Myasthenia Gravis:A Nursing Perspective

On-line Continuing Education Program

MGFA: Nurses Advisory Board

Authors: Wilma Koopman, RN (EC), MScN, TCNP, CNN(C)

Marilyn Ricci, RN, MS, CNS, CNRN

Continuing Nursing Education Approval

Registered Nurses who complete this continuing nursing

education program and achieve an 70% score on the post test

will earn 2 contact hours.

This continuing nursing education activity was approved by the

American Association of Neuroscience Nurses, an accredited approver by the

American Nurses Credentialing Center’s COA.

Program Instructions

• Study the Myasthenia Gravis Continuing Education Program.

• To receive CE contact hours:

– Complete the Post Test, recording your answers in the test answer section. Each question has only 1 correct answer.

– Complete the Program Evaluation Form.

• Email the Post Test Answers and the Evaluation Form to Kday@kellencompany.com

• A passing score is 70% (20 correct answers)

• You will be notified of your test results.

• If you pass, a CE Certificate and an answer key will be returned to you within 4 – 6 weeks.

• If you do not pass, you have the opportunity to retake the test.

Disclosure Statement:

The authors and the Myasthenia Gravis Foundation have no significant

relationship or financial interest in any commercial companies that pertain to this

educational activity.

Program Objectives

Upon completion of this program, the participant will be able to:

1. Define Myasthenia Gravis (MG).

2. Discuss the epidemiology of myasthenia gravis.

3. Discuss the predisposing factors and environmental issues that may

contribute to the onset of MG.

4. Explain the pathophysiological mechanisms and autoimmune basis of

acquired MG.

5. Describe the common clinical presentations of patients with MG.

6. Discuss the classification system used to characterize the distinct

clinical features and severity of MG.

7. Compare the procedures used in the diagnosis of MG.

8. Discuss the medical and surgical therapeutic modalities used in the

treatment of MG and compare the side effects and risk factors associated with

each treatment option.

Program Objectives (continued):

9. Identify the nursing implications associated with the various treatment

options.

10. Describe a comprehensive nursing assessment of the patient with MG.

11. Identify the potential patient problems, expected outcomes, and the

appropriate interventions used to manage MG.

12. Discuss the factors that have an adverse effect and contribute to worsening

of MG.

13 Differentiate between Myasthenic Crisis and Cholinergic Crisis and identify the appropriate management strategies.

14. Discuss the impact of MG on the patient and the family members.

15. Demonstrate knowledge of myasthenia gravis and the appropriate

patient and family management.

Myasthenia Gravis (MG)

Acquired Autoimmune MG is –

• a chronic, neuromuscular, autoimmune disease that results in muscle weakness

• induced by T-cell dependent, antibody-mediated deterioration of the neuromuscular junction (NMJ)

• an alteration in the transmission of nerve impulses

(Mays, Butts. 2011)

MG in Childhood

• Congenital MG –

– an autosomal recessive genetic mutation

– synaptic malformation involving nerve cell, muscle cell or space between each

– not associated with an autoimmune process

– present at birth but may not manifest itself until several years later

– mild to severe weakness that usually does not progress

• Neonatal Transient MG –

– infants born to mothers with autoimmune MG

– placental passage of autoantibodies

– symptoms occur within hours of birth• generalized weakness, facial weakness

• weak cry, suck, swallow

• Respiratory distress

– may last several weeks to months

(Howard, 2008)

Types of Acquired MG

• Ocular versus Generalized– Ocular - limited to eyes with no other involvement

– Generalized – involves eyes with progression to bulbar and limb muscles

• Seropositive versus Seronegative– AChR antibodies

– No AChR antibodies but MuSK or titin antibodies

– No antibodies identified

• Juvenile – early age, onset before adolescence

• Early Onset versus Late Onset– Early onset – after adolescence & before age 50, more women than men

– Late onset – presents at 40 or 50 years – few more men than women

• Thymoma associated – peak onset 30’’’’s to 50’’’’s often having antibodies to several muscle proteins including titin

(Howard, 2008)

Epidemiology:

• Prevalence rate: 20 per 100,000 in the US

• Peak incidence:

– Women –• 20 to 40’’’’s• Average – 28 years of age

– Men – have 2 peaks

• 30’’’’s• 60’’’’s• Average – 42 years of age

– Late Onset – after 50 years

• Women 3:2 men

• Mortality: less than 5%

• Full remission: Uncommon

• Races: Caucasian, African American, Japanese

(Angelini, 2011, MDA, 2009)

Predisposing Factors/Risk Factors

• Familial myasthenia gravis:– genetic predisposition – 5%

• Drug Induced:– D-penicillamine

• Other Autoimmune Diseases:– Thyroid Disease

– Diabetes Mellitus, Type I

– Rheumatoid Arthritis (RA)

– Lupus Erythematosus (SLE)

– Demyelinating CNS Diseases: Amyotrophic Lateral Sclerosis (ALS)

• Hormonal Status:– Pregnancy

– Post partum

(Grob et al, 2008, Mays et al, 2011)

Differential Diagnoses

• Lambert Eaton Myasthenic Syndrome

• Amytrophic Lateral Sclerosis (ALS)

• Brainstem glioma

• Multiple Sclerosis (MS)

• Thyroid disease –– Hyperthyroid

– Hypothyroid

• Botulinism

• Stroke

• Muscular Dystrophy

(Keesey, 2004)

Pathophysiology of

Acquired Autoimmune MG

• Involves the specific components of the nervous system, the immune system and the interaction between the following:

– Neuromuscular Transmission Mechanisms

– Autoimmune Processes

– Thymus Gland

Neuromuscular Transmission

Mechanisms:

• Neuromuscular Junction

• Neurotransmitters

• Physiology of Neurotransmission

Neuromuscular Transmission:

• Neuromuscular Junction (NMJ) also known as the motor end-plate is composed of:

