Multiple Sclerosis and Physiology of the System Affected - Term Paper Example

running head: Multiple Sclerosis Multiple Sclerosis Submitted to [Pick the Contents Introduction 3 2.Physiology of the System Affected 4 3.Pathophysiology of Multiple Sclerosis 5 3.1Causes of MS 6 3.1.1 Environmental Causes 6 3.1.2Infectious Causes 7 3.1.3Genetics 7 3.2Symptoms and Risk Factors 7 4.Diagnosis & Treatment 9 4.1Clinical manifestations and Lab tests 9 4.1.1Physical Examination Findings (include vital organs) 9 4.1.2Specialized Test Results & Laboratory Blood Test Results 9 4.1.3Regulation of Homeostasis 11 5.Pharmacological Treatment of Multiple Sclerosis 12 6.Prognosis & Complications 13 References 15 Hollsberg, P. et al. (2005). Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients, associations with disease activity, Acta Nuerologica Scandinavica, 112(6), 395-402. 15 Appendix 17 1. Introduction Mrs. Anderson is a 35 years old patient who has been admitted for reported tremors in arms, lack of visual accuracy and bladder control, and feeling of numbness in her facial muscles. Fatigue in later part of the day, problem with balancing while walking and continuous weakness were few other symptoms. Since these symptoms are mainly representing Multiple Sclerosis cumulatively despite having similarity with other disorders, therefore multiple tests including MRI, blood tests and evoked potentials were performed to identify if patient is undergoing any damage to the nervous system. Patient has also complained of having emotional outbursts and episodes of anxiety and depression. She was been diagnosed earlier with the possibility of MS but due to first incident, no concrete treatment was suggested. Any other kind of pain was not reported. Multiple Sclerosis (MS) is an autoimmune disorder which makes body attack itself. As a result of agents triggering this disease, the layer of myelin covering brain cells mainly axons of brain and spinal cord gets damaged and experience degeneration (Corthanls, 2011). Since patient suffers direct damage to the nervous system due to inflammation therefore they may undergo disability at various stages. Although there is no proper medication to cure it however pace of the disease and its related effects can be reduced with the help of proper treatment. Women are more likely to suffer from this cellular disorder then men (Taylor, 2011). Its symptoms are likely to be visible in a young age and it can be caused by various external factors and hereditary conditions. Loss of myelin makes patient incapable of performing regular life functions since connectivity between axons is damaged. Like variations in the causes and symptoms, its onsets can also appear in the form of a relapse or continuous progression. It is important to note that every patient has a different set of history. Therefore, patient’s individual characteristics, family history, symptoms shown and person’s responses to the disease itself may vary greatly. This lack of predictability and higher uncertainty has lead to absence of a specific cure that can prove to be effective. 2. Physiology of the System Affected Multiple Sclerosis is a disorder taking place in a nervous system due to autoimmune mechanism. In a normal state, human nervous system is an interlinked network covered with myelin reaching every part of body and conducting brain impulses to them (See Fig A). In a normal scenario, the immune system is expected to maintain equilibrium between elements capable of triggering inflammation in nervous system and stasis maintenance by regulator cells. For doing so, it activates effectors cells such as Th1 and Th2 (Kasper, Haque & Haque, 2007; Venken, Hellings, Libalau & Stinissen, 2010). In diseases caused by autoimmune mechanism like multiple sclerosis, equilibrium becomes upset when processes responsible for maintaining homeostatic condition begins to dysfunction. Such inflammation can be caused by excessively active or stimulated effectors cells. This hyperactivation can result in hyper-intense pro-inflammatory condition (Kasper et al., 2007). Similar condition can be caused byr insufficient performance of regulatory cells causing lack of control on stimulation of effector cells and immune tolerance. According to Haegert (2011), “T-cell homeostasis is tightly regulated and includes a balance between thymic output, which decreases exponentially with increasing age, delivery of death and survival signals, naïve T-cell differentiation into memory cells, and peripheral T-cell proliferation. This T-cell proliferation is an important contributor to T-cell homeostasis in healthy individuals, as it helps maintain T-cell numbers in the face of thymic involution (para. 6)”. It is important to note that several processes are interlinked while maintaining control over autoimmune diseases including MS, hence preventing inflammation and development of autoimmune disorders. These processes involve T cell inactivity or T cell energy [3, 9], T cell depletion by apoptosis [8, 26] and active immune suppression [18, 27] (Kasper et al., 2007). Failure in one of these systems or their collaboration can result in autoimmune disorders or inflammation. Hence, while curing diseases like multiple sclerosis; therapeutic interventions are intended to restore equilibrium and collaboration between different mechanisms and maintain the immune homeostasis again. 