Myasthenia gravis

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Myasthenia gravis

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Myasthenia gravis

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Myasthenia gravis is a type hypersensitivity disorder where autoantibodies target nicotinic acetylcholine receptors.

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A 30-year-old woman comes to the office because of weakness and fatigue for the past 4 months. She also describes double vision and says symptoms worsen at night. Physical examination shows bilateral ptosis and symmetrical weakness of the upper and lower extremities and trouble sustaining contraction. Edrophonium challenge leads to a brief improvement of the symptoms. Which of the following is the most appropriate next step in management?

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Contributors:

Tanner Marshall, MS

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.

The complement system is a family of small proteins that work in an enzymatic cascade to fight off bacterial infections.

The activation of complement causes inflammation and destruction of the muscle cells and reduces the amount of acetylcholine receptors on the surface.

Now a minority of people with myasthenia gravis produce another type of harmful antibody called muscle specific receptor tyrosine kinase antibodies, which attack proteins inside of muscle cells instead of nicotinic acetylcholine receptors on the muscle cell surface, but they similarly lead to destruction of healthy cells.