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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.

2 Nursing Management of the Patient with Multiple Sclerosis

Editors
Hilaire J. Thompson, PhD RN CNRN FAAN
Kristen L. Mauk, PhD DNP RN CRRN GCNS-B, GNP-BC
FAAN
Chairs
Amy Perrin Ross, MSN APN MSCN CNRN
Suzanne C. Smeltzer, EdD RN MSCN FAAN

Content Authors
Megan Barrett, DNP MSCN ARNP
Cheryl Blaschuk, MSN RN MSCN FNP
Kathleen Costello, MS ANP-BC MSCN
Constance Easterling, MSN MSCN ARNP
Ann Gutierrez, MSN RN CRRN CBIS
June Halper, MSN APN-C MSCN FAAN
Paule Joseph, MSN FNP-BC RN CRRN BCLNC-C
Patricia Kennedy, RN CNP MSCN
Mary Kitten, MSN RN MSCN CRRN
Martha Lightfoot, ANP
Elizabeth McAndrews, MSN CRNP
Margie O’Leary, MSN RN MSCN
Brant J. Oliver, MSN MPH FNP-BC PMHNP-BC
Patricia Pagnotta, MSN ARNP MSCN CNRN
Dorothea Cassidy Pfohl, BSN MSCN RN
Yaritza Rosario, APN MSCN
Angela Stone Schmidt, PhD MNSc RNP RN
Matthew Sorenson, PhD RN
Alpa Uchil, MPH RN

Content Reviewers
Lisa Duffy, PhD(c) CPNP-PC CNRN
Debra A. Dzenko, MSN Ed RN-BC CCM CRRN
Jennifer Smrtka, ANP-BC MSCN

American Association
of Neuroscience Nurses
4700 W. Lake Avenue
Glenview, IL 60025-1485
888.557.2266, Fax 847.375.6430
International phone 847.375.4733
[email protected] • www.AANN.org
Joan Kram, MBA RN FACHE
Executive Director
June M. Pinyo, MA
Managing Editor
Sonya L. Jones
Senior Graphic Designer

Association of Rehabilitation Nurses
4700 W. Lake Avenue
Glenview, IL 60025-1485
800.229.7530
[email protected] • www.rehabnurse.org

Karen Nason, CAE
Executive Director

International Organization of
Multiple Sclerosis Nurses
359 Main Street, Suite A
Hackensack, NJ 07601
201.487.1050, Fax 201.678.2291
www.iomsn.org

June Halper, MSN APN-C MSCN FAAN
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 re-
produced, photocopied, or republished in any form, print or electronic, in whole or in part, without written permission of
AANN, ARN, or IOMSN.

Nursing Management of the Patient with Multiple Sclerosis 3

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 rep-
resents 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 pre-
sented 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.

4 Nursing Management of the Patient with Multiple Sclerosis

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

Nursing Management of the Patient with Multiple Sclerosis 5

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

6 Nursing Management of the Patient with Multiple Sclerosis

I. Search Strategy and Levels of Evidence
A. Search strategy

A computerized search of MEDLINE, Cochrane,
and the Cumulative Index to Nursing and Allied
Health Literature was performed by using multi-
ple sclerosis, symptom, disease management, nurs-
ing, and education as keywords. The search was
restricted to works in English and adults. The ref-
erence lists of identified articles were also searched
for additional, relevant references including
books, guidelines, and articles. A panel of nursing
experts determined the level of evidence for each
study included in the guideline, summarizing the
level of evidence for each recommendation.

B. Levels of evidence supporting the
recommendations
• Class I: Randomized controlled trial without

significant limitations or meta-analysis
• Class II: Randomized controlled trial with im-

portant limitations (e.g., methodological flaws
or inconsistent results), observational studies
(e.g., cohort or case-control)

• Class III: Qualitative studies, case study, or
series

• Class IV: Evidence from reports of expert
committees and/or expert opinion of the
guideline panel, standards of care, and clinical
protocols.

The Clinical Practice Guidelines recommenda-
tions for practice are established on the basis of
the evaluation of the available evidence (AANN,
2005; adapted from Guyatt & Rennie, 2002; Mel-
nyk, 2004):

• Level 1 recommendations are supported by
Class I evidence.

• Level 2 recommendations are supported by
Class II evidence.

• Level 3 recommendations are supported by
Class III and IV evidence.

II. Scope of the Problem: Definition, Natural History,
and Epidemiology of Multiple Sclerosis (MS)
A. Definition

1. MS is a progressive, inflammatory, neurode-
generative demyelinating disease of the central
nervous system (CNS) predominantly affecting
white matter (Miller et al., 2008). It is the most
common nontraumatic cause of neurolog-
ic disability in young adults (Fleming & Car-
rithers, 2010). The cause of MS is unknown;
however, research suggests that an abnormal
autoimmune response to myelin develops in
genetically susceptible individuals after expo-
sure to one or more environmental agents.

2. The autoimmune cascade results in an inflam-
matory response against self-antigens in the
CNS, causing demyelination and axonal dam-
age. Scarring visible at magnetic resonance
imaging (MRI) represents these pathological
changes. Demyelination in the CNS disrupts
conduction in nerves, causing the hallmark
sensory, motor, and cognitive signs and symp-
toms of MS (De Jager et al., 2009; Harris &
Halper, 2004; Thrower, 2009; Trapp et al.,
1998).

3. MS may present as a case of monosymptom-
atic or polysymptomatic neurologic abnor-
mality. Most early cases are characterized by
periods of disease freedom with superim-
posed relapses characterized by signs and
symptoms of CNS dysfunction (Confavreux,
Vukusic, Moreau, & Adeleine, 2000).

B. Epidemiology
1. MS affects approximately 400,000 people in

the United States alone, and more than 50,000
Canadians (Costello & Halper, 2010a; Miller
et al., 2008). The projected prevalence rate of
MS for the white population in the year 2000
was 191/100,000, and the incidence rate was
7.3/100,000 person years at risk (Kantarci &
Weinshenker, 2005; Kantarci & Wingerchuk,
2006). There are 12,000 new cases of MS diag-
nosed per year in the United States (Alonso &
Hernán, 2008).

2. Review of incidence data suggests the lifetime
risk of MS is 2.5% for women and 1.4% for
men (Alonso & Hernán, 2008). MS is gener-
ally at least twice as common in women as it is
in men, with some data suggesting the male-
to-female ratio is as high as 1:4 (Beck et al.,
2003; Kantarci & Wingerchuk, 2006; Vukusic
& Confavreux, 2007).

3. The age of onset peaks between 25 and 35
years of age. Men may have a later onset of
disease and a worse prognosis (Kantarci &
Wingerchuk, 2006; Vukusic & Confavreux,
2007). Despite the young age of disease on-
set and the potential for neurologic disability,
the life expectancy of people with MS is only
slightly reduced (Compston et al., 2006). Fif-
ty percent of MS patients will die from causes
other than MS (Sadovnick, Eisen, Ebers, &
Paty, 1991).

C. Types of MS
1. There are four defined clinical types of MS: re-

lapsing-remitting MS (RRMS), primary pro-
gressive MS (PPMS), secondary progressive
MS (SPMS), and progressive-relapsing MS

Nursing Management of the Patient with Multiple Sclerosis 7

(PRMS). These types are described by relaps-
es, remission, and chronic progression (in-
creasing disability as time passes). Relapse can
be followed by full or partial recovery. Disease
severity varies considerably among people
with MS, no matter the type ascribed to them
(Compston et al., 2006).

2. Initially, 85% of cases are RRMS, and 15% are
PPMS. When a person with RRMS begins to
acquire disability, SPMS is said to occur. This
phase of the disease evolves owing to progres-
sive axonal injury. The median time to con-
version from RRMS to SPMS is 19 years, and
75% will reach this phase by 25 years. Approx-
imately 40% of progressive cases (SPMS and
PPMS) still experience relapses (Compston et
al., 2006; Frohman et al., 2005; Kantarci, 2008;
Runmarker & Andersen, 1993). Nonetheless,
in progressive patients, the course of disability
progression is not affected by relapses (Confa-
vreux, Vukusic, & Adeleine, 2003).

3. There is a theory that the clinical subtypes of
MS may be separate phenotypes of one dis-
ease process. The differing types of MS may
represent various points along the spectrum
of MS. However, distinct pathophysiological
processes have not yet been identified (Confa-
vreux & Vukusic, 2006; Lublin, 2010).

D. Natural history of the disease
1. Despite the unpredictable nature of MS, re-

sults of cohort studies provide general prog-
nostic factors.

2. Better disease prognosis is associated with
younger age at onset, female sex, monosymp-
tomatic presentation (particularly optic neu-
ritis or sensory symptom), complete recovery
from relapse, a long interval between presen-
tation and second event, relapsing course, and
a low number of relapses (Lisak, 2001; Miller
et al., 2008).

3. Poor long-term prognosis has been associated
with male sex; older age at disease onset (> 40
years); motor, cerebellar, or sphincter symp-
toms at initial presentation; polysymptomat-
ic presentation; frequent attacks in the first 5
years; short interval between first two attacks;
short time to reach an Expanded Disability
Status Scale (EDSS) score of 4; and a progres-
sive course (Bergamaschi, Berzuini, Romani,
& Cosi, 2001; Compston & Coles, 2002; Con-
favreux, Vukusic, Moreau, & Adeleine, 2000;
Riise et al., 1992; Trojano et al., 1995; Vuku-
sic & Confavreux, 2007). Note: A standard
measure of disability in MS is the EDSS score.

Higher EDSS scores indicate higher levels of dis-
ability (Kurtzke, 1983).

E. Genetics
1. Family history is the strongest known risk fac-

tor for MS. In fact, MS is 20–40 times more
common among first-degree relatives, with
a rapid decrease in risk with degree of relat-
edness (Ascherio & Munger, 2008; Kantarci,
2008; Kantarci & Wingerchuk, 2006; Vukusic
& Confavreux, 2007; Weinshenker, 1996).

2. There have been at least 13 genetic suscepti-
bility loci identified by scientists (Australia
and New Zealand Multiple Sclerosis Genetics
Consortium [ANZgene], 2009; International
Multiple Sclerosis Genetics Consortium, 2007;
De Jager et al., 2009), and it has been suggest-
ed that 10–50 genes are related to genetic sus-
ceptibility to MS (Baranzini, 2010).

F. Environmental risk factors
1. The estimated genetic risk of MS is 25%–35%

based on monozygotic twin studies (Kantarci,
2008). Incomplete penetrance of heritability
provides evidence that there are environmen-
tal factors at play in MS susceptibility. MS is
more common in Europe, the United States,
Canada, New Zealand, and Southern Austra-
lia than in Asia, the tropics, and the subtrop-
ics. The incidence and prevalence increases
with latitude relative to the equator. Review of
the MS literature suggests there may be atten-
uation in the latitude gradient, or MS belt, re-
inforcing the role that environmental factors
play in MS etiology (Ascherio & Munger, 2008;
Bakshi, Hutton, Miller, & Radue, 2004; Fran-
ciotta, Salvetti, Lolli, Serafini, & Aloisi, 2008).

2. Additionally, migrant studies suggest one as-
sumes the risk of one’s final place of residence,
rather than of one’s birthplace, if migration
occurs in childhood (Zivadinov et al., 2009).

a. The strongest support for environmental
risk factors is based on geographic distri-
bution and studies of migration to Israel,
from the United Kingdom to South Afri-
ca, from the United Kingdom to Australia,
and from the United Kingdom to the Unit-
ed States (Alter, Kahana, & Loewenson,
1978; Alter, Leibowitz, & Speer, 1966; Dean
& Kurtzke, 1971; Hammond, English, &
McLeod, 2000; Kurtzke, Beebe, & Norman,
1985).

b. Studies show that the risk of MS is low in
migration from the Far East to the United
Kingdom and North America as compared
with that of migration from India, when

8 Nursing Management of the Patient with Multiple Sclerosis

the risk of MS increases in the second gen-
eration. Typically, migration studies are not
able to establish timing of environmental
exposures (Ebers, 2008; Elian, Nightingale,
& Dean, 1990).

3. Other strong environmental factors associated
with MS include lack of vitamin D exposure,
smoking, and the Epstein-Barr virus (EBV).

a Past sun exposure and vitamin D supple-
mentation have been associated with de-
creased risk of MS (Coo & Aronson, 2004;
Marrie, 2004; Munger, Levin, Hollis, How-
ard, & Ascherio, 2006; Munger, et al., 2004;
Soilu-Hänninen et al., 2005).

b. Heavy smoking (defined as more than 25
pack-years) increases MS risk by approxi-
mately 70%, and the increase in risk is dose
responsive (Ascherio & Munger, 2007;
Hedström, Bäärnhielm, Olsson, & Alfreds-
son, 2009; Hernán et al., 2005; Hernán,
Olek, & Ascherio, 2001). Among MS pa-
tients, smoking is associated with higher
levels of disability, greater number of en-
hancing T2 and T1 lesions, greater lesion
volume, and more brain atrophy (Zivadi-
nov et al., 2009).

c. Data from several Class II studies support
the association of EBV with MS. There is ev-
idence that the presence of EBV in plasma is
associated with increased risk of MS (Wag-
ner, Munger, & Ascherio, 2004). MS risk in-
creases sharply after EBV infection (Levin,
Munger, O’Reilly, Falk, & Ascherio, 2010).

G. MS symptoms
1. MS is associated with numerous symptoms,

and MS symptoms vary widely from individ-
ual to individual. Symptoms of MS are unpre-
dictable and often interfere with activities of
daily living (ADLs).

2. Primary symptoms of MS are caused by the
dysfunction of nerve conduction because of
demyelination, inflammation, and axonal loss
in the CNS (Lisak, 2001).

3. MS symptoms include spasticity, fatigue, pain,
disturbance of elimination (bladder or bow-
el), unilateral vision loss, vertigo, Lhermitte’s
sign, sexual dysfunction, cognitive dysfunc-
tion, ataxia, tremor, depression, oculomotor
dysfunction, dysarthria or dysphonia, dyspha-
gia, and seizure (Compston et al., 2006; Lisak,
2001; Harris & Halper, 2004; Stuke et al., 2009).

4. A relapse (also known as an attack or exacerba-
tion) is defined as a new neurologic symptom,
or worsening of previous symptom(s), lasting

more than 24 hours that does not have an alter-
native explanation. Pseudorelapses are related
to infection or heat exposure and do not repre-
sent new disease activity.

H. Effect of the diagnosis
1. An MS diagnosis is a life-altering event. MS is

a chronic, often disabling disease that may af-
fect the physical, economic, psychological, and
social aspects of a patient’s life. The unpredict-
able nature and varied symptoms of the disease
mean that patients face a future of uncertainty.

2. Managing MS consists of primarily manag-
ing the symptoms that are associated with the
disease. For example, time management and
conservation of energy have been the recom-
mended forms of managing fatigue. If tremors
and gait imbalance are the major presenting
symptoms, medications and/or physical thera-
py have been shown to be helpful.

3. The financial effect of MS should be consid-
ered, because treatment can be costly. There
are a number of disease-modifying thera-
pies (DMTs), including interferon-beta-1a
(IFN β-1a), IFN β-1b, glatiramer acetate,
and natalizumab. Other DMTs being used or
investigated include mitoxantrone and cyclo-
phosphamide. Both direct and indirect costs
may or may not be reimbursed by insurance
plans, which vary individually. Costs and
quality of life (QOL) are significantly corre-
lated with functional capacity (Kobelt, Berg,
Atherly, & Hadjimichael, 2006).

4. Debilitating diseases with no cure can be a
burden financially for patients and families.
Patients with MS may face loss of employ-
ment. In addition, the financial effect of the
disease may be related to the cost of needed
services, other care providers, and possibly
the need to modify the patient’s home envi-
ronment to accommodate changing abilities.

5. RRMS affects a majority of the MS popula-
tion. Although there are several DMTs for
RRMS, not all are available for the same cost.
Goldberg and colleagues (2009) evaluated the
2-year effectiveness of four DMTs used for
RRMS—glatiramer acetate, IFN β-1an intra-
muscular (IM) injection, IFN β-1a subcutane-
ous (SC) injection, and IFN β-1b SC injection.
These four DMTs are the most cost-effective
treatments for RRMS (Goldberg et al.).

6. QOL may be affected by the financial costs re-
lated to MS (De Judicibus & McCabe, 2007).
Life-altering decisions can create an enor-
mous amount of uncertainty, followed by

Nursing Management of the Patient with Multiple Sclerosis 9

making adjustments to accommodate the
change. Financial stress can be caused by loss
of income and the strain that patients and
their families undergo as they adjust to loss
and the possible increased need to cover the
cost of required medical and related services
(De Judicibus & McCabe).

7. The disease affects the caregivers as well. In
a small qualitative study in the United King-
dom, interviews were conducted of 8 partners
who lived and cared for a person with MS
(Mutch, 2010). The study showed that dis-
ability due to MS significantly affected their
lifestyles after 20 years of marriage; partners
felt obligated to continue caring for the affect-
ed spouse and consequently lost their iden-
tity as husband or wife. Partners also yearned
for independence and were not satisfied with
their own QOL because MS care was a dai-
ly occurrence (Mutch, 2010). Caregivers also
go through life-altering decisions and chang-
es secondary to their partner’s health, and as
a result they have their own needs (Corry &
While, 2008). As the disease progresses, care-
givers may be increasingly required to care
for the patient because of the debilitating na-
ture of the disease (Buhse, 2008). As a result,
caregiver burden becomes a cluster of physi-
cal, social, economic, and psychological re-
sponses—caregivers who are highly burdened
were shown to have lower QOL and higher
risk for depression (Buhse). Further study of
the caregiver population is needed.

Recommendations: The model of nursing care in MS in-
cludes establishing, continuing, and sustaining care along the
MS spectrum of new or probable MS, relapsing forms of MS,
progressive MS, and advanced MS (Level 3). Nurses should
facilitate treatment and symptom management, promote and
enhance function, and support a QOL of adults with MS and
their family-care partners that is wellness focused (Level 3).
Nurses use evidence-based knowledge to determine an ef-
fective course of action for MS patients with specific needs
(Level 2). Nurses act as advocates to ensure that patients and
their family-care partners have access to needed care and as-
sistance in using resources crucial to managing MS (Level 2).
Nurses should help patients locate and develop appropriate
resources and initiate contacts as needed (Level 2).

III. Classification of MS
A. Introduction

1. MS is an immune-mediated disease of the
CNS with inflammatory and degenera-
tive characteristics (Siva, 2006). The clini-
cal course may be variable. In 1996 a formal

classification of MS clinical subgroups was
proposed from an international survey of MS
clinicians, and standardized definitions for
the most common clinical courses of MS were
defined.

a. The clinical course was defined by the fol-
lowing descriptions: RRMS, PPMS, SPMS,
PRMS, benign MS, malignant MS (Lublin
& Reingold, 1996).

b. The terms benign and malignant MS are
used to describe relatively mild and very
progressive courses of MS, respectively.
Both are relatively rare.

2. When patients receive a disease diagnosis un-
der one of the above classifications, both the
patients and families may need further ex-
planation to understand the disease’s clinical
course; the importance of disease-modifying
therapy and symptom management, if ap-
propriate; and the need for regular follow-up
with the neurologist and other care providers.

B. RRMS
1. RRMS is marked by periods of acute decline

or exacerbations in neurologic function fol-
lowed by a variable degree of recovery with
stable periods between attacks (Lublin & Re-
ingold, 1996). Patients may experience total or
partial remission of symptoms (Figure 1).

2. Relapse (exacerbation) is the appearance of
a new symptom or reappearance of a prior
symptom lasting more than 24 hours (Lublin
& Reingold, 1996). Pseudoexacerbation refers
to changes in neurologic function triggered
by infection, fever, heat, and fatigue. These
relapses occur from decompensation of exist-
ing CNS scars and are not indicative of new
inflammatory CNS lesions (Birnbaum, 2009).

3. Onset of neurologic changes may occur over
several hours or appear over days to weeks.
Symptoms may be focal and can spread over
other body regions. A relapse may last from
a few days to several weeks or more. Full
or partial recovery may occur with the dis-
ease remaining stable between relapses. This
relapsing-remitting course is seen in ap-
proximately 80%–85% of patients (Nosewor-
thy, Lucchinetti, Rodriguez, & Weinshenker,
2000). Treatment with immune-modulating
therapies and corticosteroids is indicated.

C. PPMS
1. PPMS presents with a gradual onset of symp-

toms that worsen over time with minor fluc-
tuations that progress and do not reverse
(Figure 2).

10 Nursing Management of the Patient with Multiple Sclerosis

Figure 1. Characterization of the natural history of relapsing-
remitting 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 re-
lapses are characterized by lack of disease progression. From Lublin, F. D., & Reingold,
S. C. Defining the clinical course of multiple sclerosis: Results of an international survey.
National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New
Agents in Multiple Sclerosis 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
that seen in RRMS (mean of 40 years versus
30 years).

3. Most common presenting symptoms include
progressive spastic paraparesis, usually in the
lower extremities, as well as impaired mobility
with weakness, stiffness, and dragging of the
legs. Exercise-related fatigable weakness, uri-
nary urgency, urge incontinence, and erectile
dysfunction are also common (Miller & Leary,
2007).

4. PPMS may vary significantly from patient
to patient. Some may experience profound
disability within 1–2 years, whereas in oth-
ers, progression may occur over decades. The
pathophysiology of PPMS is thought to be
different from that of RRMS, and, therefore,
long-term immune-modulating therapies are
not indicated for treatment (Birnbaum, 2009).

Figure 2. Characterization of the natural history of primary
progressive multiple sclerosis

Primary progressive (PP) MS is characterized by disease showing progression of disabil-
ity from onset (A) without plateaus or remissions or (B) with occasional plateaus or tem-
porary minor improvements. From Lublin, F. D., & Reingold, S. C. Defining the clinical
course of multiple sclerosis: Results of an international survey. National Multiple Sclero-
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.

D. SPMS
1. SPMS is seen as the long-term outcome of

RRMS, which occurs once the baseline be-
tween relapses becomes progressively worse.
Patients experience a gradual worsening of
the disease that is independent of continued
exacerbations (Figure 3; Lublin & Reingold,
1996).

2. Approximately 50% of patients with RRMS
will develop SPMS with time. The frequen-
cy of relapses decreases, and patients experi-
ence an increase in disability. The transition
from RRMS to SPMS may be rapid or gradual.
SPMS patients also present with fewer acute
inflammatory changes at brain and spine
magnetic resonance imaging (MRI); therefore,
long-term immune-modulating therapies are
not indicated for treatment (Birnbaum, 2009).

Nursing Management of the Patient with Multiple Sclerosis 11

Figure 3. Characterization of the natural history of secondary
progressive multiple sclerosis

Secondary progressive (SP) MS begins with an initial RR course, followed by (A) pro-
gression of variable rate that may also include (B) occasional relapses and minor re-
missions. From Lublin, F. D., & Reingold, S. C. Defining the clinical course of multi-
ple sclerosis: Results of an international survey. National Multiple Sclerosis Society (US)
Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis Neurology,
46(4):907–911. Reproduced with permission from Wolters Kluwer Health.

E. PRMS
1. PRMS appears to progress clinically as seen

in PPMS with acute relapses, and full recov-
ery may or may not occur. There is continued
progression between relapses (Figure 4; Lub-
lin & Reingold, 1996).

2. PRMS has a progressive onset with acute in-
flammatory activity in the CNS with relaps-
es. These relapses can respond to short-term
antiinflammatory therapies. The benefit of
long-term immune-modulating therapies is
uncertain at this time (Birnbaum, 2009).

F. Benign MS
1. All neurologic systems of patients with benign

MS appear to be fully functional 15 years after
the onset of disease (Lublin & Reingold, 1996).

2. This form of the disease is characterized by a
full recovery and normal functioning after a
symptomatic period. It is thought to occur in
about 5%–10% of cases of MS (Sayao, Devon-
shire, & Tremlett, 2007).

Figure 4. Characterization of the natural history of progres-
sive-relapsing multiple sclerosis

Progressive-relapsing (PR) MS shows proession from onset but with clear acute relaps-
es (A) with or (B) without full recovery. From Lublin, F. D., & Reingold, S. C. Defining the
clinical course of multiple sclerosis: Results of an international survey. National Multi-
ple Sclerosis Society (US) Advisory Committee on Clinical Trials of New Agents in Multi-
ple Sclerosis Neurology, 46(4):907–911. Reproduced with permission from Wolters Klu-
wer Health.

G. Malignant MS
A brief time after disease onset, the disease pro-
gresses rapidly and may lead to significant dis-
ability or death within 5 years of diagnosis; it is
thought to be extremely rare (Lublin & Reingold,
1996).

