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Home , Myasthenia gravis, Ocular myasthenia

Care of the Patient with

AANN Clinical Practice Guideline Series

This publication was made possible by an educational grant from the Myasthenia Gravis Foundation of America, Inc.

8735 W. Higgins Road, Suite 300 Chicago, IL 60631 888.557.2266 International phone: 847.375.4733 Fax: 847.375.6430 [email protected] | www.AANN.org AANN Clinical Practice Guideline Series Editor First Author Patricia A. Blissitt, PhD RN CCRN CNRN CCNS CCM Susan B. Fowler, PhD RN CNRN FAHA ACNS-BC Content Authors Editor Joni B. Herrington, MN RN CNRN SCRN ACNS-BC Patricia A. Blissitt, PhD RN CCRN CNRN CCNS CCM Wilma J. Koopman, MScN RN(EC) ACNP CNN(C) ACNS-BC Marilyn Ricci, MSN RN CNS CNRN

Editorial Board Content Reviewers Sheila Alexander, PhD RN Marcia S. Lorimer, MSN RN CPNP-PC Tess Slazinski, MSN RN CCRN CNRN CCNS Malissa Mulkey, MSN APRN CCNS CCRN Patricia Zrelak, PhD RN CNAA-BC CNRN AANN National Office Joan Kram, MBA RN FACHE Executive Director Monica Piotrowski Associate Editor Sonya L. Jones Senior Graphic Designer

Publisher’s Note The authors, editors, and publisher of this document nei- ther 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 responsibility in connection with any informa- tion or Recommendations contained in this document. These Recommendations reflect the judgment from the American Association of Neuroscience 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 ©2013. Reviewed 2014 by the American Asso- ciation of Neuroscience Nurses. No part of this publication may be reproduced, photocopied, or republished in any form, print or electronic, in whole or in part, without writ- ten permission of the American Association of Neurosci- ence Nurses.

2 Care of the Patient with Myasthenia Gravis 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 first edition guideline, Care of the Patient with Myasthenia Gravis, represents another milestone in the series. Care of the Patient with Myasthenia Gravis promotes evidence-based practice for the patient with myasthenia gravis (MG) across the life continu- um. Nursing care of the patient with MG has evolved from a focus on a singular pathology with a limited number of phar- macologic agents to more a diverse disease process amenable to various management strategies, including pharmacologic, immunomodulation, and along with consideration for self-care activities and prevention of complications. The goal of this guideline is to offer evidence-based recommendations on nursing activities that have the potential to maximize outcomes for patients of all ages and all types of MG. Not all recommendations concern activities independently performed by registered nurses (RNs), but nurses are responsible for implementing and monitoring the outcomes of these activities. The evidence presented here may help nurses make appropriate choices when caring for patients with MG. De- pendent 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 MG as well. Resources and recommendations must describe the best practices that can enable RNs to provide optimal care for persons with MG. 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 patient with MG. It is not intended to replace formal learning but rather to augment the clinician’s knowledge base and provide a readily accessible reference tool. The nursing profession and AANN are indebted to the vol- unteers who have devoted their time and expertise to this valuable resource, which was created for those who are commit- ted to excellence in the care of the patient with MG.

Care of the Patient with Myasthenia Gravis 3 Table of Contents

I. Introduction...... 7 A. Purpose...... 7 B. Guideline goal...... 7 C. Assessment of scientific evidence...... 7

II. MG Overview...... 7 A. Definition of MG...... 7 B. Scope of the problem...... 8 C. Age- and gender-related risks for developing MG...... 8 D. Age of onset...... 8 E. Racial differences...... 8 F. Additional risk factors...... 9

III. Familial/genetics...... 9 A. Familial predisposition...... 9

IV. Prognostic factors...... 9 A. The presence of ...... 9 B. Symptoms restricted to ocular muscles...... 9 C. Initial 1–2 years...... 9 D. Maximum ...... 9 E. Classification...... 9

V. Types of MG...... 9 A. AChR -positive MG...... 9 B. The seronegative patient with MG...... 9

VI. Acquired versus congenital MG...... 9 A. Acquired/autoimmune MG...... 9 B. Congenital myasthenic syndromes (CMS)...... 10 C. Transient neonatal MG...... 10

VII. Immune versus nonimmune MG...... 10 A. This MG classification may overlap with previously described subtypes...... 10 B. Immune MG...... 10 C. Nonimmune MG...... 10

VIII. Neurophysiology of the ...... 10 A. Structure of the NMJ...... 10 B. The chemistry of neurotransmission...... 11 C. Neuromuscular transmission...... 11

IX. Pathophysiology of acquired MG...... 11 A. Acquired MG...... 11 B. AChR antibody mechanism...... 11 C. Role of the ...... 11

4 Care of the Patient with Myasthenia Gravis X. Ocular only versus generalized MG...... 12 A. Ocular MG...... 12 B. Generalized...... 12

XI. Clinical MG classification...... 13 A. Classification to identify subgroups...... 13

XII. Description/clinical features of MG...... 13 A. Characterized by fatigable ...... 13 B. Weakness increases/improves...... 13 C. Clinical course is variable...... 13 D. MG is a chronic disease...... 13 E. Disease remissions...... 13

XIII. Manifestations/symptoms...... 13 A. Characteristic patterns of presenting weakness...... 13 B. Clinical features...... 13

XIV. Clinical course...... 14 A. The clinical course is variable...... 14 B. Patients may experience periods of exacerbations and remissions...... 14

XV. Diagnostic tests...... 14 A. Laboratory tests...... 14 B. Electrodiagnostic testing...... 15 C. Other...... 15

XVI. Nursing assessment of the patient with MG...... 15 A. Symptom description to be obtained during the patient history...... 15 B. Assessment techniques...... 15 C. Respiratory muscles...... 16

XVII. Treatment...... 17 A. The goal is disease and symptom management...... 17 B. Pharmacologic management...... 17 C. Other therapies...... 20

XVIII. MG Crises...... 25 A. An MG crisis occurs when there is an exacerbation of MG symptoms...... 25 B. Myasthenic crisis...... 25 C. ...... 25 D. Aggressive respiratory treatment...... 26

XIX. General nursing management of the patient with MG...... 26 A. that may worsen MG...... 26 B. Nursing management of swallowing and chewing impairment...... 26 C. Nursing management of ...... 27

Care of the Patient with Myasthenia Gravis 5 XX. Special consideration in the juvenile MG population...... 27 A. management in juvenile MG...... 27 B. Developmental issues...... 27

XXI. Psychosocial and educational needs...... 27 A. MG is characterized by relapses and exacerbations and is considered a chronic illness...... 27

XXII. Resources for patience, families, and healthcare professionals...... 29 A. Myasthenia Gravis Foundation of America...... 29

References...... 30

6 Care of the Patient with Myasthenia Gravis I. Introduction 4. TheClinical Practice Guidelines and rec- A. Purpose ommendations for practice are established 1. The purpose of this guide is to review and based upon the evaluation of the available evaluate literature about myasthenia gra- evidence (American Association of Neu- vis (MG), with a concentrated focus on the roscience Nurses [AANN], 2005; Guyatt & adult with acquired MG, and to create a Rennie, 2002; Melnyk, 2004): reference for neuroscience nurses who care a. Level 1 recommendations are support- for the patient with MG across the contin- ed by class I evidence. uum of care throughout the lifespan. b. Level 2 recommendations are support- B. Guideline goal ed by class II evidence. 1. The goal of this guideline is to help nurses c. Level 3 recommendations are support- provide consistent, current, and evidence- ed by class III and IV evidence. based care to the patient with MG. Topics II. MG Overview include epidemiology; types and classifica- A. Definition of MG tions of MG; pathophysiology; clinical and 1. MG is an autoimmune neuromuscular dis- diagnostic presentation; symptom man- ease leading to fluctuating muscle weak- agement, including surgical interventions; ness and fatigability. nursing assessment and intervention; and 2. MG is the most common primary disorder patient and family education. of neuromuscular transmission (Sanders, C. Assessment of scientific evidence 2011). 1. A review of literature published between Jan- 3. The muscle weakness is caused by a dis- uary 2000 and September 2012 was conduct- ruption in normal neuromuscular trans- ed using PubMed/MEDLINE and CINAHL mission by binding of to databases with the following search terms: proteins involved in signaling the NMJ. myasthenia gravis, neuromuscular junc- Circulating block, interfere, or tion (NMJ), neuromuscular transmission, alter receptors (AChR) at thymectomy, evidence-based practice nurs- the postsynaptic NMJ, inhibiting the stim- ing, research, and myasthenia gravis clini- ulative effect of the neurotransmitter cal trials. The search was extended to earlier Acetylcholine (ACh) (Merrigioli, 2009). years because of the lack of more recent ref- 4. MG is most commonly associated with dys- erences on select topics. Several publications function of the nicotinic AChR (Silvestri & dated earlier than 2000 are included because Wolfe, 2012). Less commonly, MG is asso- of their historical clinical significance. ciated with autoantibodies causing dysfunc- 2. The Myasthenia Gravis Foundation of tion of the muscle-specific kinase (MuSK) America guidelines (Howard, 2008) were protein (Silvestri & Wolfe, 2012). assessed and incorporated in this docu- 5. MG may be classified in a variety of ways, ment as appropriate and needed. including 3. For the AANN Clinical Reference Series, a. immune versus nonimmune (congen- data quality is classified as follows: ital) or acquired versus nonacquired a. Class I: Randomized controlled tri- (congenital) MG al without significant limitations or b. ocular versus generalized MG meta-analysis c. early-onset versus late-onset MG b. Class II: Randomized controlled trial d. thymoma-associated MG with important limitations (e.g., meth- e. MG with no detectable AChR antibod- odologic flaws or inconsistent results) ies or MuSK antibodies (antibody- and observational studies (e.g., cohort negative MG). In antibody-positive or case-control) MG, antibodies on the receptors im- c. Class III: Qualitative study, case study, pair normal neuromuscular trans- or series mission (Howard, 2008; Keesey, 2004; d. Class IV: Evidence from expert com- Trouth, Dabi, Solieman, Kurukumbi, mittee reports and/or expert opinion & Kalyanam, 2012). of the guideline panel; standards of 6. Muscles become progressively weaker care and clinical protocols that have during periods of activity or repetitive use been identified. (fatigue) and improve after periods of rest.