– Motor Nerve Terminal

• Highly specialized region containing synaptic vesicles

• Collects acetylcholine (ACh) & packages in vesicles for release into the synaptic cleft

– Synaptic Cleft• Separates motor nerve terminal from post-junctional region

– Post synaptic membrane• Enfolds to increase surface area

• Contains ACh receptors (AChR)

(Howard, 2008)

Neuromuscular Transmission:

• Neurotransmitters: Chemicals released by the neurons to signal other structures

• Neurotransmitters at the neuromuscular junction

– Acetylcholine (ACh)

• Synthesized at the nerve terminal from choline and acetate

• Stored in vesicles

• Released in response to nerve activation

• Binds with ACh receptors

– Acetylcholinesterase (AChE)

• Located in the synaptic clefts

• Hydrolyzes ACh into choline and acetate

• Choline and acetate taken back into the nerve terminal for resynthesis into ACh

(Howard, 2008)

Physiology of Neurotransmission:(pre & post synaptic depolarization)

• Acetylcholine (ACh) Pathway

– released in presence of Calcium into cleft

– binds with postsynaptic AChR receptors

– Na and K channels open ►►►►►►►► ►►►►►►►►

– depolorization produces action potential and

firing of post synaptic cell (muscle contraction)

– diffuses out of cleft

– hydrolized into choline and acetate

(Howard, 2008)

NMJ Figure from Howard 2008

Immune System Mechanisms

• Protects self from non- self :

- ability to recognize self, and not attack

- thought to develop during fetal life as immature

leukocytes are exposed to self

• Is lymphocyte driven:

- have surface receptors for a large array of possible

antigens (all are protein fragments of some kind

that are not recognized as self)

(Smeltzer & Bare, 2007 )

Immune System Mechanisms(continued)

• Several primary organs are involved– Bone marrow

– Thymus

• Consists of both humoral and cellular components– Humoral immunity – B lymphocytes

- Cell-mediated immunity - T lymphocytes/cells

- Natural killer cells

(Smeltzer & Bare, 2007)

Humoral Immunity:

Antibody-mediated immunity

• B cells are:

– derived from the bone marrow

– precursors of plasma cells (differentiated B cells)

• Plasma cells:

– are found in the plasma

– produce antibodies which are immunoglobulins (Igs)

• Antigens bind to the lymphocytes which has surface antibodies

• Some B cells remain as memory cells

• Effective against bacteria

(Smeltzer & Bare, 2007)

Cell-mediated Immunity

• T cells differentiate and mature in the thymus

• Types of T cells:– Cytotoxic T cells (CD8) – kill target cells

– T helper cells (CD4) – assist in antibody formation

Implicated in the formation of antibodies against ACh receptors.

– T supressor cells – inhibit immune responses

– T- delayed hypersensitivity cells

(Smeltzer & Bare, 2007)

Role of the Thymus

• Central organ for immunological self-tolerance, the capacity to

recognize self from non-self with the appropriate immunological

response

• Contains myoid cells that express the AChR antigen, antigen

presenting cells, immunocompetent T cells

• Normally targets and deletes AChR-specific T cells before they enter

the periphery

• Abnormal thymus results in loss of tolerance and development of

antibodies AChR and other proteins at the NMJ

• Abnormal in many patients with acquired MG

• B lymphocytes may be found in patients with MG

(Mays et al, 2011)

Autoimmune Processes in MG

• Antibody-mediated attack and complement-mediated destruction of the post-synaptic membrane (striated/voluntary muscles)

• AChRs degraded by auto-antibodies and complement activity

• Immunoglobin G (IgG) and complement components attach to and damage the muscle membrane resulting in loss of it’’’’s normal fold

• Synaptic junction distance is increased

• Reduced concentration of AChR’’’’s on muscle endplate membrane

• Antibodies block AChR binding sites

• ACh release is normal but post-synaptic membrane less sensitive

• Reduced probability that nerve impulses will be followed by a muscle action potential (AP)

(Mays et al, 2011, Howard, 2008)

Antibodies in MG

• Acetylcholine Receptor (AChR) Antibodies:– Found in 90% with generalized MG

– Found in 70% with ocular MG

– Synthesis of AChR antibodies is regulated by AChR-specific T-helper cells (CD4) which react primarily with the α subunits of the receptor

• Anti-MuSK Antibodies (10%)– postsynaptic membrane expresses muscle-specific receptor tyrosine

kinase ( MuSK)

– present as an antigen in 38 to 50 % of patients with generalized MG who are AChR antibody negative

• Muscle protein antibodies– Striated muscle antigens - titin

– Ryanodine & ryanodine receptors (RyR) (Chan et al, 2007, Mays et al, 2011)

Thymus Gland in MG

• Hyperplasic cells

– 60 - 70% of myasthenics

– B cells interact with helper T- cells

resulting in antibody production

• Thymoma

– 10-15% of myasthenics

– age 30 to 60

– more severe disease

– higher levels of AChR antibodies

Typical MG Events

• Clinical Course:– Restricted to eyes only (ocular MG) in 10%

– Progressive if not treated

– Generally weakness spreads to involve oropharyngeal muscles and limb muscles in 66 % within the first year

– Maximal weakness is reached in the first 2 - 3 years (Grob et al, 2008, Mantegazza, 1990)

• Initial Symptoms:– Ptosis or diplopia (double vision) - 2/3 of patients

– Difficulty chewing, swallowing - 16%

– Limb weakness - 10% (Howard, 2009)

• Minimal Precipitating Factors:– Infection, emotional stress(4%)

– Physical trauma ( 3%)

– Thyroid disease (1%) Ptosis in MG

– Pregnancy/delivery (1%) (Grob et al 2004)

Hallmark Characteristics of

““““Muscle Weakness”””” in MG

• Fatigability

• Fluctuates & asymmetrical – worse with

use, particularly at end of day

• Variable location of muscles involved

and severity of weakness within each myasthenic and among myasthenics

• Weakness increases with repeated activity, after effort and/or repeated testing