H. Other types
The MS spectrum includes idiopathic inflam-
matory demyelinating diseases including the
following:
1. Subclinical multiple sclerosis (SCMS), which

presents with incidental lesions at MRI with-
out clinical signs and symptoms.

2. Clinically isolated syndrome (CIS), which is
a onetime neurologic episode consistent with
demyelination or CNS inflammation (Siva,
2006). CIS may include optic neuritis, trans-
verse myelitis, or isolated brain stem or cer-
ebellar syndromes. Patients with CIS are at
high risk of developing MS (Halper, Costello,
& Harris, 2006).

12 Nursing Management of the Patient with Multiple Sclerosis

3. Other demyelinating diseases that may pres-
ent as MS are acute disseminated encephalo-
myelitis and neuromyelitis optica (or Devic’s
disease) (Wingerchuk, Lennon, Lucchinetti,
Pittock, & Weinshenker, 2007).

I. Implications for patients
1. Some patients may have some familiarity with

MS; however, they may have an incorrect un-
derstanding of MS. Patients and families may
imagine the worst case scenario and anticipate
a rapid decrease in function and the need for
assistive devices, including a wheelchair.

2. Patients and their families need a realis-
tic view of MS along with an understand-
ing about the disease-modifying agents and
symptom-management strategies.

Recommendations: Nurses caring for patients
with MS need an understanding of the various
types of MS and should be familiar with the typi-
cal clinical course of each type in order to

• provide explanations and initiate patient ed-
ucation and counseling for patients and their
families

• provide information and counseling to help
patients and care partners develop a real-
istic picture of the disease, the benefits of
treatment, and expectations related to its
management

• help patients and their families cope with a
new diagnosis of MS, adopt a healthy life-
style, and maintain a positive and hopeful
perspective

• emphasize health-promotion strategies and
preventive health care and screening, includ-
ing the importance of regular follow-up with
their neurologist and other healthcare provid-
ers (Level 3).

IV. Immunogenetics and Pathogenesis
A. General background

1. Up to 20% of MS patients have a family mem-
ber affected by the disease (Compston &
Coles, 2002).

2. The risk of developing MS is 20–30 times
higher for siblings of affected individuals than
for the general population (3:1) (Compston &
Coles, 2002).

3. An important role for the genetic factors in
determining MS susceptibility is suggested
by familial aggregation of the disease as well
as high incidence in some ethnic populations
(e.g., Northern European ancestry).

4. Genes that code for major histocompatibil-
ity complex (MHC) are part of the human

leukocyte antigen (HLA) system cluster on
chromosome 6 (Ben-Zacharia & Morgante,
2005; de Jong et al., 2002; Olerup et al., 1987).

5. HLA genes help T cells distinguish self from
nonself (Ben-Zacharia & Morgante, 2005; de
Jong et al., 2002; Olerup et al., 1987).

6. Variations in several HLA genes are seen in au-
toimmune disease, when the body mounts an
immune response (Ben-Zacharia & Morgante,
2005; de Jong et al., 2002; Olerup et al., 1987.).

B. Pathophysiology of MS (Halper, Costello, &
Harris, 2006)

1. The etiology of MS is not known.
2. It is hypothesized that MS is a virus-induced

immune-mediated disease.
3. Lesions include acute plaques with active in-

flammatory infiltrates and macrophages, and
chronic, inactive demyelinated scars.

4. Irreversible axonal damage and loss are
caused by inflammation, demyelination, and
scarring.

5. Brain atrophy may be useful in measuring
disease progression and effects of long-term
therapy.

C. Blood-brain barrier (BBB) in MS
1. BBB is formed primarily by tight junctions

between endothelial cells that are disrupted in
MS and result in lesion formation in the brain
and CNS (Riskind, 2007).

2. Proinflammatory cytokines such as interleu-
kin (IL)-1β that is expressed in MS lesions
may contribute to BBB permeability (Argaw
et al., 2006).

3. With BBB disruption, immune cells and oth-
er molecules that assist in the migration of
these immune cells called adhesion molecules,
which are the target of MS therapies (natali-
zumab), and chemokines that may attract and
stimulate the migration of leukocytes could
also play a role in MS pathology. Chemokines
could also play a role in the recruitment of oli-
godendrocytes and could be involved in re-
myelination (Riskind, 2007).

D. T cell and B cell pathogenesis of MS
1. Cellular and humoral immunity (Halper,

Costello, & Harris, 2006).
a. Cellular immunity consists of cytotoxic T

cells (cluster of differentiation [CD] 8) and
T-helper (TH) cells (CD 4).

b. Humoral immunity includes B lympho-
cytes and antibodies.

c. B cells recognize antigens outside of cells;
T cells recognize antigens from inside host
cells and those on the cell surface.

Nursing Management of the Patient with Multiple Sclerosis 13

d. Humoral immunity involves B cells
producing antibodies that work by
mechanisms including neutralization, op-
sonization, and complement activation.

e. Cellular immunity involves T cells with re-
ceptors on the cell surface.

f. T cells are activated by antigen presentation.
2. The general consensus is that MS is a disease

related to an imbalance of antiinflammatory
versus proinflammatory cytokines.

3. Proinflammatory TH-1 (CD 4+) and antiin-
flammatory TH-2 (CD 4+)

a. Proinflammatory cytokines (TH-1): IL-2,
IL-10, IFNγ, TNFα

b. Antiinflammatory cytokines (TH-2):
IL-4, IL-10, IL-13, transforming growth
factor (TGF) β (Akira, Takeda, & Kaisho,
2001)

4. T cells in the periphery are activated by anti-
gen present cells (APC).

a. Activated TH-1 cells migrate across the BBB.
b. In the CNS, the T cells are reactivated by

an APC and secrete proinflammatory cyto-
kines including CNS inflammation via ac-
tivation macrophages and other T cells and
B cells (Neuhaus, Archelos, & Hartung,
2003).

5. Recently discovered additional CD4+ subset
TH-17

a. TH-17 cytokines IL-17, IL- 6, TNFα, and
IL-17 are expressed in MS lesions (Akira,
Takeda, & Kaisho, 2001).

6. B cell pathogenesis
a. B cells have the capacity to stimulate T cells

(Bar-Or, 2010).
b. B cells produce antibodies to components

of the CNS, including myelin. This may
help determine the extent of tissue injury
in MS.

c. Antibodies bind with complement to at-
tack and destroy the myelin sheath (com-
plement fixation).

d. Complement fixation is especially effective
with oligodendrocytes, resulting in an in-
flux of calcium. This promotes phagocyto-
sis of oligodendrocytes.

e. B cells may secrete more IgM, IgG, and IgA
and bring about an antigen-dependent T
cell response (Bar-Or, 2010).

E. Neurodegeneration in MS (Trapp & Nave, 2008)
1. Trapp and colleagues (1998) performed au-

topsies and biopsies on patients with MS, and
they demonstrated greater axonal damage
than had been previously appreciated.

2. Axonal loss can be seen at MRI and magnetic
resonance (MR) spectroscopy (Filippi et al.,
2003).

3. Neurodegeneration is a major contributor to
CNS atrophy.

4. Neurodegeneration occurs with
inflammation.

5. Controversy remains regarding the re-
lationship between inflammation and
neurodegeneration.

6. Causes of neurodegenerative processes:
a. Failure of sodium channel homeostasis.
b. Excess glutamate, nitrous oxide, proteases,

cytokines, CD8 cells, oxidative products,
and free radicals generated by activated
immune and glial cells.

F. Remyelination (Chari, 2007; Franklin & Kotter,
2008)

1. Remyelination appears to be considerable
in the majority of the MS population; how-
ever, CNS remyelination does not occur as
well as peripheral nervous system (PNS)
remyelination.

2. Remyelination is a natural reparative process
in MS during which new myelin sheaths are
formed over demyelinated axons.

3. Remyelination varies from individual to
individual.

4. It is observed in individuals both early and
late in the course of disease.

5. It is present in all types of MS.
6. Favorable factors for remyelination are as

follows:
a. Presence of oligodendrocyte precursors

near the active edges of inflammatory
lesions.

b. Migration and development into mature
oligodendrocytes.

c. Inflammation appears to be necessary.
d. Clearance of myelin debris generated dur-

ing demyelination.
Recommendation: Well-designed multidisciplinary re-
search is needed for a more complete understanding of the
pathophysiology of MS (Level 3).

V. Assessment and Diagnostic Process
A. Introduction

1. A clinical diagnosis of MS is based on neu-
rologic examination. Laboratory testing
and MRI provide supporting evidence of a
diagnosis.

2. Diagnostic criteria have evolved over sev-
eral decades and include the use of clinical
(e.g., history and physical) and paraclinical

14 Nursing Management of the Patient with Multiple Sclerosis

data (e.g., MRI, serum and cerebrospinal flu-
id [CSF] sampling, visual evoked potentials,
and somatosensory and brain stem evoked
potentials). Other potential causes of CNS de-
myelination must be excluded before MS is
diagnosed (Costello & Halper, 2010b; Harris
& Halper, 2004, 2008; Miller et al., 2008; Poser
et al., 1983).

B. Diagnostic criteria for MS
1. The McDonald criteria were created to pres-

ent a better and more reliable diagnostic
scheme to diagnose MS (Polman et al., 2005;
Polman et al., 2011). The McDonald crite-
ria use history of clinical attack(s) along with
MRI lesion distribution (e.g., dissemination in
space) and lesion occurrence over time (e.g.,
dissemination in time and space via MRI,
CSF, evoked potentials) to aid in the diagnosis
of MS (Polman et al., 2011). Diagnosis is often
made by a neurologist on the basis of the Mc-
Donald criteria (Harris & Halper, 2004, 2008;
Polman et al, 2005).

2. These criteria may allow a more reliable diag-
nosis to be made sooner than otherwise pos-
sible (Bakshi et al., 2008). The criteria were
most recently revised in 2010.

3. The 2010 revisions to the McDonald criteria
for diagnosis of MS (Polman et al., 2011) are
as follows:

a. When the clinical presentation includes two
or more attacks and objective clinical evi-
dence indicating two or more lesions in dif-
ferent locations, no further confirmation is
needed.

b. If two or more attacks occur and clini-
cal evidence indicates only one lesion, dis-
semination in space must be provided by
means of MRI, or a diagnosis of MS can
be made by using the appearance of two or
more lesions at MRI plus a positive CSF.

c. In cases in which an individual has experi-
enced one attack but objective clinical evi-
dence indicates two separate lesions, MRI
is not required to prove dissemination in
space. However, MRI can prove dissemi-
nation in time, as can the occurrence of a
second attack. Dissemination in time can
be established in one of two ways: (1) de-
tection of Gadolinium (Gd) enhancement
at least 3 months after the initial event or
(2) detection of a new T2 lesion at any time
compared with reference imaging per-
formed at least 30 days after the initial clin-
ical event.

d. In clinically isolated syndromes in which
an individual has experienced only one at-
tack and clinical evidence indicates one le-
sion, an abnormality at MRI as defined in
the criteria or two lesions at MRI plus a
positive CSF would satisfy the definition of
dissemination in space. Dissemination in
time could be confirmed at MRI by the oc-
currence of a second attack.

4. The most common presentations of MS in-
clude the following:

a. Sensory disturbances such as numbness,
paresthesias, pain, or Lhermitte’s sign.

b. Motor abnormalities including cortico-
spinal, abnormal deep tendon reflexes
(DTRs), positive Babinski response, or
spastic limb weakness.

c. Visual problems including brain stem and
eye movement abnormalities, and optic
neuritis.

d. Cerebellar gait ataxia, limb ataxia, and
tremor.

e. Fatigue.
C. Assessment tools

1. Assessing a patient with MS begins with the
initial observation of the patient in any setting
and includes observing his or her ability to
move (walking, assistive devices), affect, bal-
ance and coordination, hygiene, speech.

2. Although a clinical neurologic examination
provides baseline information about how
the nervous system is functioning, there are
findings specific to MS. This information
will help identify the areas of the CNS that
may be affected by demyelinating lesions
(Rudick, 2004; van den Noort & Holland,
1999).

a. Brain stem: internuclear ophthalmoplegia
(INO), and nystagmus

b. Cerebellar: scanning speech, intention
tremor, truncal ataxia, gait ataxia, and
dysarthria

c. Motor symptoms: pyramidal tracts—
weakness typical of upper motor neuron
lesions, spasticity, hyperreflexia, dysarthria,
clonus, and extensor plantar responses

d. Motor symptoms: corticobulbar tracts—
emotional lability

e. Sensory symptoms
• Not always visible but can be elicited

with testing.
• Sensory loss may affect gait and other

motor function leading to clumsiness of
fine movements and loss of dexterity.

Nursing Management of the Patient with Multiple Sclerosis 15

f. Higher cortical function
• Short-term memory dysfunction
• Managing complex tasks
• Speed of information processing
• Visual-spatial dysfunction
• Verbal fluency

3. Patient interviews provide the greatest infor-
mation to guide caring for the patient with
MS and improving his or her QOL. Through
this process, nurses can discern if symptoms
are constant or intermittent and how they af-
fect the lives of patients at home, at work, and
in the community. Skilled interviewing will
involve asking for information not necessarily
offered by the patient.

4. Examples of topics to address include the
following:

a. ADLs: dressing, bathing, eating, and
grooming

b. Bowels: constipation, incontinence, and
diarrhea

c. Bladder: frequency, urgency, incontinence,
and infections

d. Sexual function: loss of libido, erectile dys-
function, loss of sensation, and relationship
issues

e. Vision: decreased acuity and constant or
intermittent inability to distinguish colors,
especially red

f. Cognition: word-finding problems, memo-
ry issues, poor concentration, and inability
to understand what is being said

g. Mood: depression, anxiety, depletion, ir-
ritability, sadness, anger, and mood
fluctuations

h. Diet and fluids: decreased fluids to manage
bladder, and inability to get food, prepare
food, or feed self

5. EDSS is a standard measure of disability in
MS (Kurtzke, 1983).

a. EDSS is a widely used MS outcome
measure administered by a profession-
al trained in its use (Coulthard-Morris,
2000).

b. The EDSS is based on an evaluation of a
patient’s functional systems scores as de-
termined by means of a standardized neu-
rologic examination and an assessment of
the patient’s walking ability. The EDSS is
a 20-point scale from 0 to 10 in half-point
increments (Table 1; Kurtzke, 1983).
i. 1–3 indicates minimal disability and

the patient is ambulatory.

ii. 4–7 indicates moderate disability and
the patient is ambulatory with assis-
tive device.

iii. 8–10 indicates severe disability and
the patient is confined to a wheel-
chair (Coulthard-Morris, 2000).

c. Functional systems (FS) scores are used
in the evaluation of a patient’s EDSS. FS
scores measured during a neurologic ex-
amination include visual, brain stem, py-
ramidal, cerebellar, sensory, bowel and
bladder, and cerebral and mental function.
FS scores are rated on a scale from 0 (nor-
mal function) to 6 (unable to perform the
function; Kurtzke, 1983).

d. On the basis of results from cohort studies,
once an EDSS score of 4 is reached, there is
a progression of disability regardless of ini-
tial good prognosticators. An EDSS score
of 4, therefore, heralds the onset of SPMS
(Hutchinson, 2009). Longer intervals to
progression to subsequent EDSS levels are
present in those with initial RRMS (versus
those with PPMS), those with complete re-
covery from first relapse, and those with
longer time from MS onset to second epi-
sode (Confavreux, Vukusic, & Adeleine,
2003; Confavreux, Vukusic, Moreau, &
Adeleine, 2000).

e. The risk of reaching an EDSS score of 6 is
only 20% at 10 years for the person with
one or fewer relapses in the first 2 years of
the disease. Approximately 50% of peo-
ple with MS need to use a walking aid af-
ter 15 years (Weinshenker et al., 1989a,
1989b). Freedom from major disability af-
ter 25 years occurs in approximately 10%
of people with MS (Kantarci et al., 1998). If
an EDSS score stays at or below 2 for more
than 10 years, there is a 90% chance of dis-
ease stability (Kantarci et al., 1998; Pittock
et al., 2004). In contrast, most people ex-
periencing 5 or more relapses within the
first 2 years of disease onset require use of
a cane at 10 years (Weinshenker, 1994).

6. The Multiple Sclerosis Functional Compos-
ite (MSFC; Kurtzke, 1983; Fischer, Jak, Kniker,
Rudick, & Cutter, 2001) includes three out-
come measures:

a. Nine-hole peg test—arm assessment
measurement

b. Timed 25-foot walk test—leg assessment
measurement.

16 Nursing Management of the Patient with Multiple Sclerosis

c. Paced auditory serial addition test
(PASAT)—cognitive assessment
measurement.

7. The Multiple Sclerosis Symptom Checklist
(MSSC) is a 26-item self-report measure de-
signed to assess for the presence of 26 disease
symptoms common in MS patients (Gulick,
1989). The tool consists of five subscales assess-
ing motor function, sensory disturbance, men-
tal and emotional concerns, bowel and bladder
elimination, and brain stem symptoms. Homo-
geneity reliability has been determined through
the use of the Cronbach alpha with subscale
scores ranging from .78 to .87 (Gulick, 1989).
Total scale Cronbach alpha has been shown to
be .89. Scores are determined through the use
of a six-point scale with responses ranging from
never to always. Higher scores indicate an in-
crease of symptoms (Gulick, 1998).

Recommendations: A comprehensive assess-
ment should be completed, including the follow-
ing areas: physical, cognitive, sensory, and bowel
and bladder function. The baseline functional as-
sessment can be used to compare with future neu-
rologic examinations (Level 2). For assessment of
function, frequency of evaluation has not been ex-
tensively studied. Nurses should complete an ini-
tial assessment of function and monitor on an on-
going basis for any changes in condition (Level 3).

D. Assessment charts
1. Cranial nerve assessment (Table 2)
2. Assessment of motor symptoms; range of mo-

tion and muscle strength (Table 3)
E. Assessment of reflexes (Table 4)
F. Diagnostic testing

The diagnosis of MS is essentially a clinical diag-
nosis. The McDonald criteria are used along with

other diagnostic tools, because a neurologic ex-
amination alone may not provide enough evi-
dence. These tests are used not only for early de-
tection of the disease but also for evaluating the
efficacy of current and new treatments (Laron et
al., 2009).
1. Evoked potentials: An evoked potential test

measures the time it takes for nerves to re-
spond to stimulation. The size of the response
is also measured. An advantage and reason for
using evoked potential in diagnosis is the abil-
ity to detect abnormal signs and lesions in pa-
tients who have isolated symptoms. Nerves
from different areas of the body may be tested.

a. Visual evoked potential (VEP) is the most
commonly used evoked potential test in
the diagnosis of MS. VEP tests help iden-
tify optic neuritis (ON) or other demyelin-
ating conditions along the optic nerve and
optic pathways (Laron et al., 2009; Turker
et al., 2008).

The McDonald criteria have incorporated
VEPs into the diagnosis of MS. VEPs are
recommended in patients with MRI show-
ing 4 or more, but fewer than 9, T2 lesions
consistent with MS (Evans & Boggs, 2010;
Laron et al., 2009).

b. Brainstem auditory evoked response
(BAER)
i. BAER measures the function of the

auditory nerve and auditory path-
ways in the brain stem. It provides
information about changes in the
neurophysiologic status of the pe-
ripheral nervous system and CNS
(Evans & Boggs, 2010; Laron et al.,
2009).

ii. BAERs are considered if clinical
symptoms indicate the possibility of
a lesion outside the brain. An abnor-
mal BAER would support the diag-
nosis of MS (Laron et al., 2009).

c. Somatosensory evoked potential (SSEP)
i. Sensory disturbances are com-

mon findings in patients with MS.
SSEPs detect clinical abnormali-
ties but mainly explore the lemnis-
cal pathway, which is responsible for
transmitting touch, vibration, and
conscious proprioception. In the
spinal cord, the dorsal columns are
responsible for conduction of the ac-
tivity that is demonstrated by the
SSEP, and it involves the lemniscal,

Table 1. Expanded Disability Status Scale (EDSS)
EDSS Score Clinical Finding

0.0 Normal neurologic examination

1.0–1.5 No disability

2.0–2.5 Minimal disability

3.0–3.5 Moderate disability

4.0–4.5 Fully ambulatory and self-sufficient despite severe disability

5.0–5.5 Walking restricted to 100–200 meters

6.0–6.5 Needs unilateral or bilateral constant assistance

7.0–7.5 Restricted to wheelchair; can wheel self and transfer alone

8.0–8.5 Restricted to bed or chair; retains some self-care functions

9.0–9.5 Helpless bed patient

10.0 Death due to MS

Note. From Kurtzke, J. F. (1983). Rating neurologic impairment in multiple sclerosis: An
expanded disability status scale. Neurology, 33(11), 1444–1452.

Nursing Management of the Patient with Multiple Sclerosis 17

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
cards. Have patient identify writing or symbols. Assess peripheral
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.

Comfortably and accurately reads or identi-
fies small figures. Peripheral vision intact.

III: Oculomotor Pupillary constriction Tool: penlight. Hold penlight 12 inches from patient eyes. Next,
have patient look at distant object then bring object close to
patient eyes. Assess 6 cardinal positions of gaze.

Pupils constrict equally in response to
light. Eyes are accommodating with con-
vergence and constriction of pupils. Equal
extraocular movement.

IV: Trochlear Movement of eyes toward
nose

Assess 6 cardinal positions of gaze. Eye movement is smooth toward nose.

V: Trigeminal Sensation and motor function
of face

Tools: cotton ball and dull end of an object such as a pen, reflex
hammer, or tongue depressor. Test sensation on face. Have patient
close eyes and identify when he or she feels touch. Wisp cotton
ball against cornea. Have patient open jaw against resistance.

Corneal reflex intact. Sensation intact on
forehead, jaw, and cheek. Adequate jaw
strength.

VI: Abducens Lateral movement of eyes
away from the nose

Assess 6 cardinal positions of gaze. Eye movement is smooth away from 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
reading.

Able to understand whisper.

IX: Glossopharyngeal
X: Vagus
(assess IX and X
together)

Tongue and throat movement Tools: tongue depressor, penlight
Have patient say “ahh.” Test gag reflex.

Uvula retracts evenly.
Soft palate rises. Gag reflex intact.

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
Assess joint movement of head and neck and major joints of upper and lower
extremities. Grade muscle strength by using muscle strength scale.

Grading Muscle
Strength Finding

0 No visible muscle contraction

1 Visible muscle contraction with no or trace movement

2 Limb movement when gravity is eliminated

3 Movement against gravity but not resistance

4 Movement against resistance supplied by examiner

5 Full strength
Copyright © 2011 by AANN. All rights reserved.

Table 4. Assessment of Reflexes
Assess Reflexes

Reflex Nerve Innervation

Biceps C5, C6

Triceps C7, C8

Brachioradialus C5, C6

Patellar L3, L4

Achilles Sl, S2

Plantar Reflex (Babinski) L5,Sl

Reflex Grading Scale Finding

0 Absent reflex

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.

18 Nursing Management of the Patient with Multiple Sclerosis

thalamocortical, and extralemniscal
pathways (Evans & Boggs, 2010).

ii. SSEPs are useful in diagnosing clini-
cally silent MS lesions. One third of
abnormal SSEPs occur unilaterally.
Studies that compared SSEPs with
VEPs found equal sensitivity in re-
vealing lesions in patients with MS
(Evans & Boggs, 2010; Gronseth &
Ashman, 2000).

2. Optical coherence tomography (OCT)
a. OCT is a new optical imaging technique

that measures a cross-section of the reti-
nal nerve fiber layer (RNFL) thickness with
high resolution and good reproducibility.
The RNFL consists of the unmyelinated ax-
ons of retinal ganglions that become my-
elinated past the lamina cribrosa and the
optic nerve. If the RNFL is affected as seen
in patients with MS, it will show a retro-
grade degeneration that follows the dam-
age of the optic nerve or optic tract.

b. Benefits found with OCTs are that they
are easy to perform, time efficient, and less
costly than MRI. MRI is considered the
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 diagnos-

tic tests used in diagnosing MS. In MS, clini-
cal 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 approxi-
mately 95% of patients with clinically de-
finitive MS (Nielsen, Korteweg, & Polman,
2007).

c. Two types of images are used during brain
MRI: T2-weighted and T1-weighted imag-
es (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).

iii. When brain MRI results are normal
or equivocal, spinal cord MRI is use-
ful (Figure 8).

iv. Spinal cord lesions are found in ap-
proximately 50%–90% of patients

with clinically definitive MS
(Traboulsee & Li, 2006).

v. The characteristic MS lesion ap-
pears bright at T2-weighted MRI
(secondary to inflammation, edema,
demyelination, axonal loss, and/or
Wallerian degeneration) and is found
in the periventricular, juxtacortical,
or infratentorial white matter (Bak-
shi, Hutton, Miller, & Radue, 2004).

d. Lesions can occur in any CNS tissue where
there is myelin (e.g., the brain, spinal cord,
or optic nerves; Traboulsee & Li, 2006).

e. In the brain, the periventricular (surround-
ing the ventricles) region is the typical
location where white matter lesions are lo-
cated (Figure 9).

f. Juxtacortical lesions are located in the tem-
poral lobes at the grey-white matter junc-
tion (Figure 9; Traboulsee & Li, 2006).

g. Dawson’s fingers are lesions that are per-
pendicular to the ventricles. These lesions
are a unique feature of MS (Figure 10;
Traboulsee & Li, 2006).

