Nursing Management of the Patient with Multiple Sclerosis

AANN, ARN, and IOMSN Clinical Practice Guideline Series

This publication was made possible by an educational grant from TEVA Neuroscience. Editors American Association Hilaire J. Thompson, PhD RN CNRN FAAN of Neuroscience Nurses Kristen L. Mauk, PhD DNP RN CRRN GCNS-B, GNP-BC 4700 W. Lake Avenue FAAN Glenview, IL 60025-1485 Chairs 888.557.2266, Fax 847.375.6430 Amy Perrin Ross, MSN APN MSCN CNRN International phone 847.375.4733 Suzanne C. Smeltzer, EdD RN MSCN FAAN [email protected] • www.AANN.org Joan Kram, MBA RN FACHE Content Authors Executive Director Megan Barrett, DNP MSCN ARNP June M. Pinyo, MA Cheryl Blaschuk, MSN RN MSCN FNP Managing Editor Kathleen Costello, MS ANP-BC MSCN Constance Easterling, MSN MSCN ARNP Sonya L. Jones Ann Gutierrez, MSN RN CRRN CBIS Senior Graphic Designer June Halper, MSN APN-C MSCN FAAN Paule Joseph, MSN FNP-BC RN CRRN BCLNC-C Association of Rehabilitation Nurses Patricia Kennedy, RN CNP MSCN 4700 W. Lake Avenue Mary Kitten, MSN RN MSCN CRRN Glenview, IL 60025-1485 Martha Lightfoot, ANP 800.229.7530 Elizabeth McAndrews, MSN CRNP [email protected] • www.rehabnurse.org Margie O’Leary, MSN RN MSCN Brant J. Oliver, MSN MPH FNP-BC PMHNP-BC Karen Nason, CAE Patricia Pagnotta, MSN ARNP MSCN CNRN Executive Director Dorothea Cassidy Pfohl, BSN MSCN RN Yaritza Rosario, APN MSCN International Organization of Angela Stone Schmidt, PhD MNSc RNP RN Multiple Sclerosis Nurses Matthew Sorenson, PhD RN 359 Main Street, Suite A Alpa Uchil, MPH RN Hackensack, NJ 07601 201.487.1050, Fax 201.678.2291 Content Reviewers www.iomsn.org Lisa Duffy, PhD(c) CPNP-PC CNRN Debra A. Dzenko, MSN Ed RN-BC CCM CRRN June Halper, MSN APN-C MSCN FAAN Jennifer Smrtka, ANP-BC MSCN Executive Director

Publisher’s Note The authors, editors, and publisher of this document neither represent nor guarantee that the practices described herein will, if followed, ensure safe and effective patient care. The authors, editors, and publisher further assume no liability or -re sponsibility in connection with any information or recommendations contained in this document. These recommendations reflect the judgment from the American Association of Neuroscience Nurses, the Association of Rehabilitation Nurses, and the International Organization of Multiple Sclerosis Nurses regarding the state of general knowledge and practice in our field as of the date of publication and are subject to change based on the availability of new scientific information.

Copyright ©2011 by the American Association of Neuroscience Nurses (AANN), the Association of Rehabilitation Nurses (ARN), and the International Organization of Multiple Sclerosis Nurses (IOMSN). No part of this publication may be reproduced, photocopied, or republished in any form, print or electronic, in whole or in part, without written permission of AANN, ARN, or IOMSN.

2 Nursing Management of the Patient with Multiple Sclerosis Preface In 1997, the American Association of Neuroscience Nurses (AANN) created a series of patient care guidelines, the AANN Reference Series for Clinical Practice, to meet its members’ needs for educational tools. To better reflect the nature of the guidelines and the organization’s commitment to developing each guideline based on current literature and evidence-based practice, the name of the series was changed in 2007 to the AANN Clinical Practice Guideline Series. This guideline represents a milestone in the series because AANN has now partnered with the Association of Rehabilitation Nurses (ARN) and the International Organization of Multiple Sclerosis Nurses (IOMSN) in the development of this guideline. This is the second guideline to be developed collaboratively between AANN and ARN and promotes evidence-based practice for the adult patient with multiple sclerosis (MS) across the continuum of care. Nursing care of patients with MS and their families or care partners has evolved from a focus on interventions during periods of crisis to a focus on symptom management, wellness, prevention of disease worsening, and empowerment. The goal of this guideline is to offer evidence-based recommendations on nursing activities that have the potential to maximize outcomes for adults with MS. Not all recommendations concern activities independently performed by registered nurses (RNs), but nurses are responsible for implementing and monitoring the outcomes of these activities. The evidence presented here may help nurses make appropriate choices when caring for patients with MS. Dependent on scope of practice regulations, advanced practice nurses may have independent or collaborative responsibilities for activity performance; thus, this guideline may assist them in the management of patients with MS. Resources and recommendations must describe the best practices that can enable RNs to provide optimal care for persons with MS. Accordingly, adherence to these guidelines is voluntary, and the ultimate determination regarding their application must be made by practitioners in light of each patient’s individual circumstances. This reference is an essential resource for nurses providing care to the adult patient with MS. It is not intended to replace formal learning but rather to augment clinicians’ knowledge base and provide a readily accessible reference tool. The nursing profession, AANN, ARN, and IOMSN are indebted to the volunteers who have devoted their time and expertise to this valuable resource, which was created for those who are committed to excellence in the care of patients with MS.

Nursing Management of the Patient with Multiple Sclerosis 3 Table of Contents

I. Search Strategy and Levels of Evidence...... 6 A. Search strategy...... 6 B. Levels of evidence supporting the recommendations...... 6

II. Scope of the Problem: Definition, Natural History, and Epidemiology of Multiple Sclerosis (MS)...... 6 A. Definition...... 6 B. Epidemiology...... 6 C. Types of MS...... 6 D. Natural history of the disease...... 7 E. Genetics...... 7 F. Environmental risk factors...... 7 G. MS symptoms...... 8 H. Effect of the diagnosis...... 8

III. Classification of MS...... 9 A. Introduction...... 9 B. RRMS...... 9 C. PPMS...... 9 D. SPMS...... 10 E. PRMS...... 11 F. Benign MS...... 11 G. Malignant MS...... 11 H. Other types...... 11 I. Implications for patients...... 12

IV. Immunogenetics and Pathogenesis...... 12 A. General background...... 12 B. Pathophysiology of MS...... 12 C. Blood-brain barrier (BBB) in MS...... 12 D. T cell and B cell pathogenesis of MS...... 12 E. Neurodegeneration in MS...... 13 F. Remyelination...... 13

4 Nursing Management of the Patient with Multiple Sclerosis V. Assessment and Diagnostic Process...... 13 A. Introduction...... 13 B. Diagnostic criteria for MS...... 14 C. Assessment tools...... 14 D. Assessment charts...... 16 E. Assessment of reflexes...... 16 F. Diagnostic testing...... 16 G. Laboratory testing...... 20 H. Diagnostic research studies: Biomarkers...... 22

VI. Disease Management...... 25 A. Management of MS...... 25 B. Economic considerations...... 26 C. Immunotherapies reveal aspects of MS...... 26

VII. Clinical Features and Symptom Management...... 28 A. Clinical features overview...... 28 B. Sensory symptoms...... 29 C. Visual and hearing impairment...... 31 D. Fatigue...... 31 E. Impaired mobility...... 33 F. Bladder and bowel symptoms...... 34 G. Sexual dysfunction and reproductive issues...... 35 H. Dysphagia...... 35 I. Cognitive dysfunction...... 36 J. Mood dysregulation...... 37

VIII. Patient and Care Partner Education...... 38 A. General concepts for patient and care partner education...... 38 B. Goals...... 38 C. Role of the nurse...... 39 D. Concepts of learning...... 39 E. Learning needs in MS...... 39 F. Factors that affect learning...... 40 G. Plan: Teaching strategies...... 41

References...... 42

Bibliography...... 48

Nursing Management of the Patient with Multiple Sclerosis 5 I. Search Strategy and Levels of Evidence 2. The autoimmune cascade results in an inflam- A. Search strategy matory response against self-antigens in the A computerized search of MEDLINE, Cochrane, CNS, causing demyelination and axonal dam- and the Cumulative Index to Nursing and Allied age. Scarring visible at magnetic resonance Health Literature was performed by using multi- imaging (MRI) represents these pathological ple sclerosis, symptom, disease management, nurs- changes. Demyelination in the CNS disrupts ing, and education as keywords. The search was conduction in nerves, causing the hallmark restricted to works in English and adults. The ref- sensory, motor, and cognitive signs and symp- erence lists of identified articles were also searched toms of MS (De Jager et al., 2009; Harris & for additional, relevant references including Halper, 2004; Thrower, 2009; Trapp et al., books, guidelines, and articles. A panel of nursing 1998). experts determined the level of evidence for each 3. MS may present as a case of monosymptom- study included in the guideline, summarizing the atic or polysymptomatic neurologic abnor- level of evidence for each recommendation. mality. Most early cases are characterized by . B Levels of evidence supporting the periods of disease freedom with superim- recommendations posed relapses characterized by signs and • Class I: Randomized controlled trial without symptoms of CNS dysfunction (Confavreux, significant limitations or meta-analysis Vukusic, Moreau, & Adeleine, 2000). • Class II: Randomized controlled trial with im- B. Epidemiology portant limitations (e.g., methodological flaws 1. MS affects approximately 400,000 people in or inconsistent results), observational studies the United States alone, and more than 50,000 (e.g., cohort or case-control) Canadians (Costello & Halper, 2010a; Miller • Class III: Qualitative studies, case study, or et al., 2008). The projected prevalence rate of series MS for the white population in the year 2000 • Class IV: Evidence from reports of expert was 191/100,000, and the incidence rate was committees and/or expert opinion of the 7.3/100,000 person years at risk (Kantarci & guideline panel, standards of care, and clinical Weinshenker, 2005; Kantarci & Wingerchuk, protocols. 2006). There are 12,000 new cases of MS diag- The Clinical Practice Guidelines recommenda- nosed per year in the United States (Alonso & tions for practice are established on the basis of Hernán, 2008). the evaluation of the available evidence (AANN, 2. Review of incidence data suggests the lifetime 2005; adapted from Guyatt & Rennie, 2002; Mel- risk of MS is 2.5% for women and 1.4% for nyk, 2004): men (Alonso & Hernán, 2008). MS is gener- • Level 1 recommendations are supported by ally at least twice as common in women as it is Class I evidence. in men, with some data suggesting the male- • Level 2 recommendations are supported by to-female ratio is as high as 1:4 (Beck et al., Class II evidence. 2003; Kantarci & Wingerchuk, 2006; Vukusic • Level 3 recommendations are supported by & Confavreux, 2007). Class III and IV evidence. 3. The age of onset peaks between 25 and 35 years of age. Men may have a later onset of II. Scope of the Problem: Definition, Natural History, disease and a worse prognosis (Kantarci & and Epidemiology of Multiple Sclerosis (MS) Wingerchuk, 2006; Vukusic & Confavreux, A. Definition 2007). Despite the young age of disease on- . 1 MS is a progressive, inflammatory, neurode- set and the potential for neurologic disability, generative demyelinating disease of the central the life expectancy of people with MS is only nervous system (CNS) predominantly affecting slightly reduced (Compston et al., 2006). Fif- white matter (Miller et al., 2008). It is the most ty percent of MS patients will die from causes common nontraumatic cause of neurolog- other than MS (Sadovnick, Eisen, Ebers, & ic disability in young adults (Fleming & Car- Paty, 1991). rithers, 2010). The cause of MS is unknown; C. Types of MS however, research suggests that an abnormal 1. There are four defined clinical types of MS: re- autoimmune response to myelin develops in lapsing-remitting MS (RRMS), primary pro- genetically susceptible individuals after expo- gressive MS (PPMS), secondary progressive sure to one or more environmental agents. MS (SPMS), and progressive-relapsing MS

6 Nursing Management of the Patient with Multiple Sclerosis (PRMS). These types are described by relaps- Higher EDSS scores indicate higher levels of dis- es, remission, and chronic progression (inability (Kurtzke, 1983). creasing disability as time passes). Relapse can E. Genetics be followed by full or partial recovery. Disease 1. Family history is the strongest known risk fac- severity varies considerably among people tor for MS. In fact, MS is 20–40 times more with MS, no matter the type ascribed to them common among first-degree relatives, with (Compston et al., 2006). a rapid decrease in risk with degree of relat- 2. Initially, 85% of cases are RRMS, and 15% are edness (Ascherio & Munger, 2008; Kantarci, PPMS. When a person with RRMS begins to 2008; Kantarci & Wingerchuk, 2006; Vukusic acquire disability, SPMS is said to occur. This & Confavreux, 2007; Weinshenker, 1996). phase of the disease evolves owing to progres- 2. There have been at least 13 genetic suscepti- sive axonal injury. The median time to con- bility loci identified by scientists (Australia version from RRMS to SPMS is 19 years, and and New Zealand Multiple Sclerosis Genetics 75% will reach this phase by 25 years. Approx- Consortium [ANZgene], 2009; International imately 40% of progressive cases (SPMS and Multiple Sclerosis Genetics Consortium, 2007; PPMS) still experience relapses (Compston et De Jager et al., 2009), and it has been suggest- al., 2006; Frohman et al., 2005; Kantarci, 2008; ed that 10–50 genes are related to genetic sus- Runmarker & Andersen, 1993). Nonetheless, ceptibility to MS (Baranzini, 2010). in progressive patients, the course of disability . F Environmental risk factors progression is not affected by relapses (Confa- 1. The estimated genetic risk of MS is 25%–35% vreux, Vukusic, & Adeleine, 2003). based on monozygotic twin studies (Kantarci, 3. There is a theory that the clinical subtypes of 2008). Incomplete penetrance of heritability MS may be separate phenotypes of one dis- provides evidence that there are environmen- ease process. The differing types of MS may tal factors at play in MS susceptibility. MS is represent various points along the spectrum more common in Europe, the United States, of MS. However, distinct pathophysiological Canada, New Zealand, and Southern Austra- processes have not yet been identified (Confa- lia than in Asia, the tropics, and the subtrop- vreux & Vukusic, 2006; Lublin, 2010). ics. The incidence and prevalence increases . D Natural history of the disease with latitude relative to the equator. Review of 1. Despite the unpredictable nature of MS, re- the MS literature suggests there may be atten- sults of cohort studies provide general prog- uation in the latitude gradient, or MS belt, re- nostic factors. inforcing the role that environmental factors 2. Better disease prognosis is associated with play in MS etiology (Ascherio & Munger, 2008; younger age at onset, female sex, monosymp- Bakshi, Hutton, Miller, & Radue, 2004; Fran- tomatic presentation (particularly optic neu- ciotta, Salvetti, Lolli, Serafini, & Aloisi, 2008). ritis or sensory symptom), complete recovery 2. Additionally, migrant studies suggest one as- from relapse, a long interval between presen- sumes the risk of one’s final place of residence, tation and second event, relapsing course, and rather than of one’s birthplace, if migration a low number of relapses (Lisak, 2001; Miller occurs in childhood (Zivadinov et al., 2009). et al., 2008). a. The strongest support for environmental 3. Poor long-term prognosis has been associated risk factors is based on geographic distri- with male sex; older age at disease onset (> 40 bution and studies of migration to Israel, years); motor, cerebellar, or sphincter symp- from the United Kingdom to South Afri- toms at initial presentation; polysymptomat- ca, from the United Kingdom to Australia, ic presentation; frequent attacks in the first 5 and from the United Kingdom to the Unit- years; short interval between first two attacks; ed States (Alter, Kahana, & Loewenson, short time to reach an Expanded Disability 1978; Alter, Leibowitz, & Speer, 1966; Dean Status Scale (EDSS) score of 4; and a progres- & Kurtzke, 1971; Hammond, English, & sive course (Bergamaschi, Berzuini, Romani, McLeod, 2000; Kurtzke, Beebe, & Norman, & Cosi, 2001; Compston & Coles, 2002; Con- 1985). favreux, Vukusic, Moreau, & Adeleine, 2000; . b Studies show that the risk of MS is low in Riise et al., 1992; Trojano et al., 1995; Vuku- migration from the Far East to the United sic & Confavreux, 2007). Note: A standard Kingdom and North America as compared measure of disability in MS is the EDSS score. with that of migration from India, when