• Strength improves after rest

• Periods of worsening and remissions

Classic Clinical Features: Weakness in MG

• Eyes – double vision (diplopia). droopy eye lids (ptosis)

• Face – facial weakness (flat smile, drooping lips, poor brow movement, weak pucker, unable to puff cheeks out or suck)

• Speech – slurred (dysarthria), nasal or hoarse

• Oropharyngeal - chewing fatigue and dysphagia - swallowing problems may include gagging, choking, nasal regurgitation, difficulty clearing secretions

• Diaphragm - breathing shallow, decreased chest expansion,

short of breath, increased difficulty breathing bending over

or supine

• Neck and Proximal Limb Muscles –

- Head - dropped

- Arms – difficulty carrying, lifting, gripping

- Legs – difficulty climbing stairs, getting out of chairs/bed

(Howard, 2008)

Clinical Classification of MG

• Designed to identify subgroups of patients with MG who share distinct clinical features or severity of disease that may indicate different prognoses or responses to therapy

• Classes I through V

(Jaretzki A et al. 2000)

Clinical Classification of MG

• Class I: Any ocular weakness, may have weakness of eye

closure, all other muscle strength is normal

• Class II: Mild weakness affecting other than ocular muscles,

may also have ocular weakness of any severity

• Class IIa: Predominantly affecting limb, axial muscles or both,

may also have lesser involvement of oropharyngeal

weakness

• Class IIb: Predominantly affecting oropharyngeal, respiratory

muscles or both, may also have lesser or equal

involvement of limb, axial muscles or both

• Class III: Moderate weakness affecting other than ocular

muscles

• Class IIIa: Predominantly affecting limb, axial muscles, or both;

may also have lesser involvement of oropharyngeal

weakness

Clinical Classification of MG

• Class IIIb: Predominantly affecting oropharyngeal, respiratory

muscles or both; may also have lesser or equal

involvement of limb, axial muscles or both

• Class IV: Severe weakness affecting other than ocular muscles;

may also have ocular weakness of any severity

• Class IVa: Predominantly affecting limb and/or axial muscles

• Class IVb: Predominantly affecting oropharyngeal, respiratory

muscles or both; Use of feeding tube; May also have

lesser or equal involvement of limb, axial muscles or

both.

• Class V: Defined by intubation, with or without mechanical

ventilation, except when employed during routine

postoperative care. Use of a feeding tube without

intubation places the patient in class IVb.

Diagnostic Testing for MG

• Edrophonium (Tensilon) test – rarely used

• Ice Pack Test

• Serology: Auto-antibody Tests

– AChR antibody

– MuSK antibody, if AChR seronegative

– Anti-titin antibodies

– Anti RyR antibodies

• Electrodiagnostic Studies:

– Single fiber EMG

– Nerve Conduction Studies (NCS)

• Imaging Tests of the Chest:

– Computerized Tomography (CT)

– Magnetic Resonance Imaging (MRI)

Edrophonium (Tensilon )Test:

• A cholinesterase inhibitor: inhibits the action of AChE - slowing the breakdown of ACh which then prolongs the diffusion of ACh in synapatic cleft to allow interaction with AChR’’’’s resulting in endplate depolarization

• MG weakness improves after tensilon administration ..minutes

• Positive:

– 60-95% (ocular MG)

– 72-95% (generalized MG)

• Procedure:

– Select a weak muscle and test it

– Inject 0.1 cc Tensilon IV and look for improvement or adverse effects

• Excessive cholinergic stimulation of the heart with resulting bradycardia is possible– Atropine at bedside

– If no improvement or adverse effects, inject a further 0.9 cc slowly IV

– Retest the preselected muscle group

– Ideally, have someone else do the muscle testing to control for bias

(Pascuzzi, 2003)

Ice Pack Test

• Used in patients with ptosis especially if Tensilon test risky

• Based on the physiologic principle of improving neuromuscular transmission at lower muscle temperatures, the eyelid muscles are the most easily cooled by the application of ice

• Procedure:

– a bag (or surgical glove) is filled with ice and placed on the closed (ptotic) lid for two minutes.

– The ice is then removed and the extent of ptosis is immediately assessed.

• The sensitivity appears to be about 80 percent in those with prominent ptosis. The predictive value of the test has not yet been established.

(Golnik et al , 1999)

Serology:

Anti-acetylcholine receptor antibodies

• Titres in one individual do not correlate with clinical severity

– Over time will change in parallel with disease

– Repeated testing is rarely needed - use clinical and

sometimes electrodiagnostic examinations to follow

longitudinally

• If positive - confirms the diagnosis of MG

– But does not mean symptoms are due to MG

Seronegative MG

• Undetectable antibodies against the acetylcholine receptor

– 50% of ocular MG

– 15% of generalized MG

– In generalized MG individuals with clinical history and

examination consistent with possible MG may be MuSK

antibody positive

– MuSK Ab positive MG patients have characteristic clinical

features that are different from features of the remaining

seronegative MG patients(Meriggioli & Sanders, 2009)

Electrodiagnostic Tests

• Electromyography (EMG) and Nerve Conduction studies (NCS)

• Tests used to evaluate nerve conduction and muscle function

• NCS measure the nerve conduction time and amplitude of the stimulated muscle in response to an electrical stimulus

• EMG records the rate of firing, shape and dimension of the potentials

• Single Fiber EMG (SFEMG) is a specific test of neuromuscular transmission

(Angelini, 2011)

Normal Nerve conduction

As seen on an oscilloscope during testing

Repetitive Nerve Stimulation

Decremental

response

as seen

in MG

(Oh et al, 1992)

Imaging Studies (CT or MRI) of the Chest :