Figure 5. T1-weighted axial image

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

Nursing Management of the Patient with Multiple Sclerosis 19

Figure 6. T2-weighted axial image

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

Figure 7. Sagittal FLAIR image

A FLAIR image is a type of T2 image with superior capability for demonstrating demye-
linating lesions and shows both new and old lesions clearly. Courtesy of the Internation-
al Organization of Multiple Sclerosis Nurses (IOMSN). Original MRI image provided to
IOMSN by William Stuart, MD.

Figure 8. Spinal cord MRI showing cord lesion

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-
pear (Traboulsee & Li, 2006). If these hy-
pointense areas persist, they represent
axonal loss. Permanent disability may be
related to axonal loss (Figure 11; Bakshi,
Hutton, Miller, & Radue, 2004).

20 Nursing Management of the Patient with Multiple Sclerosis

Figure 10. MRI demonstrating Dawson’s fingers

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

i. There is some consensus that patients with
PPMS have fewer lesions in the cerebrum
and possibly less enhancement in the CNS
(Bakshi et al., 2008).

j. Gadolinium is used to detect new disease
activity (inflammation). Gadolinium does
not typically cross the BBB. New MS le-
sions coincide with disruption of the BBB
and appear on T1-weighted images as gad-
olinium-enhanced lesions (Traboulsee &
Li, 2006). The lesions appear bright and of-
ten have a ringlike pattern around them
(Figure 12). On average, enhancement
lasts approximately 4 weeks, with a grad-
ual decrease during the next 2–4 weeks
(Traboulsee & Li, 2006).

k. The Consortium of MS Centers has pub-
lished 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 measure-
ment of cerebral atrophy. In comparison with
controls, patients with MS display an increased
loss of brain volume, and a means of measur-
ing this is through calculation of BPF (Rudick
et al., 1999), which is considered a sensitive in-
dicator of disease severity (Dörr et al., 2011).

G. Laboratory testing
The MS diagnosis is generally based on clinical
signs and symptoms and MRI, VEP, and labo-
ratory analyses (specifically CSF) See previous
discussion of McDonald criteria (Polman et al.,
2011).

Figure 11. MRI demonstrating “black holes”

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

Figure 12. MS lesions on enhanced T1 weighted MRI

T1-weighted gadolinium-enhanced MRI showing new and active lesions that appear
bright, reflecting areas of blood-brain disruption. Courtesy of the International Organiza-
tion of Multiple Sclerosis Nurses (IOMSN).

1. CSF tests: Examining CSF may identify abnor-
mal cells or antibodies that suggest the pres-
ence of MS. It has been the focus of testing and
research for many years (Rammohan, 2009).

a. CSF is examined by means of a lumbar
puncture (spinal tap). CSF is clear and
colorless in all MS patients (Rammohan,
2009).

Nursing Management of the Patient with Multiple Sclerosis 21

2. Tests performed on CSF include oligoclonal
bands (OCBs), IgG Index, Myelin Basic Pro-
tein (MBP), Kappa Light Chains, glucose, al-
bumin index, protein level, and white blood
cell level.

a. Oligoclonal bands: OCBs are immuno-
globulins (IgG, IgM, or IgA) or proteins of
the immune system that are generated by
plasmablasts and plasma cells in the CSF
or CNS compartment (Awad et al., 2010).
In addition to MRI, the presence of OCBs
in the CSF is the most consistent laborato-
ry abnormality found in patients with MS.
If OCBs are present, less stringent criteria
are needed to satisfy the dissemination in
space criterion (Polman et al., 2011).
i. A positive test for OCBs is the pres-

ence of two or more IgG bands in the
CSF that are not present in a blood
serum sample obtained at the same
time (Awad et al., 2010; Freedman et
al., 2005; Link & Huang, 2006; Ram-
mohan, 2009).

ii. According to Rammohan (2009),
identification of OCBs is invaluable
for diagnosis of MS. Villar and col-
leagues (2009) stated that the pres-
ence of OCBs is characteristic of MS,
and Fromont and colleagues (2005)
stated that the detection of OCBs in a
patient’s CSF is the gold standard lab-
oratory test for MS.

iii. Tintoré and colleagues (2008) exam-
ined whether OCBs added to MRI
findings as a predictor of a second at-
tack and the development of clini-
cally definite MS and disability in
patients with clinically isolated syn-
drome (CIS). The authors found that
the presence of OCBs doubles the
risk for having a second attack, inde-
pendent of MRI findings, but does
not seem to influence the develop-
ment of disability.

b. IgG Index: An increase in the level of IgG
in the CSF can be due to the increased pro-
duction of IgG in the CNS. This increase
in production can be seen with MS as with
other diseases. The increase in IgG can be
due to leakage of plasma proteins into the
CSF as might be seen with inflammation or
trauma.
i. The IgG Index is calculated from IgG

and albumin measurements in the

CSF and blood serum. The calcula-
tion is

IgG Index =
IgG (CSF)/IgG (serum)

Albumin (CSF)/Albumin (serum)

(Hische, van der Helm, & van Wal-
beek, 1982; Link & Huang, 2006).

ii. An elevated IgG Index indicates an
increase in the production of IgG
within the CNS. It is elevated in
about 70% of cases of MS. Because
of the low sensitivity of the IgG In-
dex, it cannot be recommended as
the primary laboratory test or replace
the CSF OCB in the diagnosis of MS.
However, when elevated, it can be
used as an additional tool in the di-
agnosis of MS and help to rule out
other diseases that mimic MS (Link
& Huang, 2006).

c. Myelin Basic Protein (MBP): MBP is
the major component of myelin, and in-
creased concentrations of myelin in CSF
indicate that demyelization is occurring.
Increased levels of MBP have been found
during active demyelination. Levels may
be elevated in the CSF of patients with
MS; however, it is thought not to be spe-
cific for MS, because other inflammatory
diseases of the CNS can increase the level
of MBP in the CSF. It may be used to help
rule out other diseases that mimic MS
(Rammohan, 2009).

d. Other CSF studies performed not specific
for MS
i. Color and clarity: All aspects of CSF

analysis help to distinguish between
other causes of systemic inflamma-
tion and diseases that could possibly
mimic MS. CSF in patients with MS
is generally clear and colorless.

ii. Glucose: Usually normal in MS.
iii. Albumin index: Used to rule out the

leakage of protein into the CSF from
blood caused by either a damaged
BBB or a traumatic spinal tap.

iv. Protein level: Normal or slightly el-
evated; most patients with MS have
normal total protein counts even
during an acute exacerbation (Ram-
mohan, 2009).

e. White blood cell (WBC) level: Higher than
normal CSF WBCs (predominantly mono-
nuclear cells) are found in MS, whereas

22 Nursing Management of the Patient with Multiple Sclerosis

very high CSF WBC counts (>50 x 10 L)
are unusual for MS.

3. Peripheral Blood Tests: May be helpful to rule
out other disease processes that mimic MS
(Calabresi, 2004).

a. Advancements in paraclinical investi-
gations, especially MRI, CSF, and visual
evoked potential testing, together with the
need for a definitive diagnosis at the ear-
liest time possible, are imperative for the
physician to begin treatment in a timely
manner. In making the diagnosis, a pre-
condition should include the exclusion of
diseases that mimic MS (Courtney, Tread-
away, Remington, & Frohman, 2009).
Multiple tests are needed to rule out oth-
er conditions or diseases that have simi-
lar signs and symptoms that affect the CNS
and that can be confused with MS (Cal-
abresi, 2004).

b. Table 5 lists some of the diseases that
mimic MS. This table is not all-inclusive
but lists many of the diseases most fre-
quently mentioned in the literature. (See
also Courtney, Treadaway, Remington,
and Frohman, [2009] and Rolak and Flem-
ing, [2007], who provide a more extensive
list of diseases that mimic MS).

c. Continued refinement of techniques will
generate additional information, better
methods of storage, and data analysis that
use bioinformatics. The resulting increased
availability of information from research
studies on CSF will help clinicians diag-
nose and treat MS as well as conduct fur-
ther research. Advances from these studies
will help to change the course of MS and
empower the patient and physician to treat
MS more effectively in the future (Rammo-
han, 2009).

H. Diagnostic research studies: Biomarkers
1. Introduction: A number of different biomark-

ers have been used to diagnose and differenti-
ate the different types of MS and treat MS.

a. Biomarkers, or biological markers, are nat-
urally occurring substances that can be
used as indicators of biological processes
and pathogenic processes including disease
states such as MS. Some biomarkers are
useful in assessing responses to therapeutic
interventions.

b. Discovery of new biomarkers for MS relies
on advances in proteomics research along
with microarray gene expression analyses

together with the analysis of antigens. It is
hoped that this will establish specific bio-
markers for MS (Harris & Sadiq, 2009).

2. Disease Activation Panel of Biomarkers
a. Biomarkers being researched include a

panel of biomarkers that measure MS dis-
ease activation: interleukin-6, nitric oxide,
osteopontin, and fetuin-A (Harris & Sadiq,
2009).

b. Interleukin-6: Interleukins (ILs), also
called lymphokines, are a subgroup of the
cytokines and carry messages between
cells. They are communicating proteins
that initiate or suppress inflammation.
There are more than 30 known ILs at this
time.

c. Nitric oxide (NO) and NO synthesis: NO is
a free radical signaling molecule that has a
complex biochemistry. Evidence points to
the role that NO plays in the pathogenesis
of MS and its role in various aspects of MS
such as inflammation, oligodendrocyte in-
jury, synaptic transmission changes, axonal
degeneration, and neuronal death (Enci-
nas, Manganas, & Enikolopov, 2005). Its
action may have both positive and negative
effects in MS.

d. Osteopontin: Osteopontin has been found
in the plasma levels of patients with MS
during relapses. In a study of MS patients
and healthy subjects, plasma osteopontin
levels were significantly increased in pa-
tients with RRMS and also correlated with
the IgG Index. This finding suggested that
bone-related molecules such as osteopon-
tin and vitamin D have immunomodu-
lary functions and are correlated with the
IgG Index in patients with RRMS (Vogt,
ten Kate, Drent, Polman, & Hupperts,
2010). Osteopontin is significant in MS as
it works with integrin a4b1 to block lym-
phocyte entry to the brain and to reduce
relapses (Steinman, 2009).

e. Fetuin-A: Fetuin-A is a protein found in
blood serum; 95% of it is derived from the
liver. It is implicated in the CNS as respon-
sible for increasing the permeability of the
BBB by activating matrix metalloprotein-
ase. In patients with active MS, a signifi-
cantly higher level of CSF fetuin-A is noted
than in patients with inactive disease (Yan,
Rammal, Dinzey, Donelan, & Sadiq, 2007).
Fetuin-A protein can be used to predict
the level of disease activity and to promote

Nursing Management of the Patient with Multiple Sclerosis 23

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
(ADEM)

Monophasic demyelinization occurring
with or just after infection, vaccina-
tion, or other immune-altering event
(Courtney, Treadaway, Remington, &
Frohman, 2009; Rolak & Fleming,
2007).

Frequently it is preceded by a viral infection (Gasperini,
2001). Symptoms can be identical to MS, including involve-
ment of optic nerve, brain, and spinal cord. Fifteen percent of
patients may have lesions on the brain.

MRI lesion may be hemorrhagic and involve the gray matter
(Rolak & Fleming, 2007). CSF—mild to moderate pleocytosis
(elevated WBCs in the CSF) and mild to moderate elevated
protein MBP. CSF beta-1 globulin in MS (Chopra, Abraham,
& Abraham, 2002). Gasperini (2001) states that using unen-
hanced serial MRI may be helpful, because with ADEM many
lesions resolve and new ones do not develop, but with MS,
some lesions resolve but new lesions develop.

Neuromyelitis Optica or Devic Syndrome
Monophasic

Abrupt onset of optic neuritis, transverse myelitis, brain stem
tegmentum syndrome (vomiting, oculomotor, and vestibular
problems); 10% to 50% have brain lesions (Courtney,
Treadaway, Remington, & Frohman, 2009). Frequently, it is
preceded by a viral infection (Gasperini, 2001).

CSF—marked pleocytosis (neutrophil component) and pro-
tein and albumin levels. Absent OCBs and normal IgG Index.
At MRI, lesions noted affecting the optic nerve and spinal cord
but with myelitis extending over 3 or more continuous seg-
ments of the spinal cord (Rolak & Fleming, 2007).

HIV-Associated Infections Occurs in high-risk patients that may have a decreased CD4
cell count and positive serology. May cause optic neuritis,
myelopathies, changes in mental status, and focal deficits
(Rolak & Fleming, 2007).

Increased total protein and cell count in CSF; 0 OCBs;
multiple cerebral white matter lesions at MRI indistinguishable
from those of MS (Gasperini, 2001). Positive HIV serology.

Lyme Disease
Tick exposure infected by tick-borne
spirochete, Borrelia burgdorferi.
(Courtney, Treadaway, Remington, &
Frohman, 2009).

Can cause consistent focal neurological findings Western blot. Diagnosis made based on symptoms and
evidence of tick bite. Enzyme-linked immunosorbent as-
say (ELISA); indirect fluorescent antibody (IFA); positive
polymerase chain reaction test (PCR) may be used to detect
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
Disease in which weakness occurs be-
cause the nerve impulses responsible
for initiating movement are not able to
reach muscle cells.

In myasthenia gravis, the symptoms tend to fluctuate
throughout the day, and they often worsen at night. Droopy
eyelids; facial weakness; impaired eye coordination; and
weakness of the limbs, neck, shoulders, hips, and trunk are
typical. Patients usually do not experience loss of sensation,
and fatigue is localized (Rolak & Fleming, 2007).

MRI, CSF, and visual evoked response (VER) are normal.
Eighty percent of patients have an elevated serum acetylcho-
line receptor antibody test result (Rolak & Fleming, 2007).

Pernicious Anemia
Vitamin B12 deficiency

May cause central nervous system (CNS) deficits, especially
progressive myelopathy. Rare MRI abnormalities (Rolak &
Fleming, 2007).

Serum B12 low; complete blood count may be abnormal; meth-
ylmalonic acid and homocysteine are often abnormal (Rolak &
Fleming, 2007).

Progressive Multifocal Leukoencepha-
lopathy (PML)

CNS infection by John Cunningham
(JC) virus in immunosuppressed
patient.

Can have multifocal CNS deficits. It occurs in immunocom-
promised patients. The deficits are usually progressive rather
than relapsing. Death may occur within weeks to months
if untreated (Rolak & Fleming, 2007; Courtney, Treadaway,
Remington, & Frohman, 2009).

The MRI is abnormal, usually shows lesions in white matter
that are larger and more confluent than those seen with MS.
CSF polymerase chain reaction (PCR) may be positive for JC
virus, but brain biopsy may need to be performed for definite
diagnosis (PCR is a laboratory test to detect the genetic mate-
rial of an infectious disease) (Rolak & Fleming, 2007).

Systemic Lupus Erythematosus (SLE) Systemic involvement includes hematologic, skin, and
kidney changes. Common in young women and may affect
the nervous system, especially the optic nerve and spinal
cord. MRI changes of white matter are common. Up to 60%
of patients have OCB and IgG abnormalities in CSF (Rolak &
Fleming, 2007).

Antinuclear antibody (ANA) titers levels are in increased SLE;
positive serology: double-stranded DNA autoantibodies and
ANA (Rolak & Fleming, 2007).

Syphilis
CNS infection by spirochete Trepo-
nema pallidum (Courtney, Treadaway,
Remington, & Frohman, 2009; Rolak
& Fleming, 2007)

Can cause optic neuritis, myelopathies, and other focal
neurological changes (Rolak & Fleming, 2007).

Tests for syphilis include serum VDRL, rapid plasma regain
(RPR) test, fluorescent treponemal antibody absorption (FTA-
ABS). CSF-protein (90%), WBC (90%), CSF VDRL (positive
80%). MRI usually normal. Infection considered rare except
in HIV-positive or immunocompromised patients (Rolak &
Fleming, 2007).

Continued

24 Nursing Management of the Patient with Multiple Sclerosis

faster and better therapeutic decisions by
healthcare providers.

3. Neurodegeneration proteins indicative of dis-
ease progression. Disease activity in MS is
mainly due to inflammation; however, disease
progression is most likely due to neurodegen-
eration (Harris & Sadiq, 2009).

a. CSF biomarkers (proteins) that reflect the
pathological process of MS are indicative of
demyelination as well as neuronal, axonal,
and glial loss and regeneration (Tumani et
al., 2009).
i. Neurofilaments

a) Studies have shown that an in-
crease in these antibodies may
serve as a marker of axonal dam-
age in MS (Giovannoni, 2010; Sal-
zer, Svenningsson, & Sundström,
2010; Teunissen, Dijkstra, & Pol-
man, 2005).

b) Antibodies to neurofilaments have
been identified in the serum and
CSF of patients with MS. They
have been detected in relapsing as
well as progressive disease and are
thought to be a marker of progres-
sive axonal injury (Rammohan,
2009).

ii. Total tau protein levels in CSF
a) Tau protein is a protein localized

in neuronal axons, and because
axonal damage has been proposed
as the major cause of permanent
clinical disability in patients with
MS, it is thought that it can serve
as a biochemical marker to evalu-
ate axonal damage (Brettschneider
et al., 2005).

b) Studies have been both positive
and negative for use of tau pro-
tein as a clinical marker of axo-
nal injury (Brettschneider et al.,

2005; Guimarães, Cardoso, & Sá,
2006; Jiménez-Jiménez et al., 2002;
Terzi, Birinci, Cetinkaya, & Onar,
2007; Valis, Talab, Stourac, An-
drys, & Masopust, 2008).

iii. N-acetylaspartic acid—may be an
important neuron specific marker of
disease severity and possible progres-
sion (Jasperse et al., 2007; Teunissen
et al., 2009).

iv. B cell chemokine CXCL13 (also
known as B lymphocyte chemoattrac-
tant [BLC]). Chemokines are a group
of molecules that attract leukocytes
(WBCs) from blood to the brain
when there is infection and/or an im-
mune response. B cells are a type of
WBC that develops in the bone mar-
row and works as part of the immune
system of the body. They have many
receptors that recognize invading or-
ganisms and as a result release anti-
bodies to fight the invaders. B cells
play a role in the pathogenesis of MS.
CSF and CNS tissues of patients with
MS contain B cells along with plasma
cells, antibodies, and immunoglob-
ulins, which suggests the need for
more research toward B cell–targeted
therapies (Racke, 2008).

v. Nogo-A
a) Nogo-A is a protein that is a

strong neurite inhibitor (Oertle
et al., 2003). It plays a role in re-
structuring axonal regeneration
(or regrowth) after injury and in
structural plasticity (i.e., ability
of the neural pathways to reorga-
nize as a result of new input) in the
CNS. Proteins that affect remye-
lination and regeneration are pro-
teins that are thought to provide

Table 5. Differential Diagnosis of Diseases that Mimic MS
Sarcoidosis

Granulomatous multisystem angioten-
sin disease of unknown cause (Rolak
& Fleming, 2007)

Often systemic symptoms, especially in the lungs. May
involve optic nerve or spinal cord (Rolak & Fleming, 2007).
Involvement of the optic nerve with pain in one or both eyes
and blurred vision are of importance. Facial nerve relapsing-
remitting palsies may occur (Gasperini, 2001).

CSF-protein, mononuclear pleocytosis, angiotensin-convert-
ing enzyme level. Chest X ray is a very helpful tool. Serum and
CSF ACE levels may be increased. Rare patients have OCB
in CSF. MRI may show white matter lesions and meningeal
enhancement. Positive biopsy of skin lesions, lymph nodes, or
lung is definitive diagnosis
(Rolak & Fleming, 2007).

Sjögren Syndrome
Chronic inflammatory and autoim-
mune disease

Systemic symptoms with dry eyes, dry mouth, and also
arthritis and vasculitis (Courtney, Treadaway, Remington, &
Frohman, 2009; Rolak & Fleming, 2007).

Positive serology for SS-A (Ro) and SS-B (La) autoantibodies
(Courtney, Treadaway, Remington, & Frohman, 2009; Rolak &
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).

Continued

Nursing Management of the Patient with Multiple Sclerosis 25

important information about MS
related to predicting disease sub-
types and progression (Lehmen-
siek et al., 2007).

b) Results from several studies on
Nogo-A suggest that it has mul-
tiple functions at the cell surface
and intercellular level (Harris &
Sadiq, 2009; Oertle et al., 2003).
Nogo-A plays an important role
for oliodendrocyte differentiation,
which is important in myelin re-
pair in autoimmune diseases such
as MS (Pernet, Joly, Christ, Dimou,
& Schwab, 2008), thus Nogo-A
may have a beneficial effect during
the inflammatory process of MS
but could be negative for the pro-
cess of myelin repair at a later date.

vi. Apolipoprotein (ApoE)
a) ApoE is a transport protein that

has been associated with clinical
features of MS. Liu and colleagues
(2009) reported that ApoE was de-
creased in patients with MS. It has
also been identified in CIS as one
of the proteins that may have a rel-
evant effect on early identification
of disease. However, further vali-
dation is needed (Lehmensiek et
al., 2007).

b) ApoE is considered to be a neu-
rotropic factor. Therefore, any
decrease in intrathecal ApoE syn-
thesis could possibly contrib-
ute to the progression of multiple
sclerosis.

vii. BDNF protein
a) Expression of BDNF has been as-

sociated with neural regeneration;
it is usually found wherever inner-
vations are present.

b) An increased number of BDNF
positive cells have been found in
the inflammatory lesions of those
with MS (Stadelmann et al., 2002),
and agents used to treat MS have
been found to activate cells capa-
ble of producing BDNF (Yoshimu-
ra et al., 2010; Ziemssen, Kümpfel,
Klinkert, Neuhaus, & Hohlfeld,
2002), with higher levels of BDNF
apparently playing a role in the
disease process.

Recommendation: Nurses should familiarize themselves
with published and ongoing research efforts in the area of
biomarkers for MS disease diagnosis and progression to
provide patient education regarding laboratory testing and
respond to questions from patients (Level 3).

VI. Disease Management
A. Management of MS

1. The management of MS is directed toward
disease modification, relapse management,
and symptom management. Treatment aims
include decreasing the frequency and number
of relapses, limiting disability, and relieving
symptoms (Compston & Coles, 2002; Goodin
et al., 2007).

2. There are presently six disease-modifying
treatments (DMTs) approved for use in the
United States and Canada to treat relapsing
forms of MS: glatiramer acetate (Copaxone®);
natalizumab (Tysabri®); and the interferons
(IFNs), intramuscular IFN β-1a (Avonex®),
subcutaneous IFN β-1a (Rebif®), subcutane-
ous IFN β-1b (Betaseron®, Extavia®), and fin-
golimod (Gilenyaâ„¢). Randomized clinical trials
support the favorable effects of DMTs on MS-
related disease activity as monitored by means
of MRI, relapse rate, and sustained disability
(Comi, Filippi, & Wolinsky, 2001; INFB Mul-
tiple Sclerosis Study Group & the University
of British Columbia MS/MRI Analysis Group,
1995; Jacobs et al., 1996; Johnson et al., 2003;
O’Connor, 2005; Rudick, 2005; Prevention of
Relapses and Disability by Interferon β-1a Sub-
cutaneously in Multiple Sclerosis [PRISMS]
Study Group, 1998). Mitoxantrone (Novan-
trone®) is an immunosuppressant approved to
treat secondary progressive, progressive-re-
lapsing, and worsening RRMS not responding
to other DMTs (Edan et al., 1997; Hartung et
al., 2002). The key features of DMTs for MS are
summarized in Table 6.

3. Tolerance of and willingness to adhere to treat-
ment regimen and the risk/benefit ratio drive
treatment decisions of the person with MS and
the prescriber (Freedman et al., 2008; Goodin,
2004; Goodin et al., 2007; Ross, 2008).

4. Nurses are responsible for monitoring the re-
sponse to DMT, including skin site reactions
(Figures 13–15). Strategies to manage toler-
ability issues associated with MS therapies are
presented in Table 7.