Nursing Management of the Patient with Multiple Sclerosis 7 the risk of MS increases in the second gen- more than 24 hours that does not have an alter- eration. Typically, migration studies are not native explanation. Pseudorelapses are related able to establish timing of environmental to infection or heat exposure and do not repre- exposures (Ebers, 2008; Elian, Nightingale, sent new disease activity. & Dean, 1990). H. Effect of the diagnosis 3. Other strong environmental factors associated 1. An MS diagnosis is a life-altering event. MS is with MS include lack of vitamin D exposure, a chronic, often disabling disease that may af- smoking, and the Epstein-Barr virus (EBV). fect the physical, economic, psychological, and a Past sun exposure and vitamin D supple- social aspects of a patient’s life. The unpredict- mentation have been associated with de- able nature and varied symptoms of the disease creased risk of MS (Coo & Aronson, 2004; mean that patients face a future of uncertainty. Marrie, 2004; Munger, Levin, Hollis, How- 2. Managing MS consists of primarily manag- ard, & Ascherio, 2006; Munger, et al., 2004; ing the symptoms that are associated with the Soilu-Hänninen et al., 2005). disease. For example, time management and . b Heavy smoking (defined as more than 25 conservation of energy have been the recom- pack-years) increases MS risk by approxi- mended forms of managing fatigue. If tremors mately 70%, and the increase in risk is dose and gait imbalance are the major presenting responsive (Ascherio & Munger, 2007; symptoms, medications and/or physical thera- Hedström, Bäärnhielm, Olsson, & Alfreds- py have been shown to be helpful. son, 2009; Hernán et al., 2005; Hernán, 3. The financial effect of MS should be consid- Olek, & Ascherio, 2001). Among MS pa- ered, because treatment can be costly. There tients, smoking is associated with higher are a number of disease-modifying thera- levels of disability, greater number of en- pies (DMTs), including interferon-beta-1a hancing T2 and T1 lesions, greater lesion (IFN β-1a), IFN β-1b, glatiramer acetate, volume, and more brain atrophy (Zivadi- and natalizumab. Other DMTs being used or nov et al., 2009). investigated include mitoxantrone and cyclo- c. Data from several Class II studies support phosphamide. Both direct and indirect costs the association of EBV with MS. There is ev- may or may not be reimbursed by insurance idence that the presence of EBV in plasma is plans, which vary individually. Costs and associated with increased risk of MS (Wag- quality of life (QOL) are significantly corre- ner, Munger, & Ascherio, 2004). MS risk in- lated with functional capacity (Kobelt, Berg, creases sharply after EBV infection (Levin, Atherly, & Hadjimichael, 2006). Munger, O’Reilly, Falk, & Ascherio, 2010). 4. Debilitating diseases with no cure can be a G. MS symptoms burden financially for patients and families. 1. MS is associated with numerous symptoms, Patients with MS may face loss of employ- and MS symptoms vary widely from individ- ment. In addition, the financial effect of the ual to individual. Symptoms of MS are unpre- disease may be related to the cost of needed dictable and often interfere with activities of services, other care providers, and possibly daily living (ADLs). the need to modify the patient’s home envi- 2. Primary symptoms of MS are caused by the ronment to accommodate changing abilities. dysfunction of nerve conduction because of 5. RRMS affects a majority of the MS popula- demyelination, inflammation, and axonal loss tion. Although there are several DMTs for in the CNS (Lisak, 2001). RRMS, not all are available for the same cost. 3. MS symptoms include spasticity, fatigue, pain, Goldberg and colleagues (2009) evaluated the disturbance of elimination (bladder or bow- 2-year effectiveness of four DMTs used for el), unilateral vision loss, vertigo, Lhermitte’s RRMS—glatiramer acetate, IFN β-1an intra- sign, sexual dysfunction, cognitive dysfunc- muscular (IM) injection, IFN β-1a subcutane- tion, ataxia, tremor, depression, oculomotor ous (SC) injection, and IFN β-1b SC injection. dysfunction, dysarthria or dysphonia, dyspha- These four DMTs are the most cost-effective gia, and seizure (Compston et al., 2006; Lisak, treatments for RRMS (Goldberg et al.). 2001; Harris & Halper, 2004; Stuke et al., 2009). 6. QOL may be affected by the financial costs -re 4. A relapse (also known as an attack or exacerba- lated to MS (De Judicibus & McCabe, 2007). tion) is defined as a new neurologic symptom, Life-altering decisions can create an enor- or worsening of previous symptom(s), lasting mous amount of uncertainty, followed by

8 Nursing Management of the Patient with Multiple Sclerosis making adjustments to accommodate the classification of MS clinical subgroups was change. Financial stress can be caused by loss proposed from an international survey of MS of income and the strain that patients and clinicians, and standardized definitions for their families undergo as they adjust to loss the most common clinical courses of MS were and the possible increased need to cover the defined. cost of required medical and related services a. The clinical course was defined by the fol- (De Judicibus & McCabe). lowing descriptions: RRMS, PPMS, SPMS, 7. The disease affects the caregivers as well. In PRMS, benign MS, malignant MS (Lublin a small qualitative study in the United King- & Reingold, 1996). dom, interviews were conducted of 8 partners . b The terms benign and malignant MS are who lived and cared for a person with MS used to describe relatively mild and very (Mutch, 2010). The study showed that dis- progressive courses of MS, respectively. ability due to MS significantly affected their Both are relatively rare. lifestyles after 20 years of marriage; partners 2. When patients receive a disease diagnosis un- felt obligated to continue caring for the affect- der one of the above classifications, both the ed spouse and consequently lost their iden- patients and families may need further ex- tity as husband or wife. Partners also yearned planation to understand the disease’s clinical for independence and were not satisfied with course; the importance of disease-modifying their own QOL because MS care was a dai- therapy and symptom management, if ap- ly occurrence (Mutch, 2010). Caregivers also propriate; and the need for regular follow-up go through life-altering decisions and chang- with the neurologist and other care providers. es secondary to their partner’s health, and as B. RRMS a result they have their own needs (Corry & 1. RRMS is marked by periods of acute decline While, 2008). As the disease progresses, care- or exacerbations in neurologic function fol- givers may be increasingly required to care lowed by a variable degree of recovery with for the patient because of the debilitating na- stable periods between attacks (Lublin & Re- ture of the disease (Buhse, 2008). As a result, ingold, 1996). Patients may experience total or caregiver burden becomes a cluster of physi- partial remission of symptoms (Figure 1). cal, social, economic, and psychological re- 2. Relapse (exacerbation) is the appearance of sponses—caregivers who are highly burdened a new symptom or reappearance of a prior were shown to have lower QOL and higher symptom lasting more than 24 hours (Lublin risk for depression (Buhse). Further study of & Reingold, 1996). Pseudoexacerbation refers the caregiver population is needed. to changes in neurologic function triggered Recommendations: The model of nursing care in MS in- by infection, fever, heat, and fatigue. These cludes establishing, continuing, and sustaining care along the relapses occur from decompensation of exist- MS spectrum of new or probable MS, relapsing forms of MS, ing CNS scars and are not indicative of new progressive MS, and advanced MS (Level 3). Nurses should inflammatory CNS lesions (Birnbaum, 2009). facilitate treatment and symptom management, promote and 3. Onset of neurologic changes may occur over enhance function, and support a QOL of adults with MS and several hours or appear over days to weeks. their family-care partners that is wellness focused (Level 3). Symptoms may be focal and can spread over Nurses use evidence-based knowledge to determine an ef- other body regions. A relapse may last from fective course of action for MS patients with specific needs a few days to several weeks or more. Full (Level 2). Nurses act as advocates to ensure that patients and or partial recovery may occur with the dis- their family-care partners have access to needed care and as- ease remaining stable between relapses. This sistance in using resources crucial to managing MS (Level 2). relapsing-remitting course is seen in ap- Nurses should help patients locate and develop appropriate proximately 80%–85% of patients (Nosewor- resources and initiate contacts as needed (Level 2). thy, Lucchinetti, Rodriguez, & Weinshenker, 2000). Treatment with immune-modulating III. Classification of MS therapies and corticosteroids is indicated. A. Introduction C. PPMS 1. MS is an immune-mediated disease of the 1. PPMS presents with a gradual onset of symp- CNS with inflammatory and degenera- toms that worsen over time with minor fluc- tive characteristics (Siva, 2006). The clini- tuations that progress and do not reverse cal course may be variable. In 1996 a formal (Figure 2).

Nursing Management of the Patient with Multiple Sclerosis 9 Figure 1. Characterization of the natural history of relapsing- Figure 2. Characterization of the natural history of primary remitting multiple sclerosis progressive multiple sclerosis

Relapsing-remitting (RR) MS is characterized by clearly defined acute attacks with (A) full recovery or (B) sequelae and residual deficit upon recovery. Periods between disease relapses are characterized by lack of disease progression. From Lublin, F. D., & Reingold, Primary progressive (PP) MS is characterized by disease showing progression of disabil- S. C. Defining the clinical course of multiple sclerosis: Results of an international survey. ity from onset (A) without plateaus or remissions or (B) with occasional plateaus or tem- National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New porary minor improvements. From Lublin, F. D., & Reingold, S. C. Defining the clinical Agents in Multiple Sclerosis Neurology, 46(4):907–911. Reproduced with permission course of multiple sclerosis: Results of an international survey. National Multiple Sclero- from Wolters Kluwer Health. sis Society (US) Advisory Committee on Clinical Trials of New Agents in Multiple Sclero- sis Neurology, 46(4):907–911. Reproduced with permission from Wolters Kluwer Health. 2. PPMS occurs in 10%–15% of patients, and age of onset is approximately 10 years older than D. SPMS that seen in RRMS (mean of 40 years versus 1. SPMS is seen as the long-term outcome of 30 years). RRMS, which occurs once the baseline be- 3. Most common presenting symptoms include tween relapses becomes progressively worse. progressive spastic paraparesis, usually in the Patients experience a gradual worsening of lower extremities, as well as impaired mobility the disease that is independent of continued with weakness, stiffness, and dragging of the exacerbations (Figure 3; Lublin & Reingold, legs. Exercise-related fatigable weakness, uri- 1996). nary urgency, urge incontinence, and erectile 2. Approximately 50% of patients with RRMS dysfunction are also common (Miller & Leary, will develop SPMS with time. The frequen- 2007). cy of relapses decreases, and patients experi- 4. PPMS may vary significantly from patient ence an increase in disability. The transition to patient. Some may experience profound from RRMS to SPMS may be rapid or gradual. disability within 1–2 years, whereas in oth- SPMS patients also present with fewer acute ers, progression may occur over decades. The inflammatory changes at brain and spine pathophysiology of PPMS is thought to be magnetic resonance imaging (MRI); therefore, different from that of RRMS, and, therefore, long-term immune-modulating therapies are long-term immune-modulating therapies are not indicated for treatment (Birnbaum, 2009). not indicated for treatment (Birnbaum, 2009).

10 Nursing Management of the Patient with Multiple Sclerosis Figure 3. Characterization of the natural history of secondary Figure 4. Characterization of the natural history of progres- progressive multiple sclerosis sive-relapsing multiple sclerosis

Secondary progressive (SP) MS begins with an initial RR course, followed by (A) pro- Progressive-relapsing (PR) MS shows proession from onset but with clear acute relaps- gression of variable rate that may also include (B) occasional relapses and minor re- es (A) with or (B) without full recovery. From Lublin, F. D., & Reingold, S. C. Defining the missions. From Lublin, F. D., & Reingold, S. C. Defining the clinical course of multi- clinical course of multiple sclerosis: Results of an international survey. National Multi- ple sclerosis: Results of an international survey. National Multiple Sclerosis Society (US) ple Sclerosis Society (US) Advisory Committee on Clinical Trials of New Agents in Multi- Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis Neurology, ple Sclerosis Neurology, 46(4):907–911. Reproduced with permission from Wolters Klu- 46(4):907–911. Reproduced with permission from Wolters Kluwer Health. wer Health.

E. PRMS G. Malignant MS 1. PRMS appears to progress clinically as seen A brief time after disease onset, the disease pro- in PPMS with acute relapses, and full recov- gresses rapidly and may lead to significant dis- ery may or may not occur. There is continued ability or death within 5 years of diagnosis; it is progression between relapses (Figure 4; Lub- thought to be extremely rare (Lublin & Reingold, lin & Reingold, 1996). 1996). 2. PRMS has a progressive onset with acute in- H. Other types flammatory activity in the CNS with relaps- The MS spectrum includes idiopathic inflam- es. These relapses can respond to short-term matory demyelinating diseases including the antiinflammatory therapies. The benefit of following: long-term immune-modulating therapies is 1. Subclinical multiple sclerosis (SCMS), which uncertain at this time (Birnbaum, 2009). presents with incidental lesions at MRI with- . F Benign MS out clinical signs and symptoms. 1. All neurologic systems of patients with benign 2. Clinically isolated syndrome (CIS), which is MS appear to be fully functional 15 years after a onetime neurologic episode consistent with the onset of disease (Lublin & Reingold, 1996). demyelination or CNS inflammation (Siva, 2. This form of the disease is characterized by a 2006). CIS may include optic neuritis, trans- full recovery and normal functioning after a verse myelitis, or isolated brain stem or cer- symptomatic period. It is thought to occur in ebellar syndromes. Patients with CIS are at about 5%–10% of cases of MS (Sayao, Devon- high risk of developing MS (Halper, Costello, shire, & Tremlett, 2007). & Harris, 2006).

Nursing Management of the Patient with Multiple Sclerosis 11 3. Other demyelinating diseases that may pres- leukocyte antigen (HLA) system cluster on ent as MS are acute disseminated encephalo- chromosome 6 (Ben-Zacharia & Morgante, myelitis and neuromyelitis optica (or Devic’s 2005; de Jong et al., 2002; Olerup et al., 1987). disease) (Wingerchuk, Lennon, Lucchinetti, 5. HLA genes help T cells distinguish self from Pittock, & Weinshenker, 2007). nonself (Ben-Zacharia & Morgante, 2005; de I. Implications for patients Jong et al., 2002; Olerup et al., 1987). 1. Some patients may have some familiarity with 6. Variations in several HLA genes are seen in au- MS; however, they may have an incorrect un- toimmune disease, when the body mounts an derstanding of MS. Patients and families may immune response (Ben-Zacharia & Morgante, imagine the worst case scenario and anticipate 2005; de Jong et al., 2002; Olerup et al., 1987.). a rapid decrease in function and the need for B. Pathophysiology of MS (Halper, Costello, & assistive devices, including a wheelchair. Harris, 2006) 2. Patients and their families need a realis- 1. The etiology of MS is not known. tic view of MS along with an understand- 2. It is hypothesized that MS is a virus-induced ing about the disease-modifying agents and immune-mediated disease. symptom-management strategies. 3. Lesions include acute plaques with active in- Recommendations: Nurses caring for patients flammatory infiltrates and macrophages, and with MS need an understanding of the various chronic, inactive demyelinated scars. types of MS and should be familiar with the typi- 4. Irreversible axonal damage and loss are cal clinical course of each type in order to caused by inflammation, demyelination, and • provide explanations and initiate patient ed- scarring. ucation and counseling for patients and their 5. Brain atrophy may be useful in measuring families disease progression and effects of long-term • provide information and counseling to help therapy. patients and care partners develop a real- C. Blood-brain barrier (BBB) in MS istic picture of the disease, the benefits of 1. BBB is formed primarily by tight junctions treatment, and expectations related to its between endothelial cells that are disrupted in management MS and result in lesion formation in the brain • help patients and their families cope with a and CNS (Riskind, 2007). new diagnosis of MS, adopt a healthy life- 2. Proinflammatory cytokines such as interleu- style, and maintain a positive and hopeful kin (IL)-1β that is expressed in MS lesions perspective may contribute to BBB permeability (Argaw • emphasize health-promotion strategies and et al., 2006). preventive health care and screening, includ- 3. With BBB disruption, immune cells and oth- ing the importance of regular follow-up with er molecules that assist in the migration of their neurologist and other healthcare provid- these immune cells called adhesion molecules, ers (Level 3). which are the target of MS therapies (natalizumab), and chemokines that may attract and . IV Immunogenetics and Pathogenesis stimulate the migration of leukocytes could A. General background also play a role in MS pathology. Chemokines 1. Up to 20% of MS patients have a family mem- could also play a role in the recruitment of oli- ber affected by the disease (Compston & godendrocytes and could be involved in re- Coles, 2002). myelination (Riskind, 2007). 2. The risk of developing MS is 20–30 times . D T cell and B cell pathogenesis of MS higher for siblings of affected individuals than 1. Cellular and humoral immunity (Halper, for the general population (3:1) (Compston & Costello, & Harris, 2006). Coles, 2002). a. Cellular immunity consists of cytotoxic T 3. An important role for the genetic factors in cells (cluster of differentiation [CD] 8) and determining MS susceptibility is suggested T-helper (TH) cells (CD 4). by familial aggregation of the disease as well . b Humoral immunity includes B lympho- as high incidence in some ethnic populations cytes and antibodies. (e.g., Northern European ancestry). c. B cells recognize antigens outside of cells; 4. Genes that code for major histocompatibil- T cells recognize antigens from inside host ity complex (MHC) are part of the human cells and those on the cell surface.