Visualization of the Thymus

• Thymic Hyperplasia:– 65% of MG patients

– Mainly early onset (arbitrarily less than 50 years of age)

– Not necessarily visible on CT

• Thymoma:– 30% of late onset greater than 50 years of age

– Visible on CT of the chest

– Always seropositive for AChR antibodie

(Howard, 2008)

Therapeutic Modalities

• Medications:

– Symptomatic

• Anti-Cholinergic Agents

– Immunosuppressive agents

– Immunomodulatory agents

• Immunomodulatory Therapies

– Plasmapheresis (TPE/PLEX)

– Immune Gamma Globulin (IVIg)

– Thymectomy

Anti-cholinergic Agents:

Acetylcholinesterase Inhibitors

• Pyridostigmine bromide (Oral)

– Mestinon (short-acting)

– Mestinon Time Span (long-acting)

• Neostigmine bromide (Oral)

• Neostigmine methylsulfate (IM, SC)

Pyridostigmine bromide (Mestinon)

• Most commonly used acetylcholinesterase inhibitor

• Action

– Increases the amount of acetylcholine available at the NMJ to make the muscles contract

– If it works, improvement within hours

– Symptomatic treatment only; doesn’’’’t treat underlying problem with the immune system

• Advantages – Inexpensive

– Few serious side effects

• Side Effects/Risk Factors– Diarrhea, abdominal cramps

– Nausea & vomiting

– Urinary urgency, frequency

– Muscle twitching, cramps

– Muscle weakness at high doses

– Overdose (Cholinergic Crisis) particularly if S & S occur within 15 – 60 minutes after dosing

Immunosuppressive Therapy

• General – short or long term use– Glucocorticosteroids (Prednisone, methylprednisolone)

• Targeted – long term use– Not FDA approved for MG

– ““““Off-label”””” drugs

– Used as steroid sparing option

– Available for non responders, in severe MG, or with intolerable side effects

– Typically used in • Cancer therapy

• Prevention of transplant rejection

Prednisone• General immunosupression

• Works in most people - Smallest dose for shortest time possible

• Works quickly but high doses can induce an exacerbation of weakness

to respiratory failure

• Takes months

– 1 month minimum

– 3-6 months optimum

– Sometimes 12 months

• Many side effects/Risk Factors - some serious

• Risks Factors:

– Infection

– Weight gain (Obesity)

– Hyperglycemia, Type II Diabetes

– Hypertension

– Osteopenia/Osteoporosis

– Avascular necrosis of hip joint

– Cataracts, glaucoma

– Insomnia

– Psychosis – depression,

Targeted Immunosuppressive Long Term Therapies

(Off-Label)

• Azathioprine (Imuran) – B cells and T cells

• Mycophenolate (Cell Cept) – B cells and T cells

• Cyclosporin (Restasis) – T cells

• Tacrolimus (Prograf) – T cells and IL2

• Cyclophosphamide (Cytoxan) – B cells

• Methotrexate – T cells(Mays et al, 2011)

Azathioprine (Imuran)

• Most frequently used

• Works well in MG with improvement after 6 – 12 months

• Allows the use of lower doses of prednisone

• Required monitoring: liver function tests (LFT’’’’s); blood counts

• Side effects:

– Flu-like symptoms

– Increased liver enzymes

– Decreased WBC

– Bleeding, bruising

– GI upset, loss of appetite, nausea

– Rash, darkened skin, hair loss

• Risks:– Hepatotoxic, Nephrotoxic

– Bone marrow suppression – leukopenia, anemia

– Cancer – lymphoma, skin cancer

– Infertility

Targeted Immunosuppressive

Long Term Therapies

• Effectiveness - Weeks to months

• Not compatible with pregnancy

• Typical Use:

– Cancer therapy

– Prevent transplant rejection

• Indications in MG:

– Steroid sparing

– Inhibit production of B cells and/or T cells

– Limit antibody production by B cells

• Common Risk Factors:

– Many drug – drug interactions including OTC

– Hepatotoxicity

– Nephrotoxicity

– Bone marrow suppression – leukopenia, anemia etc.

– Cardiopulmonary dysfunction

Other Drug Therapy in MG

• Rituximab (Rituxan) –

– Monoclonal antibody

– Destroys B lymphocytes

– Used in MG refractory to other long term immunosuppressive therapy

– Weight based infusions for 10 – 12 weeks for up to 2 years

– Advantage:• Lower steroid dose required

• Good with MuSK AB positive

• May result in sustained remission

– Risks:• Infusion reactions

• Neutropenia

• Progressive Multifocal Encepholopathy (PML)

Immunomodulatory Therapy

• Plasmaphoresis (TPE/PLEX) - depletes antibodies

by the bulk removal of anti-AChR & other

antibodies

• IVIG Infusions – neutralize the blocking effects of

antibodies by infusion of human polyclonal

immunoglobulin

• Thymectomy – remove the source

of dysregulated Tcells(Angelini, 2011)

Plasmaphoresis (TPE/PLEX)

• Indications:– Acute myasthenic crisis

– Uncontrolled MG with medications

– Pre-thymectomy

• Benefits in 70% of patients within 2 weeks

• Risks:– Venous access – infection, pain, nerve damage, thrombosis, perforation,

hematoma

– Paresthesia, muscle cramps

– Electrolyte imbalance

– Reduced coagulation factors

– Cardiac events and stroke(Howard, 2008)

Immune Gamma Globulin

Intravenous (IVIg)

• Indications:– Acute intervention

– Chronic maintenance

• Risk Factors:– Chills & fever (pretreat with antihistamine, antipyretic and/or steroids)

– Headache, aseptic meningitis

– Fluid overload

– Anaphylaxis

– DVT, PE(Howard, 2008)

Thymectomy

• Indications:– MG age 10 – 50 (except Ocular, MUSk +)

– Thymoma

– Non-thymomatous autoimmune MG – option to increase the probability of remission or improvement

• Approaches:– Transsternal

– Transcervical

– Endoscopic (video-assisted thorascopic)

• Note: Post operative increase in symptoms of MG may occur

(Angelini, 2011, Howard, 2008)

Comprehensive

Nursing Assessment:

• Patient History

• Neurological Examination

– Muscle Strength

– Muscle Fatigability

Patient History

• Provides direction to guide the neurological examination

• Aids in Identifying:

– Specific patient problems

– Health strengths

– Health weaknesses

– Reason for exacerbation of symptoms

• Aids in development of individualized care plan

Symptoms of MG??• Location (where/what is the

weakness – eyes, speech, swallow, breathing, upper/lower limbs, etc.)

