Management of multiple sclerosisMultiple sclerosis MS is a chronic inflammatory demyelinating disease that affects the central nervous system Mechanism of action of steroids in multiple sclerosis. Several therapies for it exist, although there is no known cure. The most common initial course of the disease is the relapsing-remitting subtype, which is characterized by unpredictable attacks relapses followed by periods of relative remission with no new signs of disease activity. After some years, many of the people who have this subtype begin to experience neurologic decline without acute relapses. When this deca durabolin 50mg organon it is called secondary progressive multiple sclerosis.
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Multiple sclerosis MS is a chronic inflammatory demyelinating disease that affects the central nervous system CNS. Several therapies for it exist, although there is no known cure. The most common initial course of the disease is the relapsing-remitting subtype, which is characterized by unpredictable attacks relapses followed by periods of relative remission with no new signs of disease activity.
After some years, many of the people who have this subtype begin to experience neurologic decline without acute relapses. When this happens it is called secondary progressive multiple sclerosis.
Other, less common, courses of the disease are the primary progressive decline from the beginning without attacks and the progressive-relapsing steady neurologic decline and superimposed attacks.
Different therapies are used for patients experiencing acute attacks, for patients who have the relapsing-remitting subtype, for patients who have the progressive subtypes, for patients without a diagnosis of MS who have a demyelinating event, and for managing the various consequences of MS. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. As with any medical treatment, medications used in the management of MS may have several adverse effects , and many possible therapies are still under investigation.
At the same time different alternative treatments are pursued by many people, despite the fact that there is little supporting, comparable, replicated scientific study. Stem cell therapy is being studied. This article focuses on therapies for standard MS; borderline forms of MS have particular treatments that are excluded.
Administration of high doses of intravenous corticosteroids , such as methylprednisolone , is the routine therapy for acute relapses. This is administered over a period of three to five days, and has a well-established efficacy in promoting a faster recovery from disability after an attack.
As of , several disease-modifying treatments have been approved by regulatory agencies of different countries, including the U. Medications approved by the FDA include currently eleven medications: In interferon beta-1b was the first drug to ever be approved for MS, being soon followed by interferon beta-1a and glatiramer acetate.
Interferon beta-1a is injected either weekly intramuscular injection or three times a week subcutaneous injection depending on commercial formulations,   while interferon beta-1b is injected subcutaneously every second day. Glatiramer acetate is a mixture of random polymers of four amino acids which is antigenically similar to the myelin basic protein , a component of the myelin sheath of nerves with which it competes for presentation to T cells.
It is injected subcutaneously on a daily basis. Mitoxantrone is an immunosuppressant also used in cancer chemotherapy which was approved for MS in the year ;  whereas natalizumab is a monoclonal antibody that was initially approved in In fingolimod , a sphingosinephosphate receptor modulator, became the first oral drug approved by the FDA, being followed in by teriflunomide , a drug that inhibits the synthesis of pyrimidine and disrupts the interaction of T cells with antigen presenting cell.
Dimethyl fumarate is taken twice daily. Another oral drug, cladribine , was approved in Russia and Australia in This led the pharmaceutical to discontinue commercialization and withdraw all marketing applications.
Both the interferons and glatiramer acetate are available only in injectable forms, and both can cause skin reactions at the injection site, specially with subcutaneous administration.
Interferons , a subclass of cytokines , are produced in the body during illnesses such as influenza in order to help fight the infection. They are responsible of many of the symptoms of influenza infections, including fever , muscle aches , fatigue , and headaches. Glatiramer acetate is generally well tolerated. Mitoxantrone therapy may be associated with immunosuppressive effects and liver damage ; however its most dangerous side effect is its dose-related cardiac toxicity.
Careful adherence to the administration and monitoring guidelines is therefore essential; this includes obtaining an echocardiogram and a complete blood count before treatment to decide whether the therapy is suitable for the patient or the risks are too great.