Care of the Patient with Myasthenia Gravis 7 a. MG weakness is fluctuating and in- C. Age- and gender-related risks for developing MG creases after use of the affected muscle 1. Women who are younger than age 40 are at groups. It typically worsens during the increased risk (Alshekhlee, Miles, Katirji, course of the day. Peston, & Kaminski, 2009; Howard, 2008). i. Mild MG is characterized by mild 2. People who are 50–70 years of age of either ocular, facial, bulbar, respiratory, sex are at increased risk (Alshekhlee et al., or limb muscle weakness with oc- 2009; Howard, 2008). casional, intermittent, or rare (not 3. Women are affected more than men at a daily) symptoms of weakness. Ear- ratio of about 3:2 (Alshekhlee et al., 2009). ly in the disease, the symptoms 4. Women are more affected during their sec- may be absent to minimal upon ond and third decades (Howard, 2008). awakening or after a period of rest 5. Among men, diagnosis commonly occurs (Grob, Brunner, Namba, & Pagala, during the sixth decade (Howard, 2008; 2008). Phillips, 2004). ii. Severe MG is characterized by D. Age of onset some, but not necessarily all, of 1. Average age of onset in women is 28 years; the following symptoms: moderate in men, the average age of onset is 42 years to severe , sponta- (MDA, 2009). neous and , reduced 2. Late-onset MG forced closure, that a. Defined as the onset of disease after age interferes with safe swallowing, 50 in the patient with no clinical or para- , dyspnea with a vital ca- clinical evidence of a thymoma, a tumor pacity of less than 50% of normal, of the thymus gland (Aarli, 1999, 2008). head drop, and proximal or distal b. Ocular symptoms are easily missed in muscle weakness severe enough to elderly people because of normal aging interfere with independent perfor- of the eyelids (Aarli, 2008). mance of activities of daily living c. The main immunological difference in (ADLs) (Grob et al., 2008). Enter- late-onset MG is the presence of anti- al feeding and/or ventilator assis- bodies to muscle , also known as tance may be required. connectin, a protein vital for muscle 7. Muscles that control and eyelids, fa- contraction (detected in approximate- cial expressions, chewing, talking, and ly 50% of patients), and lower mean swallowing are most commonly affected concentration of antibodies to AChR (Juel & Massey, 2007). (Aarli, 1999, 2008). 8. The first noticeable symptom may be weak i. Titin is a protein that plays an im- eye muscles, diplopia or ptosis (two-thirds portant role in muscles used in of patients)(Conti-Fine, Milani, & Kamins- movement and heart contraction. ki, 2006), difficulty swallowing, or slurred It is an essential component of sar- speech (Drachman, 1994). comeres, the basic unit of muscle B. Scope of the problem contractions (U.S. National Li- 1. Disease prevalence in the United States is brary of Medicine National In- estimated at 20 cases per 100,000 (Phillips, stitutes of Health Department of 2003). Health & Human Services, 2012). 2. MG is diagnosed in two to seven of every E. Racial differences 10,000 people in Western countries (Mus- 1. African Americans cular Dystrophy Association [MDA], 2009). a. In seronegative generalized MG (neg- 3. Better awareness has resulted in increasing ative for AChR antibodies), African prevalence, especially in people older than Americans have a higher rate of posi- age 50 (Aarli, 1999; Pallaver, et al., 2011; tive muscle-specific kinase antibodies Somnier, 2005). (MuSK-Ab) than Caucasians with se- 4. MG occurs in all ethnic groups (Myasthe- ronegative generalized MG (Oh, 2009). nia Gravis Foundation of America, Inc. MuSK-Ab are antibodies against [MGFA], 2012a). MuSK protein. MuSK is a polypeptide required for formation of the NMJ.

8 Care of the Patient with Myasthenia Gravis MuSK-Ab inhibit signaling of MuSK V. Types of MG (Meriggioli & Sanders, 2004). A. AChR antibody-positive MG b. In the United States, MG occurs earlier 1. Also referred to as seropositive MG and more frequently in African 2. Antibodies in the blood (serum) bind to American women. In Caucasians, dis- the AChR of muscle. ease onset is later and more common 3. Affected people often have thymoma or in men (Alshekhlee et al., 2009). thymic hyperplasia (Keesey, 2004). i. Higher percentage of abnormality B. The seronegative patient with MG on repetitive nerve stimulation 1. Also referred to as seronegative MG ii. More severe forms of MG 2. The absence of serum antibodies to AChRs c. Annual incidence is higher in African (Chan, Lachance, Harper, & Lennon, 2007) American women compared with Cauca- 3. Affects 20% of patients with generalized sian women and Caucasian and African MG (Vincent & Leite, 2005) American men (Alshekhlee et al., 2009). 4. Some patients who are seronegative for 2. The Japanese patient with late-onset MG AChR antibodies will have antibodies to frequently has the ocular form with a dif- MuSK, a protein on the muscle side of the ferent immunological profile compared NMJ. They are MuSK antibody positive. with early-onset MG. Late-onset ocular a. MuSK antibody-positive patients with MG has been associated with increased tit- MG have no evidence of thymus pa- in autoantibodies and MuSK-Ab in patients thology (Vincent & Leite, 2005). who are seronegative (Suzuki et al., 2011). b. MuSK antibody-positive patients with F. Additional risk factors (Grob et al., 2008) MG may have anticholinesterase non- 1. Familial MG responsiveness, rare facial or tongue 2. D- ingestion (drug-induced MG) atrophy, favorable response to im- 3. Other autoimmune diseases, including the munotherapy, and responsiveness to following: corticosteroids and plasma exchange a. Thyroid diseases (Pasnoor, et al., 2010). b. Diabetes mellitus type 1 c. Characteristics of the patient with c. anti-MuSK antibodies d. erythematosus i. Young, adult women (Vincent & e. Demyelinating central nervous system Leite, 2005) diseases ii. Bulbar neck or respiratory muscle weakness (Evoli et al., 2003) III. Familial/genetics iii. Thymus histology normal or mildly A. Familial predisposition: People with family abnormal (Vincente & Leite, 2005) members who have MG are 1,000 times more likely to develop MG than the general popula- VI. Acquired versus congenital MG tion (Howard, 2008). A. Acquired/autoimmune MG 1. The acquired form of MG is autoimmune. IV. Prognostic factors Antibodies produced by the patient’s own A. The presence of thymoma generally indicates immune system impair binding of the ACh more severe illness and worse prognosis (Lucchi to the AChR at the NMJ (Howard, 2008). et al., 2009). 2. The postsynaptic muscle membrane loses B. A better prognosis is expected if symptoms are its normal folded shape because of autoim- restricted to ocular muscles (10%–40% of cas- mune activity. es), but 50%–60% of patients develop gener- 3. Juvenile MG is a form of acquired (autoim- alized MG, most within 2 years (Benatar & mune) MG. Kaminski, 2006). a. This autoimmune type of MG typical- C. The most severe level of weakness and high ly presents in adolescent girls (Chiang, mortality occurs during the initial 1–2 years of Darras, & Kang, 2009). disease (Grob et al., 2008). b. Juvenile MG is a chronic disease (Evo- D. Maximum weakness occurs in 66% of patients li, 2010). within the first 2 years (Howard, 2008). c. The treatment and disease course are E. Classification identifies subgroups of patients similar to the adult form of immune with MG, which aids in prognosis. MG (Chiang et al., 2009).

Care of the Patient with Myasthenia Gravis 9 B. Congenital myasthenic syndromes (CMS) B. Immune MG (Agius et al., 2003) 1. Present at birth but may not manifest un- 1. Type 1: high AChR antibodies without tit- til childhood or adult life; symptoms usu- in or MuSK antibodies ally begin within the first 2 years of life and 2. Type 2: titin antibodies present with AChR range from mild to severe; and weakness antibodies does not usually progress. 3. Type 3: MuSK antibodies present without 2. CMS is not caused by autoimmune pro- AChR antibodies. cesses but rather synaptic malfunction, C. Nonimmune MG which in turn is caused by genetic muta- 1. Congenital, which, as described previous- tions (Engel, Ohno, & Sine, 2003). ly has a genetic etiology (Engel et al., 2003; 3. The defect may be presynaptic, synaptic, or Keesey, 2004) postsynaptic at the NMJ (Keesey, 2004). VIII. Neurophysiology of the neuromuscular junction 4. The inheritance pattern is typically autoso- A. Structure of the NMJ (Howard, 2008; Ruff, 2003) mal recessive (National Institute of Neuro- 1. The NMJ, also known as the motor end- logical Disorders and Stroke, 2012). plate, is composed of the nerve terminal, 5. The three main categories of CMS are the synaptic cleft, and the postsynaptic named for the part of the affected NMJ membrane (Figure 1). (Engel et al., 2003; Keesey, 2004; MDA, 2. The nerve terminal is a highly specialized 2009). region that forms a small bulb (the synap- a. Presynaptic (nerve cell) tic bouton or presynaptic terminal) that i. Insufficient release of ACh contains synaptic vesicles. Synthesis and b. Postsynaptic (muscle cell) packaging of the neurotransmitter, ACh, i. ACh receptors are missing or don’t occurs within the presynaptic nerve ter- stay open long enough. minal. Packaged transmitter (vesicles) col- ii. AChR deficiency or mutations in lects in regions called active release sites or membrane or ACh binding sites zones. Typically, there is one end-plate re- c. Synaptic (space between nerve and gion for one muscle fiber in most cells) muscles (Howard, 2008). i. ACh receptors stay open too long. 3. The synaptic cleft separates the nerve ter- ii. (AChE) defi- minal from the postjunctional region of ciency (Keesey, 2004) the muscle end-plate. C. Transient neonatal MG 4. The muscle membrane enfolds to increase 1. Occurs as a result of transplacental passage of surface area, and at the crests of these folds maternal autoantibodies interfering with the are the sites of the AChR. function of the NMJ (Batocchi et al., 1999). 2. Occurs in about 9%–30% of infants born Figure 1. Normal Neuromuscular Junction to mothers with autoimmune MG and is transient, lasting a few weeks to 4 months. Symptoms resolve as maternal autoanti- bodies leave the neonate’s circulation (Tellez-Zenteno, Hernández-Ronquillo, Salinas, Estanol, & da Silva, 2004). 3. Careful observation of infants is required in a special infant care unit with nurses fa- miliar with MG for the first several post- partum days (Burke, 1993). 4. Symptoms may occur within hours after birth and may include generalized weak- ness, , weak cry, poor suck and swallow, facial paresis, and respiratory dis- tress (Papazian, 1992). Artist’s rendition of the myasthenic neuromuscular junction. The nerve terminal of a single synaptic boulon contains synaptic vesicles of acetylcholine (ACh). VII. Immune versus nonimmune MG Copyright 2008 J.F. Howard, Jr., reprinted from Myasthenia Gravis: A Manual for the Health A. This MG classification may overlap with previ- Care Provider, used with permission. ously described subtypes.

