neurologic disorders
Multiple Sclerosis (MS)
Treatment of Multiple Sclerosis
Corticosteroids Immunomodulators to prevent exacerbations and delay eventual disability Baclofenortizanidinefor spasticity Gabapentinor tricyclic antidepressants for pain Supportive care Goals for treatment of multiple sclerosis include the following: Shortening acute exacerbations Decreasing frequency of exacerbations Relieving symptoms Delaying disability, particularly maintaining the patient’s ability to walk Corticosteroids, given in brief courses, are used to treat acute onset of symptoms or exacerbations that cause objective deficits sufficient to impair function (eg, loss of vision, strength, or coordination); regimens include Methylprednisolone500 to 1000 mg IV once a day for 3 to 5 days Less commonly,prednisone1250 mg orally per day (eg, 625 mg orally twice a day or 1250 mg orally once a day) for 3 to 5 days (1000 mg/day for 3 consecutive days) orally or IV may have similar efficacy ( Treatment references , If corticosteroids are ineffective in reducing the severity of an exacerbation, Plasma exchange may be used. Plasma exchange can be used for any relapsing form of MS (relapsing-remitting, progressive relapsing, secondary progressive). It is not used for primary progressive MS. Plasma exchange and Hematopoietic Stem Cell Transplantation may be somewhat useful for severe, intractable disease. For additional information, seePractice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Immunomodulatory therapy, such as interferons orglatiramer, decreases the frequency of acute exacerbations and delays eventual disability. Typical regimens include the following: Interferon beta-1b250 mcg subcutaneously every other day Interferon beta-1a(various forms, given IM or subcutaneously) Common adverse effects of interferons include flu-like symptoms and depression (which tend to decrease over time), development of neutralizing antibodies after months of therapy, and cytopenias. Glatirameracetate may be used. The following oral immunomodulatory medications can be used to treat relapsing forms of MS, including active secondary MS. Fingolimod Siponimod Ozanimod Ponesimod Teriflunomide Dimethyl fumarate Monomethyl fumarate Diroximel fumarate and the interferons ( Treatment references , Because most people are averse to self-injection, oral immunomodulatory medications are being increasingly used as first-line treatments for relapsing forms of MS. Disease-modifying therapies can be used to treat relapsing forms of MS. There is no consensus regarding choice of disease-modifying immunomodulatory therapy. Many experts recommend patient education and shared decision-making, including when disease-modifying therapies are offered to patients who have > 1 lesion (seen on imaging) and a clinically isolated syndrome. If one medication is ineffective, a different one can be tried. The immunosuppressantmitoxantronemay be helpful, particularly for progressive MS that is refractory to other treatments. However,mitoxantronehas been used less since the advent of monoclonal antibodies to treat MS. , an anti–alpha-4 integrin antibody, inhibits passage of leukocytes across the blood-brain barrier; given as a monthly infusion, it reduces number of exacerbations and new brain lesions but may increase the risk of Progressive Multifocal Leukoencephalopathy (PML) (PML). Medications that increase the risk of PML include the following (in descending order of risk): Natalizumab Fingolimod Siponimod Rituximab Ocrelizumab Ofatumumab Rarely,dimethyl fumarate If any of these medications are used, consultation with a neurologist with training in MS is highly recommended. Before these medications are started, blood tests should be done to check for antibodies to JC virus (JCV), which causes PML. Based on the results, the following is done: If results are positive, patients should be counseled about the risk of PML. If results are negative, antibody tests should be done every 6 months as long as any of these medications is used because seroconversion is common. If test results become positive, patients should be counseled again about the risk, and clinicians should consider switching to a medication without this risk. If the high-risk medication is continued, MRI of the brain should be done about every 6 months. Development of PML symptoms (eg, aphasia, change in mental status, hemianopia, ataxia) requires