It is a relatively rare autoimmune disorder in which
antibodies form against acetylcholine (ACh) nicotinic post-synaptic receptors
at the myoneural junction, resulting in impaired muscle strength with
a characteristic pattern of progressively reduced muscle strength with
repeated use of the muscle and recovery of muscle strength following a period
Female > Male (3:2). Children with MG plus associated disease: Female
> Male (5:1)
Three peaks of onset: neonatal due to transfer of maternal autoantibodies,
age 20-30 and over age 50.There are two peaks of onset in adults: age 20-30
(with a female predominance) and over age 50 (with a slight male predominance).
The role of the thymus: 75% of patients with MG have some degree of
thymus abnormality (hyperplasia in 85%, thymoma in 15%). Given the immunologic
function of the thymus and the improvement in the clinical condition of patients
following thymectomy, it is suspected that this is the site of autoantibody
Thyroid disorders may be seen in up to 4% of patients with MG and
symptoms of hyperthyroidism or hypothyroidism may be present.
Symptoms & Signs
of Myasthenia Gravis
Generalized weakness & fatigability with repeated activity, &
reduced exercise tolerance that improves with rest or specific weakness
of certain muscle groups, such as difficulty in climbing stairs.
Weakness of bulbar muscles, a prominent feature of MG, may lead to
complaints of ptosis, diplopia, blurred vision, difficulty swallowing
or dysarthria. MG may affect bulbar muscles alone in 20% of cases.
Dysarthria, Dysphagia , Neck and proximal limb weakness
The facial muscles may be slack and the face expressionless, the patient
may be unable to support his head which will fall onto the chest while the
patient is seated, the jaw is slack, the voice has a nasal quality and the
body is limp.
The gag reflex is often absent and such patients are at risk for aspiration
of oral secretions.
Of utmost concern in severe exacerbations of MG is the patient's ability
to generate adequate ventilation and to clear bronchial secretions.
Inability to cough leads to an accumulation of secretions, such that rales,
rhonchi and wheezes may be auscultated locally or diffusely. The patient
may have evidence of pneumonia (i.e., fever, cough, dyspnea and consolidation).
One of the confusing factors in managing patients with MG is that insufficient
medication (myasthenic crisis) and excessive medication (cholinergic crisis)
can present in similar ways.
Cholinergic crisis results from an excess of cholinesterase inhibitors (i.e.,
neostigmine, pyridostigmine and physostigmine) and resembles organophosphate
In this case, excessive ACh stimulation of striated muscle, at nicotinic
junctions, produces flaccid muscle paralysis that is clinically indistinguishable
from weakness due to MG.
The patient may also have bronchospasm with wheezing, bronchorrhea, respiratory
failure, diaphoresis and cyanosis from either cause.
Cholinergic crisis may also be marked by miosis and the SLUDGE syndrome (i.e.,
salivation, lacrimation, urinary incontinence, diarrhea, GI upset, hypermotility
and emesis). However, these findings are not inevitably present.
There are no laboratory tests that are available in a time frame useful to
confirm the emergency diagnosis of patients with MG.
CXR & Pulmonary function tests: as pulse oximetry, peak expiratory
flow or FEV1 or vital capacity, and ABG sampling to determine pCO2.
Evidence of hypoxemia, poor respiratory effort or CO2 retention is an indication
for intubation and mechanical ventilation.
CXR is relatively insensitive in screening for thymoma as it misses up to
CT or MRI of the chest is highly accurate in detecting thymoma. Every
MG patient should be screened for thymoma.
The Tensilon (edrophonium) challenge test
is useful in distinguishing myasthenic from cholinergic crisis. Once the
patient's airway and ventilation are secured, an initial test dose of edrophonium
(0.1 -0.2 mg IV) is given. Some patients may respond noticeably to even this
small dose. If no adverse reaction occurs following the test dose, another
dose of edrophonium (1-2 mg IV) should produce noticeable improvement in
muscle strength within one minute. If there is no improvement, an
additional dose of up to 8 mg IV can be administered to a total of 10 mg.
The patient must be monitored carefully during this procedure as
edrophonium can cause significant bradycardia, heart block and asystole.
(* Have atropine injection ready)
If muscle strength fails to improve following the maximum dose of edrophonium,
the patient is having a cholinergic crisis or has another cause of weakness
unrelated to myasthenia.
Patients with a cholinergic crisis may respond to edrophonuium challenge
by increasing salivation and bronchopulmonary secretions, diaphoresis and
gastric motility (i.e., SLUDGE syndrome).
These changes should be managed expectantly, as the half-life of edrophonium
is short (approximately 10 minutes). Patients who respond, generally show
dramatic improvement in muscle strength, regaining facial expression, posture
and respiratory function within one minute.
The effects of edrophonium are brief and repeated doses may be required before
oral anticholinesterase medication can take effect.
In patients with less severe exacerbations, the degree of improvement with
edrophonium may be subtle.
