Myasthenia Gravis



Myasthenia Gravis


James B. Eisenkraft

Stefan Samuelson





A. Medical Disease and Differential Diagnosis



  • What is myasthenia gravis (MG)?


  • What is the etiology and pathophysiology of MG?


  • Describe the clinical classification of MG.


  • How is the diagnosis of MG made?


  • What should be considered in the differential diagnosis?


  • How does myasthenic syndrome (Lambert-Eaton syndrome) differ from MG?


  • What treatments are available for a patient with MG?


B. Preoperative Evaluation and Preparation



  • Describe the preoperative evaluation of this patient.


  • What preoperative laboratory data are required?


  • How should the patient’s medications be managed preoperatively?


C. Intraoperative Management



  • What are your considerations in choice of anesthetic technique?


  • How should this patient be monitored intraoperatively?


  • What anesthetic regimen would you choose for this patient?


  • Can neuromuscular blocking drugs be used in a patient with MG?


  • Should the MG patient who is in remission be managed differently?



D. Postoperative Management



  • What factors will help you predict this patient’s need for continued intubation or other postoperative ventilatory support?


  • How will you determine if this patient can be safely extubated?


  • How will you manage postoperative analgesia?


  • How will you define and manage postextubation ventilatory failure in this patient?


A. Medical Disease and Differential Diagnosis


A.1. What is myasthenia gravis (MG)?

MG is a disorder of the neuromuscular junction and therefore of great significance to the anesthesiologist. It is a chronic disorder characterized by fluctuating painless weakness and fatigability of voluntary muscles made worse on exertion with improvement following rest. The onset is usually slow and insidious; any skeletal muscle or muscle group may be affected. The most common onset is ocular, presenting with ptosis and diplopia. If the symptoms remains localized to the eyes for 2 years, the likelihood of progression to generalized disease is low. In many cases, however, MG is generalized and may involve the bulbar musculature, causing problems with breathing, speaking, mastication, and swallowing. Proximal muscles are more commonly involved than distal. Peripheral muscle weakness may manifest as clumsiness, difficulty holding up the head, or in ambulating. Respiratory muscle weakness may cause dyspnea, a decrease in the ability to cough and therefore to remove secretions.

The incidence of MG appears to be increasing. The most accurate estimate of incidence of MG was around 30 per 1,000,000 per year. The incidence in children and adolescents aged 0 to 19 years was found to be between 1.0 and 5.0 per 1,000,000 per year. These rates may well be an underestimate of the true incidence rates because mild cases may have been missed and cases in the elderly may have been misdiagnosed. People of any age may be affected, but peaks of incidence occur in the third decade for women and the fifth decade for men.



Drachman DB. Myasthenia gravis. N Engl J Med. 1994;330:1797-1810.

McGrogan A, Sneddon S, de Vries CS. The incidence of myasthenia gravis: a systematic literature review. Neuroepidemiology. 2010;34:171-183.

Sathasivam S. Current and emerging treatments for the management of myasthenia gravis. Ther Clin Risk Manag. 2011;7:313-323.


A.2. What is the etiology and pathophysiology of MG?

In normal neuromuscular transmission, the acetylcholine released from the motor nerve terminal stimulates postsynaptic nicotinic receptors at the motor end plate to generate an action potential leading to depolarization of the membrane and contraction of the motor unit. The normal neuromuscular junction has a very large number of postsynaptic acetylcholine receptors (AChRs) such that muscle weakness only becomes apparent when 70% or more of the receptors have been blocked. This excess of receptors has been termed the “margin of safety of neuromuscular transmission.” MG patients have a significant decrease in the number of postsynaptic AChRs at the end plates of affected muscles resulting in a decreased margin of safety of neuromuscular transmission.

MG is an autoimmune disorder, and about 80% of affected patients have detectable circulating antibodies to the nicotinic AChR. These anti-AChR antibodies may cause complementmediated lysis of the postsynaptic membrane, directly block the receptors, or may modulate the receptor turnover such that the rate of degradation exceeds the rate of resynthesis. Studies of the motor end plate area show loss of synaptic folds and a widening of the synaptic cleft. Some MG patients who do not have anti-AChR antibodies, have antibodies to muscle-specific tyrosine kinase (MuSK). These MuSK-antibody-positive MG patients often develop prominent oculobulbar muscle weakness.

The cause of MG is unknown but appears to be related in some way to the thymus gland. It has been suggested that thymic T cells are stimulated to produce antibodies following
sensitization by a protein similar to the AChR. MG patients also have a higher incidence of other autoimmune diseases including thyroid, lupus, and rheumatoid.



Blichfeldt-Lauridsen L, Hansen BD. Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand. 2012;56:17-22.

Paton WD, Waud DR. The margin of safety of neuromuscular transmission. J Physiol. 1967;191:59-90.


A.3. Describe the clinical classification of MG.

Since the original clinical classification by Osserman and Genkins who described four classes and two subclasses, several others have been published. The Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America Clinical Classification describes five main classes and several subclasses as follows:



  • Class I: any ocular muscle weakness; may have weakness of eye closure; all other muscle strength is normal.