5. Intravenous methylprednisolone or oral ste-
roids are most commonly used to treat relaps-
es (Thrower, 2009).

26 Nursing Management of the Patient with Multiple Sclerosis

Recommendations: Nurses need to be aware of
the mechanism of action of MS medications to
educate and counsel patients about expected ben-
efits and adverse effects of medication therapy
(Level 3). Nurses need to be aware of the role of
personal patient preference and drug regimen
complexity related to tolerance of and willingness
to adhere to treatment protocols (Level 2).

B. Economic considerations
1. Financially, these treatments can be costly and

a significant burden to patients and families.
Both direct and indirect costs may or may not
be reimbursed by insurance plans, which vary
individually. Kobelt and colleagues (2006)
studied the estimated current costs and QOL
of patients taking disease-modifying medica-
tions, the total average annual cost in 2004 was
$47,215 (U.S. dollars) per patient. Of the total
average cost, it was determined that 53% was
for direct medical and nonmedical costs, while
37% was related to losses in productivity, in-
cluding short-term absence, reduced work-
ing time, and early retirement. Approximately
10% of the yearly costs were attributed to in-
formal care. Costs were significantly correlat-
ed with functional capacity (Kobelt, et al.).

2. Affordability of disease-modifying agents:
Studies have shown that some medications
may be more affordable than others. Newer
medications would likely be more expensive
than existing ones that have been used for a
longer time. Natalizumab (Tysabri®) has been
shown to reduce relapses and slow disease
progression, but the assessment of lifetime
cost-effectiveness of natalizumab versus other
disease-modifying drugs is inadequate (Earn-
shaw, Graham, Oleen-Burkey, Castelli-Haley,
& Johnson, 2009). Earnshaw and colleagues
(2009) show that direct costs (remaining life-
time) for patients receiving glatiramer acetate
or natalizumab compared to costs associ-
ated with symptom management were only
$408,000; $422,208; and $341,436, respectively.
Glatiramer acetate was more cost-effective than
natalizumab. Long-term evidence showed that
glatiramer acetate has similar, if not improved,
clinical benefits, despite 1- and 2-year relapse
rates being better for natalizumab (Earnshaw,
Graham, Oleen-Burkey, Castelli-Haley, &
Johnson, 2009).

3. RRMS affects the majority of the MS popu-
lation. Although there are several DMTs for
RRMS, not all are available for the same cost.
Goldberg and colleagues (2009) analyzed the

2-year effectiveness of four DMTs used for
RRMS—glatiramer acetate, interferon (IFN)
β-1a IM injection, IFN β-1a SC injection, and
IFN β-1b SC injection. Variables included re-
lapses, disability progression, and direct med-
ical costs. Medical savings were considered
in an event of an avoided relapse and disabil-
ity progression prevention. It was found that
without DMT, patients had more relapses and
pronounced disability progression. The four
DMTs previously mentioned are the most cost-
effective treatments for RRMS (Goldberg et al.).

Recommendation: Nurses can serve as advocates
for MS patients related to ensuring connection
with medication support services (Level 2).

C. Immunotherapies reveal aspects of MS
Disease-modifying medications’ mechanisms
of action provide evidence for understanding of
pathways in MS (Compston & Coles, 2002; Frank-
lin & Kotter, 2008; Olek, 2005; Chari, 2007; Yong,
2002; Neuhaus, Archelos, & Hartung, 2003).
1. Glatiramer acetate

a. Blockade of antigen presentation
b. Bystander suppression
c. Regulation of the T cells by CD 8 suppres-

sor cells
d. Enhanced neuroprotection and

remyelination
2. Interferon β

a. Stimulation of antiinflammatory cytokine
production

b. Inhibition of VLA-4 interaction with vas-
cular cell adhesion molecules (VCAMs) by
reducing increasing soluble VCAM-1

c. Inhibition of synthesis and transport of
matrix metalloproteinases

3. Fingolimod
a. Targets sphingosine-1-phosphate-1 recep-

tor on lymphocytes entrapping in lym-
phoid tissue

4. Monoclonal antibodies—reduce occurrence
of contrast-enhancing lesions suggesting:

a. Circulating immune cells expressing α-4
integrins are responsible for much of the
CNS cellular infiltration in MS.

b. Augmentation of low levels of natural kill-
er cells and their function may correct de-
fects in or provide a better level of T cell
regulation.

c. Circulating B cells are important pathogen-
ic components of immune responses in MS.

d. Circulating lymphocytes and monocytes
are important in demonstrating contrast-
enhancing MS lesions.

Nursing Management of the Patient with Multiple Sclerosis 27

Table 6. Key Features of the Disease-Modifying Agents
Agent
(Brand
Name)

Interferon ß-1b
(Betaseron®,
Extavia®)

Interferon ß-1a
(Avonex®)

Interferon ß-1a
(Rebif®)

Glatiramer ace-
tate (Copaxone®)

Natalizumab
(Tysabri®)

Mitoxantrone
(Novantrone®)

Fingolimod
(Gilenyaâ„¢)

Description • Recombinant agent,
produced in E. coli

• Unglycosylated
• Amino acid se-

quence differs from
naturally occurring
interferon with a
serine substituted
for the cysteine
residue at position
17

• Recombinant
agent produced
from Chinese
hamster ovary
cells

• Glycosylated
• Identical in

amino acid
content and
sequence to hu-
man β-interferon

• Recombinant
agent produced
from Chinese
hamster ovary
cells

• Glycosylated
• Identical in

amino acid
sequence to hu-
man ß-interferon

• Synthetic poly-
peptide

• Approximates
the antigenic
structure of
myelin basic
protein

• Recombinant
humanized
monoclonal
antibody
produced in
murine my-
eloma cells

• Synthetic
antineoplastic
anthracendione

Binds to the
sphingosine-
1-phosphate
receptor, or S1P
receptor on
immune cells,
including T cells
and B cells.
Induces immune
cells to remain
in lymph nodes,
inhibiting them
from migrating
into the brain
and spinal cord.

Indication
(United States)

Relapsing forms of MS
to reduce frequency of
relapses, CIS

Relapsing forms of
MS to slow accu-
mulation of physical
disability and
decrease frequency
of relapses, CIS

Relapsing forms of
MS, to delay accu-
mulation of physi-
cal disability and
decrease frequency
of relapses

RRMS to reduce
frequency of
relapses, CIS

Relapsing forms of
MS to delay accu-
mulation of physi-
cal disability and
reduce frequency
of relapses

SPMS, PRMS,
or abnormally
worsening RRMS,
for reducing neu-
rological disability
and frequency of
relapses

Reducing the
frequency of
clinical relapses
and delaying the
accumulation of
physical disabil-
ity in relapsing
forms of MS.

Dosage/
Route/
Admini-
stration

0.25 mg/l subcutane-
ous injection every
other day

30 μg/l intramuscu-
lar injection weekly

22 μg or 44 μg/l
subcutaneous
injection 3 times
weekly, preferably
on same 3 days and
at the same time
(e.g., late afternoon
or evening)

20 mg/l subcutane-
ous injection daily

300 mg/IV infu-
sion over 1 hour
every 4 weeks

12 mg/m2
(cumulative
lifetime dose not
to exceed 140 mg/
m2)/ IV infusion
administered for
5 to 15 minutes
every 3 months

0.5 mg orally
daily

Nursing
Consid-
erations

• Injection-site
rotation and skin
management

• Laboratory monitor-
ing*

• Neutralizing anti-
bodies

• Hematological/
hepatological
abnormalities

• Flu-like symptoms,
depression, other
side effects

• Injection-site
rotation and skin
management

• Laboratory
monitoring

• Neutralizing
antibodies

• Hematological/
hepatological
abnormalities

• Flu-like symp-
toms, depres-
sion, other side
effects

• Injection-site
rotation and skin
management

• Laboratory
monitoring

• Neutralizing
antibodies

• Hematological/
hepatological
abnormalities

• Flu-like symp-
toms, depres-
sion, other side
effects

• Injection-site
rotation and skin
management

• Immediate post-
injection reac-
tion, lipoatrophy,
other side effects

• Only available
under TOUCH®
Prescribing
Program

• PML, hyper-
sensitivity
reactions, signs
of liver injury,
other side ef-
fects

• Cardiotoxicity
(increases with
cumulative
dose):

• Patients should
be monitored
for evidence of
cardiotoxicity
prior to each
dose, and total
cumulative
lifetime dose is
not to exceed
140 mg/m2

• AML
• Other side

effects

Requires 6 hours
first dose moni-
toring. Caution
should be used
in patients who
may be at risk
of developing
bradycardia or
heart blocks,
macular edema,
active infections,
hypertension,
hepatic dysfunc-
tion, and respira-
tory disorders.

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-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-Copaxone (glatiramer acetate). Available at www.nationalmssociety.org/about-multiple-sclerosis/treatments/medications/glatiramer-acetate/index.aspx. Ac-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.

28 Nursing Management of the Patient with Multiple Sclerosis

i. Natalizumab—directed against α-4
integrins

ii. Daclizumab—directed against CD25,
the α chain of IL-2 receptor

iii. Rituximab—directed against CD20
on B cells

iv. Alemtuzumab—directed against
CD52 on T and B cells and monocytes

5. Estriol
a. Increases IL-10 and IL-5 and decreases in-

terferon γ and TNF-α
b. Provides further support of shift toward

antiinflammatory responses and is typical-
ly favorable in relapsing MS

6. Studies of agents that have been shown to
worsen MS also provide evidence for under-
standing 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

c. Antitumor necrosis factor α agents—
blocks beneficial effects of tumor necrosis
factor α, suggesting it may have immuno-
modulatory neuroprotective properties

Recommendations: Nurses must be aware of
patient responsiveness to therapy and serve as ad-
vocates for follow-up with appropriate interdisci-
plinary 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

which portion of the CNS is affected. The de-
myelination or destruction of the myelin
sheath of axons in the CNS most frequently af-
fects the optic and oculomotor cranial nerves
and the cerebellar, corticospinal, and posterior
column systems. Clinical manifestations in-
clude abnormalities of vision and eye move-
ment, 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 &
Matfin, 2008; Swann, 2006).

3. People with MS may experience a wide range
of symptoms. These may vary from person to
person, and symptoms may vary within one
individual patient (Halper, Costello, & Har-
ris, 2006). The varied range of symptoms in-
cludes fatigue, mobility, spasticity, numbness
and tingling in the extremities, general weak-
ness, visual impairments, bowel and bladder
dysfunction, sexual dysfunction, cognitive

Figure 13. Erythema, Interferon β-1a SC

Courtesy of Colleen Harris, MN MSCN

Figure 14. Erythema, bruising, glatiramer acetate

Courtesy of Kathleen Costello, MS ANP-BC MSCN

Figure 15. Lipoatrophy

Courtesy of Colleen Harris, MN MSCN

Nursing Management of the Patient with Multiple Sclerosis 29

disabilities, depression, anxiety, and dimin-
ished self-efficacy (Rumrill, 2009). Common
symptoms of MS are shown in Table 8 (Halp-
er, Costello, & Harris, 2006).

a. MS symptoms may be managed in a variety
of ways including education, counseling,
physical and occupational therapy, rehabil-
itation, and medication. Table 8 provides
a summary of the various pharmacologic
measures for selected MS symptoms.

B. Sensory symptoms
1. Paresthesias: Paresthesia can be present at

any state of the disease (Peterson, Kornbluth,
Marcus, Saulino, & Hung, 2004).

a. Paresthesia is evidenced as numbness, tin-
gling, a burning sensation, or pressure and
can range from annoying to severe in MS
patients (Porth & Matfin, 2008).

b. Symmetric paresthesis (tingling and
numbness) may occur in an unpredict-
able pattern in dorsal column symptoms
in patients with spinal cord involvement.
In patients with cerebellar involvement,
paroxysmal attacks include sensory (and
motor) symptoms, such as paresthesias,
dysarthria (and ataxia and tonic head turn-
ing) (McCance, Huether, Brashers, & Rote,
2010). Loss of neuroprotective sensation
may place patient at increased risk of pres-
sure ulcer development.

c. A common paroxysmal symptom, Lher-
mitte sign, is a shocklike or tingling sen-
sation, shooting down the trunk or limbs
during active or passive flexion of the neck.
Sensory stimulation, voluntary movement,
hyperventilation, and emotional stress may
be inciting events (McCance, Huether,
Brashers, & Rote, 2010; Porth & Matfin,
2008).

2. Pain: Pain is a complex symptom of MS and
usually involves the sensory system (Halper,
Costello, & Harris, 2006). Acute and chronic
pain may occur in MS.

a. It is subjective and is identified by the indi-
vidual with MS.

b. It is difficult for an observer to measure
pain.

c. Acute pain and paroxysmal disorders
i. Trigeminal neuralgia may be as-

sociated with transmission of
nerve impulses in severe regions of
demyelination.

ii. Tonic spasms, at times, may be relat-
ed to spasticity. Simple flexor spasms

may be related to movement or nox-
ious stimuli.

iii. Lightning-like extremity pain.
iv. Painful Lhermitte’s sign.
v. Optic neuritis results in inflamma-

tion around the pain-sensitive me-
ninges near the optic nerve and
retrobulbar pain.

d. Chronic pain with insidious onset
i. Dysesthetic extremity pain
ii. Bandlike pain in torso or extremities
iii. Back pain with radiculopathy
iv. Headache related to demyelinating

lesions
3. Management strategies (Halper, 2007b; Malo-

ni, 2007)
a. Nonpharmacologic

i. Rehabilitation evaluation for physical
therapy, occupational therapy

ii. Gait training
iii. Seating
iv. Assistive devices
v. Energy conservation
vi. Avoidance of tight clothing or nox-

ious stimuli
vii. Moist heat

b. Pharmacologic
i. If symptoms appear to be re-

lated to relapse, short course of
corticosteroids

ii. Nonsteroidal antiinflammatory drugs
(NSAIDs)

iii. Antispasticity agents
a) baclofen (Liorseal®)
b) tizandine (Zanaflex®)

iv. Antiseizure medications
a) phenytoin (Dilantin®)
b) gabapentin (Neurontin®,

Gabarone®)
c) pregabalin (Lyrica®)
d) carbamazepine (Tegretol®)

v. Antidepressant medications
a) Trazadone (Desyrel®)
b) Amitryptilline (Elavil®) switched

sequence
c. Complementary and alternative medicine

(CAM)
i. Massage
ii. Guided imagery
iii. Yoga
iv. Tai chi
v. Relaxation techniques

d. Surgical intervention for severe and intrac-
table pain

30 Nursing Management of the Patient with Multiple Sclerosis

Table 7. Symptoms of Multiple Sclerosis
Common Less Common Rare

Fatigue
Depression
Focal muscle weakness
Visual changes
Bowel, bladder, sexual dysfunction
Gait problems, spasticity
Paresthesias
Neuropathic pain
Cognitive dysfunction

Dysarthria, scanning speech, dysphagia
Lhermitte’s sign
Ataxia
Vertigo
Tremor, incoordination

Decreased hearing
Convulsions
Tinnitus
Mental disturbance
Paralysis

Table 8. Pharmacologic Management of Selected Symptoms in Multiple Sclerosis
Symptom Treatment Nursing Considerations

Fatigue CNS stimulants (pemoline, modafinil)
Amantadine
Selective serotonin reuptake inhibitors (SSRIs)
(e.g., fluoxetine)

Restlessness or sleep disturbance may occur
Help patients with dosing schedule, titrate doses up

Bladder dysfunction Anticholinergics (e.g., oxybutynin)
Antimuscarinics (e.g., tolterodine)
α-blockers (e.g., terazosin)

Determine if urinary tract infection is present
Monitor retention
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
Stool softeners
Bulk-forming agents
Mini-enemas
Stimulants
Suppositories

Urgency or diarrhea
Anticholinergics
Antimuscarinics

Provide bowel training regimens; many of the medications should not be used long term
Consider contributory effects of other medications (e.g., steroids or antibiotics)
Consider lifestyle issues
Encourage exercise
Provide diet counseling

Pain Anticonvulsants (phenytoin, carbamazepine,
abapentin, amotrigine)
Tricyclic antidepressants (amitriptyline, nortrip-
tyline)
Duloxetine hydrochloride

Watch for sedation
Start with low doses and titrate up
Monitor outcomes; alter treatment as necessary; supportive measures can help

Spasticity GABA antagonists (oral or intrathecal baclofen)
α-Agonists (tizanidine)
Anticonvulsants (diazepam, clonazepam, gaba-
pentin)
Botulinum toxin

Time doses to maintain therapeutic blood levels
Titrate doses up (especially with baclofen)
Watch for sedation or cognitive symptoms; may require a change in dosage or medication
Combination treatments may help
Intrathecal baclofen requires surgical insertion of a programmable pump

Depression SSRIs and serotonin-norepinephrine reuptake
inhibitors (e.g., fluoxetine, sertraline, paroxetine,
citalopram, duloxetine hydrochloride)
Tricyclic antidepressants (amitriptyline, nortrip-
tyline)
Atypical antidepressants (e.g., venlafaxine,
bupropion)

Evaluate type and degree of depression
Consider contribution of medications (e.g., with interferons)
Assess family situation and support network
Consider suicide risk
Promote use of psychiatric services
Advise patient that medication effects may take several weeks
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.

Nursing Management of the Patient with Multiple Sclerosis 31

Recommendations: The nurse should conduct
intermittent assessment for pain, dysthesia, and
spasticity (Level 2). Evaluate for the loss of neu-
roprotective sensation and the potential for pres-
sure ulcer development (i.e., ensure full body
assessment; Level 2). Evaluate the patient for trig-
gering and alleviating factors (Level 2). Evaluate
the effectiveness of pharmacologic therapies and
advocate for evaluation by the interdisciplinary
team (Level 1). Provide patient with emotional
support and evaluate for anxiety (Level 2). Pro-
vide patient and family education related to avail-
ability of adjuvant treatment and possible surgi-
cal interventions; assess patient’s willingness and
readiness to incorporate alternative therapies into
treatment regimen (Level 3).

C. Visual and hearing impairment
1. Visual Iimpairment

a. The demyelination or destruction of the
myelin sheath most frequently affects the
optic and oculomotor cranial nerves and
the cerebellar, corticospinal, and posterior
column systems. Vision problems are often
the first sign of MS (National MS Society,
2009).

b. Twenty-five to forty-eight percent of per-
sons initially experience optic neuritis (Pe-
terson, Kornbluth, Marcus, Saulino, &
Hung, 2004; Plant, 2008). This manifes-
tation of optic nerve axonal loss is high-
ly suggestive of MS. Diplopia and eyeball
pain are common subjective findings (Mc-
Cance, Huether, Brashers, & Rote, 2010).
High-dose glucocorticoids have been used
traditionally to accelerate recovery, and
NSAIDs may be useful for pain manage-
ment (Halper, Costello, & Harris, 2006).

c. Subjective visual symptoms that may pres-
ent unilaterally or bilaterally include im-
paired central vision (blurring, fogginess,
haziness) and impaired color perception.
Signs include decreased central visual acu-
ity; central or paracentral scotoma (area of
diminished vision); acquired color vision
deficit, especially to red and green; defec-
tive papillary reaction to light; and a va-
riety of field defects (McCance, Huether,
Brashers, & Rote, 2010).

d. Internuclear ophthalmoplegia, nystagmus,
and dysarthria are the most common brain
stem symptoms. May have significant effect
on ADLs because of diplopia or inability
to focus. These brain stem lesions involv-
ing cranial nerves III through XII may be

followed by deafness, vertigo and vomiting,
tinnitus, facial weakness, and facial sensory
deficit. Bilateral internuclear ophthalmo-
plegia (lateral gaze paralysis) is considered
diagnostic of MS. If it is acute, treatment
may include high-dose glucocorticoids to
accelerate recovery (Halper, Costello, &
Harris, 2006); otherwise, treatment is for
symptoms. There is currently no approved
U.S. Food and Drug Administration (FDA)
treatment. Prism lenses may be helpful in
some individuals with diplopia.

e. Nystagmus may be present in patients who
have cerebellar involvement with MS and
reflects cerebellar and corticospinal involve-
ment (McCance, et al.). Nystagmus is also
included in the description of the Charcot
triad, described by a combination of nystag-
mus, dysarthria, and intention tremor (Mc-
Cance, Huether, Brashers, & Rote, 2010).
For nystagmus, some benefit has been
found with the following pharmacologic
agents (Halper, Costello, & Harris, 2006):
i. Gabapentin (Neurontin®, Gabarone®)
ii. Memantine (Namenda®)
iii. 4-aminopyridine
iv. Levetiracetam (Keppra®)

2. Hearing impairment
a. The MS patient’s ability to understand

speech is markedly worse with sensorineu-
ral hearing loss (Suckfüll, 2009).

b. Young persons with hearing loss should
have MS considered as a possible diagno-
sis. Bilateral sequential hearing loss may be
considered an MS manifestation (Oh, Oh,
Jeong, Koo, & Kim, 2008).

Recommendations: Encourage regular eye ex-
aminations (Level 3). Be aware of the potential
for hearing changes and assess as needed (Lev-
el 3). Provide education regarding the patient’s
particular visual and hearing symptom experi-
ence (Level 3). Support the patient as visual and
hearing impairment may reduce overall function
(Level 2). Promote safety through education and
counseling related to effective lighting, scanning,
and environmental modifications (Level 2).

D. Fatigue
1. Fatigue is an individual’s subjective lack of

physical and/or mental energy that is perceived
as impeding his or her typical or desired activi-
ties of life (Johansson, Ytterberg, Gottberg, Wi-
dén Holmqvist, & von Koch, 2009).

2. Fatigue is considered the most common and
disabling symptom of MS; it affects between

32 Nursing Management of the Patient with Multiple Sclerosis

75% and 95% of all persons with the disease
(Egner, Phillips, Vora, & Wiggers, 2003).

3. Higher levels of general fatigue are observed
in RRMS compared with the other three sub-
types, and with increasing disease severity.
DMT generally has no effect on fatigue lev-
els (Hadjimichael, Volmer, & Oleen-Burkey,
2008).

4. Fatigue is categorized into primary and sec-
ondary forms, which are often difficult to
differentiate.

a. Primary fatigue can directly result from
MS neuropathology.

b. Secondary fatigue follows from a number
of common MS comorbidities, including
depression, medication side effects, pain,
psychosocial characteristics, thyroid dys-
function, vitamin B12 deficiency, anemia,
and sleep disorders (Johnson, 2008). Most
research to date has found fatigue to be of
the secondary rather than the primary form.

5. Trojan and colleagues (2007) differentiated fa-
tigue into three categories: (1) general or over-
all, (2) physical, and (3) mental. They found
that sleep quality, pain, and self-efficacy were
the strongest predictors of general fatigue;
self-efficacy and physical activity level were
most predictive of physical fatigue; stress level
and self-efficacy were the strongest predictors
of mental fatigue.

6. Relationships between physical fatigue and
increased MS disease severity have been ob-
served (Debouverie, Pittion-Vouyovitch,
Brissart, & Guillemin, 2008).

7. Depression has not been found to be a strong
predictor of physical fatigue in MS (Debouv-
erie, Pittion-Vouyovitch, Brissart, & Guille-
min, 2008; Trojan et al., 2007), although it has
shown relationships with mental fatigue (Sch-
reurs, de Ridder, & Bensing, 2002).

8. Along with depression, fatigue is a predictor
for decreased cognitive functioning in MS (Di-
amond, Johnson, Kaufman, & Graves, 2008).

9. Assessment of fatigue
a. Involves informal questioning of patients

and their care partners
b. Formal assessment by means of instru-

ments/tools: the Modified Fatigue Impact
Scale (MFIS), the Fatigue Severity Scale
(FSS), or the Neurological Fatigue Index-
MS (NFI-MS)

10. Management of fatigue (Bergamaschi, Ro-
mani, Versino, Poli, & Cosi, 1997; Costel-
lo, Halper, & Harris, 2003; Kos, Kerckhofs,

Nagels, D’Hooghe, & Ilsbroukx, 2008; Krupp,
2004; Markowitz, 2010; Mills, Young, Pallant,
& Tennant, 2010; Penner & Calabrese, 2010)

a. Nonpharmacological strategies
i. Gradual exercising
ii. Maintain realistic expectations
iii. Energy conservation techniques

(Fragoso, Santana, & Pinto, 2008)
a) Pace activities
b) Space activities
c) Divide activities
d) Do strenuous activities early in the

morning
e) Minimize effort
f ) Prioritize tasks
g) Schedule and plan activities
h) Schedule rest periods

iv. Keep cool during exercises
a) Exercise in air-conditioned

environment
b) Drink ice water

b. Complementary and alternative methods
i. Vitamins
ii. Nutrition
iii. Caffeine
iv. Carnitine

c. Pharmacological interventions
i. Fatigue responds to some phar-

macotherapy regimens, including
amantadine (Symadine®, Symme-
trel®), modafinil (Provigil®) and
armodafinil, selective seratonin reup-
take inhibitors (SSRIs).

ii. Less commonly used are amphet-
amines such as methylphenidate or
amphetamine and dextroamphet-
amine composite (Adderall®).

iii. Aminopyridine is a possible modula-
tor of increased conduction and in-
creasing fatigue.

iv. A key point for all medications for
MS patients is to initiate at a low dose
and increase based on effectiveness
and tolerance.

