Although there is no known cure for multiple sclerosis, several therapies have proven helpful. The primary aims of therapy are returning function after an attack, preventing new attacks, and preventing disability. Starting<unk> ions is generally recommended in people after the first attack when more than two lesions are seen on MRI. As with any<unk>  treatment,<unk> ions used in the management of MS have several adverse effects. Alternative treatments are pursued by some people, despite the shortage of supporting evidence of efficacy. Acute attacks During symptomatic attacks, administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the usual therapy, with oral corticosteroids seeming to have a similar efficacy and safety profile. Although effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. The long-term benefit is unclear in optic neuritis as of 2020. The consequences of severe attacks that do not respond to corticosteroids might be treatable by plasmapheresis. Disease-modifying treatments Relapsing remitting multiple sclerosis As of 2021, multiple disease-modifying<unk> ions are approved by regulatory agencies for relapsing-remitting multiple sclerosis (RRMS). They are interferon beta-1a, interferon beta-1b, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, ocrelizumab, siponimod, cladribine, ozanimod, and ponesimod. In March 2017, the FDA approved ocrelizumab, a humanized anti-CD20 monoclonal antibody, as a treatment for RRMS, with requirements for several Phase IV clinical trials. In RRMS they are modestly effective at decreasing the number of attacks. The interferons and glatiramer acetate are first-line treatments and are roughly equivalent, reducing relapses by approximately 30%. Early-initiated long-term therapy is safe and improves outcomes. Natalizumab reduces the relapse rate more than first-line agents; however, due to issues of adverse effects is a second-line agent reserved for those who do not respond to other treatments or with severe disease. Mitoxantrone, whose use is limited by severe adverse effects, is a third-line option for those who do not respond to other<unk> ions. Treatment of clinically isolated syndrome (CIS) with interferons decreases the chance of progressing to clinical MS. Efficacy of interferons and glatiramer acetate in children has been estimated to be roughly equivalent to that of adults. The role of some newer agents such as fingolimod, teriflunomide, and dimethyl fumarate, is not yet entirely clear. It is difficult to make firm conclusions about the best treatment, especially regarding the long‐term benefit and safety of early treatment, given the lack of studies directly comparing disease modifying therapies or long-term monitoring of patient outcomes. As of 2017, rituximab was widely used off-label to treat RRMS. There is a lack of high quality randomised control trials examining rituximab versus placebo or other disease-modifying therapies, and as such the benefits of rituximab for relapsing remitting multiple sclerosis remain inconclusive. The relative effectiveness of different treatments is unclear, as most have only been compared to placebo or a small number of other therapies. Direct comparisons of interferons and glatiramer acetate indicate similar effects or only small differences in effects on relapse rate, disease progression and magnetic resonance imaging measures. Alemtuzumab, natalizumab, and fingolimod may be more effective than other drugs in reducing relapses over the short term in people with RRMS. Natalizumab and interferon beta-1a (Rebif) may reduce relapses compared to both placebo and interferon beta-1a (Avonex) while Interferon beta-1b (Betaseron), glatiramer acetate, and mitoxantrone may also prevent relapses. Evidence on relative effectiveness in reducing disability progression is unclear. All<unk> ions are associated with adverse effects that may influence their risk to benefit profiles. Progressive multiple sclerosis , only one<unk> ion, mitoxantrone, had been approved for secondary progressive MS. In this population tentative evidence supports mitoxantrone moderately slowing the progression of the disease and decreasing rates of relapses over two years. As of 2013, review of 9 immunomodulators and immunosuppressants found no evidence of any being effective in preventing disability progression in people with progressive MS. In March 2017 the FDA approved ocrelizumab as a treatment for primary progressive MS in adults, the first drug to gain that approval,. with requirements for several Phase IV clinical trials. It is also used for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease in adults. In 2019, siponimod and cladribine were approved in the United States for the treatment of secondary progressive multiple sclerosis. Adverse effects Irritation zone after injection of glatiramer acetate. The disease-modifying treatments have several adverse effects. One of the most common is irritation at the injection site for glatiramer acetate and the interferons (up to 90% with subcutaneous injections and 33% with intramuscular injections). Over time, a visible dent at the injection site, due to the local