Table of Contents
1. History of Multiple Sclerosis (MS)
In 1946, Sylvia Lawry started Multiple sclerosis (MS) movement with the founding of the National MS Society. By that time disease diagnosis took years to and there were no therapies to slow down the disease course. Also, research into multiple sclerosis was almost non-existent. At present, a critical platform of knowledge which is serving as a springboard for progress has been built because of decades of research into MS and basic immune system working.
To fuel the progress that changes lives of MS people it is critical to help them and their family better understand this complex and unpredictable disease. Four years back in 2015 March was declared as Multiple Sclerosis Awareness Month and charities and non-profit organizations around the world are taking the opportunity to push MS into the spotlight and raise money for vital research and support for people who live with the disease.
Multiple Sclerosis Awareness is represented by orange color. MS is an autoimmune inflammatory disease of central nervous system (CNS) characterized by loss of myelin ensheathing the axons. Disease mechanisms in multiple sclerosis at the molecular level remains poorly understood. Research is ongoing in areas of immunology, epidemiology, and genetics. Scientists are also exploring the role of infectious agents. The prevalence of MS has increased progressively over time with 30/100,000 diagnosed in 2008 to 33/100,000 diagnosed in 2013 globally and affected over 400,000 individuals in the United States (1). According to several studies performed over the world, MS is an abnormal immune-mediated response causing inflammation and damage to the myelin. Myelin is a coating that covers nerve fibers (axons) in the CNS. In this disease the cells making myelin and the nerve fibers also get damaged. This damage disrupts the transmission of nerve impulses. The pathophysiological mechanisms of MS involve autoreactive T cells, primarily T helper (Th)-1 CD4+ T cells and Th17 cells. These cells secrete cytokines and activate an inflammatory cascade resulting in demyelination within the brain and spinal cord and axonal damage. MS is generally known as a chronic autoimmune disorder of the CNS (2, 3). In the disease course blood-brain barrier (BBB) breaks down leading to migration of immune cells (macrophages, T cells, B cells) and secretion of pro-inflammatory cytokines and chemokines (4) which induces inflammation, the formation of sclerotic plaques (lesions), demyelination and neurodegeneration (5). MS lesions may form in any location of the CNS white matter or in grey matter. They often lead to physical disability and sometimes, the decline in cognitive ability (4, 6). The role of viruses and bacteria like measles, canine distemper, human herpesvirus-6, Epstein-Barr virus (EBV), and Chlamydia pneumonia in the development of MS are also under investigation. EBV, the virus that causes mononucleosis, has received significant attention in recent years. A growing number of research findings indicate that previous infection with EBV contributes to the risk of developing MS.
Based upon the presentation and progression of MS, patients with the condition are subdivided into PPMS, RRMS, SPMS, and PRMS. Relapsing/remitting MS (RRMS) is the most common form, affecting 85% of all MS patients and involves relapses followed by remission. Secondary progressive MS (SPMS) develops over time following diagnosis of RRMS. Primary progressive MS (PPMS) affecting 8–10% of patients, is gradual continuous neurologic deterioration. Progressive relapsing MS (PRMS) the least common form (<5%), is similar to PPMS but with overlapping relapses (7). The examination of the cerebrospinal fluid (CSF) and visual induced potentials with MRI confirm the clinical suspicion of MS. Common methods to characterize the disease include the presence of gadolinium-enhancing lesions (GdE) in the brain, and scoring systems Expanded Disability Status Scale (EDSS), which uses a scale of 1–10 to rate a patient’s disease ranging from no disability to death due to MS (8).
MS symptoms are variable and unpredictable. The primary symptoms are the direct result of damage to the myelin and nerve fibers in the CNS. Whereas, the secondary symptoms are the complications that can arise as a result of these primary symptoms. The disabilities can present as weakness, difficulty swallowing, tremors, impaired bowel or bladder function, numbness, or visual changes. Changes in cognition (thinking ability) typically affect short-term memory, verbal fluency, and speed of information processing. Memory and reasoning problems may affect between two-thirds and three-fourths of those diagnosed with MS to varying degrees. One person might experience only one or two of the possible symptoms while another person experiences many more. MS medications are described as the first, second, or third line. Some MS drugs have the potential for complications that can be life-threatening so the drugs with higher risk profiles are considered second or third line drugs.
The selection of a treatment for MS is a complex. Typically considered second-line treatments may be recommended as a first choice based on individual circumstances. Medications used in multiple sclerosis modify the disease course, treat relapses (attacks), manage symptoms, enhance comfort and quality of life of MS patients. For severe relapses which interfere with a person’s mobility, safety or overall ability to function, corticosteroids are recommended. Alternative treatment options involve disease-modifying therapies such as interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone and humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab). Few emerging immune modulating approaches are stem cells, DNA vaccines, nanoparticles, altered peptide ligands. One of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Current management of MS is by medications focussing on inhibition of inflammation and blunting the immune system through different mechanisms. However, a number of limitations with currently available therapies makes the need for new therapies highly desirable. Ongoing efforts towards learning the immune-mediated process in MS gives a better understanding the of MS. New agents have significantly changed the dynamics of MS treatment. The treatment of multiple sclerosis (MS) has changed over the last 20 years. With the plethora of information regarding the immunopathophysiology of MS and availability of treatment options and new upcoming treatments, the future holds promise for managing and treating the disease.