12 Nursing Management of the Patient with Multiple Sclerosis . d Humoral immunity involves B cells 2. Axonal loss can be seen at MRI and magnetic producing antibodies that work by resonance (MR) spectroscopy (Filippi et al., mechanisms including neutralization, op- 2003). sonization, and complement activation. 3. Neurodegeneration is a major contributor to . e Cellular immunity involves T cells with re- CNS atrophy. ceptors on the cell surface. 4. Neurodegeneration occurs with . f T cells are activated by antigen presentation. inflammation. 2. The general consensus is that MS is a disease 5. Controversy remains regarding the re- related to an imbalance of antiinflammatory lationship between inflammation and versus proinflammatory cytokines. neurodegeneration. 3. Proinflammatory TH-1 (CD 4+) and antiin- 6. Causes of neurodegenerative processes: flammatory TH-2 (CD 4+) a. Failure of sodium channel homeostasis. a. Proinflammatory cytokines (TH-1): IL-2, . b Excess glutamate, nitrous oxide, proteases, IL-10, IFNγ, TNFα cytokines, CD8 cells, oxidative products, . b Antiinflammatory cytokines (TH-2): and free radicals generated by activated IL-4, IL-10, IL-13, transforming growth immune and glial cells. factor (TGF) β (Akira, Takeda, & Kaisho, . F Remyelination (Chari, 2007; Franklin & Kotter, 2001) 2008) 4. T cells in the periphery are activated by anti- 1. Remyelination appears to be considerable gen present cells (APC). in the majority of the MS population; how- a. Activated TH-1 cells migrate across the BBB. ever, CNS remyelination does not occur as . b In the CNS, the T cells are reactivated by well as peripheral nervous system (PNS) an APC and secrete proinflammatory cyto- remyelination. kines including CNS inflammation via ac- 2. Remyelination is a natural reparative process tivation macrophages and other T cells and in MS during which new myelin sheaths are B cells (Neuhaus, Archelos, & Hartung, formed over demyelinated axons. 2003). 3. Remyelination varies from individual to 5. Recently discovered additional CD4+ subset individual. TH-17 4. It is observed in individuals both early and a. TH-17 cytokines IL-17, IL- 6, TNFα, and late in the course of disease. IL-17 are expressed in MS lesions (Akira, 5. It is present in all types of MS. Takeda, & Kaisho, 2001). 6. Favorable factors for remyelination are as 6. B cell pathogenesis follows: a. B cells have the capacity to stimulate T cells a. Presence of oligodendrocyte precursors (Bar-Or, 2010). near the active edges of inflammatory . b B cells produce antibodies to components lesions. of the CNS, including myelin. This may . b Migration and development into mature help determine the extent of tissue injury oligodendrocytes. in MS. c. Inflammation appears to be necessary. c. Antibodies bind with complement to at- . d Clearance of myelin debris generated dur- tack and destroy the myelin sheath (com- ing demyelination. plement fixation). Recommendation: Well-designed multidisciplinary re- . d Complement fixation is especially effective search is needed for a more complete understanding of the with oligodendrocytes, resulting in an in- pathophysiology of MS (Level 3). flux of calcium. This promotes phagocyto- sis of oligodendrocytes. . V Assessment and Diagnostic Process . e B cells may secrete more IgM, IgG, and IgA A. Introduction and bring about an antigen-dependent T 1. A clinical diagnosis of MS is based on neu- cell response (Bar-Or, 2010). rologic examination. Laboratory testing E. Neurodegeneration in MS (Trapp & Nave, 2008) and MRI provide supporting evidence of a 1. Trapp and colleagues (1998) performed au- diagnosis. topsies and biopsies on patients with MS, and 2. Diagnostic criteria have evolved over sev- they demonstrated greater axonal damage eral decades and include the use of clinical than had been previously appreciated. (e.g., history and physical) and paraclinical

Nursing Management of the Patient with Multiple Sclerosis 13 data (e.g., MRI, serum and cerebrospinal flu- . d In clinically isolated syndromes in which id [CSF] sampling, visual evoked potentials, an individual has experienced only one at- and somatosensory and brain stem evoked tack and clinical evidence indicates one le- potentials). Other potential causes of CNS de- sion, an abnormality at MRI as defined in myelination must be excluded before MS is the criteria or two lesions at MRI plus a diagnosed (Costello & Halper, 2010b; Harris positive CSF would satisfy the definition of & Halper, 2004, 2008; Miller et al., 2008; Poser dissemination in space. Dissemination in et al., 1983). time could be confirmed at MRI by the oc- . B Diagnostic criteria for MS currence of a second attack. 1. The McDonald criteria were created to pres- 4. The most common presentations of MS in- ent a better and more reliable diagnostic clude the following: scheme to diagnose MS (Polman et al., 2005; a. Sensory disturbances such as numbness, Polman et al., 2011). The McDonald crite- paresthesias, pain, or Lhermitte’s sign. ria use history of clinical attack(s) along with . b Motor abnormalities including cortico- MRI lesion distribution (e.g., dissemination in spinal, abnormal deep tendon reflexes space) and lesion occurrence over time (e.g., (DTRs), positive Babinski response, or dissemination in time and space via MRI, spastic limb weakness. CSF, evoked potentials) to aid in the diagnosis c. Visual problems including brain stem and of MS (Polman et al., 2011). Diagnosis is often eye movement abnormalities, and optic made by a neurologist on the basis of the Mc- neuritis. Donald criteria (Harris & Halper, 2004, 2008; . d Cerebellar gait ataxia, limb ataxia, and Polman et al, 2005). tremor. 2. These criteria may allow a more reliable diag- . e Fatigue. nosis to be made sooner than otherwise pos- C. Assessment tools sible (Bakshi et al., 2008). The criteria were 1. Assessing a patient with MS begins with the most recently revised in 2010. initial observation of the patient in any setting 3. The 2010 revisions to the McDonald criteria and includes observing his or her ability to for diagnosis of MS (Polman et al., 2011) are move (walking, assistive devices), affect, bal- as follows: ance and coordination, hygiene, speech. a. When the clinical presentation includes two 2. Although a clinical neurologic examination or more attacks and objective clinical evi- provides baseline information about how dence indicating two or more lesions in dif- the nervous system is functioning, there are ferent locations, no further confirmation is findings specific to MS. This information needed. will help identify the areas of the CNS that . b If two or more attacks occur and clini- may be affected by demyelinating lesions cal evidence indicates only one lesion, dis- (Rudick, 2004; van den Noort & Holland, semination in space must be provided by 1999). means of MRI, or a diagnosis of MS can a. Brain stem: internuclear ophthalmoplegia be made by using the appearance of two or (INO), and nystagmus more lesions at MRI plus a positive CSF. . b Cerebellar: scanning speech, intention c. In cases in which an individual has experi- tremor, truncal ataxia, gait ataxia, and enced one attack but objective clinical evi- dysarthria dence indicates two separate lesions, MRI c. Motor symptoms: pyramidal tracts— is not required to prove dissemination in weakness typical of upper motor neuron space. However, MRI can prove dissemi- lesions, spasticity, hyperreflexia, dysarthria, nation in time, as can the occurrence of a clonus, and extensor plantar responses second attack. Dissemination in time can . d Motor symptoms: corticobulbar tracts— be established in one of two ways: (1) de- emotional lability tection of Gadolinium (Gd) enhancement . e Sensory symptoms at least 3 months after the initial event or • Not always visible but can be elicited (2) detection of a new T2 lesion at any time with testing. compared with reference imaging per- • Sensory loss may affect gait and other formed at least 30 days after the initial clin- motor function leading to clumsiness of ical event. fine movements and loss of dexterity.

14 Nursing Management of the Patient with Multiple Sclerosis . f Higher cortical function . ii 4–7 indicates moderate disability and • Short-term memory dysfunction the patient is ambulatory with assis- • Managing complex tasks tive device. • Speed of information processing . iii 8–10 indicates severe disability and • Visual-spatial dysfunction the patient is confined to a wheel- • Verbal fluency chair (Coulthard-Morris, 2000). 3. Patient interviews provide the greatest infor- c. Functional systems (FS) scores are used mation to guide caring for the patient with in the evaluation of a patient’s EDSS. FS MS and improving his or her QOL. Through scores measured during a neurologic ex- this process, nurses can discern if symptoms amination include visual, brain stem, py- are constant or intermittent and how they af- ramidal, cerebellar, sensory, bowel and fect the lives of patients at home, at work, and bladder, and cerebral and mental function. in the community. Skilled interviewing will FS scores are rated on a scale from 0 (nor- involve asking for information not necessarily mal function) to 6 (unable to perform the offered by the patient. function; Kurtzke, 1983). 4. Examples of topics to address include the . d On the basis of results from cohort studies, following: once an EDSS score of 4 is reached, there is a. ADLs: dressing, bathing, eating, and a progression of disability regardless of ini- grooming tial good prognosticators. An EDSS score . b Bowels: constipation, incontinence, and of 4, therefore, heralds the onset of SPMS diarrhea (Hutchinson, 2009). Longer intervals to c. Bladder: frequency, urgency, incontinence, progression to subsequent EDSS levels are and infections present in those with initial RRMS (versus . d Sexual function: loss of libido, erectile dys- those with PPMS), those with complete re- function, loss of sensation, and relationship covery from first relapse, and those with issues longer time from MS onset to second epi- . e Vision: decreased acuity and constant or sode (Confavreux, Vukusic, & Adeleine, intermittent inability to distinguish colors, 2003; Confavreux, Vukusic, Moreau, & especially red Adeleine, 2000). . f Cognition: word-finding problems, memo- . e The risk of reaching an EDSS score of 6 is ry issues, poor concentration, and inability only 20% at 10 years for the person with to understand what is being said one or fewer relapses in the first 2 years of . g Mood: depression, anxiety, depletion, ir- the disease. Approximately 50% of peo- ritability, sadness, anger, and mood ple with MS need to use a walking aid af- fluctuations ter 15 years (Weinshenker et al., 1989a, h. Diet and fluids: decreased fluids to manage 1989b). Freedom from major disability af- bladder, and inability to get food, prepare ter 25 years occurs in approximately 10% food, or feed self of people with MS (Kantarci et al., 1998). If 5. EDSS is a standard measure of disability in an EDSS score stays at or below 2 for more MS (Kurtzke, 1983). than 10 years, there is a 90% chance of dis- a. EDSS is a widely used MS outcome ease stability (Kantarci et al., 1998; Pittock measure administered by a profession- et al., 2004). In contrast, most people ex- al trained in its use (Coulthard-Morris, periencing 5 or more relapses within the 2000). first 2 years of disease onset require use of . b The EDSS is based on an evaluation of a a cane at 10 years (Weinshenker, 1994). patient’s functional systems scores as de- 6. The Multiple Sclerosis Functional Compos- termined by means of a standardized neu- ite (MSFC; Kurtzke, 1983; Fischer, Jak, Kniker, rologic examination and an assessment of Rudick, & Cutter, 2001) includes three out- the patient’s walking ability. The EDSS is come measures: a 20-point scale from 0 to 10 in half-point a. Nine-hole peg test—arm assessment increments (Table 1; Kurtzke, 1983). measurement . i 1–3 indicates minimal disability and . b Timed 25-foot walk test—leg assessment the patient is ambulatory. measurement.

Nursing Management of the Patient with Multiple Sclerosis 15 Table 1. Expanded Disability Status Scale (EDSS) other diagnostic tools, because a neurologic ex- EDSS Score Clinical Finding amination alone may not provide enough evidence. These tests are used not only for early de- 0.0 Normal neurologic examination tection of the disease but also for evaluating the 1.0–1.5 No disability efficacy of current and new treatments (Laron et 2.0–2.5 Minimal disability al., 2009). 3.0–3.5 Moderate disability 1. Evoked potentials: An evoked potential test 4.0–4.5 Fully ambulatory and self-sufficient despite severe disability measures the time it takes for nerves to re- 5.0–5.5 Walking restricted to 100–200 meters spond to stimulation. The size of the response 6.0–6.5 Needs unilateral or bilateral constant assistance is also measured. An advantage and reason for 7.0–7.5 Restricted to wheelchair; can wheel self and transfer alone using evoked potential in diagnosis is the abil- 8.0–8.5 Restricted to bed or chair; retains some self-care functions ity to detect abnormal signs and lesions in patients who have isolated symptoms. Nerves 9.0–9.5 Helpless bed patient from different areas of the body may be tested. 10.0 Death due to MS a. Visual evoked potential (VEP) is the most Note. From Kurtzke, J. F. (1983). Rating neurologic impairment in multiple sclerosis: An commonly used evoked potential test in expanded disability status scale. Neurology, 33(11), 1444–1452. the diagnosis of MS. VEP tests help iden- c. Paced auditory serial addition test tify optic neuritis (ON) or other demyelin- (PASAT)—cognitive assessment ating conditions along the optic nerve and measurement. optic pathways (Laron et al., 2009; Turker 7. The Multiple Sclerosis Symptom Checklist et al., 2008). (MSSC) is a 26-item self-report measure de- The McDonald criteria have incorporated signed to assess for the presence of 26 disease VEPs into the diagnosis of MS. VEPs are symptoms common in MS patients (Gulick, recommended in patients with MRI show- 1989). The tool consists of five subscales assessing 4 or more, but fewer than 9, T2 lesions ing motor function, sensory disturbance, men- consistent with MS (Evans & Boggs, 2010; tal and emotional concerns, bowel and bladder Laron et al., 2009). elimination, and brain stem symptoms. Homo- . b Brainstem auditory evoked response geneity reliability has been determined through (BAER) the use of the Cronbach alpha with subscale . i BAER measures the function of the scores ranging from .78 to .87 (Gulick, 1989). auditory nerve and auditory path- Total scale Cronbach alpha has been shown to ways in the brain stem. It provides be .89. Scores are determined through the use information about changes in the of a six-point scale with responses ranging from neurophysiologic status of the pe- never to always. Higher scores indicate an in- ripheral nervous system and CNS crease of symptoms (Gulick, 1998). (Evans & Boggs, 2010; Laron et al., Recommendations: A comprehensive assess- 2009). ment should be completed, including the follow- . ii BAERs are considered if clinical ing areas: physical, cognitive, sensory, and bowel symptoms indicate the possibility of and bladder function. The baseline functional as- a lesion outside the brain. An abnor- sessment can be used to compare with future neu- mal BAER would support the diag- rologic examinations (Level 2). For assessment of nosis of MS (Laron et al., 2009). function, frequency of evaluation has not been ex- c. Somatosensory evoked potential (SSEP) tensively studied. Nurses should complete an ini- . i Sensory disturbances are com- tial assessment of function and monitor on an on- mon findings in patients with MS. going basis for any changes in condition (Level 3). SSEPs detect clinical abnormali- . D Assessment charts ties but mainly explore the lemnis- 1. Cranial nerve assessment (Table 2) cal pathway, which is responsible for 2. Assessment of motor symptoms; range of mo- transmitting touch, vibration, and tion and muscle strength (Table 3) conscious proprioception. In the E. Assessment of reflexes (Table 4) spinal cord, the dorsal columns are . F Diagnostic testing responsible for conduction of the ac- The diagnosis of MS is essentially a clinical diag- tivity that is demonstrated by the nosis. The McDonald criteria are used along with SSEP, and it involves the lemniscal,

16 Nursing Management of the Patient with Multiple Sclerosis Table 2. Cranial Nerve Assessment Cranial Nerve Function Assessment Expected Findings I: Olfactory Sense of smell Tools: two different scents such as clove, vanilla, or coffee. Have patient close eyes and close one nostril, then identify scent. II: Optic Central and peripheral vision Tools: Snellen chart or available print version and two index Comfortably and accurately reads or identi- cards. Have patient identify writing or symbols. Assess peripheral fies small figures. Peripheral vision intact. vision by facing patient nose to nose 12 inches away. Have patient cover one eye with index card and you cover mirror image of eye (patient right eye, your left eye). Extend arm and have patient note when he or she sees fingers moving. Assess upper, middle, and lower range of inner and outer aspect of eye. You should see finger movement at about the same time as the patient. If you (the examiner) have poor peripheral vision, you will not be able to do this examination. III: Oculomotor Pupillary constriction Tool: penlight. Hold penlight 12 inches from patient eyes. Next, Pupils constrict equally in response to have patient look at distant object then bring object close to light. Eyes are accommodating with con- patient eyes. Assess 6 cardinal positions of gaze. vergence and constriction of pupils. Equal extraocular movement. IV: Trochlear Movement of eyes toward Assess 6 cardinal positions of gaze. Eye movement is smooth toward nose. nose V: Trigeminal Sensation and motor function Tools: cotton ball and dull end of an object such as a pen, reflex Corneal reflex intact. Sensation intact on of face hammer, or tongue depressor. Test sensation on face. Have patient forehead, jaw, and cheek. Adequate jaw close eyes and identify when he or she feels touch. Wisp cotton strength. ball against cornea. Have patient open jaw against resistance. VI: Abducens Lateral movement of eyes Assess 6 cardinal positions of gaze. Eye movement is smooth away from nose. away from the nose VII: Facial Facial expression Ask patient to smile, frown, or puff out cheeks. Equal facial expression. VIII: Acoustic Hearing Whisper next to patient ear but not in patient view to prevent lip Able to understand whisper. reading. IX: Glossopharyngeal Tongue and throat movement Tools: tongue depressor, penlight Uvula retracts evenly. X: Vagus Have patient say “ahh.” Test gag reflex. Soft palate rises. Gag reflex intact. (assess IX and X together) XI: Spinal Accessory Shoulder shrug Shrug shoulders against resistance. Raises shoulders with equal force. XII: Hypoglossal Tongue movement Ask patient to stick out his or her tongue. Tongue sticks out midline. Copyright © 2011 by AANN. All rights reserved.

