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Medicine and Health

Multiple sclerosis

Abstract

The purpose of this document is to offer a precise account of Multiple Sclerosis. The statement of problem related to this research reads ‘while theories pertaining to the etiology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explores the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of the disease. Consequently, the researcher will adapt a comparative analysis of the perspectives offered by theorists regarding emergence of multiple sclerosis among the twenty-first century female young adults. These will be matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management as well as current trends are explored.

Medicine and Health: Multiple Sclerosis

Introduction

Description

          Multiple sclerosis was not discovered as a disease until late 19the century. An English Physician by the name of Walter Moxon in 1873 along with American Dr. Edward Seguin in 1878 discovered multiple sclerosis as a dysfunction of the nervous system. They confirmed that it was more common in women than men. However, three notable signs of multiple sclerosis signs described as Charcot’s triad 1 being nystagmus, intention tremor, and telegraphic speech (scanning speech) have been attributed to French neurologist Jean-Martin Charcot (1825-1893). He  recognized cognition alterations, which was described as “marked enfeeblement of the memory” and “conceptions that formed slowly” (Clanet, 2008, p 58).  At the time these doctors did not project any sound etiology of the disease, but said that there was no evidence to support it being inherited. However, they confirmed that numerous diverse neurological irregularities were produced as symptoms of the condition (Terry et.al, 2012).

            Multiple sclerosis (MS); disseminated sclerosis is also known as encephalomyelitis disseminata. Scientists have described it as an inflammatory condition characterized by formation of myelin sheaths around brain and spinal axons tissue. Ultimately, these tissues are destroyed through scarring; reduction in myelin to protect brain and spinal cord. Research is still being conducted regarding its etiology, Assumptions however have been that many predisposing genetic, environmental and infection factors could initiate the inflammation (Ascherio & Munger, 2007).

      Other assumptions have been that there are mechanisms within the body chemistry, which are responsible for destruction of the immune system inhibiting production of myelin cells. Consequently, massive insidious nerve destruction occurs and nerve cells become incapable of functioning as communicators of impulses across nerve ending within the human body. Often when the etiology of a disease is obscure there is seldom a cure. Recent research has continued to advance ther theory that indeed multiple sclerosis affects more females than males (Nakahara et.al 2012)

        To date scientists have advanced from repeated research that there is no discrimination as to which neurological symptoms can emerge due to nerve destruction in the brain and spinal cord which are the primary target organs. From observation there have been immense progressive physical and mental dysfunctions. In some cases memory irregularities could develop, but a difficultly exists classifying them as purely psychiatric because they may present in conjunction with various levels of other neurological abnormalities. As the disease evolves it converges into many misleading features increasing the challenge of addressing the real symptoms in devising modes of treatment intervention. Scientists have described this phenomenon as an escalation of new symptoms, which were not formerly associated with the initial presentation. They are termed relapsing forms and progressive forms respectively (Dymentet.al, 2004)

        The period from when attacks begin end, and begin again symptoms may subside. However after these episodes permanent nerved damage occurs. As the disease advances symptoms worsens and exacerbations seems to occur leading up to when treatment becomes ineffective. This disease is more than 100 years old, but scientists have not been articulate in arriving at any profound etiology while numerous theories exist. They have not gone far beyond exploring mechanisms related to the disease process itself (Ascherio & Munger, 2007).

       Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed only at addressing the autoimmune etiology of the disease. As such, they merely focus on restoring function to affected nerves after symptoms become uncontrollable; control recurrence and limit the extent to which nerve damage produces disability (Nakahara et,al, 2012).

          However, medications used to treat multiple sclerosis are not without their serious side effects, besides being poorly tolerated by patients. Consequently, patients turn to alternative medicine for relief. Precisely, since there are few studies conducted regarding alternative remedies these remedies are considered nonscientific and are not recommended even through patient report how successful these treatments have been in restoring nerve function (Gilden, 2005).

      People diagnosed with multiple sclerosis live an average 5-10 years, less than persons who do not have the disease. There is an average of 2 persons affected by multiple sclerosis for every 150 per 100, 000 (Rosati, 2001).  However, data or theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure. This research is expected to sensitize scientists into elaborating on present research practices in arriving at a consensus regarding the reality of multiple sclerosis etiology.

Epidemiology

      Epidemiology infers a study of disease patterns that evaluates infection etiology; geographic, socioeconomic status, genetics and demographic variations. Often epidemiologists add to the multiple sclerosis body of knowledge through assessing relationships between these factors. Since there are no known causative factors for multiple sclerosis it is important that epidemiologists continue investigations regarding migration patterns. However, it must be understood that figures published in epidemiology records are all estimates. This is an attempt at establishing a more profound understanding regarding multiple sclerosis target populations across the world. It also helps identifying and explaining geographic locations containing highest and lowest multiple sclerosis rates (Merril, 2010).               

        The challenge facing the epidemiology of multiple sclerosis lays in the difficulty diagnosing the disease. No single distinct tests are being conducted in establishing a diagnosis for multiple sclerosis. As such, the argument is that diagnoses can be incorrect delayed or just bypassed. While MRI technology has been of great assistance in resolving difficult diagnoses epidemiologists question the accuracy of diagnoses produced from previous studies since they may not give a true representation of multiple sclerosis with the given population. More importantly, various methodologies used by specialists collecting data on the disease can greatly alter interpretations and outcomes. Due to these factors the epidemiology of multiple sclerosis is still in its infancy even though the disease is over 100 years old (Merril, 2010).              

                 According to Orhun Kantarci and Dean Wingerchukb (2006) multiple sclerosis claims the health of approximately 1 000 000 people between 17 and 65 years old internationally. The 2000 projected multiple sclerosis prevalence rate among white US populations showed 191 per100 000. Alternatively, the US overall incidence rate and was 7.3 per 100 000 person in the same year. Further epidemiological studies supported the theory that multiple sclerosis is two times more common in women than men. It was discovered also that there is a tendency for a later onset of the disease among men. The prognosis for them is even worse for women. Scientists attribute this difference to gender-dependent and phenotypic variability factors which may create an etiological predisposition (Kantarci & Wingerchukb, 2006).

        Multiple sclerosis care cost United States government an estimated $6.8 billion annually, which includes loss in productivity as well as actual health care interventions. A total life time cost is estimated at 2.2 million per patient (Kantarci & Wingerchukb, 2006).Similar epidemiological estimates exist around the world. There seems to be patterns of ‘a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere’ (Rosati, 2001, p 22). Multiple sclerosis is less prevalent among people who live close to the equator. Theories pertaining to climate, sunlight and vitamin D intake are variables used in relating possible causes in explaining this latitude gradient theory regarding geographic disposition multiple sclerosis prevalence among people living near to the equator (Rosati, 2001).

     Overtime other variations have appeared, which forced epidemiologist to consider environment in combination with genetics. Multiple sclerosis was discovered to be prevalent among northern European populations and most common in certain ethnic groups such as ‘Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori’ (Rosati, 2001, p 22).

       Childhood environmental factors were then considered as a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

      Critics of the environmental epidemiological theory have contended that quantification of the assumptions is difficult because data derived is obtained mainly from retrospective case-control studies whereby subjects are exposed to the same environment and results may lack internal and external validity besides containing reliability issues. ‘A practical, albeit limited, design is a nested-cohort study in which a population cohort already identified for exposure to given factor(s) for another disease is exploited for excess of -NIS occurrence after sufficient follow- up’(Kantarci & Wingerchukb, 2006, p 249). While trying to make sense of the environmental theoretical epidemiological perspectives major advances have implicate viral exposure factors. Viruses identified are canine distemper virus, Epstein-Barr virus, and human herpes virus-6) (Kantarci & Wingerchukb, 2006).

           Internationally, conclusions are that multiple sclerosis makes its first appearance in adults during their thirties. It can occur at any time in children. However, the primary progressive subtype appears later in people in their fifties.  The genetic epidemiology of multiple sclerosis seems to be overlapping with both environmental and viral/infections. Analysts have discovered that the only facts they have to support the genetic epidemiology are its high incidence among Northern Europeans in relation to indigenous populations from the ‘same geographic location, familial aggregation’(Kantarci & Wingerchukb, 2006, p 249). See appendix 1 and 2

Clinical signs and symptoms

                 Numerous signs and symptoms are associated with multiple sclerosis. However neurologists keep abreast of symptoms by applying the Expanded Disability Status Scale (EDSS).  EDSS gives a score total of a scale ranges from 0 to 10.

 ‘The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.  The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. In addition, it also provides eight subscale measurements called Functional System (FS) scores. These subscale categories are listed below.  The levels of function within each category refer to the eight functional systems affected by MS’ (Kurtzke, 1983).

  • Pain

              Pain is very common among multiple sclerosis patents and often appears after the first lesion is formed. In most occasions it is associated with the control mechanisms which regulate ascending and descending tracts in the anterolateral system. From 28 studies researchers proved taking a sample of 7101 multiple sclerosis patients that 63% complained of various degrees of pain. There were no significant differences in pain levels among men and women or people with greater disability than others.  Most pain occur as ‘headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte’s phenomenon (16%) and Trigeminal Neuralgia (3%)’ (Foley et.al, 2013, p 632).

  • Emotional disturbance

       Emotional disturbance manifests as clinical depression. This can extend into a life time complication. Present incidence rates range between 40–50% per person diagnosed with multiple sclerosis. Brain imaging studies have tried to relate findings to depression when brain lesions are found. More importantly, most neurologists have associated these brain lesions with neuropathology of the left anterior temporal/parietal regions. It is very important development that is worth monitoring carefully because emotional disturbance is responsible for 15% of deaths emerging from suicide. As such, patients are closely evaluated when signs anger, anxiety, hopelessness, and frustration surface (Siegert, Abernethy, 2005).        

  • Bladder and Bowel irritability

       Bladder disturbances occur in 70% of all multiple sclerosis patients. It presents as frequency, hesitancy and incontinence which can affect maintenance of personal hygiene. Bowel issues appear in 70% of the multiple sclerosis patients, 50% suffer from constipation 30% fecal incontinence (DasGupta & Fowler, 2003).            

  • Cognitive disturbances

       40%- 60% of multiple sclerosis patients encounter cognitive difficulties. It ranges from simple degrees of forgetfulness to severe loss of memory. Other cognitive difficulties are attention deficit; neurological fatigue; processing speed and visual spatial ability alterations (Ebers, 2008).

  • Impaired Mobility

           Mobility changes become evident when walking, moving, getting off and on the bed and balancing. Research has shown that between the onset of the disease and 5 years 50% of patient score 6 on the EDSS scale. 10 years living with multiple sclerosis 25% of patients can attain just a score of 6 on the Expanded Disability Status Scale (EDSS). This makes using a walker and other methods of mobility support necessary. Within 30 years, 83% of patients use walking aids (DasGupta & Fowler, 2003).           

  • Speech difficulties

Speech could become slurred and tone of voice altered.

  • Muscle Tremor and Ataxia

Ataxia coincides with muscle tremors. Clumsy movement occurs creating difficulty in maintaining a steady gait. Muscle tremors are often uncontrollable involuntary episodes of shaking.

  • Transverse myelitis 

When multiple sclerosis begins invading deep into spinal cord tissue lower body functions become impaired. These include bladder/irritability as well as sexual potency in males. Inability to have an erecting is possible along with ejaculation difficulties

  • Spasticity

Spasticity manifests as both a sign and symptom. Muscles, especially, in the extremities become very stiff and immobile.

Diagnosis

           Researchers have posited that multiple sclerosis is difficult to diagnose since confirmation of the disease cannot be made on clinical symptoms alone. Signs and symptoms may resemble many other neurological disorders. To facilitate diagnosis during the early stages scientists have designed standardized criteria. They include Schumacher, Poser and McDonald criteria.

Schumacher’s criterion is a neurological examination detecting central nervous system abnormalities involving two or more systemic dysfunctions. Often white matter abnormalities are evident in brain and spinal tissue. In 1983 these criteria were modified by Poser accounting for clinically definite; laboratory supported definite; clinically probable and laboratory supported probable multiple sclerosis (Royal College of Physicians of London, 2004).

                          McDonald criteria are the ones presently used in most health care institutions across the world for making a more accurate multiple sclerosis diagnosis. It includes a

  • Diagnostic criteria for suspected MS (two or more attacks)        Flowchart Icon  
  • Diagnostic criteria for suspected MS (monosymptomatic)         Flowchart Icon
  • Diagnostic criteria for suspected MS (single attack)                   Flowchart Icon
  • Diagnostic criteria for suspected MS (progressive from onset)      Flowchart Icon

                             (Royal College of Physicians of London, 2004)

               However, Schäffler, Köpke , Winkler , Schippling , Inglese , Fischer and, Heesen (2011) have reprted that the development of a new diagnostic criteria for multiple sclerosis was recently proposed after a systematic literature review  revealed that present accuracy issues made some tests invalid. The aim of this study was to validate diagnostic studies and clarify the value of diagnostic test used in offering a diagnosis. They included in their review a minimum of 40 patients who were traced for 2 years. This limitation existed in all the studies reviewed since they significantly lacked a gold standard measurement for validating the diagnostic tests that were used in those trials. A second relapse phase was adopted as a surrogate in relapsing-remitting multiple sclerosis testing. However, the lengthy 5 year follow-up created difficulty in detecting all cases. Also, quite a few studies contained various levels of validity and reliability issues. Notably, a selection bias was identified due to the indistinct classification of a clinically isolated syndrome (Schäffler et.al, 2011).

                  Based on these limitations, ‘sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%; Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%; combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%)’ (Schäffler et.al, 2011, 153). The researchers did not find justification in conclusions derived in the literature review studies. Further they suggest that ‘a combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis’ (Schäffler et.al, 2011, 153).

Prognosis

         While there is no cure for multiple sclerosis it has not been considered a fatal disease even though it severely affects a person’s quality of life. Serious disability does not occur until about 20 years after onset of the disease. Women seem to have a better prognosis than males. Factors affecting each patient’s prognosis regarding quality and length of life relate  to  adherence of health promotion strategies that will limit symptoms , doctor’s  appointment  follow up ; compliance with medication management to reduce progression of the disease. Generally life expectancy is reduced by 5-10 years with careful intervention strategies (Murray, 2002).

Immunological concepts underlying Multiple sclerosis

          Immunology relates to the body’s defense mechanisms in counteracting  the activity of invading agents. For every disease entity that enters the human internal environment there are diverse strategies employed by the immune system in a comprehensive effort to interrupt the intended invasion consequences. Consequently, the immune system builds up resistance by developing immunity to the invading organisms. There are mainly five types of immunological responses that can emerge from this activity. They are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

Humoral immunity

         Humoral immunity is also known as antibody-mediated system being mediated macromolecules located in extracellular fluids like secreted antibodies, antimicrobial peptides and complement proteins. Usually, humoral immunity reacts with substances in body fluid humors (Nakahara et.al, 2006).

Cell-mediated immunity

          Cell-mediated immunity does not rely on producing antibodies in order to defend the body against harmful organisms. Instead it activates phagocytes, antigen-specific cytotoxic T-lymphocytes, and disperses numerous cytokines in an antigen response (Nakahara et.al, 2006).

Innate or Natural Immunity

 Innate immunity is the body’s evolutionary natural mechanism used to fight invading foreign species. This is the dominant and oldest type of immunity among living creatures including unicellular organism such as amoeba, fungi, plants and insects (Nakahara et.al, 2006).

Acquired immunity

      Acquired immunity emerges after exposure to a foreign organism. It is also known as adaptive immunity due to somatic hypermutation or accelerated somatic mutations), and V (D) J recombination, which is actually a genetic antigen receptor recombination that cannot be reversed (Nakahara et.al, 2006).

Non-specific immunity

               Non-specific immunity means that the immunological response is antigen independent and unspecified. However, distinct mechanisms are activated. They include establishing anatomical barriers, stimulation of secretory molecules and integrating cellular components.  Recognizable mechanical anatomical barriers include the internal epithelia tissue such as the skin.  Intestinal mobility along with oscillation of broncho-pulmonary cilia is chemicalized because chemical messages are transmitted through biological agents present in skin, intestines and nervous system.

                   DominantImmunological concepts associated with multiple sclerosis are connected to the pathogenesis of this disease. Some basic traditional immunological concepts pertaining to multiple sclerosis are:-

  • Relapsing MS
  • Secondary progressive MS.
  • Progressive MS.
  • Progressive relapsing MS

While these are the four major immunological concepts that intermingle in explaining the pathophysiology of each stage collectively in facilitating the discussion other will be highlighted. Significantly, coinciding with the five types of immunological responses that can emerge from antigen antibody interaction are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity. Therefore, the terms that will be explained in this section are:

  • Demyelinization
  • Cell-Mediated Immunity
  • Humoral Immunity
  • Immunoregulatory Cells

              Relapsing MS is a serious symptom which progresses into a chronic inflammatory demyelinating central nervous system disorder manifesting as morphological inflammation, demyelination, axonal loss and gliosis. There is massive infiltration of heterogeneous cellular population; and soluble mediators of the immune system are activated. These include T cells, B cells, macrophages and mi croglia, cytokines, chemokines, antibodies which stimulate  humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

 Demyelinization

                Research has shown where a lymphocytes subset identified as T helper cells specifically the Th1 and Th17 play a major role in development of multiple sclerosis lesions. Also the Interleukin 12 protein causes differentiation of naive T cells producing inflammatory T cells. When there is over production of Interleukin 12 it initiates inflammatory increases that occur in patients with persistent multiple sclerosis relapses. Patients who are not affected by multiple sclerosis their lymphocytes develop innate immunity to recognize and distinguish cells what cells belong to the body and those which are foreigner (Nakahara et.al, 2006).             

       Lymphocytes, in the body of a person afflicted by multiple sclerosis cannot differentiate between healthy and non-healthy cells. They attack cells in the central nervous system as foreigners such as viruses, bacteria, fungi triggering inflammatory responses as if it were a cell-mediated immunity conflict. In this process other immune cells such as cytokines and antibodies are activated and join in the inflammatory battle. Importantly, most myelin-recognizing T cells are family to a terminally differentiated subset known as co-stimulation-independent effector-memory T cells (Nakahara et.al, 2006).   See appendix 5   

Cell-Mediated Immunity

      T cells are responsible compromising an estimated 10% of the all inflammatory cells found as active participants in demyelinating multiple sclerosis lesions. Scientists have already proven that the EAE model can adequately be transferred by injecting an animal with myelin-specific CD4+ T cells. Therefore, the acceptable assumption has been that Multiple Sclerosis is foremost a CD4+ T-cell-mediated disease. It was advised that caution must be taken when interpreting these results because CD4+ T cells can play an important role in a disease stage-specific context. Importantly, they cells are absent in chronic Multiple Sclerosis lesions apart from the T-cell repertoire shows changes (Awad & Stüve 2010).

        Different T cell subtypes play significant roles in the pathogenesis of autoimmune diseases such as multiple sclerosis. Extensive studies have been conducted to validate these interactions. These diverse subpopulations contain distinct cytokine products.  ‘TH1 CD4 + cells secrete interferon gamma, tumor necrosis factor α, IL-2, and nitric oxide’ (Awad & Stüve 2010, p, 168).  TH1 cells are responsible for activating cell-mediated immunity. Alternatively, TH2 CD4+ cells secrete IL-4, IL-5, IL-6, IL-10, IL-13. They transform the growth factor β.  TH2 cells in humans function as a regulator agent when certain inflammatory conditions occur (Awad & Stüve 2010).

      The human system does not contain distinct TH1-TH 2 dichotomy. This adds to the complexity of explaining cell mediated immunity. Significantly, there is an overlap expression of cytokine between two subtypes TH1-TH 2 dichotomy which is a subtype of CD4+ cells. These cells have been implicated in the autoimmunity as TH17 cells. They express as proinflammatory cytokine IL-17. RNA (mRNA) encoding IL-17 messengers were detected in blood at very high levels cerebro spinal fluid (CSF) and brain parenchyma of multiple sclerosis patients in active stages of the disease (Awad & Stüve 2010).

      This phenomenon is highly suggestive of the major role cell mediated immunity plays in progression of multiple sclerosis as an immunopathogenesis factor in the disease sequence.  More importantly, it is worth noting that even though multiple sclerosis is often perceived as a CD4+-mediated autoimmune disease, there are CD8+ T cells implications in its pathology. Precisely, scientists have confirmed that clonal and oligoclonal expansion of CD8+ T cells consistently have appeared in plaques obtained from multiple sclerosis patients during diagnostic testing. In a few situations when evaluations were conducted, CD8+ T cells were found to have outnumbered CD4+ T cells (Awad & Stüve 2010).

        Again this is highly suggestive of suggesting cytotoxic T cells probably participation in starting this inflammatory interaction. Another factor worthy of consideration is the knowledge that T lymphocytes express γ/δ receptors were detected in various quantities when cerebro spinal fluid (CSF) of multiple sclerosis patients experiencing early stages of the disease. However, patients who had the disease for a longer time emerging into the chronic stages, CD8+ T cells were not found. The distinction lays in a probability that these cells play a role in the early development of the disease when cell medicate immune response is being activated.  More clarification on this phenomenon is pending while the pathogenic role of CD8+ T cells in multiple sclerosis progression is further explored (Awad & Stüve 2010).

Humoral Immunity

       Scientists posit that despite the autoimmune process in multiple is perceptive mainly from the premise of it being mediated by T cells; there is just as much evidence to suggest a great degree humoral immunity activity is also involved in the progression of disease process. Fundamentally, scientists discover that there have been interactions with an antigen driven B-cell response in multiple sclerosis patients’ cerebro spinal fluid. This is highly suggestive that B- cells are implicated in the immunopathogenesis of the disease. Also, oligoclonal immunoglobulin production persists in the cerebro spinal fluid of multiple sclerosis patients. Subsequently, growth of secondary lymphoid brain tissue was detected during diagnostic evaluations in multiple sclerosis patients experiencing secondary progressive stages of the disease. Some research studies have even shown a direct relationship between intrathecal immunoglobulin levels and severity of the disease when patients present with secondary progressive multiple sclerosis (Awad & Stüve 2010).

          Scientists have continued probing for evidence of humoral immunity implication. Researchers have also detected B cells in brain cerebro spinal fluid of secondary progressive multiple sclerosis patients. There has been constant isolation of B cells in the cerebro spinal fluid of patients with secondary progressive multiple sclerosis. Evidence of clonal expansion along with extensive somatic mutation in B-cell receptor genes was observed. This phenomenon expresses the characteristic features of an antigen-driven response. Precisely, the assumption is that B-cell selection might have been initiated in peripheral lymph nodes or in lymphoid follicles of the central nervous system (Awad & Stüve 2010).

            Further studies related to investigating B-cell compartment of cerebro spinal fluid in multiple sclerosis reveal that B-cell differentiation is confirmed in the central nervous system of individuals suffering from multiple sclerosis. The dominant antibodies happen to be short-living plasmablasts. Interestingly it is not plasma cells. Precisely, plasma cells are actually the predominant antibody secreting cell found in multiple sclerosis patients’ cerebro spinal fluid.               More importantly, the phenomenon whereby upregulation of costimulatory molecules on plasma cells within central nervous system  occurs is indicative the potential of such cells to sustain their T-cell activation.  Scientifically, B cells have been known as potent antigen-presenting cells. Assumptions are that they might feature prominently in T-cell antigenic stimulation. Scientists conclude that B cell and humoral immunity might be the main factors responsible for initiating and sustaining multiple the sclerosis disease process (Awad & Stüve 2010).

Immunoregulatory Cells

          Studies have revealed that isolating myelin-reactive T cells from peripheral blood of healthy subjects is highly suggestive that, perhaps, decreasing regulatory cells interactions is the basic immunopathology concepts in multiple sclerosis evolution and not he presence or absence  of self-reactive T cells.  Scientifically,   it has been accepted that regulatory cells play a major role in controlling intensity when immune response are activated by maintaining self-tolerance. Importantly, it has been proven that CD4+ TH2 cells are active in anti-inflammatory cytokines production. They are IL-4, IL-5, and IL-13. Precisely, this CD4+ TH2 has the ability of lowering regulatory function of macrophages (Awad & Stüve 2010).

    Further developments show where a relatively little subpopulation of CD4+ T cells were identified to be naturally occurring regulatory T (CD4+CD25+Treg) cells. It is believed that they are vital participants in the immune homeostasis process too. Certainly, they were found to be expressing CD25 which is an important component of the IL-2 receptor. However, preclinical trials have revealed that Treg cells’ absence was closely associated with the emergence of autoimmunity. Overwhelming evidence exists to prove that inadequate Treg-cell activity could be a main contributory element in multiple sclerosis etiopathogenesis. Essentially, studies show where  CD4+CD25+Treg cells effector function  emerging out of multiple sclerosis patients’ peripheral blood  samples of patients was deficient in comparison to CD4+CD25+Treg cells from subjects who were not afflicted by the disease (Awad & Stüve 2010).  .

         While these findings scientifically seem profound critics argue there are no differences in Treg cell concentration and constitution in the cerebro spinal fluid among patients afflicted by multiple sclerosis and those who were healthy. A larger study conducted on 73 multiple sclerosis researchers discovered that Treg cell concentration was identical with that of healthy volunteers. . The notable difference detected was that the Treg cells obtained from multiple sclerosis patients demonstrated reduction suppressive potential on the ‘immune response directed against myelin antigens’ (Awad & Stüve 2010, p 201). Yet, in another study this theory was refuted since, there were higher Treg cell counts in multiple sclerosis patients than in the control. Alternatively,  appeared the potential of these cells suppress MBP-induced proliferation was less effective (Awad & Stüve 2010)

        Explaining the functional differences of Treg cells activity in multiple sclerosis patents and healthy subjects there has been reports of activity in RRMS and progressive stages of the diseases too.  For example, Forkhead box p3 (FOXp3) has been identified as a popular transcriptional factor. Its main role has been detected being a valuable participant in Treg-cell-suppressive molecular programmer activity (Awad & Stüve 2010)

            Many preclinical studies have supported many of these theories in confirming the linkage between autoimmunity and absence of FOXp3. An association was also discovered with ectopic FOXp3 expression conferring suppressive function on CD4+CD25+Treg cells. Further linkages posit a relationship showing significant reductions in FOXp3 mRNA transcripts and protein levels. Importantly, this occurred without any concordant decrease in CD4+CD25+Treg representation in multiple sclerosis patents. FOXp3+CD4+CD25+Treg cells popularly create infiltrations when cerebro spinal fluid of subjects afflicted with neuro inflammatory diseases. Comparatively, this multiple sclerosis patients isolated more FOXp3+CD4+CD25+Treg cells   than patients afflicted by dementia, stoke  or  any other neurological disease. In addition it was observed that Treg activity seem to be compromised when peripheral blood samples are used for the analysis in multiple sclerosis patients unlike other non-affected clients.

Therapy and management

        There is no cure for multiple sclerosis. However, scientists continue to experiment with drugs and therapies, which can be useful in relieving symptoms. For example, David Virley (2005) conducted studies to explore strategies involved in ‘Developing Therapeutics for the Treatment of Multiple Sclerosis.’ The author posited that many animal models have been used in developing therapeutic interventions for treating relapsing multiple sclerosis. The aim of preclinical research was mainly to identify and validate novel targets that are the most appropriate mimics for the specific clinical situation. Animal models therefore, become valuable subjects in establishing drug development processes that help select suitable human subjects for therapeutic interventions. This process provides the proof-of-concept for continuance of clinical trials. The author further contended that ‘although there is no gold standard model of multiple sclerosis, experimental autoimmune/allergic encephalomyelitis (EAE) models simulate the clinical and pathological hallmarks of multiple sclerosis in various guises and can provide the necessary predictive index for clinical therapeutic application’  (Virley, 2005, p 639).

         EAE was induced by generating T-cell-mediated immunity into central nervous system antigens, which was easily modeled in rodents such as rats, mice, and guinea pigs. Whole CNS homogenate (spinal cord) t purified protein and peptides were combined in preparing the autoantigen for the experiment (Virley, 20050.  ‘Myelin basic protein (MBP), proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), S100β, and glial fibrillary acidic protein as well as specific peptides from respective parent proteins are encephalitogenic in the appropriate host, as the major histocompatability complex (MHC) is one of the major determinants of immune responsiveness and disease susceptibility to these self-antigen’ (Virley, 2005, p 639).

        The author concluded that the pathogenic autoimmune mechanism steps that initiate and magnify EAE and MS damage tissue sequences are:-

  • Activation of autoreactive CD4+ T-cells in the periphery to an antigen;
  • Transmigration of proinflammatory T-cells and monocytes through the blood brain barrier (BBB)
  • Amplification of local inflammation and activation of resident antigen-presenting cells (APCs), such as microglia; and 4) destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).

(See Appendix 4).

Current Drug Therapies

The foregoing trials have emerged into distinct therapies, which are now active treatment management intervention s for multiple sclerosis. To date there are only five Food and Drug Administration (FDA) approved therapeutic treatments for relapsing – remitting multiple sclerosis. They include ‘two interferon (IFN)-β1a agents (Avonex and Rebif), one IFN-β1b (Betaseron), glatiramer acetate (GA) (Copaxone) and Mitoxanthrone (Novantrone)’ (Virley, 2005, p 639).

      Patents suffering from secondary progressive multiple cyclophosphamide (Cytoxan) and mitoxanthrone are the drugs of choice. There are no extreme benefits in using these two drugs or severe toxicity. However, the main drugs used are corticosteroids, IFNβ and GA (Virley, 2005).

Corticosteroids

             Corticosteroids are administered to raise a patient’s tolerance level tolerance during an attack and speed up recovery. Long term therapies are more effective even though short-term interventions can be useful. However, to maintain a longer period between remissions it is always better to continue treatment over a longer period of time.  Patents often receive significant results even when the clinical course of multiple sclerosis may change to secondary progressive stage. Even with so many drug trials and pre-trials being conducted scientists are still not yet sure what are the actual effects of corticosteroid on the immune system are (Virley, 2005).

         However, preclinical research evidence has verified quite a few putative mechanisms. They embody ‘an inhibition of the Th1 immune response reduction in BBB molecules and protection of oligodendrocytes from cytokine-induced cell death’ (Virley, 2005, p 639). EAE models validated the suppressive interactions produced by corticosteroid treatment in relation to clinical course disruption of multiple sclerosis, T-cell migration dampening its antigens response suppression during expression of adhesion utilization of anti-glucocorticoid, RU 38486 (mifepristone). It was revealed that these interactions have intensified as well as reversed steroid-induced inhibition of disease (Virley, 2005).

      While corticosteroids have been so effective in the treatment of multiple sclerosis in both short and long term its side effected should not be underestimated. For example, extended use can initiate transient mood changes headache, gastrointestinal disturbances, and myalgias.  Decrease in bone density can occur overtime if patients must be treated for extended periods of time. Ultimately, osteoporosis could become a real problem increasing risks for fractures and infections. When side effects have become so progressive, the patient ought to be reassessed. Often the attending physician may consider either reducing or discontinuing treatment temporarily (Virley, 2005).

IFN-β

          IFN-β therapies emerged after over 25 years of clinical trials. The aim was finding how multiple sclerosis would respond to IFNs if it is truly a virally mediated disease. Importantly the   antiviral assumption became invalid after clinical trial assessments, which revealed that IFNγ worsened symptoms.  This was highly suggestive, that IFNγ  was more influential in multiple sclerosis pathological process. it meant that IFNβ, like other IFNs, is a species-specific glycoprotein with numerous biological properties. Actually, the mechanism producing these interactions is not fully understood from a scientific perspective poorly. However assumptions have been that immunomodulatory as an alternative to antiviral and antiproliferative makes much sense in deriving at an alternative proposition (Virley, 2005).

      Importantly, IFNβ-1a is exactly like the natural IFN-β, but IFNβ-1b differs in having two amino acids as well as not being glycosylated. Despite these insidious structural differences IFNβ-1b displays comparative biological activity to IFNβ-1a. Therefore, putative responses of IFNβ on the progression of multiple sclerosis is believed to be related primarily to its  antiinflammatory influences, which demonstrates as dampening the stimulatory impact of IFNγ, tumor necrosis factor (TNF)α, interleukin (IL)-12. The lymphotoxin secretion has been identified in the sequence of controlling monocyte activation; inhibiting disruption of BBB. Consequently, the entry of lymphocytes into the CNS is reduced; antigen presentation is reduced to T-cells; and up-regulation of anti-inflammatory cytokines occurs; TGFβ and IL-10 (Virley, 2005).

        EAE pre-trial models have validated the use of IFNβ by proving its influence in limiting the   progression of multiple sclerosis. Supportively, clinical trials were done using both IFNβ formulations. Important findings indicate a one third relapse reduction rate when higher doses are administered. The onset has been observed to be rapid. Precisely, relapses occurred at a rate of 1 per year and few weeks for MRI disease activity. Conversely, there were huge inflammatory changes measured through MRI activity; accumulation of MRI disease burden was significantly slowed down. Besides, there were magnificent results shown by patients regarding relapses (Virley, 2005).

      This novel treatment is not without its adverse side effects. Some include, flu-like symptoms along with reactions emerging at the site where injections are administered. If patients do not respond to the drug after six months of therapeutic intervention, the IFNβ therapy is usually discontinued. Some patients who are already disabled with progressive or relapses occurring at a rate of more than one per year are treated with a combination of combination three or more courses of corticosteroids over a 1-year period. In addition some patents encounter extreme feelings of depression leading towards suicidal inclinations. Drug toxicity can also become a problem with patients becoming noncompliant. This initiates physicians’ decisions of considering alternatives. Neutralizing antibodies in IFNβ effectiveness ought to be addressed as an adverse reaction during treatment. This can lead to long term complications. As such, it must not be ignored if patients complain of reactions or it shows up in diagnostic testing (Virley, 20 05).

   Glatiramer acetate – GA

          GA is considered a non-IFN, nonsteroidal therapy. It is made from synthetic random base copolymers mixtures containing four amino acids namely glutamic acid, alanine, lysine, and tyrosine). The molar ratio was highly specific. Trials researched investigated the GA’s potential encephalitogenic role using EAE animal models. However, surprisingly, it was discovered that GA suppressed their acute and chronic clinical and pathological hallmarks. Importantly, translation of impacts was clinically beneficial. Importantly, GA provided evidence in the initial phase II trial as being a suitable agent for reducing relapse rates by 76% in patients with relapsing-remitting multiple sclerosis. A 5 year follow up intervention treatment confirmed

GA benefits as being capable of sustaining the initial influence on relapses in multiple sclerosis patients. The progression of the disease into the secondary stages was significantly slowed. Patients did not enter into disability as quickly as when other drug therapies were used. Also, when the Lesion burden was assessed through MRI it validated the value of GA in helping patients during the relapsing-remitting episodes. It was discovered that GA greatly reduced  frequency  rates of lesion load  and new enhancing lesions when baseline pretreatment measures are compared (Virley, 2005).

     Since then numerous mechanisms were advanced as being responsible for these fascinating results observed by GA’s intervention in the disease process. First its biological activity relapsing-in remitting MS was noted as a valuable factor. Then the antigen-specific induction suppressor T cell was remarkable. Thirdly, a MBP competitive inhibition was distinctly observed as a benefit. There was also a relationship of the interactions to -peptides from antigen-presenting cells (Virley, 2005).

       It must be noted that regardless of how beneficial a new drug therapy may be in treating a disease there are always adverse effects, which must be considered in its administration. GA is no exception even though the tolerance level in multiple sclerosis patients is great. However, subcutaneous administrations could become harmful due to increasing incidences observed whereby injection site reactions occurred in the majority of cases and they were localized proving that it was the drug interaction with human skin (Virley, 2005).

             The overall picture being communicated in the use of this drug pertains towards it being the most tolerable in terms of side effects when compared to other therapies. Reduced propensity in the development of depression, neutralizing antibodies and menstrual disorders was far less when compared to other drugs now available for treating multiple sclerosis. Despite these developments, however, it is still important for continued research in extending to multiple sclerosis patients more options. While there is no cure for the condition medical science can provide the best relief it could through timely and efficient intervention therapies that work (Virley, 2005).

      Ultimately, these interventions should aim at not only providing relief, but secure sustained drug benefits reducing symptoms of multiple sclerosis, which shows that treatments are becoming more effective. Patents should be taking lower doses and experiencing fewer side effects. As such, pharmaceutical and biotechnology industries are challenged to provide this service to the multiple sclerosis community of patients. Essentially, numerous alternative disease-modifying strategies are emerging. They will be reviewed in the following pages of this document (Virley, 2005).

           For example, Pietro Iaffaldano (2012) and a group of researchers conducted studies regarding the ‘Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study.’ These researchers contend that Natalizumab reduced relapse rate as well as magnetic resonance imaging reactions in patients experiencing Relapsing-Remitting Multiple Sclerosis (RRMS). However, its impact on fatigue cognition in patients affected by multiple sclerosis need to be validated though scientific research. There the purpose of a prospective, open-label, observational study was intended as an  evaluation relating probable impacts  natalizumab had on cognition and fatigue when measured in patients experiencing Relapsing-Remitting Multiple Sclerosis  after being treated continuous for two years (Iaffaldano et.al, 2012).

        Researchers examined cognitive performances by applying  ‘Rao’s Brief Repeatable Battery (BRB) device, the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months’ (Iaffaldano, 2012, p  201).   When patients did not respond favorable to at least 3 BRM and ST 3 they revived a cognitively impaired (CI) classification. Every 12months the Fatigue Severity Scale (FSS) was administered. This assessed the patient’s ability to self-reported incidences of fatigue. A total of 1 53 patients participated in 1 and 2 year-natalizumab continuous treatment (Iaffaldano et.al, 2012).

       Result revealed that after one year treatment the amount of’ CI sampled patients decreased from 29% (29/100) at baseline to 19% (19/100) (p=0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p=0.008). These significant effects were confirmed in the subgroup of patients treated up to two year.’ (Iaffaldano et.al, 2012, p. 201). From these results researchers concluded that

In the short-term Natalizumab can be successfully used as a treatment which could, ultimately reduce incidences of cognitive difficulties and fatigue in patients experiencing Relapsing-Remitting Multiple Sclerosis (Iaffaldano et.al, 2012).

Examples of Novel Therapeutic Challenges for Multiple sclerosis

Blockade of lymphocyte migration

       Very late antigen-4: natalizumab (Tysabri) and small molecule antagonists. There is widespread evidence implicating very late antigen-4 (VLA-4, α4-β1 integrin) in this process, via its interaction with receptors like vascular cell adhesion molecule 1 (VCAM-1) and the CS1 fibronectin domain (Virley, 2005).

Immunomodulatory agents

       Interest recently has emerged regarding development of novel Immunosuppressants. Trials have been conducted and they have been actually used in treatment of many autoimmune diseases such as psoriasis and rheumatoid arthritis. They reduced exacerbations keeping progression (Virley, 2005).

Anti-inflammatory agents

‘Cycloxygenase-1 and -2 (COX-1 and COX-2 or prostaglandin H synthases 1 and 2) catalyze the conversion of arachidonic acid and oxygen to generate inflammatory prostaglandins such as PGE2, PGD2, PGF2a, and thromboxane’ (Virley, 2005, p 201).

Neuroprotective and neuroregenerative therapeutic strategies

       Achievements in repair of myelin and immense neuroprotection though therapeutic interventions can be interpreted major research breakthrough in the attempt at providing more beneficial therapies that reverse permanent neurological disability associated multiple sclerosis.

Potential combinations of therapeutic strategies

       The heterogenic influences of clinical response as well as pathological hallmarks contained in recent multiple sclerosis drug development it would be wise considering combining therapeutic strategies that differentiate concentrating of specific aspects of the disease such as cognition memory and fatigue as espoused by Iaffaldano and his team of researchers. An area of precedence is a development stage whereby each agent independently offers a benefit distinct from the others, but is still valuable when combined in adding synergistic value to the therapeutic intervention. This approach would be extremely beneficial for patients who seldom respond favorable to therapies now available on health care markets across the country and world (Virley, 2005, p 201).

Conclusion

               While theories pertaining to the etiology/epidemiology/immunology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explored the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of this disease. Consequently, the researcher adapted a comparative analysis of the perspectives offered by theorists in discussion of epidemiology regarding emergence of multiple sclerosis among the predominantly, female young adults twenty-first century population. These were matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management, and current trends are being explored.

Current Trends

                   Precisely, Ascherio and Munger (2007) ‘Environmental risk factors for multiple sclerosis Part I: the role of infection’ contend that even through genetic susceptibility play a role in the acquisition of multiple sclerosis among families studies show where personal hygiene significantly affect occurrence of the disease. Further, they advance that genetics and environment alone cannot account explicitly for the MS frequency among geographic variations when risk changes with migration are taken into consideration. Supportive epidemiological findings highlights the “hygiene hypothesis,” showing the additional role Epstein-Barr virus (EBV) plays as evidence for MS risk factor (Ascherio & Munger, 2007)

             Another piece of research literature by the same authors ‘Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors focusing on the environment explains that the change risk factor among migrants gives profound evidence for M.S environmental determinants. Then researchers defined environment to mean variations in diet and social behavior. Main contributory factors were sunlight and cigarette smoking (Ascherio & Munger, 2007)

     Dyment, Ebers, and Sadovnick, (2004) took a stand in ‘Genetics of multiple sclerosis.’          They argue that while environment and infection may play a role many genes appear to be linked to  MS etiology. They mentioned ‘HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A’ (Dyment et.al, 2004, pp 110). These researchers advanced that future development in the MS genetic science largely depends on continuous research making data available as evidence. Also the development of appropriate statistical measurements and research methodologies could be valuable (Dyment et.al, 2004).

             George Ebers (2008) focused on ‘Environmental factors and multiple sclerosis’ in reporting that studies conducted in Canada show where environmental factors influence the distribution of MS in specific geographic locations. The researcher cited migration studies to prove that the increase incidence of MS in Canada relates to longitudinal sex ratio expansion among immigrants within the country. This was compared to studies conducted in Australia where similar geographic patterns exist. It was discovered that by modifying the environment it reduced 80% of cases. It was concluded that while genetics play a major role there are predominant environmental factors associated with MS incidences in certain geographic locations (Ebers, 2008).

       Gavin Giovannonia and George Ebers (2007) posit that ‘genes and environmental factors lead to tissue injury by autoimmune mechanisms, implicated by strong circumstantial evidence’ (Giovannonia and Ebers, 2007 pp, 261). They further contend that it is difficult to identify the specific genes responsible for MS without examining the associating influences of the environment. Actually, they argue that the impact of genes on MS emergence is modest. Additional studies were cited emphasizing irregularities in confirming the genetic theory of MS etiology (Giovannonia and Ebers, 2007).

                Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed at addressing the autoimmune etiology of the disease. These therapies are designed to reduce inflammation, but their long term effect is uncertain. Hence, a re-evaluation of both pathogenesis and etiology is suggested (Nakahara et.al, 2012).

                     Rosati offered insights to say that the childhood environmental factor was a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

               Consequently, this study’s importance pertains to advancements into understanding multiple sclerosis’ etiology, pathophysiology/immunology and treatment. As explained in the foregoing principal pieces of research literature theories relating the etiology of MS are numerous. However, theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure.

       Current therapeutic trends predict that the ideal treatment for multiple sclerosis mustconsist oftechniques aimed at increasing disease-causing/sustaining antigen(s) tolerance. Ultimately, it is expected that long-term therapy would be obviated. This is important because amidst  numerous continuous drug trials scientist still contend that none of them seem to have considerable effects on resolutions of a disease which is over 100 years old. Justifiably establishing coordination between activated T cells and B cells in the pathophysiology of multiple sclerosis is highly recommended for targeting the two cell population. These include resting and dividing cells together. The strategy may necessitate, taking control of the disease process itself (Awad & Stüve, 2010).   

          Whatever emerges from these assumptions scientist must bear in mind that other immune cell populations are playing a major role also in the sequel of this disease. They intimate and perpetuate the process. Therefore, the final proposition of this theory advanced that amplifying or sparing the pool of regulatory cells which act as mediators of immune suppression would be valuable a valuable intervention. This however must be embraced without compromising immune surveillance in the treatment of this disease (Awad & Stüve, 2010). In concluding these deliberations pertaining to current trends in multiple sclerosis therapeutic management it is expected that this research project sensitize scientists into elaborating on present research practices in order for a consensus be reached regarding the reality of multiple sclerosis etiology and its pathological implications.