Electromyography and assays of cholinesterase activity (myasthenia
panel blood tests); however, these tests are usually not available on
an emergent basis.
Ice pack test: In a myasthenic patient with ptosis, ice placed
over an eyelid will lead to cooling of the lid; the ptosis may improve
neuromuscular transmission leading to improvement of the ptosis.
Ice placed in a surgical glove or wrapped in a towel placed lightly over
the eyelid will cool it within 2 minutes.
A positive test is clear resolution of the ptosis.
Thought to be positive in about 80% of patients with ocular myasthenia.
Physical exam that shows fatigue and weakness on examination.
Diagnosis be confirmed by an edrophonium or neostigmine test.
Repetitive nerve stimulation studies demonstrate a rapid reduction (>12%
) in the amplitude of the MAP.
Single-fiber EMG demonstrates increased jitter and blocking in more than
90 percent of patients.
An MRI of the chest should be performed to search for thymic hyperplasia
The serologic diagnosis of MG is made by detecting AChR antibodies with a
radioimmunoprecipitation assay. These antibodies are present in as many as
90 percent of patients with generalized MG and in as many as 70 percent of
patients with ocular MG. Such antibodies are also found in as many as 30
percent of patients with autoimmune liver disease, in 10 percent of patients
with pernicious anemia, and in as many as 13 percent of patients with LEMS.
Generally, AChR antibody titers do not correlate with clinical severity.
MG must be differentiated from other diseases or agent-induced disorders
that present similar clinical pictures, such as botulism, organophosphate
poisoning, d-penicillamine toxic reaction, mitochondrial myopathy, compressive
lesion affecting cranial nerves, LEMS, and congenital myasthenic syndromes.
RX of Myasthenia Gravis
Patients with myasthenic crisis can develop apnea very suddenly and must
be closely observed.
Myasthenia gravis is controllable with cholinesterase inhibiting
medications. These include edrophonium, which is primarily used
as a diagnostic tool because its half-life is so brief.
Pyridostigmine /Mestinon 60 mg po q4-6 hours is used for long term
Depending on clinical response, the dosage can be increased, but incremental
benefit is not to be expected in amounts greater than 120 mg every 2 hours.
If patients have difficulty eating, doses can be taken about 30 minutes before
a meal. If patients have special difficulty on waking in the morning, a
prolonged-release 180-mg tablet of pyridostigmine (Timespan) can be taken
at bedtime. Muscarinic symptoms can be ameliorated by preparations containing
atropine, with each dose of pyridostigmine.
For NPO patients, it may be given IM or very slowly IV at dose 1/30th of
PO dose. (Watch for cholinergic reactions)
Prednisone 40-100 mg/day for an initial period of three to four weeks.
Then, over an eight-week period, the dose on alternate days is gradually
reduced by 10 mg a week (more often if side effects are severe) until the
lowest possible dose is reached that controls the disease.
Other immunosuppressive drugs, such as azathioprine 2-3
mg/kg/d or cyclosporine 5 mg/kg/d.
Bronchodilators may be useful in overcoming the bronchospasm associated
with a cholinergic crisis.
Respiratory support: O2 supplement, sputum suction, respirator if
Plasmapheresis has been found to be an effective short term treatment
for acute exacerbations of MG.
Thymectomy is associated with clinical improvement in 85% of cases
and 35% of patients appear to have complete remission.
Consultations: Emergent consultation with a neurologist is indicated.
Patients with severe exacerbations requiring intubation and mechanical
ventilation are managed in an intensive care setting with appropriate
Miscellaneous: diphenylhydantoin, lithium, chlorpromazine, muscle relaxants,
levothyroxine, ACTH and corticosteroids.
In case of endotracheal Intubation:
Rapid sequence intubation should be modified in that depolarizing paralytic
agents, such as succinylcholine, have less predictable results in patients
with myasthenia. The relative lack of ACh receptors makes these patients
relatively resistant to succinylcholine; higher doses must be used to induce
paralysis. Once paralysis is achieved, it may be prolonged. A rapid
onset nondepolarizing agent (i.e., rocuronium or vecuronium), is the preferred
paralytic agent in this circumstance. Although the onset is delayed
compared with succinylcholine, these medications will not result in unwanted
Although MG patients can develop any common infection that can result in
decompensation, the most likely source of infection is pulmonary.
Cultures of blood, sputum and urine may be indicated on an individual basis
and chest x-ray is important in detecting pneumonia.
Appropriate broad spectrum antibiotics are indicated for sepsis and pneumonia.
It is important to consider that fluoroquinones and macrolide antibiotics
may adversely affect cholinergic transmission in MG and these should be avoided,
Fever: Patients with MG are sensitive to high temperatures (core or
ambient) and their muscle strength can improve when temperature is lowered
with cooling measures or antipyretics.
SAM 8-1999 E-Medicine 8-1999 Edward Newton,
M.D., Department of Emergency Medicine, LAC-USC Medical Center
Manual of Neurologic Therapeutics - Martin A. Samuels