It is recommended that mitoxantrone be discontinued at the first signs of heart damage, infection or liver dysfunction during therapy. Soon after its approval natalizumab was withdrawn from the market by its manufacturer after it was linked with three cases of the rare but hazardous neurological condition called progressive multifocal leukoencephalopathy PML. After a safety review the drug was returned to the market in as a monotherapy for MS under a special prescription program.
During clinical trials fingolimod gave rise to side effects such as hypertension and bradycardia , macular edema , elevated liver enzymes or reduction in lymphocite levels. Nevertheless, there have been reports of liver failure, and PML. During a CIS, there is a subacute attack suggestive of demyelination but the patient does not fulfill the criteria for diagnosis of multiple sclerosis.
Medications are modestly effective at decreasing the number of attacks in RRMS and in reducing the accumulation of brain lesions, which is measured using gadolinium - enhanced magnetic resonance imaging MRI.
Natalizumab and mitoxantrone are considered highly effective both in terms of relapse rate reduction and halting disability progression, however, they are related to dangerous side-effects that have led them to be considered second-line treatments.
There are no official guidelines yet on the use of disease-modifying oral treatments due to their recent development. While more studies of the long-term effects of the drugs are needed,    specially for the newest treatments,   existing data on the effects of interferons and glatiramer acetate indicate that early-initiated long-term therapy is safe and it is related to better outcomes.
Oral contraceptive pills have contradictory results from different studies regarding any effect of decreasing relapse rate in women with multiple sclerosis. Even with appropriate use of medication, to varying degrees most people with relapsing-remitting MS still have some attacks and many develop disability.
Treatment of advanced forms of MS is more difficult than relapsing-remitting MS. A wide range of medications have been used to try to slow the progression of the disease, with results that have been at best fair. Mitoxantrone has shown positive effects in people with a secondary progressive and progressive relapsing courses. It is moderately effective in reducing the progression of the disease and the frequency of relapses in people after two years.
It is also not approved in Europe. Natalizumab has shown efficacy and has been approved for secondary progressive MS with relapses. Studies on the use of Interferon-beta-1b in secondary progressive and progressive relapsing MS do not support that it slows progression of the disease, although it is effective in reducing the number of relapses. Treatment of primary progressive multiple sclerosis PPMS is problematic as many patients do not respond to any available therapy, and no treatment has been approved specifically for use in this form of the disease.
There have been several trials investigating the efficacy of different drugs for PPMS without positive results. Drugs tested include interferon beta, mitoxantrone, glatiramer acetate or riluzole.
Disease-modifying treatments only reduce the progression rate of the disease but do not stop it. As multiple sclerosis progresses, the symptoms tend to increase.
The disease is associated with a variety of symptoms and functional deficits that result in a range of progressive impairments and handicap. Management of these deficits is therefore very important. Symptoms of MS that can be improved include fatigue , spasticity , depression , bladder dysfunction, and neurological symptoms. These symptoms can be improved by physical therapy and medication. Physical therapists can show strengthening exercises and ways to stretch; ultimately making daily tasks easier and reduces fatigue while muscle strength increases as flexibility increases.
All symptoms are common amongst MS patients. Both drug therapy and neurorehabilitation have shown to ease the burden of some symptoms, even though neither influence disease progression.
For other symptoms the efficacy of treatments is still very limited. Although there are relatively few studies of rehabilitation in MS,   its general effectiveness, when conducted by a team of specialists, has been clearly demonstrated in other diseases such as stroke  or head trauma. The comprehensive rehabilitation process for patients with multiple sclerosis is generally managed by physiatrists. Allied treatments such as physiotherapy ,   speech and language therapy  or occupational therapy  can also help to manage some symptoms and maintain quality of life.
Treatment of neuropsychiatric symptoms such as emotional distress and clinical depression should involve mental health professionals such as therapists , psychologists , and psychiatrists ,  while neuropsychologists can help to evaluate and manage cognitive deficits. More specifically psychological interventions seem useful in the treatment of depression, while evidence on effectiveness for other uses such as the treatment of cognitive impairments or vocational counseling is less strong.
