Treatment And Impact Of Multiple Sclerosis Essay
Multiple sclerosis is defined as a pharmacological disorder associated with inflammation of the myelin sheaths around axons of brain and spinal cord. The disorder is also called as disseminated sclerosis or encephalomyelitis disseminata and leads to demyelination and scarring 1.Multiple sclerosis is associated with neurological symptoms of fatigue, muscle weakness, paraesthesia, ataxia, dysphagia, diplopia, severe pain, visual impairment, cognitive impairment, Lhermitte,s sign and Uhthoff’s phenomenon (Compston and Coles, 2008).In multiple sclerosis, symptoms appear in form of acute episodic attacks termed as relapses and most of these exacerbations are unpredictable (Lublin and Reingold,1996). Treatment And Impact Of Multiple Sclerosis Essay.
Multiple sclerosis and its Impact on self and family
Multiple sclerosis has multiple effects on the individual and surrounding people. The effects range from mild to severe disruptions and last for a life time. Various symptoms of multiple sclerosis like fatigue and difficulty in walking leads to many difficulties interfering with daily activities like unemployment, lack of confidence and disturbance of life style (Halper and Holland, 2002). Many symptoms like visual impairment, dysphagia and diplopia lead to dependence on others for daily activities and increases ambulatory care in family. Memory impairment results in difficulty of reading, writing and basic learning skills and increased forgetfulness which results in hindering daily activities. The presence of these symptoms cause distress, tension, confusion and pain for the individual suffering and family of the individual.
In the course of treatment relating to multiple sclerosis, the doctor, psychologist and health care provider play a pivotal role in reducing stress and difficulty of the patient. Nurse acts as an important mediator in the entire flow and serves as one point of contact for informative and health care related issues (Halper and Holland, 2002).
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STRESS: Many studies by Warren, Warren Green hill, Warren (1982), Franklin et al., (1989), Fischer et al., (1994) have cited stress as one of the symptoms in patients suffering from multiple sclerosis by conducting specific scientific tests. Many patients have reported of occupational stress (La Rocca, 1984) and studies have revealed that stress depends on the nature and duration of patients suffering from stress. Stress management seeks essential care and investigators advice to work with stress for reducing rather than completely avoiding stress (La Rocca, 1984). Family members and health care advisors have to take an extra step to reduce the emotional stress in patients suffering from MS as this factor leads to more worsening symptoms.
Case study: Mary, a MS patient was bossy and picky before she developed the disorder and after experiencing emotional stress, behaviour of Mary turned aggressive and rude. Treatment And Impact Of Multiple Sclerosis Essay.These behaviour lead family members of Mary to avoid her and this made Mary to feel lonely and deserted (Amato et al., 1995).
The Psychosocial issues associated with stress relating to some of the real time examples are as follows (Halper and Holland, 2002):
Uncertainty and Unpredictability: This is one of the major psychosocial issues associated with MS- stress and patient cannot predict the severity of the disorder and advancement of symptoms. Uncertainty of disease progress leaves the patient confused in taking decisions in family, work and other economical issues (Archibald and Fisk, 2000). In these situations, advice from psychotherapists could be helpful in improving the situation of the patient.
Denial and Adaptation: This kind of behaviour is observed when the disease is diagnosed initially. Denial is common behavioural tendency observed in patients due to shock and disbelief caused by the diagnosis of disease progression. While some patients learn to adapt to the changing conditions, some of the patients tend to remain struck with shock. Denial makes patient condition difficult to accept changes in lifestyle and worsens symptoms of emotional and occupational stress (Beatty et al., 1995).In some cases, patients become demotivated, leading to advancement of disease. Adaptation to the new changes and acceptance of the disease is a means to increase chance of surviving disease. Support of the family and health care provider plays important role in determining these behavioural tendencies.