immediate brain MRI, with and without gadolinium. MRI can often distinguish PML from MS. After MRI, a Lumbar Puncture (Spinal Tap) should be done, and cerebrospinal fluid should be tested for JCV DNA by polymerase chain reaction (PCR). A positive result indicates PML, and emergency consultation with a neurologist and an infectious disease specialist is needed. Also, if patients with a positive result have taken If altered consciousness, aphasia, hemianopia, or ataxia develops in a patient takingnatalizumab,rituximab, orfingolimod, do immediate brain MRI, followed by lumbar puncture, to check for PML. Alemtuzumab, an anti-CD52 humanized monoclonal antibody given IV, has been shown to be effective in the treatment of MS. However, because it increases risk of autoimmune disorders, serious infusion reactions, and certain cancers,alemtuzumabis usually used only when treatment with ≥ 2 other medications has been ineffective. Cladribineis effective in relapsing forms of MS and may be an appropriate treatment for relapsing MS that is highly active.Cladribineis given orally in two yearly treatment courses. Lymphocyte counts should be monitored before, during, and after treatment, and patients should be closely monitored for adverse effects related to immunosupression. , an anti-CD20 (B-cell) humanized monoclonal antibody given as an infusion every 6 months, is also effective in the treatment of relapsing MS ( Treatment references ). , also an anti-CD20 (B-cell) humanized monoclonal antibody, is used to treat relapsing forms of MS, including clinically isolated syndrome and active secondary progressive disease. It is given by subcutaneous injection (self-administered [ Treatment references ]). Ublituximab, a chimeric monoclonal antibody is also used to treat relapsing forms of MS, including clinically isolated syndrome, and active secondary progressive disease. It is given as an IV infusion. and the interferons ( Treatment references ); it is commonly used throughout Europe and Canada because it is much less expensive than ) to treat MS early in the disease course reduces the likelihood of disability ( Treatment references , If immunomodulatory medications are ineffective, monthly IV immune globulin may help. Immunosuppressants other thanmitoxantrone(eg,methotrexate,azathioprine,mycophenolate,cyclophosphamide,cladribine) have been used for more severe, progressive MS but are controversial. Other treatments can be used to control specific symptoms: Spasticityis treated with escalating doses ofbaclofenortizanidine. Gait training and range-of-motion exercises can help weak, spastic limbs. Problems with gaitmay be treated with extended-release 4-aminopyridine (dalfampridine). Painful paresthesiasare usually treated withgabapentin100 to 800 mg orally 3 times a day orpregabalin25 to 150 mg orally twice a day; alternatives include tricyclic antidepressants (eg,amitriptyline25 to 75 mg orally at bedtime,desipramine25 to 100 mg orally at bedtime ifamitriptylinehas intolerable anticholinergic effects),carbamazepine200 mg orally 3 times a day, as well as other antiseizure medications, and opioids. is treated with counseling and Medications for Treatment of Depression . Bladder dysfunctionis treated based on its underlying mechanism. Constipationmay be treated with stool softeners or laxatives, taken regularly. Fatiguecan be treated withamantadinemodafinil,armodafinil, or extended-releaseamphetamine. (600 mg to 1800 mg a day in divided doses) may help. In severe cases, injecting botulinum toxin may help ( Treatment references ). Encouragement and reassurance help patients with multiple sclerosis. Regular exercise (eg, stationary biking, treadmill, swimming, stretching, balance exercises), with or without physical therapy, is recommended, even for patients with advanced MS, because exercise conditions the heart and muscles, reduces spasticity, prevents contractures and falls, and has psychologic benefits. supplements (eg, 600 to 4000 IU/day to achieve blood levels of 20 to 50 ng/mL [50 to 125 nmol/L] ) may decrease the risk of disease progression ( Treatment references ). Serum Patients should maintain as normal and active a life as possible but should avoid overwork, fatigue, and exposure to excess heat. Cigarette smoking should be stopped. Vaccination does not appear to increase risk of exacerbations. 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