10 Care of the Patient with Myasthenia Gravis B. The chemistry of neurotransmission (Howard, and muscle contraction. 2008; Ruff, 2003) Postsynaptic depolarization is terminat- 1. The neurotransmitter at peripheral NMJs ed by passive diffusion of ACh out of the is ACh. Synthesis occurs in the cytoplasm primary and secondary synaptic clefts and of the nerve terminal with processing of enzymatic hydrolysis of ACh into choline acetate + choline with the help of choline and acetate by AChE. acetyltransferase. Most of the transmitter IX. Pathophysiology of acquired MG is stored in vesicles. ACh is released in dis- A. Acquired MG is an autoimmune disorder that crete packages (quanta) when nerve activa- is attributable to a T-cell dependent, tion occurs. ACh molecules released by the antibody-mediated deterioration of the neuro- presynaptic bind with the AChR muscular junction, thereby altering the nerve on the postsynaptic muscle membrane impulse transmission processes (Trouth et al., folds. 2012). 2. ACh binding to the AChR stimulates B. AChR antibody mechanism (Howard, 2008; opening of sodium channels, and sodium Mays & Butts, 2011) flows into the cell while a lesser amount 1. An antibody-mediated attack on the post- of potassium flows out. The sodium influx synaptic muscle results in the loss of the causes depolarization of the muscle fiber, postsynaptic muscle’s normal folded shape. which initiates a release of calcium from AChRs are degraded by autoantibodies intracellular (sarcoplasmic reticulum) and complement activity, so the concen- stores. The increase in intracellular calci- tration of AChRs on the muscle end-plate um stimulates muscle contraction. membrane is reduced. 3. AChE is located deep in clefts of these 2. Antibodies bind to and block the AChR postsynaptic folds. Unbound ACh in the binding sites. synaptic cleft is hydrolyzed by AChE into 3. and complement com- choline and acetate, which are taken back ponents attach to and damage the muscle into the nerve terminal for resynthesis. membrane, reducing the efficiency of syn- C. Neuromuscular transmission (Howard, 2008; aptic transmission. Ruff, 2003) 4. Although ACh is released normally, its ef- 1. The presynaptic events of neuromuscular fect on the postsynaptic membrane is di- transmission include the nerve action po- minished because of decreased AChR or tential (AP) depolarizing the axonal mem- decreased AChR binding sites. The post- brane of the nerve terminus, producing synaptic membrane is less sensitive to a voltage-dependent increase in calcium ACh, and there is a reduced probability conductance. that nerve impulses will be followed by a a. Extracellular calcium enters the muscle AP. (Howard, 2008; Mays & Butts, terminal to initiate ACh release. Exo- 2011). cytosis of the contents C. Role of the thymus occurs at highly specialized release 1. There is a relationship between the thy- zones and discharges the ACh into mus gland and acquired MG, although the synaptic cleft. There is prompt dif- whether it plays a primary or secondary fusion across the synaptic cleft to the role in the pathogenesis of MG is unclear. AChR complex. The thymus is the central organ for im- 2. The postsynaptic events of neuromuscular munological self-tolerance, which is the transmission include the binding of ACh capacity to recognize self versus nonself molecules with postsynaptic AChR recep- with the appropriate immunological re- tors. These ACh receptors are located pri- sponses. It is suspected that this loss of marily at the crests of postsynaptic folds. ability to recognize self versus nonself Binding produces a change in the shape plays a role in the breakdown in tolerance of the ACh-AChR complex; with an in- that leads to the autoimmune attack on creased permeability of sodium and po- AChR in MG. tassium, the opening of individual ionic 2. The thymus contains myoid cells, which channels results in the local depolarization are striated muscle cells within thymal of the end-plate zone, which produces an tissue that express the AChR antigen,

Care of the Patient with Myasthenia Gravis 11 antigen-presenting cells, and immunocom- X. Ocular only versus generalized MG petent T cells. A. Ocular MG 3. The normal thymus targets and deletes 1. Affects 50% of the MG population (Bena- AChR-specific T cells in the thymus before tar & Kaminski, 2006). they enter the periphery. 2. Eyes 4. In the patient with MG who has an abnor- a. Ptosis and diplopia mal thymus, tolerance is lost and results b. Eyelid levator muscle and lateral rectus in the development of antibodies against muscle (Conti-Fine et al., 2006; Hsu, AChR and other proteins involved in NMJ Tsai, Wang, & Su, 2002) activity. 3. Test: positive (Prostigmin) or 5. The thymus is abnormal in most patients (Tensilon) test with acquired MG. a. Edrophonium inhibits AChE a. Thymic hyperplasia: 65% of patients b. Given intravenously (IV) with acquired MG have microscopic c. A positive result with improvement or changes of hyperplasia that resemble resolution of ptosis or muscle weakness the histology of active peripheral im- is indicative of MG (Benatar, 2010). mune organs (Angelini, 2011; Howard, 4. AChR antibody test (blood analysis) 2008; Phillips, Torner, Anderson, & a. Positive AChR antibodies (present in Cox, 1992). These hyperplastic features 30%–50%) (Conti-Fine et al., 2006) include the presence of germinal cen- 5. The “ice pack test” for diagnosis of ocular ters, which are areas within lymphoid myasthenia involves placing an ice pack on tissue at which B cells interact with the eyelids for 2 minutes. A positive result helper T cells to produce antibodies. is at least a 2-mm improvement of ptosis. The precise role of the thymus is not There is questionable specificity and sen- entirely clear (Figure 2). sitivity of this test because of the lack of b. Thymoma research on this method (Benatar, 2006, i. Among patients who have MG, 2010; Czaplinski, Steck, & Fuhr, 2003; Ellis, 10%–15% have a tumor of the thy- Hoyt, Ellis, Jeffery, & Sondhi, 2000; Ertas, mus. These patients tend to be be- Arac, Kumral, & Tuncbay, 1994; Golnik, tween the ages of 30 and 60 years Pena, Lee, & Eggenberger, 1999; Kubis, and have more severe disease and Danesh-Meyer, Savino, & Sergott, 2000). higher levels of AChR antibodies Nursing recommendation: Nurses should (Howard, 2008). monitor the results of the ice pack test with consideration for its limited value in the di-

agnosis of MG (Level 2). B. Generalized MG Figure 2. Thymus 1. Affects 70% of the MG population (Conti- Fine et al., 2006) 2. May involve eyes a. Ptosis and diplopia b. Eyelid levator muscle and lateral rectus muscles 3. Progresses to bulbar, facial, and limb muscles 4. Tests: positive neostigmine (edrophonium) test 5. Positive AChR antibodies (present in 80%– 90%) (Conti-Fine et al., 2006) 6. Positive MuSK antibodies (present in 20% if negative for AchR antibodies) (Vincente & Leite, 2005) From Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health, 7. Positive electrodiagnostic testing Seventh Edition. © 2003 by Saunders, an imprint of Elsevier, Inc. Used with permission. 8. Associated with thymoma or thymic hyperplasia

12 Care of the Patient with Myasthenia Gravis XI. Clinical MG classification by exacerbations, remissions, and lability (Kee- A. The Task Force of the Medical Scientific Advi- sey, 2004). sory Board of the Myasthenia Gravis Founda- E. Disease remissions are rarely complete or tion of America (Jaretski et al., 2000) designed permanent. a classification to identify subgroups of patients XIII. Manifestations/symptoms with MG who share distinct clinical features A. Characteristic patterns of presenting weakness or severity of disease that may indicate differ- 1. Ocular symptoms of ptosis and diplopia ent prognoses or responses to therapy (Table 1) occur in more than 50% of patients, and (Howard, 2008; Jaretski et al., 2000). half will develop generalized disease with- XII. Description/clinical features of MG (Juel & in 2 years (Benatar & Kaminski, 2006). Massey, 2007; Keesey, 2004) 2. Bulbar symptoms (dysarthria, dysphagia, A. Characterized by fatigable muscle weakness af- and fatigable chewing) may be seen ini- fecting ocular, facial, bulbar, respiratory, neck, tially in up to 15% of patients (Angelini, and limb muscles 2011). B. Weakness increases with repetitive use (fatigue) 3. Proximal limb weakness alone occurs in and improves after periods of rest or sleep. fewer than 5% of patients (Grob et al., C. The clinical course is variable and individuals 2008). may experience periods of exacerbation and re- B. Clinical features include fatigable muscle weak- mission of symptoms. ness in specific muscle groups. D. MG is a chronic disease that most often is active 1. Ocular muscles: Variable eyelid weakness during the first few years and is characterized (ptosis) occurs in either eye and can alter- nate from one eye to the other over time. Table 1. Myasthenia Gravis Foundation Clinical Classification It may be severe enough to occlude vision. and Defining Characteristics Extraocular muscle (EOM) weakness pro- Class Defining characteristics duces blurring of vision or double vision. I Any ocular weakness An abnormal pattern can occur, such as an May have weakness of eye closure isolated oculomotor neuropathy, an inter- All other muscle strength is normal nuclear opthalmoplegia presenting as im- II Mild weakness affecting other than ocular muscles paired adduction, or a vertical gaze paresis May also have ocular muscle weakness of any severity mimicking other disorders. The pupils are IIa Predominantly affecting limb, axial muscles, or both May also have lesser involvement of oropharyngeal weakness always spared (Mahadeva, Phillips, & Juel, 2008). IIb Predominantly affecting oropharyngeal, respiratory muscles, or both May also have lesser or equal involvement of limb, axial muscles, or 2. Bulbar muscles: Fatigable jaw weakness both is often noted halfway through a meal or III Moderate weakness affecting other than ocular muscles when chewing meat and other concentrat- May also have ocular muscle weakness of any severity ed solid foods. The weakness may be noted IIIa Predominantly affecting limb, axial muscles, or both by the need for patients to use their fingers May also have lesser involvement of oropharyngeal muscles under the jaw to keep their mouth closed. IIIb Predominantly affecting oropharyngeal, respiratory muscles, or both Hypophonic or nasal speech occurs with May also have lesser or equal involvement of limb, axial muscles, or both palatal weakness and may worsen with prolonged speaking. Dysphagia may also IV Severe weakness affecting other than ocular muscles May also have ocular muscle weakness of any severity be present, with symptoms of nasal regur- IVa Predominantly affecting limb and/or axial muscles gitation when swallowing fluids; choking May also have lesser involvement of oropharyngeal muscles while eating foods with certain textures, IVb Predominantly affecting oropharyngeal, respiratory muscles, or both such as peanuts, carrots, or steak; the need May also have lesser or equal involvement of limb, axial muscles, or for liquids and gravies to swallow food bo- both luses; taking a longer time to eat (fatigu- V Defined by intubation, with or without , except ing); weight loss; or aspiration pneumonia. when employed during routine postoperative management 3. : Facial weakness often pro- The use of a feeding tube without intubation places the patient in class IVb. duces a transverse smile and an expres- Adapted from Howard J.F.: Physician Issues. In Myasthenia Gravis: A Manual for the Health sionless face. A transverse smile, also Care Provider, [James F. Howard, Jr. (ed)]. Myasthenia Gravis Foundation of America, called a myasthenic snarl, is a contrac- Chapter 1, Table 2.1, pg. 13, 2008. Used with permission. tion of the middle portion of the upper lip

