1. Uncommon. Disorder of neuromuscular transmission.

Age onset is
between 2nd-3rd decades, and 6th-8th decade
2. 10-15% people with myasthenia gravis have underlying thymoma
3. epidemiology:
a. 10-20 new cases per million a year
b. prevalence: 150-200 per million
c. neonates can have transient form of MG called neonatal MG- due
to transplacental passage of maternal ab that interfere with
function of neuromuscular junction
4. pathogenesis
a. autoimmune disorder characterized by weakness and
fatiguability of skeletal muscles due to dysfunction of
neuromuscular junction
b. MG is a condition that fulfills major criteria for a disorder
mediated by autoantibodies against acetylcholine receptor.
Linkage between AchR-ab and myasthenia gravis are not
absolute. Autoantibodies directed against muscle-specific
receptor tyrosine kinase (MuSK) and other postsynaptic
neuromuscular junction are also pathogenic.
c. Some patients who are seronegative for AchR-ab have Ab
directed against another target on the surface of the muscle
membrane, MuSK.
d. Seronegative myasthenia gravis, also called Ab negative
myasthenia gravis is in 6-12% pts with MG
e. Majority of patients with AchR antibody positive MG have thymic
abnormalities: hyperplasia in 60-70% patients, thymoma in 1012% patients. The disease often improve or diappear after
thymectomy. The thymus has been evaluate as possible source
of antigen to drive this autoimmune disease
5. symptoms:
a. fluctuating muscle weakness, often with true muscle fatigue.
Fatiue is manifest by worsening contractile force of muscle
b. 2 clinical forms of MG: ocular and generalized. In ocular MG:
weakness is limited to eyelids and extraocular muscles. In
generalized MG: weakness may affect ocular muscle, but also
combination of bulvar, limb, and respiratory muscles
c. more than 50%pts present with ptosis and or diplopia
d. about 15% pts present with bulbar symptoms- fatigable
chewing, dysphagia, and dysarthria
e. less than 5% present with proximal limb weakness alone
f. eyelid muscle weakness = ptosis throughout the day, extraocular
muscle weakness = binocular diplopia that disappears when pt
closes or occludes eyes
g. prolonged chewing can cause muscle of jaw fatigue.
Oropharyngeal weakness produces dysarthria and dysphagia
h. facial muscle involvement causes expressionless

i. neck extensor and flexor muscles are commonly involved- drop

head syndrome. Proximal weakness of limbs can
j. most serious symptoms: involvement of respiratory muscles,
causing respiratory insufficiency and pending respiratory failure,
called myasthenic crisis
k. early in the disorder, symptoms can be transient, with hours,
days or even weeks free of symptoms. Maximal extent of the
disease is seen in 77% of patients by 3 yrs of onset.
6. Diagnosis
a. History and examination of finginds.
b. ice pack test for pts with ptosis (not helpful for those with
extraocular weakness)
c. edrophonium test (tensilon) for those with obvious ptosis or
ophthalmoparesis
d. confirm with immunologic and/or electrophysiologic testing
i. autoantibodies against AchR
ii. antibodies to muscle specific tyrosine kinase (MuSK)
e. repetitive nerve stimulation studies and single fiber
electromyography
i. helpful in seronegative pts
f. CT scan or US of the orbit can help differentiate ocular
myasthenia from thyroid ophthalmology.
g. Blood test should include thyroid function tests. ANA and
Rheumatoid factor are also helpful to distinguish from
rheumatologic etiology
h. Chest CT or MRI scan should be done to exclude thymoma
7. Treatment
a. 4 basic therapies for MG include: symptomatic treatment
(anticholinesterase agent), chronic immunotherapies
(glucocorticoids and other immunosuppressive drugs), rapid
immunotherapies (plasma exchange and IVIG), thymectomy
b. acetylcholinesterase inhibitors are first line treatment of
symptomatic MG
i. pyridostigmine most common
ii. starting dose is 30mg TID in adults
iii. starting dose is 0.5 to 1 mg/kg every 4-6hrs for children
c. Immunotherapy should be added in patients who remain
significantly symptomatic on pyridostigmine, or who become
symptomatic after temporary response to pyridostigmine
i. Glucocorticoids, azathioprine, mycophenolate, mofetil,
cyclosporine
d. Plasmapheresis with plasma exchange and IVIG work quickly but
short duration of action. Use to treat myasthenic crisis and
presurgical treatment of moderate to severe MG. Also used as
bridge when initiating slower acting immunotherapies, and as

periodic adjuvants to other immunologic medications in

refractory MG
e. Thymectomy suggested in pts <60yo with generalized MG and
either AchR ab, or no detectable AchR or MuSK (senonegative).
i. Do not perform thymectomy in patients with MuSK ab
associated MG without thymoma
f. Some drugs can worsen MG= aminoglycoside abx, magnesium
sulfate, penicillamine, interferon alpha, beta blocker,
procainamide, quinidine, neuromuscular blocking agents.
g. For all those with generalized MG and those with ocular MG who
are within 3 yrs of onset, pneumococcal vaccine and annual IM
influenza vaccine are recommended. Pt being treated with
immunotherapy for MG should not receive live-attenuated
intranasal influenza vaccine