Table 3. Assessment of Motor Symptoms: Muscle Strength Table 4. Assessment of Reflexes Assess joint movement of head and neck and major joints of upper and lower Assess Reflexes extremities. Grade muscle strength by using muscle strength scale. Reflex Nerve Innervation Grading Muscle Biceps C5, C6 Strength Finding Triceps C7, C8 0 No visible muscle contraction Brachioradialus C5, C6 1 Visible muscle contraction with no or trace movement Patellar L3, L4 2 Limb movement when gravity is eliminated Achilles Sl, S2 3 Movement against gravity but not resistance Plantar Reflex (Babinski) L5,Sl 4 Movement against resistance supplied by examiner Reflex Grading Scale Finding 5 Full strength 0 Absent reflex Copyright © 2011 by AANN. All rights reserved. 1+ 1+ Diminished 2+ 2+ Present, normal finding 3+ 3+ Increased 4+ 4+ Increased with clonus 5+ 5+ Increased with sustained clonus Copyright © 2011 by AANN. All rights reserved.

Nursing Management of the Patient with Multiple Sclerosis 17 thalamocortical, and extralemniscal with clinically definitive MS pathways (Evans & Boggs, 2010). (Traboulsee & Li, 2006). . ii SSEPs are useful in diagnosing clini- . v The characteristic MS lesion ap- cally silent MS lesions. One third of pears bright at T2-weighted MRI abnormal SSEPs occur unilaterally. (secondary to inflammation, edema, Studies that compared SSEPs with demyelination, axonal loss, and/or VEPs found equal sensitivity in re- Wallerian degeneration) and is found vealing lesions in patients with MS in the periventricular, juxtacortical, (Evans & Boggs, 2010; Gronseth & or infratentorial white matter (Bak- Ashman, 2000). shi, Hutton, Miller, & Radue, 2004). 2. Optical coherence tomography (OCT) . d Lesions can occur in any CNS tissue where a. OCT is a new optical imaging technique there is myelin (e.g., the brain, spinal cord, that measures a cross-section of the reti- or optic nerves; Traboulsee & Li, 2006). nal nerve fiber layer (RNFL) thickness with . e In the brain, the periventricular (surround- high resolution and good reproducibility. ing the ventricles) region is the typical The RNFL consists of the unmyelinated ax- location where white matter lesions are lo- ons of retinal ganglions that become my- cated (Figure 9). elinated past the lamina cribrosa and the . f Juxtacortical lesions are located in the tem- optic nerve. If the RNFL is affected as seen poral lobes at the grey-white matter junc- in patients with MS, it will show a retro- tion (Figure 9; Traboulsee & Li, 2006). grade degeneration that follows the dam- . g Dawson’s fingers are lesions that are per- age of the optic nerve or optic tract. pendicular to the ventricles. These lesions . b Benefits found with OCTs are that they are a unique feature of MS (Figure 10; are easy to perform, time efficient, and less Traboulsee & Li, 2006). costly than MRI. MRI is considered the Figure 5. T1-weighted axial image standard evaluative technique for diagnosis of MS. OCT has been used as a potential substitute to measure of axonal loss and neuroprotection in MS (Laron et al., 2009). 3. MRI a. MRI is one of the most important diagnostic tests used in diagnosing MS. In MS, clinical features seen at MRI include multiple plaques or lesions throughout the CNS, which is composed of the brain, optic nerves, and spinal cord (Traboulsee & Li, 2006). . b MRI will show abnormalities in approximately 95% of patients with clinically definitive MS (Nielsen, Korteweg, & Polman, 2007). c. Two types of images are used during brain MRI: T2-weighted and T1-weighted images (Traboulsee & Li, 2006). . i T1-weighted images appear dark (Figure 5), and T2-weighted images appear bright (Figure 6). . ii Fluid-attenuated inversion-recovery (FLAIR) MRI is also useful for lesion detection (Figure 7). T1 images emphasize the differences between tissues and show good anatomic detail, but do not demonstrate pathology best. Abnormalities show up dark on T1 images. Courtesy . iii When brain MRI results are normal of the International Organization of Multiple Sclerosis Nurses (IOMSN). or equivocal, spinal cord MRI is useful (Figure 8). iv. Spinal cord lesions are found in approximately 50%–90% of patients

18 Nursing Management of the Patient with Multiple Sclerosis Figure 6. T2-weighted axial image Figure 8. Spinal cord MRI showing cord lesion

T2 images are sensitive to increased water content and may be superior at demonstrating pathological changes. Gray matter appears lighter than white matter. MS lesions appear hyperintense or bright. Courtesy of the International Organization of Multiple Sclero- sis Nurses (IOMSN).

Figure 7. Sagittal FLAIR image Courtesy of the International Organization of Multiple Sclerosis Nurses (IOMSN).

Figure 9. Axial FLAIR imaging showing periventricular and juxtacortical lesions

Courtesy of the International Organization of Multiple Sclerosis Nurses (IOMSN). Original MRI image provided to IOMSN by William Stuart, MD.

h. Areas of hypointensity are called black holes. Chronic black holes are lesions that are nonenhancing and typically persist for a minimum of 6 months after they first ap- A FLAIR image is a type of T2 image with superior capability for demonstrating demye- pear (Traboulsee & Li, 2006). If these hy- linating lesions and shows both new and old lesions clearly. Courtesy of the Internation- pointense areas persist, they represent al Organization of Multiple Sclerosis Nurses (IOMSN). Original MRI image provided to IOMSN by William Stuart, MD. axonal loss. Permanent disability may be related to axonal loss (Figure 11; Bakshi, Hutton, Miller, & Radue, 2004).

Nursing Management of the Patient with Multiple Sclerosis 19 Figure 10. MRI demonstrating Dawson’s fingers Figure 11. MRI demonstrating “black holes”

Courtesy of the International Organization of Multiple Sclerosis Nurses (IOMSN).

. i There is some consensus that patients with Courtesy of the International Organization of Multiple Sclerosis Nurses (IOMSN). Original MRI image provided to IOMSN by William Stuart, MD. PPMS have fewer lesions in the cerebrum and possibly less enhancement in the CNS (Bakshi et al., 2008). Figure 12. MS lesions on enhanced T1 weighted MRI . j Gadolinium is used to detect new disease activity (inflammation). Gadolinium does not typically cross the BBB. New MS lesions coincide with disruption of the BBB and appear on T1-weighted images as gadolinium-enhanced lesions (Traboulsee & Li, 2006). The lesions appear bright and often have a ringlike pattern around them (Figure 12). On average, enhancement lasts approximately 4 weeks, with a gradual decrease during the next 2–4 weeks (Traboulsee & Li, 2006). ek. Th Consortium of MS Centers has published an MRI protocol for the diagnosis and follow-up of patients with MS. These guidelines provide details of the clinical use of MRI for patients with MS. 4. Brain parenchymal fraction (BPF) is another method of using MRI techniques to evaluate the clinical course of MS through measurement of cerebral atrophy. In comparison with T1-weighted gadolinium-enhanced MRI showing new and active lesions that appear controls, patients with MS display an increased bright, reflecting areas of blood-brain disruption. Courtesy of the International Organiza- loss of brain volume, and a means of measur- tion of Multiple Sclerosis Nurses (IOMSN). ing this is through calculation of BPF (Rudick et al., 1999), which is considered a sensitive in- 1. CSF tests: Examining CSF may identify abnor- dicator of disease severity (Dörr et al., 2011). mal cells or antibodies that suggest the pres- G. Laboratory testing ence of MS. It has been the focus of testing and The MS diagnosis is generally based on clinical research for many years (Rammohan, 2009). signs and symptoms and MRI, VEP, and labo- . a CSF is examined by means of a lumbar ratory analyses (specifically CSF) See previous puncture (spinal tap). CSF is clear and discussion of McDonald criteria (Polman et al., colorless in all MS patients (Rammohan, 2011). 2009).

20 Nursing Management of the Patient with Multiple Sclerosis 2. Tests performed on CSF include oligoclonal CSF and blood serum. The calcula- bands (OCBs), IgG Index, Myelin Basic Pro- tion is tein (MBP), Kappa Light Chains, glucose, al- IgG (CSF)/IgG (serum) bumin index, protein level, and white blood IgG Index = Albumin (CSF)/Albumin (serum) cell level. a. Oligoclonal bands: OCBs are immuno- (Hische, van der Helm, & van Wal- globulins (IgG, IgM, or IgA) or proteins of beek, 1982; Link & Huang, 2006). the immune system that are generated by . ii An elevated IgG Index indicates an plasmablasts and plasma cells in the CSF increase in the production of IgG or CNS compartment (Awad et al., 2010). within the CNS. It is elevated in In addition to MRI, the presence of OCBs about 70% of cases of MS. Because in the CSF is the most consistent laborato- of the low sensitivity of the IgG In- ry abnormality found in patients with MS. dex, it cannot be recommended as If OCBs are present, less stringent criteria the primary laboratory test or replace are needed to satisfy the dissemination in the CSF OCB in the diagnosis of MS. space criterion (Polman et al., 2011). However, when elevated, it can be . i A positive test for OCBs is the pres- used as an additional tool in the di- ence of two or more IgG bands in the agnosis of MS and help to rule out CSF that are not present in a blood other diseases that mimic MS (Link serum sample obtained at the same & Huang, 2006). time (Awad et al., 2010; Freedman et c. Myelin Basic Protein (MBP): MBP is al., 2005; Link & Huang, 2006; Ram- the major component of myelin, and in- mohan, 2009). creased concentrations of myelin in CSF ii. According to Rammohan (2009), indicate that demyelization is occurring. identification of OCBs is invaluable Increased levels of MBP have been found for diagnosis of MS. Villar and col- during active demyelination. Levels may leagues (2009) stated that the pres- be elevated in the CSF of patients with ence of OCBs is characteristic of MS, MS; however, it is thought not to be spe- and Fromont and colleagues (2005) cific for MS, because other inflammatory stated that the detection of OCBs in a diseases of the CNS can increase the level patient’s CSF is the gold standard lab- of MBP in the CSF. It may be used to help oratory test for MS. rule out other diseases that mimic MS . iii Tintoré and colleagues (2008) exam- (Rammohan, 2009). ined whether OCBs added to MRI . d Other CSF studies performed not specific findings as a predictor of a second at- for MS tack and the development of clini- . i Color and clarity: All aspects of CSF cally definite MS and disability in analysis help to distinguish between patients with clinically isolated syn- other causes of systemic inflamma- drome (CIS). The authors found that tion and diseases that could possibly the presence of OCBs doubles the mimic MS. CSF in patients with MS risk for having a second attack, inde- is generally clear and colorless. pendent of MRI findings, but does . ii Glucose: Usually normal in MS. not seem to influence the develop- . iii Albumin index: Used to rule out the ment of disability. leakage of protein into the CSF from . b IgG Index: An increase in the level of IgG blood caused by either a damaged in the CSF can be due to the increased pro- BBB or a traumatic spinal tap. duction of IgG in the CNS. This increase iv. Protein level: Normal or slightly el- in production can be seen with MS as with evated; most patients with MS have other diseases. The increase in IgG can be normal total protein counts even due to leakage of plasma proteins into the during an acute exacerbation (Ram- CSF as might be seen with inflammation or mohan, 2009). trauma. . e White blood cell (WBC) level: Higher than . i The IgG Index is calculated from IgG normal CSF WBCs (predominantly mono- and albumin measurements in the nuclear cells) are found in MS, whereas

Nursing Management of the Patient with Multiple Sclerosis 21 very high CSF WBC counts (>50 x 10 L) together with the analysis of antigens. It is are unusual for MS. hoped that this will establish specific bio- 3. Peripheral Blood Tests: May be helpful to rule markers for MS (Harris & Sadiq, 2009). out other disease processes that mimic MS 2. Disease Activation Panel of Biomarkers (Calabresi, 2004). a. Biomarkers being researched include a a. Advancements in paraclinical investi- panel of biomarkers that measure MS dis- gations, especially MRI, CSF, and visual ease activation: interleukin-6, nitric oxide, evoked potential testing, together with the osteopontin, and fetuin-A (Harris & Sadiq, need for a definitive diagnosis at the ear- 2009). liest time possible, are imperative for the . b Interleukin-6: Interleukins (ILs), also physician to begin treatment in a timely called lymphokines, are a subgroup of the manner. In making the diagnosis, a pre- cytokines and carry messages between condition should include the exclusion of cells. They are communicating proteins diseases that mimic MS (Courtney, Tread- that initiate or suppress inflammation. away, Remington, & Frohman, 2009). There are more than 30 known ILs at this Multiple tests are needed to rule out oth- time. er conditions or diseases that have simi- c. Nitric oxide (NO) and NO synthesis: NO is lar signs and symptoms that affect the CNS a free radical signaling molecule that has a and that can be confused with MS (Cal- complex biochemistry. Evidence points to abresi, 2004). the role that NO plays in the pathogenesis b. Table 5 lists some of the diseases that of MS and its role in various aspects of MS mimic MS. This table is not all-inclusive such as inflammation, oligodendrocyte in- but lists many of the diseases most fre- jury, synaptic transmission changes, axonal quently mentioned in the literature. (See degeneration, and neuronal death (Enci- also Courtney, Treadaway, Remington, nas, Manganas, & Enikolopov, 2005). Its and Frohman, [2009] and Rolak and Flem- action may have both positive and negative ing, [2007], who provide a more extensive effects in MS. list of diseases that mimic MS). d. Osteopontin: Osteopontin has been found c. Continued refinement of techniques will in the plasma levels of patients with MS generate additional information, better during relapses. In a study of MS patients methods of storage, and data analysis that and healthy subjects, plasma osteopontin use bioinformatics. The resulting increased levels were significantly increased in pa- availability of information from research tients with RRMS and also correlated with studies on CSF will help clinicians diag- the IgG Index. This finding suggested that nose and treat MS as well as conduct fur- bone-related molecules such as osteopon- ther research. Advances from these studies tin and vitamin D have immunomodu- will help to change the course of MS and lary functions and are correlated with the empower the patient and physician to treat IgG Index in patients with RRMS (Vogt, MS more effectively in the future (Rammo- ten Kate, Drent, Polman, & Hupperts, han, 2009). 2010). Osteopontin is significant in MS as H. Diagnostic research studies: Biomarkers it works with integrin a4b1 to block lym- 1. Introduction: A number of different biomark- phocyte entry to the brain and to reduce ers have been used to diagnose and differenti- relapses (Steinman, 2009). ate the different types of MS and treat MS. . e Fetuin-A: Fetuin-A is a protein found in a. Biomarkers, or biological markers, are nat- blood serum; 95% of it is derived from the urally occurring substances that can be liver. It is implicated in the CNS as respon- used as indicators of biological processes sible for increasing the permeability of the and pathogenic processes including disease BBB by activating matrix metalloprotein- states such as MS. Some biomarkers are ase. In patients with active MS, a signifi- useful in assessing responses to therapeutic cantly higher level of CSF fetuin-A is noted interventions. than in patients with inactive disease (Yan, . b Discovery of new biomarkers for MS relies Rammal, Dinzey, Donelan, & Sadiq, 2007). on advances in proteomics research along Fetuin-A protein can be used to predict with microarray gene expression analyses the level of disease activity and to promote

22 Nursing Management of the Patient with Multiple Sclerosis Table 5. Differential Diagnosis of Diseases that Mimic MS Name and Description of Disease How It Mimics MS Diagnostic Studies to Differentiate Acute Disseminated Encephalomyelitis Frequently it is preceded by a viral infection (Gasperini, MRI lesion may be hemorrhagic and involve the gray matter (ADEM) 2001). Symptoms can be identical to MS, including involve- (Rolak & Fleming, 2007). CSF—mild to moderate pleocytosis Monophasic demyelinization occurring ment of optic nerve, brain, and spinal cord. Fifteen percent of (elevated WBCs in the CSF) and mild to moderate elevated with or just after infection, vaccina- patients may have lesions on the brain. protein MBP. CSF beta-1 globulin in MS (Chopra, Abraham, tion, or other immune-altering event & Abraham, 2002). Gasperini (2001) states that using unen- (Courtney, Treadaway, Remington, & hanced serial MRI may be helpful, because with ADEM many Frohman, 2009; Rolak & Fleming, lesions resolve and new ones do not develop, but with MS, 2007). some lesions resolve but new lesions develop. Neuromyelitis Optica or Devic Syndrome Abrupt onset of optic neuritis, transverse myelitis, brain stem CSF—marked pleocytosis (neutrophil component) and pro- Monophasic tegmentum syndrome (vomiting, oculomotor, and vestibular tein and albumin levels. Absent OCBs and normal IgG Index. problems); 10% to 50% have brain lesions (Courtney, At MRI, lesions noted affecting the optic nerve and spinal cord Treadaway, Remington, & Frohman, 2009). Frequently, it is but with myelitis extending over 3 or more continuous seg- preceded by a viral infection (Gasperini, 2001). ments of the spinal cord (Rolak & Fleming, 2007). HIV-Associated Infections Occurs in high-risk patients that may have a decreased CD4 Increased total protein and cell count in CSF; 0 OCBs; cell count and positive serology. May cause optic neuritis, multiple cerebral white matter lesions at MRI indistinguishable myelopathies, changes in mental status, and focal deficits from those of MS (Gasperini, 2001). Positive HIV serology. (Rolak & Fleming, 2007). Lyme Disease Can cause consistent focal neurological findings Western blot. Diagnosis made based on symptoms and Tick exposure infected by tick-borne evidence of tick bite. Enzyme-linked immunosorbent as- spirochete, Borrelia burgdorferi. say (ELISA); indirect fluorescent antibody (IFA); positive (Courtney, Treadaway, Remington, & polymerase chain reaction test (PCR) may be used to detect Frohman, 2009). a current (active) infection by detecting the genetic material (DNA) of the Lyme disease bacteria (Rolak & Fleming, 2007; Courtney, Treadaway, Remington, & Frohman, 2009). Intrathe- cal synthesis of IgG and OCBs have been reported (Gasperini, 2001).