Care of the Patient with Myasthenia Gravis 13 while the upper mouth fails to contract XV. Diagnostic tests (Juel & Massey, 2007). A. Laboratory tests such as measuring the lev- 4. Neck and limb weakness: A dropped head el of AChR in the serum and physical exam- occurs, particularly later in the day be- ination can diagnose autoimmune MG in most cause of weakness of neck extensors. Neck patients. pain can occur due to the added effort of 1. MG can be diagnosed by serological test- trying to keep the head up. The proximal ing for AChR antibodies; specificity is arms (deltoid and triceps) are usually more higher than 98%, but sensitivity is low and involved than proximal legs (hip flexors), variable (around 85% for generalized MG, although distal presentations (wrist and 44% for ocular MG) (Benatar, 2010). finger extensors or ankle dorsiflexors) can 2. In the patient who is AChR seronegative, occur. further testing can be completed to check 5. Respiratory muscles: Breathing difficulty for MuSK antibodies. MuSK antibody test- in generalized MG is characterized by in- ing is reliable in generalized MG but not creasing difficulty while supine or bend- in ocular MG (Stickler, Massey, & Sanders, ing over; often, respiratory insufficiency 2005). is coupled with other bulbar symptoms 3. Confirmation of diagnosis and response (Grob et al., 2008). Respiratory muscle to medication can be accomplished by ad- weakness may be sufficient to result in re- ministering an IV AChE inhibitor drug spiratory failure, and the patient is said to such as edrophonium chloride (Tensilon) be in crisis. However, less severe respirato- and monitoring for a rapid but brief reso- ry muscle weakness may also interfere with lution of symptoms, such as improvement sleep, resulting in daytime sleepiness and in ptosis, dysconjugate gaze, grip strength, fatigue (Keesey, 2004). or respiratory function. (Angelini, 2011; Keesey, 2004). XIV. Clinical course a. IV edrophonium chloride is of rapid, A. The clinical course is variable. short duration, with onset in 30 sec- B. Patients may experience periods of exacerba- onds and lasting about 5 minutes. tions and remissions (Keesey, 2004). b. (0.6 mg) should be avail- 1. Exacerbations (worsening of symptoms) able in the event that side effects occur may be caused by systemic illness (e.g., (Meriggioli & Sanders, 2004). viral or respiratory infections), fever, c. Rare risk of side effects includes bra- hypo- or , surgery, emo- dycardia, asystole, and bronchocon- tional upset, , menstrual cy- striction; emergency medications must cle, and drugs that affect neuromuscular be available (Angelini, 2011; Keesey, transmission. 2004). a. Myasthenic crisis: respiratory failure d. IV edrophonium chloride is contra- attributable to myasthenic weakness. indicated in the patient with bron- Other less life-threatening signs and chial or cardiac dysrhythmias symptoms of myasthenia crisis include because edrophonium may result in increased generalized muscle weak- cholinergic side effects (Meriggioli & ness; tachycardia; and pale, cool skin. Sanders, 2004). b. Cholinergic crisis: respiratory fail- e. Edrophonium is used less often than ure resulting from a high dose of previously but remains available in the inhibitors. Other less United States (Angelini, 2011). life-threatening signs and symp- f. Sensitivity for the edrophonium test toms of cholinergic crisis include in- has been reported at 0.88 and 0.92 for creased generalized increased muscle ocular and generalized MG, respec- weakness; small pupils; ; tively; the specificity has been found to increased secretions; diarrhea and ab- be as high as 0.97 for both ocular and dominal cramping; and red, warm generalized MG (Benatar, 2006; Nich- skin. olson, McLeod, & Griffiths, 1983). 2. Remissions: inactive stage (Howard, 2008) g. If the IV test cannot be administered, a. Remissions are rarely complete or an oral anticholinesterase medication permanent.

14 Care of the Patient with Myasthenia Gravis such as (Mestinon) 2006; Keesey, 2004; Meriggioli & Sand- can be given (Gold, Hohlfeld, & Toyka, ers, 2004). 2008; Keesey, 2004). 3. Electrodiagnostic study testing is uncom- i. Symptom resolution onset will be fortable for patients. slower with oral administration, Nursing recommendation: Nurses should with response over 1–2 hours. be familiar with electrodiagnostic testing ii. If taken orally, edrophonium must in MG. Nurses should prepare patients for be taken with food or after a meal their experience, including the likelihood to lessen gastrointestinal stimula- of some discomfort (Level 2). tion (Keesey, 2004). C. Other Nursing recommendation: Nurses should 1. The “ice pack test” (see section X.A.5) know the adverse events associated with di- 2 Diagnostic imaging of the anterior medi- agnostic testing in MG and how to manage astinum can help to determine if a thymo- those side effects as needed. Nurses should ma is present. Chest X rays are inferior to monitor for results and adverse events as- computed tomography and/or magnet- sociated with the use of edrophonium for ic resonance imaging for recognition of diagnostic testing in MG and manage ad- thymoma (Benatar, 2006; Keesey, 2004, verse events appropriately (Level 2). Meriggioli & Sanders, 2004). B. Electrodiagnostic testing Nursing recommendation: Nurses should 1. Repetitive nerve stimulation (RNS) understand and explain the “ice pack test” a. In RNS, a peripheral nerve is repeti- and diagnostic imaging to the patient and tively overstimulated and the muscle family to lessen fear and anxiety and elicit action potential is recorded. cooperation and participation (Level 2). b. A surface electrode is placed over the XVI. Nursing assessment of the patient with MG (Vas- muscle, and a reference electrode is sar, Batenjany, Koopman, & Ricci, 2008) placed over a distal tendon or bony A. Symptom description to be obtained during the prominence, where minimal electrical patient history activity is recorded. 1. Location of the weakness c. RNS depletes the synaptic vesicles of 2. Quality or character of the weakness ACh, resulting in a decremental re- 3. Quantity or severity of the weakness sponse in the muscle action potential. 4. Timing (onset, duration, frequency) of d. The cutoff for normal/abnormal re- the weakness and relation to medication sponse may vary between laboratories, administration but a decrease of more than 10% is 5. Setting in which weakness occurs and/or usually considered abnormal. Reports worsens of sensitivity and specificity are vari- 6. Aggravating or trigger factors (e.g., change able related to inconsistencies in ad- in emotional state, heat, humidity, infec- ministration and interpretation of the tion, surgery, menstruation) test (Benatar, 2006; Costa, Evangelista, 7. Alleviating factors (e.g., rest) Conceicao, & de Carvalho, 2004; Kee- B. Assessment techniques (Table 2 and Table 3) sey, 2004; Meriggioli & Sanders, 2004). (Howard, 2008; MGFA, 2000) 2. Single-fiber (SFEMG) 1. Ocular muscles a. A concentric needle is used to identify a. Eyelids for ptosis, diplopia (double and record action potentials from sin- vision), gle muscle fibers. 2. Bulbar muscles b. Testing may be conducted using mild a. Chewing, swallowing, speech voluntary activation of the muscle or 3. Facial muscles with microstimulation; neuromuscular a. Flattening of the nasolabial fold, smile jitter is produced. symmetry, facial expression, resistance c. SFEMG measures the instability preced- to eyelid and lip closure, inability to ing the neuromuscular block, while RNS puff out cheeks measures the neuromuscular block. 4. Head and neck muscles d. SFEMG is highly sensitive for diagno- a. Head drop sis but is not 100% sensitive (Benatar, 5. Limb muscles

Care of the Patient with Myasthenia Gravis 15 a. Test strength and fatigability of each of Nursing recommendations: Nurses the proximal and distal muscle groups should perform a comprehensive nurs- against gravity and resistance and ob- ing assessment of the patient with MG serve and record (in seconds or min- that includes a detailed medical his- utes) how long it takes for the muscles to tory and symptom description. Nurs- fatigue. The patient with MG has asym- es should test all voluntary muscles for metrical weakness, so it is important to both muscle strength and fatigability to compare each muscle group to the cor- determine the severity of specific mus- responding muscle group on the oppo- cle weakness, the degree of functional site side of the body. Muscle strength impairment, and potential complica- can be graded using the widely accepted tions (Table 4) (Level 3). scale in Table 2 (Howard, 2008; Vassar C. Respiratory muscles et al., 2008). can be as- 1. Observations to note include breathing ac- sessed by using the Quantitative Myas- tivity and listening to the patient talk and thenia Gravis Testing Method (Table 3) count to 50, recording the number at which (Barohn 2000; Howard, 2008). the patient stops to take a breath, any short- ness of breath when the patient is lying Table 2. Muscle Strength Grades down or bending over, increased respira- Grade Interpretation tory effort, and frequent respiratory gasps. The rate, rhythm, and quality of respirations Grade 5 Normal muscle power and the presence of anxiety or restlessness Grade 4 Movement against gravity and against resistance should be noted as well (Mehta, 2006). Grade 3 Movement against gravity without resistance Nursing recommendation: Nurses should Grade 2 Movement in the plane of action with gravity eliminated perform a detailed physical assessment of Grade 1 Flicker of muscle movement in the gravity-eliminated position respiratory status (Level 3). Grade 0 No muscle movement, even with gravity eliminated 2. Pulmonary function tests include negative Sources: MGFA, 2000; Howard, 2008 inspiratory force (NIF) and forced vital

Table 3. Quantified Myasthenia Gravis (QMG) Score Test item/Grade None/0 Mild/1 Moderate/2 Severe/3 Score

Double vision on lateral gaze right or left (circle 61 11–60 1–10 Spontaneous one), seconds Ptosis (upward gaze), seconds 61 11–60 1–10 Spontaneous Facial muscles Normal lid closure Complete, weak, Complete, without Incomplete some resistance resistance Swallowing 4 oz. water (1/2 cup) Normal Minimal coughing or Severe coughing/chok- Cannot swallow throat clearing ing or nasal regurgitation (test not attempted) Speech after counting aloud from 1 to 50 (onset None at 50 Dysarthia at 30–49 Dysarthia at 10–29 Dysarthia at 9 of dysarthria) Right arm outstretched (90 deg sitting), seconds 240 90–239 10–89 0–9 Left arm outstretched (90 deg sitting), seconds 240 90–239 10–89 0–9 Vital capacity, % predicted 80 65–79 50–64 <50 Rt-hand grip, kgW Men 45 15–44 5–14 0–4 Women 30 10–29 5–9 0–4 Lt-hand grip, kgW Men 35 15–34 5–14 0–4 Women 25 10–24 5–9 0–4 Head lifted (45 deg supine), seconds 120 30–119 1–29 0 Right leg outstretched (45 deg supine), seconds 100 31–99 1–30 0 Left leg outstretched (45 deg supine), seconds 100 31–99 1–30 0 Total QMG score (range, 0–39) From Howard J. F.: Physician Issues. In Myasthenia Gravis – A Manual for the Health Care Provider, (James F. Howard Jr [ed]). Myasthenia Gravis Foundation of America, Appendix 2.1, pg. 116, 2008. Used with Permission. Refer to source for more information regarding administration of the QMG Assessment Tool.