References

Ascherio, A., & Munger, K (2007). Environmental risk factors for multiple sclerosis. Part I: the

                      role of infection. Ann. Neurol. 61(4); 288–99

Ascherio, A., & Munger, K. (2007). Environmental risk factors for multiple sclerosis. Part II:

                     Noninfectious factors. Ann. Neurol.  61(6); 504–13.

Awad, M., & Stüve, O. (2010). Immunopathogenesis of Multiple Sclerosis: New Insights and

                    Therapeutic Implications. Lifelong Learning in Neurology. 16(5); 166-180

Clanet M (2008). Jean-Martin Charcot. 1825 to 1893. Int MS J 15 (2), 59–61.

DasGupta, R., & Fowler, C. (2003). Bladder, bowel and sexual dysfunction in multiple  

                       sclerosis: management strategies.  Drugs, 63 (2): 153–66.

Dyment, A; Ebers, G; Sadovnick, A. (2004).  Genetics of multiple sclerosis. Lancet

                                 Neurol  3( 92). (2004): 104–10.

 Ebers, G. (2008). Environmental factors and multiple sclerosis. Lancet Neurol  

                              7 (3). 268–277.

Foley, P. Vesterinen, H. Laird, B. (2013). Prevalence and natural history of pain in adults with

                       multiple sclerosis: Systematic review and meta-analysis. Pain 154 (5): 632– 42

Gilden, D (2005). Infectious causes of multiple sclerosis. The Lancet Neurology 4  (3)

                                    195–202.

Giovannoni, G; Ebers, G. (2007). Multiple sclerosis: the environment and causation. Curr

                                Opin Neurol. 20( 3); 261-8.

Kantarci, O., & Wingerchukb, D. (2006). Epidemiology and natural history of multiple sclerosis:

                             new insights. New York. Lippincott Williams & Wilkins

Kurtzke, J. (1983). Rating neurologic impairment in multiple sclerosis: an expanded disability

                          status scale (EDSS). Neurology, 33 (11); 1444–52.

Iaffaldano, P. Viterbo, G. Paolicelli, D. ( 2012). Impact of Natalizumab on Cognitive

               Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label,

                  Two Years Observational Study. PLoS . 7(4)

Merril, R. (2010). An Introduction to Epidemiology, (5th Edition). Jones and Bartlett

                   Publishing.

Murray, J (2002). Infection as a cause of multiple sclerosis. Theories abound because no one

                         knows the answers yet. BMJ. 325(7373).(2002). 1128.

Nakahara, J; Maeda, M; Aiso, S; Suzuki, N ( 2012). Current concepts in multiple

                             sclerosis: autoimmunity versus oligodendrogliopathy. Clinical reviews in

                           allergy & immunology  42(1); 26–34.

 Oksenberg, J., & Barcellos, L (2000). The complex genetic etiology of multiple sclerosis.

                           Journal of NeuroVirology. 6(2), S10 ± S14

Rosati G (2001). The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 22

                (2): 117–39.

Royal College of Physicians London (2004) Multiple Sclerosis: National Clinical Guideline for

                Diagnosis and Management in Primary and Secondary Care. NICE Clinical

              Guidelines, No. 8.National Collaborating Centre for Chronic Conditions (UK).

               London

   Schäffler, N. Köpke, S. Winkler, L. Schippling, S. Inglese, M. Fischer, K.,  & Heesen, C.

      (2011). Accuracy of diagnostic tests in multiple sclerosis–a systematic review. Acta Neurol

                      Scand. 124(3), 151-64

Siegert, R., Abernethy, D. (2005). Depression in multiple sclerosis: a review. J. Neurol.

                     Neurosurg. Psychiatr. 76 (4): 469–75.

Terry, R. Miller, S. Getts, D., & Muller, M. (2012). Current Theories for Multiple Sclerosis

                    Pathogenesis and Treatment. Free Press New York. 2012.

 Virley, D. (2005). Developing Therapeutics for the Treatment of Multiple Sclerosis. NeuroRx.

                 2(4): 638–649.

Appendix 1

Table 1 Multiple sclerosis as a genetic disease

———————————————————————————

1. Racial clustering of MS cases. Resistant ethnic groups residing in high risk regions

2. Familial aggregation of MS cases. Increased relative risk to sibs (ls=20±40)

3. Low incidence of conjugal MS

4. MS sibling pairs tend to cluster by age of onset, rather than

year of onset

5. High disease concordance in monozygotic twins (25±30%) compared with dizygotic twins and non-twin siblings (3±5%)

6. No detectable effect of shared environment on MS susceptibility in first-degree non-biological relatives (spouses, adop-tees)

7. Suggestive correlations between certain polymorphic loci and disease susceptibility

————————————————————————————

Appendix 2

Table 2 Confounding factors in genetic studies of multiple

Sclerosis

————————————————————————————————-

1. Aetiologic heterogeneity identical genes, different phenotypes

2. Genetic heterogeneity Different genes, identical phenotypes

3. Unknown genetic parameters Single versus multiple genes Dominant versus recessive mode of inheritance incomplete penetrance

4. Epistatic gene interactions

5. Post-genomic mechanisms

6. Unidentied non-heritable (environmental) factors

——————————————————————————————————————

(Oksenberg & Barcellos, 2000).

Appendix 3

Medicine and Health: Multiple Sclerosis

Name of Author

Outline

Introduction

•          Description

•          Epidemiology

•          Clinical signs and symptoms

•          Diagnosis

•          Prognosis

Immunological concepts underlying the disease

Therapy and management

Conclusion

•          Current Trends

Abstract

The purpose of this document is to offer a precise account of Multiple Sclerosis. The statement of problem related to this research reads ‘while theories pertaining to the etiology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explores the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of the disease. Consequently, the researcher will adapt a comparative analysis of the perspectives offered by theorists regarding emergence of multiple sclerosis among the twenty-first century female young adults. These will be matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management as well as current trends are explored.

Medicine and Health: Multiple Sclerosis

Introduction

Description

          Multiple sclerosis was not discovered as a disease until late 19the century. An English Physician by the name of Walter Moxon in 1873 along with American Dr. Edward Seguin in 1878 discovered multiple sclerosis as a dysfunction of the nervous system. They confirmed that it was more common in women than men. However, three notable signs of multiple sclerosis signs described as Charcot’s triad 1 being nystagmus, intention tremor, and telegraphic speech (scanning speech) have been attributed to French neurologist Jean-Martin Charcot (1825-1893). He  recognized cognition alterations, which was described as “marked enfeeblement of the memory” and “conceptions that formed slowly” (Clanet, 2008, p 58).  At the time these doctors did not project any sound etiology of the disease, but said that there was no evidence to support it being inherited. However, they confirmed that numerous diverse neurological irregularities were produced as symptoms of the condition (Terry et.al, 2012).

            Multiple sclerosis (MS); disseminated sclerosis is also known as encephalomyelitis disseminata. Scientists have described it as an inflammatory condition characterized by formation of myelin sheaths around brain and spinal axons tissue. Ultimately, these tissues are destroyed through scarring; reduction in myelin to protect brain and spinal cord. Research is still being conducted regarding its etiology, Assumptions however have been that many predisposing genetic, environmental and infection factors could initiate the inflammation (Ascherio & Munger, 2007).

      Other assumptions have been that there are mechanisms within the body chemistry, which are responsible for destruction of the immune system inhibiting production of myelin cells. Consequently, massive insidious nerve destruction occurs and nerve cells become incapable of functioning as communicators of impulses across nerve ending within the human body. Often when the etiology of a disease is obscure there is seldom a cure. Recent research has continued to advance ther theory that indeed multiple sclerosis affects more females than males (Nakahara et.al 2012)

        To date scientists have advanced from repeated research that there is no discrimination as to which neurological symptoms can emerge due to nerve destruction in the brain and spinal cord which are the primary target organs. From observation there have been immense progressive physical and mental dysfunctions. In some cases memory irregularities could develop, but a difficultly exists classifying them as purely psychiatric because they may present in conjunction with various levels of other neurological abnormalities. As the disease evolves it converges into many misleading features increasing the challenge of addressing the real symptoms in devising modes of treatment intervention. Scientists have described this phenomenon as an escalation of new symptoms, which were not formerly associated with the initial presentation. They are termed relapsing forms and progressive forms respectively (Dymentet.al, 2004)

        The period from when attacks begin end, and begin again symptoms may subside. However after these episodes permanent nerved damage occurs. As the disease advances symptoms worsens and exacerbations seems to occur leading up to when treatment becomes ineffective. This disease is more than 100 years old, but scientists have not been articulate in arriving at any profound etiology while numerous theories exist. They have not gone far beyond exploring mechanisms related to the disease process itself (Ascherio & Munger, 2007).

       Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed only at addressing the autoimmune etiology of the disease. As such, they merely focus on restoring function to affected nerves after symptoms become uncontrollable; control recurrence and limit the extent to which nerve damage produces disability (Nakahara et,al, 2012).

          However, medications used to treat multiple sclerosis are not without their serious side effects, besides being poorly tolerated by patients. Consequently, patients turn to alternative medicine for relief. Precisely, since there are few studies conducted regarding alternative remedies these remedies are considered nonscientific and are not recommended even through patient report how successful these treatments have been in restoring nerve function (Gilden, 2005).

      People diagnosed with multiple sclerosis live an average 5-10 years, less than persons who do not have the disease. There is an average of 2 persons affected by multiple sclerosis for every 150 per 100, 000 (Rosati, 2001).  However, data or theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure. This research is expected to sensitize scientists into elaborating on present research practices in arriving at a consensus regarding the reality of multiple sclerosis etiology.

Epidemiology

      Epidemiology infers a study of disease patterns that evaluates infection etiology; geographic, socioeconomic status, genetics and demographic variations. Often epidemiologists add to the multiple sclerosis body of knowledge through assessing relationships between these factors. Since there are no known causative factors for multiple sclerosis it is important that epidemiologists continue investigations regarding migration patterns. However, it must be understood that figures published in epidemiology records are all estimates. This is an attempt at establishing a more profound understanding regarding multiple sclerosis target populations across the world. It also helps identifying and explaining geographic locations containing highest and lowest multiple sclerosis rates (Merril, 2010).               

        The challenge facing the epidemiology of multiple sclerosis lays in the difficulty diagnosing the disease. No single distinct tests are being conducted in establishing a diagnosis for multiple sclerosis. As such, the argument is that diagnoses can be incorrect delayed or just bypassed. While MRI technology has been of great assistance in resolving difficult diagnoses epidemiologists question the accuracy of diagnoses produced from previous studies since they may not give a true representation of multiple sclerosis with the given population. More importantly, various methodologies used by specialists collecting data on the disease can greatly alter interpretations and outcomes. Due to these factors the epidemiology of multiple sclerosis is still in its infancy even though the disease is over 100 years old (Merril, 2010).              

                 According to Orhun Kantarci and Dean Wingerchukb (2006) multiple sclerosis claims the health of approximately 1 000 000 people between 17 and 65 years old internationally. The 2000 projected multiple sclerosis prevalence rate among white US populations showed 191 per100 000. Alternatively, the US overall incidence rate and was 7.3 per 100 000 person in the same year. Further epidemiological studies supported the theory that multiple sclerosis is two times more common in women than men. It was discovered also that there is a tendency for a later onset of the disease among men. The prognosis for them is even worse for women. Scientists attribute this difference to gender-dependent and phenotypic variability factors which may create an etiological predisposition (Kantarci & Wingerchukb, 2006).

        Multiple sclerosis care cost United States government an estimated $6.8 billion annually, which includes loss in productivity as well as actual health care interventions. A total life time cost is estimated at 2.2 million per patient (Kantarci & Wingerchukb, 2006).Similar epidemiological estimates exist around the world. There seems to be patterns of ‘a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere’ (Rosati, 2001, p 22). Multiple sclerosis is less prevalent among people who live close to the equator. Theories pertaining to climate, sunlight and vitamin D intake are variables used in relating possible causes in explaining this latitude gradient theory regarding geographic disposition multiple sclerosis prevalence among people living near to the equator (Rosati, 2001).

     Overtime other variations have appeared, which forced epidemiologist to consider environment in combination with genetics. Multiple sclerosis was discovered to be prevalent among northern European populations and most common in certain ethnic groups such as ‘Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori’ (Rosati, 2001, p 22).

       Childhood environmental factors were then considered as a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

      Critics of the environmental epidemiological theory have contended that quantification of the assumptions is difficult because data derived is obtained mainly from retrospective case-control studies whereby subjects are exposed to the same environment and results may lack internal and external validity besides containing reliability issues. ‘A practical, albeit limited, design is a nested-cohort study in which a population cohort already identified for exposure to given factor(s) for another disease is exploited for excess of -NIS occurrence after sufficient follow- up’(Kantarci & Wingerchukb, 2006, p 249). While trying to make sense of the environmental theoretical epidemiological perspectives major advances have implicate viral exposure factors. Viruses identified are canine distemper virus, Epstein-Barr virus, and human herpes virus-6) (Kantarci & Wingerchukb, 2006).

           Internationally, conclusions are that multiple sclerosis makes its first appearance in adults during their thirties. It can occur at any time in children. However, the primary progressive subtype appears later in people in their fifties.  The genetic epidemiology of multiple sclerosis seems to be overlapping with both environmental and viral/infections. Analysts have discovered that the only facts they have to support the genetic epidemiology are its high incidence among Northern Europeans in relation to indigenous populations from the ‘same geographic location, familial aggregation’(Kantarci & Wingerchukb, 2006, p 249). See appendix 1 and 2

Clinical signs and symptoms

                 Numerous signs and symptoms are associated with multiple sclerosis. However neurologists keep abreast of symptoms by applying the Expanded Disability Status Scale (EDSS).  EDSS gives a score total of a scale ranges from 0 to 10.

 ‘The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.  The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. In addition, it also provides eight subscale measurements called Functional System (FS) scores. These subscale categories are listed below.  The levels of function within each category refer to the eight functional systems affected by MS’ (Kurtzke, 1983).

  • Pain

              Pain is very common among multiple sclerosis patents and often appears after the first lesion is formed. In most occasions it is associated with the control mechanisms which regulate ascending and descending tracts in the anterolateral system. From 28 studies researchers proved taking a sample of 7101 multiple sclerosis patients that 63% complained of various degrees of pain. There were no significant differences in pain levels among men and women or people with greater disability than others.  Most pain occur as ‘headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte’s phenomenon (16%) and Trigeminal Neuralgia (3%)’ (Foley et.al, 2013, p 632).

  • Emotional disturbance

       Emotional disturbance manifests as clinical depression. This can extend into a life time complication. Present incidence rates range between 40–50% per person diagnosed with multiple sclerosis. Brain imaging studies have tried to relate findings to depression when brain lesions are found. More importantly, most neurologists have associated these brain lesions with neuropathology of the left anterior temporal/parietal regions. It is very important development that is worth monitoring carefully because emotional disturbance is responsible for 15% of deaths emerging from suicide. As such, patients are closely evaluated when signs anger, anxiety, hopelessness, and frustration surface (Siegert, Abernethy, 2005).        

  • Bladder and Bowel irritability

       Bladder disturbances occur in 70% of all multiple sclerosis patients. It presents as frequency, hesitancy and incontinence which can affect maintenance of personal hygiene. Bowel issues appear in 70% of the multiple sclerosis patients, 50% suffer from constipation 30% fecal incontinence (DasGupta & Fowler, 2003).            

  • Cognitive disturbances

       40%- 60% of multiple sclerosis patients encounter cognitive difficulties. It ranges from simple degrees of forgetfulness to severe loss of memory. Other cognitive difficulties are attention deficit; neurological fatigue; processing speed and visual spatial ability alterations (Ebers, 2008).

  • Impaired Mobility

           Mobility changes become evident when walking, moving, getting off and on the bed and balancing. Research has shown that between the onset of the disease and 5 years 50% of patient score 6 on the EDSS scale. 10 years living with multiple sclerosis 25% of patients can attain just a score of 6 on the Expanded Disability Status Scale (EDSS). This makes using a walker and other methods of mobility support necessary. Within 30 years, 83% of patients use walking aids (DasGupta & Fowler, 2003).           

  • Speech difficulties

Speech could become slurred and tone of voice altered.

  • Muscle Tremor and Ataxia

Ataxia coincides with muscle tremors. Clumsy movement occurs creating difficulty in maintaining a steady gait. Muscle tremors are often uncontrollable involuntary episodes of shaking.

  • Transverse myelitis 

When multiple sclerosis begins invading deep into spinal cord tissue lower body functions become impaired. These include bladder/irritability as well as sexual potency in males. Inability to have an erecting is possible along with ejaculation difficulties

  • Spasticity

Spasticity manifests as both a sign and symptom. Muscles, especially, in the extremities become very stiff and immobile.

Diagnosis

           Researchers have posited that multiple sclerosis is difficult to diagnose since confirmation of the disease cannot be made on clinical symptoms alone. Signs and symptoms may resemble many other neurological disorders. To facilitate diagnosis during the early stages scientists have designed standardized criteria. They include Schumacher, Poser and McDonald criteria.

Schumacher’s criterion is a neurological examination detecting central nervous system abnormalities involving two or more systemic dysfunctions. Often white matter abnormalities are evident in brain and spinal tissue. In 1983 these criteria were modified by Poser accounting for clinically definite; laboratory supported definite; clinically probable and laboratory supported probable multiple sclerosis (Royal College of Physicians of London, 2004).

                          McDonald criteria are the ones presently used in most health care institutions across the world for making a more accurate multiple sclerosis diagnosis. It includes a

  • Diagnostic criteria for suspected MS (two or more attacks)        Flowchart Icon  
  • Diagnostic criteria for suspected MS (monosymptomatic)         Flowchart Icon
  • Diagnostic criteria for suspected MS (single attack)                   Flowchart Icon
  • Diagnostic criteria for suspected MS (progressive from onset)      Flowchart Icon

                             (Royal College of Physicians of London, 2004)

               However, Schäffler, Köpke , Winkler , Schippling , Inglese , Fischer and, Heesen (2011) have reprted that the development of a new diagnostic criteria for multiple sclerosis was recently proposed after a systematic literature review  revealed that present accuracy issues made some tests invalid. The aim of this study was to validate diagnostic studies and clarify the value of diagnostic test used in offering a diagnosis. They included in their review a minimum of 40 patients who were traced for 2 years. This limitation existed in all the studies reviewed since they significantly lacked a gold standard measurement for validating the diagnostic tests that were used in those trials. A second relapse phase was adopted as a surrogate in relapsing-remitting multiple sclerosis testing. However, the lengthy 5 year follow-up created difficulty in detecting all cases. Also, quite a few studies contained various levels of validity and reliability issues. Notably, a selection bias was identified due to the indistinct classification of a clinically isolated syndrome (Schäffler et.al, 2011).

                  Based on these limitations, ‘sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%; Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%; combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%)’ (Schäffler et.al, 2011, 153). The researchers did not find justification in conclusions derived in the literature review studies. Further they suggest that ‘a combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis’ (Schäffler et.al, 2011, 153).

Prognosis

         While there is no cure for multiple sclerosis it has not been considered a fatal disease even though it severely affects a person’s quality of life. Serious disability does not occur until about 20 years after onset of the disease. Women seem to have a better prognosis than males. Factors affecting each patient’s prognosis regarding quality and length of life relate  to  adherence of health promotion strategies that will limit symptoms , doctor’s  appointment  follow up ; compliance with medication management to reduce progression of the disease. Generally life expectancy is reduced by 5-10 years with careful intervention strategies (Murray, 2002).

Immunological concepts underlying Multiple sclerosis

          Immunology relates to the body’s defense mechanisms in counteracting  the activity of invading agents. For every disease entity that enters the human internal environment there are diverse strategies employed by the immune system in a comprehensive effort to interrupt the intended invasion consequences. Consequently, the immune system builds up resistance by developing immunity to the invading organisms. There are mainly five types of immunological responses that can emerge from this activity. They are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

Humoral immunity

         Humoral immunity is also known as antibody-mediated system being mediated macromolecules located in extracellular fluids like secreted antibodies, antimicrobial peptides and complement proteins. Usually, humoral immunity reacts with substances in body fluid humors (Nakahara et.al, 2006).

Cell-mediated immunity

          Cell-mediated immunity does not rely on producing antibodies in order to defend the body against harmful organisms. Instead it activates phagocytes, antigen-specific cytotoxic T-lymphocytes, and disperses numerous cytokines in an antigen response (Nakahara et.al, 2006).

Innate or Natural Immunity

 Innate immunity is the body’s evolutionary natural mechanism used to fight invading foreign species. This is the dominant and oldest type of immunity among living creatures including unicellular organism such as amoeba, fungi, plants and insects (Nakahara et.al, 2006).

Acquired immunity

      Acquired immunity emerges after exposure to a foreign organism. It is also known as adaptive immunity due to somatic hypermutation or accelerated somatic mutations), and V (D) J recombination, which is actually a genetic antigen receptor recombination that cannot be reversed (Nakahara et.al, 2006).

Non-specific immunity

               Non-specific immunity means that the immunological response is antigen independent and unspecified. However, distinct mechanisms are activated. They include establishing anatomical barriers, stimulation of secretory molecules and integrating cellular components.  Recognizable mechanical anatomical barriers include the internal epithelia tissue such as the skin.  Intestinal mobility along with oscillation of broncho-pulmonary cilia is chemicalized because chemical messages are transmitted through biological agents present in skin, intestines and nervous system.

                   DominantImmunological concepts associated with multiple sclerosis are connected to the pathogenesis of this disease. Some basic traditional immunological concepts pertaining to multiple sclerosis are:-

  • Relapsing MS
  • Secondary progressive MS.
  • Progressive MS.
  • Progressive relapsing MS

While these are the four major immunological concepts that intermingle in explaining the pathophysiology of each stage collectively in facilitating the discussion other will be highlighted. Significantly, coinciding with the five types of immunological responses that can emerge from antigen antibody interaction are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity. Therefore, the terms that will be explained in this section are:

  • Demyelinization
  • Cell-Mediated Immunity
  • Humoral Immunity
  • Immunoregulatory Cells

              Relapsing MS is a serious symptom which progresses into a chronic inflammatory demyelinating central nervous system disorder manifesting as morphological inflammation, demyelination, axonal loss and gliosis. There is massive infiltration of heterogeneous cellular population; and soluble mediators of the immune system are activated. These include T cells, B cells, macrophages and mi croglia, cytokines, chemokines, antibodies which stimulate  humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

 Demyelinization

                Research has shown where a lymphocytes subset identified as T helper cells specifically the Th1 and Th17 play a major role in development of multiple sclerosis lesions. Also the Interleukin 12 protein causes differentiation of naive T cells producing inflammatory T cells. When there is over production of Interleukin 12 it initiates inflammatory increases that occur in patients with persistent multiple sclerosis relapses. Patients who are not affected by multiple sclerosis their lymphocytes develop innate immunity to recognize and distinguish cells what cells belong to the body and those which are foreigner (Nakahara et.al, 2006).             

       Lymphocytes, in the body of a person afflicted by multiple sclerosis cannot differentiate between healthy and non-healthy cells. They attack cells in the central nervous system as foreigners such as viruses, bacteria, fungi triggering inflammatory responses as if it were a cell-mediated immunity conflict. In this process other immune cells such as cytokines and antibodies are activated and join in the inflammatory battle. Importantly, most myelin-recognizing T cells are family to a terminally differentiated subset known as co-stimulation-independent effector-memory T cells (Nakahara et.al, 2006).   See appendix 5   

Cell-Mediated Immunity

      T cells are responsible compromising an estimated 10% of the all inflammatory cells found as active participants in demyelinating multiple sclerosis lesions. Scientists have already proven that the EAE model can adequately be transferred by injecting an animal with myelin-specific CD4+ T cells. Therefore, the acceptable assumption has been that Multiple Sclerosis is foremost a CD4+ T-cell-mediated disease. It was advised that caution must be taken when interpreting these results because CD4+ T cells can play an important role in a disease stage-specific context. Importantly, they cells are absent in chronic Multiple Sclerosis lesions apart from the T-cell repertoire shows changes (Awad & Stüve 2010).

        Different T cell subtypes play significant roles in the pathogenesis of autoimmune diseases such as multiple sclerosis. Extensive studies have been conducted to validate these interactions. These diverse subpopulations contain distinct cytokine products.  ‘TH1 CD4 + cells secrete interferon gamma, tumor necrosis factor α, IL-2, and nitric oxide’ (Awad & Stüve 2010, p, 168).  TH1 cells are responsible for activating cell-mediated immunity. Alternatively, TH2 CD4+ cells secrete IL-4, IL-5, IL-6, IL-10, IL-13. They transform the growth factor β.  TH2 cells in humans function as a regulator agent when certain inflammatory conditions occur (Awad & Stüve 2010).

      The human system does not contain distinct TH1-TH 2 dichotomy. This adds to the complexity of explaining cell mediated immunity. Significantly, there is an overlap expression of cytokine between two subtypes TH1-TH 2 dichotomy which is a subtype of CD4+ cells. These cells have been implicated in the autoimmunity as TH17 cells. They express as proinflammatory cytokine IL-17. RNA (mRNA) encoding IL-17 messengers were detected in blood at very high levels cerebro spinal fluid (CSF) and brain parenchyma of multiple sclerosis patients in active stages of the disease (Awad & Stüve 2010).

      This phenomenon is highly suggestive of the major role cell mediated immunity plays in progression of multiple sclerosis as an immunopathogenesis factor in the disease sequence.  More importantly, it is worth noting that even though multiple sclerosis is often perceived as a CD4+-mediated autoimmune disease, there are CD8+ T cells implications in its pathology. Precisely, scientists have confirmed that clonal and oligoclonal expansion of CD8+ T cells consistently have appeared in plaques obtained from multiple sclerosis patients during diagnostic testing. In a few situations when evaluations were conducted, CD8+ T cells were found to have outnumbered CD4+ T cells (Awad & Stüve 2010).

        Again this is highly suggestive of suggesting cytotoxic T cells probably participation in starting this inflammatory interaction. Another factor worthy of consideration is the knowledge that T lymphocytes express γ/δ receptors were detected in various quantities when cerebro spinal fluid (CSF) of multiple sclerosis patients experiencing early stages of the disease. However, patients who had the disease for a longer time emerging into the chronic stages, CD8+ T cells were not found. The distinction lays in a probability that these cells play a role in the early development of the disease when cell medicate immune response is being activated.  More clarification on this phenomenon is pending while the pathogenic role of CD8+ T cells in multiple sclerosis progression is further explored (Awad & Stüve 2010).

Humoral Immunity

       Scientists posit that despite the autoimmune process in multiple is perceptive mainly from the premise of it being mediated by T cells; there is just as much evidence to suggest a great degree humoral immunity activity is also involved in the progression of disease process. Fundamentally, scientists discover that there have been interactions with an antigen driven B-cell response in multiple sclerosis patients’ cerebro spinal fluid. This is highly suggestive that B- cells are implicated in the immunopathogenesis of the disease. Also, oligoclonal immunoglobulin production persists in the cerebro spinal fluid of multiple sclerosis patients. Subsequently, growth of secondary lymphoid brain tissue was detected during diagnostic evaluations in multiple sclerosis patients experiencing secondary progressive stages of the disease. Some research studies have even shown a direct relationship between intrathecal immunoglobulin levels and severity of the disease when patients present with secondary progressive multiple sclerosis (Awad & Stüve 2010).

          Scientists have continued probing for evidence of humoral immunity implication. Researchers have also detected B cells in brain cerebro spinal fluid of secondary progressive multiple sclerosis patients. There has been constant isolation of B cells in the cerebro spinal fluid of patients with secondary progressive multiple sclerosis. Evidence of clonal expansion along with extensive somatic mutation in B-cell receptor genes was observed. This phenomenon expresses the characteristic features of an antigen-driven response. Precisely, the assumption is that B-cell selection might have been initiated in peripheral lymph nodes or in lymphoid follicles of the central nervous system (Awad & Stüve 2010).

            Further studies related to investigating B-cell compartment of cerebro spinal fluid in multiple sclerosis reveal that B-cell differentiation is confirmed in the central nervous system of individuals suffering from multiple sclerosis. The dominant antibodies happen to be short-living plasmablasts. Interestingly it is not plasma cells. Precisely, plasma cells are actually the predominant antibody secreting cell found in multiple sclerosis patients’ cerebro spinal fluid.               More importantly, the phenomenon whereby upregulation of costimulatory molecules on plasma cells within central nervous system  occurs is indicative the potential of such cells to sustain their T-cell activation.  Scientifically, B cells have been known as potent antigen-presenting cells. Assumptions are that they might feature prominently in T-cell antigenic stimulation. Scientists conclude that B cell and humoral immunity might be the main factors responsible for initiating and sustaining multiple the sclerosis disease process (Awad & Stüve 2010).

Immunoregulatory Cells

          Studies have revealed that isolating myelin-reactive T cells from peripheral blood of healthy subjects is highly suggestive that, perhaps, decreasing regulatory cells interactions is the basic immunopathology concepts in multiple sclerosis evolution and not he presence or absence  of self-reactive T cells.  Scientifically,   it has been accepted that regulatory cells play a major role in controlling intensity when immune response are activated by maintaining self-tolerance. Importantly, it has been proven that CD4+ TH2 cells are active in anti-inflammatory cytokines production. They are IL-4, IL-5, and IL-13. Precisely, this CD4+ TH2 has the ability of lowering regulatory function of macrophages (Awad & Stüve 2010).

    Further developments show where a relatively little subpopulation of CD4+ T cells were identified to be naturally occurring regulatory T (CD4+CD25+Treg) cells. It is believed that they are vital participants in the immune homeostasis process too. Certainly, they were found to be expressing CD25 which is an important component of the IL-2 receptor. However, preclinical trials have revealed that Treg cells’ absence was closely associated with the emergence of autoimmunity. Overwhelming evidence exists to prove that inadequate Treg-cell activity could be a main contributory element in multiple sclerosis etiopathogenesis. Essentially, studies show where  CD4+CD25+Treg cells effector function  emerging out of multiple sclerosis patients’ peripheral blood  samples of patients was deficient in comparison to CD4+CD25+Treg cells from subjects who were not afflicted by the disease (Awad & Stüve 2010).  .

         While these findings scientifically seem profound critics argue there are no differences in Treg cell concentration and constitution in the cerebro spinal fluid among patients afflicted by multiple sclerosis and those who were healthy. A larger study conducted on 73 multiple sclerosis researchers discovered that Treg cell concentration was identical with that of healthy volunteers. . The notable difference detected was that the Treg cells obtained from multiple sclerosis patients demonstrated reduction suppressive potential on the ‘immune response directed against myelin antigens’ (Awad & Stüve 2010, p 201). Yet, in another study this theory was refuted since, there were higher Treg cell counts in multiple sclerosis patients than in the control. Alternatively,  appeared the potential of these cells suppress MBP-induced proliferation was less effective (Awad & Stüve 2010)

        Explaining the functional differences of Treg cells activity in multiple sclerosis patents and healthy subjects there has been reports of activity in RRMS and progressive stages of the diseases too.  For example, Forkhead box p3 (FOXp3) has been identified as a popular transcriptional factor. Its main role has been detected being a valuable participant in Treg-cell-suppressive molecular programmer activity (Awad & Stüve 2010)

            Many preclinical studies have supported many of these theories in confirming the linkage between autoimmunity and absence of FOXp3. An association was also discovered with ectopic FOXp3 expression conferring suppressive function on CD4+CD25+Treg cells. Further linkages posit a relationship showing significant reductions in FOXp3 mRNA transcripts and protein levels. Importantly, this occurred without any concordant decrease in CD4+CD25+Treg representation in multiple sclerosis patents. FOXp3+CD4+CD25+Treg cells popularly create infiltrations when cerebro spinal fluid of subjects afflicted with neuro inflammatory diseases. Comparatively, this multiple sclerosis patients isolated more FOXp3+CD4+CD25+Treg cells   than patients afflicted by dementia, stoke  or  any other neurological disease. In addition it was observed that Treg activity seem to be compromised when peripheral blood samples are used for the analysis in multiple sclerosis patients unlike other non-affected clients.

Therapy and management

        There is no cure for multiple sclerosis. However, scientists continue to experiment with drugs and therapies, which can be useful in relieving symptoms. For example, David Virley (2005) conducted studies to explore strategies involved in ‘Developing Therapeutics for the Treatment of Multiple Sclerosis.’ The author posited that many animal models have been used in developing therapeutic interventions for treating relapsing multiple sclerosis. The aim of preclinical research was mainly to identify and validate novel targets that are the most appropriate mimics for the specific clinical situation. Animal models therefore, become valuable subjects in establishing drug development processes that help select suitable human subjects for therapeutic interventions. This process provides the proof-of-concept for continuance of clinical trials. The author further contended that ‘although there is no gold standard model of multiple sclerosis, experimental autoimmune/allergic encephalomyelitis (EAE) models simulate the clinical and pathological hallmarks of multiple sclerosis in various guises and can provide the necessary predictive index for clinical therapeutic application’  (Virley, 2005, p 639).

         EAE was induced by generating T-cell-mediated immunity into central nervous system antigens, which was easily modeled in rodents such as rats, mice, and guinea pigs. Whole CNS homogenate (spinal cord) t purified protein and peptides were combined in preparing the autoantigen for the experiment (Virley, 20050.  ‘Myelin basic protein (MBP), proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), S100β, and glial fibrillary acidic protein as well as specific peptides from respective parent proteins are encephalitogenic in the appropriate host, as the major histocompatability complex (MHC) is one of the major determinants of immune responsiveness and disease susceptibility to these self-antigen’ (Virley, 2005, p 639).

        The author concluded that the pathogenic autoimmune mechanism steps that initiate and magnify EAE and MS damage tissue sequences are:-

  • Activation of autoreactive CD4+ T-cells in the periphery to an antigen;
  • Transmigration of proinflammatory T-cells and monocytes through the blood brain barrier (BBB)
  • Amplification of local inflammation and activation of resident antigen-presenting cells (APCs), such as microglia; and 4) destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).

(See Appendix 4).

Current Drug Therapies

The foregoing trials have emerged into distinct therapies, which are now active treatment management intervention s for multiple sclerosis. To date there are only five Food and Drug Administration (FDA) approved therapeutic treatments for relapsing – remitting multiple sclerosis. They include ‘two interferon (IFN)-β1a agents (Avonex and Rebif), one IFN-β1b (Betaseron), glatiramer acetate (GA) (Copaxone) and Mitoxanthrone (Novantrone)’ (Virley, 2005, p 639).

      Patents suffering from secondary progressive multiple cyclophosphamide (Cytoxan) and mitoxanthrone are the drugs of choice. There are no extreme benefits in using these two drugs or severe toxicity. However, the main drugs used are corticosteroids, IFNβ and GA (Virley, 2005).

Corticosteroids

             Corticosteroids are administered to raise a patient’s tolerance level tolerance during an attack and speed up recovery. Long term therapies are more effective even though short-term interventions can be useful. However, to maintain a longer period between remissions it is always better to continue treatment over a longer period of time.  Patents often receive significant results even when the clinical course of multiple sclerosis may change to secondary progressive stage. Even with so many drug trials and pre-trials being conducted scientists are still not yet sure what are the actual effects of corticosteroid on the immune system are (Virley, 2005).

         However, preclinical research evidence has verified quite a few putative mechanisms. They embody ‘an inhibition of the Th1 immune response reduction in BBB molecules and protection of oligodendrocytes from cytokine-induced cell death’ (Virley, 2005, p 639). EAE models validated the suppressive interactions produced by corticosteroid treatment in relation to clinical course disruption of multiple sclerosis, T-cell migration dampening its antigens response suppression during expression of adhesion utilization of anti-glucocorticoid, RU 38486 (mifepristone). It was revealed that these interactions have intensified as well as reversed steroid-induced inhibition of disease (Virley, 2005).

      While corticosteroids have been so effective in the treatment of multiple sclerosis in both short and long term its side effected should not be underestimated. For example, extended use can initiate transient mood changes headache, gastrointestinal disturbances, and myalgias.  Decrease in bone density can occur overtime if patients must be treated for extended periods of time. Ultimately, osteoporosis could become a real problem increasing risks for fractures and infections. When side effects have become so progressive, the patient ought to be reassessed. Often the attending physician may consider either reducing or discontinuing treatment temporarily (Virley, 2005).

IFN-β

          IFN-β therapies emerged after over 25 years of clinical trials. The aim was finding how multiple sclerosis would respond to IFNs if it is truly a virally mediated disease. Importantly the   antiviral assumption became invalid after clinical trial assessments, which revealed that IFNγ worsened symptoms.  This was highly suggestive, that IFNγ  was more influential in multiple sclerosis pathological process. it meant that IFNβ, like other IFNs, is a species-specific glycoprotein with numerous biological properties. Actually, the mechanism producing these interactions is not fully understood from a scientific perspective poorly. However assumptions have been that immunomodulatory as an alternative to antiviral and antiproliferative makes much sense in deriving at an alternative proposition (Virley, 2005).

      Importantly, IFNβ-1a is exactly like the natural IFN-β, but IFNβ-1b differs in having two amino acids as well as not being glycosylated. Despite these insidious structural differences IFNβ-1b displays comparative biological activity to IFNβ-1a. Therefore, putative responses of IFNβ on the progression of multiple sclerosis is believed to be related primarily to its  antiinflammatory influences, which demonstrates as dampening the stimulatory impact of IFNγ, tumor necrosis factor (TNF)α, interleukin (IL)-12. The lymphotoxin secretion has been identified in the sequence of controlling monocyte activation; inhibiting disruption of BBB. Consequently, the entry of lymphocytes into the CNS is reduced; antigen presentation is reduced to T-cells; and up-regulation of anti-inflammatory cytokines occurs; TGFβ and IL-10 (Virley, 2005).

        EAE pre-trial models have validated the use of IFNβ by proving its influence in limiting the   progression of multiple sclerosis. Supportively, clinical trials were done using both IFNβ formulations. Important findings indicate a one third relapse reduction rate when higher doses are administered. The onset has been observed to be rapid. Precisely, relapses occurred at a rate of 1 per year and few weeks for MRI disease activity. Conversely, there were huge inflammatory changes measured through MRI activity; accumulation of MRI disease burden was significantly slowed down. Besides, there were magnificent results shown by patients regarding relapses (Virley, 2005).

      This novel treatment is not without its adverse side effects. Some include, flu-like symptoms along with reactions emerging at the site where injections are administered. If patients do not respond to the drug after six months of therapeutic intervention, the IFNβ therapy is usually discontinued. Some patients who are already disabled with progressive or relapses occurring at a rate of more than one per year are treated with a combination of combination three or more courses of corticosteroids over a 1-year period. In addition some patents encounter extreme feelings of depression leading towards suicidal inclinations. Drug toxicity can also become a problem with patients becoming noncompliant. This initiates physicians’ decisions of considering alternatives. Neutralizing antibodies in IFNβ effectiveness ought to be addressed as an adverse reaction during treatment. This can lead to long term complications. As such, it must not be ignored if patients complain of reactions or it shows up in diagnostic testing (Virley, 20 05).

   Glatiramer acetate – GA

          GA is considered a non-IFN, nonsteroidal therapy. It is made from synthetic random base copolymers mixtures containing four amino acids namely glutamic acid, alanine, lysine, and tyrosine). The molar ratio was highly specific. Trials researched investigated the GA’s potential encephalitogenic role using EAE animal models. However, surprisingly, it was discovered that GA suppressed their acute and chronic clinical and pathological hallmarks. Importantly, translation of impacts was clinically beneficial. Importantly, GA provided evidence in the initial phase II trial as being a suitable agent for reducing relapse rates by 76% in patients with relapsing-remitting multiple sclerosis. A 5 year follow up intervention treatment confirmed

GA benefits as being capable of sustaining the initial influence on relapses in multiple sclerosis patients. The progression of the disease into the secondary stages was significantly slowed. Patients did not enter into disability as quickly as when other drug therapies were used. Also, when the Lesion burden was assessed through MRI it validated the value of GA in helping patients during the relapsing-remitting episodes. It was discovered that GA greatly reduced  frequency  rates of lesion load  and new enhancing lesions when baseline pretreatment measures are compared (Virley, 2005).

     Since then numerous mechanisms were advanced as being responsible for these fascinating results observed by GA’s intervention in the disease process. First its biological activity relapsing-in remitting MS was noted as a valuable factor. Then the antigen-specific induction suppressor T cell was remarkable. Thirdly, a MBP competitive inhibition was distinctly observed as a benefit. There was also a relationship of the interactions to -peptides from antigen-presenting cells (Virley, 2005).

       It must be noted that regardless of how beneficial a new drug therapy may be in treating a disease there are always adverse effects, which must be considered in its administration. GA is no exception even though the tolerance level in multiple sclerosis patients is great. However, subcutaneous administrations could become harmful due to increasing incidences observed whereby injection site reactions occurred in the majority of cases and they were localized proving that it was the drug interaction with human skin (Virley, 2005).

             The overall picture being communicated in the use of this drug pertains towards it being the most tolerable in terms of side effects when compared to other therapies. Reduced propensity in the development of depression, neutralizing antibodies and menstrual disorders was far less when compared to other drugs now available for treating multiple sclerosis. Despite these developments, however, it is still important for continued research in extending to multiple sclerosis patients more options. While there is no cure for the condition medical science can provide the best relief it could through timely and efficient intervention therapies that work (Virley, 2005).

      Ultimately, these interventions should aim at not only providing relief, but secure sustained drug benefits reducing symptoms of multiple sclerosis, which shows that treatments are becoming more effective. Patents should be taking lower doses and experiencing fewer side effects. As such, pharmaceutical and biotechnology industries are challenged to provide this service to the multiple sclerosis community of patients. Essentially, numerous alternative disease-modifying strategies are emerging. They will be reviewed in the following pages of this document (Virley, 2005).

           For example, Pietro Iaffaldano (2012) and a group of researchers conducted studies regarding the ‘Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study.’ These researchers contend that Natalizumab reduced relapse rate as well as magnetic resonance imaging reactions in patients experiencing Relapsing-Remitting Multiple Sclerosis (RRMS). However, its impact on fatigue cognition in patients affected by multiple sclerosis need to be validated though scientific research. There the purpose of a prospective, open-label, observational study was intended as an  evaluation relating probable impacts  natalizumab had on cognition and fatigue when measured in patients experiencing Relapsing-Remitting Multiple Sclerosis  after being treated continuous for two years (Iaffaldano et.al, 2012).

        Researchers examined cognitive performances by applying  ‘Rao’s Brief Repeatable Battery (BRB) device, the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months’ (Iaffaldano, 2012, p  201).   When patients did not respond favorable to at least 3 BRM and ST 3 they revived a cognitively impaired (CI) classification. Every 12months the Fatigue Severity Scale (FSS) was administered. This assessed the patient’s ability to self-reported incidences of fatigue. A total of 1 53 patients participated in 1 and 2 year-natalizumab continuous treatment (Iaffaldano et.al, 2012).

       Result revealed that after one year treatment the amount of’ CI sampled patients decreased from 29% (29/100) at baseline to 19% (19/100) (p=0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p=0.008). These significant effects were confirmed in the subgroup of patients treated up to two year.’ (Iaffaldano et.al, 2012, p. 201). From these results researchers concluded that

In the short-term Natalizumab can be successfully used as a treatment which could, ultimately reduce incidences of cognitive difficulties and fatigue in patients experiencing Relapsing-Remitting Multiple Sclerosis (Iaffaldano et.al, 2012).

Examples of Novel Therapeutic Challenges for Multiple sclerosis

Blockade of lymphocyte migration

       Very late antigen-4: natalizumab (Tysabri) and small molecule antagonists. There is widespread evidence implicating very late antigen-4 (VLA-4, α4-β1 integrin) in this process, via its interaction with receptors like vascular cell adhesion molecule 1 (VCAM-1) and the CS1 fibronectin domain (Virley, 2005).

Immunomodulatory agents

       Interest recently has emerged regarding development of novel Immunosuppressants. Trials have been conducted and they have been actually used in treatment of many autoimmune diseases such as psoriasis and rheumatoid arthritis. They reduced exacerbations keeping progression (Virley, 2005).

