Myasthenia Gravis

Myasthenia gravis (MG) is the most common neuromuscular junction (NMJ) disorder affecting skeletal muscle. The formation of autoantibodies against post-synaptic NMJ proteins, usually acetylcholine receptors (AChRs), impedes neurotransmission across the NMJ, causing fatigue and muscle weakness.¹ Autoantibodies may also be directed at receptors for muscle-specific kinase (MuSK) and lipoprotein-related protein 4 (LRP-4); together with agrin, these are essential for NMJ homeostasis.² The muscle groups involved and the age at presentation vary among patients, although most will have some degree of extraocular muscle involvement.¹  MG can be exacerbated by infection, immunization, surgery, and drugs.² 

Clinical Features 

The hallmark feature of MG is painless weakness that is brought on or exacerbated by exertion. Fatigue itself is not always evident. The pattern of muscle involvement varies among patients; however, the extraocular muscles and the levator palpebrae muscle are usually involved, resulting in diplopia and ptosis, respectively. Limited facial expression and difficulty with speech, chewing, and swallowing are manifestations of facial and bulbar weakness, and some patients may appear to snarl when attempting to smile. Head droop may develop if the muscles of the neck are affected. Limb weakness may involve the small, distal muscles of the hands, but proximal limb weakness is the most prominent finding. Tests of fatigue, such as repetitive shoulder abduction or sustained upward gaze to precipitate ptosis, may sometimes be necessary to reveal mild muscle weakness clinically.¹ 

A potentially devastating complication of MG is myasthenic crisis—severe weakness of the respiratory muscles that can be life-threatening. Respiratory weakness is monitored by measuring forced vital capacity (rather than peak flow) on spirometry. Patients with MG are managed with anticholinesterase medications, and a cholinergic crisis may develop when these are taken in excess. Cholinergic crisis  is characterized by exacerbation of weakness (due to depolarization block of neuromuscular transmission) and an increase in cholinergic symptoms, including hypersalivation, lacrimation, sweating, vomiting, and miosis.¹ 

The age at onset of MG is variable, and the disease may present in childhood or adulthood. Symptom onset can be acute or subacute, and the course may be relapsing and remitting. A rare form of MG, called maternally mediated MG, occurs in up to 10% of babies born to women with MG and may occur even if the mother is symptom-free. This type of MG occurs when maternal immunoglobulin G AChR antibodies are transferred across the placenta. Affected newborns present with a weak cry and feeding difficulty, which usually resolve spontaneously within a few weeks. MG may present during childhood, especially in individuals of Asian ethnicity; it is rarely seen in Caucasian children.¹ Approximately 10% of patients with MG have a thymoma, and this tumor is implicated in autoantibody production. In ocular MG, symptoms are limited to the periocular muscles.² 

Clinical features are divided into 5 different classes according to disease severity; the features of each class carry a different prognosis and respond differently to therapy (Table 1).²

Table 1. The Myasthenia Gravis Foundation of America Clinical Classification Based on Disease Severity²

Classification	Description
Class I	Any ocular muscle weakness, with all other muscle groups normal.
Class II  IIa IIb	Weakness of muscles other than extraocular muscles (EOMs) with or without EOM weakness. Weakness of the limb or axial muscles. If oropharyngeal muscles are weak, the weakness is less prominent.  Oropharyngeal and respiratory muscle weakness is a predominant symptom. Limb and axial muscles may be involved.
Class III  IIIa IIIb	Moderate weakness of non-EOMs with or without EOM weakness. Involves limb or axial muscles or both, and to a lesser degree oropharyngeal muscles.  Involves predominantly oropharyngeal and respiratory muscles, and to a lesser degree limb or axial muscles.
Class IV IVa IVb	Severe weakness of affected muscles. EOM weakness of any degree of severity may be present.  Involves limb or axial muscles or both, and to a lesser degree oropharyngeal muscles.  Involves predominantly oropharyngeal and respiratory muscles, and to a lesser degree limb or axial muscles.
Class V	Severe enough for the patient to require intubation with or without mechanical ventilation.

References

1. Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. The Lancet. 2001;357(9274):2122-2128. doi:10.1016/S0140-6736(00)05186-2

2. Suresh AB, Asuncion RMD.  Myasthenia gravis. StatPearls [Internet]. Updated August 11, 2021. Accessed February 9, 2022.

Reviewed by Harshi Dhingra, MD, on 2/9/2022.

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Kyle Habet, MD

Kyle Habet, MD, is a physician at Belize International Institute of Neuroscience where he is a member of a multidisciplinary group of healthcare professionals involved in the care of patients with an array of neurological and psychiatric diseases. He is a published author, researcher and instructor of neuroscience and clinical medicine at Washington University of Health and Science.