A Study On Multiple Sclerosis Biology Essay

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It is the most common disabling neurological disease among young adults and affects around 100,000 people in the UK. MS is most often diagnosed in people between the ages of 20 and 40, and women are almost twice as likely to develop it as men. (2)

There are four main types of MS: Relapsing remitting, secondary progressive, primary progressive and progressive relapsing.

Relapsing remitting is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. (3) In between attacks the deficiencies suffered during attacks may either resolve or leave slight pathology(1) This stage is the most common in individuals with MS. Looking at the graph below the remission stages may get shorter and the degree of disability may increase.

Secondary progressive MS includes around sixty five percent of those with an initial relapsing-remitting MS, who then begin to have progressive neurologic decline between acute attacks without any definite periods of remission. (1) (5) it must be noted occasional relapses and minor remissions may appear. By studying the graph below, it can be clearly seen that there is a gradual decline but eventually the degree of disability becomes worse.

Thirdly, primary progressive is hallmarked by progression of disability from onset, with no, or only occasional and minor, remissions and improvements . (5) This describes fifteen percent of MS sufferers who never have remission after their first MS symptoms. (6)The age of onset for this subtype is later; around forty years old.

Progressive relapsing MS describes people from the start, have a gradual decline in neurological symptoms and also have attacks. This is the least common of all subtypes. (5)

Another type of MS is benign which means there has been little or no change over twenty years of the disease and the fact that the individual has a very low level of disability. (7)

MS is caused by a combination of genetic, environmental and infectious factors. No theories have been proved definitive. (1)

Beginning with genetic factors, generally MS is not said to be hereditary but there is some evidence that there is a polygenetic component. People with relatives who have MS have a greater risk of getting MS. The disease has an overall familial recurrence rate of 20% (1) Chromosome six is important in MS because a change here increases the chance of suffering MS. Chromosome six encodes the major histocompatibility complex genes which are essential in encoding cell surface presenting antigens.

In terms of environmental factors, MS is more frequent in people who live further away the equator (1). Other environmental factors include, decreased sunlight exposure - vitamin D hypothesis and smoking. (8)(9)

There is also some evidence regarding infections a person may have been exposed to in previous years before showing signs of MS (for example Epstein Barr virus (10), measles and rubella). Many pathogens have been linked as potential trigger factors of MS, but none have been substantiated. (1) (11)

In MS the immune system attacks its own myelin. T cells such as Th1 CD8 cells cannot get through the central nervous system but in MS the blood brain barrier (BBB) has been disturbed (possibly by an infection or virus) which then allows passage of T cells through the tight junctions. When the BBB is eventually restored the T cells remain inside the brain. Oligodendrocytes contain myelin associated glycoprotein, myelin oligodendrocyte protein and myelin basic protein and these are similar to viral proteins. The T cells present then are activated and attack these proteins producing demyelination and inflammation. (11)

Demyelination will firstly result in slowed axonal conduction to eventual blockage of the axons resulting in all the neurological signs mentioned in this scenario such as weakness and in coordination. (11)

It must be noted however remyelination does occur in the early parts of the disease but oligodendrocytes cannot fully repair the myelin sheath. Gradually, there is a build up of scar tissue as the attacks occur around the now destroyed axons. (12)

The other key characteristic of MS is inflammation. As described before the T cells recognize myelin as foreign and attack it which in turn triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the blood brain barrier, which in turn cause a number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins. (11)

In this scenario Alice shows classic signs of someone from suffering with MS. The criteria for diagnosis are as follows (McDonald criteria): there must be a least two episodes of the symptoms both involving different areas of the CNS. (13) In Alice s MRI scan there are white lesions which indicate areas of inflammation but it could also be useful to see previous plaques and brain atrophy. Visually evoked potential measures the electrical pathway to the cortex so MS sufferers would show abnormal and/or slow VEPs. This is a classic finding in MS. (14) (15)

Alice undergoes a lumbar puncture to see if her cerebrospinal fluid contains oligoclonal IgG bands as these are found in ninety percent of people with MS (13)(16)

Alice also presents with papillitis, a paracentral scotoma and paraesthesia. Papillitis is a specific term for a type of optic neuritis. It is inflammation of the optic disk and presents in up to fifty percent of people with MS. It is usually the earliest indicator of MS together with white lesions on the MRI. (17)(18).