16 Care of the Patient with Myasthenia Gravis Table 4. Nursing Assessment of Muscle Strength and Fatigability and Respiratory Function in Myasthenia Gravis Body System History/Observation Measurement Ocular Alignment, diplopia Extra ocular movements (H pattern testing) Ptosis Lid lag, fatigable ptosis (use pupil as a benchmark)

Bulbar Restricted to soft foods, when chewing food such as steak Count to 50, document the number at which speech changes; Chewing Drooling, difficulty handling secretions, double swallows, nasal regurgitation describe speech (e.g., slurred, nasal, soft) Swallowing Speech

Facial Flattening of nasolabial fold Resisted eyelid and lip closure, cheek puff, smile

Neck Head drop Resisted flexion and extension

Limbs Strength testing: shoulders, triceps, wrist extension Upper Strength testing: hip flexion, ankle dorsiflexion Lower

Respiratory Shortness of breath when lying down/bending over Rate, rhythm, quality of respirations Increased respiratory effort Pulmonary function tests Anxiety

Sources: Abbott, 2010; Vassar et al., 2008; Weeks, 2012

capacity (FVC) in supine and sitting posi- iv. Neostigmine: One small random- tions (Howard, 2008). ized controlled trial using intra- 3. Oxygen saturation and blood gas analysis nasal neostigmine versus placebo are not good indicators of chest muscle and showed efficacy of an AChE inhibi- diaphragm strength and the ability to sup- tor treatment (Mehndiratta, Pandey, port respiratory function (Howard, 2008). & Kuntzer, 2011). All other AChE Nursing recommendation: Nurses should drug studies have been observation- assess the appropriate- al (Mehndiratta et al., 2011). ly and support respirations as needed un- v. AchE inhibitor drugs are titrat- til additional interventions are available ed to the individual patient with (Level 3). consideration for side effects and muscle strength. Dose regimens XVII. Treatment vary between individuals (Ange- A. The goal is disease and symptom management lini, 2011; Saperstein & Barohn, (Angelini, 2011). 2004). B. Pharmacologic management (Table 5) Nursing recommendation: Nurs- 1. Symptom management es must administer and teach the a. AChE inhibitors slow the degradation patient with MG and their fami- of ACh to allow ACh to remain avail- ly to administer the correct dose able at the NMJ; adverse effects include of AChE inhibitors on time (Lev- fasciculations, abdominal cramps, and el 2). Nurses must also teach the diarrhea (Saperstein & Barohn, 2004; patient and their family the signs Skeie et al., 2010). and symptoms of overdose and i. AChE inhibitors are also first-line adverse events (Level 2). treatment for children (Finnis & b. Jayawant, 2011). i. Immunosuppressive or immuno- ii. AChE inhibitors include pyr- modulating agents can have either idostigmine (Mestinon) and a general or targeted immunosup- neostigmine. pressive effect. iii. Pyridostigmine (Mestinon) is ii. Corticosteroids such as predni- dosed up to 60 mg five times per sone have a generalized immu- day; this is usually the regimen at nosuppressive effect. While these the beginning of the disease and drugs decrease the immune at- for treatment of milder disease tack on the proteins and receptors (Skeie et al., 2010).

Care of the Patient with Myasthenia Gravis 17 Table 5. Medications Used in the Management of Myasthenia Gravis Classification Drug Dose Special Considerations (Recommendations) Symptomatic Therapy: Pyridostigmine (Mes- 30, 60, 90, mg every 4-6 Doses increased and adjusted to efficacy and side effects tinon, Mestinon Time hours orally Take 30-60 minutes before eating with bulbar symptoms Acetylcholinesterase Span) Adverse gastrointestional effects include nausea and vomiting, abdominal cramping, inhibitors and diarrhea. Effectiveness may dissipate if taken with food May require an antidiarrheal agent Other side effects include increased salivation, drooling, and tearing; increased bronchial secretions; and perspiration. Mestinon SR 180 mg of Late-evening time span preparations are indicated only with marked myasthenic a time-span (slow- weakness in the morning. release form) at bedtime A liquid form is available for children and adults with swallowing difficulties. Do not substitute regular Mestinon or generic pyridostigmine for Mestinon SR . The dose schedule for a particular patient may vary from time to time, even daily, particularly during periods of stress or infection (Mehndiratta, Pandey, & Kuntzer, 2011; MGFA, 2012b). Nursing recommendation: Nurses should administer and educate pa- tients to take pyridostigmine as prescribed. (Level 2). Glucocorticosteroids 0.75–1.0 mg/kg daily or Option to slowly increase doses; after reaching near remission, gradual dose reduc- (GCS): General immu- 60–100 mg on alternate tion nosuppressives for the days orally, option for Monitor for side effects. short or long term long-term therapy; Increased risk for osteoporosis: exercise and supplement diet with increased calcium, vitamin D Not FDA approved a lower dose (10–25mg) Increased risk for glaucoma; eye checks are needed for MG every other day may be Increased susceptibility for infection; take precautions such as immunization against used when combined the flu with other treatments to Increased risk for obesity, diabetes, hypertension, electrolyte imbalance (hypokale- decrease side effects mia) (Schneider-Gold, Gaidos, Toyka, & Hohlfeld, 2005) Nursing recommendation: Nurses should monitor for side effects associ- ated with glucocorticosteroids and adjust dosage as prescribed (Level 2). Targeted immunosup- (Imuran) 2–4 doses of 50 mg/day Use an initial trial dose of 1-50 mg as a test dose for primary . Divided pressive (long-term (2–3 mg per kg body daily doses are better tolerated than single doses. use) weight/day) oral One dosing schedule is 50 mg/day and increase by 50 mg/day every 7 days until 150–200 mg/day is obtained. Not FDA approved Often Initially combined Dose decreases may result in worsening of symptoms. for MG with GCSs May administer with corticosteroids Gradual improvement in 6–12 months May cause flu-like illness in 10% of patients (Gold, Hohlfeld, & Toyka et al., 2008; Saperstein & Barohn, 2004) Discontinue if liver enzymes are elevated or white blood cells decrease below 3,000 cells/mm3 (Saperstein & Barohn, 2004; Hart, Sathasivam, & Sharshar, 2007; Angeli- ni, 2011). Nursing recommendation: Nurses should monitor for signs and symp- toms of infection, hepatotoxicity, nephrotoxicity, bone marrow suppres- sion, and skin cancer (Level 3). Targeted immunosup- Cyclosporine A (San- Starting dose 5mg/kg Steroid sparing if intolerant of Azathioprine pressive (long-term dimmune, Neoral) body weight in 2 divided Measure blood trough levels until ideal dosing is obtained and during drug dose use) doses ( q12h) change. Not FDA approved Optimal dosing mon- Blood levels should be checked at 1 month and adjusted as needed. for MG itored by measuring Monitor serum creatinine related to nephrotoxicity. trough drug levels Monitor for side effects Off-label status despite evidence (Tindall, Phillips, Rollins, Wells, & Hall, 1993; Ciafaloni, Nikhar, Massey, & Sanders, 2000) (Nursing recommendation: Nurses should monitor for nephrotoxicity (Level 3).

Targeted immunosup- · Mycophenolate 1000–2000 mg/day Well-documented single case studies available; publication of a randomized clinical pressive (long-term mofetil (CellCept) orally trial pending use) Not FDA approved for Twice-per-day sched- Gastrointestinal symptoms and infection possible side effects. MG uling Monitor complete blood count and differential every 2 weeks six times. and then monthly (Saperstein & Barohn, 2004). Nursing recommendation: Nurses should monitor for myelosuppression (Level 3).

18 Care of the Patient with Myasthenia Gravis Table 5. Medications Used in the Management of Myasthenia Gravis Targeted immunosup- · Methotrexate sodium 7.5 mg to 15 mg/week Well-documented single case studies available; publication of a randomized clinical pressive (long-term (Methotrexate) orally trial pending use) Not FDA approved Monitor for infection. Targeted immunosup- · Cyclophosphamide 500 mg/m2 every 4–12 Well-documented single case studies available; publication of a randomized clinical pressive (long-term (Cytoxan) weeks IV or 1–2 mg/ trial pending use) kg body weight per day Adverse effects include myelosupression, hemorrhagic cystitis, and increased risk for orally malignancy (Silvestri & Wolfe, 2012). Nursing recommendation: Nurses should monitor for myelosuppression, hemorrhagic cystitis, and increased risk for malignancy (Level 3).

