Melody Ryan
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Identify risk factors for multiple sclerosis (MS).
2. Describe pathophysiologic findings of MS.
3. Recognize common presenting symptoms of MS.
4. Distinguish between the forms of MS based on patient presentation and course of disease.
5. Compare and contrast MS disease-modifying treatment choices for a specific patient.
6. Determine appropriate symptomatic treatment choices and develop a detailed therapeutic plan for a specific patient.
7. Develop a monitoring plan for a patient placed on specific medications.
KEY CONCEPTS
Multiple sclerosis (MS) symptoms are a function of the location of lesions within the CNS.
The McDonald criteria, utilizing clinical exam in combination with MRI and cerebrospinal fluid (CSF) data, facilitates earlier diagnosis, and thus earlier treatment initiation.
The clinical course of MS has four basic patterns: Relapsing remitting, secondary progressive, primary progressive, and progressive relapsing.
Acute relapses are treated with corticosteroids to speed recovery of the patient.
Disease-modifying therapies decrease the number of relapses, prevent permanent neurologic damage, and prevent disability.
Symptomatic treatment minimizes the impact of MS on quality of life.
Dose–response curves have been observed with the β-interferons.
There is no consensus on the best medication for initial therapy.
Mitoxantrone and natalizumab should be reserved for patients with rapidly advancing disease who have failed other therapies.
MS patients must be treated with agents specific for upper motor neuron spasticity.
Multiple sclerosis (MS) is an inflammatory disease of the CNS, variable in symptoms and presentation. Multiple describes the number of CNS lesions, and sclerosis refers to the demyelinated lesions, today called plaques.
EPIDEMIOLOGY AND ETIOLOGY
Epidemiology
Approximately 400,000 Americans have MS. Diagnosis usually occurs between the ages of 20 and 50. Twice as many women as men develop MS.1 Risk factors for MS include family history of MS, autoimmune diseases, or migraine; personal history of autoimmune diseases or migraine; and, in women, smoking and exposure to second-hand smoke.2,3 Prevalence decreases with decreases in latitude.4
Etiology
Inheritance Theory
MS probably has a genetic component: family members of MS patients have a 5% risk. Monozygotic twins have highest risk (25−30% concordance).5 Genetic susceptibility is probably found in the human leukocyte antigen chromosomal region.5 A straightforward inheritance pattern cannot fully explain the etiology of MS because only a small proportion of patients report a family member with MS.5
Environment Theory
Over 20 infectious agents have been suggested as etiologic agents. Currently, human herpes virus 6 (HHV-6) is the most likely causative virus. HHV-6 may initiate MS in two ways. First, HHV-6 is structurally similar to myelin basic protein. When T cells become sensitive to HHV-6, the cells may attack myelin basic protein. Second, HHV-6 may directly stimulate the complement cascade, activating autoimmune processes.6 Infection with HHV-6 cannot fully explain MS, because HHV-6 is found in 75% of the population, but MS is much less common.
PATHOPHYSIOLOGY
While the causative agent of MS is unclear, the result is the development of an autoimmune disorder with areas of CNS demyelination and axonal transection.
Demyelination
An unknown antigen presented by the major histocompatibility complex (MHC) class II molecules causes T cells to become autoreactive (Fig. 29–1). Once activated, T cells penetrate the blood–brain barrier by attachment to upregulated adhesion molecules and production of matrix metalloproteinases (MMP) that cause blood–brain barrier breakdown. In the CNS, the T cells come into contact with antigen-presenting cells (APCs) and proliferate. The T-helper cells differentiate into proinflammatory T-helper-1 cells (Th1 cells) and anti-inflammatory T helper-2 cells (Th2 cells).8 Th1 cells secrete cytokines that enhance macrophage and microglial cells that attack myelin.8
B cells cross previously damaged sections of the blood–brain barrier to arrive in the CNS, an area normally free of B cells. Autoreactive T cells trigger B cells to form myelin autoantibodies. B-cell antibodies also initiate the complement cascade, causing myelin degradation.8 These inflammatory processes probably cause relapses.5
Axonal Transection
Axonal transection disrupts nerve signals completely and irreversibly. There is growing evidence that cytotoxic T cells cause axonal injury.6 Axonal transection begins as early as 2 weeks after diagnosis and continues throughout the disease.9 Axonal loss is likely responsible for MS progression.5
CLINICAL PRESENTATION, DIAGNOSIS, AND CLINICAL COURSE
Diagnosis
MS diagnostic criteria were revised in 2001 (Fig. 29–2).17–19 Diagnosis requires that plaques be disseminated in time and space. Previously, diagnosis relied on clinical examination. The McDonald criteria, which utilizes the clinical exam in combination with MRI and (cerebrospinal fluid) CSF data, facilitates earlier diagnosis, and thus earlier treatment initiation (Table 29–1).
