot bath, which then disappear when the fever resolves or they cool down. The temperature-sensitivity is often referred to as Uhtoff's phenomenon.

Fatigue: Many pwMS notice their symptoms get worse with physical and/or mental fatigue. For example, the may notice dragging of a leg, or dropping of their foot, after 20-30 minutes of walking. This is because transmission in the functioning nerves, which have been previously damages, begin to fail. We think this failure may be related to lack of energy and/or temperature changes that occur with exercise.

Worsening MS (also called progressive MS)

In a MS lesion the axons, or nerve processes, above and below the lesion may die off. The surviving axons may sprout to take-over the function of the axons below the lesion. This puts an unnecessary strain on the surviving axons, which makes them vulnerable to die off in the future. The reduction in the number of nerves in a neuronal system reduces the neurological reserve of that system, which makes it more vulnerable to future attacks, i.e. the ability to recover from future attacks is reduced, and it makes the neuronal pathway susceptible to delayed degeneration and premature ageing. Clearly if pwMS are not treated and focal inflammatory lesions continue to come and go this in itself will cause worsening of disease. The difficulty with MS is that if enough damage is allowed to accrue even switching-off new inflammatory lesions may not prevent or stop the so called delayed neurodegeneration. This is why one of the primary treatment principles in MS is early treatment to prevent damage from occurring in the first place. What we have also discovered is the neuronal systems with the longest nerve fibres, in particular the bladder and legs, are much more susceptible to damage. We think is simply due to the longest pathways being more likely to be hit by multiple MS lesions. his occurs simply by chance

Ageing and MS

A fact of life is that as we get older our nervous systems degenerate. If we live long enough we will all develop age-related neurological problems, these include unsteadiness of gait, loss of memory, reduced vision, loss of hearing and poor coordination to highlight a few problems.

What protects pwMS from becoming disabled and developing age-related neurodegeneration are brain and cognitive reserve. Brain reserve is simply the size of your brain or the number of nerve cells you have. Cognitive reserve in comparison relates to how well these nerves function and is associated with your level of education and how well you enrich your lives by using your brains. From about 35 years of age our brains start to shrink. In MS this brain shrinkage is in general much greater than normal. The reduction in brain and cognitive reserve that occurs in MS almost certainly primes the nervous system to age earlier in pwMS. This is one of the reasons why pwMS continue too worsen, or develop worsening disability later on the course of their disease. This insight is one of the main reasons why we promote early effective treatment of MS to protect, and maintain, brain and cognitive reserve.