Anti-inflammatory agents

‘Cycloxygenase-1 and -2 (COX-1 and COX-2 or prostaglandin H synthases 1 and 2) catalyze the conversion of arachidonic acid and oxygen to generate inflammatory prostaglandins such as PGE2, PGD2, PGF2a, and thromboxane’ (Virley, 2005, p 201).

Neuroprotective and neuroregenerative therapeutic strategies

       Achievements in repair of myelin and immense neuroprotection though therapeutic interventions can be interpreted major research breakthrough in the attempt at providing more beneficial therapies that reverse permanent neurological disability associated multiple sclerosis.

Potential combinations of therapeutic strategies

       The heterogenic influences of clinical response as well as pathological hallmarks contained in recent multiple sclerosis drug development it would be wise considering combining therapeutic strategies that differentiate concentrating of specific aspects of the disease such as cognition memory and fatigue as espoused by Iaffaldano and his team of researchers. An area of precedence is a development stage whereby each agent independently offers a benefit distinct from the others, but is still valuable when combined in adding synergistic value to the therapeutic intervention. This approach would be extremely beneficial for patients who seldom respond favorable to therapies now available on health care markets across the country and world (Virley, 2005, p 201).

Conclusion

               While theories pertaining to the etiology/epidemiology/immunology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explored the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of this disease. Consequently, the researcher adapted a comparative analysis of the perspectives offered by theorists in discussion of epidemiology regarding emergence of multiple sclerosis among the predominantly, female young adults twenty-first century population. These were matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management, and current trends are being explored.

Current Trends

                   Precisely, Ascherio and Munger (2007) ‘Environmental risk factors for multiple sclerosis Part I: the role of infection’ contend that even through genetic susceptibility play a role in the acquisition of multiple sclerosis among families studies show where personal hygiene significantly affect occurrence of the disease. Further, they advance that genetics and environment alone cannot account explicitly for the MS frequency among geographic variations when risk changes with migration are taken into consideration. Supportive epidemiological findings highlights the “hygiene hypothesis,” showing the additional role Epstein-Barr virus (EBV) plays as evidence for MS risk factor (Ascherio & Munger, 2007)

             Another piece of research literature by the same authors ‘Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors focusing on the environment explains that the change risk factor among migrants gives profound evidence for M.S environmental determinants. Then researchers defined environment to mean variations in diet and social behavior. Main contributory factors were sunlight and cigarette smoking (Ascherio & Munger, 2007)

     Dyment, Ebers, and Sadovnick, (2004) took a stand in ‘Genetics of multiple sclerosis.’          They argue that while environment and infection may play a role many genes appear to be linked to  MS etiology. They mentioned ‘HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A’ (Dyment et.al, 2004, pp 110). These researchers advanced that future development in the MS genetic science largely depends on continuous research making data available as evidence. Also the development of appropriate statistical measurements and research methodologies could be valuable (Dyment et.al, 2004).

             George Ebers (2008) focused on ‘Environmental factors and multiple sclerosis’ in reporting that studies conducted in Canada show where environmental factors influence the distribution of MS in specific geographic locations. The researcher cited migration studies to prove that the increase incidence of MS in Canada relates to longitudinal sex ratio expansion among immigrants within the country. This was compared to studies conducted in Australia where similar geographic patterns exist. It was discovered that by modifying the environment it reduced 80% of cases. It was concluded that while genetics play a major role there are predominant environmental factors associated with MS incidences in certain geographic locations (Ebers, 2008).

       Gavin Giovannonia and George Ebers (2007) posit that ‘genes and environmental factors lead to tissue injury by autoimmune mechanisms, implicated by strong circumstantial evidence’ (Giovannonia and Ebers, 2007 pp, 261). They further contend that it is difficult to identify the specific genes responsible for MS without examining the associating influences of the environment. Actually, they argue that the impact of genes on MS emergence is modest. Additional studies were cited emphasizing irregularities in confirming the genetic theory of MS etiology (Giovannonia and Ebers, 2007).

                Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed at addressing the autoimmune etiology of the disease. These therapies are designed to reduce inflammation, but their long term effect is uncertain. Hence, a re-evaluation of both pathogenesis and etiology is suggested (Nakahara et.al, 2012).

                     Rosati offered insights to say that the childhood environmental factor was a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

               Consequently, this study’s importance pertains to advancements into understanding multiple sclerosis’ etiology, pathophysiology/immunology and treatment. As explained in the foregoing principal pieces of research literature theories relating the etiology of MS are numerous. However, theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure.

       Current therapeutic trends predict that the ideal treatment for multiple sclerosis mustconsist oftechniques aimed at increasing disease-causing/sustaining antigen(s) tolerance. Ultimately, it is expected that long-term therapy would be obviated. This is important because amidst  numerous continuous drug trials scientist still contend that none of them seem to have considerable effects on resolutions of a disease which is over 100 years old. Justifiably establishing coordination between activated T cells and B cells in the pathophysiology of multiple sclerosis is highly recommended for targeting the two cell population. These include resting and dividing cells together. The strategy may necessitate, taking control of the disease process itself (Awad & Stüve, 2010).   

          Whatever emerges from these assumptions scientist must bear in mind that other immune cell populations are playing a major role also in the sequel of this disease. They intimate and perpetuate the process. Therefore, the final proposition of this theory advanced that amplifying or sparing the pool of regulatory cells which act as mediators of immune suppression would be valuable a valuable intervention. This however must be embraced without compromising immune surveillance in the treatment of this disease (Awad & Stüve, 2010). In concluding these deliberations pertaining to current trends in multiple sclerosis therapeutic management it is expected that this research project sensitize scientists into elaborating on present research practices in order for a consensus be reached regarding the reality of multiple sclerosis etiology and its pathological implications.

References

Ascherio, A., & Munger, K (2007). Environmental risk factors for multiple sclerosis. Part I: the

                      role of infection. Ann. Neurol. 61(4); 288–99

Ascherio, A., & Munger, K. (2007). Environmental risk factors for multiple sclerosis. Part II:

                     Noninfectious factors. Ann. Neurol.  61(6); 504–13.

Awad, M., & Stüve, O. (2010). Immunopathogenesis of Multiple Sclerosis: New Insights and

                    Therapeutic Implications. Lifelong Learning in Neurology. 16(5); 166-180

Clanet M (2008). Jean-Martin Charcot. 1825 to 1893. Int MS J 15 (2), 59–61.

DasGupta, R., & Fowler, C. (2003). Bladder, bowel and sexual dysfunction in multiple  

                       sclerosis: management strategies.  Drugs, 63 (2): 153–66.

Dyment, A; Ebers, G; Sadovnick, A. (2004).  Genetics of multiple sclerosis. Lancet

                                 Neurol  3( 92). (2004): 104–10.

 Ebers, G. (2008). Environmental factors and multiple sclerosis. Lancet Neurol  

                              7 (3). 268–277.

Foley, P. Vesterinen, H. Laird, B. (2013). Prevalence and natural history of pain in adults with

                       multiple sclerosis: Systematic review and meta-analysis. Pain 154 (5): 632– 42

Gilden, D (2005). Infectious causes of multiple sclerosis. The Lancet Neurology 4  (3)

                                    195–202.

Giovannoni, G; Ebers, G. (2007). Multiple sclerosis: the environment and causation. Curr

                                Opin Neurol. 20( 3); 261-8.

Kantarci, O., & Wingerchukb, D. (2006). Epidemiology and natural history of multiple sclerosis:

                             new insights. New York. Lippincott Williams & Wilkins

Kurtzke, J. (1983). Rating neurologic impairment in multiple sclerosis: an expanded disability

                          status scale (EDSS). Neurology, 33 (11); 1444–52.

Iaffaldano, P. Viterbo, G. Paolicelli, D. ( 2012). Impact of Natalizumab on Cognitive

               Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label,

                  Two Years Observational Study. PLoS . 7(4)

Merril, R. (2010). An Introduction to Epidemiology, (5th Edition). Jones and Bartlett

                   Publishing.

Murray, J (2002). Infection as a cause of multiple sclerosis. Theories abound because no one

                         knows the answers yet. BMJ. 325(7373).(2002). 1128.

Nakahara, J; Maeda, M; Aiso, S; Suzuki, N ( 2012). Current concepts in multiple

                             sclerosis: autoimmunity versus oligodendrogliopathy. Clinical reviews in

                           allergy & immunology  42(1); 26–34.

 Oksenberg, J., & Barcellos, L (2000). The complex genetic etiology of multiple sclerosis.

                           Journal of NeuroVirology. 6(2), S10 ± S14

Rosati G (2001). The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 22

                (2): 117–39.

Royal College of Physicians London (2004) Multiple Sclerosis: National Clinical Guideline for

                Diagnosis and Management in Primary and Secondary Care. NICE Clinical

              Guidelines, No. 8.National Collaborating Centre for Chronic Conditions (UK).

               London

   Schäffler, N. Köpke, S. Winkler, L. Schippling, S. Inglese, M. Fischer, K.,  & Heesen, C.

      (2011). Accuracy of diagnostic tests in multiple sclerosis–a systematic review. Acta Neurol

                      Scand. 124(3), 151-64

Siegert, R., Abernethy, D. (2005). Depression in multiple sclerosis: a review. J. Neurol.

                     Neurosurg. Psychiatr. 76 (4): 469–75.

Terry, R. Miller, S. Getts, D., & Muller, M. (2012). Current Theories for Multiple Sclerosis

                    Pathogenesis and Treatment. Free Press New York. 2012.

 Virley, D. (2005). Developing Therapeutics for the Treatment of Multiple Sclerosis. NeuroRx.

                 2(4): 638–649.

Appendix 1

Table 1 Multiple sclerosis as a genetic disease

———————————————————————————

1. Racial clustering of MS cases. Resistant ethnic groups residing in high risk regions

2. Familial aggregation of MS cases. Increased relative risk to sibs (ls=20±40)

3. Low incidence of conjugal MS

4. MS sibling pairs tend to cluster by age of onset, rather than

year of onset

5. High disease concordance in monozygotic twins (25±30%) compared with dizygotic twins and non-twin siblings (3±5%)

6. No detectable effect of shared environment on MS susceptibility in first-degree non-biological relatives (spouses, adop-tees)

7. Suggestive correlations between certain polymorphic loci and disease susceptibility

————————————————————————————

Appendix 2

Table 2 Confounding factors in genetic studies of multiple

Sclerosis

————————————————————————————————-

1. Aetiologic heterogeneity identical genes, different phenotypes

2. Genetic heterogeneity Different genes, identical phenotypes

3. Unknown genetic parameters Single versus multiple genes Dominant versus recessive mode of inheritance incomplete penetrance

4. Epistatic gene interactions

5. Post-genomic mechanisms

6. Unidentied non-heritable (environmental) factors

——————————————————————————————————————

(Oksenberg & Barcellos, 2000).

Appendix 3

http://upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Ms_progression_types.svg/300px-Ms_progression_types.svg.png

                     Diagram showing immunological concepts underlying Multiple sclerosis                   

                     Progression of subtypes (Oksenberg et.al, 2000).                        

FIG. 1.

      Schematic view of the putative pathogenic steps in MS. 1: Activation of autoreactive T cells by antigen presenting cells in the periphery. 2: Migration of T cells and monocytes through the blood brain barrier. 3: Amplification of local inflammation and destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).                                         Appendix 5   – Demyelinization

Medicine and Health: Multiple Sclerosis

Name of Author

Outline

Introduction

•          Description

•          Epidemiology

•          Clinical signs and symptoms

•          Diagnosis

•          Prognosis

Immunological concepts underlying the disease

Therapy and management

Conclusion

•          Current Trends

Abstract

The purpose of this document is to offer a precise account of Multiple Sclerosis. The statement of problem related to this research reads ‘while theories pertaining to the etiology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explores the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of the disease. Consequently, the researcher will adapt a comparative analysis of the perspectives offered by theorists regarding emergence of multiple sclerosis among the twenty-first century female young adults. These will be matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management as well as current trends are explored.

Medicine and Health: Multiple Sclerosis

Introduction

Description

          Multiple sclerosis was not discovered as a disease until late 19the century. An English Physician by the name of Walter Moxon in 1873 along with American Dr. Edward Seguin in 1878 discovered multiple sclerosis as a dysfunction of the nervous system. They confirmed that it was more common in women than men. However, three notable signs of multiple sclerosis signs described as Charcot’s triad 1 being nystagmus, intention tremor, and telegraphic speech (scanning speech) have been attributed to French neurologist Jean-Martin Charcot (1825-1893). He  recognized cognition alterations, which was described as “marked enfeeblement of the memory” and “conceptions that formed slowly” (Clanet, 2008, p 58).  At the time these doctors did not project any sound etiology of the disease, but said that there was no evidence to support it being inherited. However, they confirmed that numerous diverse neurological irregularities were produced as symptoms of the condition (Terry et.al, 2012).

            Multiple sclerosis (MS); disseminated sclerosis is also known as encephalomyelitis disseminata. Scientists have described it as an inflammatory condition characterized by formation of myelin sheaths around brain and spinal axons tissue. Ultimately, these tissues are destroyed through scarring; reduction in myelin to protect brain and spinal cord. Research is still being conducted regarding its etiology, Assumptions however have been that many predisposing genetic, environmental and infection factors could initiate the inflammation (Ascherio & Munger, 2007).

      Other assumptions have been that there are mechanisms within the body chemistry, which are responsible for destruction of the immune system inhibiting production of myelin cells. Consequently, massive insidious nerve destruction occurs and nerve cells become incapable of functioning as communicators of impulses across nerve ending within the human body. Often when the etiology of a disease is obscure there is seldom a cure. Recent research has continued to advance ther theory that indeed multiple sclerosis affects more females than males (Nakahara et.al 2012)

        To date scientists have advanced from repeated research that there is no discrimination as to which neurological symptoms can emerge due to nerve destruction in the brain and spinal cord which are the primary target organs. From observation there have been immense progressive physical and mental dysfunctions. In some cases memory irregularities could develop, but a difficultly exists classifying them as purely psychiatric because they may present in conjunction with various levels of other neurological abnormalities. As the disease evolves it converges into many misleading features increasing the challenge of addressing the real symptoms in devising modes of treatment intervention. Scientists have described this phenomenon as an escalation of new symptoms, which were not formerly associated with the initial presentation. They are termed relapsing forms and progressive forms respectively (Dymentet.al, 2004)

        The period from when attacks begin end, and begin again symptoms may subside. However after these episodes permanent nerved damage occurs. As the disease advances symptoms worsens and exacerbations seems to occur leading up to when treatment becomes ineffective. This disease is more than 100 years old, but scientists have not been articulate in arriving at any profound etiology while numerous theories exist. They have not gone far beyond exploring mechanisms related to the disease process itself (Ascherio & Munger, 2007).

       Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed only at addressing the autoimmune etiology of the disease. As such, they merely focus on restoring function to affected nerves after symptoms become uncontrollable; control recurrence and limit the extent to which nerve damage produces disability (Nakahara et,al, 2012).

          However, medications used to treat multiple sclerosis are not without their serious side effects, besides being poorly tolerated by patients. Consequently, patients turn to alternative medicine for relief. Precisely, since there are few studies conducted regarding alternative remedies these remedies are considered nonscientific and are not recommended even through patient report how successful these treatments have been in restoring nerve function (Gilden, 2005).

      People diagnosed with multiple sclerosis live an average 5-10 years, less than persons who do not have the disease. There is an average of 2 persons affected by multiple sclerosis for every 150 per 100, 000 (Rosati, 2001).  However, data or theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure. This research is expected to sensitize scientists into elaborating on present research practices in arriving at a consensus regarding the reality of multiple sclerosis etiology.

Epidemiology

      Epidemiology infers a study of disease patterns that evaluates infection etiology; geographic, socioeconomic status, genetics and demographic variations. Often epidemiologists add to the multiple sclerosis body of knowledge through assessing relationships between these factors. Since there are no known causative factors for multiple sclerosis it is important that epidemiologists continue investigations regarding migration patterns. However, it must be understood that figures published in epidemiology records are all estimates. This is an attempt at establishing a more profound understanding regarding multiple sclerosis target populations across the world. It also helps identifying and explaining geographic locations containing highest and lowest multiple sclerosis rates (Merril, 2010).               

        The challenge facing the epidemiology of multiple sclerosis lays in the difficulty diagnosing the disease. No single distinct tests are being conducted in establishing a diagnosis for multiple sclerosis. As such, the argument is that diagnoses can be incorrect delayed or just bypassed. While MRI technology has been of great assistance in resolving difficult diagnoses epidemiologists question the accuracy of diagnoses produced from previous studies since they may not give a true representation of multiple sclerosis with the given population. More importantly, various methodologies used by specialists collecting data on the disease can greatly alter interpretations and outcomes. Due to these factors the epidemiology of multiple sclerosis is still in its infancy even though the disease is over 100 years old (Merril, 2010).              

                 According to Orhun Kantarci and Dean Wingerchukb (2006) multiple sclerosis claims the health of approximately 1 000 000 people between 17 and 65 years old internationally. The 2000 projected multiple sclerosis prevalence rate among white US populations showed 191 per100 000. Alternatively, the US overall incidence rate and was 7.3 per 100 000 person in the same year. Further epidemiological studies supported the theory that multiple sclerosis is two times more common in women than men. It was discovered also that there is a tendency for a later onset of the disease among men. The prognosis for them is even worse for women. Scientists attribute this difference to gender-dependent and phenotypic variability factors which may create an etiological predisposition (Kantarci & Wingerchukb, 2006).

        Multiple sclerosis care cost United States government an estimated $6.8 billion annually, which includes loss in productivity as well as actual health care interventions. A total life time cost is estimated at 2.2 million per patient (Kantarci & Wingerchukb, 2006).Similar epidemiological estimates exist around the world. There seems to be patterns of ‘a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere’ (Rosati, 2001, p 22). Multiple sclerosis is less prevalent among people who live close to the equator. Theories pertaining to climate, sunlight and vitamin D intake are variables used in relating possible causes in explaining this latitude gradient theory regarding geographic disposition multiple sclerosis prevalence among people living near to the equator (Rosati, 2001).

     Overtime other variations have appeared, which forced epidemiologist to consider environment in combination with genetics. Multiple sclerosis was discovered to be prevalent among northern European populations and most common in certain ethnic groups such as ‘Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori’ (Rosati, 2001, p 22).

       Childhood environmental factors were then considered as a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

      Critics of the environmental epidemiological theory have contended that quantification of the assumptions is difficult because data derived is obtained mainly from retrospective case-control studies whereby subjects are exposed to the same environment and results may lack internal and external validity besides containing reliability issues. ‘A practical, albeit limited, design is a nested-cohort study in which a population cohort already identified for exposure to given factor(s) for another disease is exploited for excess of -NIS occurrence after sufficient follow- up’(Kantarci & Wingerchukb, 2006, p 249). While trying to make sense of the environmental theoretical epidemiological perspectives major advances have implicate viral exposure factors. Viruses identified are canine distemper virus, Epstein-Barr virus, and human herpes virus-6) (Kantarci & Wingerchukb, 2006).

           Internationally, conclusions are that multiple sclerosis makes its first appearance in adults during their thirties. It can occur at any time in children. However, the primary progressive subtype appears later in people in their fifties.  The genetic epidemiology of multiple sclerosis seems to be overlapping with both environmental and viral/infections. Analysts have discovered that the only facts they have to support the genetic epidemiology are its high incidence among Northern Europeans in relation to indigenous populations from the ‘same geographic location, familial aggregation’(Kantarci & Wingerchukb, 2006, p 249). See appendix 1 and 2

Clinical signs and symptoms

                 Numerous signs and symptoms are associated with multiple sclerosis. However neurologists keep abreast of symptoms by applying the Expanded Disability Status Scale (EDSS).  EDSS gives a score total of a scale ranges from 0 to 10.

 ‘The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.  The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. In addition, it also provides eight subscale measurements called Functional System (FS) scores. These subscale categories are listed below.  The levels of function within each category refer to the eight functional systems affected by MS’ (Kurtzke, 1983).

  • Pain

              Pain is very common among multiple sclerosis patents and often appears after the first lesion is formed. In most occasions it is associated with the control mechanisms which regulate ascending and descending tracts in the anterolateral system. From 28 studies researchers proved taking a sample of 7101 multiple sclerosis patients that 63% complained of various degrees of pain. There were no significant differences in pain levels among men and women or people with greater disability than others.  Most pain occur as ‘headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte’s phenomenon (16%) and Trigeminal Neuralgia (3%)’ (Foley et.al, 2013, p 632).

  • Emotional disturbance

       Emotional disturbance manifests as clinical depression. This can extend into a life time complication. Present incidence rates range between 40–50% per person diagnosed with multiple sclerosis. Brain imaging studies have tried to relate findings to depression when brain lesions are found. More importantly, most neurologists have associated these brain lesions with neuropathology of the left anterior temporal/parietal regions. It is very important development that is worth monitoring carefully because emotional disturbance is responsible for 15% of deaths emerging from suicide. As such, patients are closely evaluated when signs anger, anxiety, hopelessness, and frustration surface (Siegert, Abernethy, 2005).        

  • Bladder and Bowel irritability

       Bladder disturbances occur in 70% of all multiple sclerosis patients. It presents as frequency, hesitancy and incontinence which can affect maintenance of personal hygiene. Bowel issues appear in 70% of the multiple sclerosis patients, 50% suffer from constipation 30% fecal incontinence (DasGupta & Fowler, 2003).            

  • Cognitive disturbances

       40%- 60% of multiple sclerosis patients encounter cognitive difficulties. It ranges from simple degrees of forgetfulness to severe loss of memory. Other cognitive difficulties are attention deficit; neurological fatigue; processing speed and visual spatial ability alterations (Ebers, 2008).

  • Impaired Mobility

           Mobility changes become evident when walking, moving, getting off and on the bed and balancing. Research has shown that between the onset of the disease and 5 years 50% of patient score 6 on the EDSS scale. 10 years living with multiple sclerosis 25% of patients can attain just a score of 6 on the Expanded Disability Status Scale (EDSS). This makes using a walker and other methods of mobility support necessary. Within 30 years, 83% of patients use walking aids (DasGupta & Fowler, 2003).           

  • Speech difficulties

Speech could become slurred and tone of voice altered.

  • Muscle Tremor and Ataxia

Ataxia coincides with muscle tremors. Clumsy movement occurs creating difficulty in maintaining a steady gait. Muscle tremors are often uncontrollable involuntary episodes of shaking.

  • Transverse myelitis 

When multiple sclerosis begins invading deep into spinal cord tissue lower body functions become impaired. These include bladder/irritability as well as sexual potency in males. Inability to have an erecting is possible along with ejaculation difficulties

  • Spasticity

Spasticity manifests as both a sign and symptom. Muscles, especially, in the extremities become very stiff and immobile.

Diagnosis

           Researchers have posited that multiple sclerosis is difficult to diagnose since confirmation of the disease cannot be made on clinical symptoms alone. Signs and symptoms may resemble many other neurological disorders. To facilitate diagnosis during the early stages scientists have designed standardized criteria. They include Schumacher, Poser and McDonald criteria.

Schumacher’s criterion is a neurological examination detecting central nervous system abnormalities involving two or more systemic dysfunctions. Often white matter abnormalities are evident in brain and spinal tissue. In 1983 these criteria were modified by Poser accounting for clinically definite; laboratory supported definite; clinically probable and laboratory supported probable multiple sclerosis (Royal College of Physicians of London, 2004).

                          McDonald criteria are the ones presently used in most health care institutions across the world for making a more accurate multiple sclerosis diagnosis. It includes a

  • Diagnostic criteria for suspected MS (two or more attacks)        Flowchart Icon  
  • Diagnostic criteria for suspected MS (monosymptomatic)         Flowchart Icon
  • Diagnostic criteria for suspected MS (single attack)                   Flowchart Icon
  • Diagnostic criteria for suspected MS (progressive from onset)      Flowchart Icon

                             (Royal College of Physicians of London, 2004)

               However, Schäffler, Köpke , Winkler , Schippling , Inglese , Fischer and, Heesen (2011) have reprted that the development of a new diagnostic criteria for multiple sclerosis was recently proposed after a systematic literature review  revealed that present accuracy issues made some tests invalid. The aim of this study was to validate diagnostic studies and clarify the value of diagnostic test used in offering a diagnosis. They included in their review a minimum of 40 patients who were traced for 2 years. This limitation existed in all the studies reviewed since they significantly lacked a gold standard measurement for validating the diagnostic tests that were used in those trials. A second relapse phase was adopted as a surrogate in relapsing-remitting multiple sclerosis testing. However, the lengthy 5 year follow-up created difficulty in detecting all cases. Also, quite a few studies contained various levels of validity and reliability issues. Notably, a selection bias was identified due to the indistinct classification of a clinically isolated syndrome (Schäffler et.al, 2011).

                  Based on these limitations, ‘sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%; Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%; combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%)’ (Schäffler et.al, 2011, 153). The researchers did not find justification in conclusions derived in the literature review studies. Further they suggest that ‘a combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis’ (Schäffler et.al, 2011, 153).

Prognosis

         While there is no cure for multiple sclerosis it has not been considered a fatal disease even though it severely affects a person’s quality of life. Serious disability does not occur until about 20 years after onset of the disease. Women seem to have a better prognosis than males. Factors affecting each patient’s prognosis regarding quality and length of life relate  to  adherence of health promotion strategies that will limit symptoms , doctor’s  appointment  follow up ; compliance with medication management to reduce progression of the disease. Generally life expectancy is reduced by 5-10 years with careful intervention strategies (Murray, 2002).

Immunological concepts underlying Multiple sclerosis

          Immunology relates to the body’s defense mechanisms in counteracting  the activity of invading agents. For every disease entity that enters the human internal environment there are diverse strategies employed by the immune system in a comprehensive effort to interrupt the intended invasion consequences. Consequently, the immune system builds up resistance by developing immunity to the invading organisms. There are mainly five types of immunological responses that can emerge from this activity. They are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

Humoral immunity

         Humoral immunity is also known as antibody-mediated system being mediated macromolecules located in extracellular fluids like secreted antibodies, antimicrobial peptides and complement proteins. Usually, humoral immunity reacts with substances in body fluid humors (Nakahara et.al, 2006).

Cell-mediated immunity

          Cell-mediated immunity does not rely on producing antibodies in order to defend the body against harmful organisms. Instead it activates phagocytes, antigen-specific cytotoxic T-lymphocytes, and disperses numerous cytokines in an antigen response (Nakahara et.al, 2006).

Innate or Natural Immunity

 Innate immunity is the body’s evolutionary natural mechanism used to fight invading foreign species. This is the dominant and oldest type of immunity among living creatures including unicellular organism such as amoeba, fungi, plants and insects (Nakahara et.al, 2006).

Acquired immunity

      Acquired immunity emerges after exposure to a foreign organism. It is also known as adaptive immunity due to somatic hypermutation or accelerated somatic mutations), and V (D) J recombination, which is actually a genetic antigen receptor recombination that cannot be reversed (Nakahara et.al, 2006).

Non-specific immunity

               Non-specific immunity means that the immunological response is antigen independent and unspecified. However, distinct mechanisms are activated. They include establishing anatomical barriers, stimulation of secretory molecules and integrating cellular components.  Recognizable mechanical anatomical barriers include the internal epithelia tissue such as the skin.  Intestinal mobility along with oscillation of broncho-pulmonary cilia is chemicalized because chemical messages are transmitted through biological agents present in skin, intestines and nervous system.

                   DominantImmunological concepts associated with multiple sclerosis are connected to the pathogenesis of this disease. Some basic traditional immunological concepts pertaining to multiple sclerosis are:-

  • Relapsing MS
  • Secondary progressive MS.
  • Progressive MS.
  • Progressive relapsing MS

While these are the four major immunological concepts that intermingle in explaining the pathophysiology of each stage collectively in facilitating the discussion other will be highlighted. Significantly, coinciding with the five types of immunological responses that can emerge from antigen antibody interaction are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity. Therefore, the terms that will be explained in this section are:

  • Demyelinization
  • Cell-Mediated Immunity
  • Humoral Immunity
  • Immunoregulatory Cells

              Relapsing MS is a serious symptom which progresses into a chronic inflammatory demyelinating central nervous system disorder manifesting as morphological inflammation, demyelination, axonal loss and gliosis. There is massive infiltration of heterogeneous cellular population; and soluble mediators of the immune system are activated. These include T cells, B cells, macrophages and mi croglia, cytokines, chemokines, antibodies which stimulate  humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

 Demyelinization

                Research has shown where a lymphocytes subset identified as T helper cells specifically the Th1 and Th17 play a major role in development of multiple sclerosis lesions. Also the Interleukin 12 protein causes differentiation of naive T cells producing inflammatory T cells. When there is over production of Interleukin 12 it initiates inflammatory increases that occur in patients with persistent multiple sclerosis relapses. Patients who are not affected by multiple sclerosis their lymphocytes develop innate immunity to recognize and distinguish cells what cells belong to the body and those which are foreigner (Nakahara et.al, 2006).             

       Lymphocytes, in the body of a person afflicted by multiple sclerosis cannot differentiate between healthy and non-healthy cells. They attack cells in the central nervous system as foreigners such as viruses, bacteria, fungi triggering inflammatory responses as if it were a cell-mediated immunity conflict. In this process other immune cells such as cytokines and antibodies are activated and join in the inflammatory battle. Importantly, most myelin-recognizing T cells are family to a terminally differentiated subset known as co-stimulation-independent effector-memory T cells (Nakahara et.al, 2006).   See appendix 5   

Cell-Mediated Immunity

      T cells are responsible compromising an estimated 10% of the all inflammatory cells found as active participants in demyelinating multiple sclerosis lesions. Scientists have already proven that the EAE model can adequately be transferred by injecting an animal with myelin-specific CD4+ T cells. Therefore, the acceptable assumption has been that Multiple Sclerosis is foremost a CD4+ T-cell-mediated disease. It was advised that caution must be taken when interpreting these results because CD4+ T cells can play an important role in a disease stage-specific context. Importantly, they cells are absent in chronic Multiple Sclerosis lesions apart from the T-cell repertoire shows changes (Awad & Stüve 2010).

        Different T cell subtypes play significant roles in the pathogenesis of autoimmune diseases such as multiple sclerosis. Extensive studies have been conducted to validate these interactions. These diverse subpopulations contain distinct cytokine products.  ‘TH1 CD4 + cells secrete interferon gamma, tumor necrosis factor α, IL-2, and nitric oxide’ (Awad & Stüve 2010, p, 168).  TH1 cells are responsible for activating cell-mediated immunity. Alternatively, TH2 CD4+ cells secrete IL-4, IL-5, IL-6, IL-10, IL-13. They transform the growth factor β.  TH2 cells in humans function as a regulator agent when certain inflammatory conditions occur (Awad & Stüve 2010).

      The human system does not contain distinct TH1-TH 2 dichotomy. This adds to the complexity of explaining cell mediated immunity. Significantly, there is an overlap expression of cytokine between two subtypes TH1-TH 2 dichotomy which is a subtype of CD4+ cells. These cells have been implicated in the autoimmunity as TH17 cells. They express as proinflammatory cytokine IL-17. RNA (mRNA) encoding IL-17 messengers were detected in blood at very high levels cerebro spinal fluid (CSF) and brain parenchyma of multiple sclerosis patients in active stages of the disease (Awad & Stüve 2010).

      This phenomenon is highly suggestive of the major role cell mediated immunity plays in progression of multiple sclerosis as an immunopathogenesis factor in the disease sequence.  More importantly, it is worth noting that even though multiple sclerosis is often perceived as a CD4+-mediated autoimmune disease, there are CD8+ T cells implications in its pathology. Precisely, scientists have confirmed that clonal and oligoclonal expansion of CD8+ T cells consistently have appeared in plaques obtained from multiple sclerosis patients during diagnostic testing. In a few situations when evaluations were conducted, CD8+ T cells were found to have outnumbered CD4+ T cells (Awad & Stüve 2010).

        Again this is highly suggestive of suggesting cytotoxic T cells probably participation in starting this inflammatory interaction. Another factor worthy of consideration is the knowledge that T lymphocytes express γ/δ receptors were detected in various quantities when cerebro spinal fluid (CSF) of multiple sclerosis patients experiencing early stages of the disease. However, patients who had the disease for a longer time emerging into the chronic stages, CD8+ T cells were not found. The distinction lays in a probability that these cells play a role in the early development of the disease when cell medicate immune response is being activated.  More clarification on this phenomenon is pending while the pathogenic role of CD8+ T cells in multiple sclerosis progression is further explored (Awad & Stüve 2010).

Humoral Immunity

       Scientists posit that despite the autoimmune process in multiple is perceptive mainly from the premise of it being mediated by T cells; there is just as much evidence to suggest a great degree humoral immunity activity is also involved in the progression of disease process. Fundamentally, scientists discover that there have been interactions with an antigen driven B-cell response in multiple sclerosis patients’ cerebro spinal fluid. This is highly suggestive that B- cells are implicated in the immunopathogenesis of the disease. Also, oligoclonal immunoglobulin production persists in the cerebro spinal fluid of multiple sclerosis patients. Subsequently, growth of secondary lymphoid brain tissue was detected during diagnostic evaluations in multiple sclerosis patients experiencing secondary progressive stages of the disease. Some research studies have even shown a direct relationship between intrathecal immunoglobulin levels and severity of the disease when patients present with secondary progressive multiple sclerosis (Awad & Stüve 2010).

          Scientists have continued probing for evidence of humoral immunity implication. Researchers have also detected B cells in brain cerebro spinal fluid of secondary progressive multiple sclerosis patients. There has been constant isolation of B cells in the cerebro spinal fluid of patients with secondary progressive multiple sclerosis. Evidence of clonal expansion along with extensive somatic mutation in B-cell receptor genes was observed. This phenomenon expresses the characteristic features of an antigen-driven response. Precisely, the assumption is that B-cell selection might have been initiated in peripheral lymph nodes or in lymphoid follicles of the central nervous system (Awad & Stüve 2010).

            Further studies related to investigating B-cell compartment of cerebro spinal fluid in multiple sclerosis reveal that B-cell differentiation is confirmed in the central nervous system of individuals suffering from multiple sclerosis. The dominant antibodies happen to be short-living plasmablasts. Interestingly it is not plasma cells. Precisely, plasma cells are actually the predominant antibody secreting cell found in multiple sclerosis patients’ cerebro spinal fluid.               More importantly, the phenomenon whereby upregulation of costimulatory molecules on plasma cells within central nervous system  occurs is indicative the potential of such cells to sustain their T-cell activation.  Scientifically, B cells have been known as potent antigen-presenting cells. Assumptions are that they might feature prominently in T-cell antigenic stimulation. Scientists conclude that B cell and humoral immunity might be the main factors responsible for initiating and sustaining multiple the sclerosis disease process (Awad & Stüve 2010).

Immunoregulatory Cells

          Studies have revealed that isolating myelin-reactive T cells from peripheral blood of healthy subjects is highly suggestive that, perhaps, decreasing regulatory cells interactions is the basic immunopathology concepts in multiple sclerosis evolution and not he presence or absence  of self-reactive T cells.  Scientifically,   it has been accepted that regulatory cells play a major role in controlling intensity when immune response are activated by maintaining self-tolerance. Importantly, it has been proven that CD4+ TH2 cells are active in anti-inflammatory cytokines production. They are IL-4, IL-5, and IL-13. Precisely, this CD4+ TH2 has the ability of lowering regulatory function of macrophages (Awad & Stüve 2010).

    Further developments show where a relatively little subpopulation of CD4+ T cells were identified to be naturally occurring regulatory T (CD4+CD25+Treg) cells. It is believed that they are vital participants in the immune homeostasis process too. Certainly, they were found to be expressing CD25 which is an important component of the IL-2 receptor. However, preclinical trials have revealed that Treg cells’ absence was closely associated with the emergence of autoimmunity. Overwhelming evidence exists to prove that inadequate Treg-cell activity could be a main contributory element in multiple sclerosis etiopathogenesis. Essentially, studies show where  CD4+CD25+Treg cells effector function  emerging out of multiple sclerosis patients’ peripheral blood  samples of patients was deficient in comparison to CD4+CD25+Treg cells from subjects who were not afflicted by the disease (Awad & Stüve 2010).  .

         While these findings scientifically seem profound critics argue there are no differences in Treg cell concentration and constitution in the cerebro spinal fluid among patients afflicted by multiple sclerosis and those who were healthy. A larger study conducted on 73 multiple sclerosis researchers discovered that Treg cell concentration was identical with that of healthy volunteers. . The notable difference detected was that the Treg cells obtained from multiple sclerosis patients demonstrated reduction suppressive potential on the ‘immune response directed against myelin antigens’ (Awad & Stüve 2010, p 201). Yet, in another study this theory was refuted since, there were higher Treg cell counts in multiple sclerosis patients than in the control. Alternatively,  appeared the potential of these cells suppress MBP-induced proliferation was less effective (Awad & Stüve 2010)

        Explaining the functional differences of Treg cells activity in multiple sclerosis patents and healthy subjects there has been reports of activity in RRMS and progressive stages of the diseases too.  For example, Forkhead box p3 (FOXp3) has been identified as a popular transcriptional factor. Its main role has been detected being a valuable participant in Treg-cell-suppressive molecular programmer activity (Awad & Stüve 2010)

            Many preclinical studies have supported many of these theories in confirming the linkage between autoimmunity and absence of FOXp3. An association was also discovered with ectopic FOXp3 expression conferring suppressive function on CD4+CD25+Treg cells. Further linkages posit a relationship showing significant reductions in FOXp3 mRNA transcripts and protein levels. Importantly, this occurred without any concordant decrease in CD4+CD25+Treg representation in multiple sclerosis patents. FOXp3+CD4+CD25+Treg cells popularly create infiltrations when cerebro spinal fluid of subjects afflicted with neuro inflammatory diseases. Comparatively, this multiple sclerosis patients isolated more FOXp3+CD4+CD25+Treg cells   than patients afflicted by dementia, stoke  or  any other neurological disease. In addition it was observed that Treg activity seem to be compromised when peripheral blood samples are used for the analysis in multiple sclerosis patients unlike other non-affected clients.

Therapy and management

        There is no cure for multiple sclerosis. However, scientists continue to experiment with drugs and therapies, which can be useful in relieving symptoms. For example, David Virley (2005) conducted studies to explore strategies involved in ‘Developing Therapeutics for the Treatment of Multiple Sclerosis.’ The author posited that many animal models have been used in developing therapeutic interventions for treating relapsing multiple sclerosis. The aim of preclinical research was mainly to identify and validate novel targets that are the most appropriate mimics for the specific clinical situation. Animal models therefore, become valuable subjects in establishing drug development processes that help select suitable human subjects for therapeutic interventions. This process provides the proof-of-concept for continuance of clinical trials. The author further contended that ‘although there is no gold standard model of multiple sclerosis, experimental autoimmune/allergic encephalomyelitis (EAE) models simulate the clinical and pathological hallmarks of multiple sclerosis in various guises and can provide the necessary predictive index for clinical therapeutic application’  (Virley, 2005, p 639).

         EAE was induced by generating T-cell-mediated immunity into central nervous system antigens, which was easily modeled in rodents such as rats, mice, and guinea pigs. Whole CNS homogenate (spinal cord) t purified protein and peptides were combined in preparing the autoantigen for the experiment (Virley, 20050.  ‘Myelin basic protein (MBP), proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), S100β, and glial fibrillary acidic protein as well as specific peptides from respective parent proteins are encephalitogenic in the appropriate host, as the major histocompatability complex (MHC) is one of the major determinants of immune responsiveness and disease susceptibility to these self-antigen’ (Virley, 2005, p 639).

        The author concluded that the pathogenic autoimmune mechanism steps that initiate and magnify EAE and MS damage tissue sequences are:-

  • Activation of autoreactive CD4+ T-cells in the periphery to an antigen;
  • Transmigration of proinflammatory T-cells and monocytes through the blood brain barrier (BBB)
  • Amplification of local inflammation and activation of resident antigen-presenting cells (APCs), such as microglia; and 4) destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).

(See Appendix 4).

Current Drug Therapies

The foregoing trials have emerged into distinct therapies, which are now active treatment management intervention s for multiple sclerosis. To date there are only five Food and Drug Administration (FDA) approved therapeutic treatments for relapsing – remitting multiple sclerosis. They include ‘two interferon (IFN)-β1a agents (Avonex and Rebif), one IFN-β1b (Betaseron), glatiramer acetate (GA) (Copaxone) and Mitoxanthrone (Novantrone)’ (Virley, 2005, p 639).

      Patents suffering from secondary progressive multiple cyclophosphamide (Cytoxan) and mitoxanthrone are the drugs of choice. There are no extreme benefits in using these two drugs or severe toxicity. However, the main drugs used are corticosteroids, IFNβ and GA (Virley, 2005).

Corticosteroids

             Corticosteroids are administered to raise a patient’s tolerance level tolerance during an attack and speed up recovery. Long term therapies are more effective even though short-term interventions can be useful. However, to maintain a longer period between remissions it is always better to continue treatment over a longer period of time.  Patents often receive significant results even when the clinical course of multiple sclerosis may change to secondary progressive stage. Even with so many drug trials and pre-trials being conducted scientists are still not yet sure what are the actual effects of corticosteroid on the immune system are (Virley, 2005).

         However, preclinical research evidence has verified quite a few putative mechanisms. They embody ‘an inhibition of the Th1 immune response reduction in BBB molecules and protection of oligodendrocytes from cytokine-induced cell death’ (Virley, 2005, p 639). EAE models validated the suppressive interactions produced by corticosteroid treatment in relation to clinical course disruption of multiple sclerosis, T-cell migration dampening its antigens response suppression during expression of adhesion utilization of anti-glucocorticoid, RU 38486 (mifepristone). It was revealed that these interactions have intensified as well as reversed steroid-induced inhibition of disease (Virley, 2005).

      While corticosteroids have been so effective in the treatment of multiple sclerosis in both short and long term its side effected should not be underestimated. For example, extended use can initiate transient mood changes headache, gastrointestinal disturbances, and myalgias.  Decrease in bone density can occur overtime if patients must be treated for extended periods of time. Ultimately, osteoporosis could become a real problem increasing risks for fractures and infections. When side effects have become so progressive, the patient ought to be reassessed. Often the attending physician may consider either reducing or discontinuing treatment temporarily (Virley, 2005).

IFN-β

          IFN-β therapies emerged after over 25 years of clinical trials. The aim was finding how multiple sclerosis would respond to IFNs if it is truly a virally mediated disease. Importantly the   antiviral assumption became invalid after clinical trial assessments, which revealed that IFNγ worsened symptoms.  This was highly suggestive, that IFNγ  was more influential in multiple sclerosis pathological process. it meant that IFNβ, like other IFNs, is a species-specific glycoprotein with numerous biological properties. Actually, the mechanism producing these interactions is not fully understood from a scientific perspective poorly. However assumptions have been that immunomodulatory as an alternative to antiviral and antiproliferative makes much sense in deriving at an alternative proposition (Virley, 2005).

      Importantly, IFNβ-1a is exactly like the natural IFN-β, but IFNβ-1b differs in having two amino acids as well as not being glycosylated. Despite these insidious structural differences IFNβ-1b displays comparative biological activity to IFNβ-1a. Therefore, putative responses of IFNβ on the progression of multiple sclerosis is believed to be related primarily to its  antiinflammatory influences, which demonstrates as dampening the stimulatory impact of IFNγ, tumor necrosis factor (TNF)α, interleukin (IL)-12. The lymphotoxin secretion has been identified in the sequence of controlling monocyte activation; inhibiting disruption of BBB. Consequently, the entry of lymphocytes into the CNS is reduced; antigen presentation is reduced to T-cells; and up-regulation of anti-inflammatory cytokines occurs; TGFβ and IL-10 (Virley, 2005).

        EAE pre-trial models have validated the use of IFNβ by proving its influence in limiting the   progression of multiple sclerosis. Supportively, clinical trials were done using both IFNβ formulations. Important findings indicate a one third relapse reduction rate when higher doses are administered. The onset has been observed to be rapid. Precisely, relapses occurred at a rate of 1 per year and few weeks for MRI disease activity. Conversely, there were huge inflammatory changes measured through MRI activity; accumulation of MRI disease burden was significantly slowed down. Besides, there were magnificent results shown by patients regarding relapses (Virley, 2005).