Table 29–1 Diagnostic Tests for MS
Clinical Course
The clinical course of MS has four basic patterns: Relapsing remitting, secondary progressive, primary progressive, and progressive relapsing (Fig. 29–3). Relapsing remitting MS develops into secondary progressive MS in 50% of patients within 10 years and in 75% within 25 years of diagnosis.1 Rating scales are used clinically (Table 29–2). MS reduces overall life expectancy 6 to 7 years.23 Suicide is disproportionately high in MS patients, accounting for about 15% of MS-related deaths.24
TREATMENT
Desired Outcomes and General Approach to Treatment
The overall goal of treatment is preventing permanent neurologic damage. There are three general approaches to treatment. First, acute relapses are treated with corticosteroids to speed recovery. Second, disease-modifying therapies decrease the number of relapses, prevent permanent neurologic damage, and prevent disability. Third, symptomatic treatments minimize the impact of MS on quality of life.
Pharmacologic Treatment
Treatment of Acute Relapses
The mechanism of action of corticosteroids is unclear, but may involve:
• Prevention of inflammatory cytokine activation
• Inhibition of T-cell activation
• Prevention of immune cells from entering the CNS
• Increased death of activated immune cells25
FIGURE 29–1. Synoptic view of the immune response in the pathogenesis of MS. Autoreactive T cells recognize with their TCR a specific autoantigen presented by MHC class II molecules and the simultaneous delivery of costimulatory signals (CD 28, B7, CD40, CD 40L) on the cell surface of APCs, such as macrophages, in the systemic immune compartment (panel 1). Activated T lymphocytes can cross the blood-brain barrier in order to enter the CNS. The mechanisms of transendothelial migration is mediated by the complex interplay of CAMs, chemokines, and their receptors (CCRs, CXCRs) and MMPs (panel 3). Within the CNS, T cells activate microglia cells/macrophages (Mφ) to enhanced phagocytic activity; production of cytokines, such as TNF-α and LT; and the release of toxic mediators, such as NO, propagating demyelination and axonal loss. Abs crossing the blood-brain barrier or locally produced by B cells or mast cells (B*) contribute to this process. Autoantibodies activate the complement cascade resulting in the formation of the membrane-attack complex (C5b-9) and its subsequent lysis of the target structure (panels 2 and 4). The upregulation of Na+ and Ca2+ channels on the axon as well as mitochondrial dysfunction and loss of trophic support contribute to axonal disintegration and degeneration (panel 5). The inflammatory response is regulated by anti-inflammatory cytokines, such as IL-10 or TGF-β, as well as IL-2, inducing programmed cell death (apoptosis) in immunoreactive T lymphocytes (panel 6). (Abs, autoantibodies; Ag, antigen; APC, antigen-presenting cells; CAM, cellular adhesion molecule; CNS, central nervous system; IL, interleukin; LT, lymphotoxin; MHC, major histocompatibility complex; MMP, matrix metalloproteinases; NO, nitric oxide; T, T cell; TCR, T-cell receptor; TGF, transforming growth factor; TNF, tumor necrosis factor.) (From Ref. 7.)
Clinical Presentation of MS10–16
MS symptoms are a function of the location of lesions within the CNS. Because myelin increases the speed of nerve impulse transmission, demyelination slows the speed of transmission. No impulses can be transmitted if the axon is transected. The primary symptoms of MS are caused by this delay or cessation of impulses. Secondary symptoms of MS result from the primary symptoms.
IV adrenocorticotropic hormone, IV methylprednisolone, or oral prednisone hasten functional recovery after relapses.26 Traditionally, IV methylprednisolone was the drug of choice for acute relapses because an optic neuritis study demonstrated reduced recurrence with IV methylprednisolone, but not oral prednisone.27,28 More recent studies show equal efficacy of equivalent doses of IV and oral dosage forms, and oral dosing avoids discomfort, inconvenience, and expense of IV therapy.29,30
Adverse Effects
Short-term corticosteroid use is not associated with most of the adverse effects of chronic steroid use. The most common adverse effects are GI upset, insomnia, and mood swings.27
Dosing and Administration
Methylprednisolone is given 1 g/day IV as one dose or in divided doses for 3 to 5 days. Oral prednisone 1,250 mg/day given every other day for five doses provides an equivalent dose.