• Quality or character

• Quantity or severity

• Timing (onset, duration, frequency)

• Setting

• Aggravating/alleviating factors

• Associated factors

• Disease Process

• Treatment regimen

• Concurrent Illness

• Psychosocial Issues

Myasthenia Gravis ??

• Newly or previously diagnosed

• Duration of diagnosis

• Previously in remission

• Symptoms increase after activity or stress

• Knowledge of the disease process

• Coping with the diagnosis

Treatment Regimen ??

• Prescribed medications & treatments

• Dosing and frequency schedule

• Knowledge of the medication regimen rationale

• Compliance issues

• Unpleasant side effects

• Response after taking the medications

• Fatigue/weakness noticeable before and/or after taking the medication

• Weakness after taking the medication

• New medications or other treatments

Concurrent Illness??

• Recent infection or illness

• Medications –

– Prescribed

– OTC

• Recent surgery

• Other long-standing illness -

– Primary disease process

– Secondary to MG medications

Concurrent Illness??

Psychosocial Issues ??

• Patient’’’’s and family learning level

• Available family support

• Cultural issues that can affect compliance

• Religious issues that can affect compliance

• Stressful events

Muscle Strength Testing

• Eye & Eyelid Movements

• Facial Movements

• Speech & Swallowing

• Muscle Strength Testing

(Proximal & Distal Muscles)

• Breathing Patterns

Eye & Eyelid Movements

Facial Movements

Speech, Swallowing &

Breathing Patterns

Muscle Strength Testing(Proximal & Distal Muscles)

Grade 5 = normal muscle power

Grade 4 = movement against gravity

and against resistance

Grade 3 = movement against gravity

without resistance

Grade 2 = movement in the plane of

action with gravity eliminated

Grade 1 = flicker of muscle movement in

gravity eliminated position

Grade 0 = no muscle movement

Physical Assessment:

MG Focus for Fatigability

• Eye Lids and Movement

• Facial Muscles

• Swallowing

• Speech

• Head Control

• Arms and legs including grip

• Respiratory

Physical Assessment:

Muscle Fatigue of Eyes & Lids

• Eye Movement - Looking straight ahead, right, left and down

– Reduced extraocular movements

– Diplopia occurs with prolonged gaze > 45 seconds: lateral and upward gaze

– Downward gaze may be normal

– Pattern of weakness does not map to one nerve

– No eye movement

– Pupillary response normal

• Eye Lids – Looking straight ahead

– Ptosis• With upward gaze in > 45 seconds

• Upper lid touches pupil

– Lid droop in seconds

Physical Assessment:

Muscle Fatigue of Face

• Facial Muscles – Close lids

– Reduced forced eye closure (unable to bury eyelashes

– Unable to keep eyelids squeezed shut

– Reduced ability to puff cheeks, lip seal, ability to spit

• Jaw opening and closure

– Unable to open and close jaw against resistance

– Reduced ability with repetitive attempts

Physical Assessment:

Muscle Fatigue of Pharynx/Larynx

• Speech –

– Count 1 – 50 noting the number at which

dysarthria begins

– Observe for nasal, soft and/or slurred speech

– Worsens with repetition

• Swallowing –

– May test with 4 oz of water (no ice); if clinically safe ask patient to drink as

usual

– Observe for coughing, throat clearing, double swallows, fatiguing of

swallow, choking, nasal regurgitation

Physical Assessment:

Testing for Muscle Fatigue

• Head Control– Observe head position in upright position

– Test neck flexion and extension

– Lift head off the table while in supine position

• Upper limbs– Arms extended in sitting position

– Both arms at 90°°°°, palms down

– Unable to maintain at least 240 sec.

– Strength in proximal muscles (deltoid, triceps) most affected

• Grip – Compare strength (right vs left, male vs female)

– Test distal muscles (finger extensors) against resistance

• Lower limbs - outstretched supine

– Right & left hip flexion (proximal) at 45 - 50°°°° at least 100 sec.

– Test ankle dorsiflexion (distal)

Physical Assessment:

Respiratory Function

• Breathing– Breath count: number reached counting out loud in one breath

(at a rate of 1 per second)

– Supine: test chest expansion; observe for abdominal breathing

– Short of breath (SOB) in supine position; note time of onset

• Other Pulmonary Testing that may be required:– Forced Vital Capacity

• > 80% - within normal limits

• 65 – 79% - mild impairment

• 50 – 65% - moderate impairment

• > 50% - severe impairment

– Pulmonary Function Studies

– Pulse Oximetry

– Arterial Blood Gases

Patient Problem List:

Consequences of MG

• Activity Intolerance/Mobility Problems

• Communication

• Nutrition

• Risk of Aspiration

• Sensory Perception/Visual Disturbance

• Risk of Injury

• Respiratory Dysfunction

• Body Image

• Self Care

• Knowledge

Potential Patient Problems,

Expected Outcomes,

and

Nursing Interventions

Activity intolerance related to muscle

fatigability and weakness

Outcomes:

1. Maintains muscle strength,

endurance and activity level.

2. Demonstrates energy conservation techniques.

3. Verbalizes a decrease in muscle fatigue.

Interventions:

1. Identify factors that increase activity

intolerance.