  • Class II: mild weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity



    • Class IIa: predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles


    • Class IIb: predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles, or both


  • Class III: moderate weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity



    • Class IIIa: predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles


    • Class IIIb: predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles, or both


  • Class IV: severe weakness affecting other than ocular muscles; may also have ocular muscle weakness of any severity



    • Class IVa: predominantly affecting limb, axial muscles, or both; may also have lesser involvement of oropharyngeal muscles


    • Class IVb: predominantly affecting oropharyngeal, respiratory muscles, or both; may also have lesser or equal involvement of limb, axial muscles, or both; use of a feeding tube without intubation


  • Class V: defined by the need for intubation, with or without mechanical ventilation, except when used during routine postoperative management



Jaretzki A III, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis: recommendations for clinical research standards. Task Force of the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America. Neurology. 2000;55:16-23.

Osserman KE, Genkins G. Studies in myasthenia gravis: review of a twenty-year experience in over 1200 patients. Mt Sinai J Med. 1971;38:497-537.


A.4. How is the diagnosis of MG made?

The diagnosis of MG is suspected from the patient’s history and confirmed by clinical, electrophysiologic, pharmacologic, or immunologic testing. Typically, the patient cannot sustain or repeat muscular contraction. Clinical tests of fatigability include maintaining an upward gaze, holding out an affected limb, and respiratory function testing (vital capacity, maximum breathing capacity).

The electrical counterpart of fatigability is a decrement in the compound muscle action potentials evoked by repetitive stimulation of a motor nerve. Supramaximal stimulation of a peripheral nerve at 2 Hz is applied; a decrement in the size of the fourth or fifth response compared to the first is diagnostic. This is the most specific of the nerve tests for MG, but it can be performed only on certain muscles, which may not be the ones affected in an individual patient. A more sensitive electrophysiologic test is single-fiber electromyography (EMG) where an increase in jitter is found.

Pharmacologic testing is based on administration of an anticholinesterase and observing a rapid improvement in function. Mechanical and electrical (e.g., EMG), decrements
improve with 2 to 10 mg of intravenous edrophonium (Tensilon test). MG patients characteristically are sensitive to nondepolarizing muscle relaxants. When the routine EMG results are equivocal, a regional nondepolarizing muscle relaxant test may be performed using a tourniquet to isolate the limb and limit the action of the drug. In the regional nondepolarizer muscle relaxant test, EMGs are performed before and after the administration of 0.2 mg of curare. In MG, there is an exaggerated response to this small dose of curare.

Antibodies to the AChR are detectable in 80% of patients with MG. In equivocal cases, a positive result of a test for anti-AChR antibodies is considered diagnostic. Interestingly, the anti-AChR antibody titer is unrelated to the severity of the disease or the patient’s prognosis.



Blichfeldt-Lauridsen L, Hansen BD. Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand. 2012;56:17-22.


A.5. What should be considered in the differential diagnosis?

A number of disorders can mimic MG and should be included in the initial differential diagnosis.

Thyrotoxicosis can present with generalized weakness and abnormal thyroid function. Patients with neurasthenia characteristically have weakness, which disappears when individual muscle groups are tested. Progressive external ophthalmoplegia; restrictive cardiomyopathies; muscular dystrophies; brain tumors; amyotrophic lateral sclerosis; myasthenic polymyopathy with hypersensitivity to neostigmine; and drugs such as D-penicillamine, aminoglycosides, quinine, procainamide, and calcium channel blockers can also cause myasthenia-like symptoms.



Gilhus NE, Nacu A, Andersen JB, et al. Myasthenia gravis and risks for comorbidity. Eur J Neurol. 2015; 22:17-23.


A.6. How does myasthenic syndrome (Lambert-Eaton syndrome) differ from MG?

Myasthenic syndrome is a very rare immune-mediated disorder of neuromuscular transmission, associated with antibodies to the presynaptic voltage-gated calcium channel. The prevalence is estimated to be about 1 per 100,000. It is associated with small cell carcinoma of the lung in 50% to 60% of cases. Complaints of weakness may be mistaken for MG, but in Lambert-Eaton syndrome, symptoms do not respond to administration of anticholinesterases or steroids, and activity improves strength. The defect in this condition is prejunctional, is associated with diminished release of acetylcholine from nerve terminals, and is improved by facilitating agents such as 4-aminopyridine that increase repetitive firing. Affected patients are particularly sensitive to the effects of all muscle relaxants, which should be used with great caution or avoided entirely. The possibility of Lambert-Eaton syndrome should be considered in all patients with known malignant disease and those patients undergoing diagnostic procedures for suspected carcinoma of the lung. Anesthesia considerations in these patients are essentially the same as in those with MG.



Keogh M, Sedehizadeh S, Maddison P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst Rev. 2011;(2):CD003279.

Petty R. Lambert Eaton myasthenic syndrome. Pract Neurol. 2007;7:265-267.

Weingarten TN, Araka CN, Mogensen ME, et al. Lambert-Eaton myasthenic syndrome during anesthesia: a report of 37 patients. J Clin Anesth. 2014;26:648-653.

Only gold members can continue reading. Log In or Register to continue

Mar 18, 2021 | Posted by in ANESTHESIA | Comments Off on Myasthenia Gravis

Full access? Get Clinical Tree

Get Clinical Tree app for offline access