Myasthenia Gravis

Key Features

Essentials of Diagnosis

• Fluctuating weakness of voluntary muscles, producing symptoms such as

  • Diplopia

  • Ptosis

  • Difficulty in swallowing

• Activity increases weakness of affected muscles

• Short-acting anticholinesterases transiently improve the weakness

General Considerations

• Occurs at all ages, sometimes in association with

  • Thymic tumor

  • Thyrotoxicosis

  • Rheumatoid arthritis

  • Lupus erythematosus

• Onset is usually insidious, but the disorder is sometimes unmasked by a coincidental infection

• Exacerbations may occur before the menstrual period and during or shortly after pregnancy

• Symptoms are due to blocks of neuromuscular transmission caused by autoantibodies binding to acetylcholine receptors

• The external ocular muscles and certain other cranial muscles, including the masticatory, facial, and pharyngeal muscles, are especially likely to be affected

• The respiratory and limb muscles may also be involved

Demographics

• Most common in young women with HLA-DR3

• If thymoma is associated, older men are more commonly affected

Clinical Findings

Symptoms and Signs

• Initial symptoms

  • Ptosis

  • Diplopia

  • Difficulty in chewing or swallowing

  • Respiratory difficulties

  • Limb weakness

  • Some combination of these problems

• Weakness

  • May remain localized to a few muscle groups, especially the ocular muscles

  • May become generalized

• Symptoms often fluctuate in intensity during the day

• This diurnal variation is superimposed on a tendency to longer-term spontaneous relapses and remissions that may last for weeks

• Clinical examination confirms the weakness and fatigability of affected muscles

• Extraocular palsies and ptosis, often asymmetric, are common

• Pupillary responses are normal

• The bulbar and limb muscles are often weak, but the pattern of involvement is variable

• Sustained activity of affected muscles increases the weakness, which improves after a brief rest

• Sensation is normal

• Usually no reflex changes

Differential Diagnosis

• Lambert-Eaton myasthenic syndrome (usually paraneoplastic)

• Botulism

• Aminoglycoside-induced neuromuscular weakness

Diagnosis

Laboratory Tests

• Elevated level of serum acetylcholine receptor antibodies has a sensitivity of 80–90%

• Certain patients have serum antibodies to muscle-specific tyrosine kinase (MuSK), which should be determined

  • These patients are more likely to have facial, respiratory, and proximal muscle weakness than those with antibodies to acetylcholine receptors

• Other associated antibodies

  • Low-density lipoprotein receptor-related protein 4 (LRP4)

  • Agrin

  • Tests for these antibodies are not widely commercially available

Imaging Studies

• CT scan of the chest with and without contrast

  • Should be obtained to demonstrate a coexisting thymoma

  • However, normal studies do not exclude this possibility

Diagnostic Procedures

• Electrophysiology

  • Demonstration of a decrementing muscle response to repetitive 2- or 3-Hz stimulation of motor nerves indicates a disturbance of neuromuscular transmission

  • Such an abnormality may even be detected in clinically strong muscles with certain provocative ...