Myesthenia Gravis (
Uptodate – Diagnosis of mysethenia, treatment of myasthenia, myesthenic crisis,
thymectomy
Levental, Anesthesiology, 1980, 53: 26-30
o Myasthenia gravis (MG) is the most common disorder of neuromuscular
o
o
transmission
o annual incidence of 10 to 20 new cases per million people and a
prevalence of 100 to 200 per million
o It occurs at any age, but there tends to be a bimodal distribution to the
age of onset with an early peak in the second and third decades (female
predominance) and a late peak in the sixth to eighth decade (male
predominance)
The hallmark of the disorder is a fluctuating degree and variable combination of
weakness in ocular, bulbar, limb, and respiratory muscles
Weakness is the result of an antibody-mediated attack directed at proteins in the
postsynaptic membrane of the neuromuscular junction (acetylcholine receptors
and/or receptor-associated proteins). The diagnosis of MG can be established by
clinical and serologic testing
Clinical presentation
o There are two clinical forms of myasthenia: ocular and generalized
o ocular myasthenia gravis (MG) weakness is limited to the eyelids and
extraocular muscles
o generalized disease, the weakness may also commonly affect ocular
muscles, but it also involves a variable combination of bulbar, limb, and
respiratory muscles
o The cardinal feature of myasthenia gravis (MG) is fluctuating skeletal muscle
weakness, often with true muscle fatigue. The fatigue is manifest by worsening
contractile force of the muscle, not a sensation of tiredness
o Often weakness is worst in the evening or after exercise
o >50 percent of patients present with ocular symptoms of ptosis and/or diplopia.
Of those who present with ocular manifestations, about half will develop
generalized disease within two years
o 15 percent of patients present with bulbar symptoms. These include dysarthria,
dysphagia, and fatigable chewing
o < 5 percent present with proximal limb weakness alone
o Many Drugs may exacerbate or unmask MG
o Anesthetic agents
o Antibiotics
o Cardiovascular Drugs
Diazepam
Aminoglycosides
Beta blockers
Halothane
Flouroquinolones
Verapamil and CCBs
Ketamine
Ampicillin
Magnesium
Lidocaine
Macrolides
Neuromuscular
Tetracyclines
blocking agents
o Anticonvulsants
o Antipsychotics
o
Gabapentin
Lithium
Phenytoin
Phenothiazines
Diagnosis
o Focused on confirming the clinical diagnosis as established by the history and
exam
o Bedside tests
o Tensilon Test – Where still available, the Tensilon test should be used only
in those patients with obvious ptosis or ophthalmoparesis, in whom
improvement after infusion of the drug can easily be observed.
 Draw up 10 mg (1cc) of edrophonium (Tensilon)
 Give test dose of 2mg followed by 2mg every 2 minutes up to the
total of 10mg
 Look for increase in muscle strength
 Sensitivity 80-90% but there are many false positives and false
negatives
o Ice Pack Test – a bag (or surgical glove) is filled with ice and placed on
the closed lid for two minutes. The ice is then removed and the extent of
ptosis is immediately assessed. The sensitivity appears to be about 80
percent in those with prominent ptosis. The predictive value of the test
has not yet been established
o Laboratory Methods
o Serologic tests - positive AChR-Ab or MuSK-Ab assays are present in 88 to
94 percent of patients with generalized disease, provides the laboratory
confirmation of MG
 Ideally, serologic testing for AChR-Ab should be performed prior to
initiating immune modulating therapy for MG, as such therapy can
sometimes lead to apparent seronegativity
o Electrophysiologic  Repetitive nerve stimulation
 Positive if
o Patients who have detectable antibodies to the acetylcholine receptor
(AChR) are called seropositive (SPMG) and those without are called
seronegative (SNMG)
o half of patients with purely ocular MG are seropositive, compared with
nearly four-fifths of those with generalized disease
o About 10 to 15 percent of those with MG have an underlying thymoma
Treatment
o There are 4 basic therapies for MG
o Symptomatic treatments (anticholinesterase agents)
 Pyridostigmine (mestinon)
 Prolong the action of acetylcholine at the Neuromuscular junction
leading to a variable improvement in strength
o Chronic immunomodulating treatments
 Glucocorticoids and other immunomodulating agents
 Common
 Prednisone
 Azathioprine
 Cyclosporine
 MMF
 Less common


o
o
o
Pulse cyclophosphamide
Tacrolimus
Rapid immunomodulating treatments
 Plasma exchange and IVIG
 Usually reserved asa rescue for myesthenic crisis or as a bridge to
surgery
 NOTE: Some surgeons prefer IVIG due to a mild coagulopathy that
can develop with plasma exchange
Surgical therapy
 Thymectomy
 Many believe that thymectomy is beneficial in patients <65
who have generalized MG without thymoma
o There are no prospectiverandomized, blinded,
controlled trials
 Can take years for the benefit of thymectomy to accrue
 2 approaches – transsternal or extended cervical
o Must remove all of the thymus even residual grams
can continue to cause problems
o Risk factors for post op ventilation after transsternal
thymectomy (Leventhal 1980 Anesthesiology 53, 2630)
 Disease duration >6years
 History of respiratory disease
 Pyrodostigmine dose >750mg/day
 Vital capacity <2.9L
 NOTE : these criteria, despite their wide
usage have not been validated in other
surgeries or even in other centres
Myesthenic crisis
o Myasthenic crisis is a life-threatening condition, defined as weakness
from acquired myasthenia gravis (MG) that is severe enough to
necessitate intubation, or delay extubation following surgery
o Respiratory
 When increasing weakness becomes apparent, the forced vital
capacity (FVC) is the respiratory parameter to monitor
 A patient at imminent risk for respiratory failure should
have the FVC measured every two to four hours
 Elective intubation should be considered if serial
measurements of the FVC show consistent declines
approaching 15 mL/kg body weight or if the NIF shows
declines approaching 25 cmH20
o Rapid therapies
 IVIG or plasmapheresis – no difference in efficacy but less side
effects with IVIG
o Immunomodulating therapies
 Prednisone +/- others
o Weaning form mechanical ventilation
 Start once the patient starts to improve respiratory strength
 with a forced vital capacity (FVC) >15 mL/kg and a
negative inspiratory force (NIF) >30 cmH2O
Summary of Treatment of myasthenic crisis
Admit to intensive care unit
Measure FVC frequently, as often as every two hours if respiratory status is deteriorating
Electively intubate in the presence of any of the following conditions:
FVC less than 15 mL/kg body weight
Declines in serial measurements of FVC approaching 15 mL/kg
Declines in serial measurements of NIF approaching 25 cmH2O
Clinical signs of respiratory distress
Difficulty handling oral secretions, swallowing, or speaking
Withdraw anticholinesterase medications to reduce airway secretions in patients who are
intubated
Begin rapid therapy with plasmapheresis or IVIG to treat myasthenic crises
Begin immunomodulating therapy with high dose corticosteroids (eg, prednisone 60 to 80 mg
per day). Consider azathioprine, mycophenolate mofetil, or cyclosporine if steroids are
contraindicated or previously ineffective
Initiate weaning from mechanical ventilation when respiratory muscle strength is improving
with plasmapheresis or IVIG treatment, as quantified by a FVC >15 mL/kg and NIF >30 cm
H2O