744 Myasthenia Gravis PTG

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BASIC INFORMATION
DEFINITION
Myasthenia gravis (MG) is an autoimmune dis-
order that affects postsynaptic neuromuscular
transmission classically mediated by antibodies
directed against the nicotinic acetylcholine re-
ceptor (AChR) of the neuromuscular junction,
resulting in a decrease in functional postsynap-
tic ACh receptors and consequent weakness.
ICD-9CM CODES
358.0 Myasthenia gravis
EPIDEMIOLOGY &
DEMOGRAPHICS
INCIDENCE (IN U.S.): Two to ve cases annually
per 1 million persons
PEAK INCIDENCE: Female, second to third de-
cades; male, sixth to seventh decades
PREVALENCE (IN U.S.): One per 20,000 per-
sons
PREDOMINANT SEX: Females are affected
more often than males (3:2) in adults; they are
equally affected in the elderly
GENETICS: Increased frequency of HLA-B8,
DR3
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
The hallmark of MG is uctuating weakness
worsened with exercise and improved with
rest.
Generalized weakness involving proximal
muscles, diaphragm, and neck extensors is
common.
Weakness is conned to eyelids and extra-
ocular muscles in approximately 15% of pa-
tients.
Bulbar symptoms of ptosis, diplopia, dysar-
thria, and dysphagia are common.
Reexes, sensation, and coordination are
normal.
ETIOLOGY
Antibody-mediated decrease in nicotinic AChR
in the postsynaptic neuromuscular junction re-
sulting in defective neuromuscular transmission
and subsequent muscle weakness and fatigue
Dx
DIAGNOSIS
DIFFERENTIAL DIAGNOSIS
Lambert-Eaton myasthenic syndrome, botulism,
medication-induced myasthenia, chronic pro-
gressive external ophthalmoplegia, congenital
myasthenic syndromes, thyroid disease, basilar
meningitis, intracranial mass lesion with cranial
neuropathy, Miller-Fisher variant of Guillain-
Barr syndrome
WORKUP
Edrophonium (Tensilon) test (Fig. E1-560):
useful in MG patients with ocular symptoms.
Cardiac monitoring and atropine ready at the
bedside are essential. Patients with MG may
also have a positive ice test (Fig. E1-561).
Repetitive nerve stimulation: successive
stimulation shows decrement of muscle ac-
tion potential in clinically weak muscle; may
be negative in up to 50%.
Single-ber electromyography: highly sensi-
tive; abnormal in up to 95% of patients.
Serum AChR antibodies found in up to 80% of
patients.
A subset of patients with seronegative MG
may have muscle-specic tyrosine kinase
MuSK antibodies.
ADDITIONAL TESTS
Spirometry to document pulmonary function
CT scan of anterior chest to look for thymoma
or residual thymic tissue
Thyroid-stimulating hormone, free T
4
to rule
out thyroid disease
Rx
TREATMENT
NONPHARMACOLOGIC THERAPY
Patient education to facilitate recognition of
worsening symptoms and impress need for
medical evaluation at onset of clinical dete-
rioration
Avoidance of selected drugs known to pro-
voke exacerbations of MG (beta-blockers,
aminoglycoside and quinolone antibiotics,
class I antiarrhythmics)
Prompt treatment of infections, diet modica-
tion, and speech evaluation with dysphagia
ACUTE GENERAL Rx
Symptomatic treatment with acetylcholines-
terase inhibitors:
1. Pyridostigmine 30 to 60 mg PO q4 to 6h
initially; onset of effects is 30 min, dura-
tion 4 hr
Immunosuppressive treatment with cortico-
steroids, azathioprine, cyclosporine for long-
term disease-modifying therapy
1. Prednisone initiated at 15 to 20 mg qd
titrate by 5-mg increments to effect or
dose of 1 mg/kg/day with improvement in
2 to 4 wk and maximal response by 3 to
6 mo
2. Azathioprine initiated at 50 mg qd titrated
to 2 to 3 mg/kg/day with clinical effect in
6 to 12 mo
3. Cyclosporine initiated at 5 mg/kg/day
with clinical effect within 1 to 2 mo
Plasmapheresis and IV immunoglobulin are
short-term options for immunotherapy during
an exacerbation.
Mechanical ventilation is lifesaving in setting
of a myasthenic crisis. Consider elective intu-
bation if forced vital capacity 15 ml/kg,
maximal expiratory pressure 40 cm H
2
O, or
negative inspiratory pressure 25 cm H
2
O.
SURGICAL Rx
In thymomatous MG, thymectomy is indi-
cated in all patients.
For nonthymomatous autoimmune MG, thy-
mectomy is an option in select patients, typi-
cally 40 yr.
DISPOSITION
Course of disease is highly variable.
REFERRAL
Surgical referral for thymectomy in selected
cases (see Surgical Rx)
!
PEARLS &
CONSIDERATIONS
Sustained upward or lateral gaze and arm
abduction for 120 sec may be necessary to
elicit subtle signs on examination.
Myasthenic patients can worsen rapidly and
warrant close, careful observation during an
exacerbation.
SUGGESTED READINGS
available at www.expertconsult.com
AUTHOR: TAYLOR HARRISON, M.D.
RELATED CONTENT
Myasthenia Gravis (Patient Information)
SUGGESTED READINGS
Hampton T: Trials assess myasthenia gravis therapies, JAMA 298:29-30, 2007.
Keesey JC: Clinical evaluation and management of myasthenia gravis, Muscle
Nerve 29(4):484, 2004.
Myasthenia Gravis
A
B
C
FIGURE E1-560 Positive edrophonium test in
myasthenia gravis. A, Asymmetric ptosis in the
primary position. B, Defective upgaze. C, Following
injection of edrophonium, there is marked bilateral
improvement of ptosis and modest improvement of
left upgaze. (From Kanski JJ et al: Clinical ophthal-
mology: a systematic approach, ed 7, Philadelphia,
2010, Saunders.)
A
B
C
FIGURE E1-561 Positive ice test in myasthenia
gravis. A, Asymmetricl ptosis. B, Application of ice.
C, Improvement of ptosis. (Courtesy J. Yanguela. From
Kanski JJ et al: Clinical ophthalmology: a systematic
approach, ed 7, Philadelphia, 2010, Saunders.)