2. Rest periods prior to and following

activities.

3. Develop energy conservation strategies to decrease fatigue and optimize activities.

4. Adjust medications to maximize effectiveness

Impaired verbal communication

related to weakness of the larynx, pharynx, lips,

mouth, and jaw muscles

Outcomes:

1. Decreased frustration with

communication.

2. Uses an alternative methods to

communicate.

Interventions:

1. Determine the most effective mode of

communication including the use of

alternative methods (e.g. gestures, written,

communication cards.

2. Encourage patient to speak slowly & louder.

3. Reduce environmental noise.

4. Observe for nonverbal clues.

Interventions:

5. Ask questions that require short answers.

6. Discuss frustration associated with

the inability to communicate.

7. Explain need for patience by family/friends.

8. Consult a speech pathologist.

Alteration in nutrition related to fatigue of

the muscles for chewing & impaired

swallowing

Outcomes:

1. Maintains weight within

normal limits.

2. Absence of dehydration

Interventions:

1. Rest prior to eating and drinking.

2. Provide foods easy to chew.

3. Provide highly viscous foods and thickened liquids.

4. Offer frequent, small meals including high-calorie and high-protein foods.

5. Instruct patient on principles of good dental hygiene.

6. Instruct patient to take rests while chewing and in between bitesto restore strength.

7. Serve meals at times of maximum strength (usually in the early part of the day & ½ hour after cholinesterase inhibitor medications).

Interventions:

8. Serve large meals in AM & small meals in PM.

9. Review food preparation techniques so food is easier to

consume. Use softer consistencies.

10. Review principles of nutrition and basic food groups so

patient can select food that provides a balanced diet.

11. Consult a dietitian to determine appropriate food choices.

12. Consult with a swallowing specialist to determine most

effective swallowing techniques.

High risk of aspiration due to inability to

swallow, manage own secretions, and impaired

cough and gag reflexes

Outcomes:

1. Absence of aspiration.

2. Breath Sounds within normal limits.

3. Chest X-ray within normal limits

Interventions:1. Discuss the causes and prevention of aspiration.

2. Position upright with head slightly forward when eating and drinking.

3. Encourage taking small bites, chewing well, and frequent swallowing.

4. Encourage taking small sips of liquids.

5. Encourage eating slowly – make sure patient has swallowed after each bite.

6. Provide meals at times of optimal strength. (after medications, early in the day, after rest periods).

Interventions:

7. If swallowing lightly impaired, instruct patient to lean forward, take a small breath through the nose and coughforcefully to push the irritating substance out of throat

8. If choking occurs - use emergency principles as outlined by the AHA to include the Heimlich maneuver.

9. If aspiration suspected - assess breath sounds and obtain a chest X-ray

Disturbed sensory

perception related to

double vision and ptosis

Outcome:

1. Absence of physical

injury associated with

impaired vision

Interventions:

1. Reinforce the need for rest periods.

2. Discuss the risks associated with visual

impairment.

Risk for injury related to visual

disturbance, muscle fatigue

and weakness

Outcomes:

1. Uses safety measures to

decrease risk of injury.

2. Absence of falls.

Interventions:

1. Use eye patch to eliminate double vision.

2. Use safety measures to prevent injury, e.g. remove

or anchor throw rugs, use hand

grips in bathroom, and railings on stairs.

3. Moderate exercise to maintain muscle strength.

4. Use of an alert system/mechanism in case

of increased weakness or a fall.

Ineffective respiratory function related to

weakness of inter-costal muscles &

diaphragm.Outcomes:

1. Absence of shortness of breath.

2. Adequate air exchange.

3. Effective spontaneous cough.

4. Pulmonary Function tests are within

normal limits

Interventions:

1. Assess and document respiratory status, rate,

rhythm and breath sounds.

2. Assess gag and cough reflexes.

3. Assess quality of voice – notify MD

of changes from baseline.

Interventions:

4. Obtain baseline Forced Vital Capacity (FVC)

(normal > 60 mg/kg) and Negative Inspiratory

Force (NIF) (>70cmH20) and continue to monitor

5. Notify MD for any respiratory abnormalities or

change in FVC and/or NIF from baseline value or

NIF < 30, FVC <1.5L. (Values of FVC < 1.0L <15mL/kg

body weight /NIF <20 cm H2O are indications for

mechanical ventilation.)

6. If facial weakness – obtain NIF/FVC per face mask.

Interventions:

7. Administer oxygen as needed.

8. Suction if patient unable to manage secretions.

9. Teach patient/caregiver how to perform oral

suctioning.

Disturbed body image related to inability

to maintain usual life style, role, and

responsibilities

Outcomes:

1. Demonstrates a positive self-

esteem, body image and

personal identity

2. Demonstrates adjustment to changes

in role and responsibilities.

Interventions:1. Encourage patient to verbalize the meaning of the

illness/loss (i.e., "How do you feel about what is happening to you?")

2. Listen attentively and compassionately.

3. Since appearances may greatly alter and weakness may leave patients unable to take care of grooming needs, help them to look their best.

4. Be honest about realities of the illness; encourage patients to seek help if denial becomes detrimental.

Interventions:

5. Facilitate acceptance; help patients set

realistic, short-term goals so that success

may be achieved.

6. Encourage patients to do the things that

they are capable of doing.

7. Share hopeful aspects of the disease with patients

and family.

8. Recognize that the family too will be experiencing

grief for the loss of the way

the patient "used to be."

Interventions:

9. Determine what their usual coping mechanisms are, and how they can best be used to cope with MG.

10. Assist patient in identifying factors in the

environment that have the potential to undermine

positive adaptation.

11. Involve patient in the planning and decision-

making regarding care.

Interventions:

12. Give patient/family information regarding the

disease, medications, emergency measures, and

precautions for living with MG after discharge from

the acute care setting.

13. Explore patient role changes so that they will be

less threatening.