      This novel treatment is not without its adverse side effects. Some include, flu-like symptoms along with reactions emerging at the site where injections are administered. If patients do not respond to the drug after six months of therapeutic intervention, the IFNβ therapy is usually discontinued. Some patients who are already disabled with progressive or relapses occurring at a rate of more than one per year are treated with a combination of combination three or more courses of corticosteroids over a 1-year period. In addition some patents encounter extreme feelings of depression leading towards suicidal inclinations. Drug toxicity can also become a problem with patients becoming noncompliant. This initiates physicians’ decisions of considering alternatives. Neutralizing antibodies in IFNβ effectiveness ought to be addressed as an adverse reaction during treatment. This can lead to long term complications. As such, it must not be ignored if patients complain of reactions or it shows up in diagnostic testing (Virley, 20 05).

   Glatiramer acetate – GA

          GA is considered a non-IFN, nonsteroidal therapy. It is made from synthetic random base copolymers mixtures containing four amino acids namely glutamic acid, alanine, lysine, and tyrosine). The molar ratio was highly specific. Trials researched investigated the GA’s potential encephalitogenic role using EAE animal models. However, surprisingly, it was discovered that GA suppressed their acute and chronic clinical and pathological hallmarks. Importantly, translation of impacts was clinically beneficial. Importantly, GA provided evidence in the initial phase II trial as being a suitable agent for reducing relapse rates by 76% in patients with relapsing-remitting multiple sclerosis. A 5 year follow up intervention treatment confirmed

GA benefits as being capable of sustaining the initial influence on relapses in multiple sclerosis patients. The progression of the disease into the secondary stages was significantly slowed. Patients did not enter into disability as quickly as when other drug therapies were used. Also, when the Lesion burden was assessed through MRI it validated the value of GA in helping patients during the relapsing-remitting episodes. It was discovered that GA greatly reduced  frequency  rates of lesion load  and new enhancing lesions when baseline pretreatment measures are compared (Virley, 2005).

     Since then numerous mechanisms were advanced as being responsible for these fascinating results observed by GA’s intervention in the disease process. First its biological activity relapsing-in remitting MS was noted as a valuable factor. Then the antigen-specific induction suppressor T cell was remarkable. Thirdly, a MBP competitive inhibition was distinctly observed as a benefit. There was also a relationship of the interactions to -peptides from antigen-presenting cells (Virley, 2005).

       It must be noted that regardless of how beneficial a new drug therapy may be in treating a disease there are always adverse effects, which must be considered in its administration. GA is no exception even though the tolerance level in multiple sclerosis patients is great. However, subcutaneous administrations could become harmful due to increasing incidences observed whereby injection site reactions occurred in the majority of cases and they were localized proving that it was the drug interaction with human skin (Virley, 2005).

             The overall picture being communicated in the use of this drug pertains towards it being the most tolerable in terms of side effects when compared to other therapies. Reduced propensity in the development of depression, neutralizing antibodies and menstrual disorders was far less when compared to other drugs now available for treating multiple sclerosis. Despite these developments, however, it is still important for continued research in extending to multiple sclerosis patients more options. While there is no cure for the condition medical science can provide the best relief it could through timely and efficient intervention therapies that work (Virley, 2005).

      Ultimately, these interventions should aim at not only providing relief, but secure sustained drug benefits reducing symptoms of multiple sclerosis, which shows that treatments are becoming more effective. Patents should be taking lower doses and experiencing fewer side effects. As such, pharmaceutical and biotechnology industries are challenged to provide this service to the multiple sclerosis community of patients. Essentially, numerous alternative disease-modifying strategies are emerging. They will be reviewed in the following pages of this document (Virley, 2005).

           For example, Pietro Iaffaldano (2012) and a group of researchers conducted studies regarding the ‘Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study.’ These researchers contend that Natalizumab reduced relapse rate as well as magnetic resonance imaging reactions in patients experiencing Relapsing-Remitting Multiple Sclerosis (RRMS). However, its impact on fatigue cognition in patients affected by multiple sclerosis need to be validated though scientific research. There the purpose of a prospective, open-label, observational study was intended as an  evaluation relating probable impacts  natalizumab had on cognition and fatigue when measured in patients experiencing Relapsing-Remitting Multiple Sclerosis  after being treated continuous for two years (Iaffaldano et.al, 2012).

        Researchers examined cognitive performances by applying  ‘Rao’s Brief Repeatable Battery (BRB) device, the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months’ (Iaffaldano, 2012, p  201).   When patients did not respond favorable to at least 3 BRM and ST 3 they revived a cognitively impaired (CI) classification. Every 12months the Fatigue Severity Scale (FSS) was administered. This assessed the patient’s ability to self-reported incidences of fatigue. A total of 1 53 patients participated in 1 and 2 year-natalizumab continuous treatment (Iaffaldano et.al, 2012).

       Result revealed that after one year treatment the amount of’ CI sampled patients decreased from 29% (29/100) at baseline to 19% (19/100) (p=0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p=0.008). These significant effects were confirmed in the subgroup of patients treated up to two year.’ (Iaffaldano et.al, 2012, p. 201). From these results researchers concluded that

In the short-term Natalizumab can be successfully used as a treatment which could, ultimately reduce incidences of cognitive difficulties and fatigue in patients experiencing Relapsing-Remitting Multiple Sclerosis (Iaffaldano et.al, 2012).

Examples of Novel Therapeutic Challenges for Multiple sclerosis

Blockade of lymphocyte migration

       Very late antigen-4: natalizumab (Tysabri) and small molecule antagonists. There is widespread evidence implicating very late antigen-4 (VLA-4, α4-β1 integrin) in this process, via its interaction with receptors like vascular cell adhesion molecule 1 (VCAM-1) and the CS1 fibronectin domain (Virley, 2005).

Immunomodulatory agents

       Interest recently has emerged regarding development of novel Immunosuppressants. Trials have been conducted and they have been actually used in treatment of many autoimmune diseases such as psoriasis and rheumatoid arthritis. They reduced exacerbations keeping progression (Virley, 2005).

Anti-inflammatory agents

‘Cycloxygenase-1 and -2 (COX-1 and COX-2 or prostaglandin H synthases 1 and 2) catalyze the conversion of arachidonic acid and oxygen to generate inflammatory prostaglandins such as PGE2, PGD2, PGF2a, and thromboxane’ (Virley, 2005, p 201).

Neuroprotective and neuroregenerative therapeutic strategies

       Achievements in repair of myelin and immense neuroprotection though therapeutic interventions can be interpreted major research breakthrough in the attempt at providing more beneficial therapies that reverse permanent neurological disability associated multiple sclerosis.

Potential combinations of therapeutic strategies

       The heterogenic influences of clinical response as well as pathological hallmarks contained in recent multiple sclerosis drug development it would be wise considering combining therapeutic strategies that differentiate concentrating of specific aspects of the disease such as cognition memory and fatigue as espoused by Iaffaldano and his team of researchers. An area of precedence is a development stage whereby each agent independently offers a benefit distinct from the others, but is still valuable when combined in adding synergistic value to the therapeutic intervention. This approach would be extremely beneficial for patients who seldom respond favorable to therapies now available on health care markets across the country and world (Virley, 2005, p 201).

Conclusion

               While theories pertaining to the etiology/epidemiology/immunology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explored the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of this disease. Consequently, the researcher adapted a comparative analysis of the perspectives offered by theorists in discussion of epidemiology regarding emergence of multiple sclerosis among the predominantly, female young adults twenty-first century population. These were matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management, and current trends are being explored.

Current Trends

                   Precisely, Ascherio and Munger (2007) ‘Environmental risk factors for multiple sclerosis Part I: the role of infection’ contend that even through genetic susceptibility play a role in the acquisition of multiple sclerosis among families studies show where personal hygiene significantly affect occurrence of the disease. Further, they advance that genetics and environment alone cannot account explicitly for the MS frequency among geographic variations when risk changes with migration are taken into consideration. Supportive epidemiological findings highlights the “hygiene hypothesis,” showing the additional role Epstein-Barr virus (EBV) plays as evidence for MS risk factor (Ascherio & Munger, 2007)

             Another piece of research literature by the same authors ‘Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors focusing on the environment explains that the change risk factor among migrants gives profound evidence for M.S environmental determinants. Then researchers defined environment to mean variations in diet and social behavior. Main contributory factors were sunlight and cigarette smoking (Ascherio & Munger, 2007)

     Dyment, Ebers, and Sadovnick, (2004) took a stand in ‘Genetics of multiple sclerosis.’          They argue that while environment and infection may play a role many genes appear to be linked to  MS etiology. They mentioned ‘HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A’ (Dyment et.al, 2004, pp 110). These researchers advanced that future development in the MS genetic science largely depends on continuous research making data available as evidence. Also the development of appropriate statistical measurements and research methodologies could be valuable (Dyment et.al, 2004).

             George Ebers (2008) focused on ‘Environmental factors and multiple sclerosis’ in reporting that studies conducted in Canada show where environmental factors influence the distribution of MS in specific geographic locations. The researcher cited migration studies to prove that the increase incidence of MS in Canada relates to longitudinal sex ratio expansion among immigrants within the country. This was compared to studies conducted in Australia where similar geographic patterns exist. It was discovered that by modifying the environment it reduced 80% of cases. It was concluded that while genetics play a major role there are predominant environmental factors associated with MS incidences in certain geographic locations (Ebers, 2008).

       Gavin Giovannonia and George Ebers (2007) posit that ‘genes and environmental factors lead to tissue injury by autoimmune mechanisms, implicated by strong circumstantial evidence’ (Giovannonia and Ebers, 2007 pp, 261). They further contend that it is difficult to identify the specific genes responsible for MS without examining the associating influences of the environment. Actually, they argue that the impact of genes on MS emergence is modest. Additional studies were cited emphasizing irregularities in confirming the genetic theory of MS etiology (Giovannonia and Ebers, 2007).

                Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed at addressing the autoimmune etiology of the disease. These therapies are designed to reduce inflammation, but their long term effect is uncertain. Hence, a re-evaluation of both pathogenesis and etiology is suggested (Nakahara et.al, 2012).

                     Rosati offered insights to say that the childhood environmental factor was a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

               Consequently, this study’s importance pertains to advancements into understanding multiple sclerosis’ etiology, pathophysiology/immunology and treatment. As explained in the foregoing principal pieces of research literature theories relating the etiology of MS are numerous. However, theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure.

       Current therapeutic trends predict that the ideal treatment for multiple sclerosis mustconsist oftechniques aimed at increasing disease-causing/sustaining antigen(s) tolerance. Ultimately, it is expected that long-term therapy would be obviated. This is important because amidst  numerous continuous drug trials scientist still contend that none of them seem to have considerable effects on resolutions of a disease which is over 100 years old. Justifiably establishing coordination between activated T cells and B cells in the pathophysiology of multiple sclerosis is highly recommended for targeting the two cell population. These include resting and dividing cells together. The strategy may necessitate, taking control of the disease process itself (Awad & Stüve, 2010).   

          Whatever emerges from these assumptions scientist must bear in mind that other immune cell populations are playing a major role also in the sequel of this disease. They intimate and perpetuate the process. Therefore, the final proposition of this theory advanced that amplifying or sparing the pool of regulatory cells which act as mediators of immune suppression would be valuable a valuable intervention. This however must be embraced without compromising immune surveillance in the treatment of this disease (Awad & Stüve, 2010). In concluding these deliberations pertaining to current trends in multiple sclerosis therapeutic management it is expected that this research project sensitize scientists into elaborating on present research practices in order for a consensus be reached regarding the reality of multiple sclerosis etiology and its pathological implications.

References

Ascherio, A., & Munger, K (2007). Environmental risk factors for multiple sclerosis. Part I: the

                      role of infection. Ann. Neurol. 61(4); 288–99

Ascherio, A., & Munger, K. (2007). Environmental risk factors for multiple sclerosis. Part II:

                     Noninfectious factors. Ann. Neurol.  61(6); 504–13.

Awad, M., & Stüve, O. (2010). Immunopathogenesis of Multiple Sclerosis: New Insights and

                    Therapeutic Implications. Lifelong Learning in Neurology. 16(5); 166-180

Clanet M (2008). Jean-Martin Charcot. 1825 to 1893. Int MS J 15 (2), 59–61.

DasGupta, R., & Fowler, C. (2003). Bladder, bowel and sexual dysfunction in multiple  

                       sclerosis: management strategies.  Drugs, 63 (2): 153–66.

Dyment, A; Ebers, G; Sadovnick, A. (2004).  Genetics of multiple sclerosis. Lancet

                                 Neurol  3( 92). (2004): 104–10.

 Ebers, G. (2008). Environmental factors and multiple sclerosis. Lancet Neurol  

                              7 (3). 268–277.

Foley, P. Vesterinen, H. Laird, B. (2013). Prevalence and natural history of pain in adults with

                       multiple sclerosis: Systematic review and meta-analysis. Pain 154 (5): 632– 42

Gilden, D (2005). Infectious causes of multiple sclerosis. The Lancet Neurology 4  (3)

                                    195–202.

Giovannoni, G; Ebers, G. (2007). Multiple sclerosis: the environment and causation. Curr

                                Opin Neurol. 20( 3); 261-8.

Kantarci, O., & Wingerchukb, D. (2006). Epidemiology and natural history of multiple sclerosis:

                             new insights. New York. Lippincott Williams & Wilkins

Kurtzke, J. (1983). Rating neurologic impairment in multiple sclerosis: an expanded disability

                          status scale (EDSS). Neurology, 33 (11); 1444–52.

Iaffaldano, P. Viterbo, G. Paolicelli, D. ( 2012). Impact of Natalizumab on Cognitive

               Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label,

                  Two Years Observational Study. PLoS . 7(4)

Merril, R. (2010). An Introduction to Epidemiology, (5th Edition). Jones and Bartlett

                   Publishing.

Murray, J (2002). Infection as a cause of multiple sclerosis. Theories abound because no one

                         knows the answers yet. BMJ. 325(7373).(2002). 1128.

Nakahara, J; Maeda, M; Aiso, S; Suzuki, N ( 2012). Current concepts in multiple

                             sclerosis: autoimmunity versus oligodendrogliopathy. Clinical reviews in

                           allergy & immunology  42(1); 26–34.

 Oksenberg, J., & Barcellos, L (2000). The complex genetic etiology of multiple sclerosis.

                           Journal of NeuroVirology. 6(2), S10 ± S14

Rosati G (2001). The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 22

                (2): 117–39.

Royal College of Physicians London (2004) Multiple Sclerosis: National Clinical Guideline for

                Diagnosis and Management in Primary and Secondary Care. NICE Clinical

              Guidelines, No. 8.National Collaborating Centre for Chronic Conditions (UK).

               London

   Schäffler, N. Köpke, S. Winkler, L. Schippling, S. Inglese, M. Fischer, K.,  & Heesen, C.

      (2011). Accuracy of diagnostic tests in multiple sclerosis–a systematic review. Acta Neurol

                      Scand. 124(3), 151-64

Siegert, R., Abernethy, D. (2005). Depression in multiple sclerosis: a review. J. Neurol.

                     Neurosurg. Psychiatr. 76 (4): 469–75.

Terry, R. Miller, S. Getts, D., & Muller, M. (2012). Current Theories for Multiple Sclerosis

                    Pathogenesis and Treatment. Free Press New York. 2012.

 Virley, D. (2005). Developing Therapeutics for the Treatment of Multiple Sclerosis. NeuroRx.

                 2(4): 638–649.

Appendix 1

Table 1 Multiple sclerosis as a genetic disease

———————————————————————————

1. Racial clustering of MS cases. Resistant ethnic groups residing in high risk regions

2. Familial aggregation of MS cases. Increased relative risk to sibs (ls=20±40)

3. Low incidence of conjugal MS

4. MS sibling pairs tend to cluster by age of onset, rather than

year of onset

5. High disease concordance in monozygotic twins (25±30%) compared with dizygotic twins and non-twin siblings (3±5%)

6. No detectable effect of shared environment on MS susceptibility in first-degree non-biological relatives (spouses, adop-tees)

7. Suggestive correlations between certain polymorphic loci and disease susceptibility

————————————————————————————

Appendix 2

Table 2 Confounding factors in genetic studies of multiple

Sclerosis

————————————————————————————————-

1. Aetiologic heterogeneity identical genes, different phenotypes

2. Genetic heterogeneity Different genes, identical phenotypes

3. Unknown genetic parameters Single versus multiple genes Dominant versus recessive mode of inheritance incomplete penetrance

4. Epistatic gene interactions

5. Post-genomic mechanisms

6. Unidentied non-heritable (environmental) factors

——————————————————————————————————————

(Oksenberg & Barcellos, 2000).

Appendix 3

http://upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Ms_progression_types.svg/300px-Ms_progression_types.svg.png

                     Diagram showing immunological concepts underlying Multiple sclerosis                   

                     Progression of subtypes (Oksenberg et.al, 2000).                        

FIG. 1.

      Schematic view of the putative pathogenic steps in MS. 1: Activation of autoreactive T cells by antigen presenting cells in the periphery. 2: Migration of T cells and monocytes through the blood brain barrier. 3: Amplification of local inflammation and destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).                                         Appendix 5   – Demyelinization

Medicine and Health: Multiple Sclerosis

Name of Author

Outline

Introduction

•          Description

•          Epidemiology

•          Clinical signs and symptoms

•          Diagnosis

•          Prognosis

Immunological concepts underlying the disease

Therapy and management

Conclusion

•          Current Trends

Abstract

The purpose of this document is to offer a precise account of Multiple Sclerosis. The statement of problem related to this research reads ‘while theories pertaining to the etiology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explores the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of the disease. Consequently, the researcher will adapt a comparative analysis of the perspectives offered by theorists regarding emergence of multiple sclerosis among the twenty-first century female young adults. These will be matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management as well as current trends are explored.

Medicine and Health: Multiple Sclerosis

Introduction

Description

          Multiple sclerosis was not discovered as a disease until late 19the century. An English Physician by the name of Walter Moxon in 1873 along with American Dr. Edward Seguin in 1878 discovered multiple sclerosis as a dysfunction of the nervous system. They confirmed that it was more common in women than men. However, three notable signs of multiple sclerosis signs described as Charcot’s triad 1 being nystagmus, intention tremor, and telegraphic speech (scanning speech) have been attributed to French neurologist Jean-Martin Charcot (1825-1893). He  recognized cognition alterations, which was described as “marked enfeeblement of the memory” and “conceptions that formed slowly” (Clanet, 2008, p 58).  At the time these doctors did not project any sound etiology of the disease, but said that there was no evidence to support it being inherited. However, they confirmed that numerous diverse neurological irregularities were produced as symptoms of the condition (Terry et.al, 2012).

            Multiple sclerosis (MS); disseminated sclerosis is also known as encephalomyelitis disseminata. Scientists have described it as an inflammatory condition characterized by formation of myelin sheaths around brain and spinal axons tissue. Ultimately, these tissues are destroyed through scarring; reduction in myelin to protect brain and spinal cord. Research is still being conducted regarding its etiology, Assumptions however have been that many predisposing genetic, environmental and infection factors could initiate the inflammation (Ascherio & Munger, 2007).

      Other assumptions have been that there are mechanisms within the body chemistry, which are responsible for destruction of the immune system inhibiting production of myelin cells. Consequently, massive insidious nerve destruction occurs and nerve cells become incapable of functioning as communicators of impulses across nerve ending within the human body. Often when the etiology of a disease is obscure there is seldom a cure. Recent research has continued to advance ther theory that indeed multiple sclerosis affects more females than males (Nakahara et.al 2012)

        To date scientists have advanced from repeated research that there is no discrimination as to which neurological symptoms can emerge due to nerve destruction in the brain and spinal cord which are the primary target organs. From observation there have been immense progressive physical and mental dysfunctions. In some cases memory irregularities could develop, but a difficultly exists classifying them as purely psychiatric because they may present in conjunction with various levels of other neurological abnormalities. As the disease evolves it converges into many misleading features increasing the challenge of addressing the real symptoms in devising modes of treatment intervention. Scientists have described this phenomenon as an escalation of new symptoms, which were not formerly associated with the initial presentation. They are termed relapsing forms and progressive forms respectively (Dymentet.al, 2004)

        The period from when attacks begin end, and begin again symptoms may subside. However after these episodes permanent nerved damage occurs. As the disease advances symptoms worsens and exacerbations seems to occur leading up to when treatment becomes ineffective. This disease is more than 100 years old, but scientists have not been articulate in arriving at any profound etiology while numerous theories exist. They have not gone far beyond exploring mechanisms related to the disease process itself (Ascherio & Munger, 2007).

       Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed only at addressing the autoimmune etiology of the disease. As such, they merely focus on restoring function to affected nerves after symptoms become uncontrollable; control recurrence and limit the extent to which nerve damage produces disability (Nakahara et,al, 2012).

          However, medications used to treat multiple sclerosis are not without their serious side effects, besides being poorly tolerated by patients. Consequently, patients turn to alternative medicine for relief. Precisely, since there are few studies conducted regarding alternative remedies these remedies are considered nonscientific and are not recommended even through patient report how successful these treatments have been in restoring nerve function (Gilden, 2005).

      People diagnosed with multiple sclerosis live an average 5-10 years, less than persons who do not have the disease. There is an average of 2 persons affected by multiple sclerosis for every 150 per 100, 000 (Rosati, 2001).  However, data or theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure. This research is expected to sensitize scientists into elaborating on present research practices in arriving at a consensus regarding the reality of multiple sclerosis etiology.

Epidemiology

      Epidemiology infers a study of disease patterns that evaluates infection etiology; geographic, socioeconomic status, genetics and demographic variations. Often epidemiologists add to the multiple sclerosis body of knowledge through assessing relationships between these factors. Since there are no known causative factors for multiple sclerosis it is important that epidemiologists continue investigations regarding migration patterns. However, it must be understood that figures published in epidemiology records are all estimates. This is an attempt at establishing a more profound understanding regarding multiple sclerosis target populations across the world. It also helps identifying and explaining geographic locations containing highest and lowest multiple sclerosis rates (Merril, 2010).               

        The challenge facing the epidemiology of multiple sclerosis lays in the difficulty diagnosing the disease. No single distinct tests are being conducted in establishing a diagnosis for multiple sclerosis. As such, the argument is that diagnoses can be incorrect delayed or just bypassed. While MRI technology has been of great assistance in resolving difficult diagnoses epidemiologists question the accuracy of diagnoses produced from previous studies since they may not give a true representation of multiple sclerosis with the given population. More importantly, various methodologies used by specialists collecting data on the disease can greatly alter interpretations and outcomes. Due to these factors the epidemiology of multiple sclerosis is still in its infancy even though the disease is over 100 years old (Merril, 2010).              

                 According to Orhun Kantarci and Dean Wingerchukb (2006) multiple sclerosis claims the health of approximately 1 000 000 people between 17 and 65 years old internationally. The 2000 projected multiple sclerosis prevalence rate among white US populations showed 191 per100 000. Alternatively, the US overall incidence rate and was 7.3 per 100 000 person in the same year. Further epidemiological studies supported the theory that multiple sclerosis is two times more common in women than men. It was discovered also that there is a tendency for a later onset of the disease among men. The prognosis for them is even worse for women. Scientists attribute this difference to gender-dependent and phenotypic variability factors which may create an etiological predisposition (Kantarci & Wingerchukb, 2006).

        Multiple sclerosis care cost United States government an estimated $6.8 billion annually, which includes loss in productivity as well as actual health care interventions. A total life time cost is estimated at 2.2 million per patient (Kantarci & Wingerchukb, 2006).Similar epidemiological estimates exist around the world. There seems to be patterns of ‘a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere’ (Rosati, 2001, p 22). Multiple sclerosis is less prevalent among people who live close to the equator. Theories pertaining to climate, sunlight and vitamin D intake are variables used in relating possible causes in explaining this latitude gradient theory regarding geographic disposition multiple sclerosis prevalence among people living near to the equator (Rosati, 2001).

     Overtime other variations have appeared, which forced epidemiologist to consider environment in combination with genetics. Multiple sclerosis was discovered to be prevalent among northern European populations and most common in certain ethnic groups such as ‘Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori’ (Rosati, 2001, p 22).

       Childhood environmental factors were then considered as a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

      Critics of the environmental epidemiological theory have contended that quantification of the assumptions is difficult because data derived is obtained mainly from retrospective case-control studies whereby subjects are exposed to the same environment and results may lack internal and external validity besides containing reliability issues. ‘A practical, albeit limited, design is a nested-cohort study in which a population cohort already identified for exposure to given factor(s) for another disease is exploited for excess of -NIS occurrence after sufficient follow- up’(Kantarci & Wingerchukb, 2006, p 249). While trying to make sense of the environmental theoretical epidemiological perspectives major advances have implicate viral exposure factors. Viruses identified are canine distemper virus, Epstein-Barr virus, and human herpes virus-6) (Kantarci & Wingerchukb, 2006).

           Internationally, conclusions are that multiple sclerosis makes its first appearance in adults during their thirties. It can occur at any time in children. However, the primary progressive subtype appears later in people in their fifties.  The genetic epidemiology of multiple sclerosis seems to be overlapping with both environmental and viral/infections. Analysts have discovered that the only facts they have to support the genetic epidemiology are its high incidence among Northern Europeans in relation to indigenous populations from the ‘same geographic location, familial aggregation’(Kantarci & Wingerchukb, 2006, p 249). See appendix 1 and 2

Clinical signs and symptoms

                 Numerous signs and symptoms are associated with multiple sclerosis. However neurologists keep abreast of symptoms by applying the Expanded Disability Status Scale (EDSS).  EDSS gives a score total of a scale ranges from 0 to 10.

 ‘The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.  The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. In addition, it also provides eight subscale measurements called Functional System (FS) scores. These subscale categories are listed below.  The levels of function within each category refer to the eight functional systems affected by MS’ (Kurtzke, 1983).

  • Pain

              Pain is very common among multiple sclerosis patents and often appears after the first lesion is formed. In most occasions it is associated with the control mechanisms which regulate ascending and descending tracts in the anterolateral system. From 28 studies researchers proved taking a sample of 7101 multiple sclerosis patients that 63% complained of various degrees of pain. There were no significant differences in pain levels among men and women or people with greater disability than others.  Most pain occur as ‘headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte’s phenomenon (16%) and Trigeminal Neuralgia (3%)’ (Foley et.al, 2013, p 632).

  • Emotional disturbance

       Emotional disturbance manifests as clinical depression. This can extend into a life time complication. Present incidence rates range between 40–50% per person diagnosed with multiple sclerosis. Brain imaging studies have tried to relate findings to depression when brain lesions are found. More importantly, most neurologists have associated these brain lesions with neuropathology of the left anterior temporal/parietal regions. It is very important development that is worth monitoring carefully because emotional disturbance is responsible for 15% of deaths emerging from suicide. As such, patients are closely evaluated when signs anger, anxiety, hopelessness, and frustration surface (Siegert, Abernethy, 2005).        

  • Bladder and Bowel irritability

       Bladder disturbances occur in 70% of all multiple sclerosis patients. It presents as frequency, hesitancy and incontinence which can affect maintenance of personal hygiene. Bowel issues appear in 70% of the multiple sclerosis patients, 50% suffer from constipation 30% fecal incontinence (DasGupta & Fowler, 2003).            

  • Cognitive disturbances

       40%- 60% of multiple sclerosis patients encounter cognitive difficulties. It ranges from simple degrees of forgetfulness to severe loss of memory. Other cognitive difficulties are attention deficit; neurological fatigue; processing speed and visual spatial ability alterations (Ebers, 2008).

  • Impaired Mobility

           Mobility changes become evident when walking, moving, getting off and on the bed and balancing. Research has shown that between the onset of the disease and 5 years 50% of patient score 6 on the EDSS scale. 10 years living with multiple sclerosis 25% of patients can attain just a score of 6 on the Expanded Disability Status Scale (EDSS). This makes using a walker and other methods of mobility support necessary. Within 30 years, 83% of patients use walking aids (DasGupta & Fowler, 2003).           

  • Speech difficulties

Speech could become slurred and tone of voice altered.

  • Muscle Tremor and Ataxia

Ataxia coincides with muscle tremors. Clumsy movement occurs creating difficulty in maintaining a steady gait. Muscle tremors are often uncontrollable involuntary episodes of shaking.

  • Transverse myelitis 

When multiple sclerosis begins invading deep into spinal cord tissue lower body functions become impaired. These include bladder/irritability as well as sexual potency in males. Inability to have an erecting is possible along with ejaculation difficulties

  • Spasticity

Spasticity manifests as both a sign and symptom. Muscles, especially, in the extremities become very stiff and immobile.

Diagnosis

           Researchers have posited that multiple sclerosis is difficult to diagnose since confirmation of the disease cannot be made on clinical symptoms alone. Signs and symptoms may resemble many other neurological disorders. To facilitate diagnosis during the early stages scientists have designed standardized criteria. They include Schumacher, Poser and McDonald criteria.

Schumacher’s criterion is a neurological examination detecting central nervous system abnormalities involving two or more systemic dysfunctions. Often white matter abnormalities are evident in brain and spinal tissue. In 1983 these criteria were modified by Poser accounting for clinically definite; laboratory supported definite; clinically probable and laboratory supported probable multiple sclerosis (Royal College of Physicians of London, 2004).

                          McDonald criteria are the ones presently used in most health care institutions across the world for making a more accurate multiple sclerosis diagnosis. It includes a

  • Diagnostic criteria for suspected MS (two or more attacks)        Flowchart Icon  
  • Diagnostic criteria for suspected MS (monosymptomatic)         Flowchart Icon
  • Diagnostic criteria for suspected MS (single attack)                   Flowchart Icon
  • Diagnostic criteria for suspected MS (progressive from onset)      Flowchart Icon

                             (Royal College of Physicians of London, 2004)

               However, Schäffler, Köpke , Winkler , Schippling , Inglese , Fischer and, Heesen (2011) have reprted that the development of a new diagnostic criteria for multiple sclerosis was recently proposed after a systematic literature review  revealed that present accuracy issues made some tests invalid. The aim of this study was to validate diagnostic studies and clarify the value of diagnostic test used in offering a diagnosis. They included in their review a minimum of 40 patients who were traced for 2 years. This limitation existed in all the studies reviewed since they significantly lacked a gold standard measurement for validating the diagnostic tests that were used in those trials. A second relapse phase was adopted as a surrogate in relapsing-remitting multiple sclerosis testing. However, the lengthy 5 year follow-up created difficulty in detecting all cases. Also, quite a few studies contained various levels of validity and reliability issues. Notably, a selection bias was identified due to the indistinct classification of a clinically isolated syndrome (Schäffler et.al, 2011).

                  Based on these limitations, ‘sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%; Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%; combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%)’ (Schäffler et.al, 2011, 153). The researchers did not find justification in conclusions derived in the literature review studies. Further they suggest that ‘a combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis’ (Schäffler et.al, 2011, 153).

Prognosis

         While there is no cure for multiple sclerosis it has not been considered a fatal disease even though it severely affects a person’s quality of life. Serious disability does not occur until about 20 years after onset of the disease. Women seem to have a better prognosis than males. Factors affecting each patient’s prognosis regarding quality and length of life relate  to  adherence of health promotion strategies that will limit symptoms , doctor’s  appointment  follow up ; compliance with medication management to reduce progression of the disease. Generally life expectancy is reduced by 5-10 years with careful intervention strategies (Murray, 2002).

Immunological concepts underlying Multiple sclerosis

          Immunology relates to the body’s defense mechanisms in counteracting  the activity of invading agents. For every disease entity that enters the human internal environment there are diverse strategies employed by the immune system in a comprehensive effort to interrupt the intended invasion consequences. Consequently, the immune system builds up resistance by developing immunity to the invading organisms. There are mainly five types of immunological responses that can emerge from this activity. They are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

Humoral immunity

         Humoral immunity is also known as antibody-mediated system being mediated macromolecules located in extracellular fluids like secreted antibodies, antimicrobial peptides and complement proteins. Usually, humoral immunity reacts with substances in body fluid humors (Nakahara et.al, 2006).

Cell-mediated immunity

          Cell-mediated immunity does not rely on producing antibodies in order to defend the body against harmful organisms. Instead it activates phagocytes, antigen-specific cytotoxic T-lymphocytes, and disperses numerous cytokines in an antigen response (Nakahara et.al, 2006).

Innate or Natural Immunity

 Innate immunity is the body’s evolutionary natural mechanism used to fight invading foreign species. This is the dominant and oldest type of immunity among living creatures including unicellular organism such as amoeba, fungi, plants and insects (Nakahara et.al, 2006).

Acquired immunity

      Acquired immunity emerges after exposure to a foreign organism. It is also known as adaptive immunity due to somatic hypermutation or accelerated somatic mutations), and V (D) J recombination, which is actually a genetic antigen receptor recombination that cannot be reversed (Nakahara et.al, 2006).

Non-specific immunity

               Non-specific immunity means that the immunological response is antigen independent and unspecified. However, distinct mechanisms are activated. They include establishing anatomical barriers, stimulation of secretory molecules and integrating cellular components.  Recognizable mechanical anatomical barriers include the internal epithelia tissue such as the skin.  Intestinal mobility along with oscillation of broncho-pulmonary cilia is chemicalized because chemical messages are transmitted through biological agents present in skin, intestines and nervous system.

                   DominantImmunological concepts associated with multiple sclerosis are connected to the pathogenesis of this disease. Some basic traditional immunological concepts pertaining to multiple sclerosis are:-

  • Relapsing MS
  • Secondary progressive MS.
  • Progressive MS.
  • Progressive relapsing MS

While these are the four major immunological concepts that intermingle in explaining the pathophysiology of each stage collectively in facilitating the discussion other will be highlighted. Significantly, coinciding with the five types of immunological responses that can emerge from antigen antibody interaction are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity. Therefore, the terms that will be explained in this section are:

  • Demyelinization
  • Cell-Mediated Immunity
  • Humoral Immunity
  • Immunoregulatory Cells

              Relapsing MS is a serious symptom which progresses into a chronic inflammatory demyelinating central nervous system disorder manifesting as morphological inflammation, demyelination, axonal loss and gliosis. There is massive infiltration of heterogeneous cellular population; and soluble mediators of the immune system are activated. These include T cells, B cells, macrophages and mi croglia, cytokines, chemokines, antibodies which stimulate  humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

 Demyelinization

                Research has shown where a lymphocytes subset identified as T helper cells specifically the Th1 and Th17 play a major role in development of multiple sclerosis lesions. Also the Interleukin 12 protein causes differentiation of naive T cells producing inflammatory T cells. When there is over production of Interleukin 12 it initiates inflammatory increases that occur in patients with persistent multiple sclerosis relapses. Patients who are not affected by multiple sclerosis their lymphocytes develop innate immunity to recognize and distinguish cells what cells belong to the body and those which are foreigner (Nakahara et.al, 2006).             

       Lymphocytes, in the body of a person afflicted by multiple sclerosis cannot differentiate between healthy and non-healthy cells. They attack cells in the central nervous system as foreigners such as viruses, bacteria, fungi triggering inflammatory responses as if it were a cell-mediated immunity conflict. In this process other immune cells such as cytokines and antibodies are activated and join in the inflammatory battle. Importantly, most myelin-recognizing T cells are family to a terminally differentiated subset known as co-stimulation-independent effector-memory T cells (Nakahara et.al, 2006).   See appendix 5   

Cell-Mediated Immunity

      T cells are responsible compromising an estimated 10% of the all inflammatory cells found as active participants in demyelinating multiple sclerosis lesions. Scientists have already proven that the EAE model can adequately be transferred by injecting an animal with myelin-specific CD4+ T cells. Therefore, the acceptable assumption has been that Multiple Sclerosis is foremost a CD4+ T-cell-mediated disease. It was advised that caution must be taken when interpreting these results because CD4+ T cells can play an important role in a disease stage-specific context. Importantly, they cells are absent in chronic Multiple Sclerosis lesions apart from the T-cell repertoire shows changes (Awad & Stüve 2010).

        Different T cell subtypes play significant roles in the pathogenesis of autoimmune diseases such as multiple sclerosis. Extensive studies have been conducted to validate these interactions. These diverse subpopulations contain distinct cytokine products.  ‘TH1 CD4 + cells secrete interferon gamma, tumor necrosis factor α, IL-2, and nitric oxide’ (Awad & Stüve 2010, p, 168).  TH1 cells are responsible for activating cell-mediated immunity. Alternatively, TH2 CD4+ cells secrete IL-4, IL-5, IL-6, IL-10, IL-13. They transform the growth factor β.  TH2 cells in humans function as a regulator agent when certain inflammatory conditions occur (Awad & Stüve 2010).

      The human system does not contain distinct TH1-TH 2 dichotomy. This adds to the complexity of explaining cell mediated immunity. Significantly, there is an overlap expression of cytokine between two subtypes TH1-TH 2 dichotomy which is a subtype of CD4+ cells. These cells have been implicated in the autoimmunity as TH17 cells. They express as proinflammatory cytokine IL-17. RNA (mRNA) encoding IL-17 messengers were detected in blood at very high levels cerebro spinal fluid (CSF) and brain parenchyma of multiple sclerosis patients in active stages of the disease (Awad & Stüve 2010).

      This phenomenon is highly suggestive of the major role cell mediated immunity plays in progression of multiple sclerosis as an immunopathogenesis factor in the disease sequence.  More importantly, it is worth noting that even though multiple sclerosis is often perceived as a CD4+-mediated autoimmune disease, there are CD8+ T cells implications in its pathology. Precisely, scientists have confirmed that clonal and oligoclonal expansion of CD8+ T cells consistently have appeared in plaques obtained from multiple sclerosis patients during diagnostic testing. In a few situations when evaluations were conducted, CD8+ T cells were found to have outnumbered CD4+ T cells (Awad & Stüve 2010).

        Again this is highly suggestive of suggesting cytotoxic T cells probably participation in starting this inflammatory interaction. Another factor worthy of consideration is the knowledge that T lymphocytes express γ/δ receptors were detected in various quantities when cerebro spinal fluid (CSF) of multiple sclerosis patients experiencing early stages of the disease. However, patients who had the disease for a longer time emerging into the chronic stages, CD8+ T cells were not found. The distinction lays in a probability that these cells play a role in the early development of the disease when cell medicate immune response is being activated.  More clarification on this phenomenon is pending while the pathogenic role of CD8+ T cells in multiple sclerosis progression is further explored (Awad & Stüve 2010).

Humoral Immunity

       Scientists posit that despite the autoimmune process in multiple is perceptive mainly from the premise of it being mediated by T cells; there is just as much evidence to suggest a great degree humoral immunity activity is also involved in the progression of disease process. Fundamentally, scientists discover that there have been interactions with an antigen driven B-cell response in multiple sclerosis patients’ cerebro spinal fluid. This is highly suggestive that B- cells are implicated in the immunopathogenesis of the disease. Also, oligoclonal immunoglobulin production persists in the cerebro spinal fluid of multiple sclerosis patients. Subsequently, growth of secondary lymphoid brain tissue was detected during diagnostic evaluations in multiple sclerosis patients experiencing secondary progressive stages of the disease. Some research studies have even shown a direct relationship between intrathecal immunoglobulin levels and severity of the disease when patients present with secondary progressive multiple sclerosis (Awad & Stüve 2010).

          Scientists have continued probing for evidence of humoral immunity implication. Researchers have also detected B cells in brain cerebro spinal fluid of secondary progressive multiple sclerosis patients. There has been constant isolation of B cells in the cerebro spinal fluid of patients with secondary progressive multiple sclerosis. Evidence of clonal expansion along with extensive somatic mutation in B-cell receptor genes was observed. This phenomenon expresses the characteristic features of an antigen-driven response. Precisely, the assumption is that B-cell selection might have been initiated in peripheral lymph nodes or in lymphoid follicles of the central nervous system (Awad & Stüve 2010).

            Further studies related to investigating B-cell compartment of cerebro spinal fluid in multiple sclerosis reveal that B-cell differentiation is confirmed in the central nervous system of individuals suffering from multiple sclerosis. The dominant antibodies happen to be short-living plasmablasts. Interestingly it is not plasma cells. Precisely, plasma cells are actually the predominant antibody secreting cell found in multiple sclerosis patients’ cerebro spinal fluid.               More importantly, the phenomenon whereby upregulation of costimulatory molecules on plasma cells within central nervous system  occurs is indicative the potential of such cells to sustain their T-cell activation.  Scientifically, B cells have been known as potent antigen-presenting cells. Assumptions are that they might feature prominently in T-cell antigenic stimulation. Scientists conclude that B cell and humoral immunity might be the main factors responsible for initiating and sustaining multiple the sclerosis disease process (Awad & Stüve 2010).

Immunoregulatory Cells

          Studies have revealed that isolating myelin-reactive T cells from peripheral blood of healthy subjects is highly suggestive that, perhaps, decreasing regulatory cells interactions is the basic immunopathology concepts in multiple sclerosis evolution and not he presence or absence  of self-reactive T cells.  Scientifically,   it has been accepted that regulatory cells play a major role in controlling intensity when immune response are activated by maintaining self-tolerance. Importantly, it has been proven that CD4+ TH2 cells are active in anti-inflammatory cytokines production. They are IL-4, IL-5, and IL-13. Precisely, this CD4+ TH2 has the ability of lowering regulatory function of macrophages (Awad & Stüve 2010).

    Further developments show where a relatively little subpopulation of CD4+ T cells were identified to be naturally occurring regulatory T (CD4+CD25+Treg) cells. It is believed that they are vital participants in the immune homeostasis process too. Certainly, they were found to be expressing CD25 which is an important component of the IL-2 receptor. However, preclinical trials have revealed that Treg cells’ absence was closely associated with the emergence of autoimmunity. Overwhelming evidence exists to prove that inadequate Treg-cell activity could be a main contributory element in multiple sclerosis etiopathogenesis. Essentially, studies show where  CD4+CD25+Treg cells effector function  emerging out of multiple sclerosis patients’ peripheral blood  samples of patients was deficient in comparison to CD4+CD25+Treg cells from subjects who were not afflicted by the disease (Awad & Stüve 2010).  .

         While these findings scientifically seem profound critics argue there are no differences in Treg cell concentration and constitution in the cerebro spinal fluid among patients afflicted by multiple sclerosis and those who were healthy. A larger study conducted on 73 multiple sclerosis researchers discovered that Treg cell concentration was identical with that of healthy volunteers. . The notable difference detected was that the Treg cells obtained from multiple sclerosis patients demonstrated reduction suppressive potential on the ‘immune response directed against myelin antigens’ (Awad & Stüve 2010, p 201). Yet, in another study this theory was refuted since, there were higher Treg cell counts in multiple sclerosis patients than in the control. Alternatively,  appeared the potential of these cells suppress MBP-induced proliferation was less effective (Awad & Stüve 2010)

        Explaining the functional differences of Treg cells activity in multiple sclerosis patents and healthy subjects there has been reports of activity in RRMS and progressive stages of the diseases too.  For example, Forkhead box p3 (FOXp3) has been identified as a popular transcriptional factor. Its main role has been detected being a valuable participant in Treg-cell-suppressive molecular programmer activity (Awad & Stüve 2010)

            Many preclinical studies have supported many of these theories in confirming the linkage between autoimmunity and absence of FOXp3. An association was also discovered with ectopic FOXp3 expression conferring suppressive function on CD4+CD25+Treg cells. Further linkages posit a relationship showing significant reductions in FOXp3 mRNA transcripts and protein levels. Importantly, this occurred without any concordant decrease in CD4+CD25+Treg representation in multiple sclerosis patents. FOXp3+CD4+CD25+Treg cells popularly create infiltrations when cerebro spinal fluid of subjects afflicted with neuro inflammatory diseases. Comparatively, this multiple sclerosis patients isolated more FOXp3+CD4+CD25+Treg cells   than patients afflicted by dementia, stoke  or  any other neurological disease. In addition it was observed that Treg activity seem to be compromised when peripheral blood samples are used for the analysis in multiple sclerosis patients unlike other non-affected clients.

