MULTIPLE SCLEROSIS
The symptoms appearing as a result of Multiple sclerosis are believed to be a result of blockage in the conduction as a result of defects in the synaptic junctions of the nerves, the defects could be demyelination and inflammation of the nerves (Smith and MacDonald, 1999). There is focal demyelination of the nerves, where the myelin sheath is damages but the axonal continuity remains undisturbed. The difference between Wallerian degeneration and Multiple sclerosis lies in the fact that in the former one there is degeneration of the axon also. Other features that can be observed in case of multiple sclerosis are significant loss of oligodendrocytes and very massive and rapid division of fibrous astrocytes (MCDONALD, 1974). Demyelinated nerve fibers pose great abnormalities in terms of conduction of the impulses. In nerve fibers where the demyelination is moderate, there is some decrease in the conduction velocity. Whereas in fibers where the blockage is severe, there can be total in conduction block. Myelin is highly resistive and low in terms of capacitance in case of demyelinated fibers. Thus when an impulse reaches the demyelinated point of the nerve fiber the density of current is reduced significantly due to the capacitance and the resistivity. Therefore, it either takes a longer duration for the demyelinated nerve to reach the threshold and hence the velocity of the conduction decreases or the nerve fiber does not reach the threshold at all, leading to no conduction at all, or in other words, the conduction is blocked (Waxman, 2001). The disease can be both genetic and due to environmental factors. Recently, studies that have been done to study the genetic influence of the disease reveals that there are some new alleles which are susceptible to the disease in particular, other than the HLA complex, which is a complex related with the immune factors. The environmental factor alone cannot be credited for triggering the disease, but the autoimmune mechanism can be well supported. The myelin antigen specific CD4- T cells become active in the compartments of the peripheral immune system, ultimately they cross the so called blood- brain barrier successfully and thus are able to cause the disease (Korn, 2008). The sympyoms of the disease could be many. But the most commonly found, and the most troublesome symptom that the patients complaint of, is fatigue. Around 40% of patients have admitted that this is the only symptom that they suffer from and this what makes their life complicated. The occurrence of fatigue outweighs all the other symptoms of the disease like, spasticity, weakness, bladder or bowel problems. No study has ever been successful to prove any link between fatigue and disability occurring as a result of the disease, any link with the gender or any effect of the clinical subtype could never be established. However there are evidences in the form of study data that prove the link of fatigue with depression and the quality of the patient’s life in the multiple sclerosis disease patients. Studies which undertook the imaging techniques using positron emission tomography indicates that the fatigue has some association with the hypometabolism of some specific areas of the brain, which includes the frontal and the subcortical areas. The impact of the symptom is so high on the lives of the patients that it calls for some interventional measures. Some efforts like exercising, and other strategies aimed at conserving energy do bring about some beneficial effects, but use of medicines is more effective. Medicines like amantadine, pemoline and modafinil are currently being used to manage the fatigue in the patients of multiple sclerosis (Bakshi, 2003). In recent studies using Positive emission tomography, in the relapsing and the progressive forms show reduced perfusion of the normal appearing white aater, hence supporting the previous claim. The decreased perfusion could be caused as a result of large scale dysfunction of the astrocytes (De Keyser et al., 2008). Bowel dysfunction is another important manifestation in the patients of multiple sclerosis. Both constipation and fecal incontinence may exist simultaneously in a single patient. This is a form of psychosocial disability in the patients of Multiple sclerosis (Weisel et al., 2001). Spasticity is another troublesome feature of the disease that the patients have to bear. It was shown in studies that spasticity impairs the quality of the patient to a great extent. Also the use of intrathecal baclofen over general oral drug users for multiple sclerosis are at a better position in terms of fewer spastic attacks (Rizzo et al., 2004).