Recommendations: Nurses should be aware of
and assess for secondary causes of fatigue to in-
clude depression, medication side effects, pain,
and sleep disorders (Level 2). Nurses should edu-
cate and counsel patients regarding energy con-
servation strategies, including the role of body
temperature control (Level 2). The nurse should
be aware of the optimal timing of medication ad-
ministration to enhance energy level and to avoid
interrupting sleep (Level 3).

Nursing Management of the Patient with Multiple Sclerosis 33

E. Impaired mobility
1. Physical activity is markedly decreased in MS

populations compared with that in healthy
controls, and this appears to be related to dis-
ease severity (Motl, 2008). However, it is not
clear if disease severity itself is the culprit.
Because fatigue and motor dysfunction fre-
quently present in MS, persons affected by the
disease often avoid physical exercise, believing
it may worsen fatigue or have no beneficial
effect.

2. Hand dysfunction has been found to be
more common at testing in patients with
MS when compared with that in other pa-
tients (Krishnan & Jaric, 2008). This dys-
function may include loss of strength and/or
coordination.

3. Disabling tremor or ataxia is a common fea-
ture of MS and occurs in almost 80% of pa-
tients at some point during their disease.
Research on strategies to treat disabling tremor
or ataxia with pharmacotherapy, neurosurgery,
or rehabilitation has not demonstrated effec-
tive treatment (Mills, Yap, & Young, 2007).

4. A symptom cluster of pain, depression, and
fatigue has recently been observed to be a
strong barrier to exercise, and functional im-
pairment is a predictor of the presence of the
symptom cluster (Motl & McAuley, 2009).

5. Assessment (Halper & Ross, 2010; Schapiro,
2007)

a. Subjective history
b. Objective assessment of motor strength,

muscle tone, balance, and sensory func-
tion. Specific tests include: the timed 25-
foot walk, timed up and go test, expanded
disability status scale (EDSS), and driving
evaluation.

6. Management of mobility disturbance
a. Exercise therapy: identified as an effective

treatment for MS. Results of trials show
strong evidence that exercise therapy com-
pared to no exercise therapy had positive
effects on muscle power function, exercise
tolerance functions, and mobility-related
activities (Rietberg, Brooks, Uitdehaag, &
Kwakkel, 2005). Exercise improves self-
efficacy, which in turn reduces fatigue,
pain, and depression in patients with MS
(McAuley, White, Rogers, Motl, & Cour-
neya, 2010). Meta-analyses have shown
that exercise training is associated with
a small improvement in walking mobil-
ity (Snook & Motl, 2009) and quality of

life (Motl & Gosney, 2008) among patients
with MS.
i. Exercise therapy was not found to

be effective in reducing fatigue or in
reducing the perception of disabil-
ity compared to no exercise therapy.
No evidence was found to suggest
that exercise therapy was harmful,
and it is reasonable to promote exer-
cise in patients with MS who are not
experiencing an exacerbation (Riet-
berg, Brooks, Uitdehaag, & Kwakkel,
2005).

ii. Resistance exercise has been found
to have a positive effect on function
in patients with MS. A randomized
clinical trial of exercise versus con-
trol group demonstrated that super-
vised and intense resistance training
of the lower extremities improves
muscle strength and functional ca-
pacity in patients with RRMS and
moderate impairment. Importantly,
in patients, these improvements per-
sisted after 12 weeks of self-guided
physical activity (Dalgas et al., 2009).
Resistance training of moderate in-
tensity seems to be well tolerated and
to have beneficial effects for patients
with MS.

iii. Elevated core body temperature can
sometimes present a barrier to exer-
cise (generating Uhthoff ’s phenom-
enon), but this can be addressed by
the use of affordable cooling equip-
ment (Schwid et al., 2003).

b. Use of adaptive equipment: bracing, cane,
walker, scooter, wheelchair. Ensure training
on safe use and proper maintenance. The
patient is referred for evaluation for use of
automobile hand controls; OT/PT consul-
tation is obtained as appropriate (Halper &
Ross, 2010; Schapiro, 2007).

c. Electrical stimulation devices: WalkAide®,
Bioness® (Halper & Ross, 2010; Schapiro,
2007)

d. Pharmacologic therapy: dalfampridine,
fampridine-SR (Ampyra)

Recommendations: Identify functional effect of
impaired mobility and collaborate with interdis-
ciplinary team members to promote optimal mo-
bility within the patient’s limitations (Level 3).
Evidence-based treatment interventions for mo-
bility optimization include exercise promotion

34 Nursing Management of the Patient with Multiple Sclerosis

(Level I). Educate patient and care partners re-
garding treatment, therapy recommendations,
medications, and support adherence (Level 3).
The nurse should encourage safety by reinforcing
appropriate and safe use of adaptive equipment
and aides (Level 2). Assess for the psychological
effect of reduced mobility and/or increased dis-
ability (Level 2).

F. Bladder and bowel symptoms
1. In MS with spinal cord involvement, bowel

and bladder symptoms occur. Some MS pa-
tients lose voluntary control over bladder and
bowel function (Pellat, 2008).

2. Bladder symptoms
a. There are three types of bladder dysfunc-

tion: storage dysfunction, emptying dys-
function, and combined dysfunction. In
MS, bladder dysfunction affects QOL
(Rantell, 2009).

b. Incontinence is preceded by urgency and
hesitancy. Flaccid bladder may occur with
retention problems, although bladder dys-
function most often involves a spastic
bladder.

c. Some patients with spinal cord disease may
have combined incomplete emptying and
bladder overactivity (Pellat & Geddis, 2008).

3. Bowel dysfunction
a. Neurogenic bowel dysfunction may occur

in MS. This may include fecal incontinence
or constipation, and at times may involve
both (Wollin, Bennie, Leech, Windsor, &
Spencer, 2005), and is often an underre-
ported symptom of MS (Bywater & While,
2006). In severe cases of MS, constipation
is common (McCance, Huether, Brashers,
& Rote, 2010).

b. Bowel dysfunction has a significant effect
on the QOL of patients with MS, but re-
search in this area is limited (Coggrave,
2008; Coggrave, Wiesel, & Norton, 2006).

4. Evaluation of urinary elimination in MS
patients can be multidimensional (Betts,
D’Mellow, & Fowler, 1993; DasGupta & Fowl-
er, 2003; O’Leary & Dierich, 2010)

a. Laboratory assessment
i. Urinalysis; urine culture and sensitiv-

ity (UTIs, diabetes, hematuria)
ii. Cytology (bladder cancer)
iii. Blood urea nitrogen (BUN), creati-

nine levels (renal dysfunction)
b. Urodynamics—group of tests which to-

gether measure bladder function and
pressure

c. Uroflowmetry (volume of urine voided
over time), postvoid residual (PVR; urine
volume after void)

d. Radiologic tests
i. Abdominal computed tomography

(CT) scan
ii. Renal ultrasound (renal and upper

urinary tract status)
iii. Cystoscopy (study of bladder lining

and urethra)
e. Bladder diary—voiding patterns typical

over 24–72 hours
f. Diary of food and fluid intake

5. Urinary management strategies (Betts,
D’Mellow, & Fowler, 1993; DasGupta & Fowl-
er, 2003; O’Leary & Dierich, 2010)

a. Nonpharmacologic
i. Behavior management—establish-

ing voiding schedule, diet instruction
to limit irritants and to increase fluid
intake, measures to limit fluid reten-
tion, environmental assessment of
toilet locations, proper use of absor-
bent products, biofeedback, and in-
fection prevention strategies

ii. Intermittent self-catheterization
(ISC)—used for chronic retention to
improve continence and to preserve
renal function. Frequency depends on
voids per day and resulting retention.

iii. Long-term indwelling catheters—su-
prapubic catheter recommended for
individuals who cannot toilet them-
selves, cannot perform intermittent
catheterization, or have medi-
cal issues from incontinence. Ure-
thral catheters should be used short
term only (i.e., several weeks, not
months) because of the damage that
can occur in the urethra and other
complications.

b. Pharmacologic
i. Anticholinergics—side effects of oral

forms include dry mouth, blurred vi-
sion, flushing, palpitations, nausea,
constipation, drowsiness, confusion,
and urinary retention.

ii. Alpha-adrenergic blocker—side ef-
fects include site reactions, sleepi-
ness, or blurred vision.

iii. Botulinum toxin (off-label use) injec-
tion into bladder. Side effects: pain,
urinary retention, hematuria, and
infection.

Nursing Management of the Patient with Multiple Sclerosis 35

Recommendations: Nurses should work with
the patient, care partner, and other mem-
bers of the interdisciplinary team to develop
an appropriate bladder management pro-
gram (Level 3). Assess all patients for urinary
dysfunction and assess effectiveness of treat-
ments or behavioral strategies over time (Lev-
el 3). Encourage discussion of symptoms and
effect on QOL and role function and assist
with coping strategies (Level 3). Assess for in-
fection and assist in management strategies to
reduce risk of infection, stone formation, or
worsening of neurologic condition (Level 3).

6. Evaluation of Bowel Function (DasGupta &
Fowler, 2003; Walker, 2009)

a. Assessment of frequency and type of
movement, time of day, use of any medi-
cation, laxatives and enemas, absorbent
products, comorbid conditions, and assis-
tance needed with toileting

b. Further testing as warranted
i. Laboratory—complete blood cell

count, complete metabolic profile
(CMP), pancreatic enzymes, stool
culture, and hemoccult testing

ii. Imaging—abdominal flat plate, bar-
ium enema, defecography, colon-
ic transit studies, upper GI, and CT
scan of abdomen

iii. Other tests—manometry and
electromyography

7. Bowel management strategies
a. Nonpharmacologic

i. Behavior management—establishing
consistent schedule, diet instruc-
tion to limit irritants and to increase
fluid intake, addition of dietary fi-
ber in foods the patient can tolerate,
environmental assessment of toilet
locations, proper use of absorbent
products, and biofeedback

ii. Use of reflexes. Stimulation of gas-
trocolic and duodenocolic reflex. The
best time is 30–45 minutes after a
meal or hot beverage or after digital
stimulation or enema.

b. Pharmacologic
i. Suppositories, bulk-forming agents,

stool softeners, laxatives (osmotic
and stimulant), and rectal stimulants.
(Caution: large-volume enemas can
overdistend the bowel.)

Recommendations: Nurses should work
with the patient, care partner, and other

members of the interdisciplinary team to de-
velop an appropriate bowel management
program (Level 3). Assess all patients for dis-
orders of bowel function and assess effective-
ness of treatments or behavioral strategies
over time (Level 3). Encourage discussion of
symptoms and effect on QOL and role func-
tion and assist with coping strategies (Level
3). Assess for effectiveness of management
strategies and effectiveness of medications,
understanding that bowel interventions may
take a long time to become effective and that
worsening of symptoms without any relief
from strategies may indicate disease progres-
sion (Level 3).

G. Sexual dysfunction and reproductive issues
1. Sexual dysfunction is common in MS because

of its direct neurophysiologic effects, conse-
quences of secondary conditions of MS (e.g.,
fatigue, altered sensation, muscle spasms,
bowel and bladder problems, vaginal dry-
ness), and the psychological and cognitive
changes that occur in MS (McCabe, 2002;
Smeltzer, 2002).

2. Neurogenic impotence may accompany
sphincter symptoms.

3. Despite the incidence of sexual dysfunction,
many patients with MS remain interested
in intimacy, sexual relationships, childbear-
ing, and parenting (McCabe, 2002; Smeltzer,
2002).

Recommendations: Nurses must consider MS
patients’ interest in sexuality and intimacy rather
than assume that they are asexual or uninterest-
ed (Level 2). Nurses should provide information,
education, counseling, and resources about issues
related to sexuality, reproductive function, preg-
nancy, and parenting (Level 3).

H. Dysphagia
1. Permanent and transitory swallowing disor-

ders (dysphagia) occur with high frequency in
patients with MS (Calcagno, Ruoppolo, Grass,
De Vincentiis, & Paolucci, 2002; Prosiegel,
Schelling, & Wagner-Sonntag, 2004), occur-
ring in 34.4% of patients with primary and
secondary progressive MS (Calcagno, Ruop-
polo, Grass, De Vincentiis, & Paolucci). Swal-
lowing disorders may be present long before
the person with MS experiences any other re-
lated symptoms. Patients with a mild form of
MS may experience problems swallowing flu-
ids, and patients with more advanced MS may
develop difficulties swallowing solid foods
(Bogaardt et al., 2009).

36 Nursing Management of the Patient with Multiple Sclerosis

2. A close relationship between dysphagia and
both brain stem impairment and severity of
illness has been noted. The potential risk of
aspiration and malnutrition, and the high ef-
ficacy of swallowing rehabilitation suggest
that all MS patients should have a careful
evaluation of deglutition functionality, espe-
cially those with brain stem impairment and
a high grade of disability level (Calcagno,
Ruoppolo, Grass, De Vincentiis, & Paolucci,
2002).

3. The most common MS-related swallowing
disorders in the oral and pharyngeal areas
are delays in triggering the pharyngeal swal-
low. This can cause particular difficulties with
liquid swallowing, including aspiration (Lo-
gemann, 2000). Reduction in tongue base ac-
tivity reduces the pressure generated during
the swallow, allowing residual food to remain
in the pharynx and be aspirated when the pa-
tient resumes breathing. These disorders can
be mild, without causing any significant dif-
ficulties such as aspiration or inefficient swal-
low, or they can be more severe and require
therapeutic (behavioral) management (Loge-
mann, 2000).

4. Dysphagia evaluation
a. Assessment: problem onset, duration and

severity; symptom characteristics; observa-
tion of choking, delayed swallowing, chew-
ing difficulties; nutritional status, food and
liquid intake, weight; cough or increasing
hypophonia may indicate new or pending
problems.

b. Referral should be made to a speech/
language pathologist (SLP) for evaluation
and treatment.

c. Additional assessment as needed may in-
clude video-fluoroscopic study (modified
barium swallow; Frenette, Harris, Klassen,
& McEwan, 2001).

5. Dysphagia management
a. Ensure alert and minimize distractions

at mealtimes; provide supervision as
indicated.

b. Monitor patient for signs and symptoms of
swallowing difficulty, aspiration pneumo-
nia (Frenette, Harris, Klassen, & McEwan,
2001).

c. Safe swallowing practices
i. Proper positioning
ii. Double swallow
iii. Chin tuck
iv. Other techniques as prescribed

d. Collaborate with dietician and SLP for di-
etary modifications; ensure consistency
and ordered texture of liquids and solids.

e. Suctioning if indicated
f. Monitor weight on ongoing basis.
g. Education of patient and family regarding

safety measures to include use of suction
apparatus and Heimlich maneuver

h. Advanced or worsening swallowing may
result in the need for tube feedings via na-
sogastric (NG) tube temporarily or via per-
cutaneous endoscopic gastrostomy (PEG)
on a permanent basis. Educate and coun-
sel patients and care partners about feeding
options as disease progresses.

i. Other treatment options may include neu-
romuscular electrostimulation because it
was successful in reducing pooling saliva
and in reducing aspiration in patients with
MS (Bogaardt et al., 2009).

Recommendations: Assess the patient regular-
ly for swallowing difficulties (Level 2). Nurses
should work with the patient, care partner, and
other members of the interdisciplinary team to
develop an appropriate dysphagia management
program (Level 3). Monitor weight at each vis-
it (Level 3). Educate and counsel the patient and
care partner to reinforce safe swallowing practic-
es (Level 3).

I. Cognitive dysfunction
1. Recent studies suggest a high prevalence rate

for cognitive impairment, ranging between
40% and 70%, depending on the population
and setting studied (Chwastiak & Ehde, 2007;
Siepman et al., 2008). The most common
cognitive impairments found in MS include
memory, sustained attention, and slowed in-
formation processing speed (Amato, Zipoli, &
Portaccio, 2006; Nocentini et al., 2006).

2. The relationship between MS disease sub-
type and magnitude of cognitive impairment
remains unclear (Kalmar, Gaudino, Moore,
Halper, & DeLuca, 2008). Huijbregts and col-
leagues (2004) demonstrated that cognitive
profiles in RRMS versus progressive MS dif-
fer in severity and character, with patients
with RRMS showing isolated deficits in work-
ing memory and those with progressive MS
showing more global deficits.

3. Cognitive impairment has been related to the
presence of other symptoms including fatigue,
spasticity, bowel or bladder dysfunction, and
fine motor functioning (Kalmar, Gaudino,
Moore, Halper, & DeLuca, 2008). Information

Nursing Management of the Patient with Multiple Sclerosis 37

processing speed has demonstrated relation-
ships with depression and fatigue (Diamond,
Johnson, Kaufman, & Graves, 2008).

4. Relationships have been found between MRI
measures and cognitive dysfunction in MS
(Archibald et al., 2004; Calabrese et al., 2010).
Some studies suggest a link between cogni-
tive impairment and progression in the EDSS
(Lynch, Parmenter, & Denney, 2005), where-
as others do not (Kalmar, Gaudino, Moore,
Halper, & DeLuca, 2008).

5. Cognitive impairment has also been linked to
employment status; however, education lev-
el, fatigue, and workplace characteristics were
equally important contributors (Pompeii,
Moon, & McCrory, 2005).

6. Evaluation of cognitive impairment
a. Brief batteries and clinical assessments

are under investigation for reliability and
validity.

b. Informal evaluation of cognitive strengths
and deficits by nursing professionals

c. Refer for formal neuropsychological evalu-
ation by neuropsychologist, SLP, occupa-
tional therapist or other trained provider

7. Management of cognitive impairment
a. Cognitive rehabilitation (Mattioli, Stampa-

tori, Zanotti, Parrinello, & Capra, 2010).
i. Direct retraining of impaired

functions
ii. Memory exercises
iii. Attention training
iv. Compensatory strategies
v. Notebooks, lists, organizers
vi. Substitution strategies
vii. Time and energy management

b. Pharmacologic management
i. Disease-modifying therapy (Freed-

man et al., 2008)
ii. Anticholinesterase inhibitor treat-

ment with donepezil (Krupp et al.,
2004)

iii. Antifatigue agents, stimulants
iv. SSRIs

Recommendations: Nurses should work with
the patient, care partner, and other members of
the interdisciplinary team to develop an appro-
priate cognitive management program and re-
evaluate on an ongoing basis (Level 3). The nurse
should screen for factors that could increase cog-
nitive problems such as medications, sleep dis-
turbance, inadequately treated pain, and other
untreated symptoms (Level 2). Nurses need to
recognize and acknowledge the distressing nature

of cognitive deficits (Level 3). Patients should be
provided with verbal and written instructions re-
garding the need to reduce distractions and im-
plement safety measures (Level 3).

J. Mood dysregulation
1. Anxiety: Lifetime prevalence of any anxiety

disorder in MS is 36%, compared with 25% in
the general population (Korostil & Feinstein,
2007). Generalized anxiety disorder lifetime
prevalence in MS is substantially higher at
18.6% than in the general population, where it
is only 3% (Korostil & Feinstein). Lower EDSS
scores, fatigue, pain, and younger age at dis-
ease onset have been associated with symp-
toms of anxiety (Beiske et al., 2008).

2. Sleep disorders are also common in MS, with a
cumulative prevalence of all forms of sleep dys-
function reaching 47.5% (Merlino et al., 2009).

3. Depression
a. Prevalence studies demonstrate that de-

pressive symptoms occur in MS with a
range from 31.4% (Beiske et al., 2008) to
41.8% (Chwastiak & Ehde, 2007). Stud-
ies of lifetime prevalence of major depres-
sive disorder in MS find rates ranging from
22.8% to more than 50%, which is signifi-
cantly higher than that of the general pop-
ulation (Patten, Beck, Williams, Barbui, &
Metz, 2003).

b. Depression has been linked to neurobi-
ological changes in brain structure and
function in persons with MS (Passamonti
et al., 2009). Beta interferon, a commonly
used disease modifying therapy, has also
garnered interest as a potential cause of the
increased depression prevalence rate (Pan-
dya & Patten, 2002), but this association
has not held up in more rigorous studies
(Patten & Metz, 2002).

c. A direct relationship between depression
and disease severity has not been found.
Studies have found no relationship be-
tween depression and increased EDSS
scores (Brajković et al., 2009; Dahl, Stordal,
Lydersen, & Midgard, 2009). Comorbid fa-
tigue and younger age of MS onset have
been associated with depressive symptoms
(Beiske et al., 2008).

d. Depression has been shown to have direct
effects on multiple aspects of functional
impairment, including disease severity, ad-
herence to disease-modifying treatments,
and multiple QOL domains (Chwastiak &
Ehde, 2007; Paparrigopoulos, Ferentinos,

38 Nursing Management of the Patient with Multiple Sclerosis

Kouzoupis, Koutsis, & Papadimitriou,
2010).

e. Effective treatment of depression, includ-
ing telehealth modalities (Egner et al.), has
shown significant improvements in quality
of life (Hart, Vella, & Mohr, 2008).

f. Studies have found the suicide rate in per-
sons with MS to be twice that of a non-MS
sample (Caine & Schwid, 2002). Suicid-
al ideation is common in MS and appears
to be associated with depression, alcohol
abuse, and social isolation. Further, the se-
verity of depression and not the presence
of major depression alone is a strong pre-
dictor of suicide intent (Feinstein, 2002).

g. Despite the availability of effective treat-
ment and the high prevalence of depression
and suicide in MS, less than 30% of MS pa-
tients with depressive symptoms actively
seek care (Sollom & Kneebone, 2007).

h. Assessment of depressive symptoms and
suicidality
i. Ongoing assessment and monitoring

for depressive symptoms with stan-
dardized instruments (e.g., PSQ-9,
Beck Depression Inventory II, Center
for Epidemiologic Studies Depres-
sion Scale [CES-D])

ii. Positive endorsement of items should
prompt screening for suicidality.

iii. Evaluate medication profile for drugs
that may influence mood.

iv. Consult and refer with the multi-
disciplinary team as indicated by
assessment.

i. Management of depressive symptoms
i. Acknowledge existence of complex

and diverse changes caused by MS
and their effect on patients and care
partners.

ii. Activity and exercise (Reitberg,
Brooks, Uitdehaag, & Kwakkel, 2005;
Springer, Clark, Price, & Weldon,
2001)

iii. Counseling/cognitive behavioral
therapy (Thomas, Hillier, Galvin, &
Baker, 2006)

iv. Pharmacologic management (Table 8)
Recommendations: Nurses should work with
the patient, care partner, and other members of
the interdisciplinary team to manage depression
appropriately (Level 2). Other roles are to assist
patients and care partners to adjust to changes
involved in living with MS (Level 2); identify the

physical, emotional, spiritual, and educational
needs of the patient and family (Level 2); rein-
force the importance of medication regimen and
be aware of medication side effects (Level 2); be
alert to cues related to mood changes and treat-
ment outcomes (Level 2); and encourage par-
ticipation in a regular pattern of exercise to im-
prove mood (Level 1).

VIII. Patient and Care Partner Education
A. General concepts for patient and care partner

education
1. Successful combination requires prepared ed-

ucator and motivated, ready learner
2. More effective when every member of multi-

disciplinary team works toward agreed-on pa-
tient and family outcomes

3. Adult learning theory (Knowles, Holton, &
Swanson, 2005)

a. Because most people with MS are adults,
andragogy rather than pedagogy (focus is
on children) usually applies. Adult learning
theory is based on principles that adults as-
sume responsibility for learning and that
learning improves when the topic directly
relates to their lives.

b. Assumptions of learning
i. Adults with MS seek information

with a desire to improve their ability
to cope with the issues that MS pres-
ents in their lives.

ii. Learning is enhanced if patients per-
ceive education as increasing control
over their lives.

4. Domains of learning: Teaching patients with
MS and their care partners typically ad-
dresses the domains of knowledge (cogni-
tive), attitudes (affective), and behaviors
(psychomotor).

B. Goals (Holland, 2002; London, 2009; Syx, 2008)
1. Patient and family education provides MS

patients and their families with informa-
tion needed to promote active participation
in care, and enables patients and families to
make informed choices about health behav-
iors and engage in self-care with confidence
and competence.

2. Additional objectives include promoting max-
imum health potential toward wellness, cop-
ing and adaptation of the patient and family,
and empowerment toward improved quality
of life and hope.