Targeted immunosup- · Tacrolimus (FK506) 0.1 mg/kg/day orally Adverse effects include nephrotoxicity and hyperglycemia (Angelini, 2011) pressive (long-term (Prograf) titrated to blood levels Nursing recommendation: Nurses should monitor for nephrotoxicity and use) 0.2 (2 x 2-5mg/day) hyperglycemia. (Level 3). orally Other · (Rituxin) 375 mg/m2 IV weekly For refractory MG, and MuSK MG Immunosuppressive Adverse effects include pancytopenia (Ibrahim, Dimachkie, & Shaibani, 2010; Silvestri & Wolfe, 2012). Nursing recommendation: Nurses should monitor pancytopenia associat- ed with long-term immunosuppression (Level 3). · Off-label option; available for nonresponders, in cases of very severe MG, or when intolerable side effects occur. Abbreviations: FDA, U.S. Food and Drug Administration; IV, intravenous; MG, myasthenia gravis. Source: Tindall et al., 1993; Ciafaloni et al., 2000; Schneider-Gold et al., 2005; Gold et al., 2008; Hart et al., 2007; Vassar et al., 2008; Meriggioli, 2009; Mehndri- atta et al., 2011; Saperstein & Barohn, 2004; Angelini, 2011; Myasthenia Gravis Foundation of America, 2012b; Silvestri & Wolfe, 2012; Myasthenia Gravis Foundation of America, 2012b; Schneider-Gold, Gaidos, Toyka, & Hohifeld, 2005; Vessar et al., 2008)

involved in MG, they also sup- et al., 2006) and provide targeted press general immune function immunosuppression. Side effects significantly, increasing the risk include infection, nephrotoxici- for infection. Side effects to mon- ty and hypertension (Saperstein & itor include signs of infection, Barohn, 2004). weight gain, hypertension, dia- Nursing recommendation: Nurses should betes, osteoporosis, and psycho- advise patients who are taking corticoste- sis (Gold et al., 2008; Saperstein & roids to be aware of infection risk, practice Barohn, 2004). Other signs of in- good hand hygiene practices, and avoid ex- fection may be masked and can posure to people with infection (Level 2). delay wound healing (Zaiontz & Nursing recommendation: Nurses should Lewis, 2011). monitor for side effects associated with im- iii. Immunosuppressive agents with a munosuppressants and minimize patient targeted immunosuppressive effect risk for infection by maintaining appropri- in MG include azathioprine (Im- ate infection-control practices, including muran), cyclosporine (Sandim- good hand hygiene and sterile technique mune, Neoral), mycophenolate for invasive procedures (Level 2). Nurses mofetil (CellCept), mycopheno- should administer antimicrobials as pre- late sodium (Myfortic), cyclophos- scribed (Level 2). phamide (Cytoxan), tacrolimus Nursing recommendation: Nurses should (Prograf), methotrexate sodium monitor for of adverse (Methotrexate), and rituximab effects associated with all medications used (Rituxan). These agents block lym- in the management of MG as previously phocyte production. Side effects described, including those most common- to monitor include signs of infec- ly associated with long-term immuno- tion, bone marrow suppression, suppressants/immunomodulating agents, nephrotoxicity, and hepatotoxicity specifically, infection, hepatotoxicity, neph- (Angelini, 2011; Gold et al., 2008; rotoxicity, bone marrow suppression, and Saperstein & Barohn, 2004). skin cancer (Level 3). iv. Drugs such as cyclosporine alter T-cell response (Conti-Fine

Care of the Patient with Myasthenia Gravis 19 C. Other therapies venous access (Level 2). 1. Immunomodulation (Conti-Fine et al., 2006) v. Adverse reactions associated with a. (therapeutic plasma plasmapheresis relate to replace- exchange [TPE]) ment fluids and are more common i. Plasmapheresis, or TPE, has been with fresh frozen plasma than used in acute myasthenic crisis with albumin (20% versus 1.4 %) and for treatment prior to thymec- (Sutton, Nair, & Rock, 1989). tomy (surgical removal of the a) Side effects include thymus gland). The American hypotension resulting from Academy of has pub- fluid volume changes and lished a guideline for the use of hypocalcemia from citrate plasmapheresis for neurologic dis- used during plasmapheresis, orders including MG, but, because causing dizziness, paresthe- of the lack of large randomized sias, and headache (Zaiontz & controlled trials, cannot support Lewis, 2011). Fluid overload, or refute the use of plasmapheresis congestive heart failure, in- in MG (Gajdos, Chevret, & Toyka, fections, and thrombotic and 2002; Cortese et al., 2011). bleeding tendencies have been ii. The goal of plasmapheresis is the observed as well (Trouth et al., removal of antibodies 2012; Juel & Massey, 2007). from the circulation (Gold et al., Nursing recommendation: Nurses 2008; Keesey, 2004). One retro- should monitor for side effects asso- spective study demonstrated im- ciated with plasmapheresis including provement with plasmapheresis fatigue and hypotension (Level 2). (Cortese et al., 2011). b. Intravenous immunoglobulin G Nursing recommendation: Nurses (IVIG) infusions should monitor for improvement i. IVIG is a blood product composed following plasmapheresis (Level 2). of purified and concentrated im- iii. Plasmapheresis separates the plas- munoglobulins (antibodies) from ma from other components in the pooled plasma of many healthy blood, especially red blood cells. donors. It binds circulating anti- The patient’s plasma is exchanged bodies, thereby promoting ACh with donor plasma or albumin solu- availability and muscle function. tion, and new plasma or albumin ii. Randomized controlled trials and red blood cells are returned to (Gajdos, Chevret, Clair, Tran- the patient (Cortese et al., 2011). chant, & Chastang, 1997; Gajdos iv. Plasmapheresis requires venous et al., 2005; Ronager, Ravnborg, access, which involves either two Hermansen, & Vorstrup, 2001; large, durable peripheral veins or Wolfe et al.; 2002; Zinman, Ng, & a central line using a catheter that Brill, 2007) have been published has a dual lumen and is large and regarding the use of IVIG in the sturdy enough to withstand management of MG. One ran- significant flow and pressures (Juel domized controlled trial showed & Massey, 2007). efficacy in management of exacer- a) Complications of venous bations of MG compared with pla- access (peripheral or central) cebo (Patwa, Chaudry, Katzberg, include infection, pain, nerve Rae-Grant, & So, 2012). Other damage, thrombosis, perfora- studies did not show any differ- tion, dissecting hematomas, or ence in regard to the efficacy of arteriovenous fistulas (Vassar IVIG compared with plasma ex- et al., 2008). change (Patwa et al, 2012) nor Nursing recommendation: any difference in dosages of 1 g/ Nurses should monitor for kg versus 2 g/kg nor IVIG versus complications associated with methylprednisolone.

20 Care of the Patient with Myasthenia Gravis iii. IVIG can be used as an acute in- x. Hypersensitivity reactions present tervention to decrease the sever- in about 1 of 300 patients receiv- ity of MG exacerbations or as a ing IVIG. These patients typically chronic maintenance therapy in have a selective immunoglobulin MG or prethymectomy (Gold et A (IgA) deficiency and then devel- al., 2008; Skeie et al., 2010). op anti-IgA antibodies. Symptoms iv. Response varies between 60% and include those of , such 70% (Gold et al., 2008; Saperstein as respiratory distress, chest tight- & Barohn, 2004). ness, tachycardia hypotension, an- a) Inconsistent improvement is gioedema, erythema, fever, chills, seen among patients with MG and urticaria (Keesey, 2004). who have acute exacerbations xi. In the case of hypersensitivity re- and in chronic maintenance actions, appropriate agents for therapy (Saperstein & Barohn, treatment (e.g., epinephrine, di- 2004). phenhydramine, oxygen, vasopres- b) IVIG is administered as daily sors) should be readily available infusions over 2–5 days (Juel (Gahart & Nazareno, 2012). & Massey, 2007; Saperstein & xii. Pretreatment with an antipyret- Barohn, 2004; Trouth et al., ic, antihistamine, and/or cortico- 2012). steroid to prevent chills and fever c) Onset of benefit begins about may reduce the frequency and se- 3–10 days after beginning verity of hypersensitivity reactions treatment and may last for up (Gahart & Nazareno, 2012; Juel & to 4 months, with 21–45 days Massey, 2007). being average (Gold et al., xiii. IVIG should be used with caution 2008; Keesey, 2004). in the older adult population with v. IVIG may be combined with im- multiorgan disease because of munosuppressive medications. risk for complications (Gold et al., vi. IVIG is costly, and supply may be 2008). limited (Gold et al., 2008). Nursing recommendation: Nurses vii. IVIG may be administered via a must understand the rationale for the central venous implanted port, use of IVIG in the management of MG percutaneously inserted central and its reported benefits and limita- catheter line, or large-bore periph- tions (Level 2). Nurses must be knowl- eral IV catheter. edgeable of different brands of IVIG viii. Each infusion takes approximately and institution-specific protocols re- 4–6 hours, depending on the dos- garding dosage and rates, which may age and infusion rate. The usual include a test dose and then a gradu- dose is 1–2 g/kg. The rate of infu- al increase in rate as tolerated to less- sion may be gradually increased en risk for adverse effects. Action plans over the course of a single dose to for adverse effects must be followed lessen risk for side effects. (Keesey, (Level 2). 2004). The frequency is individu- c. Thymectomy alized (Vassar et al., 2008). i. Surgical removal of the thymus ix. Adverse reactions have been seen gland has been found to decrease in fewer than 10% of patients re- MG symptoms in as many as 70% ceiving IVIG (Gold et al., 2008) of patients who have and include circulatory overload, or dysplasia of the thymus gland renal failure, nausea and vomit- (Gold et al., 2008). ing, headaches, aseptic meningi- ii. The benefit of thymectomy in se- tis, thrombosis, stroke, seizures, ronegative MG, nonthymomatous retinal vasculitis, skin rashes, and MG with exclusively ocular MG, alopecia (Gold et al., 2008; Juel & or seronegative MG with MuSK Massey, 2007; Keesey, 2004). antibodies is less likely and not