In regards to well-being, physical therapy focused on gait training can be vital to maximizing MS patient participation via reduction of fatigue during walking and activities of daily living ADLs. Robotic-assisted body weight-supported treadmill training may be an effective therapeutic option in MS patients with severe walking impairments.
Historically, individuals with MS were advised against participation in physical activity due to worsening symptoms. An elevated core temperature, leading to increased symptom presentation has been noted during exercise, due to variations in circadian body temperature throughout the day, and due to heat exposure including warm temperatures, warm showers, sun bathing, etc.
Care should be taken not to overheat a person with MS during the course of exercise. There is some evidence that cooling measures are effective in allowing a greater degree of exercise: These strategies are effective when attempting to decrease core temperature post-exercise, and as a method of pre-cooling prior to physical activity or heat exposure. These effects translate to reduced patient safety and performance of ADLs, however there are viable prevention strategies.
Behavioral strategies to minimize heat exposure include performing outdoor physical activity when temperatures are cooler, or installing an air conditioner. Multiple sclerosis can cause a variety of symptoms including changes in sensation hypoesthesia , muscle weakness, abnormal muscle spasms, impaired movement, difficulties with coordination and balance, problems in speech known as dysarthria or swallowing dysphagia , visual problems nystagmus , optic neuritis , or diplopia , fatigue and acute or chronic pain syndromes, bladder and bowel difficulties, cognitive impairment, or emotional symptoms mainly depression.
At the same time for each symptom there are different treatment options. Treatments should therefore be individualized depending both on the patient and the physician. Unfortunately, other symptoms, such as ataxia , tremor or sensory losses , do not have proven treatments. Research directions on MS treatments include investigations of MS pathogenesis and heterogeneity; research of more effective, convenient, or tolerable new treatments for RRMS; creation of therapies for the progressive subtypes; neuroprotection strategies; and the search for effective symptomatic treatments.
Advances during the last decades has led to the recent approval of several oral drugs. These drugs are expected to gain in popularity and frequency of use at the expense of previously existing therapies. Monoclonal antibodies, which are drugs of the same family as natalizumab, have also raised high levels of interest and research. Alemtuzumab , daclizumab and CD20 monoclonal antibodies such as rituximab , ocrelizumab and ofatumumab have all shown some benefit and are under study as potential treatments for MS.
Another research strategy is to evaluate the combined effectiveness of two or more drugs. Nevertheless, there can also appear important drawbacks such as antagonizing mechanisms of action or potentiation of deleterious secondary effects. Likewise, there are not any effective treatments for the progressive variants of the disease. Many of the newest drugs as well as those under development are probably going to be evaluated as therapies for PPMS or SPMS, and their improved effectiveness when compared with previously existing drugs may eventually lead to a positive result in these groups of patients.
Finally, regarding neuroprotective and specially regenerative treatments, such as stem cell therapy , while their research is considered of high importance at the moment they are only a promise of future therapeutic approaches. A study found promising results in relapsing-remitting MS but more research is needed. In , vascular surgeon Paolo Zamboni suggested that MS involves a vascular process he referred to as chronic cerebrospinal venous insufficiency CCSVI , in which veins from the brain are constricted.
The rationale behind the use of Vitamin D supplementation is that studies show an association between vitamin D deficiency and increasing progression of MS, as well as the anti-inflammatory effects of vitamin D. For antioxidant therapy, studies have shown that reactive oxidative species lead to the formation of multiple sclerosis lesions in which antioxidants can help induce neuroprotective and immunomodulatory effects.
Other alternative treatments include relaxation techniques such as yoga ,  herbal medicine including the use of medical cannabis ,   hyperbaric oxygenation ,  self-infection with hookworm known generally as helminthic therapy and bee venom therapy , reflexology or acupuncture. Moreover, they also have lower levels of satisfaction with conventional healthcare. From Wikipedia, the free encyclopedia. Multiple sclerosis drug pipeline.