Mariano Marcos State University: UPTRC

Myasthenia Gravis
(MG)
MEDICAL BACKGROUND

Paula Jeanne H. Gaoat & Princess Joy L. Salvador

7/17/2010
 I. DEFINITION (O’ Sullivan & Schmitz, 2007)
Myasthenia gravis is thought to be an autoimmune d/o often associated w/
other immunological dse. It is characterized by weakness and extensive fatigability,
and frequently manifested by weakness and fatigability.
II. EPIDEMIOLOGY (Howard, Jr., 2008)
The current prevalence of MG in the US is estimated to be 20 per 100,000 –
between 53,000 and 60,000 cases. The true prevalence is probably higher because
MG is frequently undiagnosed.
Women are affected more often in the second and third decades and men, in the
sixth. As the population ages, the average age at onset has increased
correspondingly. More men are now affected than women and the majority of MG
patients in the US are over age 50.
III. ETIOLOGY (Goodman & Fuller, 2009)
Action takes place at the site of the neuromuscular junction and motor
endplate.
Increased incidence of MG are thymic disorders such as hyperthyroidism,
thymic tumor, or thyrotoxicosis; association with diabetes and immune disorders such
as rheumatoid arthritis or lupus; Exacerbations may occur before the menstrual
period or shortly after pregnancy
IV. PATHOPHYSIOLOGY (Goodman and Fuller, 2009)
In MG, the fundamental defect is at the neuromuscular junction. Receptors at the
motor endplate normally receive acetylcholine (ACh) from the motor nerve terminal.
An action potential occurs that leads to a muscle contraction. In MG the numbers of
ACh receptors are decreased and those that remain are flattened, which results in
decreased efficiency of neuromuscular transmission. The neuromuscular junction can
normally transmit at high frequencies so that the muscle does not fatigue. Without
ACh, the nerve impulses fail to pass across the neuromuscular junction to stimulate
muscle contraction. The neuromuscular abnormalities in MG are brought about by an
autoimmune response mediated by specific anti-ACh receptor antibodies. The
antibodies may block the site that normally binds ACh, or the antibodies may damage
the postsynaptic muscle membrane. There may be endocytosis (pinching off of
regions of the cell's membrane) of the receptor site.
Although the cause of the autoimmune response in MG is not well understood, the
thymus appears to play a role in the disease; 75 % of persons with MG have
abnormalities of the thymus (e.g., thymic hyperplasia or thymoma). Cells within the
thymus bear ACh receptors on their surface, and may serve as a source of
autoantigen to trigger the autoimmune reaction within the thymus gland when an
immunologic abnormality causes a breakdown an autoimmune attack on
acetylcholine (ACh) receptors.
V. Myasthenia Gravis Foundation of America (MFGA) Clinical Classifications
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 muscle weakness of any severity
o IIa: predominantly affecting limb, axial muscles or both; may also have
lesser involvement of oropharyngeal weakness
 o IIb: predominantly affecting oropharyngeal respiratory muscles, or both;
may also have lesser involvement of oropharyngeal weakness
CLASS III: moderate weakness affecting other than ocular muscles; may also
have ocular muscle weakness of any severity
o IIIa: predominantly affecting limb, axial muscles or both; may also have
lesser involvement of oropharyngeal muscles
o 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 muscle weakness of any severity
o IVa: predominantly affecting limb and/or axial muscles
o IVb: predominantly affecting oropharyngeal, respiratory muscles, or
both; 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 management. The use of feeding
tube without intubation places the patient in class IVb.
VI. CLINICAL MANIFESTATIONS
Although MG encompasses a spectrum of mild to severe, its cardinal features are
skeletal muscle weakness and fatigability. (Goodman & Fuller, 2009)
Cardinal Features
o Diplopia
o Ptosis
Visual symptoms
o Blurry/Double Vision
Emotional symtoms
Motor symptoms
o Fatigue
o Muscle weakness
 Facial Muscles
 eyelids are separated against forced eye closure
 slight involuntary opening of the eyes as the patient tries
to keep the eyes closed
 Snarling expression on attempted smile
 Neck muscles; causes head bobbing due to weak neck flexors
 Intercostal and diaphragm muscles; SOB
 Proximal limb weakness;
 having difficulty raising arms above the head
 having difficulty climbing up stairs
 having difficulty arising from a chair
Speech, voice and swallowing disorders
o Chewing of meat produces fatigue
o Dysphagia
o Dysarthria
o Jaw weakness
 o Oropharyngeal muscle weakness; changes in the voice, difficulty
chewing and swallowing; nasal regurgitation or aspiration;
o Weakness of laryngeal muscles; hoarseness
Cardiopulmonary function
o weak bulbar muscles; aspiration pneumonia
o weak chest wall muscles; respiratory failure
Pattern of Symptom
o Fatigability of the muscles with recovery to the baseline strength after a
short period of rest
o Proximal muscles are affected more than distal muscles
o Symptoms fluctuate throughout the day and are provoked by exertion
o Fluctuations also occur with superimposed illness, menses, and air
temperature
o Neurologic findings are normal except for muscle weakness
o No muscular atrophy
o Reflexes and sensation normal
VII. Differential Dx
Lambert-Eaton Syndrome
Neurasthenia
Botulism
Intracranial mass lesion
Progressive external opthalmoplegia
VIII. MGFA DIAGNOSTIC PROCEDURES
Edrophonium Chloride Test
Auto-Antibodies in MG
o Anti-striational muscle anti-bodies
o Acetylcholine receptor antibodies (AChR-ab)
o Anti-musK antibodies
o Other auto-antibodies
 Anti-titin antibodies
 Anti-RyR
Electrodiagnostic Testing
o Repetitive nerve stimulation
o Single fiber EMG
Ocular cooling/Ice Pack test
Other studies
o Complete blood count
o Thyroid Function Test
o Thyroid Antibodies
IX. PROGNOSIS (KAMINSKI)
The prognosis of MG in infancy is usually favorable, although exacerbations may
occur in fevers. In sporadic case, a fulminating onset with life-threatening respiratory
insufficiency may occur.
Progression to severe disease may be more common in MG with onset after the
age of 50.
X. TREATMENT PROGRAM BASED ON MGFA PROFESSIONAL MANUAL
Medical, Surgical and Pharmacological management
o Thymectomy
o Plasma exchange (PLEX)
o Intravenous Immunoglobulin (IGIv)
o Cholinesterase inhibitor drugs (ChI)
 Pyridostigmine bromide
 Neostigmine
o Corticosteroid
 Prednisone
o Immunomodulatory drugs
 Azathioprine
 Cyclosporine
 Mycophenolate mofetil
o Miscellanous
 Ephedrine
 Terbutaline
Rehabilitation management
o Walking
o Stationary ergometer
o Weight training
o Treadmill
o Swimming