Care of the Patient with Myasthenia Gravis 21 recommended (Howard, 2008; 2009; University of Maryland, Jacob, Viegas, Hilton-Jones, & 2008). Wilcox, 2007; Magee & Mack, e) When VATS is used, a small 2009; Sanders, El-Salem, & incision is made on the left Massey, 2003; Skeie et al., 2010). or right side of the chest. iii. No published randomized con- Fiber-optic instruments are trolled trials regarding efficacy used to visualize and remove exist, although a trial is in prog- the thymus. In the extended ress that compares thymectomy form, additional incisions in nonthymomatous MG with are made on both sides of thymectomy and thymectomy and the chest and in the neck. prednisone (NINDS & National (Figure 3d) (Magee & Mack, Institutes of Health, 2006). 2009; University of Maryland, iv. Different surgical approaches may 2008). be undertaken in centers with ex- f) VATS and VATET may perienced thoracoscopic surgeons require longer operative time, in collaboration with neurologists but these procedures reduce specializing in neuromuscular dis- the length of the hospital stay, ease (Figures 3a-d) postoperative pain, and blood a) Surgical approaches include loss and result in a better cos- transsternal, transcervical, and metic result than transsternal video-assisted thoracoscopic thymectomy (Zahid, Sharif, surgery (VATS) or video-as- Routledge, & Scarci, 2011). sisted thoracoscopic extended v. Complications of thymectomy in- thymectomy (VATET) (Magee clude respiratory failure related to & Mack, 2009; University of myasthenic crisis (6%), infection Maryland, 2008). (11%), and laryngeal or phrenic b) The transsternal approach nerve injury (Juel & Massey, 2007; involves making a midline Watanabe et al., 2004). incision through the sternum a) For the patient with preop- to expose the thymus and erative respiratory or bulbar remove it. A chest tube is symptoms, treatment with one inserted (Figure 3a) (Magee of the rapid immunotherapies, & Mack, 2009; University of plasmapheresis, or IVIG may Maryland, 2008). be warranted prior to surgery c) A partial transsternal ap- or during the postoperative proach is possible as well, with period. an incision through only half b) Bulbar symptoms, a preopera- of the sternum to expose and tive history of myasthenic cri- remove the thymus (Figure sis, and a preoperative serum 3b) (Magee & Mack, 2009; AChR antibody value higher University of Maryland, 2008). than 100 nmol/L is associated d) In a transcervical thymec- with a higher likelihood of tomy, a horizontal incision postoperative MG (Watanabe is made at the lower part of et al., 2004). the neck; a scope is inserted vi. Age under the sternum to visualize a) There is no official age-related the thymus and remove it contraindication for thymec- using small instruments. This tomy (Saperstein & Barohn, approach is less invasive than 2004). transsternal but may be more b) The patient more than 60–65 likely to result in incomplete years of age does not usually removal of the thymus undergo thymectomy, except (Figure 3c) (Magee & Mack, those with thymoma (Gold,

22 Care of the Patient with Myasthenia Gravis Figure 3. Surgical Approaches for Thymectomy

a) Transsternal Approach b) Partial Transsternal Approach

c) Transcervical Approach d) VATS or VATET

Copyright University of Maryland Medical Center. (August 7, 2008). Myasthenia Gravis Center. In University of Maryland Medical Center. Retrieved September 6, 2012, from http://www.umm. edu/mg/surgery.htm. Used with permission.

2008). Gronseth & Barohn, 2000). c) If malignant thymoma is • A better prognosis has present, thymectomy is been reported at less than recommended for patients of 1 year of disease duration any age (Gold et al., 2008). (Aghajanzadeh, Khoshrang, d) In nonmalignant thymoma, Mohammadzadeh, Roud- surgical thymectomy is bari, & Ghayeghran, 2007). usually performed on patients • A better prognosis has also 10–50 years of age (Gold et al., been reported within 5 2008). years since first manifesta- e) A thymectomy in the patient tion (Gold et al., 2008). older than age 60 may not b) The average daily dose of an be as beneficial because of anticholinesterase drug may atrophy of the thymus gland decrease after thymectomy. (Saperstein & Barohn, 2004). (Durieux et al., 2008). f) Thymectomy benefits patients c) Improvement in the MG may at all stages of MG (Durieux, not occur immediately and Radermecker, Dekoster, & may take up to several months Limet, 2008). or years to reach maximal vii. Prognosis after thymectomy benefits (Juel & Massey, 2007; a) A better prognosis is likely for Keesey, 2004; Saperstein & patients receiving thymecto- Barohn, 2004). my early after initial symptom d) The degree of improvement onset (Gold et al., 2008; may be related to preoperative

Care of the Patient with Myasthenia Gravis 23 MG status and rate of decrease approach, after thymectomy, pa- in AChR antibody titer (Agha- tients may need a chest tube(s) janzadeh et al., 2007; Hase et al., to control and monitor thoracic 2006). drainage. Hourly chest tube drain- Nursing recommendation: In col- age of greater than 100 ml is ex- laboration with the multidisci- cessive (Durai, Hoque, & Davies, plinary team, nurses should educate 2010; Jacob et al., 2007; Malone, the patient and family regarding 2010). indications, pre- and postopera- Nursing recommendation: Nurs- tive care, and prognosis for patients es should follow the manufactur- undergoing thymectomy (Level er’s direction for the chest tube 3). Following thymectomy, nurses drainage system and monitor should monitor the patient close- chest tube(s) for patency, under- ly for complications related to MG water seal, evidence of air leak, and the thymectomy procedure and drainage output, and signs and manage them effectively (Level 3). symptoms of infection. Nurs- d. Postoperative care after thymectomy es should monitor for signs and i. Close monitoring in an intensive symptoms of increasing pneumo- care unit setting is usually needed thorax or hemothorax (Level 3). for monitoring of respiratory sta- e. Factors that may increase the likeli- tus. Pulmonary function testing, hood for crisis and result in prolonged specifically forced vital capaci- neuromuscular weakness after surgery ty (FVC) and negative inspirato- include the following (Watanabe et al., ry force (NIF), are recommended 2004): (Jacob et al., 2007; Mehta, 2006). i. Preoperative vital capacity of less Nursing recommendation: Nurs- than 1.2 L es should monitor respiratory sta- ii. Preoperative bulbar symptoms tus, including rate, depth, work of such as dysphagia, difficulty chew- breathing, breath sounds, oxygen- ing, dysphonia, and dysarthria ation, and ventilation tolerance. iii. History of preoperative myasthen- Spontaneous breathing trials, pul- ic crisis monary function studies, FVC, iv. Preoperative AChR antibody se- and NIF should be ordered as rum level higher than 100 nmo/L. available (Level 3). v. Intraoperative blood loss exceed- ii. An increase in myasthenia symp- ing 1,000 ml toms can occur postoperatively; Nursing recommendation: Nurs- these symptoms are related to an- es should be aware of patients who esthesia, analgesia, and sedation have factors that may increase the and omission of medications ad- likelihood of a postoperative MG ministered intraoperatively, which crisis that could complicate their may result in prolonged postoper- recovery (Level 3). ative mechanical ventilation (Ja- f. Patients undergoing thymectomy for cob et al., 2007; Mehta, 2006). MG have an impaired immune system Nursing recommendation: as a result of their disease and medical Nurses must administer MG management. They are at risk for post- medications postoperatively as operative infection related to invasive prescribed. Nurses should balance devices and surgical incisions (Jacob et the administration of medications al., 2007). that may worsen MG, including Nursing recommendation: Nurses opioids, with a comfort level that should monitor closely for signs and will allow the patient to breathe symptoms of infection and minimize with the least amount of effort and a patient’s risk for infection by consis- discomfort (Level 3). tently complying with infection-con- iii. Depending upon the surgical trol measures (Level 3).

24 Care of the Patient with Myasthenia Gravis XVIII. MG Crises commercial, agricultural, military, and bio- A. An MG crisis occurs when there is an exacerba- terrorism chemicals that have cholinergic tion of MG symptoms (myasthenia crisis) or as a properties. result of treatment associated with excess doses of 2. Symptoms of cholinergic excess include a , a cholinergic crisis. DUMBBELL, a mnemonic for diaphoresis, 1. Differentiation of crisis is a priority (Table 6). urination, miosis, bradycardia, bronchial B. Myasthenic crisis is defined as any provoked secretions, emesis, lacrimation, and loose MG exacerbation necessitating mechanical ven- stools (Krob, 2008).Worsening of symp- tilation that results from weakness of the respi- toms in response to an edrophonium chlo- ratory and bulbar muscles. ride injection is indicative of cholinergic 1. Most patients presenting with myasthenic excess. Withdrawing the anticholinesterase crisis have an identifiable risk factor such medication should result in improvement. as infection, drug use, stress, endocrine Edrophonium may cause an interaction disorder, or metabolic imbalance (Krob, with antiarrhythmics. Respiratory manage- 2008). ment for ineffective respiratory and bulbar 2. Myasthenic crisis should be suspected in function is related to the weakness of in- all patients with respiratory failure, partic- tercostal muscles, diaphragm, larynx and ularly those with unclear etiology. pharynx (Barrick & Kyle, 2008). 3. Additional manifestations of myasthenic Nursing recommendation: Nurses should crisis include generalized increased weak- be knowledgeable in the differentiation of ness; tachycardia; pale, cool skin; and the two different types of MG crises, my- hypertension. asthenic crisis or cholinergic crisis, and 4. The in-hospital mortality rate is higher in should recognize that both are care pri- myasthenic crisis than for overall inpa- orities. In either situation, nurses should tient MG mortality, at 4.47% versus 2.20% perform a complete respiratory and neuro- (Alshekhlee et al., 2009). muscular assessment, which is essential to 5. Acute management requires comprehensive identify ineffective respiratory function and care with attention to all systems and venti- impaired gag and swallow, and initiate the latory support and institution of measures appropriate airway-management strategies to minimize neuromuscular blockade. and oxygen delivery (Level 3) (Vassar et al., a. Plasma exchange or IV 2008). immunoglobulin 3. Assess and document respiratory status, b. Identification and removal of offend- rate, rhythm, and breath sounds. ing trigger(s) 4. Assess gag and cough reflexes and quali- C. Cholinergic crisis is defined as neuromuscular ty of voice; notify the physician of changes weakness and respiratory failure resulting from from baseline. a high dose of cholinesterase inhibitors (see Ta- 5. Obtain baseline FVC (normal > 60 mg/kg). ble 2) and may present with symptoms similar 6. Obtain NIF (normal > -70 cmH2O) and to myasthenic crisis. continue to monitor (Mehta, 2006; Vassar 1. Although less common, cholinergic cri- et al., 2008). sis may be associated with the use of

Table 6. Differentiating Myasthenia Crisis and Cholinergic Crisis Clinical Features Myasthenic Crisis Cholinergic Crisis Heart rate Tachycardia Bradycardia Muscles (including respiratory) Flaccid Flaccid and fasciculations Pupil size Normal or large Small Skin Pale, cool Red, warm Gastrointestinal No change Diarrhea, cramps Secretions No change Increased Tensilon (edrophonium) test Improvement Worsening

