Multiple sclerosis is an inflammatory demylinating disease directed at the brain and spinal cord characterized by lesions that are due to the perivascular infiltration of monocytes and lymphocytes into the brain parenchyma, brain stem, optic nerve, and spinal cord. There is evidence that its etiology might be viral in origin but the data are inconclusive. The resulting demyelination leads to impaired nerve signaling and subsequent impairment in vision, sensation, movement, and cognition. Multiple sclerosis lesions tend to be focal, and therefore the symptoms are often discretely tied to a particular body region, and multiple symptoms may occur in a single patient. Multiple sclerosis primarily affects adults, with a typical age of onset between 20 and 50 years. An estimated 300 000 individuals in the USA are afflicted with multiple sclerosis. While a relationship between multiple sclerosis risk and latitude exists in North America, Australia, and New Zealand, this is not consistent. Israel, a country with a high immigration rate, has a higher incidence of multiple sclerosis than its latitude would predict. The highest rates of multiple sclerosis are found in the Orkney and Shetland Isles in the UK, and multiple sclerosis is rare in native Africans and Japanese, suggesting a genetic component, supported by association with certain HLA alleles.
Multiple sclerosis patients present with a broad array of symptoms including reduced or abnormal sensations, weakness, vision changes, clumsiness, and loss of bladder control. The diversity of initial symptoms is a reflection of the focal nature of the disease and makes accurate diagnosis a challenge. A number of signs can be assessed to help in making the diagnosis including abnormal eye movements or pupillary response, altered reflex responses, impaired coordination or sensation, and evidence of spasticity or weakness in the arms or legs. Definitive diagnosis is made by a number of tests including blood tests to rule out other possible diagnoses (e.g., Lyme disease), an examination of cerebrospinal fluid to assess the presence of elevated immunoglobulin G (IgG), and oligoclonal banding, a visual evoked potential test to determine if there is a slowing in signal conduction, and a magnetic resonance imaging (MRI) scan to assess the presence of periventricular lesions. Multiple sclerosis patients can go through remission periods that last for as long as 5 years in which the disease is relatively stable.
Glucocorticoid therapy and immunomodulatory drugs are used for the treatment of multiple sclerosis. The former include cyclophosphamide, cladribine, methotrexate, azathiopurine, cyclosporine, and interferon, the latter include Type I (IFN-a and IFN-b) and Type II (IFN-g). Glatiramer acetate, a mixture of synthetic polypeptides composed of the acetate salts of the L-amino acids glutamic acid, alanine, glycine, and lysine that are found in high abundance in myelin basic protein (MBP), reduces the frequency of relapse in patients with relapsing-remitting multiple sclerosis. It is thought to either binding directly to major histocampatibility complex (MHC) class II complexes or induce MBP-specific suppressor cells.
Natalizumab is a humanized monoclonal antibody to a4 integrin that was approved for the treatment of relapsing forms of multiple sclerosis. It has robust effects on relapse rate and lesion activity in multiple sclerosis and may affect disease progression. Following three cases of progressive multifocal leukoencephalopathy (PML) in patients treated with natalizumab in combination with immunosuppressant therapy, the compound was put on a clinical hold which has now been removed following an additional assessment of the risk-benefit ratio for the use of this biological.
The overall prognosis for patients with autoimmune or neuroinflammatory disease appears good. While there is currently no drug available that will elicit a full remission or reversal of symptoms, there are a variety of choices for both palliative control of symptoms and modification of disease progression. There are significant adverse effects associated with corticosteroid, immunosuppression, and immunomodulation; however, the immunomodulators are relatively well tolerated.
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