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Myasthenia gravis

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High Yield Notes

5 pages

Flashcards

Myasthenia gravis

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Questions

USMLE® Step 1 style questions USMLE

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A 38-year-old man comes to his primary care physician for evaluation of intermittent muscle weakness that began around three months ago. He reports having episodes of “seeing-double” and having difficulty chewing that occur in the evening and resolve the next morning. Past medical history is notable for asthma, for which he intermittently uses an albuterol inhaler. His temperature is 37.6°C (99.7°F), pulse is 65/min and blood pressure is 122/71 mmHg. During the physical examination, the patient is asked to look upwards toward the ceiling for 60 seconds. This maneuver elicits bilateral diplopia. The remainder of the examination is noncontributory. Workup is sent to confirm the diagnosis, and the patient is started on the first-line medication for his condition. Which of the following is a likely side-effect from overdose of this medication?

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Diplopia

myasthenia gravis p. 480

Edrophonium p. 239, 565

myasthenia gravis diagnosis p. 479

Myasthenia gravis p. 480

autoantibody p. 113

diagnosis of p. 239

neostigmine for p. 239

as paraneoplastic syndrome p. 219

pyridostigmine for p. 239

restrictive lung disease p. 694

thymoma association p. 96

type II hypersensitivity p. 110

Ptosis (eyelids)

myasthenia gravis p. 479

Pyridostigmine p. 239

myasthenia gravis treatment p. 480

Thymic hyperplasia

myasthenia gravis association p. 479

Thymomas

myasthenia gravis and p. 219, 479

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Transcript

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Content Reviewers

Rishi Desai, MD, MPH

Myasthenia gravis, is a Latin expression that literally means “grave muscle weakness,” which perfectly describes the weakness that happens when this autoimmune disease affects the skeletal muscles.

People with myasthenia gravis might wake up feeling fine, but get progressively weaker as the day goes on and by the end of the day they might feel very weak, sometimes even getting weaker with repetitive movements like chopping vegetables.

Myasthenia gravis can affect the extraocular muscles, which control movement of the eye as well as the eyelids, so individuals might have diplopia or double vision, as well as ptosis, or drooping eyelids.

Myasthenia gravis preferentially affects young women in their 20s and 30s and older men in their 60s and 70s, but the cause of this odd “bimodal” distribution of age-of-onset isn’t quite clear.

To better understand myasthenia gravis, let’s review normal muscle contraction but at the cellular level.

First you’ve got your motor neurons that release the neurotransmitter acetylcholine at the neuromuscular junction, which then binds to nicotinic acetylcholine receptors on muscle cell membranes.

Binding of acetylcholine to its receptor activates a chain reaction in the muscle cell that ultimately results in muscle contraction.

But what happens in myasthenia gravis though? Well remember that it’s an autoimmune disease, specifically one that’s categorized as a type II hypersensitivity which causes cytotoxic injury meaning that it results in the lysis or death of host cells, which is mediated by autoantibodies, which are antibodies that are specific for our own cells or proteins.

Alright, so in this case, the patient’s B cells inappropriately make antibodies that bind to nicotinic acetylcholine receptors on the muscle cells.

Once acetylcholine receptors are bound by the antibody, they are unable to bind to acetylcholine, and therefore don’t respond to the “contract” signal from the central nervous system.

Anti-acetylcholine receptor antibodies can also activate the classical pathway of the complement.

Summary

Myasthenia gravis is an autoimmune disease, specifically a type II hypersensitivity disorder, which is characterized by autoantibodies against nicotinic acetylcholine receptors on the surface of muscle cells.

The antibodies block the receptors which means the signal to contract isn't received. Those antibodies also activate the complement pathway which leads to muscle cell destruction.

Symptoms can range from mild to severe and may include drooping eyelids, difficulty speaking or swallowing, and muscle weakness in the arms and legs. Treatment involves immunosuppressive drugs like prednisolone, and acetylcholinesterase inhibitors like neostigmine. The purpose is to reduce the immune system's attack on the muscle and to increase muscle strength.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine" McGraw Hill Education/ Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Ephedrine for myasthenia gravis, neonatal myasthenia and the congenital myasthenic syndromes" Cochrane Database of Systematic Reviews (2014)
  6. "The myasthenic patient in crisis: an update of the management in Neurointensive Care Unit" Arquivos de Neuro-Psiquiatria (2013)