Rapid Review: Myasthenia Gravis

In the Rapid Review series, I briefly review the key points of a clinical review paper.

The topic: Myasthenia gravis

The paper: Spillane J, Higham E, Kullmann DM. Myasthenia gravis. BMJ (Clinical research ed.). 2012; 345:e8497. PMID: 23261848

What is it?

Myasthenia gravis is an autoimmune disorder inhibiting transmission of impulses through the neuromuscular junction. There are a number of targets, but it is typically caused by autoantibodies against the postsynaptic acetylcholine receptor or against muscle specific tyrosine kinase.

What are the symptoms?

Myasthenia gravis is characterized by fatigable muscle weakness. Any muscle group can be involved, but the initial presentation typically involves the ocular muscles, with diplopia and ptosis. Weakness is usually worse at the end of the day, and symptoms can also be exacerbated by other stressors, such as heat, infections, surgery, and menstruation. The symptoms tend to fluctuate with time, which is one reason the diagnosis is often missed initially.

What should I look for on physical exam?

A number of physical exam maneuvers have been described aiming to elicit fatigable muscle weakness. Watch for worsening ptosis with sustained upward gaze or after repetitive blinking. Ask the patient to flex their neck to hold their head off the mattress when lying down. You can also test shoulder abduction before and after repetitive arm movements.

What is the ice test?

In patients with ptosis, if application of ice to the eye for 3 minutes improves the ptosis, that finding indicates myasthenia gravis with a sensitivity and specificity both >90%.

How is it diagnosed?

Blood work can detect antibodies against the acetylcholine receptor or muscle specific tyrosine kinase. The serology is highly specific, but false negatives are as common as 10%. The edrophonium test was classically used, but because of adverse events is rarely recommended anymore. The key in the emergency department is to recognize the symptoms and get a neurologist involved.

How is it managed?

Acetylcholinesterase inhibitors, such as pyridostigmine, are used for symptomatic relief. The mainstay of therapy is immunomodulation. If a thymoma is suspected, thymectomy will be performed.

Anything I should know about managing patient with myasthenia gravis who present with other complaints?

It is important not to abruptly discontinue medications for myasthenia gravis. If the patient is unable to take their medications by mouth, an alternative such as NG tube should be urgently sought.

Patients may require increased doses of their usual medications when sick.

There are a number of medications that are contraindicated in myasthenia gravis. Aminoglycosides, fluoroquinolones, beta-blockers, and magnesium are common medications to avoid. A more in depth list can be found on myasthenia.org. Paralytics deserve special consideration. Depolarizing agents (succinylcholine) are less effective and have an unpredictable effect, so should be avoided. Patients with myasthenia gravis are more sensitive to non-depolarizing paralytics (eg. rocuronium) and a decreased dose is recommended.

What is the most dangerous complication?

Myasthenic crisis occurs in about 20% of patients, and is an emergency requiring ICU admission for respiratory support. In a patient with known myasthenia gravis, red flags of an imminent myasthenic crisis include: rapid worsening of primary symptoms or bulbar weakness, tachypnea, tachycardia, respiratory infection, or a decreased forced vital capacity.

How to I monitor for myasthenic crisis?

It any patient with known myasthenia gravis, clinicians should perform a careful respiratory exam. Pulmonary function testing is generally recommended. If pulmonary function testing is not feasible, one could use the single breath test: ask the patient to take a single breath and then count as high as possible before needing another breath. Getting to 40-50 words is normal. Patients who are unable to count higher than 20 should be considered for ventilatory support.

You can read about the emergency management of myasthenic crisis in this “first 10 minutes” blog post.

Other References

Roper J, Fleming ME, Long B, Koyfman A. Myasthenia Gravis and Crisis: Evaluation and Management in the Emergency Department. The Journal of emergency medicine. 2017; 53(6):843-853. PMID: 28916122