Myasthenia Gravis In myasthenia gravis, the symptoms tend to fluctuate MRI, CSF, and visual evoked response (VER) are normal. Disease in which weakness occurs be- throughout the day, and they often worsen at night. Droopy Eighty percent of patients have an elevated serum acetylcho- cause the nerve impulses responsible eyelids; facial weakness; impaired eye coordination; and line receptor antibody test result (Rolak & Fleming, 2007). for initiating movement are not able to weakness of the limbs, neck, shoulders, hips, and trunk are reach muscle cells. typical. Patients usually do not experience loss of sensation, and fatigue is localized (Rolak & Fleming, 2007). Pernicious Anemia May cause central nervous system (CNS) deficits, especially Serum B12 low; complete blood count may be abnormal; meth- Vitamin B12 deficiency progressive myelopathy. Rare MRI abnormalities (Rolak & ylmalonic acid and homocysteine are often abnormal (Rolak & Fleming, 2007). Fleming, 2007). Progressive Multifocal Leukoencepha- Can have multifocal CNS deficits. It occurs in immunocom- The MRI is abnormal, usually shows lesions in white matter lopathy (PML) promised patients. The deficits are usually progressive rather that are larger and more confluent than those seen with MS. CNS infection by John Cunningham than relapsing. Death may occur within weeks to months CSF polymerase chain reaction (PCR) may be positive for JC (JC) virus in immunosuppressed if untreated (Rolak & Fleming, 2007; Courtney, Treadaway, virus, but brain biopsy may need to be performed for definite patient. Remington, & Frohman, 2009). diagnosis (PCR is a laboratory test to detect the genetic material of an infectious disease) (Rolak & Fleming, 2007).

Systemic Lupus Erythematosus (SLE) Systemic involvement includes hematologic, skin, and Antinuclear antibody (ANA) titers levels are in increased SLE; kidney changes. Common in young women and may affect positive serology: double-stranded DNA autoantibodies and the nervous system, especially the optic nerve and spinal ANA (Rolak & Fleming, 2007). cord. MRI changes of white matter are common. Up to 60% of patients have OCB and IgG abnormalities in CSF (Rolak & Fleming, 2007). Syphilis Can cause optic neuritis, myelopathies, and other focal Tests for syphilis include serum VDRL, rapid plasma regain CNS infection by spirochete Trepo- neurological changes (Rolak & Fleming, 2007). (RPR) test, fluorescent treponemal antibody absorption (FTA- nema pallidum (Courtney, Treadaway, ABS). CSF-protein (90%), WBC (90%), CSF VDRL (positive Remington, & Frohman, 2009; Rolak 80%). MRI usually normal. Infection considered rare except & Fleming, 2007) in HIV-positive or immunocompromised patients (Rolak & Fleming, 2007). Continued

Nursing Management of the Patient with Multiple Sclerosis 23 Table 5. Differential Diagnosis of Diseases that Mimic MS Continued Sarcoidosis Often systemic symptoms, especially in the lungs. May CSF-protein, mononuclear pleocytosis, angiotensin-convert- Granulomatous multisystem angioten- involve optic nerve or spinal cord (Rolak & Fleming, 2007). ing enzyme level. Chest X ray is a very helpful tool. Serum and sin disease of unknown cause (Rolak Involvement of the optic nerve with pain in one or both eyes CSF ACE levels may be increased. Rare patients have OCB & Fleming, 2007) and blurred vision are of importance. Facial nerve relapsing- in CSF. MRI may show white matter lesions and meningeal remitting palsies may occur (Gasperini, 2001). enhancement. Positive biopsy of skin lesions, lymph nodes, or lung is definitive diagnosis (Rolak & Fleming, 2007). Sjögren Syndrome Systemic symptoms with dry eyes, dry mouth, and also Positive serology for SS-A (Ro) and SS-B (La) autoantibodies Chronic inflammatory and autoim- arthritis and vasculitis (Courtney, Treadaway, Remington, & (Courtney, Treadaway, Remington, & Frohman, 2009; Rolak & mune disease Frohman, 2009; Rolak & Fleming, 2007). Fleming, 2007). MRI may show white matter lesions, and CSF may show OCBs with increased IgG. Biopsy of the salivary gland can be definitive (Rolak & Fleming, 2007).

faster and better therapeutic decisions by 2005; Guimarães, Cardoso, & Sá, healthcare providers. 2006; Jiménez-Jiménez et al., 2002; 3. Neurodegeneration proteins indicative of dis- Terzi, Birinci, Cetinkaya, & Onar, ease progression. Disease activity in MS is 2007; Valis, Talab, Stourac, An- mainly due to inflammation; however, disease drys, & Masopust, 2008). progression is most likely due to neurodegen- . iii N-acetylaspartic acid—may be an eration (Harris & Sadiq, 2009). important neuron specific marker of a. CSF biomarkers (proteins) that reflect the disease severity and possible progres- pathological process of MS are indicative of sion (Jasperse et al., 2007; Teunissen demyelination as well as neuronal, axonal, et al., 2009). and glial loss and regeneration (Tumani et iv. B cell chemokine CXCL13 (also al., 2009). known as B lymphocyte chemoattrac- . i Neurofilaments tant [BLC]). Chemokines are a group a) Studies have shown that an in- of molecules that attract leukocytes crease in these antibodies may (WBCs) from blood to the brain serve as a marker of axonal dam- when there is infection and/or an image in MS (Giovannoni, 2010; Sal- mune response. B cells are a type of zer, Svenningsson, & Sundström, WBC that develops in the bone mar- 2010; Teunissen, Dijkstra, & Pol- row and works as part of the immune man, 2005). system of the body. They have many b) Antibodies to neurofilaments have receptors that recognize invading or- been identified in the serum and ganisms and as a result release anti- CSF of patients with MS. They bodies to fight the invaders. B cells have been detected in relapsing as play a role in the pathogenesis of MS. well as progressive disease and are CSF and CNS tissues of patients with thought to be a marker of progres- MS contain B cells along with plasma sive axonal injury (Rammohan, cells, antibodies, and immunoglob- 2009). ulins, which suggests the need for . ii Total tau protein levels in CSF more research toward B cell–targeted a) Tau protein is a protein localized therapies (Racke, 2008). in neuronal axons, and because . v Nogo-A axonal damage has been proposed a) Nogo-A is a protein that is a as the major cause of permanent strong neurite inhibitor (Oertle clinical disability in patients with et al., 2003). It plays a role in re- MS, it is thought that it can serve structuring axonal regeneration as a biochemical marker to evalu- (or regrowth) after injury and in ate axonal damage (Brettschneider structural plasticity (i.e., ability et al., 2005). of the neural pathways to reorga- b) Studies have been both positive nize as a result of new input) in the and negative for use of tau pro- CNS. Proteins that affect remye- tein as a clinical marker of axo- lination and regeneration are pro- nal injury (Brettschneider et al., teins that are thought to provide

24 Nursing Management of the Patient with Multiple Sclerosis important information about MS Recommendation: Nurses should familiarize themselves related to predicting disease sub- with published and ongoing research efforts in the area of types and progression (Lehmen- biomarkers for MS disease diagnosis and progression to siek et al., 2007). provide patient education regarding laboratory testing and b) Results from several studies on respond to questions from patients (Level 3). Nogo-A suggest that it has multiple functions at the cell surface VI. Disease Management and intercellular level (Harris & A. Management of MS Sadiq, 2009; Oertle et al., 2003). 1. The management of MS is directed toward Nogo-A plays an important role disease modification, relapse management, for oliodendrocyte differentiation, and symptom management. Treatment aims which is important in myelin re- include decreasing the frequency and number pair in autoimmune diseases such of relapses, limiting disability, and relieving as MS (Pernet, Joly, Christ, Dimou, symptoms (Compston & Coles, 2002; Goodin & Schwab, 2008), thus Nogo-A et al., 2007). may have a beneficial effect during . 2 There are presently six disease-modifying the inflammatory process of MS treatments (DMTs) approved for use in the but could be negative for the pro- United States and Canada to treat relapsing cess of myelin repair at a later date. forms of MS: glatiramer acetate (Copaxone®); vi. Apolipoprotein (ApoE) natalizumab (Tysabri®); and the interferons a) ApoE is a transport protein that (IFNs), intramuscular IFN β-1a (Avonex®), has been associated with clinical subcutaneous IFN β-1a (Rebif®), subcutane- features of MS. Liu and colleagues ous IFN β-1b (Betaseron®, Extavia®), and fin- (2009) reported that ApoE was de- golimod (Gilenya™). Randomized clinical trials creased in patients with MS. It has support the favorable effects of DMTs on MS- also been identified in CIS as one related disease activity as monitored by means of the proteins that may have a rel- of MRI, relapse rate, and sustained disability evant effect on early identification (Comi, Filippi, & Wolinsky, 2001; INFB Mul- of disease. However, further vali- tiple Sclerosis Study Group & the University dation is needed (Lehmensiek et of British Columbia MS/MRI Analysis Group, al., 2007). 1995; Jacobs et al., 1996; Johnson et al., 2003; b) ApoE is considered to be a neu- O’Connor, 2005; Rudick, 2005; Prevention of rotropic factor. Therefore, any Relapses and Disability by Interferon β-1a Sub- decrease in intrathecal ApoE syn- cutaneously in Multiple Sclerosis [PRISMS] thesis could possibly contrib- Study Group, 1998). Mitoxantrone (Novan- ute to the progression of multiple trone®) is an immunosuppressant approved to sclerosis. treat secondary progressive, progressive-re- vii. BDNF protein lapsing, and worsening RRMS not responding a) Expression of BDNF has been as- to other DMTs (Edan et al., 1997; Hartung et sociated with neural regeneration; al., 2002). The key features of DMTs for MS are it is usually found wherever inner- summarized in Table 6. vations are present. 3. Tolerance of and willingness to adhere to treat- b) An increased number of BDNF ment regimen and the risk/benefit ratio drive positive cells have been found in treatment decisions of the person with MS and the inflammatory lesions of those the prescriber (Freedman et al., 2008; Goodin, with MS (Stadelmann et al., 2002), 2004; Goodin et al., 2007; Ross, 2008). and agents used to treat MS have 4. Nurses are responsible for monitoring the re- been found to activate cells capa- sponse to DMT, including skin site reactions ble of producing BDNF (Yoshimu- (Figures 13–15). Strategies to manage toler- ra et al., 2010; Ziemssen, Kümpfel, ability issues associated with MS therapies are Klinkert, Neuhaus, & Hohlfeld, presented in Table 7. 2002), with higher levels of BDNF 5. Intravenous methylprednisolone or oral ste- apparently playing a role in the roids are most commonly used to treat relaps- disease process. es (Thrower, 2009).

Nursing Management of the Patient with Multiple Sclerosis 25 Recommendations: Nurses need to be aware of 2-year effectiveness of four DMTs used for the mechanism of action of MS medications to RRMS—glatiramer acetate, interferon (IFN) educate and counsel patients about expected ben- β-1a IM injection, IFN β-1a SC injection, and efits and adverse effects of medication therapy IFN β-1b SC injection. Variables included re- (Level 3). Nurses need to be aware of the role of lapses, disability progression, and direct med- personal patient preference and drug regimen ical costs. Medical savings were considered complexity related to tolerance of and willingness in an event of an avoided relapse and disabil- to adhere to treatment protocols (Level 2). ity progression prevention. It was found that . B Economic considerations without DMT, patients had more relapses and 1. Financially, these treatments can be costly and pronounced disability progression. The four a significant burden to patients and families. DMTs previously mentioned are the most cost- Both direct and indirect costs may or may not effective treatments for RRMS (Goldberg et al.). be reimbursed by insurance plans, which vary Recommendation: Nurses can serve as advocates individually. Kobelt and colleagues (2006) for MS patients related to ensuring connection studied the estimated current costs and QOL with medication support services (Level 2). of patients taking disease-modifying medica- C. Immunotherapies reveal aspects of MS tions, the total average annual cost in 2004 was Disease-modifying medications’ mechanisms $47,215 (U.S. dollars) per patient. Of the total of action provide evidence for understanding of average cost, it was determined that 53% was pathways in MS (Compston & Coles, 2002; Frank- for direct medical and nonmedical costs, while lin & Kotter, 2008; Olek, 2005; Chari, 2007; Yong, 37% was related to losses in productivity, in- 2002; Neuhaus, Archelos, & Hartung, 2003). cluding short-term absence, reduced work- 1. Glatiramer acetate ing time, and early retirement. Approximately a. Blockade of antigen presentation 10% of the yearly costs were attributed to in- . b Bystander suppression formal care. Costs were significantly correlat- c. Regulation of the T cells by CD 8 suppres- ed with functional capacity (Kobelt, et al.). sor cells 2. Affordability of disease-modifying agents: . d Enhanced neuroprotection and Studies have shown that some medications remyelination may be more affordable than others. Newer 2. Interferon β medications would likely be more expensive a. Stimulation of antiinflammatory cytokine than existing ones that have been used for a production longer time. Natalizumab (Tysabri®) has been . b Inhibition of VLA-4 interaction with vas- shown to reduce relapses and slow disease cular cell adhesion molecules (VCAMs) by progression, but the assessment of lifetime reducing increasing soluble VCAM-1 cost-effectiveness of natalizumab versus other c. Inhibition of synthesis and transport of disease-modifying drugs is inadequate (Earn- matrix metalloproteinases shaw, Graham, Oleen-Burkey, Castelli-Haley, 3. Fingolimod & Johnson, 2009). Earnshaw and colleagues a. Targets sphingosine-1-phosphate-1 recep- (2009) show that direct costs (remaining life- tor on lymphocytes entrapping in lym- time) for patients receiving glatiramer acetate phoid tissue or natalizumab compared to costs associ- 4. Monoclonal antibodies—reduce occurrence ated with symptom management were only of contrast-enhancing lesions suggesting: $408,000; $422,208; and $341,436, respectively. a. Circulating immune cells expressing α-4 Glatiramer acetate was more cost-effective than integrins are responsible for much of the natalizumab. Long-term evidence showed that CNS cellular infiltration in MS. glatiramer acetate has similar, if not improved, . b Augmentation of low levels of natural kill- clinical benefits, despite 1- and 2-year relapse er cells and their function may correct de- rates being better for natalizumab (Earnshaw, fects in or provide a better level of T cell Graham, Oleen-Burkey, Castelli-Haley, & regulation. Johnson, 2009). c. Circulating B cells are important pathogen- 3. RRMS affects the majority of the MS popu- ic components of immune responses in MS. lation. Although there are several DMTs for . d Circulating lymphocytes and monocytes RRMS, not all are available for the same cost. are important in demonstrating contrast- Goldberg and colleagues (2009) analyzed the enhancing MS lesions.

26 Nursing Management of the Patient with Multiple Sclerosis Table 6. Key Features of the Disease-Modifying Agents Agent Interferon ß-1b (Brand (Betaseron®, Interferon ß-1a Interferon ß-1a Glatiramer ace- Natalizumab Mitoxantrone Fingolimod Name) Extavia®) (Avonex®) (Rebif®) tate (Copaxone®) (Tysabri®) (Novantrone®) (Gilenya™)

Description • Recombinant agent, • Recombinant • Recombinant • Synthetic poly- • Recombinant • Synthetic Binds to the produced in E. coli agent produced agent produced peptide humanized antineoplastic sphingosine- • Unglycosylated from Chinese from Chinese • Approximates monoclonal anthracendione 1-phosphate • Amino acid se- hamster ovary hamster ovary the antigenic antibody receptor, or S1P quence differs from cells cells structure of produced in receptor on naturally occurring • Glycosylated • Glycosylated myelin basic murine my- immune cells, interferon with a • Identical in • Identical in protein eloma cells including T cells serine substituted amino acid amino acid and B cells. for the cysteine content and sequence to hu- Induces immune residue at position sequence to human ß-interferon cells to remain 17 man β-interferon in lymph nodes, inhibiting them from migrating into the brain and spinal cord.

Indication Relapsing forms of MS Relapsing forms of Relapsing forms of RRMS to reduce Relapsing forms of SPMS, PRMS, Reducing the (United States) to reduce frequency of MS to slow accu- MS, to delay accu- frequency of MS to delay accu- or abnormally frequency of relapses, CIS mulation of physical mulation of physi- relapses, CIS mulation of physi- worsening RRMS, clinical relapses disability and cal disability and cal disability and for reducing neu- and delaying the decrease frequency decrease frequency reduce frequency rological disability accumulation of of relapses, CIS of relapses of relapses and frequency of physical disabil- relapses ity in relapsing forms of MS.