Grief and Clinical depression: Denial behaviour towards the disease leads to grief and depression in patients. There are recorded examples of some people who have stepped down into depression due to denial. These patients have been active throughout their life before outbreak of the disease. In these people where activeness is a predominant factor, lifestyle modifications become difficult (Kalb, 1998). Family members have tough time with these kinds of patients leading to grief over the patient’s situation. Patients grief leads to reactions like asking why me only, anger and distress, denial, fear, crying, longing for improvement of health, recollecting past etc. Grieving is temporary and dependent on time and mood however constant grieving leads to more persistent and permanent disorders like clinical and mental depression. Treatment And Impact Of Multiple Sclerosis Essay. Depression is dangerous and is characterised by lack of appetite, lack of sleep, suicidal and death tendencies, feeling of guilt and worthlessness and inability to focus orientation towards betterment of life (Kalb and Miller, 2000).
Psychotherapy can improve the situation in depression patients (Halper and Holland, 2002). Medications like SSRI anti-depressants and tricyclic antidepressants are used extensively in treating depression.
Mood swings: Mood swings occur regularly in patients suffering from Multiple sclerosis. Patients could either change moods rapidly, or continue to be in the same mood for a long time or depict moods unreflective to the context (Halper and Holland, 2002). These emotions can further be described by:
Emotional Instability: Certain patients suffering from multiple sclerosis suffer from emotional instability which is characterised by hypersensitivity, irritability, anger and mood fragility. Mood gets easily changed over a short period of time and person becomes gloomy and irritable suddenly. This condition is experienced along with the family members in response to patient behaviour. The main cause attributed to this change is distortion of limbic system (Kalb and Miller, 2000).
Increased sensitization: In these conditions, patient suffering from MS reacts extensively to a particular mood for a long period of time. Small issues could provoke extreme reactions in these patients leading to irritability and stress (Kalb and Miller, 2000).
Release of emotions or pseudobulbar effect: Patients suffering from MS, sometimes release emotions of happiness or dullness without self intention (Halper and Holland, 2002). The patients express emotions unknowingly or without intention. In certain cases, emotions could be expressed in opposite situations leading to mental distress for self and family members. Use of drug amitryptiline was found effective in treatment of this (Schiffer et al., 1985).
PSYCOSOCIAL ISSUES PERTAINING TO FAMILY
When a person is diagnosed with multiple sclerosis, suffering begins with the patient and spreads along the family. According to Gonzales, family members have to accept the challenge of incorporating multiple sclerosis in their entire life and learn living along with the disease (Halper and Holland, 2002). There are many challenges faced by the family and some of these issues include (Kalb and Miller, 2000):
Conflicting coping styles: Family members behave and think different from each other and coping with different attitudes may sometimes lead to misunderstandings.
Change in roles: When a person of a family suffers from MS, his role is shared or replaced by other family members. This could result in guilt and emotional stress of the patient.
Sharing grief: Person suffering from MS faces many neurological symptoms over a period of time and the family has to cope with the changing disabilities.
Changes in communication pattern within a family: Communication pattern may change in a family with the advent of the disease and this may cause trouble for the family members.
Parenting Issues: Unlike the previous times, patients with MS, are advised to bear children, but the challenging issue is in relation to managing parenting after children are born.
Susan is a MS patient who likes family members to talk and discuss about her disorder to learn coping with the disorder however Jim, her husband feels it unnecessary. This attitude of family member caused Susan to go through emotional stress and irritability. Consulting a Psychotherapist and extended support of family could be a better approach in this regard (Halper and Holland, 2002).
Richard was a responsible husband and father of two kids before he suffered from MS. After the advent of the disorder, due to his inability to take care of the family, his wife had to bear the responsibility with great difficulty. This role change in his family created guilt and shame causing periodic grieves leading to severe depressive attacks. Spending time with Richard by friends and family members could improve the situation (Halper and Holland, 2002). Treatment And Impact Of Multiple Sclerosis Essay.
Multiple sclerosis is a disease involving high stress levels in patient and family. There are many psychosocial disorders associated with the patient and family. The health care provider and family members have to extend their support in reducing the pain and grief of the patient.