Now coming to the current and future treatments of the disease. in a study the researchers wanted to prove the efficacy of interferon beta in the treatment or management of the multiple sclerosis. The medication was given to those patients who had the first ever episode of symptoms suggestive of multiple sclerosis. These patients are yet to develop a clinically definitive disease form. The results were positive, they concluded that administration of interferon beta 1a in the earlier stages can greatly affect the prognosis of the disease. the MRI results and the clinical manifestations were positive and quite reassuring (Comi et al., 2001). Studies showed that the administration of intravenous cyclophosphamide along with adrenocorticotrophic hormone for a period of two to three weeks can help in delaying the progress of the disease. In a similar study, the researchers wanted to prove the efficacy of pulse cyclophosphamide therapy in delaying the progress and to their delight, the researchers obtained positive result (Weiner et al., 1993). In another study which was conducted to determine the efficiency of azathioprine, consisted of a meta analysis with randomized controlled trials. The results showed freedom from relapses foe up to three years, with the intake of azathioprine (Yudkin et al., 1991). Another such drug that was studied by experimentation was oral simvastatin 80 mg, the study was conducted on 30 patients with remitting and relapsing form of the disease. the results concluded that there is a possibility that oral simvastatin can reduce the neurological symptoms occurring as a result of the disease (Vollmer et al., 2004).
References
Bakshi, R. (2003). Fatigue associated with multiple sclerosis: diagnosis, impact and management.Multiple Sclerosis, 9(3), pp.219-227.
Comi, G., Filippi, M., Barkhof, F., Durelli, L., Edan, G., Fernández, O., Hartung, H., Seeldrayers, P., Sørensen, P., Rovaris, M., Martinelli, V. and Hommes, O. (2001). Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. The Lancet, 357(9268), pp.1576-1582.
De Keyser, J., Steen, C., Mostert, J. and Koch, M. (2008). Hypoperfusion of the cerebral white matter in multiple sclerosis: possible mechanisms and pathophysiological significance. Journal of Cerebral Blood Flow & Metabolism, 28, pp.1645-1651.
Korn, T. (2008). Pathophysiology of multiple sclerosis. J Neurol, 255(S6), pp.2-6.
MCDONALD, W. (1974). PATHOPHYSIOLOGY IN MULTIPLE SCLEROSIS. Brain, 97(1), pp.179-196.
Rizzo, M., Hadjimichael, O., Preiningerova, J. and Vollmer, T. (2004). Prevalence and treatment of spasticity reported by multiple sclerosis patients. Multiple Sclerosis, 10(5), pp.589-595.
Smith, K. and McDonald, W. (1999). The pathophysiology of multiple sclerosis the mechanisms underlying the production of symptoms and the natural history of the disease. Philosophical Transactions of the Royal Society B: Biological Sciences, 354(1390), pp.1649-1673.
Vollmer, T., Key, L., Durkalski, V., Tyor, W., Corboy, J., Markovic-Plese, S., Preiningerova, J., Rizzo, M. and Singh, I. (2004). Oral simvastatin treatment in relapsing-remitting multiple sclerosis. The Lancet, 363(9421), pp.1607-1608.
Waxman, S. (2001). Form and function in the brain and spinal cord. Cambridge, Mass.: MIT Press.
Weiner, H., Mackin, G., Orav, E., Hafler, D., Dawson, D., LaPierre, Y., Herndon, R., Lehrich, J., Hauser, S., Turel, A., Fisher, M., Birnbaum, G., McArthur, J., Butler, R., Moore, M., Sigsbee, B. and Safran, A. (1993). Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: Final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.Neurology, 43(5), pp.910-910.
Wiesel, P., Norton, C., Glickman, S. and Kamm, M. (2001). Pathophysiology and management of bowel dysfunction in multiple sclerosis. European Journal of Gastroenterology & Hepatology, 13(4), pp.441-448.
Yudkin, P., Ellison, G., Ghezzi, A., Goodkin, D., Hughes, R., McPherson, K., Mertin, J. and Milanese, C. (1991). Overview of azathioprine treatment in multiple sclerosis. The Lancet, 338(8774), pp.1051-1055.
