Multiple sclerosis [MS] is a chronic, autoimmune, inflammatory, neurodegenerative condition of the central nervous system [CNS] (Boppanna, Huang, Ito & Dhib-Jalbut, 2011) characterized by demyelination and axonal loss (Chastain, Duncan, Rodgers & Miller, 2011). MS expresses itself in 4 forms: relapsing remitting MS [RRMS], secondary progressive MS [SPMS], primary progressive MS [PPMS], and progressive relapsing MS [PRMS] (Boppanna, Huang, Ito & Dhib-Jalbut, 2011). MS affects 0.
1 per cent of the world’s population (Chastain, Duncan, Rodgers & Miller, 2011), occurring 2- and 2. 5-fold more frequently in women than in men, having an incidence range of post-pubertal teenagers to adults in their 50’s (Calabresi, 2011). The exact cause of MS is unknown (Boppanna, Huang, Ito & Dhib-Jalbut, 2011; Chastain, Duncan, Rodgers & Miller, 2011). Boppanna, Huang, Ito and Dhib-Jalbut (2011) suggest that MS is a result of an immunological response against the CNS as well as genetic factors.
Owens, Gilden, Burgoon, Yu and Bennet (2011) suggest that a virus or virus-triggered immunopathology causes MS. Vitamin D deficiency is also regarded as a cause for MS as Vitamin D is an immune regulator (Burton, Kimball, Vieth, Bar-Or, Dosche, Chung, Gagne, D’Souza, Ursell & Connor, 2010). Signs and symptoms of MS vary, based on the location of lesions, and may change throughout the duration of the disease (Schapiro, 2005). Sensory abnormalities, optic neuritis, motor symptoms, organ dysfunction, systemic symptoms, etc.
, are some aspects of the body in which may be affected by MS and are a result of debilitating transmission of an action potential from nerve cells from the brain to the spinal chord due to the demyelination of the axon (Calabresi, 2011). MS is an incurable disease (Boppanna, Huang, Ito & Dhib-Jalbut, 2011). According to Kargiotis, Paschali, Messinis and Papathanaspolous (2010), treatment options for MS are divided into two categories: disease modifying agents and symptomatic medications. Where pharmacological agents are used to manage pain in patients (Solaro & Uccelli, 2010).
Meletis and Zabriskie (2007) present a natural approach to MS suggesting that vitamins, anti-oxidants and diet provide benefits for patients suffering from the disease. The cause of MS is still unknown (Chastain, Duncan, Rodgers & Miller, 2011), however, the demyelination of axons within the brain is the foundation in which acts as the catalyst for neurological deficits affecting the transmission of signals by the nerve cells within the CNS therefore affecting other systemic functions (Haines, Inglese & Casaccia, 2011).
As MS is an autoimmune disease, this results with the differentiation of self and non-self being hindered whereby cells attack the myelin of an axon as if it were a foreign body causing demyelination and axonal damage (Boppana, Huang, Ito & Dhib-Jalbut, 2011). Demyelination is a result of the formation of lesions on the myelin sheath as well as the breakdown of the blood brain barrier [BBB] (Boppanna, Huang, Ito & Dhib-Jalbut, 2011) and inflammation of the CNS is the primary cause of damage in MS (Loma & Heyman, 2011).
Chastain, Duncan, Rodgers and Miller (2011) suggest that antigen-presenting cells are necessary for the pathogenesis of MS. Inflammation in MS is mediated by a coordinated attack by T-cells, monocytes and B-cells against the CNS tissue (Boppanna, Huang, Ito & Dhib-Jalbut, 2011). Antigen presenting cells [APC’s] encounter myelin, which is presented to CD4+ naive T cells in the lymph nodes (Chastain, Duncan, Rodgers & Miller, 2011) and differentiate naive T cells into effector T-helper cells [Th1], influenced by the proteins, Interluken-12 [Il-12], producing pro-inflammatory cytokines (Boppanna, Huang, Ito & Dhib-Jalbut, 2011).
Interluken-1 [Il-1] and interluken-23 [Il-23] promote the development of a T cell lineage, Th17 cells, which is a mediator for inflammation (Chastain, Duncan, Rodgers & Miller, 2011). Pithadia, Jain and Navale (2009) state that activated T-cells can cross a healthy BBB when expressed with adhesion proteins on endothelial cells, specifically matrix metalloproteinase’s, which increases T-cell permeability of the BBB and allows for the infiltration into the CNS parenchyma.
The disruption of the BBB is a central event in MS immunopathogenesis (Niaragh & Mirshafiey, 2011). In the CNS microglia further activate Th1 cells causing an activation of pro-inflammatory macrophages to kill intracellular pathogens by the secretion of tumour-necrosis factor-alpha and interferon-gamma (Cornabella & Khoury, 2011). Th17 cells induce pro-inflammatory cytokines and chemokines, enhancing dendritic cell maturation and promotes neutrophil function, further initiating an inflammatory response in the CNS (Boppanna, Huang, Ito & Dhib-Jalbut, 2011).
Th1 and Th17 cells activate monocytes to mediate myelin and axonal injury as well producing soluble products (glutamate) contributing to tissue damage (Chastain, Duncan, Rodgers & Miller, 2011). Th2 cells induce B cell activation, differentiation and maturation, as well as, possessing anti-inflammatory regulation. Boster, Ankeny and Racke (2010) state that B cells not only play a role in antigen presentation and priming of naive T cells but also play a role in the mediation of demyelinating axons.