Clinical improvement usually begins during corticosteroid treatment. Neurologic recovery is equivalent with or without a subsequent oral prednisone taper.31
Outcome Evaluation
• Monitor for improvement of symptoms
• Educate regarding adverse effects and reporting directions
Disease-Modifying Therapies
Six agents are indicated for MS: subcutaneous interferon β-1a (Rebif); intramuscular interferon β-1a (Avonex); interferon β-1b (Betaseron); glatiramer acetate (Copaxone); mitoxantrone (Novantrone); and natalizumab (Tysabri). A broad look across all studies of these immunomodulators shows about 30% relapse reduction.32
β-Interferons
Pharmacology and Mechanism of Action. The mechanism of action of β-interferons is incompletely understood. The following properties are thought to be important:
• Decrease in T-cell activation, decreasing cytokine secretion and preserving myelin
• Prevention of upregulation of adhesion molecules on activated T cells, limiting the number of T cells that can get into the brain
• Suppression of MMPs, maintaining the integrity of the blood-brain barrier
FIGURE 29–2. McDonald diagnostic criteria for MS.17–19 MRI evidence of dissemination over time is a gadolinium-enhancing lesion on an MRI done at least 3 months following onset of clinical attack at a site different from the initial attack, or a gadolinium-enhancing lesion or new T2-weighted lesion 6 months following onset of clinical attack. Positive CSF is oligoclonal immunoglobulin G bands in CSF but not serum or elevated immunoglobulin G index. Positive evoked potentials are delayed, but maintain a well-preserved waveform. (CSF, cerebrospinal fluid.)
* Dissemination in space by MRI evidence of nine or more T2-weighted brain lesions, or two or more cord lesions, or four to eight brain and one cord lesion, or positive visual evoked potentials with four to eight MRI lesions, or positive visual evoked potentials with less than four brain lesions plus one cord lesion.
• Decrease in microglial proliferation, preserving myelin
• Promotion of formation of Th2 cells rather than Th1 cells, decreasing inflammation
• Inhibition of viruses, important if MS has a viral etiology8,33
Efficacy
Patients With Relapsing Remitting MS. A meta analysis of all β-interferons determined that treated patients were 27% and 19% less likely to have a relapse during the first and second years of treatment, respectively, compared to placebo.34 Early treatment after a first clinical attack delayed time to a second attack by 9 to 13 months compared to placebo.35,36 Treating early is also associated with a lower incidence of developing clinically definite MS compared to delaying treatment.37,38
Patients With Secondary Progressive Ms Who Experience Relapses. β-Interferons have mixed results for slowing disease progression in secondary progressive MS. Treatment is most likely to be effective if clinical relapses or MRI signs of inflammatory activity are present.39
Adverse Effects. Adverse effects are common with the β-interferons (Table 29–3). Flu-like symptoms include fever, fatigue, muscle aches, malaise, and chills. Symptoms begin a few hours postinjection and dissipate within 8 to 24 hours.40 Preventive measures can be employed (Table 29–4). In temperature-sensitive patients, β-interferon–induced fever can transiently worsen MS symptoms. Injection site reactions range from redness to necrosis. There are preventive and treatment measures for these reactions (Table 29–4). At the threshold laboratory values (Table 29–4), interferon should be suspended. When values normalize, interferon is resumed with gradual dose increases and careful monitoring.40α-and γ-interferons are associated with depression. Up to 50% of MS patients experience depression, even without β-interferon treatment.14 Because of conflicting data, it is difficult to determine whether β-interferons cause or worsen MS-related depression.14
FIGURE 29–3. Comparison of clinical course of MS by type.
Table 29–2 Clinical Rating Scales Used in MS
|
EDSS |
|
Rates functional systems from 0 (normal) to 10 (death due to MS) Emphasis is on ambulation over other symptoms |
|
MSFC |
|
Three-part tool rating ambulation, limb function, and cognitive function |
|
Composite score is compared to standardized population |
|
Correlates better with MRI data than EDSS |
|
MS, multiple sclerosis; EDSS, Expanded Disability Status Scale; MSFC, multiple sclerosis functional composite. |
|
From Refs. 21, 22. |
Patient Encounter, Part 1
CN is a 28-year-old woman who complains of a 2-day history of weakness and tingling in her right arm and leg. These symptoms began over a 4-hour period. She also reports an episode 2 years ago of right eye pain and blurred vision that resolved over 1 month. She was diagnosed with optic neuritis at that time. Following an MRI, she is diagnosed with relapsing remitting MS today.