Therapy and management

        There is no cure for multiple sclerosis. However, scientists continue to experiment with drugs and therapies, which can be useful in relieving symptoms. For example, David Virley (2005) conducted studies to explore strategies involved in ‘Developing Therapeutics for the Treatment of Multiple Sclerosis.’ The author posited that many animal models have been used in developing therapeutic interventions for treating relapsing multiple sclerosis. The aim of preclinical research was mainly to identify and validate novel targets that are the most appropriate mimics for the specific clinical situation. Animal models therefore, become valuable subjects in establishing drug development processes that help select suitable human subjects for therapeutic interventions. This process provides the proof-of-concept for continuance of clinical trials. The author further contended that ‘although there is no gold standard model of multiple sclerosis, experimental autoimmune/allergic encephalomyelitis (EAE) models simulate the clinical and pathological hallmarks of multiple sclerosis in various guises and can provide the necessary predictive index for clinical therapeutic application’  (Virley, 2005, p 639).

         EAE was induced by generating T-cell-mediated immunity into central nervous system antigens, which was easily modeled in rodents such as rats, mice, and guinea pigs. Whole CNS homogenate (spinal cord) t purified protein and peptides were combined in preparing the autoantigen for the experiment (Virley, 20050.  ‘Myelin basic protein (MBP), proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), S100β, and glial fibrillary acidic protein as well as specific peptides from respective parent proteins are encephalitogenic in the appropriate host, as the major histocompatability complex (MHC) is one of the major determinants of immune responsiveness and disease susceptibility to these self-antigen’ (Virley, 2005, p 639).

        The author concluded that the pathogenic autoimmune mechanism steps that initiate and magnify EAE and MS damage tissue sequences are:-

  • Activation of autoreactive CD4+ T-cells in the periphery to an antigen;
  • Transmigration of proinflammatory T-cells and monocytes through the blood brain barrier (BBB)
  • Amplification of local inflammation and activation of resident antigen-presenting cells (APCs), such as microglia; and 4) destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).

(See Appendix 4).

Current Drug Therapies

The foregoing trials have emerged into distinct therapies, which are now active treatment management intervention s for multiple sclerosis. To date there are only five Food and Drug Administration (FDA) approved therapeutic treatments for relapsing – remitting multiple sclerosis. They include ‘two interferon (IFN)-β1a agents (Avonex and Rebif), one IFN-β1b (Betaseron), glatiramer acetate (GA) (Copaxone) and Mitoxanthrone (Novantrone)’ (Virley, 2005, p 639).

      Patents suffering from secondary progressive multiple cyclophosphamide (Cytoxan) and mitoxanthrone are the drugs of choice. There are no extreme benefits in using these two drugs or severe toxicity. However, the main drugs used are corticosteroids, IFNβ and GA (Virley, 2005).

Corticosteroids

             Corticosteroids are administered to raise a patient’s tolerance level tolerance during an attack and speed up recovery. Long term therapies are more effective even though short-term interventions can be useful. However, to maintain a longer period between remissions it is always better to continue treatment over a longer period of time.  Patents often receive significant results even when the clinical course of multiple sclerosis may change to secondary progressive stage. Even with so many drug trials and pre-trials being conducted scientists are still not yet sure what are the actual effects of corticosteroid on the immune system are (Virley, 2005).

         However, preclinical research evidence has verified quite a few putative mechanisms. They embody ‘an inhibition of the Th1 immune response reduction in BBB molecules and protection of oligodendrocytes from cytokine-induced cell death’ (Virley, 2005, p 639). EAE models validated the suppressive interactions produced by corticosteroid treatment in relation to clinical course disruption of multiple sclerosis, T-cell migration dampening its antigens response suppression during expression of adhesion utilization of anti-glucocorticoid, RU 38486 (mifepristone). It was revealed that these interactions have intensified as well as reversed steroid-induced inhibition of disease (Virley, 2005).

      While corticosteroids have been so effective in the treatment of multiple sclerosis in both short and long term its side effected should not be underestimated. For example, extended use can initiate transient mood changes headache, gastrointestinal disturbances, and myalgias.  Decrease in bone density can occur overtime if patients must be treated for extended periods of time. Ultimately, osteoporosis could become a real problem increasing risks for fractures and infections. When side effects have become so progressive, the patient ought to be reassessed. Often the attending physician may consider either reducing or discontinuing treatment temporarily (Virley, 2005).

IFN-β

          IFN-β therapies emerged after over 25 years of clinical trials. The aim was finding how multiple sclerosis would respond to IFNs if it is truly a virally mediated disease. Importantly the   antiviral assumption became invalid after clinical trial assessments, which revealed that IFNγ worsened symptoms.  This was highly suggestive, that IFNγ  was more influential in multiple sclerosis pathological process. it meant that IFNβ, like other IFNs, is a species-specific glycoprotein with numerous biological properties. Actually, the mechanism producing these interactions is not fully understood from a scientific perspective poorly. However assumptions have been that immunomodulatory as an alternative to antiviral and antiproliferative makes much sense in deriving at an alternative proposition (Virley, 2005).

      Importantly, IFNβ-1a is exactly like the natural IFN-β, but IFNβ-1b differs in having two amino acids as well as not being glycosylated. Despite these insidious structural differences IFNβ-1b displays comparative biological activity to IFNβ-1a. Therefore, putative responses of IFNβ on the progression of multiple sclerosis is believed to be related primarily to its  antiinflammatory influences, which demonstrates as dampening the stimulatory impact of IFNγ, tumor necrosis factor (TNF)α, interleukin (IL)-12. The lymphotoxin secretion has been identified in the sequence of controlling monocyte activation; inhibiting disruption of BBB. Consequently, the entry of lymphocytes into the CNS is reduced; antigen presentation is reduced to T-cells; and up-regulation of anti-inflammatory cytokines occurs; TGFβ and IL-10 (Virley, 2005).

        EAE pre-trial models have validated the use of IFNβ by proving its influence in limiting the   progression of multiple sclerosis. Supportively, clinical trials were done using both IFNβ formulations. Important findings indicate a one third relapse reduction rate when higher doses are administered. The onset has been observed to be rapid. Precisely, relapses occurred at a rate of 1 per year and few weeks for MRI disease activity. Conversely, there were huge inflammatory changes measured through MRI activity; accumulation of MRI disease burden was significantly slowed down. Besides, there were magnificent results shown by patients regarding relapses (Virley, 2005).

      This novel treatment is not without its adverse side effects. Some include, flu-like symptoms along with reactions emerging at the site where injections are administered. If patients do not respond to the drug after six months of therapeutic intervention, the IFNβ therapy is usually discontinued. Some patients who are already disabled with progressive or relapses occurring at a rate of more than one per year are treated with a combination of combination three or more courses of corticosteroids over a 1-year period. In addition some patents encounter extreme feelings of depression leading towards suicidal inclinations. Drug toxicity can also become a problem with patients becoming noncompliant. This initiates physicians’ decisions of considering alternatives. Neutralizing antibodies in IFNβ effectiveness ought to be addressed as an adverse reaction during treatment. This can lead to long term complications. As such, it must not be ignored if patients complain of reactions or it shows up in diagnostic testing (Virley, 20 05).

   Glatiramer acetate – GA

          GA is considered a non-IFN, nonsteroidal therapy. It is made from synthetic random base copolymers mixtures containing four amino acids namely glutamic acid, alanine, lysine, and tyrosine). The molar ratio was highly specific. Trials researched investigated the GA’s potential encephalitogenic role using EAE animal models. However, surprisingly, it was discovered that GA suppressed their acute and chronic clinical and pathological hallmarks. Importantly, translation of impacts was clinically beneficial. Importantly, GA provided evidence in the initial phase II trial as being a suitable agent for reducing relapse rates by 76% in patients with relapsing-remitting multiple sclerosis. A 5 year follow up intervention treatment confirmed

GA benefits as being capable of sustaining the initial influence on relapses in multiple sclerosis patients. The progression of the disease into the secondary stages was significantly slowed. Patients did not enter into disability as quickly as when other drug therapies were used. Also, when the Lesion burden was assessed through MRI it validated the value of GA in helping patients during the relapsing-remitting episodes. It was discovered that GA greatly reduced  frequency  rates of lesion load  and new enhancing lesions when baseline pretreatment measures are compared (Virley, 2005).

     Since then numerous mechanisms were advanced as being responsible for these fascinating results observed by GA’s intervention in the disease process. First its biological activity relapsing-in remitting MS was noted as a valuable factor. Then the antigen-specific induction suppressor T cell was remarkable. Thirdly, a MBP competitive inhibition was distinctly observed as a benefit. There was also a relationship of the interactions to -peptides from antigen-presenting cells (Virley, 2005).

       It must be noted that regardless of how beneficial a new drug therapy may be in treating a disease there are always adverse effects, which must be considered in its administration. GA is no exception even though the tolerance level in multiple sclerosis patients is great. However, subcutaneous administrations could become harmful due to increasing incidences observed whereby injection site reactions occurred in the majority of cases and they were localized proving that it was the drug interaction with human skin (Virley, 2005).

             The overall picture being communicated in the use of this drug pertains towards it being the most tolerable in terms of side effects when compared to other therapies. Reduced propensity in the development of depression, neutralizing antibodies and menstrual disorders was far less when compared to other drugs now available for treating multiple sclerosis. Despite these developments, however, it is still important for continued research in extending to multiple sclerosis patients more options. While there is no cure for the condition medical science can provide the best relief it could through timely and efficient intervention therapies that work (Virley, 2005).

      Ultimately, these interventions should aim at not only providing relief, but secure sustained drug benefits reducing symptoms of multiple sclerosis, which shows that treatments are becoming more effective. Patents should be taking lower doses and experiencing fewer side effects. As such, pharmaceutical and biotechnology industries are challenged to provide this service to the multiple sclerosis community of patients. Essentially, numerous alternative disease-modifying strategies are emerging. They will be reviewed in the following pages of this document (Virley, 2005).

           For example, Pietro Iaffaldano (2012) and a group of researchers conducted studies regarding the ‘Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study.’ These researchers contend that Natalizumab reduced relapse rate as well as magnetic resonance imaging reactions in patients experiencing Relapsing-Remitting Multiple Sclerosis (RRMS). However, its impact on fatigue cognition in patients affected by multiple sclerosis need to be validated though scientific research. There the purpose of a prospective, open-label, observational study was intended as an  evaluation relating probable impacts  natalizumab had on cognition and fatigue when measured in patients experiencing Relapsing-Remitting Multiple Sclerosis  after being treated continuous for two years (Iaffaldano et.al, 2012).

        Researchers examined cognitive performances by applying  ‘Rao’s Brief Repeatable Battery (BRB) device, the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months’ (Iaffaldano, 2012, p  201).   When patients did not respond favorable to at least 3 BRM and ST 3 they revived a cognitively impaired (CI) classification. Every 12months the Fatigue Severity Scale (FSS) was administered. This assessed the patient’s ability to self-reported incidences of fatigue. A total of 1 53 patients participated in 1 and 2 year-natalizumab continuous treatment (Iaffaldano et.al, 2012).

       Result revealed that after one year treatment the amount of’ CI sampled patients decreased from 29% (29/100) at baseline to 19% (19/100) (p=0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p=0.008). These significant effects were confirmed in the subgroup of patients treated up to two year.’ (Iaffaldano et.al, 2012, p. 201). From these results researchers concluded that

In the short-term Natalizumab can be successfully used as a treatment which could, ultimately reduce incidences of cognitive difficulties and fatigue in patients experiencing Relapsing-Remitting Multiple Sclerosis (Iaffaldano et.al, 2012).

Examples of Novel Therapeutic Challenges for Multiple sclerosis

Blockade of lymphocyte migration

       Very late antigen-4: natalizumab (Tysabri) and small molecule antagonists. There is widespread evidence implicating very late antigen-4 (VLA-4, α4-β1 integrin) in this process, via its interaction with receptors like vascular cell adhesion molecule 1 (VCAM-1) and the CS1 fibronectin domain (Virley, 2005).

Immunomodulatory agents

       Interest recently has emerged regarding development of novel Immunosuppressants. Trials have been conducted and they have been actually used in treatment of many autoimmune diseases such as psoriasis and rheumatoid arthritis. They reduced exacerbations keeping progression (Virley, 2005).

Anti-inflammatory agents

‘Cycloxygenase-1 and -2 (COX-1 and COX-2 or prostaglandin H synthases 1 and 2) catalyze the conversion of arachidonic acid and oxygen to generate inflammatory prostaglandins such as PGE2, PGD2, PGF2a, and thromboxane’ (Virley, 2005, p 201).

Neuroprotective and neuroregenerative therapeutic strategies

       Achievements in repair of myelin and immense neuroprotection though therapeutic interventions can be interpreted major research breakthrough in the attempt at providing more beneficial therapies that reverse permanent neurological disability associated multiple sclerosis.

Potential combinations of therapeutic strategies

       The heterogenic influences of clinical response as well as pathological hallmarks contained in recent multiple sclerosis drug development it would be wise considering combining therapeutic strategies that differentiate concentrating of specific aspects of the disease such as cognition memory and fatigue as espoused by Iaffaldano and his team of researchers. An area of precedence is a development stage whereby each agent independently offers a benefit distinct from the others, but is still valuable when combined in adding synergistic value to the therapeutic intervention. This approach would be extremely beneficial for patients who seldom respond favorable to therapies now available on health care markets across the country and world (Virley, 2005, p 201).

Conclusion

               While theories pertaining to the etiology/epidemiology/immunology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explored the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of this disease. Consequently, the researcher adapted a comparative analysis of the perspectives offered by theorists in discussion of epidemiology regarding emergence of multiple sclerosis among the predominantly, female young adults twenty-first century population. These were matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management, and current trends are being explored.

Current Trends

                   Precisely, Ascherio and Munger (2007) ‘Environmental risk factors for multiple sclerosis Part I: the role of infection’ contend that even through genetic susceptibility play a role in the acquisition of multiple sclerosis among families studies show where personal hygiene significantly affect occurrence of the disease. Further, they advance that genetics and environment alone cannot account explicitly for the MS frequency among geographic variations when risk changes with migration are taken into consideration. Supportive epidemiological findings highlights the “hygiene hypothesis,” showing the additional role Epstein-Barr virus (EBV) plays as evidence for MS risk factor (Ascherio & Munger, 2007)

             Another piece of research literature by the same authors ‘Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors focusing on the environment explains that the change risk factor among migrants gives profound evidence for M.S environmental determinants. Then researchers defined environment to mean variations in diet and social behavior. Main contributory factors were sunlight and cigarette smoking (Ascherio & Munger, 2007)

     Dyment, Ebers, and Sadovnick, (2004) took a stand in ‘Genetics of multiple sclerosis.’          They argue that while environment and infection may play a role many genes appear to be linked to  MS etiology. They mentioned ‘HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A’ (Dyment et.al, 2004, pp 110). These researchers advanced that future development in the MS genetic science largely depends on continuous research making data available as evidence. Also the development of appropriate statistical measurements and research methodologies could be valuable (Dyment et.al, 2004).

             George Ebers (2008) focused on ‘Environmental factors and multiple sclerosis’ in reporting that studies conducted in Canada show where environmental factors influence the distribution of MS in specific geographic locations. The researcher cited migration studies to prove that the increase incidence of MS in Canada relates to longitudinal sex ratio expansion among immigrants within the country. This was compared to studies conducted in Australia where similar geographic patterns exist. It was discovered that by modifying the environment it reduced 80% of cases. It was concluded that while genetics play a major role there are predominant environmental factors associated with MS incidences in certain geographic locations (Ebers, 2008).

       Gavin Giovannonia and George Ebers (2007) posit that ‘genes and environmental factors lead to tissue injury by autoimmune mechanisms, implicated by strong circumstantial evidence’ (Giovannonia and Ebers, 2007 pp, 261). They further contend that it is difficult to identify the specific genes responsible for MS without examining the associating influences of the environment. Actually, they argue that the impact of genes on MS emergence is modest. Additional studies were cited emphasizing irregularities in confirming the genetic theory of MS etiology (Giovannonia and Ebers, 2007).

                Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed at addressing the autoimmune etiology of the disease. These therapies are designed to reduce inflammation, but their long term effect is uncertain. Hence, a re-evaluation of both pathogenesis and etiology is suggested (Nakahara et.al, 2012).

                     Rosati offered insights to say that the childhood environmental factor was a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

               Consequently, this study’s importance pertains to advancements into understanding multiple sclerosis’ etiology, pathophysiology/immunology and treatment. As explained in the foregoing principal pieces of research literature theories relating the etiology of MS are numerous. However, theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure.

       Current therapeutic trends predict that the ideal treatment for multiple sclerosis mustconsist oftechniques aimed at increasing disease-causing/sustaining antigen(s) tolerance. Ultimately, it is expected that long-term therapy would be obviated. This is important because amidst  numerous continuous drug trials scientist still contend that none of them seem to have considerable effects on resolutions of a disease which is over 100 years old. Justifiably establishing coordination between activated T cells and B cells in the pathophysiology of multiple sclerosis is highly recommended for targeting the two cell population. These include resting and dividing cells together. The strategy may necessitate, taking control of the disease process itself (Awad & Stüve, 2010).   

          Whatever emerges from these assumptions scientist must bear in mind that other immune cell populations are playing a major role also in the sequel of this disease. They intimate and perpetuate the process. Therefore, the final proposition of this theory advanced that amplifying or sparing the pool of regulatory cells which act as mediators of immune suppression would be valuable a valuable intervention. This however must be embraced without compromising immune surveillance in the treatment of this disease (Awad & Stüve, 2010). In concluding these deliberations pertaining to current trends in multiple sclerosis therapeutic management it is expected that this research project sensitize scientists into elaborating on present research practices in order for a consensus be reached regarding the reality of multiple sclerosis etiology and its pathological implications.

References

Ascherio, A., & Munger, K (2007). Environmental risk factors for multiple sclerosis. Part I: the

                      role of infection. Ann. Neurol. 61(4); 288–99

Ascherio, A., & Munger, K. (2007). Environmental risk factors for multiple sclerosis. Part II:

                     Noninfectious factors. Ann. Neurol.  61(6); 504–13.

Awad, M., & Stüve, O. (2010). Immunopathogenesis of Multiple Sclerosis: New Insights and

                    Therapeutic Implications. Lifelong Learning in Neurology. 16(5); 166-180

Clanet M (2008). Jean-Martin Charcot. 1825 to 1893. Int MS J 15 (2), 59–61.

DasGupta, R., & Fowler, C. (2003). Bladder, bowel and sexual dysfunction in multiple  

                       sclerosis: management strategies.  Drugs, 63 (2): 153–66.

Dyment, A; Ebers, G; Sadovnick, A. (2004).  Genetics of multiple sclerosis. Lancet

                                 Neurol  3( 92). (2004): 104–10.

 Ebers, G. (2008). Environmental factors and multiple sclerosis. Lancet Neurol  

                              7 (3). 268–277.

Foley, P. Vesterinen, H. Laird, B. (2013). Prevalence and natural history of pain in adults with

                       multiple sclerosis: Systematic review and meta-analysis. Pain 154 (5): 632– 42

Gilden, D (2005). Infectious causes of multiple sclerosis. The Lancet Neurology 4  (3)

                                    195–202.

Giovannoni, G; Ebers, G. (2007). Multiple sclerosis: the environment and causation. Curr

                                Opin Neurol. 20( 3); 261-8.

Kantarci, O., & Wingerchukb, D. (2006). Epidemiology and natural history of multiple sclerosis:

                             new insights. New York. Lippincott Williams & Wilkins

Kurtzke, J. (1983). Rating neurologic impairment in multiple sclerosis: an expanded disability

                          status scale (EDSS). Neurology, 33 (11); 1444–52.

Iaffaldano, P. Viterbo, G. Paolicelli, D. ( 2012). Impact of Natalizumab on Cognitive

               Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label,

                  Two Years Observational Study. PLoS . 7(4)

Merril, R. (2010). An Introduction to Epidemiology, (5th Edition). Jones and Bartlett

                   Publishing.

Murray, J (2002). Infection as a cause of multiple sclerosis. Theories abound because no one

                         knows the answers yet. BMJ. 325(7373).(2002). 1128.

Nakahara, J; Maeda, M; Aiso, S; Suzuki, N ( 2012). Current concepts in multiple

                             sclerosis: autoimmunity versus oligodendrogliopathy. Clinical reviews in

                           allergy & immunology  42(1); 26–34.

 Oksenberg, J., & Barcellos, L (2000). The complex genetic etiology of multiple sclerosis.

                           Journal of NeuroVirology. 6(2), S10 ± S14

Rosati G (2001). The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 22

                (2): 117–39.

Royal College of Physicians London (2004) Multiple Sclerosis: National Clinical Guideline for

                Diagnosis and Management in Primary and Secondary Care. NICE Clinical

              Guidelines, No. 8.National Collaborating Centre for Chronic Conditions (UK).

               London

   Schäffler, N. Köpke, S. Winkler, L. Schippling, S. Inglese, M. Fischer, K.,  & Heesen, C.

      (2011). Accuracy of diagnostic tests in multiple sclerosis–a systematic review. Acta Neurol

                      Scand. 124(3), 151-64

Siegert, R., Abernethy, D. (2005). Depression in multiple sclerosis: a review. J. Neurol.

                     Neurosurg. Psychiatr. 76 (4): 469–75.

Terry, R. Miller, S. Getts, D., & Muller, M. (2012). Current Theories for Multiple Sclerosis

                    Pathogenesis and Treatment. Free Press New York. 2012.

 Virley, D. (2005). Developing Therapeutics for the Treatment of Multiple Sclerosis. NeuroRx.

                 2(4): 638–649.

Appendix 1

Table 1 Multiple sclerosis as a genetic disease

———————————————————————————

1. Racial clustering of MS cases. Resistant ethnic groups residing in high risk regions

2. Familial aggregation of MS cases. Increased relative risk to sibs (ls=20±40)

3. Low incidence of conjugal MS

4. MS sibling pairs tend to cluster by age of onset, rather than

year of onset

5. High disease concordance in monozygotic twins (25±30%) compared with dizygotic twins and non-twin siblings (3±5%)

6. No detectable effect of shared environment on MS susceptibility in first-degree non-biological relatives (spouses, adop-tees)

7. Suggestive correlations between certain polymorphic loci and disease susceptibility

————————————————————————————

Appendix 2

Table 2 Confounding factors in genetic studies of multiple

Sclerosis

————————————————————————————————-

1. Aetiologic heterogeneity identical genes, different phenotypes

2. Genetic heterogeneity Different genes, identical phenotypes

3. Unknown genetic parameters Single versus multiple genes Dominant versus recessive mode of inheritance incomplete penetrance

4. Epistatic gene interactions

5. Post-genomic mechanisms

6. Unidentied non-heritable (environmental) factors

——————————————————————————————————————

(Oksenberg & Barcellos, 2000).

Appendix 3

http://upload.wikimedia.org/wikipedia/commons/thumb/3/3c/Ms_progression_types.svg/300px-Ms_progression_types.svg.png

                     Diagram showing immunological concepts underlying Multiple sclerosis                   

                     Progression of subtypes (Oksenberg et.al, 2000).                        

FIG. 1.

      Schematic view of the putative pathogenic steps in MS. 1: Activation of autoreactive T cells by antigen presenting cells in the periphery. 2: Migration of T cells and monocytes through the blood brain barrier. 3: Amplification of local inflammation and destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).                                         Appendix 5   – Demyelinization

Medicine and Health: Multiple Sclerosis

Name of Author

Outline

Introduction

•          Description

•          Epidemiology

•          Clinical signs and symptoms

•          Diagnosis

•          Prognosis

Immunological concepts underlying the disease

Therapy and management

Conclusion

•          Current Trends

Abstract

The purpose of this document is to offer a precise account of Multiple Sclerosis. The statement of problem related to this research reads ‘while theories pertaining to the etiology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explores the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of the disease. Consequently, the researcher will adapt a comparative analysis of the perspectives offered by theorists regarding emergence of multiple sclerosis among the twenty-first century female young adults. These will be matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management as well as current trends are explored.

Medicine and Health: Multiple Sclerosis

Introduction

Description

          Multiple sclerosis was not discovered as a disease until late 19the century. An English Physician by the name of Walter Moxon in 1873 along with American Dr. Edward Seguin in 1878 discovered multiple sclerosis as a dysfunction of the nervous system. They confirmed that it was more common in women than men. However, three notable signs of multiple sclerosis signs described as Charcot’s triad 1 being nystagmus, intention tremor, and telegraphic speech (scanning speech) have been attributed to French neurologist Jean-Martin Charcot (1825-1893). He  recognized cognition alterations, which was described as “marked enfeeblement of the memory” and “conceptions that formed slowly” (Clanet, 2008, p 58).  At the time these doctors did not project any sound etiology of the disease, but said that there was no evidence to support it being inherited. However, they confirmed that numerous diverse neurological irregularities were produced as symptoms of the condition (Terry et.al, 2012).

            Multiple sclerosis (MS); disseminated sclerosis is also known as encephalomyelitis disseminata. Scientists have described it as an inflammatory condition characterized by formation of myelin sheaths around brain and spinal axons tissue. Ultimately, these tissues are destroyed through scarring; reduction in myelin to protect brain and spinal cord. Research is still being conducted regarding its etiology, Assumptions however have been that many predisposing genetic, environmental and infection factors could initiate the inflammation (Ascherio & Munger, 2007).

      Other assumptions have been that there are mechanisms within the body chemistry, which are responsible for destruction of the immune system inhibiting production of myelin cells. Consequently, massive insidious nerve destruction occurs and nerve cells become incapable of functioning as communicators of impulses across nerve ending within the human body. Often when the etiology of a disease is obscure there is seldom a cure. Recent research has continued to advance ther theory that indeed multiple sclerosis affects more females than males (Nakahara et.al 2012)

        To date scientists have advanced from repeated research that there is no discrimination as to which neurological symptoms can emerge due to nerve destruction in the brain and spinal cord which are the primary target organs. From observation there have been immense progressive physical and mental dysfunctions. In some cases memory irregularities could develop, but a difficultly exists classifying them as purely psychiatric because they may present in conjunction with various levels of other neurological abnormalities. As the disease evolves it converges into many misleading features increasing the challenge of addressing the real symptoms in devising modes of treatment intervention. Scientists have described this phenomenon as an escalation of new symptoms, which were not formerly associated with the initial presentation. They are termed relapsing forms and progressive forms respectively (Dymentet.al, 2004)

        The period from when attacks begin end, and begin again symptoms may subside. However after these episodes permanent nerved damage occurs. As the disease advances symptoms worsens and exacerbations seems to occur leading up to when treatment becomes ineffective. This disease is more than 100 years old, but scientists have not been articulate in arriving at any profound etiology while numerous theories exist. They have not gone far beyond exploring mechanisms related to the disease process itself (Ascherio & Munger, 2007).

       Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed only at addressing the autoimmune etiology of the disease. As such, they merely focus on restoring function to affected nerves after symptoms become uncontrollable; control recurrence and limit the extent to which nerve damage produces disability (Nakahara et,al, 2012).

          However, medications used to treat multiple sclerosis are not without their serious side effects, besides being poorly tolerated by patients. Consequently, patients turn to alternative medicine for relief. Precisely, since there are few studies conducted regarding alternative remedies these remedies are considered nonscientific and are not recommended even through patient report how successful these treatments have been in restoring nerve function (Gilden, 2005).

      People diagnosed with multiple sclerosis live an average 5-10 years, less than persons who do not have the disease. There is an average of 2 persons affected by multiple sclerosis for every 150 per 100, 000 (Rosati, 2001).  However, data or theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure. This research is expected to sensitize scientists into elaborating on present research practices in arriving at a consensus regarding the reality of multiple sclerosis etiology.

Epidemiology

      Epidemiology infers a study of disease patterns that evaluates infection etiology; geographic, socioeconomic status, genetics and demographic variations. Often epidemiologists add to the multiple sclerosis body of knowledge through assessing relationships between these factors. Since there are no known causative factors for multiple sclerosis it is important that epidemiologists continue investigations regarding migration patterns. However, it must be understood that figures published in epidemiology records are all estimates. This is an attempt at establishing a more profound understanding regarding multiple sclerosis target populations across the world. It also helps identifying and explaining geographic locations containing highest and lowest multiple sclerosis rates (Merril, 2010).               

        The challenge facing the epidemiology of multiple sclerosis lays in the difficulty diagnosing the disease. No single distinct tests are being conducted in establishing a diagnosis for multiple sclerosis. As such, the argument is that diagnoses can be incorrect delayed or just bypassed. While MRI technology has been of great assistance in resolving difficult diagnoses epidemiologists question the accuracy of diagnoses produced from previous studies since they may not give a true representation of multiple sclerosis with the given population. More importantly, various methodologies used by specialists collecting data on the disease can greatly alter interpretations and outcomes. Due to these factors the epidemiology of multiple sclerosis is still in its infancy even though the disease is over 100 years old (Merril, 2010).              

                 According to Orhun Kantarci and Dean Wingerchukb (2006) multiple sclerosis claims the health of approximately 1 000 000 people between 17 and 65 years old internationally. The 2000 projected multiple sclerosis prevalence rate among white US populations showed 191 per100 000. Alternatively, the US overall incidence rate and was 7.3 per 100 000 person in the same year. Further epidemiological studies supported the theory that multiple sclerosis is two times more common in women than men. It was discovered also that there is a tendency for a later onset of the disease among men. The prognosis for them is even worse for women. Scientists attribute this difference to gender-dependent and phenotypic variability factors which may create an etiological predisposition (Kantarci & Wingerchukb, 2006).

        Multiple sclerosis care cost United States government an estimated $6.8 billion annually, which includes loss in productivity as well as actual health care interventions. A total life time cost is estimated at 2.2 million per patient (Kantarci & Wingerchukb, 2006).Similar epidemiological estimates exist around the world. There seems to be patterns of ‘a north-to-south gradient in the northern hemisphere and a south-to-north gradient in the southern hemisphere’ (Rosati, 2001, p 22). Multiple sclerosis is less prevalent among people who live close to the equator. Theories pertaining to climate, sunlight and vitamin D intake are variables used in relating possible causes in explaining this latitude gradient theory regarding geographic disposition multiple sclerosis prevalence among people living near to the equator (Rosati, 2001).

     Overtime other variations have appeared, which forced epidemiologist to consider environment in combination with genetics. Multiple sclerosis was discovered to be prevalent among northern European populations and most common in certain ethnic groups such as ‘Samis, Turkmen, Amerindians, Canadian Hutterites, Africans, and New Zealand Māori’ (Rosati, 2001, p 22).

       Childhood environmental factors were then considered as a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

      Critics of the environmental epidemiological theory have contended that quantification of the assumptions is difficult because data derived is obtained mainly from retrospective case-control studies whereby subjects are exposed to the same environment and results may lack internal and external validity besides containing reliability issues. ‘A practical, albeit limited, design is a nested-cohort study in which a population cohort already identified for exposure to given factor(s) for another disease is exploited for excess of -NIS occurrence after sufficient follow- up’(Kantarci & Wingerchukb, 2006, p 249). While trying to make sense of the environmental theoretical epidemiological perspectives major advances have implicate viral exposure factors. Viruses identified are canine distemper virus, Epstein-Barr virus, and human herpes virus-6) (Kantarci & Wingerchukb, 2006).

           Internationally, conclusions are that multiple sclerosis makes its first appearance in adults during their thirties. It can occur at any time in children. However, the primary progressive subtype appears later in people in their fifties.  The genetic epidemiology of multiple sclerosis seems to be overlapping with both environmental and viral/infections. Analysts have discovered that the only facts they have to support the genetic epidemiology are its high incidence among Northern Europeans in relation to indigenous populations from the ‘same geographic location, familial aggregation’(Kantarci & Wingerchukb, 2006, p 249). See appendix 1 and 2

Clinical signs and symptoms

                 Numerous signs and symptoms are associated with multiple sclerosis. However neurologists keep abreast of symptoms by applying the Expanded Disability Status Scale (EDSS).  EDSS gives a score total of a scale ranges from 0 to 10.

 ‘The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.  The range of main categories include (0) = normal neurologic exam; to (5) = ambulatory without aid or rest for 200 meters; disability severe enough to impair full daily activities; to (10) = death due to MS. In addition, it also provides eight subscale measurements called Functional System (FS) scores. These subscale categories are listed below.  The levels of function within each category refer to the eight functional systems affected by MS’ (Kurtzke, 1983).

  • Pain

              Pain is very common among multiple sclerosis patents and often appears after the first lesion is formed. In most occasions it is associated with the control mechanisms which regulate ascending and descending tracts in the anterolateral system. From 28 studies researchers proved taking a sample of 7101 multiple sclerosis patients that 63% complained of various degrees of pain. There were no significant differences in pain levels among men and women or people with greater disability than others.  Most pain occur as ‘headaches (43%), dysesthetic limb pain (26%), back pain (20%), painful spasms (15%), painful Lhermitte’s phenomenon (16%) and Trigeminal Neuralgia (3%)’ (Foley et.al, 2013, p 632).

  • Emotional disturbance

       Emotional disturbance manifests as clinical depression. This can extend into a life time complication. Present incidence rates range between 40–50% per person diagnosed with multiple sclerosis. Brain imaging studies have tried to relate findings to depression when brain lesions are found. More importantly, most neurologists have associated these brain lesions with neuropathology of the left anterior temporal/parietal regions. It is very important development that is worth monitoring carefully because emotional disturbance is responsible for 15% of deaths emerging from suicide. As such, patients are closely evaluated when signs anger, anxiety, hopelessness, and frustration surface (Siegert, Abernethy, 2005).        

  • Bladder and Bowel irritability

       Bladder disturbances occur in 70% of all multiple sclerosis patients. It presents as frequency, hesitancy and incontinence which can affect maintenance of personal hygiene. Bowel issues appear in 70% of the multiple sclerosis patients, 50% suffer from constipation 30% fecal incontinence (DasGupta & Fowler, 2003).            

  • Cognitive disturbances

       40%- 60% of multiple sclerosis patients encounter cognitive difficulties. It ranges from simple degrees of forgetfulness to severe loss of memory. Other cognitive difficulties are attention deficit; neurological fatigue; processing speed and visual spatial ability alterations (Ebers, 2008).

  • Impaired Mobility

           Mobility changes become evident when walking, moving, getting off and on the bed and balancing. Research has shown that between the onset of the disease and 5 years 50% of patient score 6 on the EDSS scale. 10 years living with multiple sclerosis 25% of patients can attain just a score of 6 on the Expanded Disability Status Scale (EDSS). This makes using a walker and other methods of mobility support necessary. Within 30 years, 83% of patients use walking aids (DasGupta & Fowler, 2003).           

  • Speech difficulties

Speech could become slurred and tone of voice altered.

  • Muscle Tremor and Ataxia

Ataxia coincides with muscle tremors. Clumsy movement occurs creating difficulty in maintaining a steady gait. Muscle tremors are often uncontrollable involuntary episodes of shaking.

  • Transverse myelitis 

When multiple sclerosis begins invading deep into spinal cord tissue lower body functions become impaired. These include bladder/irritability as well as sexual potency in males. Inability to have an erecting is possible along with ejaculation difficulties

  • Spasticity

Spasticity manifests as both a sign and symptom. Muscles, especially, in the extremities become very stiff and immobile.

Diagnosis

           Researchers have posited that multiple sclerosis is difficult to diagnose since confirmation of the disease cannot be made on clinical symptoms alone. Signs and symptoms may resemble many other neurological disorders. To facilitate diagnosis during the early stages scientists have designed standardized criteria. They include Schumacher, Poser and McDonald criteria.

Schumacher’s criterion is a neurological examination detecting central nervous system abnormalities involving two or more systemic dysfunctions. Often white matter abnormalities are evident in brain and spinal tissue. In 1983 these criteria were modified by Poser accounting for clinically definite; laboratory supported definite; clinically probable and laboratory supported probable multiple sclerosis (Royal College of Physicians of London, 2004).

                          McDonald criteria are the ones presently used in most health care institutions across the world for making a more accurate multiple sclerosis diagnosis. It includes a

  • Diagnostic criteria for suspected MS (two or more attacks)        Flowchart Icon  
  • Diagnostic criteria for suspected MS (monosymptomatic)         Flowchart Icon
  • Diagnostic criteria for suspected MS (single attack)                   Flowchart Icon
  • Diagnostic criteria for suspected MS (progressive from onset)      Flowchart Icon

                             (Royal College of Physicians of London, 2004)

               However, Schäffler, Köpke , Winkler , Schippling , Inglese , Fischer and, Heesen (2011) have reprted that the development of a new diagnostic criteria for multiple sclerosis was recently proposed after a systematic literature review  revealed that present accuracy issues made some tests invalid. The aim of this study was to validate diagnostic studies and clarify the value of diagnostic test used in offering a diagnosis. They included in their review a minimum of 40 patients who were traced for 2 years. This limitation existed in all the studies reviewed since they significantly lacked a gold standard measurement for validating the diagnostic tests that were used in those trials. A second relapse phase was adopted as a surrogate in relapsing-remitting multiple sclerosis testing. However, the lengthy 5 year follow-up created difficulty in detecting all cases. Also, quite a few studies contained various levels of validity and reliability issues. Notably, a selection bias was identified due to the indistinct classification of a clinically isolated syndrome (Schäffler et.al, 2011).

                  Based on these limitations, ‘sensitivity of magnetic resonance imaging (MRI) criteria was between 35% and 100%, and specificity was between 36% and 92%; Cerebrospinal fluid (CSF) oligoclonal banding showed sensitivities between 69% and 91% with specificities between 59% and 94%; combination studies of MRI and CSF indicate enhanced sensitivity (56-100%) and specificity (53-96%)’ (Schäffler et.al, 2011, 153). The researchers did not find justification in conclusions derived in the literature review studies. Further they suggest that ‘a combination of simplified MRI criteria with CSF might be the best approach for an early MS diagnosis’ (Schäffler et.al, 2011, 153).

Prognosis

         While there is no cure for multiple sclerosis it has not been considered a fatal disease even though it severely affects a person’s quality of life. Serious disability does not occur until about 20 years after onset of the disease. Women seem to have a better prognosis than males. Factors affecting each patient’s prognosis regarding quality and length of life relate  to  adherence of health promotion strategies that will limit symptoms , doctor’s  appointment  follow up ; compliance with medication management to reduce progression of the disease. Generally life expectancy is reduced by 5-10 years with careful intervention strategies (Murray, 2002).

Immunological concepts underlying Multiple sclerosis

          Immunology relates to the body’s defense mechanisms in counteracting  the activity of invading agents. For every disease entity that enters the human internal environment there are diverse strategies employed by the immune system in a comprehensive effort to interrupt the intended invasion consequences. Consequently, the immune system builds up resistance by developing immunity to the invading organisms. There are mainly five types of immunological responses that can emerge from this activity. They are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

Humoral immunity

         Humoral immunity is also known as antibody-mediated system being mediated macromolecules located in extracellular fluids like secreted antibodies, antimicrobial peptides and complement proteins. Usually, humoral immunity reacts with substances in body fluid humors (Nakahara et.al, 2006).

Cell-mediated immunity

          Cell-mediated immunity does not rely on producing antibodies in order to defend the body against harmful organisms. Instead it activates phagocytes, antigen-specific cytotoxic T-lymphocytes, and disperses numerous cytokines in an antigen response (Nakahara et.al, 2006).

Innate or Natural Immunity

 Innate immunity is the body’s evolutionary natural mechanism used to fight invading foreign species. This is the dominant and oldest type of immunity among living creatures including unicellular organism such as amoeba, fungi, plants and insects (Nakahara et.al, 2006).

Acquired immunity

      Acquired immunity emerges after exposure to a foreign organism. It is also known as adaptive immunity due to somatic hypermutation or accelerated somatic mutations), and V (D) J recombination, which is actually a genetic antigen receptor recombination that cannot be reversed (Nakahara et.al, 2006).

Non-specific immunity

               Non-specific immunity means that the immunological response is antigen independent and unspecified. However, distinct mechanisms are activated. They include establishing anatomical barriers, stimulation of secretory molecules and integrating cellular components.  Recognizable mechanical anatomical barriers include the internal epithelia tissue such as the skin.  Intestinal mobility along with oscillation of broncho-pulmonary cilia is chemicalized because chemical messages are transmitted through biological agents present in skin, intestines and nervous system.

                   DominantImmunological concepts associated with multiple sclerosis are connected to the pathogenesis of this disease. Some basic traditional immunological concepts pertaining to multiple sclerosis are:-

  • Relapsing MS
  • Secondary progressive MS.
  • Progressive MS.
  • Progressive relapsing MS

While these are the four major immunological concepts that intermingle in explaining the pathophysiology of each stage collectively in facilitating the discussion other will be highlighted. Significantly, coinciding with the five types of immunological responses that can emerge from antigen antibody interaction are humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity. Therefore, the terms that will be explained in this section are:

  • Demyelinization
  • Cell-Mediated Immunity
  • Humoral Immunity
  • Immunoregulatory Cells

              Relapsing MS is a serious symptom which progresses into a chronic inflammatory demyelinating central nervous system disorder manifesting as morphological inflammation, demyelination, axonal loss and gliosis. There is massive infiltration of heterogeneous cellular population; and soluble mediators of the immune system are activated. These include T cells, B cells, macrophages and mi croglia, cytokines, chemokines, antibodies which stimulate  humoral immunity; cell-mediated immunity; innate (or Natural Immunity); acquired immunity, and non-specific immunity (Nakahara et.al, 2006).

 Demyelinization

                Research has shown where a lymphocytes subset identified as T helper cells specifically the Th1 and Th17 play a major role in development of multiple sclerosis lesions. Also the Interleukin 12 protein causes differentiation of naive T cells producing inflammatory T cells. When there is over production of Interleukin 12 it initiates inflammatory increases that occur in patients with persistent multiple sclerosis relapses. Patients who are not affected by multiple sclerosis their lymphocytes develop innate immunity to recognize and distinguish cells what cells belong to the body and those which are foreigner (Nakahara et.al, 2006).             

       Lymphocytes, in the body of a person afflicted by multiple sclerosis cannot differentiate between healthy and non-healthy cells. They attack cells in the central nervous system as foreigners such as viruses, bacteria, fungi triggering inflammatory responses as if it were a cell-mediated immunity conflict. In this process other immune cells such as cytokines and antibodies are activated and join in the inflammatory battle. Importantly, most myelin-recognizing T cells are family to a terminally differentiated subset known as co-stimulation-independent effector-memory T cells (Nakahara et.al, 2006).   See appendix 5   

Cell-Mediated Immunity

      T cells are responsible compromising an estimated 10% of the all inflammatory cells found as active participants in demyelinating multiple sclerosis lesions. Scientists have already proven that the EAE model can adequately be transferred by injecting an animal with myelin-specific CD4+ T cells. Therefore, the acceptable assumption has been that Multiple Sclerosis is foremost a CD4+ T-cell-mediated disease. It was advised that caution must be taken when interpreting these results because CD4+ T cells can play an important role in a disease stage-specific context. Importantly, they cells are absent in chronic Multiple Sclerosis lesions apart from the T-cell repertoire shows changes (Awad & Stüve 2010).

        Different T cell subtypes play significant roles in the pathogenesis of autoimmune diseases such as multiple sclerosis. Extensive studies have been conducted to validate these interactions. These diverse subpopulations contain distinct cytokine products.  ‘TH1 CD4 + cells secrete interferon gamma, tumor necrosis factor α, IL-2, and nitric oxide’ (Awad & Stüve 2010, p, 168).  TH1 cells are responsible for activating cell-mediated immunity. Alternatively, TH2 CD4+ cells secrete IL-4, IL-5, IL-6, IL-10, IL-13. They transform the growth factor β.  TH2 cells in humans function as a regulator agent when certain inflammatory conditions occur (Awad & Stüve 2010).

      The human system does not contain distinct TH1-TH 2 dichotomy. This adds to the complexity of explaining cell mediated immunity. Significantly, there is an overlap expression of cytokine between two subtypes TH1-TH 2 dichotomy which is a subtype of CD4+ cells. These cells have been implicated in the autoimmunity as TH17 cells. They express as proinflammatory cytokine IL-17. RNA (mRNA) encoding IL-17 messengers were detected in blood at very high levels cerebro spinal fluid (CSF) and brain parenchyma of multiple sclerosis patients in active stages of the disease (Awad & Stüve 2010).