B cells activating in the CNS differentiate into plasma cells in which produce and secrete immunoglobulin (Abel & Burgoyne, 2008) and myelin specific anti-bodies (Loma & Heyman, 2011) resulting in the phagocytosis and breakdown of the myelin mediated by macrophages (Boster, Ankeny & Racke, 2010) as well as targeting and attacking oligodendrocytes further breaking down the myelin sheath (Abel & Burgoyne, 2008). Research indicates that there is a presence of polyclonal antibodies, olgioclonal bands [OCB], produced by B cells, in the cerebrospinal fluid [CSF] of patients with MS (Loma & Heyman, 2011).
Regulatory T [Treg] cells in individuals who have MS and those who do not have MS are quantifiably the same, however patients with MS have reduced Treg function resulting in decreased regulation of inflammatory responses and increased axonal damage (Loma & Heyman, 2011). T cell and B cell mediated inflammation in the CNS is the main cause for demyelination of the axon and cell death. Locations of lesions, as well as, severity of axonal damage directly effect the clinical manifestations presented in individuals with MS (Schapiro, 2005).
The degree in which MS is expressed further differentiates the signs and symptoms being experienced by individuals with the disease; RRMS, SPMS, PPMS, PRMS (Boppana, Huang, Ito & Dhib-Jalbut, 2011). Fatigue is the most common and most disabling symptom of MS (Schapiro, 2005) affecting more than 80% of people with MS (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010). Fatigue is closely linked with having depressive symptoms (Schapiro, 2005).
Demyelinated nerve fibres send continuous impulses at a higher rate in order to maintain a repetitive task, resulting in energy and transmission of impulses decreasing and “shorting” causing weakness, lethargy and sometimes depressive symptoms (Schapiro, 2005). Spasticity can range from non-existent to severe depending on a patients current status of MS and is a result of disequilibrium in the ascending and descending excitatory and inhibitory pathways in the brain and spinal cord (Schapiro, 2005).
Bladder dysfunction occurs in at least 70% of people with MS (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010). Bladder dysfunction develops due to nerve signals being blocked in the CNS which control the bladder and urinary sphincter whereby the sphincter either contains urine and allows for continuous release (Schapiro, 2005). Continuous bladder problems may lead to infections and more importantly kidney impairment eventually affecting most bodily systems (Schapiro, 2005). Around 50% of patients with MS will develop a degree of cognitive impairment (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010).
MS causes cognitive dysfunction due to the damaged myelin and nerve cells in the brain affecting functions in which are handled by the brain (Schapiro, 2005). Optic neuritis is a result of the inflammation of the optic nerve, which sends transmits light from the retina to the brain (Schapiro, 2005) and affects 55% of people with MS (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010). Signs and symptoms of MS are a result of transmission of nerve signals in the axon being hindered due to the breakdown of the myelin sheath (Boppana, Huang, Ito & Dhib-Jalbut, 2011).
Where treatment of symptoms is most important. As MS is an incurable disease (Boppana, Huang, Ito & Dhib-Jalbut, 2011), treatment of MS comprises of treatment of symptoms, treatment of acute relapses and management of the disease itself (Blasier, 2008). The use of disease modifying agents, pharmacological management of symptoms and natural approaches should be individualized (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010; Meletis & Zabriskie, 2007). Interferon-B (IFNB), glatiramer acetate, mitoxantrone and natalizumab are the most common forms of disease modifying agents used today (Blasier, 2008).
Two types of IFNB have been approved, 1a and 1b, in which the use of IFNB effects MS by inhibiting cytokine production and reducing infiltration of immune cells into the CNS (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010) and have shown effectiveness in treating RRMS and SPMS patients and delaying neurological dysfunctions (Blasier, 2008). Glatiramer acetate affects MS by altering T-helper cells phenotype and function (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010) as well as being an artificial protein that resembles the natural myelin protein in which protects nerve fibres (Blasier, 2008).
It imitates myelin basic protein and interrupts the inflammatory response to prevent damage to the myelin sheath (Blasier, 2008). Mitxonatrone is a second line agent for MS, which is directly used to treat SPMS (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010). It reduces cytokine production as well as progression and clinical exacerbations of MS as it inhibits lymphocytes and macrophages (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010). Natalizumab is a recombinant monoclonal antibody that binds to alpha-4 integrin (NNMS, 2008, as cited by, Blasier, 2008) present on the surface of activated T-helper cells.
Binding to integrins prevents the association of adhesion molecules on endothelial cell surface, blocking migration of lymphocytes into the CNS, resulting in reduced numbers of T-cells in the CSF (Kargiotis, Paschali, Messinis & Papathanaspolous, 2010). This agent is used for treatment of RRMS if a first line agent is unresponsive (Blasier, 2008). Meletis and Zabriskie (2007) suggest that in relation to pharmacotherapy, the use of anti-oxidants, vitamins and change in diet directly affect cyokine production and the inflammatory response as well as the affecting the immune system.
In conclusion it can be seen that MS is a disease in which further needs to be researched in order to efficiently treat. Incurable, symptomatic management and treatment is vital for patients with MS in order to provide a sustained quality of life. Individualized, holistic care is essential. References Blasier, M. (2008). Pharmacologic Management of Multiple Sclerosis. Urologic Nursing, 28(3), 217-219. Boppana, S. , Huang, H. , Ito, K. , & Dhib-Jalbut, S. (2011). Immunologic aspects of multiple sclerosis. The Mount Sinai
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