Myasthenia Gravis

Sean Green
July 31, 2013
Definition: A chronic disease characterized by rapid fatigue of striated muscle; most
commonly caused by autoantibody-mediated neuromuscular blockade at the post-synaptic
motor-end plate.
Epidemiology: Ranges from 0.5-2 million cases per 100,000 to 1,000,000 live births in the
US.
Can occur at any age
o Female incidence peaks in 30s, while male incidence peaks in 60s
Females are more likely to be diagnosed with a 3:2, F:M ratio
o Males more likely to develop ocular symptomology with 1.5:1 ratio
On average, younger age of onset for those of Asian ancestry
Clinical Manifestations:
Three clinical variants In childhood disease:
o Neonatal myasthenia gravis: Infants born to MG mothers can have transient
secondary syndrome due to circulating maternal antibodiesresp
insufficiency, inability to suck/swallow, general hypotonia/weakness
Duration of days to weeks requiring vent support and gavage feeding
Regain normal strength after Auto-Ab disappearance and no increased
risk of MG devo later in life
o Juvenile myasthenia gravis: occurs in late infancy and childhood
o Congenital myasthenia gravis: Severe, permanent disorder without
spontaneous remission
Episodic apnea is common! Resp insufficiency often preceded by viral
illness
Tranmitted by autosomal recessive defects in post-synaptic molecules
(rapsyn in >85% cases) NO circulating auto-antibodies!
>60 ID genetic mutations
RAPID MUSCLE FATIGUE! Upward gaze examining ptosis after 30-90 sec, repetitive
fist/hand closings producing fatigue
o Symptomatic most late in day and when tired
Diplopia and ptsosis are common; younger children may hold open eyelids is severe
ptosis obstructing vision; pupillary response to light is preserved
Dysphagia and facial weakness are common with feeding difficulties often being a
cardinal sign (impaired chewing)
Poor head control due to weakness of neck flexor muscles; limb-girdle/distal muscles
of hands can be affected in most cases
Left untreated MG is progressive and can lead to respiratory muscle involvement
ASPIRATION RISK!
Common Comorbidities:
Occasionally associated with Hashimotos disease hypothyroidism
In children/adults, thymomas result in unique Eaton-Lambert syndrome
Diagnosis:
EMG more specific vs. muscle biopsy
o Normal motor nerve conduction velocity with progressive diminishes in muscle
potential with repeated stimulation usually limited to clinically affected
muscles

Auto-Ach antibodies are inconsistently demonstrated

o Anti-AChR Ab and Anti-MuSK Ab (+) in 30% of adolescents and adults, but rare
in prepubertal children
Anti-MuSK Ab key to fetal development
o Possible mutated AChE gene in congential cases
Immune/inflammatory markers usually elevated: ANA, CK, ESR, elevated IgG
CT abdo (anterior mediatstinum) may show thymic hypertrophy or thymoma
Clinical Myasthenia Gravis Test: requires administration in-house due to
likelihood of complications such as arrhythmia or cholinergic crisis!
o Children >2 y/o
Required specific fatigable weakness!
AChE Challenge: Edrophonium 0.04mg/kg administered IV dose to r/o
allergic rxn/extreme AntiACh SE sensitivity; followed by 0.1-0.2mg/kg
(max 10mg) IV infusion
Effects should be seen w/i 10 sec and disappear w/i 120 sec (e.g.
distance between upper and lower eyelids or ability to swallow)
LA AChE not useful in Dx; Neostigmine test also useful, but not as
definitively diagnostic
Atropine (0.01mg/kg) should be available to block aute muscarinic
effects (abdo cramps/diarrhea, broncotracheal secretions, arrhythmia)
o Children <2 y/o
EKG monitoring required b/c increased susceptibility to cardiac
arrhythmia; IV neostigmine is contraindicated!!
Atropine rescue of 0.1/kg should be available
Neostigmine IM 0.04mg/kg; repeat dose may be administered 4hr after
if equivocal effect seen
Peak effect seen in 2- to 40 min post-dose

Treatment:
Cholinesterase-inhibitors: Primary therapeutic agents
o Neostigmine IM 0.04mg/kg Q4H to Q6H
o Most tolerate PO neostigmine 0.4mg/kg Q4H to Q6H
Give 30min prior to meal if dysphagia to improve swallowing
o Pyridostigmine is slightly longer acting and may provide an alternative
o OD can lead to cholinergic crisis tx w/ atropine which blocks muscarinic
effects w/o blocking nicotinic effects
Long-term steroid treatment and thymectomy can be considered curative in patients
with thymus hypertrophy/tumor
o Especially pts with high Anti-AChR plasma auto-Ab w/ sx < 2 yrs
Plamapheresis and IVIG have shown benefit in steroid-resistant patients, especially
those with high circulating levels of Anti-AChR plasma auto-Ab
o Pheresis only provides temporary remission
Rituximab has shown benefit as therapy in refractory patients
Prognosis:
Many experience spontaneous remission after a period of months to years while
others have permanent disease extending into adulthood
Immunosupression, thymectomy and hypothyroidism may provide a cure
Mortality is now 3-4%, with principal risk factors being age older than 40 years, short
history of progressive disease, and thymoma