      This phenomenon is highly suggestive of the major role cell mediated immunity plays in progression of multiple sclerosis as an immunopathogenesis factor in the disease sequence.  More importantly, it is worth noting that even though multiple sclerosis is often perceived as a CD4+-mediated autoimmune disease, there are CD8+ T cells implications in its pathology. Precisely, scientists have confirmed that clonal and oligoclonal expansion of CD8+ T cells consistently have appeared in plaques obtained from multiple sclerosis patients during diagnostic testing. In a few situations when evaluations were conducted, CD8+ T cells were found to have outnumbered CD4+ T cells (Awad & Stüve 2010).

        Again this is highly suggestive of suggesting cytotoxic T cells probably participation in starting this inflammatory interaction. Another factor worthy of consideration is the knowledge that T lymphocytes express γ/δ receptors were detected in various quantities when cerebro spinal fluid (CSF) of multiple sclerosis patients experiencing early stages of the disease. However, patients who had the disease for a longer time emerging into the chronic stages, CD8+ T cells were not found. The distinction lays in a probability that these cells play a role in the early development of the disease when cell medicate immune response is being activated.  More clarification on this phenomenon is pending while the pathogenic role of CD8+ T cells in multiple sclerosis progression is further explored (Awad & Stüve 2010).

Humoral Immunity

       Scientists posit that despite the autoimmune process in multiple is perceptive mainly from the premise of it being mediated by T cells; there is just as much evidence to suggest a great degree humoral immunity activity is also involved in the progression of disease process. Fundamentally, scientists discover that there have been interactions with an antigen driven B-cell response in multiple sclerosis patients’ cerebro spinal fluid. This is highly suggestive that B- cells are implicated in the immunopathogenesis of the disease. Also, oligoclonal immunoglobulin production persists in the cerebro spinal fluid of multiple sclerosis patients. Subsequently, growth of secondary lymphoid brain tissue was detected during diagnostic evaluations in multiple sclerosis patients experiencing secondary progressive stages of the disease. Some research studies have even shown a direct relationship between intrathecal immunoglobulin levels and severity of the disease when patients present with secondary progressive multiple sclerosis (Awad & Stüve 2010).

          Scientists have continued probing for evidence of humoral immunity implication. Researchers have also detected B cells in brain cerebro spinal fluid of secondary progressive multiple sclerosis patients. There has been constant isolation of B cells in the cerebro spinal fluid of patients with secondary progressive multiple sclerosis. Evidence of clonal expansion along with extensive somatic mutation in B-cell receptor genes was observed. This phenomenon expresses the characteristic features of an antigen-driven response. Precisely, the assumption is that B-cell selection might have been initiated in peripheral lymph nodes or in lymphoid follicles of the central nervous system (Awad & Stüve 2010).

            Further studies related to investigating B-cell compartment of cerebro spinal fluid in multiple sclerosis reveal that B-cell differentiation is confirmed in the central nervous system of individuals suffering from multiple sclerosis. The dominant antibodies happen to be short-living plasmablasts. Interestingly it is not plasma cells. Precisely, plasma cells are actually the predominant antibody secreting cell found in multiple sclerosis patients’ cerebro spinal fluid.               More importantly, the phenomenon whereby upregulation of costimulatory molecules on plasma cells within central nervous system  occurs is indicative the potential of such cells to sustain their T-cell activation.  Scientifically, B cells have been known as potent antigen-presenting cells. Assumptions are that they might feature prominently in T-cell antigenic stimulation. Scientists conclude that B cell and humoral immunity might be the main factors responsible for initiating and sustaining multiple the sclerosis disease process (Awad & Stüve 2010).

Immunoregulatory Cells

          Studies have revealed that isolating myelin-reactive T cells from peripheral blood of healthy subjects is highly suggestive that, perhaps, decreasing regulatory cells interactions is the basic immunopathology concepts in multiple sclerosis evolution and not he presence or absence  of self-reactive T cells.  Scientifically,   it has been accepted that regulatory cells play a major role in controlling intensity when immune response are activated by maintaining self-tolerance. Importantly, it has been proven that CD4+ TH2 cells are active in anti-inflammatory cytokines production. They are IL-4, IL-5, and IL-13. Precisely, this CD4+ TH2 has the ability of lowering regulatory function of macrophages (Awad & Stüve 2010).

    Further developments show where a relatively little subpopulation of CD4+ T cells were identified to be naturally occurring regulatory T (CD4+CD25+Treg) cells. It is believed that they are vital participants in the immune homeostasis process too. Certainly, they were found to be expressing CD25 which is an important component of the IL-2 receptor. However, preclinical trials have revealed that Treg cells’ absence was closely associated with the emergence of autoimmunity. Overwhelming evidence exists to prove that inadequate Treg-cell activity could be a main contributory element in multiple sclerosis etiopathogenesis. Essentially, studies show where  CD4+CD25+Treg cells effector function  emerging out of multiple sclerosis patients’ peripheral blood  samples of patients was deficient in comparison to CD4+CD25+Treg cells from subjects who were not afflicted by the disease (Awad & Stüve 2010).  .

         While these findings scientifically seem profound critics argue there are no differences in Treg cell concentration and constitution in the cerebro spinal fluid among patients afflicted by multiple sclerosis and those who were healthy. A larger study conducted on 73 multiple sclerosis researchers discovered that Treg cell concentration was identical with that of healthy volunteers. . The notable difference detected was that the Treg cells obtained from multiple sclerosis patients demonstrated reduction suppressive potential on the ‘immune response directed against myelin antigens’ (Awad & Stüve 2010, p 201). Yet, in another study this theory was refuted since, there were higher Treg cell counts in multiple sclerosis patients than in the control. Alternatively,  appeared the potential of these cells suppress MBP-induced proliferation was less effective (Awad & Stüve 2010)

        Explaining the functional differences of Treg cells activity in multiple sclerosis patents and healthy subjects there has been reports of activity in RRMS and progressive stages of the diseases too.  For example, Forkhead box p3 (FOXp3) has been identified as a popular transcriptional factor. Its main role has been detected being a valuable participant in Treg-cell-suppressive molecular programmer activity (Awad & Stüve 2010)

            Many preclinical studies have supported many of these theories in confirming the linkage between autoimmunity and absence of FOXp3. An association was also discovered with ectopic FOXp3 expression conferring suppressive function on CD4+CD25+Treg cells. Further linkages posit a relationship showing significant reductions in FOXp3 mRNA transcripts and protein levels. Importantly, this occurred without any concordant decrease in CD4+CD25+Treg representation in multiple sclerosis patents. FOXp3+CD4+CD25+Treg cells popularly create infiltrations when cerebro spinal fluid of subjects afflicted with neuro inflammatory diseases. Comparatively, this multiple sclerosis patients isolated more FOXp3+CD4+CD25+Treg cells   than patients afflicted by dementia, stoke  or  any other neurological disease. In addition it was observed that Treg activity seem to be compromised when peripheral blood samples are used for the analysis in multiple sclerosis patients unlike other non-affected clients.

Therapy and management

        There is no cure for multiple sclerosis. However, scientists continue to experiment with drugs and therapies, which can be useful in relieving symptoms. For example, David Virley (2005) conducted studies to explore strategies involved in ‘Developing Therapeutics for the Treatment of Multiple Sclerosis.’ The author posited that many animal models have been used in developing therapeutic interventions for treating relapsing multiple sclerosis. The aim of preclinical research was mainly to identify and validate novel targets that are the most appropriate mimics for the specific clinical situation. Animal models therefore, become valuable subjects in establishing drug development processes that help select suitable human subjects for therapeutic interventions. This process provides the proof-of-concept for continuance of clinical trials. The author further contended that ‘although there is no gold standard model of multiple sclerosis, experimental autoimmune/allergic encephalomyelitis (EAE) models simulate the clinical and pathological hallmarks of multiple sclerosis in various guises and can provide the necessary predictive index for clinical therapeutic application’  (Virley, 2005, p 639).

         EAE was induced by generating T-cell-mediated immunity into central nervous system antigens, which was easily modeled in rodents such as rats, mice, and guinea pigs. Whole CNS homogenate (spinal cord) t purified protein and peptides were combined in preparing the autoantigen for the experiment (Virley, 20050.  ‘Myelin basic protein (MBP), proteolipid protein, myelin oligodendrocyte glycoprotein (MOG), S100β, and glial fibrillary acidic protein as well as specific peptides from respective parent proteins are encephalitogenic in the appropriate host, as the major histocompatability complex (MHC) is one of the major determinants of immune responsiveness and disease susceptibility to these self-antigen’ (Virley, 2005, p 639).

        The author concluded that the pathogenic autoimmune mechanism steps that initiate and magnify EAE and MS damage tissue sequences are:-

  • Activation of autoreactive CD4+ T-cells in the periphery to an antigen;
  • Transmigration of proinflammatory T-cells and monocytes through the blood brain barrier (BBB)
  • Amplification of local inflammation and activation of resident antigen-presenting cells (APCs), such as microglia; and 4) destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).

(See Appendix 4).

Current Drug Therapies

The foregoing trials have emerged into distinct therapies, which are now active treatment management intervention s for multiple sclerosis. To date there are only five Food and Drug Administration (FDA) approved therapeutic treatments for relapsing – remitting multiple sclerosis. They include ‘two interferon (IFN)-β1a agents (Avonex and Rebif), one IFN-β1b (Betaseron), glatiramer acetate (GA) (Copaxone) and Mitoxanthrone (Novantrone)’ (Virley, 2005, p 639).

      Patents suffering from secondary progressive multiple cyclophosphamide (Cytoxan) and mitoxanthrone are the drugs of choice. There are no extreme benefits in using these two drugs or severe toxicity. However, the main drugs used are corticosteroids, IFNβ and GA (Virley, 2005).

Corticosteroids

             Corticosteroids are administered to raise a patient’s tolerance level tolerance during an attack and speed up recovery. Long term therapies are more effective even though short-term interventions can be useful. However, to maintain a longer period between remissions it is always better to continue treatment over a longer period of time.  Patents often receive significant results even when the clinical course of multiple sclerosis may change to secondary progressive stage. Even with so many drug trials and pre-trials being conducted scientists are still not yet sure what are the actual effects of corticosteroid on the immune system are (Virley, 2005).

         However, preclinical research evidence has verified quite a few putative mechanisms. They embody ‘an inhibition of the Th1 immune response reduction in BBB molecules and protection of oligodendrocytes from cytokine-induced cell death’ (Virley, 2005, p 639). EAE models validated the suppressive interactions produced by corticosteroid treatment in relation to clinical course disruption of multiple sclerosis, T-cell migration dampening its antigens response suppression during expression of adhesion utilization of anti-glucocorticoid, RU 38486 (mifepristone). It was revealed that these interactions have intensified as well as reversed steroid-induced inhibition of disease (Virley, 2005).

      While corticosteroids have been so effective in the treatment of multiple sclerosis in both short and long term its side effected should not be underestimated. For example, extended use can initiate transient mood changes headache, gastrointestinal disturbances, and myalgias.  Decrease in bone density can occur overtime if patients must be treated for extended periods of time. Ultimately, osteoporosis could become a real problem increasing risks for fractures and infections. When side effects have become so progressive, the patient ought to be reassessed. Often the attending physician may consider either reducing or discontinuing treatment temporarily (Virley, 2005).

IFN-β

          IFN-β therapies emerged after over 25 years of clinical trials. The aim was finding how multiple sclerosis would respond to IFNs if it is truly a virally mediated disease. Importantly the   antiviral assumption became invalid after clinical trial assessments, which revealed that IFNγ worsened symptoms.  This was highly suggestive, that IFNγ  was more influential in multiple sclerosis pathological process. it meant that IFNβ, like other IFNs, is a species-specific glycoprotein with numerous biological properties. Actually, the mechanism producing these interactions is not fully understood from a scientific perspective poorly. However assumptions have been that immunomodulatory as an alternative to antiviral and antiproliferative makes much sense in deriving at an alternative proposition (Virley, 2005).

      Importantly, IFNβ-1a is exactly like the natural IFN-β, but IFNβ-1b differs in having two amino acids as well as not being glycosylated. Despite these insidious structural differences IFNβ-1b displays comparative biological activity to IFNβ-1a. Therefore, putative responses of IFNβ on the progression of multiple sclerosis is believed to be related primarily to its  antiinflammatory influences, which demonstrates as dampening the stimulatory impact of IFNγ, tumor necrosis factor (TNF)α, interleukin (IL)-12. The lymphotoxin secretion has been identified in the sequence of controlling monocyte activation; inhibiting disruption of BBB. Consequently, the entry of lymphocytes into the CNS is reduced; antigen presentation is reduced to T-cells; and up-regulation of anti-inflammatory cytokines occurs; TGFβ and IL-10 (Virley, 2005).

        EAE pre-trial models have validated the use of IFNβ by proving its influence in limiting the   progression of multiple sclerosis. Supportively, clinical trials were done using both IFNβ formulations. Important findings indicate a one third relapse reduction rate when higher doses are administered. The onset has been observed to be rapid. Precisely, relapses occurred at a rate of 1 per year and few weeks for MRI disease activity. Conversely, there were huge inflammatory changes measured through MRI activity; accumulation of MRI disease burden was significantly slowed down. Besides, there were magnificent results shown by patients regarding relapses (Virley, 2005).

      This novel treatment is not without its adverse side effects. Some include, flu-like symptoms along with reactions emerging at the site where injections are administered. If patients do not respond to the drug after six months of therapeutic intervention, the IFNβ therapy is usually discontinued. Some patients who are already disabled with progressive or relapses occurring at a rate of more than one per year are treated with a combination of combination three or more courses of corticosteroids over a 1-year period. In addition some patents encounter extreme feelings of depression leading towards suicidal inclinations. Drug toxicity can also become a problem with patients becoming noncompliant. This initiates physicians’ decisions of considering alternatives. Neutralizing antibodies in IFNβ effectiveness ought to be addressed as an adverse reaction during treatment. This can lead to long term complications. As such, it must not be ignored if patients complain of reactions or it shows up in diagnostic testing (Virley, 20 05).

   Glatiramer acetate – GA

          GA is considered a non-IFN, nonsteroidal therapy. It is made from synthetic random base copolymers mixtures containing four amino acids namely glutamic acid, alanine, lysine, and tyrosine). The molar ratio was highly specific. Trials researched investigated the GA’s potential encephalitogenic role using EAE animal models. However, surprisingly, it was discovered that GA suppressed their acute and chronic clinical and pathological hallmarks. Importantly, translation of impacts was clinically beneficial. Importantly, GA provided evidence in the initial phase II trial as being a suitable agent for reducing relapse rates by 76% in patients with relapsing-remitting multiple sclerosis. A 5 year follow up intervention treatment confirmed

GA benefits as being capable of sustaining the initial influence on relapses in multiple sclerosis patients. The progression of the disease into the secondary stages was significantly slowed. Patients did not enter into disability as quickly as when other drug therapies were used. Also, when the Lesion burden was assessed through MRI it validated the value of GA in helping patients during the relapsing-remitting episodes. It was discovered that GA greatly reduced  frequency  rates of lesion load  and new enhancing lesions when baseline pretreatment measures are compared (Virley, 2005).

     Since then numerous mechanisms were advanced as being responsible for these fascinating results observed by GA’s intervention in the disease process. First its biological activity relapsing-in remitting MS was noted as a valuable factor. Then the antigen-specific induction suppressor T cell was remarkable. Thirdly, a MBP competitive inhibition was distinctly observed as a benefit. There was also a relationship of the interactions to -peptides from antigen-presenting cells (Virley, 2005).

       It must be noted that regardless of how beneficial a new drug therapy may be in treating a disease there are always adverse effects, which must be considered in its administration. GA is no exception even though the tolerance level in multiple sclerosis patients is great. However, subcutaneous administrations could become harmful due to increasing incidences observed whereby injection site reactions occurred in the majority of cases and they were localized proving that it was the drug interaction with human skin (Virley, 2005).

             The overall picture being communicated in the use of this drug pertains towards it being the most tolerable in terms of side effects when compared to other therapies. Reduced propensity in the development of depression, neutralizing antibodies and menstrual disorders was far less when compared to other drugs now available for treating multiple sclerosis. Despite these developments, however, it is still important for continued research in extending to multiple sclerosis patients more options. While there is no cure for the condition medical science can provide the best relief it could through timely and efficient intervention therapies that work (Virley, 2005).

      Ultimately, these interventions should aim at not only providing relief, but secure sustained drug benefits reducing symptoms of multiple sclerosis, which shows that treatments are becoming more effective. Patents should be taking lower doses and experiencing fewer side effects. As such, pharmaceutical and biotechnology industries are challenged to provide this service to the multiple sclerosis community of patients. Essentially, numerous alternative disease-modifying strategies are emerging. They will be reviewed in the following pages of this document (Virley, 2005).

           For example, Pietro Iaffaldano (2012) and a group of researchers conducted studies regarding the ‘Impact of Natalizumab on Cognitive Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label, Two Years Observational Study.’ These researchers contend that Natalizumab reduced relapse rate as well as magnetic resonance imaging reactions in patients experiencing Relapsing-Remitting Multiple Sclerosis (RRMS). However, its impact on fatigue cognition in patients affected by multiple sclerosis need to be validated though scientific research. There the purpose of a prospective, open-label, observational study was intended as an  evaluation relating probable impacts  natalizumab had on cognition and fatigue when measured in patients experiencing Relapsing-Remitting Multiple Sclerosis  after being treated continuous for two years (Iaffaldano et.al, 2012).

        Researchers examined cognitive performances by applying  ‘Rao’s Brief Repeatable Battery (BRB) device, the Stroop test (ST) and the Cognitive Impairment Index (CII), every 12 months’ (Iaffaldano, 2012, p  201).   When patients did not respond favorable to at least 3 BRM and ST 3 they revived a cognitively impaired (CI) classification. Every 12months the Fatigue Severity Scale (FSS) was administered. This assessed the patient’s ability to self-reported incidences of fatigue. A total of 1 53 patients participated in 1 and 2 year-natalizumab continuous treatment (Iaffaldano et.al, 2012).

       Result revealed that after one year treatment the amount of’ CI sampled patients decreased from 29% (29/100) at baseline to 19% (19/100) (p=0.031) and the mean baseline values of CII (13.52±6.85) and FSS (4.01±1.63) scores were significantly reduced (10.48±7.12, p<0.0001 and 3.61±1.56, p=0.008). These significant effects were confirmed in the subgroup of patients treated up to two year.’ (Iaffaldano et.al, 2012, p. 201). From these results researchers concluded that

In the short-term Natalizumab can be successfully used as a treatment which could, ultimately reduce incidences of cognitive difficulties and fatigue in patients experiencing Relapsing-Remitting Multiple Sclerosis (Iaffaldano et.al, 2012).

Examples of Novel Therapeutic Challenges for Multiple sclerosis

Blockade of lymphocyte migration

       Very late antigen-4: natalizumab (Tysabri) and small molecule antagonists. There is widespread evidence implicating very late antigen-4 (VLA-4, α4-β1 integrin) in this process, via its interaction with receptors like vascular cell adhesion molecule 1 (VCAM-1) and the CS1 fibronectin domain (Virley, 2005).

Immunomodulatory agents

       Interest recently has emerged regarding development of novel Immunosuppressants. Trials have been conducted and they have been actually used in treatment of many autoimmune diseases such as psoriasis and rheumatoid arthritis. They reduced exacerbations keeping progression (Virley, 2005).

Anti-inflammatory agents

‘Cycloxygenase-1 and -2 (COX-1 and COX-2 or prostaglandin H synthases 1 and 2) catalyze the conversion of arachidonic acid and oxygen to generate inflammatory prostaglandins such as PGE2, PGD2, PGF2a, and thromboxane’ (Virley, 2005, p 201).

Neuroprotective and neuroregenerative therapeutic strategies

       Achievements in repair of myelin and immense neuroprotection though therapeutic interventions can be interpreted major research breakthrough in the attempt at providing more beneficial therapies that reverse permanent neurological disability associated multiple sclerosis.

Potential combinations of therapeutic strategies

       The heterogenic influences of clinical response as well as pathological hallmarks contained in recent multiple sclerosis drug development it would be wise considering combining therapeutic strategies that differentiate concentrating of specific aspects of the disease such as cognition memory and fatigue as espoused by Iaffaldano and his team of researchers. An area of precedence is a development stage whereby each agent independently offers a benefit distinct from the others, but is still valuable when combined in adding synergistic value to the therapeutic intervention. This approach would be extremely beneficial for patients who seldom respond favorable to therapies now available on health care markets across the country and world (Virley, 2005, p 201).

Conclusion

               While theories pertaining to the etiology/epidemiology/immunology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explored the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of this disease. Consequently, the researcher adapted a comparative analysis of the perspectives offered by theorists in discussion of epidemiology regarding emergence of multiple sclerosis among the predominantly, female young adults twenty-first century population. These were matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon as data relevant to its epidemiology; clinical symptoms; immunological concepts underlying the disease; therapy and management, and current trends are being explored.

Current Trends

                   Precisely, Ascherio and Munger (2007) ‘Environmental risk factors for multiple sclerosis Part I: the role of infection’ contend that even through genetic susceptibility play a role in the acquisition of multiple sclerosis among families studies show where personal hygiene significantly affect occurrence of the disease. Further, they advance that genetics and environment alone cannot account explicitly for the MS frequency among geographic variations when risk changes with migration are taken into consideration. Supportive epidemiological findings highlights the “hygiene hypothesis,” showing the additional role Epstein-Barr virus (EBV) plays as evidence for MS risk factor (Ascherio & Munger, 2007)

             Another piece of research literature by the same authors ‘Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors focusing on the environment explains that the change risk factor among migrants gives profound evidence for M.S environmental determinants. Then researchers defined environment to mean variations in diet and social behavior. Main contributory factors were sunlight and cigarette smoking (Ascherio & Munger, 2007)

     Dyment, Ebers, and Sadovnick, (2004) took a stand in ‘Genetics of multiple sclerosis.’          They argue that while environment and infection may play a role many genes appear to be linked to  MS etiology. They mentioned ‘HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A’ (Dyment et.al, 2004, pp 110). These researchers advanced that future development in the MS genetic science largely depends on continuous research making data available as evidence. Also the development of appropriate statistical measurements and research methodologies could be valuable (Dyment et.al, 2004).

             George Ebers (2008) focused on ‘Environmental factors and multiple sclerosis’ in reporting that studies conducted in Canada show where environmental factors influence the distribution of MS in specific geographic locations. The researcher cited migration studies to prove that the increase incidence of MS in Canada relates to longitudinal sex ratio expansion among immigrants within the country. This was compared to studies conducted in Australia where similar geographic patterns exist. It was discovered that by modifying the environment it reduced 80% of cases. It was concluded that while genetics play a major role there are predominant environmental factors associated with MS incidences in certain geographic locations (Ebers, 2008).

       Gavin Giovannonia and George Ebers (2007) posit that ‘genes and environmental factors lead to tissue injury by autoimmune mechanisms, implicated by strong circumstantial evidence’ (Giovannonia and Ebers, 2007 pp, 261). They further contend that it is difficult to identify the specific genes responsible for MS without examining the associating influences of the environment. Actually, they argue that the impact of genes on MS emergence is modest. Additional studies were cited emphasizing irregularities in confirming the genetic theory of MS etiology (Giovannonia and Ebers, 2007).

                Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed at addressing the autoimmune etiology of the disease. These therapies are designed to reduce inflammation, but their long term effect is uncertain. Hence, a re-evaluation of both pathogenesis and etiology is suggested (Nakahara et.al, 2012).

                     Rosati offered insights to say that the childhood environmental factor was a single variable in the emergence of multiple sclerosis at a later stage in the child’s life. Consequently, epidemiologists began investigating numerous diverse migrant populations which revealed that once children were removed from the location before attaining 15 years of age it was less likely for him/her to develop the disease. When children remain in the geographic space the predisposition of contracting multiple sclerosis is sustained. Further investigations revealed that the birth season also had a relationship towards development of the disease which makes epidemiological estimation ns more complicated. This confirmed the vitamin D sunlight theory since people born in November were less likely to contact multiple sclerosis regardless the geographic location (Rosati, 2001).

               Consequently, this study’s importance pertains to advancements into understanding multiple sclerosis’ etiology, pathophysiology/immunology and treatment. As explained in the foregoing principal pieces of research literature theories relating the etiology of MS are numerous. However, theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure.

       Current therapeutic trends predict that the ideal treatment for multiple sclerosis mustconsist oftechniques aimed at increasing disease-causing/sustaining antigen(s) tolerance. Ultimately, it is expected that long-term therapy would be obviated. This is important because amidst  numerous continuous drug trials scientist still contend that none of them seem to have considerable effects on resolutions of a disease which is over 100 years old. Justifiably establishing coordination between activated T cells and B cells in the pathophysiology of multiple sclerosis is highly recommended for targeting the two cell population. These include resting and dividing cells together. The strategy may necessitate, taking control of the disease process itself (Awad & Stüve, 2010).   

          Whatever emerges from these assumptions scientist must bear in mind that other immune cell populations are playing a major role also in the sequel of this disease. They intimate and perpetuate the process. Therefore, the final proposition of this theory advanced that amplifying or sparing the pool of regulatory cells which act as mediators of immune suppression would be valuable a valuable intervention. This however must be embraced without compromising immune surveillance in the treatment of this disease (Awad & Stüve, 2010). In concluding these deliberations pertaining to current trends in multiple sclerosis therapeutic management it is expected that this research project sensitize scientists into elaborating on present research practices in order for a consensus be reached regarding the reality of multiple sclerosis etiology and its pathological implications.

References

Ascherio, A., & Munger, K (2007). Environmental risk factors for multiple sclerosis. Part I: the

                      role of infection. Ann. Neurol. 61(4); 288–99

Ascherio, A., & Munger, K. (2007). Environmental risk factors for multiple sclerosis. Part II:

                     Noninfectious factors. Ann. Neurol.  61(6); 504–13.

Awad, M., & Stüve, O. (2010). Immunopathogenesis of Multiple Sclerosis: New Insights and

                    Therapeutic Implications. Lifelong Learning in Neurology. 16(5); 166-180

Clanet M (2008). Jean-Martin Charcot. 1825 to 1893. Int MS J 15 (2), 59–61.

DasGupta, R., & Fowler, C. (2003). Bladder, bowel and sexual dysfunction in multiple  

                       sclerosis: management strategies.  Drugs, 63 (2): 153–66.

Dyment, A; Ebers, G; Sadovnick, A. (2004).  Genetics of multiple sclerosis. Lancet

                                 Neurol  3( 92). (2004): 104–10.

 Ebers, G. (2008). Environmental factors and multiple sclerosis. Lancet Neurol  

                              7 (3). 268–277.

Foley, P. Vesterinen, H. Laird, B. (2013). Prevalence and natural history of pain in adults with

                       multiple sclerosis: Systematic review and meta-analysis. Pain 154 (5): 632– 42

Gilden, D (2005). Infectious causes of multiple sclerosis. The Lancet Neurology 4  (3)

                                    195–202.

Giovannoni, G; Ebers, G. (2007). Multiple sclerosis: the environment and causation. Curr

                                Opin Neurol. 20( 3); 261-8.

Kantarci, O., & Wingerchukb, D. (2006). Epidemiology and natural history of multiple sclerosis:

                             new insights. New York. Lippincott Williams & Wilkins

Kurtzke, J. (1983). Rating neurologic impairment in multiple sclerosis: an expanded disability

                          status scale (EDSS). Neurology, 33 (11); 1444–52.

Iaffaldano, P. Viterbo, G. Paolicelli, D. ( 2012). Impact of Natalizumab on Cognitive

               Performances and Fatigue in Relapsing Multiple Sclerosis: A Prospective, Open-Label,

                  Two Years Observational Study. PLoS . 7(4)

Merril, R. (2010). An Introduction to Epidemiology, (5th Edition). Jones and Bartlett

                   Publishing.

Murray, J (2002). Infection as a cause of multiple sclerosis. Theories abound because no one

                         knows the answers yet. BMJ. 325(7373).(2002). 1128.

Nakahara, J; Maeda, M; Aiso, S; Suzuki, N ( 2012). Current concepts in multiple

                             sclerosis: autoimmunity versus oligodendrogliopathy. Clinical reviews in

                           allergy & immunology  42(1); 26–34.

 Oksenberg, J., & Barcellos, L (2000). The complex genetic etiology of multiple sclerosis.

                           Journal of NeuroVirology. 6(2), S10 ± S14

Rosati G (2001). The prevalence of multiple sclerosis in the world: an update. Neurol. Sci. 22

                (2): 117–39.

Royal College of Physicians London (2004) Multiple Sclerosis: National Clinical Guideline for

                Diagnosis and Management in Primary and Secondary Care. NICE Clinical

              Guidelines, No. 8.National Collaborating Centre for Chronic Conditions (UK).

               London

   Schäffler, N. Köpke, S. Winkler, L. Schippling, S. Inglese, M. Fischer, K.,  & Heesen, C.

      (2011). Accuracy of diagnostic tests in multiple sclerosis–a systematic review. Acta Neurol

                      Scand. 124(3), 151-64

Siegert, R., Abernethy, D. (2005). Depression in multiple sclerosis: a review. J. Neurol.

                     Neurosurg. Psychiatr. 76 (4): 469–75.

Terry, R. Miller, S. Getts, D., & Muller, M. (2012). Current Theories for Multiple Sclerosis

                    Pathogenesis and Treatment. Free Press New York. 2012.

 Virley, D. (2005). Developing Therapeutics for the Treatment of Multiple Sclerosis. NeuroRx.

                 2(4): 638–649.

Appendix 1

Table 1 Multiple sclerosis as a genetic disease

———————————————————————————

1. Racial clustering of MS cases. Resistant ethnic groups residing in high risk regions

2. Familial aggregation of MS cases. Increased relative risk to sibs (ls=20±40)

3. Low incidence of conjugal MS

4. MS sibling pairs tend to cluster by age of onset, rather than

year of onset

5. High disease concordance in monozygotic twins (25±30%) compared with dizygotic twins and non-twin siblings (3±5%)

6. No detectable effect of shared environment on MS susceptibility in first-degree non-biological relatives (spouses, adop-tees)

7. Suggestive correlations between certain polymorphic loci and disease susceptibility

————————————————————————————

Appendix 2

Table 2 Confounding factors in genetic studies of multiple

Sclerosis

————————————————————————————————-

1. Aetiologic heterogeneity identical genes, different phenotypes

2. Genetic heterogeneity Different genes, identical phenotypes

3. Unknown genetic parameters Single versus multiple genes Dominant versus recessive mode of inheritance incomplete penetrance

4. Epistatic gene interactions

5. Post-genomic mechanisms

6. Unidentied non-heritable (environmental) factors

——————————————————————————————————————

(Oksenberg & Barcellos, 2000).

Appendix 3

   s                        

Diagram showing immunological concepts underlying Multiple sclerosis               Progression of subtypes (Oksenberg et.al, 2000).                        

      Schematic view of the putative pathogenic steps in MS. 1: Activation of autoreactive T cells by antigen presenting cells in the periphery. 2: Migration of T cells and monocytes through the blood brain barrier. 3: Amplification of local inflammation and destruction of oligodendrocytes, myelin sheath, and axons culminating in demyelination and axonal pathology (Virley, 2005, p 639).                                

         Appendix 5   – Demyelinization

Categories
Medicine and Health

Multiple sclerosis

The statement of problem related to this research reads ‘while theories pertaining to the etiology of multiple sclerosis predominantly focus on genetics and infection various environmental risks can be predisposing influences also. As such, this research explores the extent to which genetic and infection theories defining causative factors influencing the development of multiple sclerosis can really explain the pathophysiology of the disease. Consequently, the researcher will adapt a comparative analysis of the perspectives offered by theorists regarding emergence of multiple sclerosis among the twenty-first century female young adults. These will be matched with critiques from scientists advocating an environmental approach towards explaining the phenomenon.

                    My justification for selecting this topic and the investigation approach lays in the premise that so far medical science is inconclusive regarding causes for multiple sclerosis within our generation and beyond (Murray, 2002). More importantly, there is no cure for this disease. Often when an etiology is unknown scientist find it difficult to detect a cure. Contemporary measures are aimed at treating symptoms while no profound interventions are made to reduce incidences of debilitating of the disease which has a short life expectancy profile after its initial diagnosis (Terry et.al, 2012). Hence, it is imperative that a consensus be reached and health promotion measures designed for controlling multiple sclerosis among high risk populations. This can only be achieved if the predisposing factors have been clearly identified (Gilden, 2005)

                    Six principal pieces of literature will be embraced in this research project pertaining to the etiology of multiple sclerosis from a genetic, infection and environmental perspective. Ascherio and Munger (2007) ‘Environmental risk factors for multiple sclerosis Part I: the role of infection’ contend that even through genetic susceptibility play a role in the acquisition of multiple sclerosis among families studies show where personal hygiene significantly affect occurrence of the disease. Further, they advance that genetics and environment alone cannot account explicitly for the MS frequency among geographic variations when risk changes with migration. Supportive epidemiological findings highlights the “hygiene hypothesis,” showing the additional role Epstein-Barr virus (EBV) as evidence for MS risk factor (Ascherio & Munger, 2007)

             Another piece of research literature by the same authors ‘Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors focusing on the environment explains that the change risk factor among migrants gives profound evidence for M.S environmental determinants. Then researchers defined environment to mean variations in diet and social behavior. Main contributory factors were sunlight and cigarette smoking (Ascherio & Munger, 2007)

     Dyment, Ebers, and Sadovnick, (2004) took a stand in ‘Genetics of multiple sclerosis.’          They argue that while environment and infection may play a role many genes appear to be linked to  MS etiology. They mentioned ‘HLA classes I and II, T-cell receptor beta, CTLA4, ICAM1, and SH2D2A’ (Dyment et.al, 2004, pp 110). These researchers advanced that future development in the MS genetic science largely depends on continuous research making data available as evidence. Also the development of appropriate statistical measurements and research methodologies could be valuable (Dyment et.al, 2004).

             George Ebers (2008) focused on ‘Environmental factors and multiple sclerosis’ in reporting that studies conducted in Canada show where environmental factors influence the distribution of MS in specific geographic locations. The researcher cited migration studies to prove that the increase incidence of MS in Canada relates to longitudinal sex ratio expansion among immigrants within the country. This was compared to studies conducted in Australia where similar geographic patterns exist. It was discovered that by modifying the environment it reduced 80% of cases. It was concluded that while genetics play a major role there predominant environmental factors are associated with MS incidences in certain geographic locations (Ebers, 2008).

       Gavin Giovannonia and George Ebers (2007) posit that ‘genes and environmental factors lead to tissue injury by autoimmune mechanisms, implicated by strong circumstantial evidence’ (Giovannonia and Ebers, 2007 pp, 261). They further contend that it is difficult to identify the specific genes responsible for MS without examining the associating influences of the environment. Actually, they argue that the impact of genes on MS emergence is modest. Additional studies were cited emphasizing irregularities in confirming the genetic theory of MS etiology (Giovannonia and Ebers, 2007).

                Nakahara, Maeda, Aiso and Suzuki (2012) offer evidence as they explain ‘Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy’ showing where without relevant etiology appropriate treatment cannot be adapted for MS intervention. These researchers argue that present interventions, disease modifying therapies (DMT) are aimed at addressing the autoimmune etiology of the disease. These therapies are designed to reduce inflammation, but their long term effect is uncertain. Hence, a re-evaluation of both pathogenesis and etiology is suggested (Nakahara et.al, 2012).

                    Consequently, the study’s importance pertains towards advancements into understanding multiple sclerosis’ etiology, pathophysiology and treatment. As explained in the foregoing principal pieces of research literature theories relating the etiology of MS are numerous. However theories have no value if they cannot be used to enhance an understanding of the disease ultimately providing better treatment methods, leading towards a cure. This research is expected to sensitize scientists into elaborating on present research practices in arriving at a consensus regarding the reality of MS etiology.

Works cited

Ascherio A, Munger K. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann. Neurol. 61(4) 2007). 288–99 Print

Ascherio A, Munger K. Environmental risk factors for multiple sclerosis. Part II: Noninfectious factors. Ann. Neurol.  61(6). (2007): 504–13. Print

Dyment, A; Ebers, G; Sadovnick, A.  Genetics of multiple sclerosis. Lancet

Neurol  3( 92). (2004): 104–10. Print

 Ebers, George. Environmental factors and multiple sclerosis. Lancet Neurol   

7 (3). (2008):268–277. Print

Gilden D. Infectious causes of multiple sclerosis. The Lancet Neurology 4  (3)

(2005): 195–202.Print

Giovannoni, G; Ebers, G. Multiple sclerosis: the environment and causation. Curr

Opin Neurol. 20( 3). (2007): 261-8.Print

Murray, Jock. Infection as a cause of multiple sclerosis. Theories abound because no one knows the answers yet. BMJ. 325(7373).(2002). 1128.Print

Nakahara, J; Maeda, M; Aiso, S; Suzuki, N (February 2012). Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy. Clinical reviews in allergy & immunology  42(1). (2012) 26–34. Print

 Terry, Racheal; Miller, Stephen; Getts, Daniel Muller, Marcus. Current Theories for Multiple Sclerosis Pathogenesis and Treatment. Free Press New York. 2. Print

Categories
Art

The Rebirth of Art: Renaissance and Baroque

Chapter Two of “The Annotated Mona Lisa” explores the historical periods known as the Renaissance and the Baroque. Artistic expression in the Middle Ages abandoned many of the traditions of the Classical period, and focused primarily on cathedrals and other architectural works that were intended to glorify God rather than the human form and the natural world. At the dawn of the Renaissance, the world “came back to life,” and artists once again began to focus on anatomical accuracy and capturing the human form and the natural world realistically and accurately. Many works of art from these historical periods reflected the rebirth of humanity’s interest in knowledge, learning and exploration.

            Leonardo Da Vinci, of Florence, Italy is one of the most well-known and respected artists of the Renaissance era. Only a small number of Da Vinci’s paintings still survive, and one of those surviving paintings is one of the most famous works of art in history: The Mona Lisa. This portrait of a young woman was painted with oil on canvas, and was “one of the first easel paintings intended to be framed and hung on a wall” (Strickland and Boswell, 2007, p.34). Da Vinci’s work on the Mona Lisa incorporated several of the new techniques seen in Renaissance-era paintings, such as the use of light and dark known as chiaroscuro and the use of linear perspective that drew all the lines on the painting to a distant point hidden by the young woman’s head. These techniques made her image appear much more lifelike than earlier, more two-dimensional techniques, were capable of doing.

            Another famous work of Michelangelo’s, and one that was done on a very different scale, is “The Last Supper,” a fresco that portrays the last meal Jesus shared with his disciples. The wall-sized mural, painted in Milan, uses perspective and chiaroscuro techniques and a pyramidal structure to place Jesus at the center of the image as all the lines converge at his head. The other figures in the image are captured in various poses that make them appear very lifelike, revealing “the fundamental character and psychological state of each apostle” (Strickland and Boswell, p.35).

            Along with these well-known works from Da Vinci the chapter covers other artists and works from the Renaissance and Baroque periods, and demonstrates that many of the contemporary elements of art as they are known today were developed in these eras. I would define many of the works of art produced during these periods as exciting new forms of artistic expression that set the standard for what it mean to be an artist, and formed the foundation of the contemporary world of art.

Works Cited

Strickland, Carol, and John Boswell. The Annotated Mona Lisa: A Crash Course in Art History, from Prehistoric to Post-Modern. Kansas City, Mo: Andrews McMeel, 2007. Print.

Categories
Accounting

Interpretation of Sarbanes-Oxley Act

Over the course of the decade, there have been many publicized corporate scandals from the much publicized downfall of Enron, to WorldCom, Arthur Anderson, Tyco International, and a host of other major corporations that scandals rocked the accounting world. These companies were cooking the books, hiding accounting practices not reported in audits, and stealing from clients. From the number of corporations involved in scandals, thousands lost their jobs, and millions more lost their trust in major corporations. Out of this mistrust, President Bush acted in a reasonable response by creating the Sarbanes-Oxley Act of 2002 that was enacted in July 2002. This new law targeted other major corporations with the primary goal of protecting investors and the public in providing accurate and true reporting of auditing and accounting services. These were set in place in order to restore confidence in major corporations, and honestly the government that mostly bails these companies out.

Congress actions in passing the law were out of growing public scrutiny of auditing services that were mostly done internally, turning a blind out to the misdeeds of the executives and the heads of the companies. The little guys which were usually the lower level employees were the ones that were left without jobs. This is where the public was most upset about that the CEO’s and executives were riding high, but the lower employees were left broke and without benefits. The requirements in SOX, have shifted the focused on the importance of outside auditing firms double checking the company’s books, and the growing importance of the Securities and Exchange Commission in getting back public trust.

According to the textbook, Irwin suggest that Sarbanes-Oxley Act was to hold businesses accountable for their auditing duty. When all these scandals happen the bigger question was, “where were the auditors?” (Louwers, 2013) This question is crucial in understanding the importance of how these companies were able to commit fraudulent activities long before being caught. Attention was only brought because of whistleblowers, or suspicions from the SEC. Auditing is the key in holding businesses to the standards that the SEC has entrusted in them to follow the letter of the law in operating within the United States. Internal audits that are done by the company is how most of the companies are able to get by. Internal audits are supposed to ensure the public of a company’s honesty. “Internal auditing is an independent, objective assurance and consulting activity that adds value to and improves and organization’s operations.” (Louwers, 2013) The end result of the SOX is to provide insurance to investors that the company is operating legitimately.

The impact of the law for the future is meant to be positive for investors, studies have proven that SOX has not only instilled faith in investors, but has uncovered other scandals, such as Value Line, that was committing fraud for over 20 years was discovered by the SEC credit from the SOX. (Bhaktavatsalam, Condon, 2009) However there has been criticism that SOX has prevented IPO’s and foreign investors from entering the market. Many representatives have asked for a repeal that feel are hurting the U.S economy. However the future impact is unseen as many have believed including investors that the law supports a market and business culture that breeds honesty in operations that show the public that they are able to remain successful and turn a profit in a legitimate fashion that contributes to the economy.

References

Bhaktavatsalam, Sree Vidya, Condon, Christopher. “Value Line Settlement Marks End of Buttner Reign.” (2009). Bloomberg. Retrieved from http://www.bloomberg.com/apps/news?pid=newsarchive&sid=aPpxj3FdB0uM

Landers, Guy. “What is Sarbanes-Oxley?” (2003). McGraw-Hill. New York, NY

Louwers, T. Auditing & Assurance Services. 5th edition. (2013). McGraw-Hill

Categories
Nursing

Cultural Impact

Introduction

Crack cocaine is a very addictive substance that had a unique beginning. Cocaine was initially extracted from the coca plant in 1862 and used in various medicines, some that could be purchased over the counter. It was even one of the common ingredients in the first Coca-Cola drink (Baumer, p. 312   ). Powder cocaine was first used recreationally by affluent member of society. It was very expensive to buy pure cocaine. Crack cocaine became a cheaper substitute for pure powder cocaine. Crack cocaine is produced by adding water and baking soda to pure cocaine. The substance is then baked and “cracked” into small pieces. This product produces an intense high, but only lasts about fifteen minutes. Crack cocaine became popular in the 1980’s and has had lasting negative effects on the black community. Black males are more likely to use crack cocaine than members of any other race. Crack cocaine has negatively affected the African-American community in several ways: crack cocaine usage increases sexual risk taking behaviors and violence among its users, users are at a higher risk of mental health issues, and chronic users develop health issues over time that could lead to heart attacks, strokes, and other gastronomical complications. Nonetheless, there are treatment plans geared toward helping African –American individuals overcome crack addiction. These programs range from out-patient to extended in-patient stays. They are operated by various organizations from hospitals to religious organizations.