Why was her MS classified as relapsing remitting?
How would you treat the episode today?
Tests for Responsiveness. Antibodies to β-interferons can reduce their clinical benefit.41 Neutralizing antibodies develop 18 to 24 months after treatment begins.41 Neutralizing antibodies can form against any β-interferon, but frequency and route of administration affect neutralizing antibody development: 28% to 47% for subcutaneous interferon β-1b; 12% to 28% for subcutaneous interferon β-1a; and 2% to 6% for intramuscular interferon β-1a.41
Issues surround neutralizing antibodies including standardization of the neutralizing antibody assay, testing recommendations, and treatment recommendations for positive tests.42 Neutralizing antibodies may disappear even during continued treatment.43 Neutralizing antibodies exhibit cross-reactivity with other β-interferons.42
Table 29–3 Comparison of Disease-Modifying Therapies
Table 29–4 Prevention or Treatment Strategies for β- Interferon Adverse Effects
β-Interferons induce the expression of interferon-responsive genes, such as myxovirus-resistance-protein A (MxA). The ability of the patient to respond to β-interferons can be determined by testing MxA gene expression. Lack of expression is associated with MS relapses.44
Dosing and Administration. Dose, frequency, and route of administration differ between the β-interferon products (Table 29–3). Dose-response curves have been observed with the β-interferons. However, it is unknown if the total weekly dose or the frequency of administration is more important.39
Glatiramer Acetate
Pharmacology and Mechanism of Action. The mechanism of action of glatiramer acetate is unknown; the following properties have been observed:
• Binds to MHC class II, blocking the activation of T cells
• Activates Th2 cells, preventing inflammation
• Activated Th2 cells secrete brain-derived neurotrophic factor, which may be neuroprotective.8,33
Efficacy. Glatiramer acetate reduces relapses by 28% each year compared to placebo. Additionally, relapses occur later compared to placebo (322 vs 219 days).45
Adverse Effects. Patients report pain, redness, itching, swelling, and bruising at injection sites (Table 29–3). Icing the injection site pre-and post-injection improves these reactions; topical anesthetics can also be used. Systemic reactions involve flushing, chest tightness, palpitations, anxiety, and shortness of breath. This reaction usually occurs within 30 minutes of the injection; recurrence is infrequent. Doses may be reduced by 75% for the week following the reaction, then increased by 25% per week to the full dose.46
Issues With Self-Injected Disease-Modifying Therapies
Adherence. Adherence to injectable medications is a significant problem; but there is no significant difference in rates of discontinuation between products (17%–41%). Main reasons for discontinuation are adverse effects and lack of efficacy. Realistic expectations regarding therapy and higher educational levels improve adherence rates.47
Choosing Therapy. There is no consensus on the best medication for initial therapy. Comparative β-interferon trials indicate better efficacy with more frequent and/or higher dosing.39 This consideration must be balanced with neutralizing antibody development, patient acceptance, and tolerance.
Patient Education. Refer to Table 29–5 for key components of patient self-injection education.