destruction of fat tissue, known as lipoatrophy, may develop. Interferons may produce flu-like symptoms; some people taking glatiramer experience a post-injection reaction with flushing, chest tightness, heart palpitations, and anxiety, which usually lasts less than thirty minutes. More dangerous but much less common are liver damage from interferons, systolic dysfunction (12%), infertility, and acute myeloid leukemia (0.8%) from mitoxantrone, and progressive multifocal leukoencephalopathy occurring with natalizumab (occurring in 1 in 600 people treated). Fingolimod may give rise to hypertension and slowed heart rate, macular edema, elevated liver enzymes or a reduction in lymphocyte levels. Tentative evidence supports the short-term safety of teriflunomide, with common side effects including: headaches, fatigue, nausea, hair loss, and limb pain. There have also been reports of liver failure and PML with its use and it is dangerous for fetal development. Most common side effects of dimethyl fumarate are flushing and gastrointestinal problems. While dimethyl fumarate may lead to a reduction in the white blood cell count there were no reported cases of opportunistic infections during trials. Associated symptoms Both<unk> ions and neurorehabilitation have been shown to improve some symptoms, though neither changes the course of the disease. Some symptoms have a good response to<unk> ion, such as bladder spasticity, while others are little changed. Equipment such as catheters for neurogenic bladder or mobility aids can be helpful in improving functional status. A multidisciplinary approach is important for improving quality of life; however, it is difficult to specify a 'core team' as many health services may be needed at different points in time. Multidisciplinary rehabilitation programs increase activity and participation of people with MS but do not influence impairment level. Studies investigating information provision in support of patient understanding and participation suggest that while interventions (written information, decision aids, coaching, educational programmes) may increase knowledge, the evidence of an effect on decision making and quality of life is mixed and low certainty. There is limited evidence for the overall efficacy of individual therapeutic disciplines, though there is good evidence that specific approaches, such as exercise, and psychological therapies are effective. Cognitive training, alone or combined with other neuropsychological interventions, may show positive effects for memory and attention though firm conclusions are not currently possible given small sample numbers, variable methodology, interventions and outcome measures. The effectiveness of palliative approaches in addition to standard care is uncertain, due to lack of evidence. The effectiveness of interventions, including exercise, specifically for the prevention of falls in people with MS is uncertain, while there is some evidence of an effect on balance function and mobility. Cognitive behavioral therapy has shown to be moderately effective for reducing MS fatigue. The evidence for the effectiveness of non-pharmacological interventions for chronic pain is insufficient to recommend such interventions alone, however their use in combination with<unk> ions may be reasonable. Non-pharmaceutical There is some evidence that aquatic therapy is a beneficial intervention. The spasticity associated with MS can be difficult to manage because of the progressive and fluctuating course of the disease. Although there is no firm conclusion on the efficacy in reducing spasticity, PT interventions can be a safe and beneficial option for patients with multiple sclerosis. Physical therapy including vibration interventions, electrical stimulation, exercise therapy, standing therapy, and radial shock wave therapy (RSWT), were beneficial for limiting spasticity, helping limit excitability, or increasing range of motion. Alternative treatments Over 50% of people with MS may use complementary and alternative medicine, although percentages vary depending on how alternative medicine is defined. Regarding the characteristics of users, they are more frequently women, have had MS for a longer time, tend to be more disabled and have lower levels of satisfaction with conventional healthcare. The evidence for the effectiveness for such treatments in most cases is weak or absent. Treatments of unproven benefit used by people with MS include dietary supplementation and regimens, vitamin D, relaxation techniques such as yoga, herbal medicine (including<unk>  cannabis), hyperbaric oxygen therapy, self-infection with hookworms, reflexology, acupuncture, and mindfulness. Evidence suggests vitamin D supplementation, irrespective of the form and dose, provides no benefit for people with MS; this includes for measures such as relapse recurrence, disability, and MRI lesions while effects on health‐related quality of life and fatigue are unclear. Clinical trials of high-dose biotin (300 mg/day = 10,000 times adequate intake) have also been conducted for treatment of multiple sclerosis. The
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