Dosage/ 0.25 mg/l subcutane- 30 μg/l intramuscu- 22 μg or 44 μg/l 20 mg/l subcutane- 300 mg/IV infu- 12 mg/m2 0.5 mg orally Route/ ous injection every lar injection weekly subcutaneous ous injection daily sion over 1 hour (cumulative daily Admini- other day injection 3 times every 4 weeks lifetime dose not stration weekly, preferably to exceed 140 mg/ on same 3 days and m2)/ IV infusion at the same time administered for (e.g., late afternoon 5 to 15 minutes or evening) every 3 months

Nursing • Injection-site • Injection-site • Injection-site • Injection-site • Only available • Cardiotoxicity Requires 6 hours Consid- rotation and skin rotation and skin rotation and skin rotation and skin under TOUCH® (increases with first dose moni- erations management management management management Prescribing cumulative toring. Caution • Laboratory monitor- • Laboratory • Laboratory • Immediate post- Program dose): should be used ing* monitoring monitoring injection reac- • PML, hyper- • Patients should in patients who • Neutralizing anti- • Neutralizing • Neutralizing tion, lipoatrophy, sensitivity be monitored may be at risk bodies antibodies antibodies other side effects reactions, signs for evidence of of developing • Hematological/ • Hematological/ • Hematological/ of liver injury, cardiotoxicity bradycardia or hepatological hepatological hepatological other side ef- prior to each heart blocks, abnormalities abnormalities abnormalities fects dose, and total macular edema, • Flu-like symptoms, • Flu-like symp- • Flu-like symp- cumulative active infections, depression, other toms, depres- toms, depres- lifetime dose is hypertension, side effects sion, other side sion, other side not to exceed hepatic dysfunc- effects effects 140 mg/m2 tion, and respira- • AML tory disorders. • Other side effects

AML, acute myelogenous leukemia; CIS, clinically isolated syndrome; IV, intravenous; PML, progressive multifocal leukoencephalopathy; PRMS, progressive-relaping MS; RRMS, relapsing- remitting MS; SPMS, secondary-progressive MS. *Laboratory monitoring for hematological/hepatological changes is done usually at month 3, 6, 9, 12, 18, 24 and annually after that. Neutralizing antibodies can be detected at 12–24 months. Adapted with permission from Costello, K., & Halper, J. (Eds.). (2010). Multiple Sclerosis: Key issues in nursing management—adherence, cognitive function, quality of life. (3rd edition.). Wash- ington, D.C.: Expert Medical Education.

References: Betaseron® (interferon beta-1b) [package insert]. Montville, NJ: Bayer HealthCare Pharmaceutical; 2008. Extavia® (interferon beta-1b) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2009. Avonex® (interferon beta-1a) [package insert]. Cambridge, MA: Biogen, Inc; 2009. Rebif® (interferon beta-1a) [package insert]. Rockland, MA: Serono, Inc; New York, NY: Pfizer, Inc; 2009. Copaxone® (glatiramer acetate) [package insert]. Kansas City, MO: Teva Neuroscience, Inc; 2009. Novantrone® (mitoxantrone) [package insert]. Rockland,�� MA: Se- rono, Inc; 2008. National MS Society. Copaxone�� (glatiramer acetate). Available at www.nationalmssociety.org/about-multiple-sclerosis/treatments/medications/glatiramer-acetate/index.aspx. Ac��- cessed November 18, 2009. Tysabri® (natalizumab) [package insert]. Cambridge, MA: Biogen Idec, Inc.; 2008. National MS Society. Gilenya (fingolimod). Available at www.nationalmssociety.org/ about-multiple-sclerosis/what-we-know-about-ms/treatments/medications/fingolimod/index.aspx. Accessed January 7, 2011.

Nursing Management of the Patient with Multiple Sclerosis 27 Figure 13. Erythema, Interferon β-1a SC 5. Estriol a. Increases IL-10 and IL-5 and decreases interferon γ and TNF-α . b Provides further support of shift toward antiinflammatory responses and is typically favorable in relapsing MS 6. Studies of agents that have been shown to worsen MS also provide evidence for understanding of pathways in MS (Panitch, Hirsch, Schindler, & Johnson, 1987). a. Interferon γ—augments helper T cell-1 response . b Granulocyte colony-stimulating factor— stimulates autoreactive lymphocytes Courtesy of Colleen Harris, MN MSCN c. Antitumor necrosis factor α agents— blocks beneficial effects of tumor necrosis Figure 14. Erythema, bruising, glatiramer acetate factor α, suggesting it may have immuno- modulatory neuroprotective properties Recommendations: Nurses must be aware of patient responsiveness to therapy and serve as advocates for follow-up with appropriate interdisciplinary team providers (Level 3). Nurses should monitor MS patients for medication-related side effects and use appropriate strategies to manage their manifestations (Level 2).

VII. Clinical Features and Symptom Management A. Clinical features overview 1. MS is first and foremost a clinical diagnosis. 2. Clinical manifestations in MS depend on Courtesy of Kathleen Costello, MS ANP-BC MSCN which portion of the CNS is affected. The demyelination or destruction of the myelin sheath of axons in the CNS most frequently af- Figure 15. Lipoatrophy fects the optic and oculomotor cranial nerves and the cerebellar, corticospinal, and posterior column systems. Clinical manifestations include abnormalities of vision and eye movement, motor skills, coordination, and gait, as well as spasticity and sensory disturbances, such as pain and paresthesia (Hoeman, 2008). The interruption of neural conduction in the demyelinated nerves is manifested by a variety of symptoms, depending on the location and extent of the lesion (Hoeman, 2008; Porth & Courtesy of Colleen Harris, MN MSCN Matfin, 2008; Swann, 2006). 3. People with MS may experience a wide range . i Natalizumab—directed against α-4 of symptoms. These may vary from person to integrins person, and symptoms may vary within one . ii Daclizumab—directed against CD25, individual patient (Halper, Costello, & Har- the α chain of IL-2 receptor ris, 2006). The varied range of symptoms in- . iii Rituximab—directed against CD20 cludes fatigue, mobility, spasticity, numbness on B cells and tingling in the extremities, general weak- iv. Alemtuzumab—directed against ness, visual impairments, bowel and bladder CD52 on T and B cells and monocytes dysfunction, sexual dysfunction, cognitive

28 Nursing Management of the Patient with Multiple Sclerosis disabilities, depression, anxiety, and dimin- may be related to movement or nox- ished self-efficacy (Rumrill, 2009). Common ious stimuli. symptoms of MS are shown in Table 8 (Halp- . iii Lightning-like extremity pain. er, Costello, & Harris, 2006). iv. Painful Lhermitte’s sign. a. MS symptoms may be managed in a variety . v Optic neuritis results in inflamma- of ways including education, counseling, tion around the pain-sensitive me- physical and occupational therapy, rehabil- ninges near the optic nerve and itation, and medication. Table 8 provides retrobulbar pain. a summary of the various pharmacologic . d Chronic pain with insidious onset measures for selected MS symptoms. . i Dysesthetic extremity pain . B Sensory symptoms . ii Bandlike pain in torso or extremities 1. Paresthesias: Paresthesia can be present at . iii Back pain with radiculopathy any state of the disease (Peterson, Kornbluth, iv. Headache related to demyelinating Marcus, Saulino, & Hung, 2004). lesions a. Paresthesia is evidenced as numbness, tin- 3. Management strategies (Halper, 2007b; Malo- gling, a burning sensation, or pressure and ni, 2007) can range from annoying to severe in MS a. Nonpharmacologic patients (Porth & Matfin, 2008). . i Rehabilitation evaluation for physical . b Symmetric paresthesis (tingling and therapy, occupational therapy numbness) may occur in an unpredict- . ii Gait training able pattern in dorsal column symptoms . iii Seating in patients with spinal cord involvement. iv. Assistive devices In patients with cerebellar involvement, . v Energy conservation paroxysmal attacks include sensory (and vi. Avoidance of tight clothing or nox- motor) symptoms, such as paresthesias, ious stimuli dysarthria (and ataxia and tonic head turn- vii. Moist heat ing) (McCance, Huether, Brashers, & Rote, . b Pharmacologic 2010). Loss of neuroprotective sensation . i If symptoms appear to be re- may place patient at increased risk of pres- lated to relapse, short course of sure ulcer development. corticosteroids c. A common paroxysmal symptom, Lher- . ii Nonsteroidal antiinflammatory drugs mitte sign, is a shocklike or tingling sen- (NSAIDs) sation, shooting down the trunk or limbs . iii Antispasticity agents during active or passive flexion of the neck. a) baclofen (Liorseal®) Sensory stimulation, voluntary movement, b) tizandine (Zanaflex®) hyperventilation, and emotional stress may iv. Antiseizure medications be inciting events (McCance, Huether, a) phenytoin (Dilantin®) Brashers, & Rote, 2010; Porth & Matfin, b) gabapentin (Neurontin®, 2008). Gabarone®) 2. Pain: Pain is a complex symptom of MS and c) pregabalin (Lyrica®) usually involves the sensory system (Halper, d) carbamazepine (Tegretol®) Costello, & Harris, 2006). Acute and chronic . v Antidepressant medications pain may occur in MS. a) Trazadone (Desyrel®) a. It is subjective and is identified by the indi- b) Amitryptilline (Elavil®) switched vidual with MS. sequence . b It is difficult for an observer to measure c. Complementary and alternative medicine pain. (CAM) c. Acute pain and paroxysmal disorders . i Massage . i Trigeminal neuralgia may be as- . ii Guided imagery sociated with transmission of . iii Yoga nerve impulses in severe regions of iv. Tai chi demyelination. . v Relaxation techniques . ii Tonic spasms, at times, may be relat- . d Surgical intervention for severe and intrac- ed to spasticity. Simple flexor spasms table pain

Nursing Management of the Patient with Multiple Sclerosis 29 Table 7. Symptoms of Multiple Sclerosis Common Less Common Rare Fatigue Dysarthria, scanning speech, dysphagia Decreased hearing Depression Lhermitte’s sign Convulsions Focal muscle weakness Ataxia Tinnitus Visual changes Vertigo Mental disturbance Bowel, bladder, sexual dysfunction Tremor, incoordination Paralysis Gait problems, spasticity Paresthesias Neuropathic pain Cognitive dysfunction

Table 8. Pharmacologic Management of Selected Symptoms in Multiple Sclerosis Symptom Treatment Nursing Considerations Fatigue CNS stimulants (pemoline, modafinil) Restlessness or sleep disturbance may occur Amantadine Help patients with dosing schedule, titrate doses up Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine) Bladder dysfunction Anticholinergics (e.g., oxybutynin) Determine if urinary tract infection is present Antimuscarinics (e.g., tolterodine) Monitor retention α-blockers (e.g., terazosin) Monitor fluid balance Follow overall elimination pattern Consider contribution of other medications Provide strategies to avoid side effects (e.g., dry mouth) Bowel dysfunction Constipation Provide bowel training regimens; many of the medications should not be used long term Stool softeners Consider contributory effects of other medications (e.g., steroids or antibiotics) Bulk-forming agents Consider lifestyle issues Mini-enemas Encourage exercise Stimulants Provide diet counseling Suppositories Urgency or diarrhea Anticholinergics Antimuscarinics Pain Anticonvulsants (phenytoin, carbamazepine, Watch for sedation abapentin, amotrigine) Start with low doses and titrate up Tricyclic antidepressants (amitriptyline, nortrip- Monitor outcomes; alter treatment as necessary; supportive measures can help tyline) Duloxetine hydrochloride Spasticity GABA antagonists (oral or intrathecal baclofen) Time doses to maintain therapeutic blood levels α-Agonists (tizanidine) Titrate doses up (especially with baclofen) Anticonvulsants (diazepam, clonazepam, gaba- Watch for sedation or cognitive symptoms; may require a change in dosage or medication pentin) Combination treatments may help Botulinum toxin Intrathecal baclofen requires surgical insertion of a programmable pump Depression SSRIs and serotonin-norepinephrine reuptake Evaluate type and degree of depression inhibitors (e.g., fluoxetine, sertraline, paroxetine, Consider contribution of medications (e.g., with interferons) citalopram, duloxetine hydrochloride) Assess family situation and support network Tricyclic antidepressants (amitriptyline, nortrip- Consider suicide risk tyline) Promote use of psychiatric services Atypical antidepressants (e.g., venlafaxine, Advise patient that medication effects may take several weeks bupropion) Advise patient not to stop medications suddenly Reassess patient regularly Paroxetine can be taken in the morning or at night and can help with anxiety Monitor urinary function with venlafaxine (may cause fluid retention) From Singer, B., Lucas, S., Kresa-Reahl, K., Perrin Ross, A., & Blake, P. (2008). Optimizing adherence to multiple sclerosis therapies: Managing tolerability and monitoring safety. International Journal of MS Care, 10(4), 113–126. Reproduced with permission.

30 Nursing Management of the Patient with Multiple Sclerosis Recommendations: The nurse should conduct followed by deafness, vertigo and vomiting, intermittent assessment for pain, dysthesia, and tinnitus, facial weakness, and facial sensory spasticity (Level 2). Evaluate for the loss of neu- deficit. Bilateral internuclear ophthalmo- roprotective sensation and the potential for pres- plegia (lateral gaze paralysis) is considered sure ulcer development (i.e., ensure full body diagnostic of MS. If it is acute, treatment assessment; Level 2). Evaluate the patient for trig- may include high-dose glucocorticoids to gering and alleviating factors (Level 2). Evaluate accelerate recovery (Halper, Costello, & the effectiveness of pharmacologic therapies and Harris, 2006); otherwise, treatment is for advocate for evaluation by the interdisciplinary symptoms. There is currently no approved team (Level 1). Provide patient with emotional U.S. Food and Drug Administration (FDA) support and evaluate for anxiety (Level 2). Pro- treatment. Prism lenses may be helpful in vide patient and family education related to avail- some individuals with diplopia. ability of adjuvant treatment and possible surgi- . e Nystagmus may be present in patients who cal interventions; assess patient’s willingness and have cerebellar involvement with MS and readiness to incorporate alternative therapies into reflects cerebellar and corticospinal involve- treatment regimen (Level 3). ment (McCance, et al.). Nystagmus is also C. Visual and hearing impairment included in the description of the Charcot 1. Visual Iimpairment triad, described by a combination of nystag- a. The demyelination or destruction of the mus, dysarthria, and intention tremor (Mc- myelin sheath most frequently affects the Cance, Huether, Brashers, & Rote, 2010). optic and oculomotor cranial nerves and For nystagmus, some benefit has been the cerebellar, corticospinal, and posterior found with the following pharmacologic column systems. Vision problems are often agents (Halper, Costello, & Harris, 2006): the first sign of MS (National MS Society, . i Gabapentin (Neurontin®, Gabarone®) 2009). . ii Memantine (Namenda®) . b Twenty-five to forty-eight percent of per- . iii 4-aminopyridine sons initially experience optic neuritis (Pe- iv. Levetiracetam (Keppra®) terson, Kornbluth, Marcus, Saulino, & 2. Hearing impairment Hung, 2004; Plant, 2008). This manifes- a. The MS patient’s ability to understand tation of optic nerve axonal loss is high- speech is markedly worse with sensorineu- ly suggestive of MS. Diplopia and eyeball ral hearing loss (Suckfüll, 2009). pain are common subjective findings (Mc- . b Young persons with hearing loss should Cance, Huether, Brashers, & Rote, 2010). have MS considered as a possible diagno- High-dose glucocorticoids have been used sis. Bilateral sequential hearing loss may be traditionally to accelerate recovery, and considered an MS manifestation (Oh, Oh, NSAIDs may be useful for pain manage- Jeong, Koo, & Kim, 2008). ment (Halper, Costello, & Harris, 2006). Recommendations: Encourage regular eye ex- c. Subjective visual symptoms that may pres- aminations (Level 3). Be aware of the potential ent unilaterally or bilaterally include im- for hearing changes and assess as needed (Lev- paired central vision (blurring, fogginess, el 3). Provide education regarding the patient’s haziness) and impaired color perception. particular visual and hearing symptom experi- Signs include decreased central visual acu- ence (Level 3). Support the patient as visual and ity; central or paracentral scotoma (area of hearing impairment may reduce overall function diminished vision); acquired color vision (Level 2). Promote safety through education and deficit, especially to red and green; defec- counseling related to effective lighting, scanning, tive papillary reaction to light; and a va- and environmental modifications (Level 2). riety of field defects (McCance, Huether, D. Fatigue Brashers, & Rote, 2010). 1. Fatigue is an individual’s subjective lack of . d Internuclear ophthalmoplegia, nystagmus, physical and/or mental energy that is perceived and dysarthria are the most common brain as impeding his or her typical or desired activi- stem symptoms. May have significant effect ties of life (Johansson, Ytterberg, Gottberg, Wi- on ADLs because of diplopia or inability dén Holmqvist, & von Koch, 2009). to focus. These brain stem lesions involv- 2. Fatigue is considered the most common and ing cranial nerves III through XII may be disabling symptom of MS; it affects between