Mitoxantrone
Pharmacology and Mechanism of Action. Mitoxantrone is an anthracenedione antineoplastic indicated for MS. The mechanisms of action thought to be important for MS are as shown below:
Table 29–5 Patient Education for Self-Injection
|
Keep all nonrefrigerated supplies together and out of the reach of children and pets |
|
If refrigerated, allow medication to warm to room temperature |
|
Wash hands thoroughly |
|
Choose injection site, rotating among sites |
|
Ice area to be injected for no more than 15 minutes, if desired |
|
Clean injection site thoroughly with alcohol or soap and water |
|
Administer injection |
|
Ice injection site for no more than 15 minutes after injection, if desired |
• Causes apoptosis in T and APCs, preventing initial T cell activation
• Inhibits DNA and RNA synthesis, decreasing the proliferation of T cells, B cells, and macrophages
• Decreases cytokine release, preventing inflammation
• Inhibits macrophages, preventing myelin degradation48
Efficacy. Mitoxantrone is indicated for secondary progressive MS, progressive relapsing MS, and for patients with worsening relapsing remitting MS. It reduces the clinical attack rate and attack-related MRI outcome measures in patients with relapsing disease. Because of significant potential for toxicities, mitoxantrone should be reserved for patients with rapidly advancing disease who have failed other therapies.26
Adverse Effects. Adverse effects are seen regularly in patients given mitoxantrone (Table 29–3). Bluish discoloration of the sclera and the urine often lasts 24 hours postinfusion.49 Transient leukopenia and neutropenia are common (nadir 10−14 days after the infusion); exposure to infectious individuals during this time should be avoided.49 Patients taking mitoxantrone should not receive live virus vaccines; other vaccines should be held for 4 to 6 weeks after a mitoxantrone dose.49 Amenorrhea may be permanent, an important consideration in women of child-bearing potential.26
Arrhythmias may occur shortly after the drug is given. Cardiotoxicity is a serious, rare adverse effect of mitoxantrone. The incidence of congestive heart failure was 0.15% in patients with normal left ventricular ejection fraction and 2.18% in those who had asymptomatic left ventricular ejection fraction of less than 50% at baseline.49 Therefore, mitoxantrone should not be used in patients with baseline cardiomyopathy, even if asymptomatic. The risk of cardiotoxicity is dose related. The maximum lifetime dose of mitoxantrone is 140 mg/m2 (about 3 years of therapy). Cyclooxygenase-2 inhibitors should be avoided in patients receiving mitoxantrone because of a potential for worsening cardiac toxicity.49
Acute myelogenous leukemia occurred in 0.07% of mitoxantrone-treated patients.49 This acute leukemia appears within 2 to 4 years of initiating mitoxantrone and is generally responsive to standard antileukemic therapy.
Table 29–6 Monitoring Disease-Modifying Therapies
Dosing and Administration Mitoxantrone is infused intravenously over 30 minutes to reduce the chance of cardiotoxicity.49 Mitoxantrone is administered every 3 months, if cardiac function and laboratory values are normal (Table 29–6).
Natalizumab
Pharmacology and Mechanism of Action. Natalizumab is α4-integrin antagonist indicated for relapsing forms of MS. Its postulated mechanism of action follows:
• Binds to α4β7 and α4β7 integrins, preventing migration of lymphocytes into the CNS and inflammation
• Inhibits binding of α4-positive leukocytes to fibronectin and osteopontin, decreasing the activation of leukocytes already within the CNS50
Efficacy. Treatment with natalizumab reduced relapses by 68% at 1 year and disability by 42% at 2 years compared to placebo.50
Adverse Effects. Adverse effects of natalizumab include infection, arthralgia, headache, and fatigue.50 Hypersensitivity reactions have been observed; symptoms may include itching, dizziness, fever, rash, hypotension, dyspnea, chest pain, and anaphylaxis, usually within 2 hours of administration. A much more serious, but rare, adverse effect is progressive multifocal leukoencephalopathy (PML). PML, caused by the JC polyomavirus virus, is rapidly progressive and usually results in death or permanent disability. Shortly after natalizumab was introduced, three patients developed PML, leading to temporary withdrawal of the medicine. Natalizumab was reintroduced through a restricted distribution program. These concerns lead to the recommendation that natalizumab be reserved for patients with rapidly advancing disease who have failed other therapies. Specific recommendations are to avoid in patients with PML, HIV, immunodeficiency, or hematological malignancy; to carefully assess for immune compromise in patients previously treated with immunosuppression or chemotherapy; and to perform a baseline cranial MRI for later comparison if new neurologic symptoms develop.51
Antinatalizumab antibodies develop in 9% to 12% of patients. If patients are persistently antibody-positive, relapse rates and disability increase; antibody development is also associated with hypersensitivity reactions.52
Dosing and Administration. Natalizumab should be used as monotherapy for MS.51 Natalizumab is administered 300 mg in 100 mL normal saline over a 1-hour IV infusion every 4 weeks. Patients have not been treated for more than 2 years with natalizumab.
Outcome Evaluation
• Assess periodically for changes in symptoms.
• In patients taking β-interferons with frequent relapses, testing for neutralizing antibodies and/or MxA gene expression may assist in choosing therapy.
• Monitor the patient for medication-specific adverse effects (Tables 29–3 and 29–6).
• Assess regularly for adherence with all components of therapy.
Symptomatic Therapies
MS patients develop many symptoms that require treatment. The symptoms most unique to MS are fatigue and spasticity. Other important symptoms such as urinary incontinence, pain, depression, cognitive impairment, and sexual dysfunction are discussed only briefly (refer to other chapters).
