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
leads to destruction of healthy cells.
In very rare cases, myasthenia gravis can present as a paraneoplastic syndrome, which
means that an underlying cancer like bronchogenic carcinoma or thymic neoplasm (also known as
thymoma) generates an immune response which results in generation of autoantibodies.
In some cases, if certain muscles are affected, myasthenic patients can experience a myasthenic
crisis, which is a life-threatening manifestation of the disease.
An example of this might be a decreased function of the muscles that control breathing.
The good news is is that treatment has been able to reduce mortality from myasthenia gravis.
One type of medication is an acetylcholinesterase inhibitor, like neostigmine or pyridostigmine.
Acetylcholinesterase degrades acetylcholine, so acetylcholinesterase inhibitors stop acetylcholinesterase
from breaking down acetylcholine, which ends up increasing the concentration of acetylcholine
around muscle cells and helps counteract the effects of acetylcholine receptor antibodies.
Myasthenia gravis is also treated with immunosuppressive drugs (like prednisone), which reduce the
production of the harmful antibodies.
Finally, a lot of people with myasthenia gravis undergo surgical removal of the thymus.
This seems to reduce the muscle weakness symptoms even in people that don’t appear to have
any identifiable problems with the thymus gland itself.
It's possible that this is because helper T cells, which originate in the thymus, help
B cells make antibodies to the acetylcholine receptor.
Alright, as a quick review—myasthenia gravis is a type II hypersensitivity disorder where
the body produces antibodies that most commonly target 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.
Myasthenia gravis preferentially affects young women or older men and commonly affects the
extraocular muscles leading to eyelid drooping or double vision, but it might affect any
skeletal muscle.
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