3. Pathophysiology of Multiple Sclerosis Multiple Sclerosis can be caused by three major factors that can have a permanent effect in central nervous system (Jefferies, 2006). Where its related outcomes are known, factors causing it are still difficult to identify. Current research shows that genetics play a vital role in occurrence of this disease although there are other researches that undermine the severity of its effect (National Centre for Biotechnology Information, 2011; Taylor, 2011). Furthermore, there are various environmental factors and lifestyle changes that may trigger this disease. In most of the cases, it targets myelin basic protein. It usually appears in the form of lesions that attack areas like cerebellum, brain stem, spinal cord and optic nerve (Compston & Coles, 2001). It is mainly known for attacking CNS and peripheral parts become the target in rare cases. As a result of reduction in myelin, the surface supporting connection between axons is compromised therefore neural transmission is disrupted. Although, as a result of this diseases, defense mechanism called remyelination takes place however it is usually effective in early phases and therefore, repeated attacks gain dominance over this defense mechanism. 3.1 Causes of MS 3.1.1 Environmental Causes Where it has been established that MS is a result of immunity disorder against lipid-protein layer (myelin) in central nervous system which includes brain, spinal cord, and optic nerves, the fundamental cause of it remains unknown (Compston & Coles, 2007). However, environmental factors are considered as a basic agent triggering MS (Taylor, 2011). According to Jefferies (2006), “multiple sclerosis is seen with greater frequency as the distance from the equator increases. It is twice as common in women as in men”. Hence, geographic and demographic conditions have a direct relevance to this factor (Soilu-Hanninen et al., 2008). There are evidences present that explain relevance of vitamin D deficiency to autoimmune mechanism. Exposure to toxins, malnutrition, hormonal imbalance and tobacco intake as a result of smoking are also considered as a fundamental risk resulting in MS. According to Taylor (2011), “There is now ample evidence for a profound effect of the environment on MS causality, with at least four and probably more factors directly contributing, with the reported effect sizes significantly greater than any identified genetic factor. 1. latitude, sunlight exposure (UVR), and vitamin D (odds ratio [OR] ≈ 20);1 2. prior Epstein–Barr Virus (EBV) infection timing and adaptive immune response to EBV (OR = 12.5);2 3. cigarette smoking (OR = 1.4);2 4. the hygiene hypothesis (OR ≈ 3).3 9 (p. 1171)” 3.1.2 Infectious Causes MS can be caused by infectious agents as well. Various viruses are known for causing demyelination therefore there is a possibly that similar virus can trigger multiple sclerosis as well. Drastic changes in demography and geography make individuals more susceptible to risk of having MS. Several viruses like human herpes and Epstien-Barr are known as risk factors for MS (Hollsberg et al., 2005). 3.1.3 Genetics Although Multiple Sclerosis is not a genetic disorder however certain genetic mutations and variations can be considered as its cause. Taylor (2011) argues that environmental factors have more effect on occurrence and recurrence of MS. He restates that genetic risks are higher in monozygotic twins instead of other cases and this ratio of concordance is about 25% of the total population. However, effects of inheritance cannot be denied. In addition to that, there are several genes that are specifically linked with MS. 3.2 Symptoms and Risk Factors Severity of the disease acts as the major factor affecting symptoms and signs. Same goes for the duration of the occurrence. Factors like fever and sun exposure and other activities that are connected with increase in temperature are susceptible of increasing risks for occurrence or appearance of the symptoms. On the other end, relapse of this disorder is also common in patients of MS. Since this disease can attack multiple or different sites in CNS therefore it is likely that symptoms may vary from patient to patient dependent on the targeted site. In case where muscular nervous system is under attack, signs like