Risky Behavior

Many crack addicts take part in risky sexual behaviors in order to fund their habits. When one thinks of prostitution or the exchange of sex for something else, one often thinks of women only. However, in the drug world men exchange sex for drugs just as often as women do. For example, one study conducted in an urban area found that both men and women engaged in trading oral sex for drugs or money; further, male respondents who acknowledged trading sex for drugs or money were more likely than women respondents to acknowledge having engaged in anal sex in trading for drugs ( Maranda, M.J., Han, C., & Rainone, G.A , p. 318) Also, more women reported using condoms than men, but also confirmed that if the customer insisted on not using a condom they would oblige. The study found that women often traded sex in efforts to gain access to more crack or to mentally escape the horrors of prostitution, while men reported heightened sexual urges when they were high on crack cocaine.  Maranda, M.J., Han, C., & Rainone, G.A reported, “Some women reported that they traded sex to support their drug addiction, others seemed to use drugs to cope with trading sex.” Consequently, the AIDS epidemic is growing due to the crack epidemic.  Maranda, M.J., Han, C., & Rainone, G.A adds that the best way to prevent the spread of HIV is to prevent behaviors that put people at risk. Using drugs often make people participate in risky behaviors in efforts to gain access to the drug.  (Maranda, M.J., Han, C., & Rainone p. 320)

Mental Illness

Crack cocaine use has also has been linked to onset mental issues.  Chronic crack use has been reported to produce side effects such as anxiety, paranoia, egocentric behavior, dysphoria, anorexia, and delusions. According to Baumer,

“Different routes of using cocaine are associated with different negative consequences. Crack users have a greater number of symptoms, and higher levels of anxiety, depression, paranoid ideation, and psychoticism. Psychiatric comorbidity among cocaine dependent users is not only increased for other substance disorders, but also for personality disorders.” (Baumer, p. 319).

Years of chronic use has been linked to more serious mental illnesses like schizophrenia. Scientists believe that because crack alters brain activity the imbalance can lead to the disease. Crack use blocks certain neurotransmitters and substances that allow brain cells to communicate with each other. The brains of people with the schizophrenia have less gray matter and some areas of the brain display less or more activity, just as the brains of crack users.  Baumer adds that using drugs also adds to the probability that a person will be violent. When persons with mental illness or drug dependency become violent, it is usually directed towards a family member (Baumer, p. 321)

Effects on Black Community

            Although crack cocaine is use by people from various races, it attacked the black community the hardest. Cocaine use has been linked to the increases in murder and incarcerations. High school drop-out rates have also increased since the introduction of crack cocaine. It is estimated that crack markets account for between 40-73 percent of drop in black males’ high school graduation rate. In essence, the introduction of crack cocaine to the black community did three things: increased the probability of a black being murdered, increased risk of incarceration, and increased the likelihood of selling crack as a potential income in the black home. All of the scenarios limit the benefits of a proper education. Consequently, high school seems less attractive to the black because he/she will only end up in jail, or he/or she could be earning some fast money by selling it.

Incidence and Prevalence

            According to the data from the National Survey on Drug Use and Health (NSDUH), young black adults  aged 18 to 25 years of age represent the highest rates of lifetime (60.5%), past year (34.6%) and past month (20.3%) use of crack cocaine. In 2007, 17 percent of state inmates and 18 percent of federal inmate’s admitted that they commit their crimes while high or in efforts to get money for drugs.  Also, 60 percent of prisoners polled reported prior drug use, while 79 percent reportedly were still using drugs. Sadly, nearly 75 percent of addicts that enter a recovery program will relapse. In 2008, 18.8 percent of blacks reported using crack cocaine, while the national average of crack use in 19.9 percent. Astoundingly, blacks only make up about 11.3 percent of the U.S. population.

Treatment Options

            Implementing an intervention program can be difficult; it depends on each individual addict. If the addict has family, the family needs to be equipped with the tools to help the addict. However, if the addict is alone, he needs an appointed support system to help him maintain his sobriety. Financial difficulty is the main obstacle that addicts deal with. Most of them do not have insurance or the funds to pay for a treatment program. Often non-profit organizations may be willing to help out financially. There are some free programs that addicts may enter into, but these programs are often overcrowded and cold take as long as a year waiting period before being admitted. Some addicts chose to go through a detox program and then continue with an out-patient facility. With out-patient, the addict is able to go home daily, but is required to attend certain meetings. With in-patient facilities the addict is required to remain in the facility for the duration of the program. Often many addicts are more successful with in-patient facilities. Sadly, many of them relapse after they complete the program and are back in their old environments. Consequently, many therapists suggest that the addict moves to another location in order to have a better chance at remaining sober.  Consequently, the program has to be designed based upon the needs of the addict and his/her family.

                                     Specific Treatment for African-Americans

A range of treatment programs have been developed in the last few decades that endeavor to address the issue of substance abuse within members of the African-American community. A 2006 report (Liddle et al) examined an intervention and treatment program developed within the larger context of family therapy that was designed to address the specific needs and concerns of adolescent African-American males in terms of substance abuse. This program aims to be “culturally specific,” and is based on a several core components intended to provide a therapeutic framework that both considers and derives utility from a number of cultural references and touchstones relevant to the African-American community in general and adolescent African-American males in particular.

            The therapeutic framework is predicated on the notion that African-American adolescent males live in an “intersection” of cross-cultural frameworks (Liddle et al, 2006). These include the overarching mainstream American culture, the American minority culture, and the African-American-specific culture. As such the therapeutic framework utilizes culturally-relevant components, such as music and movies, which address issues related to the specific issue of substance abuse as well as larger issues about family, inner-city life, and other cultural components that may be relevant to African-American male adolescents. This culturally-specific therapeutic framework is intended to promote a strong level of engagement and participation among subjects, as opposed to a top-down model of information dissemination.

            The culturally-specific therapy is considered to be an adjunct of the larger model of Multi-Dimensional Family Therapy (MDFT), and it attempts to address the “oppositional culture” and the “code of the street” in which young African-Americans are often raised. By developing a treatment program which embraces these cultural components –rather than attempting to subvert the or simply ignore them- the treatment approach seeks to draw out positive cultural references that support the avoidance of substance abuse and to emphasize and reinforce such references as a means of promoting abstinence and avoidance of drug and alcohol use. In short, the MDFT approach attempts to make it “cool” to not use drugs and alcohol by promoting this view through the use of culturally-specific references that are likely to be acknowledged and accepted by subjects. The report asserts that this culturally-specific MDFT approach shows strong promise as an effective approach to helping young African-American males develop and individual identity that aligns well with their larger cultural frameworks and promotes the choice not to use drugs and alcohol.

Implications

            Crack addiction is just as much an emotional and psychological addiction as it is a physical addiction. Many crack addicts are afraid of being without the drug.  Crack addicts are often dual drug users, which mean their crack addiction is often brought on by the use of some other illicit drug. As a result, healthcare providers must address the problem in a dual method. They must first address the psychological issues that the addict may be dealing with. Once that is done, they can give the addict tools to use to handle stress and other life issues without turning to crack as a coping mechanism. Most African Americans are afraid of being labeled as mentally ill or a “crack head”. As a result, healthcare providers have to careful to treat them with respect in order to gain their much needed trust. Health care providers and mental health workers must collaborate, which will bring expertise from both backgrounds to the forefront in order to help crack addicts gain and maintain sobriety. Most importantly, health care providers must convey that they understand that crack addicts are essentially just like any other person. They have just made bad decisions, but have the potential to become productive members on society once again.

References

Baumer, Eric P. (1994).  Poverty, Crack, and Crime: A Cross-City Analysis. Journal of Research in Crime and Delinquency, 31. 311-327.

 Liddle, H. A., Jackson-Gilfort, A., & Marvel, F. A. (2006). An empirically-supported and culturally-specific engagement and intervention strategy for African-American adolescent males. American Journal of Orthopsychiatry75(2), 215-225.

Maranda, M.J., Han, C., & Rainone, G.A. (2004). Crack cocaine and sex. Journal of Psychoactive Drugs, 36, 315-322.

Substance Abuse and Mental Health Services Administration (2012). Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings. Retrieved from http://www.samhsa.gov/data/nsduh/2k11results/nsduhresults2011.pdf

Categories
Technology

Current and potential uses of technology for the global success of business objective

In a world where global competition is a common ground for ongoing business operations, technology becomes an element of operational success. Considerably, the modern world of business has began to embrace the fact that it needs to thrive in the constancy of making well established connections with other organizations from all around the globe. Establishing alliances and expanding towards the outskirts of the traditional locations of the organizations has become a sign of growth and business progress. In this case, technology becomes the bridge that connects the gap between business and branches as they entail to accept the mandate of operating globally and expanding their market control through affecting the global response to what they have to offer the public with.

            For organizations like the Microsoft Company, technology plays a primary role in the hope of gaining the attention of the global market while it operates on different parts of the world. The desire to expand has already become a reality for the company. As of now, its retaining power  in the industry still depends on the manner by which it is able to effectively manage technology as a source of its primary strength. To note, it utilizes technology for three primary operations. One is to connect its branches around the globe through a networked system of communication between its people. This way, it is able to establish a common organizational culture amidst the distance of its branches. Another process is that of its marketing. It entails to reach out to the market it hopes to serve through social media and other forms of technological operations such as that cloud computing to be able to make sure that its operation is able to mandate the growth of its market scope to the best of its ability. Third is operating its transaction with the clients it serves through the internet. Microsoft Company hopes to retain its market control through maintaining close control on its assets especially relating to how it functions with the technology it uses to manage major corporate operations.

Reference

Gremberge, W. Van , and S. De Haes, “A Research Journey into Enterprise Governance of IT, Business/IT Alignment and Value Creation”, International Journal of IT/Business Alignment and Governance, Vol. No. 1, 2010, pp. 1–13.

De Haes, S. and W. Van Grembergen, “An Exploratory Study into the Design of an IT Governance Minimum Baseline through Delphi Research”, Communications of AIS, No. 22, 2008, pp. 443–458.

Categories
Psychology

Reading Report

Source: Rutter, M., & O’Connor, T.G. (2004). Are there biological programming effects for psychological development? Findings from a study of Romanian adoptees. Developmental Psychology. 40.1, 81-94.

Problem: “The key question is whether, given the high quality of the later environment,

there were any persisting sequelae (among Romanian orphans who were later adopted into British homes) and, if there were, to what they might be due.” (p.81)

Procedure: The researchers began this study with an examination of a selection of children who lived in the difficult and challenging conditions presented in a number of Romanian orphanages from birth to ages four and five. The basic premise of their study was that these children, who were adopted out of these orphanages and into middle-class British homes, made an appropriate group of test subjects for research into what, if any,  effect(s) the difficult conditions in which they lived for their first few years of life would have on their development and behavior in adolescence and adulthood after they were adopted. The researchers considered three possible mediators for persisting psychosocial adversity (i.e.- developmental and/or behavioral issues) among the Romanian adoptees. The first was that ongoing psychosocial adversity, if it was demonstrated,  was a result of current conditions in their new environments; the second was that early-age cognitive processing either would or would not allow children to process and adapt to their early environments in positive ways; the third was that early adversity would bring about lasting physiological, psychological, and developmental changes that would make it impossible (or at least less likely) for these adoptees to avoid psychosocial adversity later in life. The researchers posited several hypotheses based on these three factors, with the aim of determining whether any of the three appeared to provide an adequate explanation for the presence or lack of post-adoption psychosocial adversity

In order to test their premises, the researchers drew from the “324 children adopted into UK families (from other countries) between February 1990 and September 1992” (p.84). Of this pool, 144 children were selected who had lived “in very depriving institutions and who were adopted into UK families at various ages up to 42 months” (p.84). The comparison sample consisted of 54 UK-born children who had been adopted at or near birth into UK families. The study considered a number of developmental measures, including physical measurements of height and weight at birth and at the time of the study, as well as information available about each child’s height and weight at various points in between. A number of psychological tests were administered as well, primarily intended to assess the existence of attachment disorders and psychological development disorders.

Findings: the study concluded that there was a strong association between early deprivation and poor physical, cognitive, and psychological development after adoption. The researchers found that most of the children demonstrated a “catch-up” (p.89) period in the first few years of life in their new homes where they tended to make notable improvements both physically and psychologically. This catch-up period seemed to last an average of 2-2.5 years, with any subsequently-remaining physical, psychological, or cognitive deficits appearing to become permanent.

The researchers concluded that early deprivation was an accurate determinant of lasting physiological and psychological adversity, and that subsequent environmental improvements were not adequate for completely reversing the damage of such early deprivation. Reaction: This study seems to demonstrate in very clear terms how important the first few years of life are in terms of physical and psychological development. When adverse conditions exist in this period of life, the damage can be severe, and regardless of whether later conditions are less adverse, much of the damage done in early childhood cannot be overcome or reversed.

Categories
Accounting

Balanced Scorecard Theory

Key performance indicators, financial assessments, return on investment, project schedules, budget estimates and a plethora of other tools and metrics are used to measure quantitative and qualitative variables in performance.  While there are key performance indicators and other metrics to manage, understand and provide data to make informed decisions there is still a need to have a more granular view on what is expected of the group being measured and the expected outcomes of the performance.  There are multiple areas that can be measured and analyzed to provide the data required to make informed business decisions.  These areas can be defined as financial, external, internal and growth.  By applying metrics across a broad spectrum of opportunities each area of the business can be measured and compared between each other.  This scorecard method allows insight into key metrics of the organization and allows a concise and focused effort that ultimately aligns the strategic intent of the organization to the defined measurements of the organization. 

Balanced Scorecard Definition

The objective of the balanced scorecard is to provide a quick and powerful tool so that anyone in the organization that has the need to know or understand the performance of their specific function can view and gain the perspective needed (Kaplan, R. and Norton, D).  This visual assessment allows for the managers and leaders of the organization to make informed business decisions to take the appropriate actions.  These actions taken by leadership would drive the change in the organization based upon achieving the performance standards outlined on the balanced scorecard (Monk, E., and Wagner, B).  This tool is used as a planning tool that aligns those actions on the tactical business operations level to the strategic intent of the business.  Prior to the utilization of the balanced scorecard theory businesses relied heavily on financial measurements to drive actions within the organization (Kanaracus, C.).  While this did provide a certain level of validity to the management decisions it did not provide the full picture required to make those tough business decisions in an ever changing and dynamic environment.

The early implementation of the balanced scorecard, although not officially named balanced scorecard until the 1990’s, was used by the General Electric Company in the 1950’s (Cooper, D. F., Grey, S., Raymond, G., and Walker, P).  The General Electric Company was driving toward a new and innovative way to align what was happening in the business and how to make changes in the manufacturing process to impact the final results of their process.  By measuring different variables in the organization the sourcing buyers, engineers, manufacturing team leaders and other members of the manufacturing and sourcing supply chains could make decisions based on these financial and non-financial key performance indicators to better their metrics.  Each change was then compiled into a scorecard to determine the strategic health of the organization.  The intention of the balanced scorecard has remained the same over the years but the ability to define metrics, measure variables and report results have become increasing intricate and beneficial across multiple business units in virtually all industries.

Balanced Scorecard Perspectives

The essence of the Balanced Scorecard Theory is to provide a fair and balanced approach that deviated from the original metrics associated with the business decisions.  The balance comes from defining metrics that work in a complimentary fashion as opposed to a financial centric focus that was previously used.  There were some inherent weaknesses and opaque perspectives that came from the pure financial view and the balanced scorecard approach provided a balance to the over strategic performance of the organization.  The balance also is seen as taking a different perspective on the company as noted before.  The four areas encapsulate the business in unique ways and can provide insight and vision into an area of the business that would be completed overlooked by other functions of the business (Leach, L).  The first are is the financial portion.  While this has always been included in the views and analysis of companies since the beginning of trade, the financial perspective is crucial to business decisions.  The question on what should be measured is based on how the success of the company is view by the shareholders of the company.  Financially, what is important to those with a vested interest in the success of the company?  The answers to this question will help drive the metrics needed to drive the objectives, measures, targets to the measures and the projects or programs that will drive these changes.

While the financial portion is aligned, measured and analyzed there are three other areas that need to be taken into account.  The next is the customer’s view.  This could be customers within the same organization or those customers in the traditional sense that are utilizing the final good or service as intended by the organization’s business model.  The leaders of the business must have a vision on what the organization will do in the future.  This could be growth in certain sectors of the business or expansion into new markets or product opportunities.  The vision is established by leadership so that the projects, objectives and efforts of the organization can drive the results required.  With the customer section of the balanced scorecard, the focus is centered on the ability to achieve the vision of leadership and how the customer measures that success.  These objectives are viewed as key performance indicators from the perspective of the customer. These objectives could be increased efforts for after hour support or availability of web-based applications.  These types of focus areas would drive the objectives, metrics and actions of the organization to meet the criteria outlined by the customer’s perspective.  This external view of the organization can shed light onto areas that may be neglected based on the mere fact that those creating the metrics and defining key targets do not have the external focus necessary to drive those types of changes.  Also without metrics based on these external focuses the business is not as likely to allocated resources to those types of projects considering they do not have the support or focus needed to be successful.  Without a measurement it is hard to determine progress or definitive results and benefits from a project (Prencipe, Davies, and Hobday).

After looking externally to drive results, the next area is internally focused based on processes, procedures and core capabilities.  The internal focus looks at the business functions that provide value to the organization, product or service that are seen as critical to satisfy the shareholders, customers, leadership and other entities that are reliant or collaborative with the business processes.  In order to satisfy those requirements, what business processes and functions are needed to run at the optimal performance level?  This question will drive the goals and objectives as well as the level of the target assigned to that objective.  Another area of focus for the balanced scorecard is neglected most of all in terms of a pure financial analysis of the company.  This area is the growth of the organization.  This growth is more than real estate, capital, work force or markets but it focuses on talent, agility, change management, functional expertise, adaptability and learning.  These areas are measured by their ability to improve the organization and change to meet the vision of the organization.

With all four areas the objectives there is a focus on building the objectives, measurements, target metrics and the projects.  Each perspective of the balanced scorecard will result in the definition of key requirements of the perspective.  These areas start with the objectives of the perspective.  These objectives are the outlined end states that are required from each perspective.  The end state is the deliverable or result of the business.  Within the objectives there are examples for each perspective.  The customer perspective could entail the view that each customer should have access to their accounts regardless of the core business hours.  This objective is from the customer’s perspective but does not have a definitive measurement around it.  The objectives tie into the measureable statistic of that objective.  For this example the measurement could become the amount of time the system is available each day.  This is the measurable aspect of the objective.  The metric is simple, measureable, attainable, relevant and simple.  These criteria should be present in all the measurable metric criteria on the balanced scorecard.  With the objective identified and the key performance measure outlined there must be a line or target established so that the person or group reviewing the balanced scorecard know how they are performing against the outlined indicators.  This target is established and provides that much needed sanity check for the team.  This target drives actions.  The actions required by the business lead to projects or other initiatives of the organization so that they can make the necessary adjustments to meet the objectives, measures and targets of the organization.

Alignment and Benefits

The vision and strategy is in the epicenter of this balanced scorecard.  Since the business has an overall view of the internal processes, external customer centric view, financial health and metrics of the organization and the growth metrics assigned there is an overall view of the business and its performance.  The crucial portion of all those metrics is how they measure the health of the organization, the progress toward the business’ vision and the success of maintaining those efforts to ensure a sustainable operating model.  The vision of the business and the results of the business’s financial and operational actions are linked together through the actions taken based on the balanced scorecard.  This strategic mapping of tactical actions to the vision of the organization is facilitate by the insight and guidance offered by the balanced scorecard.

As the objectives lead to metrics and the metrics establish targets which ultimately lead to the initiatives and projects of the organization there is a logical and deliberate map from the smallest enhancement project to the overall vision of the organization.  This linkage is one of the major benefits of the balanced scorecard and its application to business.  The actions on the lowest level of the organization have a direct correlation to the successful implementation and intent of the leadership of the organization.  Not only is the purpose and intent of those actions attached to the vision the actions are also measured and reported upon with the visibility required to garner the support and input by the key leadership positions.

The benefits of the using the balanced scorecard are just as varied as the inputs of the perspectives.  The overall objective and benefit of the balanced scorecard includes the ability to monitor, track and align the actions of the organization with definitive deliverables align to the vision of the organization.  Strategically aligning these actions allows the limited resources of time, funding and people to be adequately and effectively allocated to the project and programs that benefit the organization in the most impactful manner.  This alignment of key performance indicators aligns all levels of the organization and instills a sense of purpose knowing that the operation of a specific functional area of the organization is executing has purpose and direction.  The alignment of the vision to the operationalize functions also creates an opportunity for increased communication and collaboration between units since their scorecard metrics are also aligned with the vision of the organization.  This increased opportunity lends itself to increased creativity and innovation to solve real world issues and still understand what the end state must be and what key performance indicators are measuring success (Highsmith, J. A., & Highsmith, J.).  This clear picture of what success is and what areas require focus can facilitate the problem solving aspect of business and allow the ingenuity and innovation of the organization to solve those problems.

The balanced scorecard, if executed correctly, can create value within itself that could potentially create a competitive advantage.  This advantage comes from the inherent ability to create the translation between the vision of the leadership to the concrete and achievable actions throughout the organization.  The balanced scorecard also creates the opportunity to improve business processes, make informed decisions on business tactics and reduce the amount of noise in the data analysis and alignment process.  This is accomplished by analyzing already established business metrics that are continually reported upon and the variations from one reporting cycle to the next can be traced by to specific actions that occurred through the projects outlined in the scorecard.  Clarity and visibility into the key functions of the operations that are driving the key performance indicators allows a greater command and control upon the inputs of the operation and the manipulation of the expected results.  Understanding the needs of the company and how they align to the organizational vision can create that much needed clarity advantage throughout the organization (Kaplan, R. and Norton, D).

While the benefits of the balanced scorecard include the visibility into four different areas of the business including finance, internal business processes, customer or external focus and growth as well as the alignment to the vision of the organization there are still some potential disadvantages to the scorecard.  To execute the balanced scorecard there is a tremendous amount of preparation and planning to effectively and efficiently implement the use of the balanced scorecard.  The vision of the organization must be firm and established and the objectives of the organization must be clear and understood by those developing the balanced scorecard.  The balanced scorecard is also not the only tool needed to run the business.  While the tool is very useful it is not an all-encompassing metric and analysis tool to base all business decisions upon.

Case Study

Through the understanding of what the balanced scorecard stands for and looking to implement the tool into the organizational culture, the case study hits on some of the key fundamentals of the advantages and disadvantages of the balanced scorecard theory.  The advantages are sought out by the company to create that strategic alignment and visibility needed to be successful but the forethought and effort for the development of those metrics; deliverables and targets were not fully vetted and aligned with the vision of the company.  The Young, Martinez and Cheung (YMC) firm developed a set of strategic objectives which are aligned with the position of the firm and their core values.  The first step is complete but there still needs to have a measureable assigned to each strategic goal.  With each objective listed below there is a corresponding measure for that objective.

Financial

  1. Steadily increase the firm’s revenues and profits

Measure: 

  1. Determine the operating profit of the organization
  2. Determine the Revenue generated by services by function
  3. Determine Earnings before interest and tax            

Customer

  1. Understand the firm’s customers and their needs.

Measure:

  1. Count the number of customer complaints
  2. Count the types of services used by the customer
  3. Quantify the services provided by function
  4. Value customer service over self-interest.

Measure:

  1. Calculate work level for core operations
  2. Calculate Pro-Bono effort

Internal Business Process

  1. Encourage knowledge sharing among the legal staff

Measure:

  1. Track knowledge management inputs
  2. Track knowledge management views
  3. Calculate knowledge transfer/exchange session held
  4. Communicate with each other openly, honestly, and often

Measure:

  1. Count the number of brown bag lunch sessions
  2. Determine number of round table discussions held
  3. Count the number of closed door offices
  4. Empower staff to make decisions that benefit clients

Measure:

  1. Review quantity of decision review boards
  2. Quantify types of decisions being reviewed up the chain of command
  3. Measure the dollar amount associated with each decision type

Organizational Learning

  1. Maintain an open and collaborative environment that attracts and retains the best legal staff.

Measure:

  1. Count employee turnover
  2. Calculate case winning percentage
  3. Calculate settlement winning percentage
  4. Quantify attendance and sick leave
  5. Seek staff diversity

Measure:

  1. Calculate education
  2. Calculate experience in core business functions

While these measures are not all encompassing of the metrics required they are specific to each one of the objectives and are aligned with the vision of the company.  From those metrics a target will be established and from that target the company would know how to allocate their resources to fund and support the initiatives needed to meet those targets.

            The law firm can use the balanced scorecard to evaluate staff and make key business decisions regarding their performance and what the expectation are regarding their level of effort in different areas of the business.  With each different perspective there are measureable areas that can help guide the staff and provide a visual cue into what success looks like.  The balanced scorecard is utilized as more than a dashboard to key metrics.  The balanced scorecard allows the staff to determine the actions, efforts and level of performance required to meet the targets set forth by the organization.  These targets would provide the baseline measurement on the performance of the staff.  While the balanced scorecard can encapsulate what is required by the staff it must also be understood that many intangible assets of an employee must also be taken into consideration by the evaluating team.

Performance Based Incentives

When reviewing staff based upon the balanced scorecard there is a by-product of that analysis.  There is an inherent prioritization or rack-and-stack of staff on how well they execute the tasks outlined in the metrics of the balanced scorecard.  The question then becomes how to reward the high performers and how to raise the performance of those on the opposite end of the spectrum.  The balanced scorecard is an effective way to tie performance indicators from multiple different perspectives to the performance results of the staff.  This correlation provides a framework for tying compensation to the balanced scorecard results.  With the metrics that are individually based and focused this is possible but there are also other metrics that must be met as a group or functional area of the organization that cannot be tied back to a specific individual.  This could be a great way to promote incentive pay to user change in the organization but there is a fine line between driving results and pay for performance.  These types of decisions will also need to incorporate the culture of the organization and the type of environment the organization is trying to build.  The metrics will drive the actions of the organization and that can have a positive or negative impact depending on the end state deliverable.

Application

As previously discussed the application of the balanced scorecard is focused on the strategic alignment with the vision of the organization and the actions of the staff to achieve that vision.  The arduous part of utilizing the balanced scorecard is the preparation and implementation of the management tool.  There are key areas that must be taken into consideration for the implementation of the tool.  The first is the buy-in from leadership of the organization. The balanced scorecard is a top down implementation that requires the foundation to be laid and supported by leadership.  The success of the balanced scorecard hinges upon the correlation between the actions derived from the projects and the vision of the organization. To employ the balanced scorecard there must be an understanding of what results the organization wants to achieve from the implementation of the scorecard.  The objectives, metrics, targets and projects that result from the implementation of the scorecard are the real drivers of the change and the scorecard is the vessel into the visibility of that change.  The effort to commercialize the idea throughout the organization will also provide the opportunity to garner feedback and critical information on what to measure, how to measure it and what the intended results are.

            The balanced scorecard is a tool that will allow the strategic mapping of the vision developed by leadership to the key performance indicators that visually depict what success looks like for the organization.  The alignment of key functional actions throughout the organization will provide a synergistic approach to achieving success.  The balanced scorecard is the management tool that can provide that guidance and feedback needed to allocate resources to achieve the outcomes outlined by leadership in the vision.

Works Citied

Cooper, D. F., Grey, S., Raymond, G., and Walker, P. Project risk management guidelines, managing risk in large projects and complex procurements. John Wiley & Sons. 2005. Print.

Highsmith, J. A., & Highsmith, J. Agile project management, creating innovative products. Addison-Wesley Professional. Print.

Kanaracus, C. Survey finds erp software project overruns ‘distressingly common’. 22 June. 2013. Web. http://www.cio.com/article/710777/Survey_Finds_ERP_Software_Project_Overruns_39_distressingly_Common_39_?taxonomyId=3009

Leach, L. P. “Critical chain project management”. Norwood, MA: Artech House, INC. 2005. Print.

Magal, S. R., and Word, J. (2011). Integrated business processes with erp systems. RRD/Jefferson City: Wiley. 2011. Print.

Miller, D. “Building a project work breakdown structure: visualizing objectives, deliverables, activities, and schedules.” ESI international Project Management Series. Auerbach Publications. (2009). Print.

Monk, E., and Wagner, B. Concepts in enterprise resource planning. (3 ed.). Boston, MA: Course Technology Cengage Learning. 2009. Print.

Prencipe, A., A. Davies, and M. Hobday. The business of systems integration. Oxford University Press, USA, 2007. Print.

Project Management Institute. “A Guide to the Project Management Body of Knowledge (PMBOK Guide) Fourth Edition.” Project Management Institute. Newtown Square, PA. (2008). Print.

Kaplan, R. and Norton, D. “Using the Balanced Scorecard as a Strategic Management System,” Harvard Business Review (January-February 1996): 76. Print.

Wheelen, T. L., and Hunger, D. Strategic management and business policy, achieving sustainability. (12th ed.). Upper Saddle River, NJ: Pearson College Div. 2010. Print.

Categories
Accounting

Independent Auditors of the organisation’s accounts

The role of the independent auditor is to plan and perform the audits in order to obtain reasonable assurance of the financial records of the business and ensure these records are free from material errors. The independent auditor assesses the effectiveness of a company’s internal control system and its financial statements in order to develop an opinion as to the accuracy of these systems. Additionally the independent auditor’s task aims at addressing the risk of material errors and misstatements in the company’s financial records. The primary goal of external auditing conducted by independent auditors is to determine the extent to which the company adheres to managerial policies, procedures, and requirements. The independent auditor then forms an opinion as to the fairness and dependability of the statements of the company. This opinion is communicated to the appropriate body or board in the form of a report.

An independent auditor’s report is a formal opinion or disclaimer issued by the auditor concerning the accounting records, financial position, and the internal control system of a company. These reports are not evaluations but merely opinion as to whether the information existing is accurate and free from errors. These reports can contain unqualified opinion and this implies that the auditor’s opinion is that the financial accounts give a true and fair representation of the company. On the other hand, a qualified opinion report indicates that the auditor identified a few areas that do not comply with the required standards but the rest of the financial statements are presented fairly. An auditor can also give an adverse opinion report where the auditor establishes that the financial reports of the company are materially misstated and when considered in its entity they do not conform to the required standards. However, an auditor can fail to form a formal opinion usually due to various reasons and such an opinion is termed as a disclaimer of opinion.

The independent auditors make these reports on the fair presentation of the company financial records in accordance with any professional standards. The standards that govern independent auditors are either the Generally Accepted Auditing Standards (GAAS) or International Standards on Auditing (ISA). The independent auditors make reference to these standards in forming an opinion on the company’s financial presentation and in coming up with the auditor’s report. The purpose of these auditing standards is to provide engagement standards for the profession, outline the procedures to be followed, establish a guideline on engagement and set out professional ethics. The Generally Accepted Auditing Standards provide for the qualifications on an auditor and provides for the standard of work expected from an auditor. It also provides for the performance of the audit report and sets out the prerequisites necessary for the auditor to act independently. In essence, these standards govern the engagement of an auditor in conducting the audits. Similarly, the International Standards on Auditing governs the engagement of the auditor   in forming an opinion on the financial position of the company.  In addition, these standards provide for the responsibilities of the auditors and provide standards for the performance of audits. Conversely, the standards set out how audits are conducted including planning of audits, the collection of evidence, working with experts and the formulation of audit reports. Simply put, these standards define how auditors should conduct audits

Categories
Nursing

Global Health Issues

Global health issues affecting undeveloped countries have long been on the radar in the public eye, due to numerous infomercials and televised awareness campaigns to raise money for people in poor countries so that they have access to food, water, and healthcare. These awareness campaigns often report on millions of people in undeveloped countries dying due to the lack of resources and healthcare (Shah, 2011). This is an inequity in life that still exists in many parts of the world.

The World Health Organization (WHO) reports that almost 80 percent of noncommunicable disease deaths occur in lower income countries. In 2008, it is reported that 57 million people, globally, died from noncommunicable diseases such as cancer, diabetes, lung, and cardiovasular diseases, and about 25 percent of these deaths were people under 60 years of age. In addition, it is stated that improved healthcare, detecting diseases early, and getting people treated in time would result in a reduction of these deaths (WHO, 2010).

Scope of the Problem

            According to the Council on Foreign Relations, disease and death in undeveloped countries continues to rise inspite of new medical technologies and improved conditions in sanitation, nutrition, housing, and education. This is not just related to noncommunicable diseases; infectious diseases such as malaria, AIDS, SARS, the flu, and tuberculosis are also culprits and much of these occur in developing countries (CFR, 2013). The scope of this problem involves factors such as environmental health, maternal and child health, nutrition, ethics, and human rights issues.

            As it relates to environmental health, global health issues are often caused or made worse by negative environmental impacts such as pollution and health hazards caused by a lack in adequate sanitation of waste and water supplies. Satisfactory maternal and child health is affected by lack of resources, education, and healthcare access. Nutrition issues stem from low or non-existent food sources and little access to healthy food choices. In addition, ethics and human rights issues are related to all of the above. There is an unfair disparity in access to basic human necessities such as food, water, and healthcare, in undeveloped countries, and this speaks to a lack of ethics on the part of developed countries as well as of the governments of the undeveloped countries.

Solutions to the Problem

            As mentioned, improvements in healthcare access, early detection, and timely interventions are keys to eliminating much of the problems surrounding global health issues. However, most developing countries depend on health system funds from donors, which is not always reliable. Many developing countries receive up to 40 percent of their financial help from donor funds; however, there are times when the developing countries’ governments reduce their resource allocation, by up to 43 percent, to their needy when receiving assistance for health from other countries. Furthermore, many health systems in developing countries are undermined because of a shortage of healthcare professionals (less than 2.3 per thousand people), and this causes disparities in delivery of care (CFR, 2013).

Conclusion

            Unfortunately, it seems that there really is no immediate solution to the problem of global health issues, as long as obstacles such as governments blocking needed help from their countries and issues with poverty, sanitation, nutrition, education, and access exists. Poverty is the main cause of many global health issues. Poorer countries are often victims of the wealthy such as powerful pharmaceutical companies which is an example of a human cause, due to politics. Not all causes are natural causes. Addressing the problem of global health issues, therefore, is more a matter of social, ethical, and political factors that need to be changed before the world sees a reduction in unnecessary poverty, diseases, and deaths.

References

CFR. (2013, June 6). The Global Health Regime. Retrieved from Council on Foreign Relations: http://www.cfr.org/health-science-and-technology/global-health-regime/p22763

Shah, A. (2011, September 12). Global Health Overview. Retrieved from Global Issues: http://www.globalissues.org/article/588/global-health-overview

WHO. (2010). Global status report on noncommunicable diseases. World Health Organization.

Categories
Psychology

Week 3 Psych – Classmate Responses

  1. Question: Explain the three stages of memory. How might understanding how your memory works help you learn? What type of things can negatively impact your memory abilities?

Classmate Response: The sensory memory is the first part of the memory process. The sensory memory stores all stimuli that register on the senses, holding literal copies for a brief moment. The initial, momentary storage of information is typically forgotten within 1 second. Short-term is the second stage in the memory process. It can hold up to 7 items of information for about 30 seconds. In this stage of memory information is being encoded into long-term memory. Long-term memory is the third part of the memory process. This stage of memory is capable of storing unlimited amounts of information indefinitely. Information that is stored in this stage of the memory can later be retrieved for use. Some information can be lost with the passage of time. Understanding how my memory works is important for my learning process. By understanding how my memory works I will know what I need to do in order to probably store the information that I am learning in my academics. I will also be able to fix any issues in my memory so it does not affect my learning. Dramatic situations can affect the ability of my memory because they happen so fast and because I tend to block them. Trying to memorize too many things at the same time can affect my memory negatively. DQ1WK3 Lopez

The three stages of the memory process, namely, the sensory, the short-term and the long-term memory process, seem to be based upon a priority conferred to the initial sensory stage. For this schema implies that the sensory can thereafter become short-term or long-term; however, without the initial short-term phase, then the subsequent stages become impossible. Nevertheless, the question remains open: how does a sensory memory, for example, become a long-term memory? The answer of my classmate accurately addresses the importance of memory for learning: this can lead to academic success. However, arguably, what remains open is the following question: if we want to make a memory a long-term memory, what are the processes that allow this to happen? As my colleague writes, negative traumatic incidents may block “useful” memories – yet the question remains open, why do such traumatic sensory incidents become long-term memories, instead of something more useful to the organism? Here, it seems theories of memory must interact with theories of psychology and perhaps psychoanalysis.

Question: Explain the three stages of memory. How might understanding how your memory works help you learn? What type of things can negatively impact your memory abilities?

Classmate Response: The three stages of memory is first the sensory store which is the first part of the memory process. This section stores all stimuli that register on the senses and holds it for brief moments. The second stage is short term memory. This area has a limited capacity on what it can hold and will store up to 7 different items of information for about 30 seconds. Last is long term memory. Here is an unlimited memory store that holds information indefinitely.
I think that better understanding our memory and how it works will better help us learn by allowing us to explore what types of ways we learn best. Once we know this then we can stick to the best learning style we know. I also think that fully understanding and knowing a subject will better help us to understand all of it.
One of the main things that can negatively impact my memory abilities is when I am doing too many things at once. When this happens I tend to forget little things that I have done along the way and these things can end up being important areas that I need to remember. I can not overwhelm myself and add too much to my plate that I am forgetting important details. DQ1WK3 Burling

There seems to be, as my classmate points out, an undeniable connection between learning and memory. Basically, it comes down to an epistemological question: what does it mean for us to know something? As my colleage writes, “fully understanding and knowing a subject will better help us to understand all of it”; but what does fully understanding mean? For example, let us say I know all the processes by memory of how to drive a car with a gear-shift as opposed to an automatic car. I know in my memory from experience how this is done. However, if I cannot actualize this in practice, this memory is for naught. Therefore, understanding or knowing would seem to contain an element of being able to put this into practice: what negatively impacts our memory abilities can only be judged in this regard of our failures to practically actualize these same memories.

Question: Determine your memory style and explain how you might apply this information at work and at school.

Classmate Response: According to the questionnaire, my main memory style is visual. It states that my preference is to remember things in terms of the way they appear. In a past course I did a similar questionnaire. The questionnaire was to determent what kind of learner I am. That questionnaire stated that I am a visual learner. Both coincided that my preference is visual. I have always known that I am a visual person. If I see something or visualize something a couple of time it will go into my long-term memory. At school I can apply my memory style by taking notes to remember what I hear and to remember main things in my reading. For example, I can print transcript on video or audio in order to memorize the information. Most of my career is going to be based on paper work. Because of this paper work I will be able to memorize things. Social work has a lot of visualization, so it fits me good. For example, when I am at a meeting I will take notes to remember what happened during the meeting. DQ2WK3 Lopez

The memory style of my client is visual, and this means that an emphasis on, for example, visual stimulants is crucial to the learning process. However, what are the limits of visualization? For example, when we read a textbook, this information is presented to us in a visualized form according to the words given. However, the mere visual sensory perception does not mean that we understand what the words themselves mean. An element of speculative, critical and rational thinking seems to be part of understanding: it is not merely that we “photocopy” the visual elements before us in our memory, we must also critically and rationally think about them in order to grasp them and truly state that we have learned.

Question: Determine your memory style and explain how you might apply this information at work and at school.

Classmate Response: The test showed that my memory style is a tie between visual and kinesthetic. This means that my memory style is best used through remembering things in terms of the way in which they appear and also remembering things using my sense of touch. This will best apply to the information I utilize during work and school by reminding me to take extra good notes. I can refer back to my notes and easily remember the lesson that was taught. I also can utilize tools such as videos or hands on experience that I received. I have always considered myself a hands on learner, in order to learn something best I need to try it myself and do it over and over. I also at first need to watch a person and I take notes either on paper or in my head which help me remember important steps so when I get to doing the hands on part I am somewhat prepared. DQ2WK3 Burling

The test that showed my classmate’s memory style is a cross between visual and kinesthetic perhaps more captures what is at stake in memory: we cannot merely remember things to say that we understand them, in order to how to apply this information for school. As mentioned above, there is a question of knowledge, as opposed to merely a question of recollection which is at stake in this learning process. In this sense, the emphasis on what kind of a learner one is perhaps overlooks the question of what it means to learn and truly master a subject matter: can memory styles tell us this? They certainly can tell us what kind of learning is better suited for the individual. But how to translate this is a question I think that cannot be reduced to the memory style model for the above reasons.

Question: Based on the Bandura’s Bobo Doll experiment, in the social cognitive approach to earning, observation learning occurs by watching the behavior of others. What have you learned just by observation alone? Share your example.

Classmate Response: I observed a man giving an other man instructions on what to do with the doll when the child was present. The man hit the doll three different ways and each way had a different sound. The man punched the doll and kicked the doll. He also hits the doll with a wooden hammerer. He did all this while the child observed him. The child sat on the chair and keep his eyes on the doll and the man. The child kept close attention to what the man was doing. After the man stopped hitting the doll, the child got up and hit the doll. He copied every hit and sound the man made while he was hitting the doll. This video was very interesting, but the behavior of the child was noting new for me. As a foster parent I take a lot of  classes on the was children behave. Plus, the experience as a parent has taught me a lot. For example, my husband always makes a distinctive sound with is throat when he is upset. Well, now my daughter does the same thing and it makes me laugh. Children are very easily influenced and they will copy anything they see or hear. DQ3WK3 Lopez My classmate gives an example of the social cognitive approach that emphasizes learning from the behavior of others, whereby certain practices and reactions to phenomena dictate how the one learning reacts. In other words, we see behavior performed, and then perform in a similar fashion. However, how does this model understand diversity and originality in terms of our existences? The behavioral model, in other words, seems to be reductionist, reducing human existence to a human behavior that is always a copy of another previously viewed behavior. In this regard, we have to qualify what we learn from behavior, and distinguish it from instances of creativity that, to the extent that they produce something new, cannot be reduced to behaviorist model.

Categories
Communications and Media

Week 3 Humanities – Classmate Responses

  • Question: The Net Neutrality Case Study in Chapter 11 of Exploring Media and Culture talks about net neutrality and concerns regarding speed and access on the Internet. What are the implications of a potential decline of neutrality on the Internet? Would you personally be affected if neutrality on the Internet ceased to exist? If so, how? If not, why not?

Classmate Response: The decline of neutrality on the Internet as expressed in our reading would mean that service providers will no longer be treated equal.  This would open the door for a tiered system which would allow companies to pay to have their information delivered faster.  This would harm small companies who could not compete with the larger companies in paying for faster services.  The smaller companies would be put out of business.  I believe I, the consumer, would be affected if neutrality on the Internet ceased to exist.  The cost of doing business on the Internet would be passed to the consumer.  The companies, who are now paying more to have faster delivery of information, would in turn charge their customers more money for the service.  The smaller companies who were forced out of business are no longer an option to compete.  This would limit us to the companies available who would now be those that are paying top dollar to compete.  The cost will be passed to me, the consumer.  I think having laws in place is a good thing to prevent larger companies from squeezing out the smaller companies and from squeezing more money out of the consumer.  DQ1WK3Cohn

My colleague’s response concentrates on what he terms “service providers being treated equal.”  My classmate then goes on to speculate that this would lead to a “tiered system”, whereby capital determines whose information could be delivered faster. Certainly, the very phenomenon of net neutrality and its loss seems to depend on someone holding “power” in the system: in other words, neutrality is a synonym for a certain equality and democracy, whereas any loss of neutrality means that this same equality has been compromised. And certainly, it seems that the loss of this neutrality is tied to an economic concept of power, as my classmate points out: those who have access to capital may ultimately eliminate those who have less capital, and thereby decrease such neutrality.

Question: The Net Neutrality Case Study in Chapter 11 of Exploring Media and Culture talks about net neutrality and concerns regarding speed and access on the Internet. What are the implications of a potential decline of neutrality on the Internet? Would you personally be affected if neutrality on the Internet ceased to exist? If so, how? If not, why not?

