An Overview of Multiple Sclerosis: Diagnosis and Management Strategies

Kathleen Costello, RN, MS, CRNP, MSCN; Colleen J. Harris, RN, MN, NP, MSCN


Topics in Advanced Practice Nursing eJournal. 2006;6(1) 

In This Article

Disease Management

Disease management in MS involves treatment of acute relapses, disease modification, and symptom management. All 3 aspects of care require an individualized approach based on illness course and tolerability of treatments.

A relapse is defined as new or worsening neurologic symptoms of greater than 24 hours' duration.[15] Relapses usually evolve over 24-48 hours, plateau for several weeks, and resolve to some degree over weeks to several months.[3] A true acute relapse should not be confused with a pseudorelapse, which is a temporary worsening of symptoms due to concurrent illness, fever, or infection.

Diagnosing a true relapse requires a clinician to take a detailed history that includes a description of relapse symptoms, including the onset, severity, impact on functional abilities, and effects of activity and time of day on symptoms. General symptoms of infection should be assessed, such as fever, chills, muscle and joint aches, and increased fatigue level. A urine culture should be obtained, as urinary tract infections often go undetected in MS and will affect symptoms significantly. In addition, a recent exposure to excessive heat or increased aerobic activity will cause a temporary worsening of symptoms. Waxman[16] determined that the demyelinated nerve is sensitive to heat and will conduct messages with less efficiency with heat exposure.

Once a true relapse is determined, the decision to treat must be made. If a relapse is severe enough to significantly affect an individual's activities of daily living, then treatment with high-dose glucocorticoids either by oral or intravenous route is indicated. There is little evidence that high-dose steroids alter the course of the disease, but they are believed to hasten the resolution of acute relapses.[17]

Researchers involved in the Optic Neuritis Treatment Trial suggested that intravenous steroids were superior to oral steroids for acute optic neuritis,[18] and although more expensive, this route is used most often to treat relapses in North American MS Centers. However, The Multiple Sclerosis Council for Clinical Practice Guidelines stated that there is no strong evidence to suggest that one type of glucocorticoid is more beneficial than the other, nor does route of administration affect outcome for treatment of acute relapses.[19]

A common dose schedule for the intravenous route is methylprednisolone 1 g each day for 3 to 5 days, and this is often followed by an oral prednisone taper. High oral doses of prednisone, 1250 mg on alternate or daily dose schedules of 3 to 5 days, have also been used and found to be as safe and effective as the intravenous route.[20,21]

Patients receiving glucocorticoids need to be appraised of the purpose and expectations of treatment as well as both the short- and long-term side effects. The outcome of shortening the duration and alleviating relapse symptoms should be emphasized. Short-term side effects include metallic taste in the mouth, facial flushing, altered appetite, weight gain, stomach upset, restlessness, mood swings, insomnia, and fluid retention. A small percentage of patients may experience psychosis secondary to the administration of steroids, and it is advisable that patients have friends or family monitor them at home during the course of their treatment.

Long-term side effects can include cataract formation, GI bleeding, osteoporosis, osteonecrosis of the hip, and diabetes. The occurrence of serious side effects can be diminished by treating the more serious relapses only and using brief courses of steroids. All patients who have received steroid treatment for relapses should be followed on an ongoing basis for potential long-term side effects.

Over the past 12 years, rapid advances have been made in MS treatment and care. In 1993, interferon beta-1b (Betaseron) was approved by the US Food and Drug Administration (FDA) for the treatment of ambulatory patients with relapsing-remitting MS to reduce the frequency of clinical relapses,[22] which was followed by the subsequent approval of 2 other drugs in this class including interferon beta-1a by intramuscular route (Avonex) and interferon beta-1a by subcutaneous injection (Rebif). Avonex was approved by the FDA in 1996 for the treatment of relapsing forms of MS, to delay disability and reduce relapses.[23]Rebif was FDA approved in 2002 for the treatment of relapsing forms of MS to decrease the frequency of clinical relapses and delay the accumulation of physical disability.[24]

Glatiramer acetate (Copaxone), another type of disease-modifying medication, was approved in 1996 for the treatment of relapsing-remitting MS to reduce the frequency of clinical relapses.[25] Together, these medications have dramatically changed how we treat relapsing forms of MS. Mitoxantrone (Novantrone), an immunosuppressant drug, was approved in 1999 for the treatment of worsening MS. The FDA indication reads "for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary progressive, progressive-relapsing, and worsening relapsing-remitting MS."[26] Mitoxantrone is not indicated for primary-progressive MS.

The actions of the disease-modifying therapies are thought to affect abnormal immune activity in different ways. In MS, it is thought that inflammatory T cells are stimulated, migrate into the CNS, and are reactivated. Once reactivated, they release damaging cytokines and stimulate cells that injure and/or destroy myelin and axons. The interferon beta medications are thought to interfere with the initial stimulation and proliferation of the T cell in the periphery. At the same time, they block certain types of enzyme activity at the blood brain barrier, which helps restore the integrity of the barrier, making migration of T cells into the CNS more difficult.[27,28]

Glatiramer acetate is thought to work by stimulating T cells to behave in an anti-inflammatory manner. Once the glatiramer acetate-induced T cells enter the CNS, they reduce the MS inflammatory process.[29] Mitoxantrone suppresses bone marrow production of lymphocytes, thereby reducing the numbers of circulating T and B lymphocytes.[26]

Interferon Dosing. Interferon beta-1b, given subcutaneously at a dose of 250 mcg on alternate days, interferon beta-1a by subcutaneous injection, given at a dose of 22 or 44 mcg 3 times weekly, and interferon beta-1a by intramuscular injection, given at a dose of 30 mcg once weekly, all have been shown to reduce the frequency and severity of acute relapses.[30,31,32] In addition, all of these interferon preparations have an impact on the formation of new and enhancing MRI lesions.