14. Supply information on local MG chapter.

Relationships can be formed with others

with the disease and be a great source of

strength to patients and family

Self care deficit related to muscle fatigue and

weakness, and

visual impairment

Outcomes:1. Able to perform activities of daily living within limits

of weakness and fatigability.

2. Demonstrates increased strength, endurance, and mobility

Interventions:

1. Assess ability to carry out ADL’’’’s (feed, dress, groom, bathe,

toilet, transfer, and ambulate).

2. Assess specific cause – weakness, vision.

3. Assess need for assistive devices.

4. Encourage as much independence as possible.

5. Use consistent routines and allow sufficient time to perform

each activity.

Interventions:6. Provide positive reinforcement.

7. Position in optimal position to perform activity.

8. Plan activities so patient is rested.

9. Ensure needed equipment is available.

10. Encourage use of clothing that is easy to put on and remove.

11. Consult with Physiotherapist and/or

Occupational Therapist.

Knowledge deficit related to the disease

and its management.

Outcomes:

1. Verbalizes knowledge of

the disease, management,

potential side effects, and

fatigue management.

Interventions:1. Assess any barriers to learning and

readiness to learn by patient and

family.

2. Education about the disease process,

the treatment options, their effects

and side effects.

3. Education regarding fatigue

management.

Fatigue Worsening in MG:

• Activity level/overexertion

• Stress – physical & emotional

• Warm temperature

• High humidity

• Physical inactivity

Consequences of Physical

Inactivity in MG:

• De-conditioning

– Increases muscle atrophy and weakness

– Decreased cardiovascular fitness

• Increases obesity

• Increases insulin resistance & diabetes risk

• Accelerates osteoporosis

– Aging process

– Prednisone administration

Other Factors Exacerbating MG:

• Infections

• Surgery

• Anemia

• Thyroid problems

• Menses

• Pregnancy and post-partum

• Low testosterone

• Vitamin deficiencies (B12 and D)

• Loss of potassium – diuretic, vomiting

• Sleep disorders

• Medications

(Howard, 2008)

Drug Alert:Classes of Drugs that may exacerbate MG

Use with caution & monitor

• Antibiotics

• Neuromuscular Blocking Agents

• Beta Blockers

• Calcium Channel Blockers

• Anticonvulsants

• Ophthomologics

• Psychiatric Drugs

• Hormones

• Electrolyte related

(Pascuzzi, 2007)

Specific Drug Alerts:

Use with caution & monitor

• Neuromuscular blocking agents: succinylcholine and vecuronim

• Quinine, quinidine, procainamide

• Antibiotics:

– aminoglycosides - (-mycins) Erythromycin

– Quinolones (-oxacin) - Cipro, Levaquin,

• Beta-blockers: propranolol, timolol eyedrops

• Calcium channel blockers: Norvasc, Procardia

• Magnesium salts: laxatives, antacids

• Iodine based contrast dye

• Local anesthetics: lidocaine

• Analgesics: narcotics (Demerol, morphine)

• Anxiolytics

• Sedatives

• Hypnotics(Pascuzzi, 2007)

Other Related Drugs/Factors

may worsen MG:

• Statins

• Hormones:

– Estrogen therapy

– Thyroid therapy/imbalance

• Electrolyte related:

– Magnesium (eclampsia, pre-term labor)

– Hypokalemia (Diuretics)

– Hypocalcemia (Plasma exchange)

• Over-the-Counter Drugs

• ““““Natural ““““ or herbal preparations

(Pascuzzi, 2007)

Drug Alert:Medications that should

NOT be used in myasthenics

• Alpha-interferon

• d-Penicillamine

• Botulinum toxin (Botox)

• Telithromycin (Ketek)

(Howard, 2008)

►►►►Myasthenic Crisis

versus

►►►► Cholinergic Crisis

MG Crisis Situation:

Key Issues

• 12-16% of generalized MG patients experience crisis

• Respiratory and swallowing impairment are the hallmark

symptoms

• Priority - differentiate between cholinergic or myasthenic

crises

– Method: Edrophonium: Tensilon challenge test

Characteristics of Crisis

• Worsening dysphagia and dysarthria despite taking

medication

• Severe choking

• Weak breathing - breathing worsening 30 minutes after

taking pyridostigmine

• Fast shallow breathing when beginning to feel tired

• Weak voice

• Head drop

Crisis: Signs and Symptoms

• Restlessness, apprehension

• Generalized muscle weakness

• Dyspnea

• Increased bronchial secretions, sweating

• Dysarthria, dysphagia

Complications of Crisis

• Respiratory failure

• Hypoxemia and respiratory acidosis may render

the patient somnolent,

and unresponsive

• Pneumonia may be a cause of death

• Chronic respiratory failure

Myasthenic Crisis

• Prodrome - infection

• Worsening MG

Cholinergic Crisis

• Cause - Over medication with anticholinesterase drugs

• Symptoms:

– Abdominal cramping/diarrhea/vomiting

(MUSCARINIC Effects-slow)

– Profound generalized weakness

– Diaphoresis

– Excessive bronchial & nasal secretions and impaired

respiratory function (NICOTINIC Effects-rapid)

– Bradycardia, A-V block

Emergency Management

• Both are medical emergencies

• Both may require tracheal intubation and assisted

ventilation

• Parameters: Negative Inspiratory Force (NIF) <

20cm H20

• FVC <15cc/kg body weight

• Humidified Air and Oxygen (if PO2 <70)

Cholinergic Crisis Management

• Stop Acetylcholinesterase Inhibitors

• Bronchospasm associated with cholinergic crisis may

respond to bronchodilator

• Intubate and Ventilate

• Treat underlying cause:

– Infection, electrolyte disturbance (hypokalemia,

hypocalcemia, hypermagnesium)

• Resume ChE at lower dose and increase slowly

MG Crisis Management

• Intravenous immunoglobulin ( IVIg)

– Blood product – safe

– Modulates the immune system

– Benefits seen in 70%of patients within 2 weeks

– Common side effects – mild

• IVIg and TPE equal in terms of efficacy

MG Crisis Management

• Plasma Exchange (TPE)

– Removes the antibodies which cause weakness

– Benefits in 70% of patients within

2 weeks

• More difficult to arrange on short notice unless a

major medical center

Impact of MG on the myasthenic

and the family members

• Life Style

• Role Changes

• Energy Conservation– Home

– Community

– Work

• Challenges– Vocational

– Financial

• Caregiver Issues

Life Style Changes

• Modify home and work environment to reduce fatigue and frustration associated with the limitations related to the disease process.

