Review Question - QID 216491

This patient who presents with progressive weakness after activity that is worse at the end of the day and ptosis (unable to keep her eyes open) most likely has myasthenia gravis. This disease is caused by the autoimmune destruction of postsynaptic nicotinic acetylcholine receptors.

Myasthenia gravis is an autoimmune disorder that targets the neuromuscular junction. It is predisposed in patients who express the HLA-B8 antigen but is often idiopathic in onset. The key pathophysiological mechanism in this disease is the expression of autoantibodies that bind to proteins on the postsynaptic side of the neuromuscular junction. Most commonly, this is the nicotinic acetylcholine receptor, but the antibodies can also target the muscle-specific receptor tyrosine kinase. Over time, these autoantibodies will result in reduced numbers of these proteins such that an increased level of acetylcholine is required to stimulate muscle contraction.

Rath et al. discuss the clinical features of patients who are resistant to acetylcholinesterase inhibitor treatment. They find that these patients often need plasmapheresis or maintenance immunoglobulins to prevent autoimmune destruction of postsynaptic receptors.

Incorrect Answers:
Answer 1: Demyelination of central nerves is seen in multiple sclerosis, which may also present with difficulty reading due to internuclear ophthalmoplegia causing dysfunction in conjugate gaze; however, this disease usually presents with asymmetric weakness, intention tremor, sensory symptoms, and bladder or bowel incontinence.

Answer 2: Demyelination of peripheral nerves is seen in Guillain-Barre syndrome, which may also present with symmetrical weakness; however, this disease presents with an ascending flaccid paralysis, is often preceded by a viral illness, and does not vary over the course of the day or with physical activity.

Answer 3: Destruction of SNARE protein complexes is seen in botulinum toxin poisoning, which may also present with global weakness that is descending; however, this disease presents acutely after ingestion of the toxin and would not have a waxing and waning pattern over the course of 3 months.

Answer 5: Reduced number of presynaptic calcium channels is seen in Lambert-Eaton syndrome, which may present with similar patterns of weakness as myasthenia gravis; however, the weakness seen in this disease improves with use due to sustained release of synaptic vesicles.

Bullet Summary:
Myasthenia gravis is caused by autoimmune-mediated destruction of post-synaptic nicotinic acetylcholine receptors.