Nursing Management of the Patient with Multiple Sclerosis 31 75% and 95% of all persons with the disease Nagels, D’Hooghe, & Ilsbroukx, 2008; Krupp, (Egner, Phillips, Vora, & Wiggers, 2003). 2004; Markowitz, 2010; Mills, Young, Pallant, 3. Higher levels of general fatigue are observed & Tennant, 2010; Penner & Calabrese, 2010) in RRMS compared with the other three sub- a. Nonpharmacological strategies types, and with increasing disease severity. . i Gradual exercising DMT generally has no effect on fatigue lev- . ii Maintain realistic expectations els (Hadjimichael, Volmer, & Oleen-Burkey, . iii Energy conservation techniques 2008). (Fragoso, Santana, & Pinto, 2008) 4. Fatigue is categorized into primary and sec- a) Pace activities ondary forms, which are often difficult to b) Space activities differentiate. c) Divide activities a. Primary fatigue can directly result from d) Do strenuous activities early in the MS neuropathology. morning . b Secondary fatigue follows from a number e) Minimize effort of common MS comorbidities, including f) Prioritize tasks depression, medication side effects, pain, g) Schedule and plan activities psychosocial characteristics, thyroid dys- h) Schedule rest periods function, vitamin B12 deficiency, anemia, iv. Keep cool during exercises and sleep disorders (Johnson, 2008). Most a) Exercise in air-conditioned research to date has found fatigue to be of environment the secondary rather than the primary form. b) Drink ice water 5. Trojan and colleagues (2007) differentiated fa- . b Complementary and alternative methods tigue into three categories: (1) general or over- . i Vitamins all, (2) physical, and (3) mental. They found ii. Nutrition that sleep quality, pain, and self-efficacy were . iii Caffeine the strongest predictors of general fatigue; iv. Carnitine self-efficacy and physical activity level were c. Pharmacological interventions most predictive of physical fatigue; stress level . i Fatigue responds to some phar- and self-efficacy were the strongest predictors macotherapy regimens, including of mental fatigue. amantadine (Symadine®, Symme- 6. Relationships between physical fatigue and trel®), modafinil (Provigil®) and increased MS disease severity have been ob- armodafinil, selective seratonin reup- served (Debouverie, Pittion-Vouyovitch, take inhibitors (SSRIs). Brissart, & Guillemin, 2008). . ii Less commonly used are amphet- 7. Depression has not been found to be a strong amines such as methylphenidate or predictor of physical fatigue in MS (Debouv- amphetamine and dextroamphet- erie, Pittion-Vouyovitch, Brissart, & Guille- amine composite (Adderall®). min, 2008; Trojan et al., 2007), although it has . iii Aminopyridine is a possible modula- shown relationships with mental fatigue (Sch- tor of increased conduction and in- reurs, de Ridder, & Bensing, 2002). creasing fatigue. 8. Along with depression, fatigue is a predictor iv. A key point for all medications for for decreased cognitive functioning in MS (Di- MS patients is to initiate at a low dose amond, Johnson, Kaufman, & Graves, 2008). and increase based on effectiveness 9. Assessment of fatigue and tolerance. a. Involves informal questioning of patients Recommendations: Nurses should be aware of and their care partners and assess for secondary causes of fatigue to in- . b Formal assessment by means of instru- clude depression, medication side effects, pain, ments/tools: the Modified Fatigue Impact and sleep disorders (Level 2). Nurses should edu- Scale (MFIS), the Fatigue Severity Scale cate and counsel patients regarding energy con- (FSS), or the Neurological Fatigue Index- servation strategies, including the role of body MS (NFI-MS) temperature control (Level 2). The nurse should 10. Management of fatigue (Bergamaschi, Ro- be aware of the optimal timing of medication ad- mani, Versino, Poli, & Cosi, 1997; Costel- ministration to enhance energy level and to avoid lo, Halper, & Harris, 2003; Kos, Kerckhofs, interrupting sleep (Level 3).

32 Nursing Management of the Patient with Multiple Sclerosis E. Impaired mobility life (Motl & Gosney, 2008) among patients 1. Physical activity is markedly decreased in MS with MS. populations compared with that in healthy . i Exercise therapy was not found to controls, and this appears to be related to dis- be effective in reducing fatigue or in ease severity (Motl, 2008). However, it is not reducing the perception of disabil- clear if disease severity itself is the culprit. ity compared to no exercise therapy. Because fatigue and motor dysfunction fre- No evidence was found to suggest quently present in MS, persons affected by the that exercise therapy was harmful, disease often avoid physical exercise, believing and it is reasonable to promote exer- it may worsen fatigue or have no beneficial cise in patients with MS who are not effect. experiencing an exacerbation (Riet- 2. Hand dysfunction has been found to be berg, Brooks, Uitdehaag, & Kwakkel, more common at testing in patients with 2005). MS when compared with that in other pa- . ii Resistance exercise has been found tients (Krishnan & Jaric, 2008). This dys- to have a positive effect on function function may include loss of strength and/or in patients with MS. A randomized coordination. clinical trial of exercise versus con- 3. Disabling tremor or ataxia is a common fea- trol group demonstrated that super- ture of MS and occurs in almost 80% of pa- vised and intense resistance training tients at some point during their disease. of the lower extremities improves Research on strategies to treat disabling tremor muscle strength and functional ca- or ataxia with pharmacotherapy, neurosurgery, pacity in patients with RRMS and or rehabilitation has not demonstrated effec- moderate impairment. Importantly, tive treatment (Mills, Yap, & Young, 2007). in patients, these improvements per- 4. A symptom cluster of pain, depression, and sisted after 12 weeks of self-guided fatigue has recently been observed to be a physical activity (Dalgas et al., 2009). strong barrier to exercise, and functional im- Resistance training of moderate in- pairment is a predictor of the presence of the tensity seems to be well tolerated and symptom cluster (Motl & McAuley, 2009). to have beneficial effects for patients 5. Assessment (Halper & Ross, 2010; Schapiro, with MS. 2007) . iii Elevated core body temperature can a. Subjective history sometimes present a barrier to exer- . b Objective assessment of motor strength, cise (generating Uhthoff’s phenom- muscle tone, balance, and sensory func- enon), but this can be addressed by tion. Specific tests include: the timed 25- the use of affordable cooling equip- foot walk, timed up and go test, expanded ment (Schwid et al., 2003). disability status scale (EDSS), and driving . b Use of adaptive equipment: bracing, cane, evaluation. walker, scooter, wheelchair. Ensure training 6. Management of mobility disturbance on safe use and proper maintenance. The a. Exercise therapy: identified as an effective patient is referred for evaluation for use of treatment for MS. Results of trials show automobile hand controls; OT/PT consul- strong evidence that exercise therapy com- tation is obtained as appropriate (Halper & pared to no exercise therapy had positive Ross, 2010; Schapiro, 2007). effects on muscle power function, exercise c. Electrical stimulation devices: WalkAide®, tolerance functions, and mobility-related Bioness® (Halper & Ross, 2010; Schapiro, activities (Rietberg, Brooks, Uitdehaag, & 2007) Kwakkel, 2005). Exercise improves self- . d Pharmacologic therapy: dalfampridine, efficacy, which in turn reduces fatigue, fampridine-SR (Ampyra) pain, and depression in patients with MS Recommendations: Identify functional effect of (McAuley, White, Rogers, Motl, & Cour- impaired mobility and collaborate with interdis- neya, 2010). Meta-analyses have shown ciplinary team members to promote optimal mo- that exercise training is associated with bility within the patient’s limitations (Level 3). a small improvement in walking mobil- Evidence-based treatment interventions for mo- ity (Snook & Motl, 2009) and quality of bility optimization include exercise promotion

Nursing Management of the Patient with Multiple Sclerosis 33 (Level I). Educate patient and care partners re- c. Uroflowmetry (volume of urine voided garding treatment, therapy recommendations, over time), postvoid residual (PVR; urine medications, and support adherence (Level 3). volume after void) The nurse should encourage safety by reinforcing . d Radiologic tests appropriate and safe use of adaptive equipment . i Abdominal computed tomography and aides (Level 2). Assess for the psychological (CT) scan effect of reduced mobility and/or increased dis- . ii Renal ultrasound (renal and upper ability (Level 2). urinary tract status) . F Bladder and bowel symptoms . iii Cystoscopy (study of bladder lining 1. In MS with spinal cord involvement, bowel and urethra) and bladder symptoms occur. Some MS pa- . e Bladder diary—voiding patterns typical tients lose voluntary control over bladder and over 24–72 hours bowel function (Pellat, 2008). . f Diary of food and fluid intake 2. Bladder symptoms 5. Urinary management strategies (Betts, a. There are three types of bladder dysfunc- D’Mellow, & Fowler, 1993; DasGupta & Fowl- tion: storage dysfunction, emptying dys- er, 2003; O’Leary & Dierich, 2010) function, and combined dysfunction. In a. Nonpharmacologic MS, bladder dysfunction affects QOL . i Behavior management—establish- (Rantell, 2009). ing voiding schedule, diet instruction . b Incontinence is preceded by urgency and to limit irritants and to increase fluid hesitancy. Flaccid bladder may occur with intake, measures to limit fluid reten- retention problems, although bladder dys- tion, environmental assessment of function most often involves a spastic toilet locations, proper use of absor- bladder. bent products, biofeedback, and in- c. Some patients with spinal cord disease may fection prevention strategies have combined incomplete emptying and . ii Intermittent self-catheterization bladder overactivity (Pellat & Geddis, 2008). (ISC)—used for chronic retention to 3. Bowel dysfunction improve continence and to preserve a. Neurogenic bowel dysfunction may occur renal function. Frequency depends on in MS. This may include fecal incontinence voids per day and resulting retention. or constipation, and at times may involve . iii Long-term indwelling catheters—su- both (Wollin, Bennie, Leech, Windsor, & prapubic catheter recommended for Spencer, 2005), and is often an underre- individuals who cannot toilet them- ported symptom of MS (Bywater & While, selves, cannot perform intermittent 2006). In severe cases of MS, constipation catheterization, or have medi- is common (McCance, Huether, Brashers, cal issues from incontinence. Ure- & Rote, 2010). thral catheters should be used short . b Bowel dysfunction has a significant effect term only (i.e., several weeks, not on the QOL of patients with MS, but re- months) because of the damage that search in this area is limited (Coggrave, can occur in the urethra and other 2008; Coggrave, Wiesel, & Norton, 2006). complications. 4. Evaluation of urinary elimination in MS . b Pharmacologic patients can be multidimensional (Betts, . i Anticholinergics—side effects of oral D’Mellow, & Fowler, 1993; DasGupta & Fowl- forms include dry mouth, blurred vi- er, 2003; O’Leary & Dierich, 2010) sion, flushing, palpitations, nausea, a. Laboratory assessment constipation, drowsiness, confusion, . i Urinalysis; urine culture and sensitiv- and urinary retention. ity (UTIs, diabetes, hematuria) . ii Alpha-adrenergic blocker—side ef- . ii Cytology (bladder cancer) fects include site reactions, sleepi- . iii Blood urea nitrogen (BUN), creati- ness, or blurred vision. nine levels (renal dysfunction) . iii Botulinum toxin (off-label use) injec- . b Urodynamics—group of tests which to- tion into bladder. Side effects: pain, gether measure bladder function and urinary retention, hematuria, and pressure infection.

34 Nursing Management of the Patient with Multiple Sclerosis Recommendations: Nurses should work with members of the interdisciplinary team to de- the patient, care partner, and other mem- velop an appropriate bowel management bers of the interdisciplinary team to develop program (Level 3). Assess all patients for dis- an appropriate bladder management pro- orders of bowel function and assess effective- gram (Level 3). Assess all patients for urinary ness of treatments or behavioral strategies dysfunction and assess effectiveness of treat- over time (Level 3). Encourage discussion of ments or behavioral strategies over time (Lev- symptoms and effect on QOL and role func- el 3). Encourage discussion of symptoms and tion and assist with coping strategies (Level effect on QOL and role function and assist 3). Assess for effectiveness of management with coping strategies (Level 3). Assess for in- strategies and effectiveness of medications, fection and assist in management strategies to understanding that bowel interventions may reduce risk of infection, stone formation, or take a long time to become effective and that worsening of neurologic condition (Level 3). worsening of symptoms without any relief 6. Evaluation of Bowel Function (DasGupta & from strategies may indicate disease progres- Fowler, 2003; Walker, 2009) sion (Level 3). a. Assessment of frequency and type of G. Sexual dysfunction and reproductive issues movement, time of day, use of any medi- 1. Sexual dysfunction is common in MS because cation, laxatives and enemas, absorbent of its direct neurophysiologic effects, conse- products, comorbid conditions, and assis- quences of secondary conditions of MS (e.g., tance needed with toileting fatigue, altered sensation, muscle spasms, . b Further testing as warranted bowel and bladder problems, vaginal dry- . i Laboratory—complete blood cell ness), and the psychological and cognitive count, complete metabolic profile changes that occur in MS (McCabe, 2002; (CMP), pancreatic enzymes, stool Smeltzer, 2002). culture, and hemoccult testing 2. Neurogenic impotence may accompany . ii Imaging—abdominal flat plate, bar- sphincter symptoms. ium enema, defecography, colon- 3. Despite the incidence of sexual dysfunction, ic transit studies, upper GI, and CT many patients with MS remain interested scan of abdomen in intimacy, sexual relationships, childbear- . iii Other tests—manometry and ing, and parenting (McCabe, 2002; Smeltzer, electromyography 2002). 7. Bowel management strategies Recommendations: Nurses must consider MS a. Nonpharmacologic patients’ interest in sexuality and intimacy rather . i Behavior management—establishing than assume that they are asexual or uninterest- consistent schedule, diet instruc- ed (Level 2). Nurses should provide information, tion to limit irritants and to increase education, counseling, and resources about issues fluid intake, addition of dietary fi- related to sexuality, reproductive function, preg- ber in foods the patient can tolerate, nancy, and parenting (Level 3). environmental assessment of toilet H. Dysphagia locations, proper use of absorbent 1. Permanent and transitory swallowing disor- products, and biofeedback ders (dysphagia) occur with high frequency in . ii Use of reflexes. Stimulation of gas- patients with MS (Calcagno, Ruoppolo, Grass, trocolic and duodenocolic reflex. The De Vincentiis, & Paolucci, 2002; Prosiegel, best time is 30–45 minutes after a Schelling, & Wagner-Sonntag, 2004), occur- meal or hot beverage or after digital ring in 34.4% of patients with primary and stimulation or enema. secondary progressive MS (Calcagno, Ruop- . b Pharmacologic polo, Grass, De Vincentiis, & Paolucci). Swal- . i Suppositories, bulk-forming agents, lowing disorders may be present long before stool softeners, laxatives (osmotic the person with MS experiences any other re- and stimulant), and rectal stimulants. lated symptoms. Patients with a mild form of (Caution: large-volume enemas can MS may experience problems swallowing flu- overdistend the bowel.) ids, and patients with more advanced MS may Recommendations: Nurses should work develop difficulties swallowing solid foods with the patient, care partner, and other (Bogaardt et al., 2009).

Nursing Management of the Patient with Multiple Sclerosis 35 2. A close relationship between dysphagia and . d Collaborate with dietician and SLP for di- both brain stem impairment and severity of etary modifications; ensure consistency illness has been noted. The potential risk of and ordered texture of liquids and solids. aspiration and malnutrition, and the high ef- . e Suctioning if indicated ficacy of swallowing rehabilitation suggest . f Monitor weight on ongoing basis. that all MS patients should have a careful . g Education of patient and family regarding evaluation of deglutition functionality, espe- safety measures to include use of suction cially those with brain stem impairment and apparatus and Heimlich maneuver a high grade of disability level (Calcagno, h. Advanced or worsening swallowing may Ruoppolo, Grass, De Vincentiis, & Paolucci, result in the need for tube feedings via na- 2002). sogastric (NG) tube temporarily or via per- 3. The most common MS-related swallowing cutaneous endoscopic gastrostomy (PEG) disorders in the oral and pharyngeal areas on a permanent basis. Educate and coun- are delays in triggering the pharyngeal swal- sel patients and care partners about feeding low. This can cause particular difficulties with options as disease progresses. liquid swallowing, including aspiration (Lo- . i Other treatment options may include neu- gemann, 2000). Reduction in tongue base ac- romuscular electrostimulation because it tivity reduces the pressure generated during was successful in reducing pooling saliva the swallow, allowing residual food to remain and in reducing aspiration in patients with in the pharynx and be aspirated when the pa- MS (Bogaardt et al., 2009). tient resumes breathing. These disorders can Recommendations: Assess the patient regular- be mild, without causing any significant dif- ly for swallowing difficulties (Level 2). Nurses ficulties such as aspiration or inefficient swal- should work with the patient, care partner, and low, or they can be more severe and require other members of the interdisciplinary team to therapeutic (behavioral) management (Loge- develop an appropriate dysphagia management mann, 2000). program (Level 3). Monitor weight at each vis- 4. Dysphagia evaluation it (Level 3). Educate and counsel the patient and a. Assessment: problem onset, duration and care partner to reinforce safe swallowing practic- severity; symptom characteristics; observa- es (Level 3). tion of choking, delayed swallowing, chew- I. Cognitive dysfunction ing difficulties; nutritional status, food and 1. Recent studies suggest a high prevalence rate liquid intake, weight; cough or increasing for cognitive impairment, ranging between hypophonia may indicate new or pending 40% and 70%, depending on the population problems. and setting studied (Chwastiak & Ehde, 2007; . b Referral should be made to a speech/ Siepman et al., 2008). The most common language pathologist (SLP) for evaluation cognitive impairments found in MS include and treatment. memory, sustained attention, and slowed in- c. Additional assessment as needed may information processing speed (Amato, Zipoli, & clude video-fluoroscopic study (modified Portaccio, 2006; Nocentini et al., 2006). barium swallow; Frenette, Harris, Klassen, 2. The relationship between MS disease sub- & McEwan, 2001). type and magnitude of cognitive impairment 5. Dysphagia management remains unclear (Kalmar, Gaudino, Moore, a. Ensure alert and minimize distractions Halper, & DeLuca, 2008). Huijbregts and col- at mealtimes; provide supervision as leagues (2004) demonstrated that cognitive indicated. profiles in RRMS versus progressive MS dif- . b Monitor patient for signs and symptoms of fer in severity and character, with patients swallowing difficulty, aspiration pneumo- with RRMS showing isolated deficits in work- nia (Frenette, Harris, Klassen, & McEwan, ing memory and those with progressive MS 2001). showing more global deficits. c. Safe swallowing practices 3. Cognitive impairment has been related to the . i Proper positioning presence of other symptoms including fatigue, . ii Double swallow spasticity, bowel or bladder dysfunction, and . iii Chin tuck fine motor functioning (Kalmar, Gaudino, iv. Other techniques as prescribed Moore, Halper, & DeLuca, 2008). Information