Classmate Response: The implications of a potential decline of neutrality on the internet is that it will decline or slow down internet growth with large and small companies.  It will force internet providers to a second tier.  By reading the course material it will effect large companies such as AT&T, Comast, Verizon and others. These companies of course will not be happy about the speed and accessing the internet.  By doing this companies have to spend out more money to utilize a higher speed of internet.  It will have a downfall on small business as well and may put small business out of business or loose customers.  Yes I would personally be affect by neutrality on the internet if it cease to exit because I rely on my internet daily.  It will hinder me with my business and probably force me to shut down my office. DQ1WK3 Bailey

My classmate here makes an interesting point: he does not look at the decline of net neutrality in terms of an equality of equal voice, but rather in terms of the growth of the Internet as a whole. Namely, it is only through a diversity of voices that have access to the Internet which will allow the Internet to become plural and heterogeneous. This point seems to be entirely accurate: growth is dependent not on dominance, but rather on allowing new opportunities, which by definition combat stagnation. Accordingly, my classmate makes the quite crucial point that the decrease in net neutrality is an affront to the Internet itself.

Question: Do you think the Internet can make democracy work better? If so, how? If not, why not?

Classmate Response: If when you speak of a democracy, you are speaking of the way we vote in elections?  Then I would say no.  It would not make a Democracy work better.  There is no accountability and no way to verify who people say they are.  In the United States, if the state you live in grants you the right to vote in state and federal elections.  You can not do so legally until you reach the age of eighteen, and then you get one and only one vote per ballot per candidate.  There is no way to be certain that I am not going under another name to vote using the internet.  It’s bad enough that people will already vote more than once in person using different means of deception.  Just imagine what would happen if it were done over the internet.  We would have people from Tibet voting in our elections just to mess with us. DQ2WK3 Sloan 

The classmate frames the question in fully specific terms: that is, if the Internet may serve as a pragmatic tool for democracy, namely, how the Internet may be used in the voting process. Afterwards, the colleague gives various examples of how such a voting system in regards to the Internet may be the victim of electoral fraud. However, this is only the question of how a democracy would pragmatically implement the Internet for voting; my classmate therefore overlooks the democratic essence of the Internet itself. As I stated in my own answer, in so far as the Internet is democratic, that is, that it allows for a plurality of voices, the Internet can be used as a model for how democracy should function, instead of merely the Internet being a tool which existing political systems can use: in short, the Internet forces political systems to think if they are truly democratic, because of the Internet’s democratic plurality.

Question: Do you think the Internet can make democracy work better? If so, how? If not, why not?

Classmate Response: I personally believe that the internet would hold no value to democracy except for maybe getting issues out into the public. Government controls and biases of the people posting information on political heads would make to much noise and cloud issues even further. This could flood the knowledge pool with more deception and misinformation than we already receive, and create more serious issues. If there were sites that were third party reviewed for factual content then the internet could possibly work for democracy. Questions could be answered and facts that politicians speak on could be verifiable. It is an interesting concept but, in the terms of using the internet to better democracy I can not see it working well. There are to many influential people setting the pace for our opinions and beliefs and what we are exposed to in our media. These powers that be have been studying the human reaction and actions for way to long not to be able to steer the public opinion. DQ2WK3 Alger

My classmate looks at the question from the perspective of what the Internet can do for the existing political establishment. However, as I noted in my own response, I think this overlooks the fundamental point: it looks at the question from the perspective of the political establishment and how they can use the Internet. As I have suggested the more fundamental question is as follows: because of the very plurality of the Internet, there is a sense in which the Internet is more democratic than the political institutions that claim to be democratic. We have to understand that democracy is an idea that does not belong entirely to the political sphere, and can be realized in other forms, such as the Internet, after which the task becomes, if we are tied to democracy, to make our political institutions more democratic based on non-political examples.

Question: Do you think the concentration of media ownership limits the number of voices in the marketplace? Explain.

Classmate Response: Yes, I think the concentration of media ownership could limit the number of voices in the marketplace.  I think it mainly has to do with the motivation of the owner.  If the owner’s only agenda is to make money then it would be wise to own a little chunk on both sides of the isle.  This way you sell a little to the left, a little to the right, and then sell what’s left to those in the middle.  Who really cares about the views of the red or the blue because all of their money is green.  Now, on the other side of the coin.  If the owner does have a right/left side leaning in politics and his holdings reflect his views.  Then the owner will only profit off of the one side.  This could also be said of sports media as well.  Someone selling a magazine devoted exclusively to Ping Pong may appeal to some.  But if the owner had a magazine that appeals to more than just this one game of this type.  Now you have cast a broader net to catch more readers. DQ3WK3 Sloan 

My classmate makes the crucial point, in my view, that if the motivation behind media concentration is money, then corruption can occur, in so far as this approach means to limit voices to accrue a profit. But is this not the same problem with any type of domination and control? Any time power is at stake, some one is trying to silence the voice of another, and media concentration by definition means that only one voice is heard: in this regard, concepts such as hegemony, from political science, can help us understand that any exertion of “media concentration” implies an attempt to dominate another and thereby eliminate a democratic plurality of voices.

Question: How do you know whether you can trust Wikipedia or another online resource?

Classmate Response: First of all, I have to mention that I do use Wikipedia more often that not when it comes to non-academic research. I think that it can provide some good information; however, I would never use it as a reference for any of my academic research essays, nor anything that had to do with school. Even though sites like Wikipedia are somewhat trustworthy, there is also some reason to not trust it’s sources sometimes. On sites such as Wikipedia there are thousands – if not millions – of information that has been typed up by any person, in other words, a non-authentic source — and authenticity is a big deal for me(!). Authenticity is something we as university students should focus on with emphasis because in the end we always have to provide a good batch of from where we got our references from. For example, if we ever come across a search result off of Wikipedia and it does not have it’s direct informational source(s), then it is not something we can trust! DQ4WK3 Hernandez

My client notes that Wikipedia itself should never be cited for academic research, which is entirely accurate, because a given Wikipedia article may be changed at a whim by whomever and at whatever time. This, however, does not mean that Wikipedia articles cannot provide a starting point for research, since most Wikipedia articles include sources and quotations, which allow us to cross-reference the information: Wikipedia can be a constructive tool, but the research, student or academic cannot merely accept it at face value, which is both naïve and ignorant. Rather, Wikipedia becomes a source just like any other source for the academic: if one finds a quote in a printed book, this does not mean that this information is accurate, simply because it is printed. One has to continually double and triple check sources, and Wikipedia, in this sense, can help us become even more rigorous in our studies, since it forces us to think about where our information is coming from.

Question: The digital divide refers to people that have access to digital media versus those that do not. Are people who do not have a smartphone at a disadvantage (that is, are they on the wrong side of the digital divide)?

Classmate Response: I do not think that people that do not have a smartphone or any other new device is at any disadvantage more than anyone else.  If this is how they wish to live, I do not see a problem with it.  I look at what all smartphones are capable of like texting, surfing the internet, taking pictures, playing games, multiple apps, listening to music, and I almost forgot.  You can even make a phone call from them. Now, I look at what all I use one for.  I do like having internet access available to me if I need to use it, but I will not have a fit if I do not use it.  In fact, I like to leave my phone in the car whenever my family and I go into restaurants.  It is very seldom that I will take a cell phone in there while I’m with my family.  I just think it is not needed especially while I am eating with the people that I would get up from the table and leave for.  Everybody else can wait thirty minutes or so until I finish and check my phone for calls when we get back into our vehicle. DQ5WK3 Sloan 

My classmate discusses the possible advantages or disadvantages of having a smartphone in terms of individual choice: in other words, the decision to now have a smartphone or have one is merely an autonomous decision. My colleague then mentions some of the pragmatic advantages of a smartphone. The question I would ask from this answer is as follows: to what extent are individual choices and pragmatic choices interrelated? In other words, sometimes, if something is practical and we need it, we have no individual choice: for example, the modern student seems to be unable to function with a computer or the Internet. Therefore, reducing everything to merely individual choice overlooks the role the social discourse and social structure plays in shaping our choices.

Question: The digital divide refers to people that have access to digital media versus those that do not. Are people who do not have a smartphone at a disadvantage (that is, are they on the wrong side of the digital divide)?

Classmate Response: The digital divide also explains and is defined in the text as the knowledge on how to use the technology that is currently available to access the media. So I would have to say, yes, a person without a smart phone is on one side of the digital divide. I can not say if it would be on the right or wrong side, because after reading some of the downsides of technology and there affects on culture, I do not know if technology is such a positive thing for everybody. Personally I do not have a smart phone, I never had one so I do not miss it. That being said my wife has one and every now and then I get a little jealous because of the things she can do with her phone any where she goes. I still need to get up and go to a computer, or stop and ask for directions. DQ5WK3 Alger

My client addresses the digital divide in terms of the textbook definition, whereby the digital divide refers to the knowledge of how to use the current technologies. But I would ask a subsequent question: why does this divide itself exist and who controls these accesses to knowledge? It would seem that such access is inevitably not the result of technology, but rather economics and social discourses which allow such access and potentially knowledge. Therefore, as I argued in my own answer, the digital divide and whether or not one has a smartphone has to be seen as symbolic of a greater social question: firstly, who controls the access to technology and its mastery?; and secondly, if such access is not free to all, why is this the case? This would seem to introduce a political element into the concept of the digital divide, however, one that seems entirely justified.

Categories
Nursing

Heart Disease in Baltimore

Introduction

            The development of a successful framework for managing heart disease in any community requires an effective understanding of the demographics and the challenges that groups face in support of developing strategies to improve outcomes. In particular, heart disease is a challenging condition that must be considered and evaluated in order to reduce risks and improve outcomes for community members. The following discussion will evaluate heart disease in Baltimore, MD in order to identify different strategies that might be useful in expanding knowledge and information regarding this condition to prevent serious complications.

This discussion will also address the importance of communication within nursing practice as a means of exploring the different dimensions of care and treatment that is required for communities such as Baltimore, MD. Nursing possesses a series of different ideas and expectations within the culture that must be addressed in an effort to produce successful outcomes in the area that emphasizes various communication strategies. These efforts will provide support in determining how to best utilize group communication as well as one-on-one communication to identify and solve problems effectively. These efforts will demonstrate the importance of nursing communication in supporting successful patient care and treatment outcomes at all times.

Part 1: Community/State Demographics     

            Baltimore, Maryland is a very diverse community with many different health concerns and a strong necessity to facilitate health promotion activities. Heart disease is a number one killer throughout the United States and carries a high degree of risk for many communities, including the Baltimore area. With the 2012 Census, the city of Baltimore had approximately 621,342 residents, of which 52.9 percent are females and 63.6 percent are African Americans (US Census Bureau, 2012). Whites make up 31.5 percent of the population and only 4.3 percent are of Hispanic or Latino origin (US Census Bureau, 2012). Almost 80 percent of this population has a high school diploma and 26 percent has earned a Bachelor’s degree or higher, with 50% owning their own homes (US Census Bureau, 2012). The median household income for 2007-2011 was $40,100 and 22.4 percent of the population is below the poverty level (US Census Bureau, 2012).  

            In the State of Maryland, there are 5,884,563 residents, with females comprising 51.6 percent of the population, while 61.1 percent are White, 30 percent are African American, and 8.4 percent are Hispanic or Latino (US Census Bureau, 2012). Within the State, 88.2 percent of the population has earned a high school diploma and 36.1 percent has earned a Bachelor’s Degree or higher, with a home ownership rate of 68.7 percent (US Census Bureau, 2012). Finally, the median household income for the State is $35,751 and 9 percent of the population lives below the poverty line (US Census Bureau, 2012). Based on these statistics, the City of Baltimore faces greater socioeconomic challenges than those of the State of Maryland, including the potential for greater health disparities. Therefore, it is important to identify these disparities and to address cardiovascular disease within the City as a serious health issue and a formidable threat to this population.

Part 2: Health Status

            The Baltimore City Health Department routinely provides reports regarding the health status of its local residents and identifies specific health disparities that require further consideration. Although some areas have experienced slight improvement, there continue to be many health disparities that must be addressed to improve outcomes throughout the city (Baltimore City Health Department, 2010). In general, the city fares worse than the State of Maryland in such areas as heart disease and infant mortality; therefore, the City must utilize its available resources in order to accomplish improved health outcomes throughout this community (Baltimore City Health Department, 2010).

Within Baltimore County, cardiovascular disease claims approximately2,000 lives annually; therefore, this community must identify methods to better manage existing disparities and to encourage greater compliance to improve health and wellbeing (Baltimore City Health Department, 2009). An agenda was established by the City Health Department in an effort to reduce the risks associated with cardiovascular disease and included such topics as reducing salt intake, expanding blood pressure screenings, enhancing health education by using Faith-based approaches, and smoking cessation efforts (Baltimore City Health Department, 2009). These efforts demonstrate the important impact of health promotion for this population group in order to reduce disparities and to improve outcomes (Baltimore City Health Department, 2009).

Within the City of Baltimore, there were approximately 200 deaths per 100,000 members of the population as a result of coronary heart disease in 2008, which is 53 deaths above the state average (Maryland Department of Health & Mental Hygiene, 2009).These findings suggest that Baltimore residents do not manage their overall cardiovascular health and face critical challenges that require additional education and guidance from community members (Maryland Department of Health & Mental Hygiene, 2009).Within the City of Baltimore, evidence also demonstrates that African Americans experience higher rates of death as a result of cardiovascular disease as compared to other population groups, thereby mandating additional education and prevention efforts within this community (Johns Hopkins Urban Health Institute). Furthermore, African Americans within the city have a higher rate of obesity than Whites (Johns Hopkins Urban Health Institute). These statistics provide further evidence that cardiovascular disease in Baltimore is higher in some population groups than in others, supporting the belief that these groups experience greater health disparities (Johns Hopkins Urban Health Institute).

In an examination of statistics evaluating specific neighborhoods of Baltimore, every single neighborhood that was evaluated, from wealthiest to poorest, reported heart disease as the leading cause of death (The Baltimore Sun, 2011). Therefore, it is important to identify different methods to promote the expanded delivery of healthcare services and health promotion activities to improve outcomes for this population group (The Baltimore Sun, 2011). In addition, it is important to recognize the value of surveys and discussion groups to identify health disparities in order to improve outcomes and to reflect on existing frameworks to achieve greater results. According to a study conducted by the National Heart, Lung, and Blood Institute (NHLBI) in public housing units in Baltimore, “Public housing residents had a preexisting knowledge and awareness of heart healthy lifestyles and CVD risk factors…One cardiovascular risk behavior, cigarette smoking, is pervasive among the demographic groups probed (excluding teen females) and accordingly smoking cessation is a critical element of any community outreach strategy that would be developed. Stress, from environmental and personal stimuli, is also cited by participants as a major barrier to improving health, including young adults ages 15–18. In fact, many participants cite stress as a primary risk factor for heart disease and a barrier to heart disease prevention” (NHLBI, p. 2). Based upon these indicators, it is necessary to evaluate the conditions that are evident within this community in an effort to improve knowledge and prevention strategies to reduce cardiovascular risks (NHLBI). The efforts that are made to conduct interventions throughout Baltimore are likely to be effective in providing knowledge and information to local residents who might improve their own health outcomes in the process.

One of the most staggering discrepancies in Baltimore regarding the health of its population is life expectancy, which differs by 20 years in some communities (Cohn and Marton, 2012). For example, the Roland Park community has a much higher life expectancy rate and a higher median income at $90,000, while Upton has a much lower life expectancy rate and a lower median income at $13,000 (Cohn and Marton, 2012). Nonetheless, heart disease is the number one killer in both communities; however, prevention and awareness of the disease vary dramatically (Cohn and Marton, 2012). These findings suggest that the residents of Baltimore in throughout all communities must be aware of the risks associated with heart disease, but that those in lower income communities must be provided with greater interventions in order to improve their cardiovascular health and wellbeing over time (Cohn and Marton, 2012). It is important to recognize these disparities and how to overcome the discrepancies in the health of Baltimore residents so that the risks associated with heart attack, stroke, and other conditions are reduced as best as possible (Cohn and Marton, 2012). In addition, this population group must be provided with the appropriate level of access to healthcare screenings and services in an effort to produce successful outcomes for individuals and families who are at the greatest risk for cardiovascular disease (Cohn and Marton, 2012).

            Finally, the development of a successful approach to prevent heart disease and improve disease management to prevent high mortality rates requires an effective understanding of the disparities that exist throughout Baltimore, particularly those that occur across minority groups. Since there are significant discrepancies in Baltimore in regards to specific populations, it is important to evaluate these differences and to take the steps that are necessary to provide local residents across different communities with     the tools and resources that are required to improve their health and reduce their risk of heart disease through healthy lifestyle choices and other factors that will improve their health and wellbeing in different ways.

Part 3: Communication Methods

            Nurses must exercise different methods of communication in the workplace and in working specifically with patients. One of the key factors to consider in this practice is time because there is typically limited time to address concerns with patients and with colleagues in the face of significant workload concerns (Hemsley et.al, 2012). Therefore, time is a critical component in managing communication between nurses and patients in different settings and in supporting the development of new perspectives to ensure that patient care is not compromised as a result of time constraints (Hemsley et.al, 2012). These efforts are important because they provide greater evidence of the ability of time to play a substantial role in how communication is addressed between nurses and their patients in different ways (Hemsley et.al, 2012).

            In the context of quality patient care, nurses must demonstrate their willingness to communicate with their patients through the utilization of structure and leadership in supporting effective communication between patients and with colleagues (Baird et.al, 2012). Nurse leaders must recognize that communication is a critical component of nursing practice and that nurses must identify areas of strength and weakness to ensure that patient care is not compromised in any way (Baird et.al, 2012). In addition, nurse leaders must establish the tone and an example for other nurses to follow in their efforts to develop effective communication in group settings and in one-on-one exchanges (Baird et.al, 2012). Also, nurses must develop effective skills to encourage interdisciplinary collaborations with colleagues to promote greater quality of care and treatment in these settings (Coeling and Cukr, 2000). Collaborations of an interdisciplinary nature are designed to strengthen knowledge and address weaknesses within team-based settings to facilitate improved quality of care over time (Coeling and Cukr, 2000). Similarly, team-based environments often encourage new approaches to common patient care problems and facilitate holistic strategies to promote care and treatment that not only support patients, but also clinical staff members in their own learning (Kvarnstrom, 2008).

Effective Communication Strategies

            Communication throughout nursing practice requires an effective understanding of the different elements that support idea sharing and positive outcomes. To be specific, “The main intention of communication and interaction in the health setting is to influence the patient’s health status or state of well-being… The process of communication is often described with a phase model; communication often happens during other interventions and tasks. In general, influencing factors can be organized into the categories of provider variables, patient variables, environmental and situational variables” (Fleischer et.al, 2009). From this perspective, it is important to demonstrate that nursing communication strategies are dependent on specific models and indicators that are grounded in other experiences to ensure that patient care experiences and interactions are not compromised (Fleischer et.al, 2009). At the same time, it is important to identify the specific phases of communication that are common in nursing practice in order to accomplish the needs of patient care and treatment in different ways to improve patient wellbeing (Fleischer et.al, 2009).

            Many different communication strategies are available to nurses to enable communication to be effective in their associations with other nurses and with patients. Therefore, one strategy to consider is collaborative communication, whereby “Collaborative communication and teamwork are essential elements for quality care and patient safety. Adverse patient occurrences are an extremely common outcome of communication failures…Although improving communication has been included as a Joint Commission’s National Patient Safety Goal for hospitals since 2003, in 2006, handoff communications were included as a specific communication subset” (Beckett and Kipnis, 2009). Under these conditions, it is expected that effective nursing care and treatment will be achieved through the continued efforts by nurses and nurse leaders to exercise effective communication at all times and to demonstrate the importance of collaborative communication in supporting all aspects of patient care at all times (Beckett and Kipnis, 2009). In particular, situations involving handoffs of patients to the next shift are particularly important in demonstrating that nurses are capable of handling communication in an effective manner (Beckett and Kipnis, 2009). These efforts are also important because they convey the importance of specific needs and challenges that patients face when nurses are unable to communicate effectively with their colleagues and with patients (Beckett and Kipnis, 2009). For many organizations, the basic task of shifting communication styles is important because it provides significant evidence that there are improvements in patient communication by nurses once these strategies are rolled out (Beckett and Kipnis, 2009). Therefore, it is important to identify the strategies that are likely to be most effective in this process and to ensure that they are executed as best as possible in nursing settings and across all population group (Beckett and Kipnis, 2009). This practice is essential to the discovery of new ideas and techniques to demonstrate the successful impact of patient care and treatment in a manner that is consistent with nurse professionalism and strength (Beckett and Kipnis, 2009).

Barriers to Communication

            In working with specific population groups, nurses must also demonstrate their ability to engage patients by expressing communication with respect to culture and language differences. Therefore, nurses must be able to effectively communicate with all patients and to recognize that in some cases, there are likely to be barriers to this communication unless interventions are conducted for these patients, such as the use of an interpreter for patients who speak a different language (Fatahi et.al, 2010). This is particularly important when providing technical information to patients to remove language barriers whenever possible so patients better understand what is taking place (Fatahi et.al, 2010).

            Oncology nurses, for example, barriers to communication are a common phenomenon that is characterized by the development of specific limitations in communication as a result of the poor translation of information by other healthcare providers, perhaps on different shifts or in different departments, thereby leaving patients and their family members confused regarding the information that they have received (Wittenberg-Lyles et.al, 2013). In addition, the article indicates that “Physician assumptions about nursing left nurses feeling uncomfortable asking for clarification, creating a barrier to team communication processes. Patient-centered communication and care cannot be actualized for nurses unless team roles are clarified and nurses receive training in how to communicate with physicians, patients, and family” (Wittenberg-Lyles et.al, 2013). This example demonstrates that there are significant barriers to effective communication by nurses to patients and their family members, often based upon confusion created by other healthcare providers (Wittenberg-Lyles et.al, 2013). These efforts are important because they convey that there are considerable weaknesses in the communication practices of other nurses and physicians, thereby creating much communication across different departments and nursing units (Wittenberg-Lyles et.al, 2013). As a result, it may be difficult for organizations to overcome these barriers unless additional training and clarification is provided to nurses to ensure that these barriers are eliminated or minimized as best as possible (Wittenberg-Lyles et.al, 2013).

            For nurses working with children and parents, there are other types of barriers and challenges that may exist that must be addressed as best as possible. However, some nurses might not possess the appropriate method of working with these patients and should be sensitive to the needs of this specific population group (Redsell et.al, 2010). Therefore, these needs must be met through the understanding of nursing-based perspectives and how these might influence communication in different ways so that the needs of this population are better met during nursing communication practices (Redsell et.al, 2010). The efforts that are made also demonstrate the attitudes of nurses regarding their patients and the treatments that they receive, because in some cases, these perceptions could be distorted by specific beliefs or judgments that are not beneficial to patients (Redsell et.al, 2010). As a result, it is important to identify the specific indicators of communication that are necessary to ensure that patient care is optimized at all times (Redsell et.al, 2010).

            For nurses seeking to improve their communication skills, it is important to recognize the value of developing new perspectives and approaches to nursing practice that will enhance communication in different ways. This may involve interventions that are likely to identify problems in such settings as chronic care, for example, so that there are sufficient opportunities to recognize problems to improve communication as best as possible (Boscart, 2009). In many organizations, ”Positive nurse–patient communication in chronic care is crucial to the quality of life and well-being of patients. Despite this, patients are dissatisfied with these interactions and nursing staff indicate the need for additional training” (Boscart, 2009). Therefore, it is necessary to identify specific areas where communication might be improved to reduce barriers and to expand patient compliance in chronic care settings (Boscart, 2009).

            Collaborative learning requires successful communication and the elimination of barriers through role clarification and trust amongst team members (U.S. Office of Personnel Management). This is best accomplished through flexibility and a full commitment to the team’s purpose and function (U.S. Office of Personnel Management). Furthermore, the development of effective critical thinking skills is essential in promoting productivity and encouraging a clear approach to a given problem in order to develop an effective solution (Elder and Paul). Higher level thinking and analysis must evolve so that individual contributions to teams and to the patient care experience are effective (Elder and Paul).

Health Assessment

            Baltimore, MD is a large metropolitan community that faces similar health risks to other communities with respect to heart disease and related conditions. It is important to identify the specific population groups that are most affected by this condition and to determine how to best approach disease management in order to facilitate optimal outcomes for this community. The City of Baltimore faces a great risk of heart disease that is not that unique from other communities; however, Baltimore has its own set of population demographics that must be properly identified and addressed so that the proposed action plan will be most effective for this community. Therefore, nurses and other healthcare professionals must take the steps that are necessary to create an action plan that will target this community and provide the necessary benefits as effectively as possible. An effective community-based assessment is critical to the success of a given strategic approach to improve public health initiatives and wellbeing (Williams, 2009; Walker et.al, 2011). Health assessments also require an analysis of specific populations in order to improve health promotion activities across these groups (Harris-Roxas and Harris, 2011).

            From an environmental perspective, it is important to identify specific indicators that may impact health assessments and promotion activities within communities (Collins and Koplan, 2009). Team-based activities are critical during the assessment process and support the expansion of activities for a given purpose (Elder and Paul), while also considering the impact of these activities in the team setting (U.S. Office of Personnel Management). Perhaps one area to consider is specific needs assessments for elderly persons versus younger age groups, with the former more likely to require advanced directives due to age and other factors (Taylor, 2012). Miller (2005) demonstrates that communication within a given setting is critical to the success of a healthcare directive and should be utilized in team settings to facilitate positive outcomes. Furthermore, collaborative efforts in a community-based setting should signify a commitment to the initiative and the people that it serves through effective communication channels, rather than weak ones (Kvarnstrom, 2008; Coeling and Cukr, 2000). Laverack (2006) encourages community empowerment through the development of specific initiatives that are designed to promote health and wellbeing. A successful example is the Kaiser Permanente Community Health Initiative, which has been effective in providing tools to local residents who otherwise might not have access (Cheadle et.al, 2010). Some community members may possess specific beliefs regarding therapies that may support improved health, but these are not always easily understood, including the use of alternative therapies to treat chronic illnesses (Fennell et.al, 2009; Hassan et.al, 2010; Ndao-Brumblay and Green, 2010).

            For the City of Baltimore, approximately 200 deaths occur per 100,000 members of the population resulting from coronary artery disease, which is well above the state average (Maryland Department of Health & Mental Hygiene, 2009). Therefore, it is strongly evident that many residents in Baltimore who face a greater risk of heart disease may not recognize this risk or are not taking the steps that are necessary to improve and maintain their own health (Maryland Department of Health & Mental Hygiene, 2009). In particular, African Americans face the greatest risk as a result of this condition and their needs must be addressed as a key component of a larger community-based effort to promote heart health and wellbeing, including the reduction of obesity rates within this population group (Johns Hopkins Urban Health Institute).

            According to the Baltimore City Health Department, “Baltimore, home to 637,455 people, is located in the wealthiest state in the nation, yet has nearly 20% of its residents living in poverty. Many of these are the working poor who cannot afford health insurance and who are frequent, but inefficient users of the healthcare system” (Baltimore City Health Department, 2009, p. 4). Under these conditions, it is important to identify the specific factors that play a critical role in the continued growth of the heart disease epidemic within Baltimore, given that poverty impacts approximately one-fifth of the City’s population (Baltimore City Health Department, 2009). Under these circumstances, outreach and prevention are difficult to accomplish when this population group do not have access to health insurance and services at all, or this access is severely limited (Baltimore City Health Department, 2009). These findings suggest that it is necessary to identify specific indicators that may reduce the risk of heart disease within this population through the development of an action plan that will address these concerns in a comprehensive manner to improve overall awareness of heart disease and the risks associated with this condition throughout the City of Baltimore.

Action Plan

            An action plan to reduce the risk of heart disease for Baltimore residents requires an effective understanding of the specific risks and challenges of this group and their level of understanding of this condition and how it impacts their daily lives. Some of the most important factors to consider include the following: “Cardiovascular disease behavioral risk factors include: inadequate physical activity and exercise, poor dietary habits, tobacco abuse and excessive alcohol intake. Community-based approaches seek to understand and address aspects of the socio-cultural environments that impact behavioral risk factors. Using the affected communities as the setting for intervention allows increased awareness and better understanding of the barriers and facilitators to behavior change” (Baltimore City Health Department, 2009, p. 9). These circumstances coincide with the lack of understanding of the specific factors that contribute to negative outcomes for this population and the challenges that they face, either without any form or health insurance or very limited coverage, both of which may lead to considerable consequences for their health and wellbeing (Baltimore City Health Department, 2009). Under these conditions, it is important to identify the specific factors that are represented by these phenomena in order to determine how to best move forward with action plan that is most appropriate for the needs of this population (Baltimore City Health Department, 2009).

            The utilization of local community-based services and principles is essential to the discovery of new perspectives and strategies to improve the cardiovascular health and wellbeing of Baltimore’s population. This is challenging because it requires an effective understanding of the limitations placed on residents due to their lack of knowledge and experience with cardiovascular disease and how it impacts their health in different ways. It is likely that a lack of knowledge regarding diet, nutrition, physical activity, tobacco use, and alcohol consumption are key contributors to the elevated risk of heart disease within this community (Baltimore City Health Department, 2009). Therefore, it is recommended that there must be additional factors in place that will promote a successful action plan for widespread implementation throughout this community (Baltimore City Health Department, 2009).

            Baltimore’s population faces risks that are not that different from other communities with respect to heart disease. Therefore, lessons learned across other populations might be useful in developing a strategy for this community and its people. The action plan that is chosen for implementation must consider the following key areas of development: long-term impact, the capacity for continuous development and expansion, improving policy, moving forward with an action strategy, and expanding collaborations with other communities (CDC). It is known that “The economic costs of heart disease and stroke rise each year. These costs include the numbers of people requiring treatment for risk factors or early signs of disease; emergency treatment for first or recurrent episodes of heart attack, heart failure, or stroke; and efforts to reduce disability and prevent recurrent episodes” (CDC, p. 4). These findings suggest that it is more important than ever to develop strategic approaches that will facilitate the support of new ideas and community-based initiatives to encourage cardiovascular disease prevention as best as possible for Baltimore residents (CDC).

            The impact of a strategic action plan to reduce the risk of heart disease also requires an effective understanding of the risks associated with this condition. Behaviors are perhaps the key to understanding how individuals respond to heart disease and in establishing its overall impact on health and wellbeing for a given community. In Baltimore, this appears to be particularly relevant because lifestyle behaviors for many members of the affected population lead to greater risks, including poor dietary consumption, smoking, excessive sodium intake, and limited physical activity, amongst others. Under these conditions, it is important to identify the specific areas where behavioral improvements might occur so that cardiovascular disease risk is significantly reduced.

            An action plan to reduce heart disease risk for Baltimore residents requires a detailed assessment of the population and its current lifestyle behaviors because this practice will facilitate the development of new ideas to promote positive lifestyle behavioral changes for the residents of Baltimore. Due to the costs of prevention programs and their limited impact in many cases, it is necessary to identify the specific factors that are relatively easy to measure and that might have a greater and lasting impact on the community at large. These efforts will demonstrate the importance of specific factors that will support long-term behavioral and lifestyle changes within this population.

            From a public-based perspective, the development of a strategic approach to reduce the risks associated with heart disease requires public support and intervention not only through financial means, but also through the utilization of knowledge and experience that is present within the Baltimore community. This coincides with national public initiatives to improve health and promote awareness of heart disease and other conditions that impact communities throughout the United States. These factors play an important role in reducing these risks and in enabling community residents to better understand how their own behaviors impact their health and wellbeing in different ways. This is an important step towards the discovery of new insights and approaches that will positively influence outcomes for these residents.

            Public health initiatives and other challenges must evolve so that there are significant opportunities for growth and development within communities such as Baltimore. In particular, this community faces significant racial disparities and such factors as low education levels and low incomes that may prohibit access to routine healthcare services (Shaya et.al, 2006). In addition, “People with lower socioeconomic status (SES) are more likely to be uninsured, have low-quality heath care, and seek health care less often; when they do seek care, the problem is more likely to be an emergency” (Shaya et.al, 2006, p. 140). Under these conditions, it is expected that there will be significant problems that continue over time that must be addressed through action plan efforts so that local residents will benefit from these initiatives and will improve their own cardiovascular health by utilizing these offerings (Shaya et.al, 2006).

            Establishing an effective action plan for the Baltimore community also requires an effective screening tool that will be utilized on a regular basis within the community to support long-term growth and wellbeing for this population, and in particular, African Americans (Shaya et.al, 2006). These efforts must coincide with other strategies in place within the community and should also reflect a means of expanding knowledge and growth of specific factors associated with community-based support of these offerings (Shaya et.al, 2006). From a behavioral perspective, enabling this community to recognize the benefits of positive behavioral changes may make an important difference in their ability to remain compliant in these endeavors (Shaya et.al, 2006). These creative approaches must demonstrate the importance of specific interventions and other factors that are instrumental in shaping outcomes for this group of residents (Shaya et.al, 2006).

            From a compliance-based perspective, the ability of local residents to accomplish the objectives of the action plan requires a continuous effort from social service and healthcare providers to motivate residents so that they are able to reduce their risk of cardiovascular disease over time. This is an important and meaningful accomplishment for the community and requires a greater understanding of the different challenges and limitations that exist in supporting the development of new ideas and approaches to facilitate improvements not only in lifestyle behaviors, but also in the ability to access specific healthcare services within the community setting. This is a critical offering that must be provided through the efforts made with the action plan and should be effective in supporting the development of new ideas and approaches to encourage growth and change within the members of this community, and in particular, those who face the highest risk of cardiovascular disease. With these steps in mind, local residents are likely to experience greater benefits and will be empowered to improve their health and wellbeing through specific lifestyle changes and behavioral modifications to accomplish these efforts in an effective manner.

            Key community organizations and professionals, such as nurses, social workers, pharmacists, churches, hospitals, clinics, schools, and others must identify areas where collaboration might be beneficial in supporting the long-term growth and sustainability of the chosen action plan. It is necessary to identify specific factors that are associated with positive outcomes for local residents that also address disparities in healthcare access, screening, and treatment for this population group. With these efforts in mind, it is necessary to also address methods of developing and sustaining an action plan that is cost effective and appropriate for the population in question and the needs of the local community at large. These efforts will provide significant and meaningful benefits to local residents in their efforts to achieve positive health outcomes for the foreseeable future. Since the risk of cardiovascular disease is significant for many residents of Baltimore, it is more important than ever to address these disparities and to consider the challenges of creating an environment that supports these objectives and developments over the long term.

Conclusion

            The disparities in health in Baltimore are best represented by the development of strategic approaches in community –based settings in order to gather data and to develop specific frameworks that will generate healthier outcomes for this group. Within this context, it is important to recognize the value of interventions that provide education and support to those persons at risk for cardiovascular disease in order to improve outcomes and create new opportunities for expanded health. With a diverse range of life expectancy within the City of Baltimore, it is more important than ever to recognize the different concerns associated with lower income communities and how this impacts health over the long term. From this perspective, it is likely that organizations that work collaboratively towards a set of common goals and objectives will achieve greater than anticipated outcomes in different ways to reduce their risk of heart attack, stroke, and other cardiovascular concerns. For the residents of Baltimore, it is more important than ever to provide them with a framework for the achievement of successful outcomes and the development of healthier lifestyle choices to improve general health and wellbeing over time.

            The identification and development of successful nursing-based communication strategies with patients and colleagues requires an effective recognition of the different challenges that exist in expanding communication to improve the quality of care. Recognizing barriers to communication is important in demonstrating the value of taking the steps that are required to improve communication to improve the quality of care. All populations deserve quality care and treatment from nurses at all times; therefore, continuous efforts must be made to accommodate these needs and to eliminate barriers to communication in order to promote successful outcomes and wellbeing for all patients. These contributions to nursing practice are critical because they shape the manner in which nurses identify with their patients and are able to communicate with them in different ways to ensure that patient care and treatment are not compromised in any way.

            The people of Baltimore face significant risks associated with cardiovascular disease and its impact on their lives. In particular, African Americans face a greater risk of cardiovascular disease due to various disparities within the culture itself and in obtaining routine access to quality healthcare services. Community-based initiatives must be established to expand knowledge and awareness of heart disease and its overall impact on local community residents. It is important for local community members with experience in public health and social services to participate in these endeavors to ensure that local residents are taking the steps that are necessary to improve their health and to minimize their risk of cardiovascular disease. Therefore, greater access to healthcare services must be achieved to improve lifestyle behaviors, screening mechanisms, and other factors that are active contributors to the reduction of risk associated with cardiovascular disease within this community. Finally, it is important for local organizations and professionals to identify areas where disparities exist and to address those disparities as directly as possible to reduce the long-term impact of heart disease on the community as a whole. These efforts will demonstrate the importance of specific factors and approaches that will facilitate greater outcomes and that will utilize specific community-based knowledge and experience to develop efforts to improve outcomes for local community members that will be consistent and routine over time.

            The proposed action plan must demonstrate that cardiovascular disease in the Baltimore area is taken seriously and requires a collaborative effort from a variety of community-based sources in order to accomplish the desired objectives and to facilitate successful results in reducing disparities and in shaping a healthier community for all residents. These efforts must utilize existing resources wisely and develop new strategies to facilitate growth and change within the Baltimore community setting. With these practices in place, the people of Baltimore will achieve greater than anticipated health outcomes and improved longevity over time.

References

Baird, B.K., Funderburk, A., and Whitt, M. (2012). Structure strengthens nursing                                    communication. Nurse Leader, 10(2), 48-49, 52.

Baltimore City Health Department (2009). Agenda to reduce cardiovascular disease                     

http://www.baltimorehealth.org/info/Keep%20the%20Beat%20-%20Baltimore%27s%20Cardiovascular%20Disease%20Agenda.pdf

disparities in Baltimore City. Retrieved from

 Baltimore City Health Department (2010). 2010 Baltimore City health disparities report

card.  Retrieved from http://baltimorehealth.org/info/2010_05_25_HDR-FINAL.pdf

 The Baltimore Sun (2011). Mapping the health of Baltimore’s neighborhoods.

Retrieved              

from http://data.baltimoresun.com/baltimore-healthy-neighborhoods/

 Beckett, C.D., and Kipnis, G. (2009). Collaborative communication: integrating SBAR to                     improve quality/patient safety outcomes. Journal for Healthcare Quality, 31(5),                         19-28.

Boscart, V.M. (2009). A communication intervention for nursing staff in chronic care.                            Journal of Advanced Nursing, 65(9), 1823-1832.

Centers for Disease Control and Prevention. A public health action plan to prevent heart disease                        and stroke. Retrieved from

http://www.cdc.gov/dhdsp/action_plan/pdfs/action_plan_full.pdf\

Cheadle, A., Schwartz, P.A., Rauzon,S., Beery, W.L., Gee, S., and Solomon, L. (2010).  The                 Kaiser Permanente Community Health Initiative: overview and evaluation design.                     American Journal of Public Health,100(11), 2111-2113.

Coeling, HVE, and Cukr, P.L. (2000). Communication styles that promote perceptions of                      collaboration, quality, and nurse satisfaction. Journal of Nursing Care Quality, 14(2),                 63-74.

Cohn, M., and Marton, A. (2012). City health data illustrates chasm between rich and poor                       neighborhoods. The Baltimore Sun, retrieved from

http://articles.baltimoresun.com/2012-07-12/news/bal-baltimore-health-data-map-illustrates-chasm-between-rich-and-poor-neighborhoods-20120712_1_life-expectancy-city-health-heart-disease

Collins, J., and Koplan, J.P. (2009). Health impact assessment: a step toward health in all                       policies. Journal of the American Medical Association,302(3), 315-317.

Elder, L., and Paul, R. Learning the art of critical thinking, pp. 1-6.

Fatahi, N., Mattsson, B., Lundgren, S.M., and Hellstrom, M. (2010). Nurse radiographers’                     experiences of communication with patients who do not speak the native language.                     Journal of Advanced Nursing, 66(4), 774-783.

Fennell, D., Liberato, ASQ, and Zsembik, B. (2009). Definitions and patterns of CAM use by               the lay public. Complementary therapies in medicine, 17(2), 71-77.

Fleischer, S., Berg, A., Zimmerman, M., Wuste, K., and Behrens, J. (2009). Nurse-patient                      interaction and communication: a systematic literature review. Journal of Public             Health, 17(5), 339-353.

Harris-Roxas, B., and Harris, E. (2011). Differing forms, differing purposes: a typology of health                      impact assessment. Environmental Impact Assessment Review, 31(4), 396-403.

Hassan, S.S., Ahmed, S.I., Bukhari, N.I., and Loon, W.C. (2009). Use of complementary           and                  alternative medicine among patients with chronic diseases at outpatient clinics.               Complementary Therapies in Clinical Practice, 15(3), 152-157.

Hemsley, B., Balandin, S., and Worrall, L. (2012). Nursing the patient with complex                  communication needs: time as a barrier and a facilitator to successful communication                 in hospital. Journal of Advanced Nursing, 68(1), 116-126.

Johns Hopkins Urban Health Institute. Health disparities in Baltimore City: is geography             

destiny? Retrieved from http://urbanhealth.jhu.edu/media/reports/healthdis_baltimore.pdf

Kvarnstrom, S. (2008). Difficulties in collaboration: a critical incident study of interprofessional                       healthcare teamwork. Journal of Interprofessional Care, 22(2), 191-203.

Laverack, G. (2006).Improving health outcomes through community empowerment: a review of                       the literature. Journal of Health, Population and Nutrition, 24(1).

Maryland Department of Health & Mental Hygiene (2009). The Maryland burden of

heart disease and stroke. Retrieved from

http://phpa.dhmh.maryland.gov/cdp/pdf/Report-Heart-Stroke.pdf

Miller, L.A. (2005). Patient safety and teamwork in perinatal care. Journal of Perinatal Neonatal                      Nursing, 19(1), 46-51.

National Heart, Lung, and Blood Institute (NHLBI). Cardiovascular health small group               

discussion in Baltimore City public housing: consumer assessment for community-            based outreach and education. Retrieved from

Ndao-Brumblay, S.K., and Green, C.R. (2010). Predictors of complementary and alternative                  medicine use in chronic pain patients. Pain Medicine, 11(1), 16-24.

Redsell, S.A., Bedford, H., Siriwardena, A.N., Collier, J., and Atkinson, P. (2010). Exploring                 communication strategies to use with parents on childhood immunization. Nursing                     Times, 106(19), 19-22.

Shaya, F.T., Gu, A., and Saunders, E. (2006). Addressing cardiovascular disparities through                  community interventions. Ethnicity & Disease, 16, 138-144.

Taylor, B.J. (2012). Developing an integrated assessment tool for the health and social care of               older people. British Journal of Social Work, 42(7), 1293-1314.

United States Census Bureau (2012). Baltimore city, Maryland. Retrieved from

U.S. Office of Personnel Management. Building a collaborative team environment, pp. 1-2.

Walker, A. Bezyak, J., Gilbert, E., and Trice, A. (2011). A needs assessment to develop             community partnerships. American Journal of Health Education, 42(5), 270-275.

Williams, K.J., Bray, P.G., Shapiro-Mendoza, C.K., Reisz, H., and Peranteau, J. (2009).             Modeling the principles of community-based participatory research in a community                  health assessment conducted by a health foundation. Health Promotion Practice, 10(1),             67-75.

Wittenberg-Lyles, E., Goldsmith, J., and Ferrell, B. (2013). Oncology nurse communication                  barriers to patient-centered care. Clinical Journal of Oncology Nursing, 17(2), 152-158.

Categories
Communications and Media

Week 3 Humanities

  1. Question: The Net Neutrality Case Study in Chapter 11 of Exploring Media and Culture talks about net neutrality and concerns regarding speed and access on the Internet. What are the implications of a potential decline of neutrality on the Internet? Would you personally be affected if neutrality on the Internet ceased to exist? If so, how? If not, why not?

The speed and access to the Internet are synonymous with the freedom associated with this medium; namely, these two components of the Internet ensure an accessibility to the content which web users wish to access. Net neutrality in this sense entails a concept whereby precisely such an accessibility to content is preserved; the conversing decline in such neutrality means the loss of accessibility, and is therefore a loss of the freedom which the Internet offers. In this regard, I would personally be affected by such a change, in so far as much of my time, for example, reading, watching videos, communicating with friends and acquaintances are entirely dependent upon the access to the Internet. According to such a change, I would be forced to not only alter how I gather information and ultimately, how I learn, but I would also be forced to alter how I communicate with those close to me. Accordingly, a decline in net neutrality would have a profound existential impact not only for me personally, but for the majority whose lives have been affected in a diverse number of ways by the Internet.