3. Specific goals of patient and family education
in MS include (Halper, 2007a)

Nursing Management of the Patient with Multiple Sclerosis 39

a. Understanding the diagnosis and success-
fully coping with the potential effects on
one’s life

b. Planning in critical areas such as relation-
ships, parenting, employment, and lifestyle

c. Preventing potentially disabling outcomes,
with specific goals related to new symptoms

C. Role of the nurse (Halper, 2007a; Craven & Hirn-
le, 2008)

1. Assist individuals with activities that contrib-
ute to health or recovery that patients perform
unaided when possible (patient must have
strength, will, and knowledge)

2. Help individuals carry out prescribed therapy
3. Contribute to behavior change, resulting in

the knowledge and skills necessary to main-
tain and improve health

4. Assess and reassess patient understanding and
behavioral change

5. Promote and encourage adherence to
treatment

D. Concepts of learning
1. Experience is the richest source of adult learn-

ing. Although many patients and family
members have not had previous experience
with MS, most individuals have experienced
health-related issues that require coping skills.

2. Readiness to learn is important. Adults typi-
cally need and want to be self-directing, which
encourages independence.

3. Problem-solving approach to learning is pre-
ferred. Adults typically learn best when infor-
mation is presented in real-life context.

E. Learning needs in MS
The complexity of MS and its management re-
sult in a variety of learning needs for patients and
their families. The scope and depth of informa-
tion listed below depend on the patient’s and fam-
ily’s preferences (Fraser, Hadjimichael, & Vollmer,
2003; Halper, Costello, & Harris, 2006; Heesen,
Köpke, Richter, & Kasper, 2007; Köpke, Kasper,
Mühlhauser, Nübling, & Heesen, 2009; Kennedy,
2005; Pfohl, Costello, & Kennedy, 2005).
1. MS

a. Definition
b. Epidemiology
c. Pathophysiology
d. The disease course; classifications of MS;

long-term needs
e. Diagnosis: McDonald criteria
f. Diagnostics: laboratory and diagnostic tests

2. Treatment of the disease
a. Provide information about all treatment

options so patient can make an informed

commitment to therapy. Adherence is
greater when information includes realistic
expectations.

b. Include information on basic clinical tri-
al outcomes, mechanism of action, treat-
ments (administration, adverse effects and
management, resources for information
and financial assistance)

c. Disease-modifying therapies
d. Adherence (discuss benefits and identify

barriers to adherence)
3. MS-related symptoms

a. Common symptoms
b. Uncommon symptoms
c. Management of symptoms

4. Plan of care
a. Developed by the patient and the healthcare

team to include goals and interventions that
will delay progression of disability

b. Discuss when patient should call health-
care provider, and review process specific
to your office routine

5. Role of team members (Craven & Hirnle, 2008)
a. Physicians

i. Primary care physician: Emphasizes
the importance of regular and ongo-
ing follow-up of all primary health-
care needs, including preventive care
and appropriate screening. Often, pa-
tients with MS ignore general health
screening and checkups with primary
care physicians.

ii. Neurologist: Provides ongoing follow-
up and management of MS and MS-
related symptoms

b. MS nurses/advanced practice nurse (APN)
or physician’s assistant (PA)
i. Provides ongoing follow-up and

management of MS and MS-related
symptoms

ii. Healthcare promotion
a) Assesses patient and family for

health risks
b) Facilitates learner involvement in

setting healthy goals
c) Guides and supports problem

solving and decision making
d) Promotes self-care strategies to

enhance wellness
e) Reinforces health-promoting

behaviors
f ) Models healthy behaviors
g) Encourages primary health care

and preventive health screenings

40 Nursing Management of the Patient with Multiple Sclerosis

c. Other health care professionals
i. Rehabilitation specialists: physiatrist,

physical therapist, occupational ther-
apist, SLP

ii. Specialists: urologist, orthopedist, gy-
necologist, psychiatrist

iii. Counselor/Psychologist/Licensed-
certified Social Worker (LCSW)

iv. Case Manager
6. Relapse management options

a. Support network
i. Benefits of staying socially connected
ii. Family and friends
iii. MS support groups
iv. MS organizations
v. Religious organizations
vi. Volunteer support

b. Resources
i. Healthcare providers
ii. MS organizations
iii. Literature
iv. Websites

F. Factors that affect learning (Chiovetti, 2006;
Donaldson, Rutledge, & Pravikoff, 1999; Giger &
Davidhizar, 2004; Glick, 2005; London, 2008)

1. Patient’s understanding of the health problem
2. Health beliefs and practices
3. Cultural competence

a. Defined as working relationship within a
system of language and culture that is de-
pendent on history and heritage

b. Cultural health benefits
i. Affect how individuals think and feel

about health and health problems
ii. Affect when and from whom they

seek health care
iii. Affect how they respond to health-

care recommendations
iv. Provide a context through which

meaning is gained
v. Cultural values guide actions and de-

cision making that facilitates self-
worth and self-esteem

c. Influence of culture on the individual: each
patient is culturally unique
i. Identify patients at risk and adapt

teaching method
ii. Promote cultural literacy

4. Health literacy (will affect how nurse teaches
patients and their families; Cutilli, 2005)

a. Defining attributes
i. Reading and numeracy skills
ii. Comprehension

iii. Capacity to obtain, understand, and
use information in healthcare deci-
sion making

b. Health literacy empowers individuals to
i. navigate healthcare system
ii. act appropriately in new health-

related circumstances.
c. Consequences of health literacy

i. Increased healthcare knowledge
ii. Improved health status
iii. Adherence to healthcare

recommendations
iv. Appropriate use of healthcare

services
5. Support system and role of the family

a. Recognize the power and importance of
family

b. Assess the extent to which others (family,
significant other, friends, support groups)
may enhance learning and offer support
and encouragement

6. Cognitive dysfunction
a. Approximately 50% of individuals with

MS will experience cognitive dysfunction,
which may affect their ability to concen-
trate, learn, and recall new information
and make it difficult for them to follow the
plan of care.

b. Providing information verbally as well as
in writing enables patients, families, and
care partners to review information later.

7. Learning style
a. Individualize learning for patient’s pre-

ferred learning style.
b. Select tools to meet the patient and family’s

needs.
c. Use a variety of teaching methods.

8. Economic factors
a. Financial concerns regarding healthcare

costs may affect the patient’s ability to ad-
here to treatment recommendations.

b. Financial concerns may increase anxiety,
which in turn may affect learning.

9. Emotional state
a. Patients with MS may experience mood

disorders such as depression, which can
significantly affect readiness to learn.

b. Be alert to symptoms, discuss with patient
and family, and refer the patient for inter-
vention as needed.

10. Acute illness, such as relapse or an illness un-
related to MS, can affect patient’s readiness
and ability to learn.

Nursing Management of the Patient with Multiple Sclerosis 41

11. Psychomotor ability
a. Physical disability may lead to difficulty in

performing demonstrations requiring co-
ordination and strength.

b. Modify teaching strategy and include fam-
ily and/or care partner for support.

G. Plan: Teaching strategies
1. Lectures and groups

a. Involve learners and individualize the
teaching session by using interactive
exercises.

b. Connect content to real-life experiences.
c. Ask open-ended questions that require

thought.
2. One-to-one discussions with patient and

family
a. Give the patient and family time to take

notes. At end of the session, ask patient
and family to discuss their notes to ensure
accuracy of information.

b. The act of writing may help patients under-
stand and remember the information.

3. Demonstrations, such as injection technique
a. Choose appropriate hands-on tools.
b. Demonstrate procedure several times,

then ask the patient and family to return
demonstration.

c. Acknowledge and reinforce success.
4. Pamphlets, books, pictures

a. Discuss written information. Allow time
for questions and answers.

5. Audiovisuals
a. Choose videos and DVDs that are 20 min-

utes or less in length; use clear, direct,
and accurate language; and are culturally
appropriate

6. Internet programs
a. Use recognized authorities and provide pa-

tients with a list of recommended websites.
Ensure the information is evidence based
and current (i.e., are certified by the Health
On the Net Foundation [HON]).

H. Models of learning for wellness and healthcare
promotion (Anspaugh, Hamrick, & Rosato, 1991;
Stuifbergen, Becker, Rogers, Timmerman, &
Kullberg, 1999; Stuifbergen, Seraphine, & Rob-
erts, 2000)

1. Wellness: an expanded idea of health, mean-
ing more than “absence of disease.” The pres-
ence of well-being and dignity in the lives of
individuals, communities, and cultures. It is
the holistic integration of six interactive di-
mensions that continually influence each
other.

a. Environmental: healthy setting and self
protection

b. Physical: nutrition, fitness, and lifestyle
changes

c. Social: respect, relationships, intimacy, and
and tolerance

d. Spiritual: life meaning, purpose, and values
e. Intellectual: learning, growth, and new

challenges
f. Emotional: stress management, acceptance,

and expression of feelings
2. Clark (1986) describes wellness as striving in

a positive way, unique to an individual. People
can have MS and strive to be well and enjoy
life with meaning and purpose.

3. Processes to promote wellness
a. Provision of accurate information
b. Individual goal setting
c. Enhancement of self-efficacy
d. Patient recognizes the need for learning

and acceptance of new information.
e. Patient believes in his or her own abil-

ity to make and implement appropriate
behaviors.

f. Patient and family assume responsibility
for health care and self-monitoring.

Recommendations: Nurses should use an
evidence-based and wellness-focused approach
to education and counseling to assist patients
with MS and their families to adhere to the treat-
ment regimen, manage their symptoms, and cope
with their chronic disease (Level 3). The nurse
should screen for factors that could influence the
ability to learn, such as cognitive difficulties and
health literacy issues, and adapt teaching as ap-
propriate (Level 2).

42 Nursing Management of the Patient with Multiple Sclerosis

References
Akira, S., Takeda, K., & Kaisho, T. (2001). Toll-like receptors: Critical

proteins linking innate and acquired immunity. Natural Immunology,
2(8), 675–680.

Amato, M. P., Zipoli, V., & Portaccio, E. (2006). Multiple sclerosis-related
cognitive changes: A review of cross-sectional longitudinal studies.
Journal of the Neurological Sciences, 245, 41–46.

Anspaugh, D. J., Hamrick, M. H., & Rosato, F. D. (1991). Wellness: Con-
cepts and applications (p. 3). St. Louis, MO: Mosby.

Alonso, A., & Hernán, M. A. (2008). Temporal trends in the incidence of
multiple sclerosis: A systematic review. Neurology, 71(2), 129–135.

Alter, M., Kahana, E., & Loewenson, R. (1978). Migration and risk of
multiple sclerosis. Neurology, 28, 1089–1093.

Alter, M., Leibowitz, U., & Speer, J. (1966). Risk of multiple sclerosis
related to age at immigration to Israel. Archives of Neurology, 15,
234–237.

Archibald, C. J., Wei, X., Scott, J. N., Wallace, C. J., Zhang, Y., Metz, L. M.,
et al. (2004). Posterior fossa lesion volume and slowed information
processing in multiple sclerosis. Brain, 124(Pt. 7), 1526–1534.

Argaw, A. T., Zhang, Y., Snyder, B. J., Zhao, M., Kopp, N., Lee, S. C., et
al. (2006). IL-1 beta regulates blood-brain barrier permeability via
reactivation of the hypoxia-angiogenesis program. The Journal of
Immunology, 177(8), 5574–5584.

Ascherio, A., & Munger, K. (2007). Environmental risk factors for
multiple sclerosis. Part I: The role of injection. Annals of Neurology,
61, 288–299.

Ascherio, A., & Munger, K. (2008). Epidemiology of multiple sclerosis:
From risk factors to prevention. Seminars in Neurology, 28, 17–28.

Australia and New Zealand Multiple Sclerosis Genetics Consortium
(2009). Genome-wide association study identifies new multiple scle-
rosis susceptibility loci on chromosomes 12 and 20. Nature Genetics,
41(7), 824–828.

Awad, A., Hemmer, B., Hartung, H. P., Kieseier, B., Bennett, J. L., &
Stuve, O. (2010). Analyses of cerebrospinal fluid in the diagnosis
and monitoring of multiple sclerosis. Journal of Neuroimmunology,
219(1-2), 1–7.

Bader, M. K., & Littlejohns, L. L. (Eds.). (2010). AANN Core Curriculum
for Neuroscience Nursing. Glenview, IL: American Association of
Neuroscience Nurses.

Bakshi, R., Hutton, G. J., Miller, J. R., & Radue, E. W. (2004). The use of
magnetic resonance imaging in the diagnosis and long-term mana-
gement of multiple sclerosis. Neurology, 63(11 Suppl. 5), S3–S11.

Bakshi, R., Thompson, A. L., Rocca, M. A., Pelletier, D., Dousset, V.,
Barkhof, F., et al. (2008). MRI in multiple sclerosis: Current status
and future persepectives. The Lancet Neurology, 7, 615–625.

Bar-Or, A. (2010). Immunology and pathology of primary progressive
multiple sclerosis. International Journal of MS Care, 12(Suppl. 2),
16–18.

Baranzini, S. (2010). The genetics of primary progressive multiple sclero-
sis. International Journal of MS Care, 12(Suppl. 2), 19–21.

Beck, R. W., Trobe, J. D., Moke, P. S., Gal, R. L., Xing, D., Bhatti, M. T.,
et al. (2003). High- and low-risk profiles for the development of
multiple sclerosis within 10 years after optic neuritis: Experience of
the optic neuritis treatment trial. Archives of Ophthalmology, 121(7),
944–949.

Beiske, A. G., Svensson, E., Sandanger, I., Czujko, B., Pedersen, E. D.,
Aarseth, J. H., et al. (2008). Depression and anxiety among multiple
sclerosis patients. European Journal of Neurology, 15, 239–245.

Ben-Zacharia A., & Morgante, L. (2005). Genetics in multiple sclerosis: A
guide for nurses (2nd ed.). Hackensack, NJ: International Organizati-
on of Multiple Sclerosis Nurses.

Bergamaschi, R., Berzuini, C., Romani, A., & Cosi, V. (2001). Predicting
secondary progression in relapsing-remitting multiple sclerosis: A
Bayesian analysis. Journal of Neurological Science, 189(1-2), 34–44.

Bergamaschi, R., Romani, A., Versino, M., Poli, R., & Cosi, V. (1997).
Clinical aspects of fatigue in multiple sclerosis. Functional Neurology,
12(5), 247–251. 

Betts, C. D., D’Mellow, M. T., & Fowler, C. J. (1993). Urinary symptoms
and the neurological features of bladder dysfunction in multiple
sclerosis. Journal of Neurology, Neurosurgery, and Psychiatry, 56(3),
245–250.

Birnbaum, G. (2009). Multiple sclerosis: Clinician’s guide to diagnosis and
treatment. New York: Oxford University Press.

Bogaardt, H., van Dam, D., Wever, N., Bruggeman, C., Koops, J., &
Fokkens, W. (2009). Use of neuromuscular electrostimulation in the
treatment of dysphagia in patients with multiple sclerosis. Annals of
Otology, Rhinology & Laryngology, 8(4), 241–246.

Brajković, L., Bras, M., Milunovic, V., Busic, I., Boban, M., Loncar, Z., et
al. (2009). The connection between coping mechanisms, depression,
anxiety, and fatigue in multiple sclerosis. Collegium Antropologicum,
33(Suppl. 2), 135–140.

Brettschneider, J., Maier, M., Arda, S., Claus, A., Sussmuth, S. D.,
Kassaubek, J., et al. (2005). Tau protein level in cerebrospinal fluid is
increased in patients with early multiple sclerosis. Multiple Sclerosis,
11(3), 261–265.

Buhse, M. (2008). Assessment of caregiver burden in families of persons
with multiple sclerosis. The Journal of Neuroscience Nursing, 40(1),
25–31.

Bywater, A., & While, A. (2006). Management of bowel dysfunction in
people with multiple sclerosis. The British Journal of Nursing¸ 11(8),
333–334.

Caine, E. D., & Schwid, S. R. (2002). Multiple sclerosis, depression, and
the risk of suicide. Neurology, 59(5), 662–663.

Calabrese, M., Rinaldi, F., Mattsi, I., Grossi, P., Favaretto, A., Atzori, M.,
et al. (2010). Widespread cortical thinning characterizes patients
with MS with mild cognitive impairment. Neurology, 74(4), 321–328.

Calabresi, P. A. (2004). Diagnosis and management of multiple sclerosis.
American Family Physician, 70(10), 1935–1944.

Calcagno, P., Ruoppolo, G., Grass, M. G., De Vincentiis, M., & Paolucci,
S. (2002). Dysphagia in multiple sclerosis—Prevalence and prognos-
tic factors. Acta Neurologica Scandinavica, 105(1), 40–43.

Chari, D. M. (2007). Remyelination in multiple sclerosis. International
Review of Neurobiology, 79, 589–620.

Chiovetti, A. (2006). Bridging the gap between health literacy and patient
education for people with multiple sclerosis. Journal of Neuroscience
Nursing, 38(5), 374–378.

Chopra B., Abraham R., & Abraham A. (2002). CSF beta-1 Globulin—a
potential marker in differentiating multiple sclerosis and acute dis-
seminated encephalomyelitis: A preliminary study. Neurology India,
50(1):41–44.

Chwastiak, L. A., & Ehde, D. M. (2007). Psychiatric issues in multiple
sclerosis. Psychiatric Clinics of North America, 30(4), 803–817.

Clark, C. (1986). Wellness nursing: Concepts, theory, research, and practi-
ce. New York: Springer-Verlag.

Coggrave, M. (2008). Neurogenic continence. Part 3: Bowel management
strategies. The British Journal of Nursing, 17(15), 962–968.

Coggrave, M., Wiesel, P., & Norton, C. (2006). Management of faecal
incontinence and constipation in adults with central neurological
diseases. Cochrane Database of Systematic Reviews, 2, CD002115.

Nursing Management of the Patient with Multiple Sclerosis 43

Comi, G., Filippi, M., & Wolinsky, J. S. (2001). European/Canadian
multicenter, double-blind, randomized, placebo-controlled study
of the effects of glatiramer acetate on magnetic resonance imaging-
measured disease activity and burden in patients with relapsing
multiple sclerosis. Annals of Neurology, 49(3), 290–297.

Compston, A., & Coles, A. (2002). Multiple sclerosis. Lancet, 359(9313),
1221–1231.

Compston, A., Confavreux, C., Lassmann, H., McDonald, I., Miller, D.,
Noseworthy, J. et al. (2006). McAlpine’s multiple sclerosis (4th ed.).
Philadelphia: Elsevier.

Confavreux, C., & Vukusic, S. (2006). Natural history of multiple sclero-
sis: A unifying concept. Brain, 129, 606–616.

Confavreux, C., Vukusic, S., & Adeleine, P. (2003). Early clinical predic-
tors and progression of irreversible disability in multiple sclerosis: An
amnesic process. Brain, 126, 770–782.

Confavreux, C., Vukusic, S., Moreau, T., & Adeleine, P. (2000). Relapses
and progression of disability in multiple sclerosis. New England
Journal of Medicine, 343, 1430–1438.

Coo, H., & Aronson, K. J. (2004). A systematic review of several potential
non-genetic risk factors for multiple sclerosis. Neuroepidemiology, 23,
1–12.

Corry, M., & While, A. (2008). The needs of carers of people with
multiple sclerosis: A literature review. Scandavian Journal of Caring
Sciences, 23(3), 569–588.

Costello, K., & Halper, J. (Eds.). (2010a). Advanced practice nursing in
multiple sclerosis: Advanced skills, advancing responsibilities (3rd ed.).
New York: Bioscience Communications.

Costello, K., & Halper, J. (Eds.). (2010b). Multiple sclerosis: Key issues in
nursing management—Adherence, cognitive function, quality of life.
(3rd ed.). Washington, DC: Expert Medical Education.

Costello, K., Halper, J., & Harris, C. (Eds.). (2003). Nursing practice in
multiple sclerosis: A core curriculum. New York: Demos Medical
Publishing.

Coulthard-Morris, L. (2000). Clinical and rehabilitation outcome measu-
res. In J. S. Burks & K. P. Johnson (Eds.), Multiple sclerosis: Diagnosis,
medical management, and rehabilitation (pp. 221–228). New York:
Demos Medical Publishing.

Courtney, A. M., Treadaway, K., Remington, R., & Frohman, E. (2009).
Multiple sclerosis. Medical Clinics of North America, 93(2), 451–476.

Craven, R., & Hirnle, C. (2008). Fundamentals of nursing (6th ed.).
Philadelphia: Lippincott.

Cutilli, C. (2005). Health literacy: What you need to know. Orthopaedic
Nursing, 24(3), 227–233.

Dahl, O. P., Stordal, E., Lydersen, S., & Midgard, R. (2009). Anxiety and
depression in multiple sclerosis: A comparative population-based
study in Nord-Trøndelag County, Norway. Multiple Sclerosis, 15(12),
1495–1501.

Dalgas, U., Stenager, E., Jakobsen, J., Petersen, T., Hansen, H. J., Knudsen,
C., et al. (2009). Resistance training improves muscle strength
and functional capacity in multiple sclerosis. Neurology, 73(18),
1478–1484.

DasGupta, R., & Fowler, C. (2003). Bladder, bowel and sexual dysfun-
ction in multiple sclerosis: Management strategies. Drugs, 63(2),
153–166.

De Jager, P. L., Jia, X., Wang, J., de Bakker, P. I., Ottoboni, L., Aggarwal,
N., et al. (2009). Meta-analysis of genome scans and replications
identify CD6, RF8, TNFRSF1A as new multiple sclerosis susceptibili-
ty loci. Nature Genetics, 41(7), 776–782.

de Jong, B. A., Huizinga, T. W., Zanelli, E., Giphart, M. J., Bollen, E. L.,
Uitdehaag, B. M., et al. (2002). Evidence for additional genetic risk
indicators of relapse-onset MS within the HLA region. Neurology, 59,
549–555.

De Judicibus, M. A., & McCabe, M. P. (2007). The impact of the financial
costs of multiple sclerosis on quality of life. International Journal of
Behavioral Medicine, 14(1), 3–11.

Dean, G. K., & Kurtzke, J. F. (1971). On the risk of multiple sclerosis
according to age at immigration to South Africa. British Medical
Journal, 3, 725–729.

Debouverie, M., Pittion-Vouyovitch, S., Brissart, H., & Guillemin, F.
(2008). Physical dimension of fatigue correlated with disability chan-
ge over time in patients with multiple sclerosis. Journal of Neurology,
255(5), 633–636.

Diamond, B. J., Johnson, S. K., Kaufman, M., & Graves, L. (2008). Rela-
tionships between information processing, depression, fatigue and
cognition in multiple sclerosis. Archives of Clinical Neuropsychology,
23(2), 189–199.

Donaldson, N. E., Rutledge, D. N., & Pravikoff, D. S. (1999). Principles of
effective adult-focused patient education in nursing. Online Journal
of Clinical Innovations, 2(2), 1–22.

Dörr, J., Wernecke, K. D., Bock, M., Gaede, G., Wuerfel, J. T., Pfueller,
C.F., et al. (2011). Association of retinal and macular damage with
brain atrophy in multiple sclerosis. PLoS One, 6(4), e18132.

Earnshaw, S. R., Graham, J., Oleen-Burkey, M., Castelli-Haley, J., &
Johnson, K. (2009). Cost effectiveness of glatiramer acetate and
natalizumab in relapsing-remitting multiple sclerosis. Applied Health
Economics and Health Policy, 7(2), 91–108.

Ebers, G. C. (2008). Environmental factors and multiple sclerosis. Lancet
Neurology, 7, 268–277.

Edan, G., Miller, D., Clanet, M., Confavreux, C., Lyon-Caen, O.,
Lubetzki, C., et al. (1997). Th erapeutic eff ect of mitoxantrone com-(1997). Therapeutic effect of mitoxantrone com-
bined with methylprednisolone in multiple sclerosis: A randomised
multicentre study of active disease using MRI and clinical criteria.
Journal of Neurology, Neurosurgery, and Psychiatry, 62(2), 112–118.

Egner, A., Phillips, V. L., Vora, R., & Wiggers, E. (2003). Depression,
fatigue, and health-related quality of life among people with advan-
ced multiple sclerosis: Results from an exploratory telerehabilitation
study. NeuroRehabilitation, 18(2), 125–133.

Elian, M., Nightingale S., & Dean, G. (1990). Multiple sclerosis among
United Kingdom-born children of immigrants from the Indian
subcontinet, Africa and the West Indies. Journal of Neurology, Neu-
rosurgery, and Psychiatry, 53, 821–823.

Encinas, J. M., Manganas, L., & Enikolopov, G. (2005), Nitric oxide and
multiple sclerosis. Current Neurology and Neuroscience Reports, 5(3),
232–238.

Evans, A., & Boggs, J. (2010). Clinical utility of evoked potentials.
Retrieved January 27, 2011, from http://emedicine.medscape.com/
article/1137451-overview.

