Myasthenia gravis

Last revised by Julius Rozmiarek on 26 Mar 2024

Myasthenia gravis is the most common disease of the neuromuscular junction and presents with weakness worsened by exertion but improving with rest. 

The incidence is estimated at 15-20 per 100,000 1,2. Females are more affected (3:1) under the age of 40 years, but males are more affected by the age of 50 years 2

The classic feature of myasthenia gravis is fatiguable muscle weakness, that is, weakness that is worse with activity and improves with rest 2. This can manifest in a number of ways and may be influenced by the antibody that is positive in the patient:

  • ocular weakness: e.g. ptosis (most common), binocular diplopia, complex ophthalmoplegia

    • this is the most common presenting reason, with the majority proceeding to experience generalized weakness 1

  • facial and bulbar weakness: e.g. fatigable mastication, choking, dysarthria

  • limb and neck weakness

A feared presentation of myasthenia gravis is that of a myasthenic crisis, which may be triggered by intercurrent illness or medications or non-adherence to therapy, which is characterized by respiratory function compromise and severe dysphagia.

Myasthenia gravis is an autoimmune disease. The disease can be associated with multiple antibodies, which include:

  • AChR (postsynaptic acetylcholine receptor) antibody: 85% patients

  • MuSK (muscle-specific kinase) antibody: 5%

  • LRP4 (low-density lipoprotein receptor-related protein 4) antibody: 2%

Other antibodies, to both intra- and extracellular targets, have a poorly defined role in the pathogenesis of the condition and are found in some patients 9:

  • titin (a striated muscle protein) antibody

  • RyR (ryanodine receptor) antibody

The primary role of imaging is to assess the mediastinum for thymic pathology such as thymic hyperplasia or thymoma, which may alter management 14. Otherwise, myasthenia gravis does not have any particular radiographic features, with some studies noting evidence of non-specific muscle atrophy on cross-sectional imaging in affected muscles 15,16.

It is worth noting that the use of iodinated contrast media may worsen myasthenic symptoms and thus, should be used very cautiously especially if the patient is already very unwell with myasthenic weakness 18.

Initial pharmacological treatment is with acetylcholinesterase inhibitors (e.g. pyridostigmine), however, many patients will require immunosuppression as the disease progresses. Immunosuppression options include corticosteroids, oral steroid-sparing agents (e.g. azathioprine, mycophenolate mofetil), and other immunosuppressive agents (e.g. immunoglobulin therapy, rituximab, eculizumab) and techniques (e.g. plasmapheresis) 2,6,17. The choice of which immunosuppressive therapy (or therapies) to use is complex, and depends on many factors including severity of presentation, which antibody is positive, and patient preference 17.

Thymectomy for all patients with a thymoma is usually recommended 2,17. Thymectomy may further be indicated for young patients seropositive for AChR antibodies with thymic hyperplasia 17.

There are a number of medications and other substances which can make myasthenia gravis worse and thus should be avoided or used with caution in affected patients, including (but not limited to) neuromuscular blocking agents used in anesthesia, certain antibiotics (e.g. aminoglycosides, fluoroquinalones, macrolides), beta blockers, botulinum toxin, checkpoint inhibitors, magnesium sulfate, and iodinated contrast media 2,19.

The clinical differential for a myasthenia-like state is quite broad 12:

ADVERTISEMENT: Supporters see fewer/no ads

Updating… Please wait.

 Unable to process the form. Check for errors and try again.

 Thank you for updating your details.