Biology 202

2006 First Web Paper

On Serendip

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. "In multiple sclerosis, the body incorrectly directs antibodies and white blood cells against proteins in the myelin sheath, which surrounds nerves in the brain and spinal cord" (1). This causes inflammation and injury to the sheath, disrupting or slowing nerve impulses and leaving areas of scarring (sclerosis). The disruption of nerve signals causes a variety of symptoms that can affect vision, sensation, cognitive abilities, and body movements (2). "Multiple sclerosis is classified according to frequency and severity of neurological symptoms, the ability of the CNS to recover, and the accumulation of damage" (6). The four classifications of MS are primary progressive MS, relapsing-remitting MS, secondary progressive MS, and relapsing-progressive MS.

The exact cause of MS is still unknown. However, it is speculated that MS is an autoimmune disease, which means that the immune system mistakenly attacks its own body, in this case, the myelin sheaths of the nerves. It is also unclear whether viruses or infectious agents play a role. In addition, other physical or emotional stressors may be a contributing factor.

The disease usually manifests itself in young adulthood; most people experience their first symptoms between ages 20 and 40. Multiple Sclerosis is approximately three times as common in women as in men. The course of the illness is enormously variable, ranging from death in less than a year, to little disability even after 50 years. "However, the majority, after an initially relapsing and remitting course, enter a phase in which there is continuous deterioration superimposed on which may be acute exacerbations of neurological deficit" (3). Exacerbations can last days, weeks, or even months.

At this time, there is no specific test for MS. Therefore, the diagnosis is primarily clinical, based on medical history, physical and neurological examination, blood tests, MRI, spinal tap, and neurological tests. However, in order to be diagnosed with MS, the patient must exhibit at least two separate sites of central nervous system damage and have a history of at least two episodes of neurological disturbance of the kind encountered in MS.

Treatments for MS vary considerably. "There is no cure for MS, but there are two types of treatments: those that modify the immune system to suppress the disease, and those that improve the symptoms of MS" (2). Examples of these types of treatments are immune modulators, steroids, cholinergic medications, antidepressants, physical therapy, speech therapy, occupational therapy, and exercise. A healthy lifestyle is encouraged, including good nutrition, adequate rest, and relaxation. "Attempts should be made to avoid fatigue, stress, temperature extremes, and illness to reduce factors that may trigger an MS attack" (4).

Due to the unknown origins of the disease and the inability to cure it, doctors are constently looking for new treament options. It is important to examine any abnormalities of function in patients with MS. One such abnormality found is the hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA axis). It is believed that the dysregulation of the HPA axis reflects a disturbance of negative feedback at the level of the hypothalmus or pituitary gland. The overacitivity of the HPA system may contribute to the pathogenisis of the disease and its normalization may be beneficial (5).

During an exacerbation, active peptides and cytokines, secreted by the immune system, exert various effects on the HPA axis, for example, increased secretion of ACTH and cortisol during acute inflammtory reactions (5). Hyperresponsiveness of the HPA axis is due to diminished corticosteroid receptor function. Chronic hypersecretion of cortisol leads to a desensitization of immune cells toward the effects of corticosteroids, making steroid medication for acute relapse less effective (5). "Recent evidence suggests that in aged rats, hypercortisolism is a crucial factor limiting the proliferation of neural stem cells in the hippocampus, and that reduction of corticosteroid levels restores normal formation of neurons even in adult mammals" (5).

It has also been found that hyperactivity of the HPA system is associated with major depression. Successful treatments with antidepressants (such as MOA inhibitors) are associated with normalization of HPA hyperactivity because they increase glucocorticoid receptor messanger ribonucleic acid in the hypothalamus. A higher number of glucocorticoid receptors improves the disturbed feedback regulation of the HPA system. Due to the ineffectiveness of corticosteroids alone, it has been found that moclobemide (an MOA inhibitor) combined with corticosteroids will normalize the dysregulation of the HPA axis that's exhibited in patients with MS.

References
1)Mayo Clinic, information about Multiple Sclerosis
2)Aetna InteliHealth, information about Multiple Sclerosis
3) McDonald, W. & Ron, M. Multiple Sclerosis: The Disease and Its Manifestations. Philosophical Transactions: Biological Sciences, Vol. 354, 1615-1622.
4)Medline Plus Medical Encyclopedia, information about Multiple Sclerosis
5) Bergh, F., Kumpfel, T., Grasser, A., Rupprecht, R., Holsboer, F., & Trenkwalder, C. Combined Treatment with Corticosteroids and Moclobemide Favors Normalization of Hypothalamo-Pituitary-Adrenal Axis Dysregulation in Relapsing-Remitting Multiple Sclerosis: A Randomized, Double Blind Trial. Journal of Clinical Endocrinology and Metabolism, Vol. 86, 1610-1615.
6)Neurology Channel, information about Multiple Sclerosis


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