She also presents with a paracentral scotoma which is a scotoma that is adjacent to the fixation point (19) Parasthesia which is a sensation of tingling or numbness of a person s skin. (20)

Now I am going to discuss the cerebellar tests performed starting with Romberg s test. Ask the patient to stand with their feet together, initially with eyes open then with them shut. There should be minimal or no sway this tests balance for the vestibular and cerebellar system (dorsal column). (21) (22) (23)

Alice has dysdiadochokinesia in her right hand. This is the inability to do rapidly alternating movements such as supinating and pronating the hand, the cause of which is a cerebellar lesion. The patient cannot switch on and off antagonising muscle groups. (24)

Alice also has a mildly unstable tandem gait. This is a test for the cerebellar and vestibular system also. Ask the patient to walk barefoot along a straight-line so that the heel of one foot comes into contact with the toes of the other foot (25)

Alice has a positive Babinski sign indicating an upper motor neuron lesion. We would see plantar extension of the toes to a blunt stimulus to the lateral side of the foot . (26)

Alice has hyperreflexia which again is a sign of upper motor neuron lesion. Finally, Alice has bladder problems which would be due to the demyelination affecting the autonomic nervous system thus affecting control.

The key factor in the management of MS is to maintain the quality of the patient s life at a high level as possible because there is no actual cure for MS. The main areas of the therapy are to reduce the symptoms after an attack, stop new attacks and overall preventing disability. The drugs used in MS have many side effects which I will discuss below.

Intravenous (IV) corticosteroids are used during the attacks, steroids such as methylprednisolone as they are thought to restore the BBB thus stop the activity of toxic cytokines that are produced by the T cells and overall reduce the strength of the immune response. Overall steroids are good for relieving short term symptoms they do not appear to be effective on long term symptoms.(27) It must be noted that also other routes of administration are just as effective as IV such as oral (28)

The drugs used in the treatment of MS are aimed to reduce the number and severity of relapses.

Natalizumab (Tysabri) is a is a humanized monoclonal antibody against the cellular adhesion molecule ?4-integrin. (29) This drug works by reducing the ability of the immune cells to attach and go through the BBB and the cell lining of the intestine. This is given once every twenty eight days via IV. This drug seems to be effective at reducing all the symptoms of the attacks and also preventing relapse itself.

Another drug used in the management of MS is beta interferon 1a (Avonex and Rebif) and beta interferon 1b (Betaferon and Extavia). (30) Interferons are proteins that are found in the body. There are three types: alpha, beta and gamma and each have important properties in order to fight against diseases and pathogens. Gamma interferon causes damage to the myelin during attacks and because it was known that beta interferon suppresses gamma interferon activity, this reduced the relapse rate by thirty percent. Other reasons why beta interferon is effective are that it also stops the passage of T cells through the BBB, overall suppresses T lymphocyte activity and increases the number of T2 (suppressor) cells to weaken the immune response. Side effects include influenza like symptoms (31)

Glatiramer acetate (Copaxone) is another drug used the management of MS. It is a synthetic compound which is homologous with MBP and is shown to reduce relapse rates by thirty percent. It is given daily under the skin via injection. It acts by binding to the inflammatory cells and block them from attacking the myelin. This drug is also effective at stimulating the body to change the inflammatory response by reducing the attacking T1 cells and increasing the stimulation of T2 suppressor cells (32). Side effects for this drug are a post-injection reaction manifested by flushing, chest tightness, heart palpitations, breathlessness, and anxiety. (33)

Mitoxantrone is an anticancer drug also used in the management of MS. It can be prescribed to certain patients on a named patient basis in the UK. This drug will slow the progression of secondary progressive MS and increases the time between relapses by disrupting DNA synthesis and repair (34) (35). A major side effect is that the drug itself can be toxic to the heart so the treatment is carefully regulated, also by using this drug there is an increased chance of developing leukemia. (36)

Drugs are very important in the management of MS however what is just as important if not more important, is a multidisciplinary team working with the patient to improve their overall quality of life. But with MS it is difficult to have a set team as MS sufferers may need help from nearly all areas of the health team (1). As the disease progresses though, the symptoms tend to get worse and lead to increasing levels of disability in the patient. It is very important that thee deficits are addressed by neurorehabilitation.