36 Nursing Management of the Patient with Multiple Sclerosis processing speed has demonstrated relation- of cognitive deficits (Level 3). Patients should be ships with depression and fatigue (Diamond, provided with verbal and written instructions re- Johnson, Kaufman, & Graves, 2008). garding the need to reduce distractions and im- 4. Relationships have been found between MRI plement safety measures (Level 3). measures and cognitive dysfunction in MS . J Mood dysregulation (Archibald et al., 2004; Calabrese et al., 2010). 1. Anxiety: Lifetime prevalence of any anxiety Some studies suggest a link between cogni- disorder in MS is 36%, compared with 25% in tive impairment and progression in the EDSS the general population (Korostil & Feinstein, (Lynch, Parmenter, & Denney, 2005), where- 2007). Generalized anxiety disorder lifetime as others do not (Kalmar, Gaudino, Moore, prevalence in MS is substantially higher at Halper, & DeLuca, 2008). 18.6% than in the general population, where it 5. Cognitive impairment has also been linked to is only 3% (Korostil & Feinstein). Lower EDSS employment status; however, education lev- scores, fatigue, pain, and younger age at dis- el, fatigue, and workplace characteristics were ease onset have been associated with symp- equally important contributors (Pompeii, toms of anxiety (Beiske et al., 2008). Moon, & McCrory, 2005). 2. Sleep disorders are also common in MS, with a 6. Evaluation of cognitive impairment cumulative prevalence of all forms of sleep dys- a. Brief batteries and clinical assessments function reaching 47.5% (Merlino et al., 2009). are under investigation for reliability and 3. Depression validity. a. Prevalence studies demonstrate that de- . b Informal evaluation of cognitive strengths pressive symptoms occur in MS with a and deficits by nursing professionals range from 31.4% (Beiske et al., 2008) to c. Refer for formal neuropsychological evalu- 41.8% (Chwastiak & Ehde, 2007). Stud- ation by neuropsychologist, SLP, occupa- ies of lifetime prevalence of major depres- tional therapist or other trained provider sive disorder in MS find rates ranging from 7. Management of cognitive impairment 22.8% to more than 50%, which is signifi- a. Cognitive rehabilitation (Mattioli, Stampa- cantly higher than that of the general pop- tori, Zanotti, Parrinello, & Capra, 2010). ulation (Patten, Beck, Williams, Barbui, & . i Direct retraining of impaired Metz, 2003). functions . b Depression has been linked to neurobi- . ii Memory exercises ological changes in brain structure and . iii Attention training function in persons with MS (Passamonti iv. Compensatory strategies et al., 2009). Beta interferon, a commonly . v Notebooks, lists, organizers used disease modifying therapy, has also vi. Substitution strategies garnered interest as a potential cause of the vii. Time and energy management increased depression prevalence rate (Pan- . b Pharmacologic management dya & Patten, 2002), but this association . i Disease-modifying therapy (Freed- has not held up in more rigorous studies man et al., 2008) (Patten & Metz, 2002). . ii Anticholinesterase inhibitor treat- c. A direct relationship between depression ment with donepezil (Krupp et al., and disease severity has not been found. 2004) Studies have found no relationship be- . iii Antifatigue agents, stimulants tween depression and increased EDSS iv. SSRIs scores (Brajković et al., 2009; Dahl, Stordal, Recommendations: Nurses should work with Lydersen, & Midgard, 2009). Comorbid fa- the patient, care partner, and other members of tigue and younger age of MS onset have the interdisciplinary team to develop an appro- been associated with depressive symptoms priate cognitive management program and re- (Beiske et al., 2008). evaluate on an ongoing basis (Level 3). The nurse . d Depression has been shown to have direct should screen for factors that could increase cog- effects on multiple aspects of functional nitive problems such as medications, sleep dis- impairment, including disease severity, ad- turbance, inadequately treated pain, and other herence to disease-modifying treatments, untreated symptoms (Level 2). Nurses need to and multiple QOL domains (Chwastiak & recognize and acknowledge the distressing nature Ehde, 2007; Paparrigopoulos, Ferentinos,

Nursing Management of the Patient with Multiple Sclerosis 37 Kouzoupis, Koutsis, & Papadimitriou, physical, emotional, spiritual, and educational 2010). needs of the patient and family (Level 2); rein- . e Effective treatment of depression, includ- force the importance of medication regimen and ing telehealth modalities (Egner et al.), has be aware of medication side effects (Level 2); be shown significant improvements in quality alert to cues related to mood changes and treat- of life (Hart, Vella, & Mohr, 2008). ment outcomes (Level 2); and encourage par- . f Studies have found the suicide rate in per- ticipation in a regular pattern of exercise to im- sons with MS to be twice that of a non-MS prove mood (Level 1). sample (Caine & Schwid, 2002). Suicid- al ideation is common in MS and appears VIII. Patient and Care Partner Education to be associated with depression, alcohol A. General concepts for patient and care partner abuse, and social isolation. Further, the se- education verity of depression and not the presence 1. Successful combination requires prepared ed- of major depression alone is a strong pre- ucator and motivated, ready learner dictor of suicide intent (Feinstein, 2002). 2. More effective when every member of multi- . g Despite the availability of effective treat- disciplinary team works toward agreed-on pa- ment and the high prevalence of depression tient and family outcomes and suicide in MS, less than 30% of MS pa- 3. Adult learning theory (Knowles, Holton, & tients with depressive symptoms actively Swanson, 2005) seek care (Sollom & Kneebone, 2007). a. Because most people with MS are adults, h. Assessment of depressive symptoms and andragogy rather than pedagogy (focus is suicidality on children) usually applies. Adult learning . i Ongoing assessment and monitoring theory is based on principles that adults as- for depressive symptoms with stan- sume responsibility for learning and that dardized instruments (e.g., PSQ-9, learning improves when the topic directly Beck Depression Inventory II, Center relates to their lives. for Epidemiologic Studies Depres- . b Assumptions of learning sion Scale [CES-D]) . i Adults with MS seek information . ii Positive endorsement of items should with a desire to improve their ability prompt screening for suicidality. to cope with the issues that MS pres- . iii Evaluate medication profile for drugs ents in their lives. that may influence mood. . ii Learning is enhanced if patients per- iv. Consult and refer with the multi- ceive education as increasing control disciplinary team as indicated by over their lives. assessment. 4. Domains of learning: Teaching patients with . i Management of depressive symptoms MS and their care partners typically ad- . i Acknowledge existence of complex dresses the domains of knowledge (cogni- and diverse changes caused by MS tive), attitudes (affective), and behaviors and their effect on patients and care (psychomotor). partners. . B Goals (Holland, 2002; London, 2009; Syx, 2008) . ii Activity and exercise (Reitberg, 1. Patient and family education provides MS Brooks, Uitdehaag, & Kwakkel, 2005; patients and their families with informa- Springer, Clark, Price, & Weldon, tion needed to promote active participation 2001) in care, and enables patients and families to . iii Counseling/cognitive behavioral make informed choices about health behav- therapy (Thomas, Hillier, Galvin, & iors and engage in self-care with confidence Baker, 2006) and competence. iv. Pharmacologic management (Table 8) 2. Additional objectives include promoting max- Recommendations: Nurses should work with imum health potential toward wellness, cop- the patient, care partner, and other members of ing and adaptation of the patient and family, the interdisciplinary team to manage depression and empowerment toward improved quality appropriately (Level 2). Other roles are to assist of life and hope. patients and care partners to adjust to changes 3. Specific goals of patient and family education involved in living with MS (Level 2); identify the in MS include (Halper, 2007a)

38 Nursing Management of the Patient with Multiple Sclerosis a. Understanding the diagnosis and success- commitment to therapy. Adherence is fully coping with the potential effects on greater when information includes realistic one’s life expectations. . b Planning in critical areas such as relation- . b Include information on basic clinical tri- ships, parenting, employment, and lifestyle al outcomes, mechanism of action, treat- c. Preventing potentially disabling outcomes, ments (administration, adverse effects and with specific goals related to new symptoms management, resources for information C. Role of the nurse (Halper, 2007a; Craven & Hirn- and financial assistance) le, 2008) c. Disease-modifying therapies 1. Assist individuals with activities that contrib- . d Adherence (discuss benefits and identify ute to health or recovery that patients perform barriers to adherence) unaided when possible (patient must have 3. MS-related symptoms strength, will, and knowledge) a. Common symptoms 2. Help individuals carry out prescribed therapy . b Uncommon symptoms 3. Contribute to behavior change, resulting in c. Management of symptoms the knowledge and skills necessary to main- 4. Plan of care tain and improve health a. Developed by the patient and the healthcare 4. Assess and reassess patient understanding and team to include goals and interventions that behavioral change will delay progression of disability 5. Promote and encourage adherence to . b Discuss when patient should call health- treatment care provider, and review process specific . D Concepts of learning to your office routine 1. Experience is the richest source of adult learn- 5. Role of team members (Craven & Hirnle, 2008) ing. Although many patients and family a. Physicians members have not had previous experience . i Primary care physician: Emphasizes with MS, most individuals have experienced the importance of regular and ongo- health-related issues that require coping skills. ing follow-up of all primary health- 2. Readiness to learn is important. Adults typi- care needs, including preventive care cally need and want to be self-directing, which and appropriate screening. Often, pa- encourages independence. tients with MS ignore general health 3. Problem-solving approach to learning is pre- screening and checkups with primary ferred. Adults typically learn best when infor- care physicians. mation is presented in real-life context. . ii Neurologist: Provides ongoing follow- E. Learning needs in MS up and management of MS and MS- The complexity of MS and its management re- related symptoms sult in a variety of learning needs for patients and . b MS nurses/advanced practice nurse (APN) their families. The scope and depth of informa- or physician’s assistant (PA) tion listed below depend on the patient’s and fam- . i Provides ongoing follow-up and ily’s preferences (Fraser, Hadjimichael, & Vollmer, management of MS and MS-related 2003; Halper, Costello, & Harris, 2006; Heesen, symptoms Köpke, Richter, & Kasper, 2007; Köpke, Kasper, ii. Healthcare promotion Mühlhauser, Nübling, & Heesen, 2009; Kennedy, a) Assesses patient and family for 2005; Pfohl, Costello, & Kennedy, 2005). health risks 1. MS b) Facilitates learner involvement in a. Definition setting healthy goals . b Epidemiology c) Guides and supports problem c. Pathophysiology solving and decision making . d The disease course; classifications of MS; d) Promotes self-care strategies to long-term needs enhance wellness . e Diagnosis: McDonald criteria e) Reinforces health-promoting . f Diagnostics: laboratory and diagnostic tests behaviors 2. Treatment of the disease f) Models healthy behaviors a. Provide information about all treatment g) Encourages primary health care options so patient can make an informed and preventive health screenings

Nursing Management of the Patient with Multiple Sclerosis 39 c. Other health care professionals . iii Capacity to obtain, understand, and . i Rehabilitation specialists: physiatrist, use information in healthcare deci- physical therapist, occupational ther- sion making apist, SLP . b Health literacy empowers individuals to . ii Specialists: urologist, orthopedist, gy- . i navigate healthcare system necologist, psychiatrist . ii act appropriately in new health- . iii Counselor/Psychologist/Licensed- related circumstances. certified Social Worker (LCSW) c. Consequences of health literacy iv. Case Manager . i Increased healthcare knowledge 6. Relapse management options . ii Improved health status a. Support network . iii Adherence to healthcare . i Benefits of staying socially connected recommendations . ii Family and friends iv. Appropriate use of healthcare . iii MS support groups services iv. MS organizations 5. Support system and role of the family . v Religious organizations a. Recognize the power and importance of vi. Volunteer support family . b Resources . b Assess the extent to which others (family, . i Healthcare providers significant other, friends, support groups) . ii MS organizations may enhance learning and offer support . iii Literature and encouragement iv. Websites 6. Cognitive dysfunction . F Factors that affect learning (Chiovetti, 2006; a. Approximately 50% of individuals with Donaldson, Rutledge, & Pravikoff, 1999; Giger & MS will experience cognitive dysfunction, Davidhizar, 2004; Glick, 2005; London, 2008) which may affect their ability to concen- 1. Patient’s understanding of the health problem trate, learn, and recall new information 2. Health beliefs and practices and make it difficult for them to follow the 3. Cultural competence plan of care. a. Defined as working relationship within a . b Providing information verbally as well as system of language and culture that is de- in writing enables patients, families, and pendent on history and heritage care partners to review information later. . b Cultural health benefits 7. Learning style . i Affect how individuals think and feel a. Individualize learning for patient’s pre- about health and health problems ferred learning style. . ii Affect when and from whom they . b Select tools to meet the patient and family’s seek health care needs. . iii Affect how they respond to health- c. Use a variety of teaching methods. care recommendations 8. Economic factors iv. Provide a context through which a. Financial concerns regarding healthcare meaning is gained costs may affect the patient’s ability to ad- . v Cultural values guide actions and de- here to treatment recommendations. cision making that facilitates self- . b Financial concerns may increase anxiety, worth and self-esteem which in turn may affect learning. c. Influence of culture on the individual: each 9. Emotional state patient is culturally unique a. Patients with MS may experience mood . i Identify patients at risk and adapt disorders such as depression, which can teaching method significantly affect readiness to learn. . ii Promote cultural literacy . b Be alert to symptoms, discuss with patient 4. Health literacy (will affect how nurse teaches and family, and refer the patient for inter- patients and their families; Cutilli, 2005) vention as needed. a. Defining attributes 10. Acute illness, such as relapse or an illness un- . i Reading and numeracy skills related to MS, can affect patient’s readiness . ii Comprehension and ability to learn.

40 Nursing Management of the Patient with Multiple Sclerosis 11. Psychomotor ability 1. Wellness: an expanded idea of health, mean- a. Physical disability may lead to difficulty in ing more than “absence of disease.” The pres- performing demonstrations requiring co- ence of well-being and dignity in the lives of ordination and strength. individuals, communities, and cultures. It is . b Modify teaching strategy and include fam- the holistic integration of six interactive di- ily and/or care partner for support. mensions that continually influence each G. Plan: Teaching strategies other. 1. Lectures and groups a. Environmental: healthy setting and self a. Involve learners and individualize the protection teaching session by using interactive . b Physical: nutrition, fitness, and lifestyle exercises. changes . b Connect content to real-life experiences. c. Social: respect, relationships, intimacy, and c. Ask open-ended questions that require and tolerance thought. . d Spiritual: life meaning, purpose, and values 2. One-to-one discussions with patient and . e Intellectual: learning, growth, and new family challenges a. Give the patient and family time to take . f Emotional: stress management, acceptance, notes. At end of the session, ask patient and expression of feelings and family to discuss their notes to ensure 2. Clark (1986) describes wellness as striving in accuracy of information. a positive way, unique to an individual. People . b The act of writing may help patients under- can have MS and strive to be well and enjoy stand and remember the information. life with meaning and purpose. 3. Demonstrations, such as injection technique 3. Processes to promote wellness a. Choose appropriate hands-on tools. a. Provision of accurate information . b Demonstrate procedure several times, . b Individual goal setting then ask the patient and family to return c. Enhancement of self-efficacy demonstration. . d Patient recognizes the need for learning c. Acknowledge and reinforce success. and acceptance of new information. 4. Pamphlets, books, pictures . e Patient believes in his or her own abil- a. Discuss written information. Allow time ity to make and implement appropriate for questions and answers. behaviors. 5. Audiovisuals . f Patient and family assume responsibility a. Choose videos and DVDs that are 20 min- for health care and self-monitoring. utes or less in length; use clear, direct, Recommendations: Nurses should use an and accurate language; and are culturally evidence-based and wellness-focused approach appropriate to education and counseling to assist patients 6. Internet programs with MS and their families to adhere to the treat- a. Use recognized authorities and provide pa- ment regimen, manage their symptoms, and cope tients with a list of recommended websites. with their chronic disease (Level 3). The nurse Ensure the information is evidence based should screen for factors that could influence the and current (i.e., are certified by the Health ability to learn, such as cognitive difficulties and On the Net Foundation [HON]). health literacy issues, and adapt teaching as ap- H. Models of learning for wellness and healthcare propriate (Level 2). promotion (Anspaugh, Hamrick, & Rosato, 1991; Stuifbergen, Becker, Rogers, Timmerman, & Kullberg, 1999; Stuifbergen, Seraphine, & Rob- erts, 2000)

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