Source: Krob, 2008

Care of the Patient with Myasthenia Gravis 25 7. Notify a physician or advanced practice d-penicillamine (known to cause MG), nurse regarding respiratory abnormalities botulinum, and telithromycin (Howard, or change in FVC and/or NIF from base- 2008; Pascuzzi, 2007). line value or NIF < -30, FVC < 1.5 liter 3. Agents commonly used for surgical and (Mehta, 2006; Vassar et al., 2008). dental procedures may also exacerbate or a. Values of FVC < 1.0 liter or < 15 mL/ have the potential to worsen MG; conse-

kg body weight/NIF < -20 cm H2O are quently, they should be used with extreme indications for mechanical ventilation caution and require careful monitoring. (Mehta, 2006; Vassar et al., 2008). Examples include certain neuromuscular 8. If facial weakness is present, obtain NIF/ blocking agents (e.g., succinylcholine ve- FVC via face mask. curonium), local anesthetics, analgesics, 9. Administer intubation, mechanical ventila- and anxiolytics, sedatives, and hypnotics tion, intermittent positive-pressure breath- (Howard, 2008; Pascuzzi, 2007). ing (IPPB), and oxygen as needed. Note: The above lists are not all-inclusive, 10. Suction and chest physiotherapy to man- are current at the time of this publication, age secretions and may change in the future. Numerous D. Aggressive respiratory treatment (e.g., suction- additional medications are reported to in- ing, IPPB, sighs [mechanical ventilator breaths crease weakness in some patients with of greater tidal volume than the set tidal vol- MG. Refer to all current drug information umes delivered several times each hour to less- as it relates to the patient with MG. en atelectasis], chest physiotherapy) diminishes Nursing recommendation: Nurses should the risk for prolonged respiratory complications, administer drugs that may worsen MG including prolonged mechanical ventilation and with caution. Review medication profiles risk for pneumonia (Varelas et al., 2002). with the pharmacist and licensed indepen- Nursing recommendation: Nurses should as- dent provider (Level 3). sess respiratory status, including pulmonary B. Nursing management of swallowing and chewing function tests (i.e., NIF and FVC); provide pul- impairment (Butler, 2008; Vassar et al., 2008). monary hygiene as needed; and alert the licensed 1. Adjust the patient’s eating schedule to op- independent provider regarding indications for timize medication efficacy. Typically, meals additional respiratory therapy management to should be taken during periods of optimal minimize respiratory complications, including strength (such as during the earlier part of prolonged ventilation and pneumonia (Level 3). the day, 30 minutes after administration of cholinesterase inhibitor medications, or af- XIX. General nursing management of the patient with ter rest periods). MG a. Because muscle fatigue impairs chew- A. Medications that may worsen MG ing and swallowing, the following will 1. Many drugs used in the treatment of other facilitate maintaining nutritional status conditions may exacerbate or have the po- and decreasing the risk for aspiration: tential to worsen MG by increasing weak- i. Allow the patient to rest before ness; consequently, they should be used eating and drinking. with extreme caution and require care- ii. Provide foods that are soft, tender, ful monitoring. Examples include quinine, and not sticky and do not require , procainamide, and lidocaine; a lot of chewing. macrolide and aminoglycoside antibiot- iii. Provide highly viscous foods and ics (erythromycin, azithromycin, gentam- thickened liquids that are easy to ycin, kanamycin, neomycin, vancomycin); chew and swallow. quinolone antibiotics (, levo- iv. Offer the patient small bites and floxacin, ); beta-blockers such instruct him or her to chew well, as and dorzolamide eye drops; eat slowly, swallow after each bite, calcium channel blockers; magnesium salts and swallow frequently. (laxatives, antacids, magnesium sulfate); v. Allow the patient to rest while and iodine-based contrast dye (Howard, chewing and in between bites to 2008, Pascuzzi, 2007). restore strength. 2. The following drugs should not be used vi. Allow the patient to take small in patients with MG: alpha-interferon, sips of liquids. 26 Care of the Patient with Myasthenia Gravis vii. Provide frequent, small meals that a. Identify self-care techniques and de- include high-calorie and high- velop strategies to decrease activi- protein foods. ty intolerance and risk for injury and viii. Offer large meals in the morning promote energy conservation at home, and small meals in the evening. at work, and in the community. a) Offer softer consistencies and b. Fatigue worsening occurs with overex- moisten dry food. ertion, physical and emotional stress, b) Position the patient upright warm temperatures, high humidity, with his or her head slightly and other exacerbating factors. forward when eating and c. Mental and physical self-care inter- drinking, using compensatory ventions include stress-reduction maneuvers (chin tuck, head techniques, pacing all activities, in- turn) as necessary. creased rest or sleep, and aerobic ex- c) Discourage talking and eating ercise (remaining physically active is at the same time and avoid the hallmark of fatigue management) distractions while eating. (Grohar-Murray, Becker, Reilly, & Ric- d) Review principles of nutrition ci, 1998; Vassar et al., 2008). and basic food groups so Nursing recommendation: Nurs- patients can select foods that es should apply the above strategies in provide a balanced diet. managing fatigue for the patient with b. Consult with a dietitian to determine MG (Level 3). nutritious food choices. XX. Special consideration in the juvenile MG c. Consult with a speech pathologist to population determine the safest, most effective A. Medication management in juvenile MG swallowing technique. 1. Azathioprine, cyclosporine, mycopheno- Nursing recommendation: Nurses late, and cyclophosphamide should adopt the previous protocols to 2. It may be necessary to avoid these drugs in facilitate swallowing, avoid aspirations, women of reproductive age because of pos- and optimize nutritional and fluid sta- sible teratogenic effects on the fetus (Ciafa- tus (Level 3). loni & Massey, 2004). C. Nursing management of fatigue 3. Birth control is required for sexually active 1. Assess a patient’s abilities and restric- women to avoid birth defects. tions to carry out daily activities including Nursing recommendation: Nurses should ADLs. Assess for weakness and/or visual be aware of the teratogenic effects of immu- impairment associated with self-care defi- nosuppressive medications on the fetus and cits and the need for assistive devices. provide appropriate education to women 2. Collaborate with licensed independent with MG of childbearing age (Level 3). providers to adjust medication dosage and B. Developmental issues schedule to maximize effectiveness. 1. The transition from juvenile to adult re- 3. Use consistent routines, allowing for suf- quires coordination and collaboration, ficient time. Use optimal positioning, and with a focus on transitions of care for is- offer positive reinforcement. sues such as childbearing, career, and 4. Plan activities to provide periods of rest. lifestyle. 5. Consult with a physical therapist and/or 2. Promote independence and a lifelong occupational therapist (Holmes, 2008). relationship with specialty healthcare 6. Consult with a psychologist or other qual- providers. ified professional to screen the patient for depression. Research has demonstrated XXI. Psychosocial and educational needs that depression, activity restrictions, and A. MG is characterized by relapses and exacerba- number of years since diagnosis can nega- tions and is considered a chronic illness. Edu- tively influence fatigue (Kittiwatanapaisan, cation regarding strategies to deal with disease Gauthier, Williams, & Oh, 2003). fluctuations includes appropriate goal setting. 7. Address activity abilities and restrictions. 1. Patient organizations and their sup- port groups that are devoted to MG are

Care of the Patient with Myasthenia Gravis 27 resources for patients and families. En- a. Teach the patient the strategies to courage visits to MGFA at www.myas- manage fatigue and conserve energy as thenia.org and the outlined in section C 1-7. Association at www.mda.org. Other un- b. Limit fatigue by pacing and planning, biased reputable Internet sources include using the following guiding principles www.MayoClinic.com, WebMD, and Med- (Holmes, 2008) line Plus. i. Prioritize. What is the most im- 2. General educational needs of the patient portant activity? What else do you with MG and their family (Vassar et al., want to do? 2008) ii. Listen to your body. Know when a. Knowledge of the disease and methods to push, and know when to rest. to control it iii. Plan the day. Pace; know limits, b. An understanding of the treatments strengths, and ; avoid and drugs used to control and manage overdoing and crashing; build in symptoms and disease rest periods; prepare for upcoming c. Awareness of all interactions that activities; go slow/get rest earlier drugs unrelated to MG may have on in the day; and recognize that exer- MG or the ways in which these drugs cise should not cause more fatigue. may interfere with drugs used to treat iv. Teach energy conservation strate- MG (refer to the drugs identified in gies applicable to various settings section XIX, General nursing manage- (Holmes, 2008; Thomas, 2008). ment of the patient with MG) a) Home: Sit during chores, d. Knowledge of the need to wear a med- delegate to family members, ical alert bracelet or medallion in- keep objects at an appropriate scribed with the words, “Myasthenia height, schedule rest periods, Gravis: Use Drug Precautions” and to plan activities, break an activ- carry an emergency alert card with an ity into parts, and use power accompanying drug list card available tools/electrical appliances. from MGFA b) Grooming: Sit on a stool to e. Awareness of birth defects that may shave or brush teeth, use an occur in offspring of women taking elbow prop and electric tooth- some classes of MG drugs brushes, take rest breaks, take f. Adjustment of eating schedules to op- shorter showers/baths with timize medication efficacy (Vassar et warm water, and sit to dress. al., 2008) c) Community: Park close to g. Knowledge regarding potential over- your destination, ask to get the-counter drug interactions with MG dropped off, or use a disabled h. Instructing the patient to discuss tak- parking permit. Avoid ing any newly prescribed medications peak shopping times, wear or over-the-counter drugs with their supportive walking shoes, physician or neurologist stay balanced (use a walker, i. Instructing the patient that if he or she cane, etc.), use a cart for is undergoing surgical or dental pro- merchandise, plan according cedures, he or she should request that to medication schedules, the surgeon, anesthesiologist, and/or unload perishables, shop by dentist consult with the physician or mail order, and bear in mind neurologist that small sizes weigh less. 3. Educational strategies to manage swallow- d) Work: Ensure proper neck and ing and chewing impairment (Butler, 2008) back support, sit rather than a. Teach the patient the strategies to stand, avoid eye strain, take manage swallowing and chewing as breaks, use proper air condi- outlined in sections B1 a.i through xii. tioning, and consider learning 4. Strategies to manage fatigue and conserve more about Family and energy Medical Leave Act provisions.

28 Care of the Patient with Myasthenia Gravis e) Lifestyle management to family regarding management optimize living with MG: Tar- of the disease; influence get good nutrition, physical of the disease on lifestyle, activity, stress management swallowing, and chewing and coping skills. Observe impairment; and fatigue and infection control and health energy conservation (Level 3). maintenance guidelines, XXII. Resources for patients, families, and healthcare medication guidelines, and professionals emergency alerts. A. Myasthenia Gravis Foundation of America: Nursing recommendation: www.myasthenia.org Nurses should educate the patient with MG and their

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32 Care of the Patient with Myasthenia Gravis Care of the Patient with Myasthenia Gravis 33