balance loss, spasms, abnormal and irregular sensations, difficulty in movement o limbs, problem in movement and making small gestures with body parts, coordination difficulties, tremors in limbs and continuous weakness are the possible causes as illustrated in Figure B (NCBI, 2011). Bowel and bladder symptoms may include constipation, diarrhea, problem related to urination, frequent and strong urge to urinate and lack of control over urination. In patients’ with disorders affecting eyes, patients are likely to experience double vision, burning sensation, tremors in eyelids, subsequent loss of sight and continuous discomforting feeling in the eyes. In this case, Mrs. Anderson is suffering from optic neuritis. Patients of MS are also likely to experience pain in muscles of face, spasms and inflammatory feelings in limbs and during movement as well. Where MS attacks nervous system near and in brain, poor cognitive and physical ability is likely to occur. Subsequent memory loss, depression, anxiety, hearing loss, lack of sexual drive and trouble in performing regular functions like talking, chewing and swallowing are also some of the major symptoms of MS (NCBI, 2011). Out of these, Mrs. Anderson is facing depression followed by attacks of hyper anxiety. Symptoms of MS are quite similar to other disorders of nervous system and other body parts as well. Therefore, it is important to look for specific signs while assessing occurrence of MS. While doing so, it is important to perform analysis of reduced activity in two different body parts while patient has experienced more than two incidents of MS with or without gap. Through neurological exam, span of irregularity can be identified. Common indications can be decreased mobility, lack of movement, poor pupil responses and changes in visual strength, lack of sensation, rapid eye movement etc (NCBI, 2011). 4. Diagnosis & Treatment While examining MS, it is important to perform multiple tests in order to distinguish between other disorders of nervous system. Furthermore, due to multiple location and unknown causative agents, it is difficult to identify it through a single test. In addition to that, relapse is another criterion for examination of MS as single attacks of similar symptoms may not help in diagnosing the disease. Furthermore, patients with relapsing-remitting MS history are likely to have secondary-progressive MS whereas rate of progression may vary accordingly (Brodkey et al. 2011). 4.1 Clinical manifestations and Lab tests There are three major tools that assist in diagnosis of MS due to their specific nature and sensitivity towards diagnosis of this nervous system’s disorder. These tools include magnetic resonance imaging (MRI), evoked potentials; and cerebrospinal fluid (CSF) examination for the presence of oligoclonal bands (OCBs) (Palace, 2001). In case of Mrs. Anderson, she was recommended to undergo MRI for further examination along with blood tests. 4.1.1 Physical Examination Findings (include vital organs) Physical examination of Mrs. Anderson indicated internuclear opgthaumoplegia due to which she was having problem with eye movement and was also experiencing difficulty in visual accuracy. 4.1.2 Specialized Test Results & Laboratory Blood Test Results According to Palace (2001), almost 95% of the MS patients show T2 weighted brain which makes it fit the clinical criteria of MS. Visible pathological plaques or lesions on the white area of nervous system demonstrate occurrence of MS. It is also important to note that age related and vascular causes in MRI can differ from those of MS greatly. Symptoms like Periventricular distribution, Ovoid lesions long axis 90° to plane of lateral ventricles/point to cortex, Subcortical lesions involve U fibres, Infratentorial lesions (brainstem/cerebellum), Corpus callosum lesions typical and Spinal cord lesions common, can indicate age related developments from that of MS (Palace, 2001). Other specialized tools include evoked potentials which involve placements of small electrodes on patient’s head. Although amplitude of nerve impulse of visual, auditory, sensory posterior column and motor systems, from cortex to stimulus’s site is used for identification purposes however out of these, visual nerve impulse give more accurate indicate in most of MS patients. Delays in responsiveness indicate that demyelination is or has taken place. There are various types of evoked potentials including visual evoked potential, somatosensory evoked potentials, brain stream auditory evoked potentials and magnetic evoked potentials (Palace, 2001). Monitoring of brain waves illustrate if overall cognition process is taking longer than normal time. Application of electrodes on the scalp makes primary motor cortex region activated. Current produced in the cerebral cortex leads to activation of primary