• Myasthenia gravis (MG) is an autoimmune postsynaptic neuromuscular junction (NMJ) transmission disorder. In the majority of cases (85%), MG is associated with auto-antibodies against the acetylcholine (ACh) receptor.
• The hallmark of the disorder is weakness and fatigability in ocular, bulbar, limb, and respiratory muscles.

• Cause remains unknown. It is an autoimmune disorder and does not appear to have a genetic predisposition. In some cases, it may be associated with a thymoma or other autoimmune disorders.
• Myasthenic crisis:
  • Infection
  • Hypothermia
  • Hypokalemia, hypophosphatemia
  • Surgical intervention
  • Pregnancy, childbirth
  • Tapering of immunosuppressive medications
  • Drugs that may worsen the muscular weakness: Aminoglycosides, fluoroquinolones, macrolides, beta-blockers, diuretics, procainamide, magnesium salts, calcium channel blockers, intravenous iodinated contrast agents, glucocorticoids

• Normal muscle contraction is the result of pre-synaptic release of ACh into the NMJ. ACh binds to acetylcholine receptors (AChR) on the postjunctional membrane; when both subunits of the AChR are bound, it undergoes a conformational change that allows sodium and calcium to flow intracellularly and increase the voltage (make positive). The membrane resting potential is ~-90 mV, and when a membrane threshold of -30 mV is attained (~10–20% of AChR are opened), voltage-gated ion channels open and fully depolarize the membrane, producing an action potential.
• MG is the result of an antibody-mediated attack against ACh postsynaptic receptors of the NMJ, leading to a reduction in the number of ACh receptors. Consequently, there is a decrease in the agonist effect of ACh on the postsynaptic NMJ; therefore, the membrane threshold is less easily attained.
• This results in a characteristic pattern of progressively reduced muscle strength with repeated use of the muscle and recovery of muscle strength following a period of rest.
• Myasthenic crisis is an exacerbation and can result in a life-threatening condition, characterized by neuromuscular respiratory failure. Severe bulbar muscle weakness often accompanies the respiratory muscle weakness or may be the predominant feature. Myasthenic crisis may be precipitated by a variety of factors (see Risk Factors). In addition, it can occur spontaneously as part of the natural history of MG itself.
• Cholinergic crisis results from an excess of anticholinesterase drugs. Excessive ACh stimulation produces flaccid muscle paralysis and pupil constriction.

• Assess the severity of disease, evaluate pulmonary function, and optimize medications.
• Continue anticholinesterase drugs in the preoperative period. In the postoperative period, anticholinesterase drugs should be administered slowly and cautiously. Patients may have a decreased requirement of these drugs in the first 48 hours.
• Avoid muscle relaxants in MG patients, if possible. MG patients have an abnormal response to depolarizing (i.e., relative resistance) and non-depolarizing (i.e., more prolonged action) blocking agents.
• The anesthetic plan should consider the use of ultra-short–acting anesthetics in order to avoid postoperative respiratory depression and hypoventilation.
• Avoid postoperative mechanical ventilation (MV), whenever possible. Most patients may be safely extubated at the end of the procedure, but those with severe MG may benefit from a period of MV.

• Fatigable weakness that worsens after exercise and improves with rest
• Chronic, fixed weakness may also be present

Evaluate the adequacy of drug therapy

• Anticholinesterases
• Immune suppression (steroids, azathioprine, cyclosporine)
• Thymectomy (for patients with generalized MG with thymoma or who are less than age 60 without thymoma)
• Plasmapheresis and intravenous immune globulin.

• Thymoma: The majority of patients with AChR antibody-positive MG have thymic abnormalities; hyperplasia in 60–70% and thymoma in 10–15%.
• Other autoimmune disorders that may be present include systemic lupus erythematous, rheumatoid arthritis, pernicious anemia, thyrotoxicosis.

If the patient is poorly controlled, a course of plasmapheresis may be of benefit in the preoperative period. There should a 24-hour delay between the last plasmapheresis and surgery to restore clotting factors.

• Grades
  • Grade I: Only eyes affected
  • Grade IIa: Mild generalized MG responding well to therapy
  • Grade IIb: Moderate generalized MG responding less well
  • Grade III: Severe generalized disease
  • Grade IV: Myasthenic crisis requiring MV
• Preoperative factors associated with need for prolonged postoperative MV include: FVC <2.9 L, history of MG >6 years, major surgery, co-existing lung disease, and grades III and IV MG

• Postoperative care should take place in the ICU with monitoring of respiratory function as well as chest physiotherapy for 12 hours.
• Meticulous attention to pulmonary toilet is required, particularly since respiratory secretions may be increased by anticholinesterase drugs
• Good pain control, especially after thymectomy
• Avoid drugs that may exacerbate MG.

• Weakness after surgery presents a special problem in MG patients. The differential diagnosis includes myasthenic crisis, residual effects of anesthetic drugs, non-anesthetic drugs interfering with neuromuscular transmission, and cholinergic crisis. for these reasons, many clinicians prefer to avoid the use of muscle relaxants, or if they use muscle relaxants, allow the neuromuscular block to recover spontaneously. Tensilon (edrophonium) challenge test is useful in distinguishing myasthenic crisis from cholinergic crisis.
• Aspiration, pneumonia, inadequate cough, atelectasis
• Need of ventilatory assistance in the postoperative period due to respiratory failure
• Rule out pneumothorax and phrenic nerve damage in case of thymectomy.

• Pulmonary Function Tests
• Functional Residual Capacity
• Anterior Mediastinal Mass
• Flow Volume Loops

• 358.00 Myasthenia gravis without (acute) exacerbation
• 358.01 Myasthenia gravis with (acute) exacerbation

• G70.00 Myasthenia gravis without (acute) exacerbation
• G70.01 Myasthenia gravis with (acute) exacerbation

Fabrizio Racca , MD

Elena C. Capello , MD

Federica Manfroi , MD

V. Marco Ranieri , MD