Feinstein, A. (2002). An examination of suicidal intent in patients with
multiple sclerosis. Neurology, 59(5), 674–678.

Filippi, M., Bozzali, M., Rovaris, M., Gonen, O., Kesavadas, C., Ghezzi,
A., et al. (2003). Evidence for widespread axonal damage at the
earliest clinical stage of multiple sclerosis. Brain, 126(Pt. 2), 433–443.

Fischer, J., Jak, A., Kniker, J., Rudick, M., & Cutter, G. (2001). Multiple
Sclerosis Functional Composite (MSFC): Administration and scoring
manual, revised. New York: National Multiple Sclerosis Society.

Fleming, J. O., & Carrithers, M. D. (2010). Diagnosis and management of
multiple sclerosis: A handful of patience. Neurology, 74, 876–877.

Fragoso, Y. D., Santana, D. L. B., & Pinto, R. C. (2008). The positive
effects of a physical activity program for multiple sclerosis patients
with fatigue. NeuroRehabilitation, 23(2), 153–157.

Franciotta, D., Salvetti, M., Lolli, F., Serafini, B., & Aloisi, F. (2008). B cells
and multiple sclerosis. Lancet Neurology, 7(9), 852–858.

Franklin, R. J., & Kotter, M. R. (2008). The biology of CNS remyelination:
The key to therapeutic advances. Journal of Neurology, 255(Suppl. 1),
19–25.

44 Nursing Management of the Patient with Multiple Sclerosis

Fraser, C., Hadjimichael, O., & Vollmer, T. (2003). Predictors of adhe-
rence to glatiramer acetate therapy in individuals with self-reported
progressive forms of multiple sclerosis. Journal of Neuroscience
Nursing, 35(3), 163–170.

Freedman, M. S., Hughes, B., Mikol, D. D., Bennett, R., Cuffel, B., Divan,
V., et al. (2008). Efficacy of disease-modifying therapies in relapsing-
remitting multiple sclerosis: A systematic comparison. European
Journal of Neurology, 60, 1–11.

Freedman, M. S., Thompson, E. J., Deisenhammer, F., Giovannoni, G.,
Grimsley, G., Keir, G., et al. (2005). Recommended standard of
cerebrospinal fluid analysis in the diagnosis of multiple sclerosis.
Archives of Neurology, 62, 865–870.

Frenette, J., Harris, C., Klassen, L., & McEwan, L. (2001). Symptom ma-
nagement. In J. Halper (Ed.), Advanced Concepts in Multiple Sclerosis
Nursing Care (pp. 207–210). New York: Demos Medical Publishing.

Frohman, E. M., Filippi, M., Stuve, O., Waxman, S. G., Corboy, J., Phil-
lips, J. T., et al. (2005). Characterizing the mechanisms of progression
in multiple sclerosis: Evidence and new hypothesis for future direc-
tions. Archives of Neurology, 62(9), 1345–1356.

Fromont, A., Couvreur, G., Guiguet, M., Giroud, M., Caudie, C., &
Moreau, T. (2005). Immunofixation compared to isoelectric focusing
in the detection of oligoclonal bands in cerebrospinal fluid of
multiple sclerosis patients. Review Neurology (Paris), 161(12 Pt. 1),
1183–1190.

Gasperini, C. (2001). Differential diagnosis in multiple sclerosis. Neuro-
logical Sciences. 22 Suppl 2:S93–97.

Giger, J. N., & Davidhizar, R. E. (2004). Transcultural Nursing (4th ed.).
St. Louis, MO: Mosby.

Giovannoni, G. (2010). Cerebrospinal fluid neurofilament: The bio-
marker that will resuscitate the ‘spinal tap.’ Multiple Sclerosis, 16(3),
285–286.

Glick, T. H. (2005). Evidence-guided education: Patient’s outcome data
should influence our teaching priorities. Academic Medicine, 80(2),
147–151.

Goldberg, L. D., Edwards, N. C., Fincher, C., Doan, Q. V., Al-Sabbagh,
A., & Meletiche, D. M. (2009). Comparing the cost-effectiveness of
disease-modifying drugs for the first-line treatment of relapsing-
remitting multiple sclerosis. Journal of Managed Care Pharmacy,
15(7), 543–555.

Goodin, D. S. (2004). Disease-modifying therapy in MS: A critical review
of the literature. Part II: Assessing efficacy and dose-response. Journal
of Neurology, 251(Suppl. 5), v50–v56.

Goodin, D. S., Biermann, L. D., Bohlega, S., Boiko, A., Chofflon, M.,
Gebeily, S., et al. (2007). Integrating an evidence-based assessment of
benefit and risk in disease-modifying treatment of multiple sclerosis.
Current Medical Research and Opinion, 23(11), 2823–2832.

Gronseth, G., & Ashman, E. (2000). Practice parameter: The usefulness
of evoked potentials in identifying clinically silent lesions in patients
with suspected multiple sclerosis. An evidence-based review: Report
of the Quality Standards Subcommittee of the American Academy of
Neurology. Neurology, 54(9), 1720–1725.

Guimarães, I., Cardoso, M. I., & Sá, M. J. (2006). Tau protein seems not
to be a useful routine clinical marker of axonal damage in multiple
sclerosis. Multiple Sclerosis, 12(3), 354–356.

Gulick, E. E. (1989). Model confirmation of the MS-related symptom
checklist. Nursing Research, 38(3):147–153.

Gulick, E. E. (1998). Symptom and activities of daily living trajectory in
multiple sclerosis: A 10-year study. Nursing Research, 47(3):137–146.

Hadjimichael, O., Volmer, T., & Oleen-Burkey, M. (2008). Fatigue
characteristics in multiple sclerosis: The North American Research
Committee on Multiple Sclerosis (NARCOMS) survey. Health &
Quality of Life Outcomes, 6, 100–102.

Halper, J. (Ed.). (2007a). Advanced concepts in multiple sclerosis nursing
care. New York: Demos Medical Publishing.

Halper, J. (2007b). Managing difficult symptoms. In J. Halper (Ed.), Ad-
vanced concepts in multiple sclerosis nursing care (2nd ed., pp. 11–12).
New York: Demos Medical Publishing.

Halper, J., Costello, K., & Harris, C. (Eds.). (2006). Nursing practice in
multiple sclerosis: A core curriculum (2nd ed.). New York: Demos
Medical Publishing.

Halper, J., & Ross, A. P. (2010) Challenges in the treatment of mobility
loss and walking impairment in multiple sclerosis. International
Journal of MS Care, 13, 13–16.

Hammond, S. R., English, D. R., & McLeod, J. G. (2000). The age-range
of risk of developing multiple sclerosis: Evidence from a migrant
population in Australia. Brain, 123, 968–974.

Harris, C. J., & Halper, J. (Eds.). (2004). Multiple sclerosis: Best practices in
nursing care—Disease management, pharmacologic treatment, nursing
research. (2nd ed.). New York: Bioscience Communications.

Harris, C. J., & Halper, J. (2008). (Eds.). Multiple sclerosis: Best practices in
nursing care—Disease management, pharmacologic treatment, nursing
research (3rd ed.). New York: Bioscience Communications.

Harris, V. K., & Sadiq, S. A. (2009). Disease biomarkers in multiple
sclerosis: Potential for use in therapeutic decision making. Molecular
Diagnosis & Therapy, 13(4), 225–244.

Hart, S. L., Vella, L., & Mohr, D. C. (2008). Relationships among dep-
ressive symptoms, benefit-finding, optimism, and positive affect in
multiple sclerosis patients after psychotherapy for depression. Health
Psychology, 27(2), 230–238.

Hartung, H., Gonsette, R., Konig, N., Kwiecinski, H., Guseo, A., Morris-
sey, S. P., et al. (2002). Mitoxantrone in progressive multiple sclerosis:
A placebo-controlled, double-blind, randomised, multicentre trial.
Lancet, 360(9350), 2018–2025.

Hedström, A. K., Bäärnhielm, M., Olsson, T., & Alfredsson, L. (2009).
Tobacco smoking, but not Swedish snuff use, increases the risk of
multiple sclerosis. Neurology, 73(9), 696–701.

Heesen, C., Köpke, S., Richter, T., & Kasper, J. (2007). Shared decision
making and self-management in multiple sclerosis: A consequence of
evidence. Journal of Neurology, 254(Suppl. 2), 116–121.

Hernán, M. A., Jick, S. S., Lorgroscino, G., Olek, M. J., Ascherio, A., &
Jick, H. (2005). Cigarette smoking and the progression of multiple
sclerosis. Brain, 128, 1461–1465.

Hernán, M. A., Olek, M. J., & Ascherio, A. (2001). Cigarette smoking and
incidence of multiple sclerosis. American Journal of Epidemiology,
154, 69–74.

Hische, E. A., van der Helm, H. J., & van Walbeek, H. K. (1982). The
cerebrospinal fluid immunoglobulin G index as a diagnostic aid in
multiple sclerosis: A Bayesian approach. Clinical Chemistry, 28(2),
354–355.

Hoeman, S. P. (2008). Rehabilitation nursing: Prevention, intervention,
and outcomes (4th ed.). St. Louis, MO: Mosby Elsevier.

Holland, N. J. (2002). Patient and family education. In J. Hapler & N. J.
Holland (Eds.), Comprehensive nursing care in multiple sclerosis (2nd
ed., pp. 193). New York: Demos Medical Publishing.

Huijbregts, S. C. J., Kalkers, N. F., de Sonneville, L. M. J., de Groot, V.,
Reuling, I. E. W., & Polman, C. H. (2004). Differences in cognitive
impairment of relapsing remitting, secondary, and primary progres-
sive MS. Neurology, 63, 335–339.

Hutchinson, M. (2009). Predicting and preventing the future: Actively
managing multiple sclerosis. Practical Neurology, 9(3), 133–143.

The INFB Multiple Sclerosis Study Group & the University of British Co-
lumbia MS/MRI Analyses Group. (1998). Randomized double-blind
placebo-controlled study of interferon B-1a in relapsing remitting
multiple sclerosis. Lancet, 352, 1498–1504.

International Multiple Sclerosis Genetics Consortium. (2007). Risk
alleles for multiple sclerosis identified in genome wide study. New
England Journal of Medicine, 357, 851–862.

Nursing Management of the Patient with Multiple Sclerosis 45

Jacobs, L. D., Cookafiar, D. L., Rudick, R. A., Herndon, R. M., Richert,
J. R., Salazar, A. M., et al. (1996). Intramuscular interferon beta-1a
for disease progression in relapsing multiple sclerosis. Annals of
Neurology, 39(3), 285–294.

Jasperse, B., Jakobs, C., Eikelenboom, M. J., Dijkstra, C. D., Uitdehaag, B.
M., Barkhof, F., et al. (2007). N-acetylaspartic acid in cerebrospinal
fluid of multiple sclerosis patients determined by gas-chromato-
graphy-mass spectrometry. Journal of Neurology, 254(5), 631–637.

Jiménez-Jiménez, F. J., Zurdo, J. M., Hernanz, A., Medina-Acebron, S., de
Bustos, F., Barcenilla, B., et al. (2002). Tau protein concentrations in
cerebrospinal fluid of patients with multiple sclerosis. Acta Neurologi-
ca Scandinavica, 106(6), 351–354.

Johansson, S., Ytterberg, C., Gottberg, K., Widén Holmqvist, L., & von
Koch, L. (2009). Use of health services in people with multiple sclero-
sis with and without fatigue. Multiple Sclerosis, 15, 88–95.

Johnson, K. P., Brooks, B. R., Ford, C. C., Goodman, A. D., Lisak, R. P.,
Myers, L.W., et al. (2003). Glatiramer acetate (Copaxone): Compa-
rison of continuous versus delayed therapy in a six-year organized
multiple sclerosis trial. Multiple Sclerosis, 9(6), 585–591.

Johnson, S. L. (2008). The concept of fatigue in multiple sclerosis. Journal
of Neuroscience Nursing, 40(2), 72–77.

Kalmar, J. H., Gaudino, E. A., Moore, N. B., Halper, J., & DeLuca, J.
(2008). The relationship between cognitive deficits and everyday
functional activities in multiple sclerosis. Neuropsychology, 22(4),
442–449.

Kantarci, O. (2008). Genetics and natural history of multiple sclerosis.
Seminars in Neurology, 28(1), 7–16.

Kantarci, O., Siva, A., Eraksoy, M., Karabudak, R., Sütlas, N., Ağaoğlu,
J., et al. (1998). Survival and predictors of disability in Turkish MS
patients. Neurology, 51(3), 765–772.

Kantarci, O., & Weinshenker, B. G. (2005). Natural history of multiple
sclerosis. Neurology Clinics, 23, 17–38.

Kantarci, O., & Wingerchuck, D. (2006). Epidemiology and natural histo-
ry of multiple sclerosis: New insights. Current Opinions in Neurology,
19(3), 248–254.

Kennedy, P. (2005). Patient expectations of therapy combining reality
and hope. International Journal of MS Care, 7(Suppl. 4), 15–19.

Knowles, M., Holtron, E., & Swanson, R. (2005). The adult learner (6th
ed., pp. 11, 14, 49, 62–63, 94–96). Burlington, MA: Elsevier.

Kobelt, G., Berg, J., Atherly, D., & Hadjimichael, O. (2006). Costs and
quality of life in multiple sclerosis: A cross-sectional study in the
United States. Neurology, 66(11), 1696–1702.

Köpke, S., Kasper, J., Mühlhauser, I., Nübling, M., & Heesen, C. (2009).
Patient education program to enhance decision autonomy in mul-
tiple sclerosis relapse management: A randomized-controlled trial.
Multiple Sclerosis, 15(1), 96–104.

Korostil, M., & Feinstein, A. (2007). Anxiety disorders and their clinical
correlates in multiple sclerosis patients. Multiple Sclerosis, 13(1),
67–72.

Kos, D., Kerckhofs, E., Nagels, G., D’Hooghe, M. B., & Ilsbroukx, S.
(2008). Origin of fatigue in multiple sclerosis: Review of the literatu-
re. Neurorehabilitation and Neural Repair, 22, 91–100.

Krishnan, V., & Jaric S. (2008). Hand function in multiple sclerosis:
Force coordination in manipulation tasks. Clinical Neurophysiology,
119(10), 2274–2281.

Krupp, L. (2004). Fatigue in multiple sclerosis: A guide to diagnosis and
management. New York: Demos Medical Publishing.

Krupp, L. B., Christodoulou, C., Melville, P., Scherl, W. F., MacAllister, W.
S., & Elkins, L. E. (2004). Donezepil improved memory in multiple
sclerosis in a randomized clinical trial. Neurology, 63(9), 1579–1585.

Kurtzke, J. F. (1983). Rating neurological impact in multiple sclerosis: An
expanded disability scale. Neurology, 33, 1444–1452.

Kurtzke, J. F., Beebe, G. W., & Norman, J. E. (1985). Epidemiology of
multiple sclerosis in US Veterans: III. Migration and the risk of MS.
Neurology, 35, 672–678.

Laron, M., Cheng, H., Zhang, B., Schiffman, J. S., Tang, R. A., & Fri-
shman, L. J. (2009). Assessing visual pathway function in multiple
sclerosis with multifocal visual evoked potentials. Multiple Sclerosis,
15(12), 1431–1441.

Lehmensiek, V., Süssmuth, S. D., Tauscher, G., Brettschneider, J., Felk, S.,
Gillardon, F., et al. (2007). Cerebrospinal fluid proteome profile in
multiple sclerosis. Multiple Sclerosis, 13(7), 840–849.

Levin, L. I., Munger, K. L., O’Reilly, E. J., Falk, K. I., & Ascherio, A.
(2010). Primary infection with the Epstein Barr virus and risk of
multiple sclerosis. Annals of Neurology, 67(6), 824–830.

Link, H., & Huang, Y. M. (2006). Oligoclonal bands in multiple sclerosis
cerebrospinal fluid: An update on methodology and clinical useful-
ness. Journal of Neuroimmunology, 180(1-2), 17–28.

Lisak, D. (2001). Overview of symptomatic management of multiple
sclerosis. Journal of Neuroscience Nursing, 33(5), 224–230.

Liu, S., Bai, S., Qin, Z., Yang, Y., Cui, Y., & Qin, Y. (2009). Quantitative
proteomic analysis of the cerebrospinal fluid of patients with multiple
sclerosis. Journal of Cellular and Molecular Medicine, 13(8A),
1586–1603.

Logemann, J. A. (2000). Dysphagia in multiple sclerosis. In J. Burks & K.
Johnson (Eds.), Multiple sclerosis: Diagnosis, medical management,
and rehabilitation (pp. 485–490). New York: Demos Medical Publis-
hing.

London, F. (2008). Meeting the challenge: Patient education in diverse
America. Journal for Nurses in Staff Development, 24(6), 283–285.

London, F. (2009). No time to teach: The essence of patient and family
education for healthcare providers. Atlanta, GA: Pritchett and Hull.

Lublin, F. D. (2010). Issues related to the diagnosis of primary progressi-
ve multiple sclerosis. International Journal of MS Care, 12(Suppl. 2),
9–11.

Lublin, F. D., & Reingold, S. C. (1996). Defining the clinical course of
multiple sclerosis: Results of an international survey. Neurology, 46,
907–911.

Lynch, S. G., Parmenter, B. A., & Denney, D. R. (2005). The association
between cognitive impairment and physical disability in multiple
sclerosis. Multiple Sclerosis, 11(4), 469–476.

Maloni, H. (2007). Pain in mutiple sclerosis. In J. Halper (Ed.), Advanced
concepts in multiple sclerosis nursing care (2nd ed., pp. 187–212). New
York: Demos Medical Publishing.

Markowitz, C. (2010). Symptomatic therapy of multiple sclerosis.
Continuum: Lifelong learning in neurology. Multiple Sclerosis, 16(5),
90–104.

Marrie, R. A. (2004). Environmental risk factors in multiple sclerosis
aetiology. Lancet Neurology, 3, 709–718.

Mattioli, F., Stampatori, C., Zanotti, D., Parrinello, G., & Capra, R.
(2010). Efficacy and specificity of intensive cognitive rehabilitation of
attention and executive functions in multiple sclerosis. Journal of the
Neurological Sciences, 288(1-2), 101–105.

McAuley, E., White, S. M., Rogers, L. Q., Motl, R. W., & Courneya, K.
S. (2010). Physical activity and fatigue in breast cancer and multiple
sclerosis: Psychosocial mechanisms. Psychosomatic Medicine, 72(1),
88–96.

McCabe, M. P. (2002). Relationship functioning and sexuality among
people with multiple sclerosis. Journal of Sex Research, 39(4),
302–309.

McCance, K. L., Huether, S. E., Brashers, V. L., & Rote, N. S. (2010).
Pathophysiology: The biologic basis for disease in adults and children
(6th ed.). Maryland Heights, MO: Mosby Elsevier.

Melnyk, B. M. (2004). Evidence digest: Levels of evidence. Worldviews on
Evidence-Based Nursing, 1, 142–145.

46 Nursing Management of the Patient with Multiple Sclerosis

Merlino, G., Fratticci, L., Lenchig, C., Valente, M., Cargnelutti, D., Picel-
lo, M., et al. (2009). Prevalence of “poor sleep” among patients with
multiple sclerosis: An independent predictor of mental and physical
status. Sleep Medicine, 10(1), 26–34.

Miller, D. H., & Leary, S. M. (2007). Primary-progressive multiple sclero-
sis. Lancet Neurology, 6, 903–912.

Miller, D. H., Weinshenker, B. G., Filippi, M., Banwell, B.I., Cohen, J. A.,
Freedman, M. S., et al. (2008). Differential diagnosis of suspected
multiple sclerosis: A consensus approach. Multiple Sclerosis, 14(9),
1157–1174.

Mills, R. J., Yap, L., & Young, C. A. (2007). Treatment for ataxia in
multiple sclerosis. Cochrane Database of Systematic Reviews, 1,
CD005029.

Mills, R. J., Young, C. A., Pallant, J. F., & Tennant, A. (2010). Develop-
ment of a patient reported outcome scale for fatigue in multiple
sclerosis: The Neurological Fatigue Index (NFI-MS). Health and
Quality of Life Outcomes, 8, 22. 

Motl, R. W. (2008). Physical activity and its measurement and determi-
nants in multiple sclerosis. Minerva Medica, 99(2), 157–165.

Motl, R. W., & Gosney, J. L. (2008). Effect of exercise training on quality
of life in multiple sclerosis: A meta-analysis. Multiple Sclerosis, 14(1),
129–135.

Motl, R. W., & McAuley, E. (2009). Pathways between physical activity
and quality of life in adults with multiple sclerosis. Health Psychology,
28(6), 682–689.

Munger, K. L., Levin, L. I., Hollis, B. W., Howard, N. S., & Ascherio,
A. (2006). Serum 25-hydroxyvitamin D levels and risk of multiple
sclerosis. The Journal of the American Medical Association, 296,
2832–2838.

Munger, K. L., Zhang, S. M., O’Reilly, E., Hernán, M. A., Olek, M. J., Wil-
lett, W. C., et al. (2004). Vitamin D intake and incidence of multiple
sclerosis. Neurology, 62, 60–65.

Mutch, K. (2010). In sickness and in health: Experience of caring for a
spouse with MS. British Journal of Nursing, 19(4), 214–219.

National Multiple Sclerosis Society (2009). Vision Problems: The Basic
Facts. Retrieved September 19, 2011, from www.nationalmssociety.
org/multimedia-library/brochures/managing-specific-issues/index.
aspx.

Neuhaus, O., Archelos, J. J., & Hartung, H. P. (2003). Immunomodulati-
on in multiple sclerosis: From immunosuppression to neuroprotecti-
on. Trends in Pharmacological Sciences, 24, 131–138.

Nielsen, J. M., Korteweg, T., & Polman C. H. (2007). Diagnosing MS:
Recent guidelines and future goals focusing on magnetic resonance
imaging. The International MS Journal, 14, 29–34.

Nocentini, U., Pasqualetti, P., Bonavita, S., Buccafusca, M., De Caro,
M. F., Farina, D., et al. (2006). Cognitive dysfunction in patients
with relapsing-remitting multiple sclerosis. Multiple Sclerosis,
12, 77–87. Noseworthy, J. H., Lucchinetti, C., Rodriguez, M., &
Weinshenker, B. G. (2000). Multiple sclerosis. New England Journal of
Medicine, 343, 938–952.

O’Connor, P. (2005). Clinical results from AFFIRM: A randomized,
double-blind, placebo-controlled, multicenter trial to determine the
efficacy and safety of natalizumab in patients with relapsing multiple
sclerosis (MS). Paper presented at the 57th Annual Meeting of the
American Academy of Neurology, Miami Beach, FL.

Oertle, T., van der Haar, M. E., Bandtlow, C. E., Robeva, A., Burfeined,
P., Buss, A., et al. (2003). Nogo-A inhibits neurite outgrowth and cell
spreading with three discrete regions. The Journal of Neuroscience,
23(13), 5393–5406.

Oh, Y., Oh, D., Jeong, S., Koo, J., & Kim, J. (2008). Sequential bilateral
hearing loss in multiple sclerosis. Annals of Otology, Rhinology &
Laryngology, 117(3), 186–191.

O’Leary, M. L., & Dierich, M. (2010). Urinary tract dysfunction in neu-
rological disorders: The nurses role in assessment and management.
Journal of Neuroscience Nursing, 42(2), E8–E23.

Olek, M. J. (Ed.). (2005). Multiple sclerosis: Etiology, diagnosis, and new
treatment strategies. Totowa, NJ: Humana Press.

Olerup, O., Carlsson, B., Wallin, J., Olsson, T., Fredrikson, S., Ernerudh,
J., et al. (1987). Genomic HLA typing by RFLP analysis, using DR
beta and DQ cDNA beta probes reveals normal DR-DQ linkages in
patients with multiple sclerosis. Tissue Antigens, 38, 1–15.

Pandya, R., & Patten, S. (2002). Depression in multiple sclerosis asso-
ciated with interferon beta-1a. Canadian Journal of Psychiatry, 47(7),
686.

Panitch, H. S., Hirsch, R. L., Schindler, J., & Johnson, K. P. (1987). Exa-
cerbations associated with activation of the immune system. Lancet,
1(8538), 893–895.

Paparrigopoulos, T., Ferentinos, P., Kouzoupis, A., Koutsis, G., & Papa-
dimitriou, G. N. (2010). The neuropsychiatry of multiple sclerosis:
Focus on disorders of mood, affect, and behavior. International
Review of Psychiatry, 22(1), 14–21.

Passamonti, L., Ceresa, A., Liguori, M., Gioia, M. C., Valentino, P.,
Nisticò, R., et al. (2009). Neurobiological mechanisms underlying
emotional processing in relapsing-remitting multiple sclerosis. Brain,
132(12), 3380–3391.