• Alter life style to decrease physical and mental stress

• Encourage patient to discuss concerns with health professionals and family

Role Changes

• Promote positive body image, self esteem and avoid social isolation.

• Assist patient to identify and utilize effective coping mechanisms.

• Educate family and friends about the disease and associated limitations.

• Connect with other MG patients and families.

Energy Conservation

• Modify daily routine to maximize optimum functional

level.

• Plan activities with rest periods.

• Balance strenuous activities with others that require less

exertion.

• Organize day according to medication timing

(mestinon).

• Use assistive devices to promote optimal and safe activity

level.

Energy Conservation: Home

• Sit during chores

• Delegate to family members

• Keep objects at appropriate height

• Schedule rest periods

• Plan activities

– Break the activity to its parts

– Prepare everything ahead

• Use power tools/electrical appliances

Energy Conservation: Eating

• Eat when muscle strength is good.

• Take time to eat and rest between bites.

• Frequent small meals.

• Soft foods and not sticky.

• Foods that do not require a lot of chewing.

Energy Conservation: Grooming

• Sit on stool to shave or brush teeth

• Elbow prop

• Electric tooth brushes

• Take rest breaks

• Shorter shower/bath with warm water

• Sit to dress

Energy Conservation: Community

• Park close (drop off or handicap tag)

• Avoid peak shopping times

• Wear supportive walking shoes

• Stay balanced (walker, cane, etc.)

• Use cart for merchandise

• Plan according to medications

• Unload perishables

• Shop by mail order

• Small size weighs less

Energy Conservation at Work

• Proper neck and back support

• Sit rather than stand

• Avoid eye strain

• Take breaks

• Proper air conditioning • Family medical leave act

Major Challenges

• Vocational impact

• Employment issues

• Disability issues

• Insurance coverage

• Financial impact

Caregiver Issues

• Recognize limitations as a caregiver.

• Care for self as well as the person with MG.

• Recognize when it is time to nurture and care for self.

• Seek assistance from another caretaker as necessary.

• Utilize community resources to assist in providing care.

GOALS:

���� Maximize function

���� Promote quality of life

���� Prevent life threatening events

References

• Angelini, C. (2011). Diagnosis and management of autoimmune myasthenia gravis. Clinical Drug Investigation, 3(1), 1-14. DOI : 10.2165/1158/4740.

• Benetar, M. (2006). A systematic review of diagnostic studies in myasthenia gravis. Neuromuscular Disorders, 16(7), 459-467.

• Chan KH, Lachance DH, Harper CM, Lennon VA. Frequency of seronegativity in adult-acquired generalized myasthenia gravis. Muscle Nerve 2007; 36:651.

• Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology 1999; 106:1282.

• Grob, D., Brunner, N., Namba, T., & Pagala, M. ( 2008). Lifetime course of myasthenia gravis. Muscle & Nerve, 37(2), 141-149.

• Howard, J. F. (2008). (ed.) Myasthenia Gravis: A Manual for the Health Care Provider. (1st ed.). St. Paul, MN. Myasthenia Gravis Foundation of America.

• Jaretzki A et al.Myasthenia gravis. Recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America Neurology , v.55 , p.16 , 2000 ,

• Keesey JC. Clinical evaluation and management of myasthenia gravis. Muscle Nerve

2004; 29:484.

• Mantegazza R, Beghi E, Pareyson D, Antozzi C, Peluchetti D, Sghirlanzoni A, Cosi V, Lombardi M, Piccolo G, Tonali P, et al. A multicentre follow-up study of 1152 patients with myasthenia gravis in Italy.J Neurol. 1990 Oct;237(6):339-44.

References

• Mays, J., Butts, C.L. (2011). Intercommunication between the Neuroendocrine and Immune Systems: Focus on Myasthenia Gravis, Neuroimmunomodulation, 18, 320-327.

• Meriggioli, M. Sanders, DB (2009). Autoimmune myasthenia gravis: emerging clinical and biological heterogenicity. Neurology, 8, 475-486.

• Muscular Dystrophy Association (MDA). (2009). Facts about Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenic Syndrome. Muscular Dystrophy Association, Inc., Tucson, AZ.

• Oh SJ, Kim DE, Kuruoglu R, et al. Diagnostic sensitivity of the laboratory tests in myasthenia gravis. Muscle Nerve 1992; 15:720.

• Pascuzzi, R.M (2003). The edrophonium test. Semin Neurol 23(1):83-8.

• Pascuzzi, R. (2007). Medications and Myasthenia Gravis: A Reference for Health Care Professionals. Myasthenia Gravis Foundation of America, New York, N.Y.

• Phillips, L. H. 2nd .( 2003). The epidemiology of myasthenia gravis. Annals of the New York Academy of Science, 998, 407-412.

• Smeltzer, S.C. Bare, B.G. (ed) (2007). 10th Brunner & Suddath's Textbook of Medical Surgical Nursing,1520-1530.

Post Test Instructions

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Perspective”.

• Take the test, recording your answers in the test answer section. Each

question has only one correct answer.

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Evaluation Form to: kday@kellencompany.com

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certificate of earned contact hours and the answer key. If you fail, you

have the option of taking the test again.