Myasthenia Gravis

Today in morning report we heard about a patient with dysarthria, dysphagia and ptosis. The diagnosis was Myasthenia Gravis.

Pathophysiology: 

- antibodies bind to the post-synaptic acetylcholine receptors

- this blocks acetylcholine binding, lead to crosslinking of receptors promoting internalization and degradation. 

- thus the number and availability of receptors are reduced

- thus end-plate potentials are insufficient to generate action potentials in a number of muscle fibers, causing weakness.

Presentation: 

- Up to 65% of patients initially have ocular symptoms of double vision and drooping of the eyelids.Less than 1/4 present with bulbar symptoms (dysarthria, dysphagia, altered voice). 

- Symptoms are typically better in the morning and after rest. 

Most Useful on history and physical:

- To rule in: “speech becoming unintelligible during prolonged speaking” (LR 4.5), peek sign (LR 30- illustrated in the third frame above), but their absence does not rule it out

- To confirm diagnosis or rule it out:  ice test (positive LR 24, negative LR 0.16), sleep test (positive LR 53, negative LR 0.01) or edrophonium (acetylcholinesterase inhibitor) test (positive LR 15, negative LR 0.11)

Confirming the diagnosis:

1. Acetylcholine receptor antibody test: most specific for MG. Sensitivity in generalized MG is 80%-96%,  but up to 50% of patients with purely ocular myasthenia are seronegative.

2. Single-fiber electromyography: highly sensitive for disorders of the neuromuscular junction but is not specific for myasthenia gravis.

Management:

- Rule out associated condition such as thymoma with CT chest and hyperthyrdoidism with TFTs. 

- Work up for other inflammatory conditions (ANA, RF)

- PFTs to assess for respiratory muscle weakness 

- Symptomatic treatment with pyridostigmine

- Indications for thymectomy: all patients with thymoma, some patients without thymoma (if generalised MG and under age 55 as 85% will have an improvement... however benefit takes years)

- Immunosuppression with glucocorticoids, azathioprine and others

- Avoid exacerbating drugs (including magnesium, beta-blockers, quinolones and macrolides)

Myasthenia Crisis:

- Myasthenic crisis is defined as an exacerbation of weakness sufficient to endanger life

- Close monitoring is key: Vital capacity (VC) and/or maximal inspiratory force (MIF) should be measured frequently, as often as every two hours. May need BiPAP or intubation if VC falling.

- Treat infectious triggers

- Immunomodulator: start prednisone or other immunosuppressive. With steroids, consider slow up-titration as high doses of steroids can exacerbate weakness.

-  IVIG 2g/kg over 5 days- improvement expected within a week

- Can also use Plasmapharesis but this is less well studied than IVIG

- Some advocate holding the anticholinesterase medication as "cholinergic crisis" can contribute to weakness

Here is a link to the JAMA article "Does this patient have Myasthenia Gravis?"