Patten, S. B., Beck, C. A., Williams, J. V., Barbui, C., & Metz, L. M. (2003).
Major depression in multiple sclerosis: A population-based perspec-
tive. Neurology, 61(11), 1524–1527.

Patten, S. B., & Metz, L. M. (2002). Interferon B-1a and depression in se-
condary progressive MS: Data from the SPECTRIMS trial. Neurology,
59, 744–746.

Pellat, G. (2008). Neurogenic continence. Part 1: Pathophysiology and
quality of life. British Journal of Nursing, 17(13), 836–841.

Pellat, G., & Geddis, T. (2008). Neurogenic continence. Part 2: Neuroge-
nic bladder management. British Journal of Nursing, 17(14), 904, 906,
908–913.

Penner, I., & Calabrese, P. (2010). Managing fatigue: Clinical correlates,
assessment procedures and therapeutic strategies. The International
MS Journal, 17(1), 28–34.

Pernet, V., Joly, S., Christ, F. D., Dimou, L., & Schwab, M. E. (2008).
Nogo-A and myelin-associated glycoprotein differently regulate
oligodendrocyte maturation and myelin formation. The Journal of
Neuroscience, 28(29), 7435–7444.

Peterson, A. T., Kornbluth, I., Marcus, D. B., Saulino, M. F., & Hung, C.
H. (2004). Handbook of Physical medicine & rehabilitation. Philadel-
phia: Elsevier, Inc.

Pfohl, D., Costello, K., & Kennedy, P. (2005). Managing patient expecta-
tions. Multiple Sclerosis Counseling Points, 1(1), 3.

Pittock, S. J., McClelland, R. L., Mayr, W. T., Jorgensen, N. W., Wein-
shenker, B. G., Noseworthy, J., et al. (2004). Clinical implications of
benign multiple sclerosis: A 20-year population-based follow-up
study. Annals of Neurology, 56(2), 303–306.

Plant, G. T. (2008). Optic neuritis and multiple sclerosis. Curriculum
Opinion In Neurology, 21(1), 16–21.

Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H., Kap-
pos, L., et al. (2005). Diagnostic criteria for multiple sclerosis: 2005
revisions to the “McDonald Criteria.” Annals of Neurology, 58(6),
840–846.

Polman, C. H., Reingold, S. C., Edan, G., Filippi, M., Hartung, H., Kap-
pos, L., et al. (2011). Diagnostic criteria for multiple sclerosis: 2010
revisions to the “McDonald Criteria.” Annals of Neurology, 29(2),
292–302.

Pompeii, L. A., Moon, S. D., & McCrory, D. C. (2005). Measures of phy-
sical and cognitive function and work status among individuals with
multiple sclerosis: A review of the literature. Journal of Occupational
Rehabilitation, 15(1), 69–84.

Nursing Management of the Patient with Multiple Sclerosis 47

Porth, C. M., & Matfin, G. (2008). Pathophysiology: Concepts of altered
health states (8th ed.). Philadelphia: Lippincott Williams & Wilkins.

Poser, C. M., Paty, D. W., Scheinberg, L., McDonald, W. I., Davis, F. A.,
Ebers, G. C., et al. (1983). New diagnostic criteria for multiple scle-
rosis: Guidelines for research protocols. Annals of Neurology, 13(3),
227–231.

Prevention of Relapses and Disability by Interferon beta-1a Subcuta-
neously in Multiple Sclerosis (PRISMS) Study Group. (1998). Rando-
mised double-blind placebo-controlled study of interferon beta-1a in
relapsing/remitting multiple sclerosis. Lancet, 352(9139), 1498–1504.

Prosiegel, M., Schelling, A., & Wagner-Sonntag, E. (2004). Dysphagia
and multiple sclerosis. International Multiple Sclerosis Journal, 11(1),
22–31.

Racke, M. K. (2008). The role of B cells in multiple sclerosis: Rationale
for B cell targeted therapies. Current Opinion in Neurology, 21(Suppl.
1), S9–S18.

Rammohan, K. W. (2009). Cerebrospinal fluid in multiple sclerosis.
Annals of Indian Academy of Neurology, 12(4), 246–253.

Rantell, A. (2009). Lower urinary tract symptoms in women with
multiple sclerosis: 2. The British Journal of Nursing, 18(15), 922–925.

Rietberg, M. B., Brooks, D., Uitdehaag, B. M .J., & Kwakkel, G. (2005).
Exercise therapy for multiple sclerosis. Cochrane Database of Syste-
matic Reviews, 1, CD003980.

Riise, T., Gronning, M., Fernandez, O., Lauer, K., Midgard, R., Minder-
hound, J. M., et al. (1992). Early prognostic factors for disability in
mulitple sclerosis, a European multicenter study. Acta Neurologica
Scandinavica, 85(3), 212–218.

Riskind, P. N. (2007). Multiple sclerosis; Continuum: Lifelong learning in
neurology. Neuroendocrinology, 15(2), 148–178.

Rolak, L. A., & Fleming, J. O. (2007). The differential diagnosis of multip-
le sclerosis. The Neurologist, 13(2), 57–72.

Ross, A. P. (2008). Tolerability, adherence, and patient outcomes. Neuro-
logy, 71(Suppl. 3), S21–S23.

Rudick, R. A., Fisher, E., Lee, J. C., Simon, J., & Jacobs, L., Multiple
Sclerosis Collaborative Research Group. (1999). Use of the brain
parenchymal fraction to measure whole brain atrophy in relapsing-
remitting MS. Neurology, 53, 1698–1704.

Rudick, R. (2004). Contemporary diagnosis and management of multiple
sclerosis. Newtown, PA: Hand Books in Health Care.

Rudick, R. (2005). SENTINEL: A randomized, double-blind, placebo-
controlled, multicenter trial to determine the efficacy and safety of
natalizumab, when added to intramuscular interferon beta-1a, in
patients with relapsing multiple sclerosis (MS)—One-year clinical
and MRI results. Paper presented at the 57th Annual Meeting of the
American Academy of Neurology, Miami Beach, FL.

Rumrill, P. (2009). Multiple sclerosis: Medical and psychosocial aspects,
etiology, incidence and prevalence. Journal of Vocational Rehabilitati-
on¸ 31(1), 75–82.

Runmarker, B., & Andersen, O. (1993). Prognostic factors in a multiple
sclerosis incidence cohort with twenty-five years of follow-up. Brain,
116(Pt. 1),117–134.

Sadovnick, A. D., Eisen, K., Ebers, G. C., & Paty, D. W. (1991). Cause of
death in patients attending multiple sclerosis clinics. Neurology,41(8),
1193–1196.

Salzer, J., Svenningsson, A., & Sundström, P. (2010). Neurofilament light
as a prognostic marker in multiple sclerosis. Multiple Sclerosis, 16(3),
287–292.

Sayao, A. L., Devonshire, V., & Tremlett, H. (2007). Longitudinal follow-
up of “benign” multiple sclerosis at 20 years. Neurology, 68, 496–500.

Schapiro, R. T. (2007). Managing the symptoms of multiple sclerosis (5th
ed.). New York: Demos Medical Publishing.

Schreurs, K., de Ridder, D. T., & Bensing, J. M. (2002). Fatigue in mul-Fatigue in mul-
tiple sclerosis: Reciprocal relationships with physical disabilities and
depression. Journal of Psychosomatic Research, 53, 775–781.

Schwid, S. R., Petrie, M. D., Murray, R., Leitch, J., Bowen, J., Alquist, A.,
et al. (2003). A randomized controlled study of the acute and chronic
effects of cooling therapy for MS. Neurology, 60(12), 1955–1960.

Siepman, T. A., Janssens, A. C., de Koning, I., Polman, C. H., Boringa, J.
B., & Hintzen, R. Q. (2008). The role of disability and depression in
cognitive functioning within 2 years after multiple sclerosis diagno-
sis. Journal of Neurology, 255(6), 910–916.

Siva, A. (2006). The spectrum of multiple sclerosis and treatment decisi-
ons. Clinical Neurology and Neurosurgery, 108, 333–338.

Smeltzer, S. C. (2002). Reproductive decision making in women with
multiple sclerosis. Journal of Neuroscience Nursing, 34(3), 115–167.

Snook, E. M., & Motl, R. W. (2009). Effect of exercise training on walking
mobility in multiple sclerosis: A meta-analysis. Neurorehabilitation
and Neural Repair, 23(2), 108–116.

Soilu-Hanninen, M., Airas, L., Mononen, I., Heikkila, A., Viljanen, M.,
& Hanninen, A. (2005). 25-Hydrocyvitamin D levels in serum at the
onset of multiple sclerosis. Multiple Sclerosis, 11, 266–271.

Sollom, A. C., & Kneebone, I. L. (2007). Treatment of depression in
people who have multiple sclerosis. Multiple Sclerosis, 13, 632–635.

Springer, R. A., Clark, S., Price, E., & Weldon, P. (2001). Psychosocial
implications of multiple sclerosis. In J. Halper (Ed.), Advanced
concepts in multiple sclerosis nursing care (pp. 213–224). New York:
Demos Medical Publishing.

Stadelmann, C., Kerschensteiner, M., Misgeld, T., Brück, W., Hohlfeld,
R., & Lassmann, H. (2002). BDNF and gp145trkB in multiple sclero-
sis brain lesions: Neuroprotective interactions between immune and
neuronal cells? Brain, 125(Pt. 1), 75–85.

Steinman, L. (2009). Shifting therapeutic attention in multiple sclerosis
to osteopontin, type 1 and type 2 IFN. European Journal of Immuno-
logy, 39(9), 2358–2360.

Stuifbergen, A., Becker, H., Rogers, S., Timmerman, G., & Kullberg,
V. (1999). Wellness for women with MS. Journal of Neuroscience
Nursing, 31(2), 73–79.

Stuifbergen, A., Seraphine, A., & Roberts, G. (2000). An explanatory
model of health promoting behavior and quality of life for persons
with chronic disabling conditions. Nursing Research, 49(3), 122–129.

Stuke, K., Flachenecker, P., Zettl, U., Elias, W., Friedel, M., Haas, J., et al.
(2009). Symptoms of multiple sclerosis: Results from the German
multiple sclerosis registry. Journal of Neurology, 256, 1932–1935.

Suckfüll, M. (2009). Perspectives on the pathophysiology and treatment
of sudden idiopathic sensorineural hearing loss. Deutsches Arzteblatt
International, 106(41), 669–676.

Swann, J. (2006). Understanding multiple sclerosis. Nursing & Residential
Care, 8(8), 358–360.

Syx, R. L. (2008). The practice of patient education: The theoretical
perspective. Orthopaedic Nursing, 27(1), 5.

Terzi, M., Birinci, A., Cetinkaya, E., & Onar, M. K. (2007). Cerebrospinal
fluid total tau protein levels in patients with multiple sclerosis. Acta
Neurologica Scandinavica, 115(5), 325–330.

Teunissen, C. E., Dijkstra, C., & Polman, C. (2005). Biological markers in
CSF and blood for axonal degeneration in multiple sclerosis. Lancet
Neurology, 4(1), 32–41.

Teunissen, C. E., Iacobaeus, E., Khademi, M., Brundin, L., Norgren,
N., Koel-Simmelink, M.J., et al. (2009). Combination of CSF N-
acetylaspartate and neurofilaments in multiple sclerosis. Neurology,
72(15), 1322–1329.

Thomas, P. W., Thomas, S., Hillier, C., Galvin, K., & Baker, R. (2006).
Psychological interventions for multiple sclerosis. Cochrane Database
Systematic Review, Jan 25(1), CD004431.

Thrower, B. W. (2009). Relapse management in multiple sclerosis. Neuro-
logist, 15(1), 1–5.

Tintoré, M., Rovira, A., Rio, J., Tur, C., Pelayo, R., Nos, C., et al. (2008).
Do oligoclonal bands add information to MRI in first attacks of
multiple sclerosis? Neurology, 70(13 Pt. 2), 1079–1083.

48 Nursing Management of the Patient with Multiple Sclerosis

Traboulsee, A. L., & Li, D. K. (2006). The role of MRI in the diganosis of
multiple sclerosis. Advances in Neurology, 98, 125–146.

Trapp, B. D., & Nave, K. A. (2008). Multiple sclerosis: An immune or
neurodegenerative disorder? Annual Review of Neuroscience, 31,
247–269.

Trapp, B. D., Peterson, J., Ransohoff, R. M., Rudick, R., Mork, S., & Bo, L.
(1998). Axonal transection in the lesions of multiple sclerosis. New
England Journal of Medicine, 338, 278–285.

Trojan, D. A., Arnold, D., Collet, J. P., Shapiro, S., Bar-Or, A., Robinson,
A., et al. (2007). Fatigue in multiple sclerosis: Association with
disease-related, behavioural and psychosocial factors. Multiple
Sclerosis, 13(8), 985–995.

Trojano, M., Avolio, C., Manzari, C., Calò, A., De Robertis, F., Serio, G.,
et al. (1995). Multivariate analysis of predictive factors of mulitple
sclerosis course with a validated method to assess clinical events.
Journal of Neurology, Neurosurgery, and Psychiatry, 58(3), 300–306.

Tumani, H., Hartung, H. P., Hemmer, B., Teunissen, C., Deisenhammer,
F., Giovannoni, G., et al. (2009). Cerebrospinal fluid biomarkers in
multiple sclerosis. Neurobiology of Disease, 35(2), 117–127.

Turker, H., Terzi, M., Bayrak, O., Cengiz, N., Onar, M., & Us, O. (2008).
Visual evoked potentials in differential diagnosis of multiple sclerosis
and neurobehcet’s disease. The Tohoku Journal of Experimental
Medicine, 216(2), 109–116.

Valis, M., Talab, R., Stourac, P., Andrys, C., & Masopust, J. (2008). Tau
protein, phosphorylated tau protein and beta-amyloid42 in the ce-
rebrospinal fluid of multiple sclerosis patients. Neuro Endocrinology
Letters, 29(6), 971–976.

van den Noort, S., & Holland, N. (1999). Multiple sclerosis in clinical
practice. New York: Demos Medical Publishing.

Villar, L., Masterman, T., Casanova, B., Gomez-Rial, J., Espino, M., Sáda-
ba, M.C., et al. (2009). CSF oligoclonal band patterns reveal disease
heterogeneity in multiple sclerosis. Journal of Neuroimmunology,
211(1-2), 101–104.

Vogt, M. H., ten Kate, J., Drent, R. J., Polman, C. H., & Hupperts, R.
(2010). Increased osteopontin plasma levels in multiple sclerosis
patients correlate with bone-specific markers. Multiple Sclerosis,
16(4), 443–449.

Vukusic, S., & Confavreux, C. (2007). Natural history of multiple
sclerosis: Risk factors and prognostic indicators. Current Opinions in
Neurology, 20(3), 269–274.

Wagner, H. J., Munger, K. L., & Ascherio, A. (2004). Plasma viral load of
Epstein-Barr virus and risk of multiple sclerosis. European Journal of
Neurology, 11, 833–834.

Walker, L. (2009). Bowel dysfunction in multiple sclerosis. Retrieved
December 27, 2010, from www.va.gov/MS/articles/Bowel_Dysfunc-
tion_in_Multiple_Sclerosis.asp.

Weinshenker, B. G. (1994). Natural history of multiple sclerosis. Annals
of Neurology, 36, S6–S11.

Weinshenker, B. G. (1996). Epidemiology of multiple sclerosis. Neurolo-
gic Clinics, 14(2), 291–308.

Weinshenker, B. G., Bass, B., Rice, G. P., Noseworthy, J., Carriere, W.,
Baskerville, J., et al. (1989a). The natural history of multiple sclerosis:
A geographically based study. 1. Clinical course and disability. Brain,
112, 133–146.

Weinshenker, B. G., Bass, B., Rice, G. P., Noseworthy, J., Carriere, W.,
Baskerville, J., et al. (1989b). The natural history of multiple sclerosis:
A geographically based study. 2. Predictive value of the early clinical
course. Brain, 112, 1419–1428.

Wingerchuk, D. M., Lennon, V. A., Lucchinetti, C. F., Pittock, S. J., &
Weinshenker, B. J. (2007). The spectrum of neuromyelitis optica.
Lancet Neurology, 6, 805–815.

Wollin, J., Bennie, M., Leech, C., Windsor, C., & Spencer, N. (2005). Mul-
tiple sclerosis and continence issues: An exploratory study. British
Journal of Nursing, 14(8), 439–440, 442, 444–446.

Yan, Q. J., Rammal, M., Dinzey, J., Donelan, N. R., & Sadiq, S. A. (2007).
Increased Fetuin-A in acute demylinating lesions in experimental
autoimmune encephalomyelitis and multiple sclerosis. Poster pre-
sentation presented at the 37th Annual Meeting of the Society for
Neuroscience, San Diego, CA.

Yoshimura, S., Ochi, H., Isobe, N., Matsushita, T., Motomura, K.,
Matsuoka, T., et al. (2010). Altered production of brain-derived
neurotrophic factor by peripheral blood immune cells in multiple
sclerosis. Multiple Sclerosis, 16(10), 1178–1188.

Yong, V. W. (2002, December). Pathology, immunology, and neuro-
protection in MS: Mechanisms and influence of MS therapeutics.
International Journal of MS Care, (Suppl.), 4–9.

Ziemssen, T., Kümpfel, T., Klinkert, W.E., Neuhaus, O., & Hohlfeld, R.
(2002). Glatiramer acetate-specific T-helper 1- and 2-type cell lines
produce BDNF: Implications for multiple sclerosis therapy. Brain-
derived neurotrophic factor. Brain. 125(Pt. 11), 2381–2391.

Zivadinov, R., Weinstock-Guttman, B., Hashmi, K., Abdelrahman, N.,
Stosic, M., Dwyer, M., et al. (2009). Smoking is associated with
increased lesion volumes and brain atrophy in multiple sclerosis.
Neurology, 73(7), 504–510.

Bibliography
Barkhof, F., Filippi, M., Miller, D. H., Scheltens, P., Campi, A., Polman,

C. H., et al. (1997). Comparison of MRI criteria at first presentation
to predict conversion to clinically definite multiple sclerosis. Brain,
129(11), 2059–2069.

Bielekova, B., & Martin, R. (2004). Development of biomarkers in mul-
tiple sclerosis. Brain, 127, 1463–1478.

Chopra, B., Abraham, R., & Abraham, A. (2002). CSF beta-1 Globulin-a
potential marker in differentiating multiple sclerosis and acute dis-
seminated encephalomyelitis: A preliminary study. Neurology India,
50(1), 41–44.

Das, S., Nikolaidis, N., Klein, J., & Nei, M. (2008). Evolutionary rede-Evolutionary rede-
finition of immunoglobulin light chain isotypes in tetrapods using
molecular markers. Proceedings of the National Academy of Sciences
of the United States of America,105(43), 16647–16652.

Festa, E. D., Hankiewicz, K., Kim, S., Skurnick, J., Wolansky, L. J., Cook,
S. D., et al. (2009). Serum levels of CXCL13 are elevated in active
multiple sclerosis. Multiple Sclerosis, 15(11), 1271–1279.

Foley, F. W., & Werner, M. A. (2004). Sexuality. In R. Kalb, (Ed.), Multiple
sclerosis: The questions you have—The answers you need (3rd ed.).
New York: Demos Medical Publications.

Gasperini, C. (2001). Differential diagnosis in multiple sclerosis. Neuro-
logical Sciences, 22(8), S93–S97.

Hamers-Casterman, C., Atarhouch, T., Muyldermans, S., Robinson, G.,
Hamers, C., Songa, E., et al. (1993). Naturally occurring antibodies
devoid of light chains. Nature, 363(6428), 446–448.

Hasse, C. G., Lienemann, M., & Faustmann, P. M. (2008). Neuropsycholo-
gical deficits but not coping strategies are related to physical disability
in multiple sclerosis. European Archives of Psychiatry and Clinical
Neuroscience, 258(1), 35–39.

The INFB Multiple Sclerosis Study Group & the University of British
Columbia MS/MRI Analysis Group. (1995). Interferon beta-1b in
the treatment of multiple sclerosis: Final outcome of a randomized
controlled trial. Neurology, 45, 1277–1285.

Janeway, C., Travers, P., Walport, M., & Shlomchik, M. (2001). Immu-
nobiology (5th ed.). New York: Garland Publishing.

Krumbholz, M., Theil, D. Cepok, S., Hemmer, B., Kivisäkk, P., Ransohoff,
R. M., et al. (2006). Chemokines in multiple sclerosis: CXCL12 and
CXCL13 up-regulation is differentially linked to CNS immune cell
recruitment. Brain, 129(1), 200–211.

Nursing Management of the Patient with Multiple Sclerosis 49

LaRocca, N. G. (2000). Cognitive and emotional disorders. In J. S. Burks
& K. P. Johnson (Eds.), Multiple sclerosis: Diagnosis, medical ma-
nagement, rehabilitation (pp. 411–413). New York: Demos Medical
Publishing.

LaRocca, N. G., & Kalb, R. C. (2002). Psychosocial issues in multiple
sclerosis. In J. Halper & N. Holland (Eds.), Comprehensive nursing
care in multiple sclerosis (pp. 103–111). New York: Demos Medical
Publishing.

Lester, K., Stepleman, L., & Hughes, M. (2007). The association of illness
severity, self-reported cognitive impairment, and perceived illness
management with depression and anxiety in a multiple sclerosis
clinic population. Journal of Behavioral Medicine, 30(2), 177–186.

McDonald, W. I., Compston, A., Edan, G., Goodkin, D., Hartung, H.
P., Lublin, F. D., et al. (2001). Recommended diagnostic criteria for
multiple sclerosis: Guidelines from the international panel on the
diagnosis of multiple sclerosis. Annals of Neurology, 50, 121–127.

Michalowska-Wender, G., Losy, J., Biernacka-Lukanty, L. J., & Wender,
M. (2008). Impact of methylprednisolone treatment on the expres-Impact of methylprednisolone treatment on the expres-
sion of macrophage inflammatory protein 3alpha and B lymphocyte
chemoattractant in serum of multiple sclerosis patients. Pharmacolo-
gical Report, 60(4), 549–554.

Miller, C. M. (2001). Recognizing and treating cognitive impairment. In
J. Halper (Ed.), Advanced concepts in multiple sclerosis nursing care
(pp. 109–116). New York: Demos Medical Publishing.

Ness, J. M., Chabas, D., Sadovnick, A.D., Phol, D., Banwell, B., &
Weinstock-Guttman, B. (2007). Clinical features of children and ado-
lescents with multiple sclerosis. Neurology, 68(16 Suppl. 2), S37–S45.

Osterberg, L., & Blaschke, T. (2005). New England Journal of Medicine,
353, 487–497.

Patti, F. (2009). Cognitive impairment in multiple sclerosis. Multiple
Sclerosis, 15, 2–8.

Paty, D. W., Noseworthy, J. H., & Ebers, G. C. (1998). Diagnosis of mul-
tiple sclerosis. In D. W. Paty & G. C. Ebers (Eds.), Multiple sclerosis
(pp. 55–56). Philadelphia: FA Davis.

Presslauer, S., Milosavljevic, S., Brücke, T., Bayer, P., & Hübl, W. (2008).
Elevated levels of kappa free light chains in CSF support the diagno-
sis of multiple sclerosis. Journal of Neurology, 255(10), 1508–1514.

Racke, M. K. (2009). Immunopathogenesis of multiple sclerosis. Annals
of Indian Academy of Neurology, 12(4), 215–220.

Ramritu, P., Finlayson, K., Mitchell, A., & Croft, G. (2000). Identification
and nursing management of dysphagia in adults with neurological
impairment. Best practices: Evidence based practice information
sheet for health professionals. The Joanna Briggs Institute for Evidence
Based Practice and Midwifery, 4(2), 1–6.

Rao, S. M. (1995). Neuropsychology of multiple sclerosis. Current Opini-
on in Neurology, 8(3), 216–220.

Singer, B., Lucas, S., Kresa-Reahl, K., Perrin Ross, A., & Blake, P. (2008,
Winter). Review: Optimizing adherence to multiple sclerosis thera-
pies. International Journal of MS Care, 10, 113–127.

Spinal tap. (2008). In Encyclopaedia of Multiple Sclerosis. Retrieved Sep-
tember 2, 2011, from www.mult-sclerosis.org/spinaltap.html.

Thomas, F. J., & Wiles, C. M. (1999). Dysphagia and nutritional status in
multiple sclerosis. Journal of Neurology, 246(8), 677–682.

Van Hoeven, K. (2006). Serum free light chain assays for the diagnosis
and monitoring of multiple myeloma and other monoclonal
gammopathies. Retrieved May 1, 2010, from www.aacc.org/events/
expert-access/2006/serumoet06/pages/defaultaspt.

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