Multiple sclerosis (MS) is a chronic inflammatory disease characterized by central nervous system (CNS) lesions that can lead to severe physical or cognitive disability as well as neurological defects. Although the etiology and pathogenesis of MS remains unclear, the present documents illustrate that the cause of MS is multifactorial and include genetic predisposition together with environmental factors such as exposure to infectious agents, vitamin deficiencies, and smoking. These agents are able to trigger a cascade of events in the immune system which lead to neuronal cell death accompanied by nerve demyelination and neuronal dysfunction. Conventional therapies for MS are based on the use of anti-inflammatory and immunomodulatory drugs, but these treatments are not able to stop the destruction of nerve tissue. Treatment And Impact Of Multiple Sclerosis Essay.Thus, other strategies such as stem cell transplantation have been proposed for the treatment of MS. Overall, it is important that neurologists be aware of current information regarding the pathogenesis, etiology, diagnostic criteria, and treatment of MS. Thus, this issue has been discussed according to recent available information.
Multiple sclerosis (MS), the most prevalent neurological disability, is an autoimmune-mediated disorder that affects the central nervous system (CNS) and often leads to severe physical or cognitive incapacitation as well as neurological problems in young adults (1). Multifocal zones of inflammation due to focal T-lymphocytic and macrophage infiltrations, and oligodendrocyte death are the primary causes of myelin sheath de- struction (2) that result in the formation of CNS plaques composed of inflammatory cells and their products, demyelinated and transected axons, and astrogliosis in both white and gray matter. These lesions can cross-talk with the correct transmission of nerve impulses and lead to neuronal dysfunction such as autonomic and sensorimotor defects, visual disturbances, ataxia, fatigue, difficulties in thinking, and emotional problems (1).
Subtypes of MS are considered important not only for prognosis but also for treatment decisions and include: relapsing remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS), and progressive relapsing MS (PRMS). RRMS is the most common subtype (approximately 87%) which characterized by unpre- dictable acute attacks followed by periods of remission (3). During RRMS, inflammatory attacks on myelin and nerve fibers occur. Activated immune cells cause lesions in the CNS which generate symptoms of visual impairments, tingling and numbness, episodic bouts of fatigue, intestinal and urinary system disorders, spasticity, and learning and memory impairment. Approximately 10-15% of MS patients are diagnosed with PPMS which largely affect the nerves of the spinal cord. Treatment And Impact Of Multiple Sclerosis Essay. PPMS patients tend to have fewer brain lesions. Induced symptoms include problems with walking, weakness, stiffness, and trouble with balance. Nearly 65% of patients with RRMS will subsequently develop SPMS which is considered the second phase of this disease. Many individuals experience increased weakness, intestinal and urinary system disorders, fatigue, stiffness, mental disorders, and psychological impairment. Finally, PRMS is the least common type of MS that occurs in approximately 5% of patients and is associated with symptoms such as eye pain and double vision, along with sexual, intestinal and urinary system dysfunction, dizziness, and depression. Generally MS is detected between the ages of 20 and 40 years, but less than 1% can occur in childhood and approximately 2-10% after 50 years of age (4, 5).
This pathologic condition affects women more than men (sex ratio 2.5:1) and the prevalence varies by geographic area, ranging from 120 per 100,000 individuals (6, 7). The etiology of MS remains unclear, however it can be considered a multifactorial disease and include a genetic predisposition combined with environmental influences (8).
The initial treatment strategy for MS is largely based on disease-modifying drugs such as interferon-β and glatiramer acetate (9, 10). The effects of these treat- ments are partially for symptomatic alleviation and do not stop the ongoing neurodegeneration.
Currently, a stem cell-based regenerative medicine paradigm has been proposed for the treatment of MS (11-13). Adult stem cells, including hematopoietic and mesenchymal stem cells (MSCs), are undifferentiated cells used to treat MS due to their immunomodulatory effects and neuroprotective potential (14).
We review the pathogenesis, a number of environmental factors, genetic susceptibility, diagnostic criteria, and treatment of MS.