Fatigue
There are nonpharmacologic and pharmacologic strategies for decreasing the impact of fatigue on the lifestyle of MS patients (Table 29–7). Pharmacologic management of fatigue includes amantadine or stimulants; however, evidence of efficacy from randomized controlled trials is limited.
Spasticity
The goals of treating spasticity are patient-specific. For ambulatory patients, reducing spasticity may improve mobility. For bed-bound patients, treating spasticity may relieve pain and facilitate transfers and care. Physical therapy is a nonpharmacologic treatment for spasticity.10
Patient Encounter, Part 2
CN begins to improve after 2 days of methylprednisolone 1 g IV daily. The treatment team wants to begin a disease-modifying treatment.
Do you agree that she should be on a disease-modifying treatment? Why?
If so, which treatment would you choose? Recommend a dosing regimen.
How should the patient be counseled on the chosen treatment?
MS patients usually have upper motor neuron spasticity; this type of spasticity cannot be treated with muscle relaxants (i.e., carisoprodol). MS patients must be treated with agents specific for upper motor neuron spasticity (Table 29–8).10 MS spasticity is classified as focal or generalized. If the spasticity involves only one muscle group, it is focal and may benefit from botulinum toxin administration.10Systemic medications are used for generalized spasticity. No clear conclusion can be reached regarding the superiority in efficacy of one agent; medication selection is usually based on adverse effects (see Table 29–8).10
Other Symptoms
Two types of urinary tract symptoms are commonly seen in MS: Incomplete bladder emptying and incontinence. Incomplete bladder emptying is due to dyscoordination of the external urethral sphincter and detrusor activity.13 Most patients who develop this condition require intermittent or permanent urinary catheterization.13 Incontinence in most MS patients is caused by neurogenic detrusor overactivity. First-line treatments are anticholinergics such as oxybutynin, tolterodine, flavoxate, or antimuscarinic tricyclic antidepressants.
Bowel symptoms in MS patients can include both fecal incontinence and constipation. Fecal incontinence is difficult to treat; a regular schedule for emptying the bowel with laxative suppositories or enemas may be helpful. Alternatively, antidiarrheal medications such as loperamide can be used.13
Pain may occur in up to 86% of patients with MS. Pain may be neuropathic, related to spasticity, related to treatment, or unrelated to MS. Correct pain type classification is necessary for effective treatment.16
Desipramine and sertraline are efficacious for MS-related depression.14 If β-interferon treatment appears to be causing depression, discontinuation could be considered.
Table 29–7 Pharmacologic and Nonpharmacologic Treatments for Fatigue
Table 29–8 Comparison of Antispasticity Agents
Patient Encounter, Part 3
After 3 years of treatment, CN has had one additional relapse, but otherwise is doing fairly well. At her routine clinic appointment, she describes some difficulty walking due to leg spasticity and urinary incontinence episodes that occur about twice a week.
What treatment options are available for spasticity, and which would you choose?
Should this patient’s incontinence be treated? If so, what medication would you recommend?
Cognitive impairment and memory dysfunction can be troublesome, affecting 40% to 60% of patients. Treatment with β-interferon has demonstrated improvement. Acetylcholinesterase inhibitors may also be beneficial.55
Phosphodiesterase type 5 inhibitors are effective for MS-induced erectile dysfunction.13 In women, vaginal dryness or dyspareunia may respond to lubricating jellies.
Outcome Evaluation
• Assess for improvement/recurrence of symptoms.
• Monitor for adverse effects of medications.
• Monitor for adherence.
Patient Care and Monitoring
1. Once diagnosed, work with the patient to select either a β-interferon or glatiramer acetate, considering:
• Route of administration
• Frequency of administration
• Adverse-effect profile and other concerns (e.g., neutralizing antibodies and concomitant depression)
2. Obtain the required baseline laboratory studies (Table 29–6).
3. Educate the patient regarding self-injection (Table 29–5).
4. Assess the patient for symptomatic treatment needs.
5. Initiate needed symptomatic treatments.
6. Refer the patient to the National MS Society for information, newsletters, and local support groups (www.nmss.org).
7. Instruct the patient to contact the clinician for any sudden changes in symptoms that may suggest a relapse.
8. Monitor the patient for efficacy and adverse effects of disease-modifying and symptomatic therapies every 3 months for the first year and every 6 months thereafter and as required for selected therapy (Table 29–6).
9. Treat any relapses with methylprednisolone IV or prednisone orally.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.comlpp.html.
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