motor neurons. Periodic readings help in assessing the responsiveness of brain to the current produced. As compared to MRI, evoked potentials is considered to be less specific and sensitive in nature. Another tool for examination includes Lumbar puncture. It is also known as spinal tap. During this procedure, lumbar puncture, a needle is inserted in the area of spinal cord in order to collect samples of cerebrospinal fluid. Presence of antibodies will indicate if there is any resistance from immune system to any disorder. This approach is adopted when other two methods remain inconclusive (Palace, 2001). In case of Mrs. Anderson, MRI was performed in the preliminary phase of the diagnosis after her physical examination. It was found that her MRI has demonstrated multiple hypointense white lesions in the corpus callosum which are an indicator of MS if coupled with other physical symptoms. These lesions can be distinguished from any other age related factor. The patient matches McDonald Criteria for MS as she has undergone two attacks and there is a clinical evidence of one lesion showing cerebral plaque (Polman et al., 2011). Hypointense T1-weighted imagery supported this notion. In order to support her MRI results, blood tests were also taken that showed various indications. She was asked to take antinuclear antibody (ANA) test that was intended to determine amount and behavior of antibodies. A complete blood count along with rheumatoid factor was analyzed to identify possible presence of excessive white blood cells in the serum. In patient’s blood, low levels of Creatine, Uric acid were found. Her reports from first attack and subsequent remission were also compared to analyze the changes. Her blood tests later on showed CD46 defective. As a result of this defective, interleukin-10 (IL-10) indicated occurrence of inflammation (Malmeström et al., 2008). In order to have a final verdict, a sample of cerebral fluid was taken which showed high quantities of Glutamate Presence of this element in higher quantities is more common in the cases of relapse of MS. Furthermore, presence of Chromogranin A indicated that axons in the nervous system have been degenerating (Stoop et al., 2008). 4.1.3 Regulation of Homeostasis Analysis of MRI and blood test indicated that Mrs. Anderson’s body was trying to regulate Inflammation by two populations of T cells, natural (constitutive) T regulatory cells and induced T regulatory cells. According to Kasper et al. (2007), “Natural Treg cells are a population of CD4+ lymphocytes residing in the thymus that express the interleukin (IL)-2 receptor CD25 and the transcription repression factor FoxP3. These cells constitute 5–12% of the entire CD4+ cell population. Specific populations of natural Treg cells are generated by interaction with immature antigen-presenting cells (APCs) in the periphery. They recognize major histocompatibility complex (MHC) molecules in association with autoantigens with high specificity. These natural Treg cells are normally anergic, but can be activated by exposure to antigens or to high concentrations of IL-2 released from activated TH1 cells (p.11)”. Patient’s history indicated that she was shifted from Abu Dhabi to New York when she was 10 years old. Environmental changes made her more prone to MS. Therefore after second incident deficiency of vitamin D has triggered excessive reaction due to which homeostasis could not be attained. 5. Pharmacological Treatment of Multiple Sclerosis After careful analysis of Mrs. Anderson’s case, it was found that she has a relapse of MS which requires steroids as a preliminary step in order to assist her in recovery from the second episode. It is important to note that this second episode was a recurrent event and not an aggravation of earlier stage. Use of corticosteroids through venous insertion was suggested. In order to assist patients of relapse, beta interferons namely Avonex and Betaferon along with Glatiramer Acetate (Copaxone) were prescribed (Polman & Uitdehaag, 2000). According to Polman & Uitdehaag (2000), “Interferon beta-1a (Avonex, Rebif) is a glycosylated, recombinant product from mammalian cells, with an amino acid sequence identical to that of natural interferon beta. Interferon beta-1b (Betaseron [Betaferon]) is a nonglycosylated recombinant product from bacterial cells in which serine is substituted for cysteine at position 17.