Pathogenesis of multiple sclerosis
Inflammation of the white and gray matter tissues in the CNS due to focal immune cell infiltration and their cytokines are the incipient cause of damage in MS. Many studies have suggested T helper (Th) cell (also known as CD4+ T cells) intervention and adaptive immune responses which initiated by interaction between antigen presenting cells (APCs) with T lymphocytes play an important role in the initiation and progression of MS (15, 16). Pathogen-associated molecules simultaneously bind to toll-like receptors on APCs and production of specific cytokines that include interleukin (IL)-12, IL-23 and IL-4 begins that these cytokines induce CD4+ T cell differentiation intoTh1, Th2, or Th17 phenotypes which have ability to release special cytokines. Interferon gamma (IFNγ) or type II interferon and tumor necrosis factor alpha (TNF-α) are proinflammatory cytokines critical for innate and adaptive immunity. These cytokines are produced by Th1 cells (17).They have the ability to promote inflammation by suppressing Th2 differentiation. Th2 cells secrete the anti-inflammatory cytokines, IL-4 and IL-13 (18, 19). IL-4 reduces pathological inflammation via increase in M2 macrophage (or repair macrophages) and alternative activation of M1 macrophages that promote inflammation. The effects of IL-13 on immune cells is similar to IL-4. This cytokine, by secretion of matrix metalloproteinase, has anti-inflammatory properties especially during allergic inflammation (20). Th17 is another CD4+ T cells which induces a large number of cytokines (IL-17, IL-21, IL-22 and IL-26) which are capable of promoting inflammation (Fig.1A) (21). Treatment And Impact Of Multiple Sclerosis Essay.
B lymphocytes and their cytokines are other factors in the pathogenesis of MS. Lymphotoxin [or transforming growth factor beta (TGF-β)] and TNF-α produced by these cells promotes inflammation. In addition, these cells are capable of producing IL-10 which is an anti-inflammatory cytokine. Hence, B lymphocytes have both positive and negative effects in the development of MS (22).
Many studies have shown that in addition to the above-mentioned cells, CD8+ T cells (or cytotoxic T cells) can be found in MS lesions (23). These cells, via the production of cytolytic proteins such as perforin, mediate suppression and inactivation of CD4+ T cells. Moreover, these cells thorough increase vascular permeability, glial cells destroy and trigger of oligodendrocyte death play an important role in the pathogenesis of MS. In addition to CNS inflammation, the myelin repair process due to oligodendrocyte death is also impaired (16).
Fas ligand (FasL) is produced by lymphocyte cells. This ligand binds to Fas receptors [cell surface receptor that belongs to the TNF receptor superfamily] on oligodendrocyte cells which begins the apoptosis process of these cells (24). Therefore, the numbers of myelin synthesis cells reduce and will impair synthesis of the myelin sheath (Fig.1B). Treatment And Impact Of Multiple Sclerosis Essay.
Environmental factors, including exposure to viral and bacterial agents such as Epstein Barr virus (EBV), human herpes virus type 6, and mycoplasma pneumonia (25), in addition to smoking (26), vitamin deficiency (27), diet (28, 29), and exposure to UV radiation (30) are associated with the onset of MS.
The foreign agents may have a nuclear antigen that is structurally homologous with myelin sheet components such as proteolipid protein, myelin basic protein, and myelin-associated glycoprotein. Thus, when immune cells are activated by these pathogens, myelin sheath lesions will form.
Currently, evidence suggests that smoking, due to nitric oxide (NO) and carbon monoxide (CO) production, plays an important role in MS. NO is a toxic soluble gas that in pathological concentrations can damage neurons and oligodendrocytes (31, 32). Lipid peroxidation and mitochondrial damage that result from NO can lead to oligodendrocytes apoptosis, axonal degeneration, and demyelination (33).
A previous study has shown that CO exposure leads to blockage of tissue oxygenation (34), myelin basic protein (MBP) degradation, and axonal injury as well as a subsequent inflammatory response including activated microglia and CD4+ lymphocyte invasion of the CNS, which results in demyelination (35).
Vitamin deficiency (especially vitamins D and B12) are considered risk factors for MS. Vitamin D comprises a group of fat-soluble secosteroids that include vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Cholecalciferol can be produced in the skin via the action of ultraviolet B radiation on 7-dehydrocholesterol which is the precursor to cholecalciferol.