Although all must be given by injection, most patients learn to self-administer their therapies and manage their side effects. Like other chronic illnesses, long-term medication adherence issues remain a challenge and require close follow-up with health professionals. Common side effects of the interferons include flu-like symptoms, injection site reactions, and laboratory abnormalities that require ongoing surveillance.

Glatiramer Acetate. Glatiramer acetate, given at a dose of 20 mg by subcutaneous injection on a daily basis, has been shown to reduce the frequency of relapses as well as reduce the number and volume of new enhancing lesions on MRI.[33,34] Side effects of glatiramer acetate include injection site reactions and pain and an immediate systemic post-injection reaction consisting of flushing, anxiety, and chest discomfort. The post-injection reaction rarely requires discontinuation of therapy, but therapy initiation education should include details on the possible occurrence and appropriate management to ensure that it is not mistaken for true anaphylactic reaction to the medication.

Lipoatrophy has also been associated with longer-term use of glatiramer acetate, making ongoing involvement of a nurse to promote injection site rotation and education on appropriate injection technique important to long-term adherence to treatment.

Mitoxantrone. Previously approved for the treatment of various types of cancers, mitoxantrone is an anthracenedione with broad immunosuppressive and cytotoxic activity. It reduces the number of B lymphocytes, inhibits T-helper lymphocytes, and blocks macrophages from degrading myelin.[35] Clinical trials of mitoxantrone in MS demonstrated a significant reduction in relapses and worsening, and MRI lesion development.[36] Mitoxantrone is administered via intravenous infusion once every 3 months. The usual dose is 12 mg/m2, although some individual practitioners alter this amount. Due to a significant risk of cardiotoxicity, the cumulative lifetime maximum dose in MS treatment for mitoxantrone is 140 mg/m2.

Other side effects include mild to moderate gastrointestinal symptoms, including nausea, mild alopecia, menstrual disorders (eg, amenorrhea), elevations in liver enzymes, and bone marrow suppression.[37] Mitoxantrone must be administered with caution, and patients must have close follow-up. Hematology, blood chemistry, and left ventricular ejection fraction (LVEF) must be monitored prior to each dose of the agent. Patients who have an LVEF of < 50%, a clinically significant drop in LVEF, or have reached the lifetime maximum dosage of 140 mg/m2 should not receive additional doses of mitoxantrone.[26]

Disease-modifying therapies have added new hope to the treatment of MS. Prior to their introduction, there were no proven treatments that affected the course of MS. The approval of these therapies for the treatment of relapsing forms of MS has stimulated more research into the disease and has allowed us to intervene early in the course of MS. Unfortunately, all current disease-modifying treatments are imperfect and the emphasis of MS care still is directed toward symptom management and the prevention of complications from disability.

Healthcare providers, in collaboration with patients and significant others, make decisions regarding which of the approved therapies to initiate. There is no "right" answer. It is generally recommended that persons with relapsing forms of MS be on 1 of the 4 approved therapies indicated for relapsing MS. Those with worsening MS may be offered mitoxantrone therapy in an effort to slow the progression of disease.

New therapies are on the horizon for MS and may provide improved efficacy in relapse reduction and delay of disability. In November 2004, the FDA approved natalizumab (Tysabri), a monoclonal antibody, for the treatment of relapsing MS. In February 2005, the drug was voluntarily removed from the market due to 2 cases of progressive multifocal leukoencephalopathy (PML) that were thought to possibly be related to natalizumab treatment. A third case was subsequently identified in a Crohn's disease study population. Two of these 3 patients died. The company is working closely with the FDA to determine whether natalizumab can reenter the market. The drug works by blocking the ability of T cells to adhere to blood vessel endothelium, thereby preventing the trafficking of lymphocytes into tissues, including the brain. The drug showed remarkable efficacy in the reduction of relapses and MRI enhancement. It is administered monthly by intravenous infusion.[38]

Other monoclonal antibodies such as daclizumab, alemtizumab, and rituximab are also under study for the treatment of MS. Cladribine, an immunosuppressive agent, is under study in an oral form for the treatment of relapsing MS. This is just a partial list of the many compounds in various stages of development for the treatment of MS.

In spite of these efforts, currently there is no cure for MS. Symptoms still occur in patients, and many will worsen. Fortunately, many of the common symptoms of MS can be controlled significantly, leading to a better quality of life and a reduction of life-threatening complications.

Symptoms in MS vary depending on the location of the inflammation and demyelination in the brain and spinal cord. Symptoms can originate directly from the result of demyelination in the brain and spinal cord or from secondary complications of the disease.[39] As noted earlier, there is variability of symptom presentation in patients, but those commonly associated with the disease include fatigue, spasticity, elimination dysfunction, visual changes, and altered mobility, tremor, depression, and cognitive changes.

Approaches to management are geared to the initial use of practical strategies and rehabilitation measures followed by symptom-focused medication therapies. Due to the complex nature of the disease, the use of multiple therapeutic interventions is often necessary to manage symptoms in an individual patient.[40] (See Table 4 .)


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