​17.” Main purpose of this combination is to assist reduction of total lesions in brain. These medicines have been clinically tested and have shown positive responsiveness in load reduction. Betaferon is found to be more effective in patients showing relapsing-remitting multiple Sclerosis. Suggested quantities are Avonex, 6 million units (30 μg) by intramuscular injection once a week; Betaseron, 8 million units (250 μg) by subcutaneous administration every other day; and Rebif, 6 million units (22 μg) by subcutaneous administration 3 times a week (Polman & Uitdehaag, 2000). On the other hand, Glatiramer Acetate is suggested due to its immunologic similarities with myelin basic protein 1. Main purpose of suggesting this medicine is to facilitate regeneration of axons and also reduction in relapsing. Suggested quantity for Glatiramer Acetate is subcutaneous administration of 20 mg. The goal of initialing such treatment is to ensure reduction in size of lesions leading to decrease in brain load. Furthermore, recurrent and progressive nature of MS is meant to be curtailed. In order to treat patient’s related disorders, various other interventions were suggested. Mrs. Anderson was suggested to perform light excessive to help her with balancing problems and fatigue. She was also recommended to undergo cognitive behavioral therapy that was supposed to help her with depression and anxiety. For optic neuritis, use of corticosteroids was recommended. 6. Prognosis & Complications The expected future outlook of the disease depends on numerous factors such as gender, age, frequency of attacks, patient’s history of relapsing, extent of disease, duration between attacks. Disability is also directly related to the severity of patients’ conditions and also the location of MS in central nervous system. In case the suggested medication proves less effective, there are several complications that are likely to emerge. These complications include severe depression, difficulty in performing regular functions like swallowing. Cognitive abilities and problem solving skills are likely to get impaired. Patient may become dependent on others due to less ability of taking care of one’s self. Other complications include urinary tract infections, osteoporosis, pressure sores and related side effects of medicines (NCBI, 2011). References Brodkey, M.B. et al. (2011). Living Well with Multiple Sclerosis. American Journal of Nursing, 111(7), 40-48. Corthanls, A.P. (2011). Multiple Sclerosis is Not a Disease of the Immune System. The Quarterly Review of Biology, 86(4), 287-321. Compston, A. & Coles, A. (2002). Multiple sclerosis. Lancet, 359(9313), 1221–31. Encyclopedia Britannica. (n.d.). Autonomic Nervous System. Retrieved from http://www.britannica.com.ph/medicine/autonomic-nervous-system-356196.html Haegert, D.G. (2011). Multiple Sclerosis, A Disorder of Altered T-Cell Homeostasis, Multiple Sclerosis International. doi,10.1155/2011/461304. Hollsberg, P. et al. (2005). Presence of Epstein-Barr virus and human herpesvirus 6B DNA in multiple sclerosis patients, associations with disease activity, Acta Nuerologica Scandinavica, 112(6), 395-402. Inglese, M. (2006). Multiple Sclerosis, New Insights and Trends. American Journal of Neuroradiology, 27, 954-957. Kasper, L.H., Haque, A. & Haque, S. (2007). Regulatory Mechanisms Of The Immune System In Multiple Sclerosis. T Regulatory Cells, Turned On To Turn Off, Journal of Neurology, 254(1), 10-14. Malmeström, C. et al. (2008). Relapses in multiple sclerosis are associated with increased CD8(+) T-cell mediated cytotoxicity in CSF Journal of Neuroimmunology, 196(1), 159-165. National Centre for Biotechnology Information-NCBI. (2011). Multiple Sclerosis, Retrieved from http,//www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001747/ Palace, J. (2001). Making the Diagnosis of Multiple Sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, 71, 3-8. Polman, C.H. & Uitdehaag, B.M. (2000). Drug Treatment of Multiple Sclerosis. Western Journal of Medicine, 173(6), 398-402. Polman, C.H. et al. (2011). Diagnostic Criteria for Multiple Sclerosis, 2010 revisions to the McDonalds Criteria. Annals of Neurology, 69(2), 292-302. Soilu-Hanninen, M., Laaksonen, M. Laitinen,I., Eralinna, J., Lilius, E-M. & Mononen, I. (2008). “A longitudinal study of serum 25-hydroxyvitamin D and intact PTH levels indicate the importance of vitamin D and calcium homeostasis regulation in Multiple Sclerosis”, Journal of Neurology, Neurosurgery & Psychiatry, 79(2), 152-7. Steenblock, D.A. (n.d). Multiple Sclerosis. Retrieved from http://www.stemcellmd.org/conditions-treated/neurological-conditions/multiple-sclerosis/ Stoop M.P. et al. (2008). Multiple sclerosis-related proteins identified in cerebrospinal fluid by advanced mass spectrometry. Proteomics, 8(8), 1576–85. Taylor, B.V. (2011). The major cause of a multiple sclerosis is environmental, genetics has minor role – Yes. Multiple Sclerosis Journal, 17(10), 1171–1173. Venken, K., Hellings, N. Libalau, R. & Stinissen, P. (2010). Distributed Regulatory T Cells Homeostasis in Multiple Sclerosis. Trends in Molecular Medicine, 16(2), 58-68. Appendix Figure A Central Nervous System Function at Homeostasis Source: Encyclopedia Britannica Figure B Multiple Sclerosis Source: Steenblock (n.d) Read More