In the liver, through hepatic hydroxylation, cholecalciferol is transformed into the prohormone calcidiol [25(OH)D3]. In the kidneys, by a renal hydroxylation step, a part of the calcidiol is changed to calcitriol which is the biologically active form of vitamin D. In the circulatory system calcitriol binds to a vitamin D-binding protein and is transported to various target tissues where it binds to specific intracellular receptors and has an important role in cell proliferation and differentiation (36). In addition, this vitamin has a role in gene expression and regulation of immunity (37), as well as induction of B lymphocyte apoptosis (38), IL-10 synthesis (39), and suppression of proinflammatory cytokines such as IFN-γ (40) and IL-2 (41). Treatment And Impact Of Multiple Sclerosis Essay.
Vitamin B12 is an important factor in the generation of myelin shell components. Thus, deficiency of this vitamin can be a major cause for neurological diseases such as MS. The results of a previous study on MS patients have indicated that the application of vitamin B12 benefitted the clinical course of MS (42).
Beyond vitamin deficiency, low-term sunlight exposure has been identified as a potential risk factor for MS. The results of a previous study have demonstrated a reverse association among exposure to ultraviolet radiation and the incidence of MS (30). In justifying this relationship, it can be said that sun light is a principal source of vitamin D3 and via induction of T regulatory (Treg) cells and anti-inflammatory cytokines such as IL-10 and TNF-α, it may have immunomodulatory effects in MS (43).
According to previous reports, diet could be an environmental factor involved in MS (44). Studies reported a significant negative association between MS risk and high fish intake (45), a positive significant association between high animal fat-based caloric intake and MS risk (46), a non-significant lower risk between incidence of MS and a higher intake of linoleic acid (28), and a positive significant association between obesity in adolescent girls and MS risk (47).
A genetic predisposition may be involved in MS. Studies show that the risk of MS in family members of a patient depends on the amount of genetic information they share (48-50). Thus, the risk rate in monozygotic-twins that have 100% genetic similarity is approximately 25%. In all individuals who have 50% genetic similarities such as dizygotic twins and first degree relatives, this risk is 2-5% (51, 52). In addition, the risk in second degree relatives with 25% genetic similarity is 1-2%, whereas in third degree relatives with 12.5% genetic similarity, this risk is less than 1% (48-50). It has been shown that in the human leukocyte antigen (HLA) region of chromosome 6 exists a group of genes associated with an increased risk of MS. Within this region HLA-DR2+ (53), HLA-DQ6 (1), DQA 0102 and DQB1 0602 (54), HLA-DRB1 (54), DR15 (55), DRB1*1501, and DRB1*1503 (56) are genes susceptible to the onset of MS. In addition to these alleles, IL-7 and IL-2 receptor alpha are other sensitive genes associated with MS (57). Unlike the aforementioned genes, HLA-C554 and HLA- DRB1*11 have protective effects (1).
Usually, MS symptoms are unpredictable and uncertain. Since this disease can affect any region of the CNS, it can generate almost any neurologic symptom. In addition, symptoms vary greatly among patient and within one patient over time. During the course of MS, some abnormalities appear to be more dominant or have a greater effect on functional ability. Table 1 lists the more common symptoms of MS that may appear during different courses of the disease (58).
Diagnosis of multiple sclerosis
Early detection of MS is important because it gives us the opportunity to seek treatment and plan for the future. An exact diagnosis of MS is based on medical history and neurological examination using imaging techniques such as magnetic resonance imaging (MRI), lumbar punctures (LP) for cerebrospinal fluid (CSF) analysis, evoked potentials, and blood samples analysis (59). Obtaining a history about the onset of the first symptoms, any neurological disorders as well as illnesses such as diabetes and thyroid diseases, food habits, geographic locations, and history of medications taken and substance abuse is important. In addition, an eye examination and evaluation of Babinski’s reflexes can be useful. MRIs can identify any scar tissue formation and damage in the CNS. Evoked potentials test (60) that include visual, brain stem auditory, and somatosensory evoked potentials offers information about demyelination in the optic nerve and CNS. In addition, CSF analysis for myelin basic protein and immunoglobulin- gamma (IgG) determinations (61) and blood sample analysis for detect of vitamin deficiencies may be diagnostically helpful (62). Treatment And Impact Of Multiple Sclerosis Essay.