A 31-year-old woman is brought to the hospital due to respiratory difficulty. She has had trouble performing her daily activities for the past few weeks due to fatigue. In particular, her arms seem to "just drop" when she combs her hair or brushes her teeth. The patient's symptoms are generally better in the morning and worsen throughout the day. She does not use tobacco, alcohol, or illicit drugs. Examination shows diplopia. Chest auscultation shows normal heart and breath sounds. Deep tendon reflexes are normal. Babinski sign is absent. The results of arterial blood gas analysis are as follows:
| pH | 7.32 |
| pCO2 | 60 mm Hg |
| pO2 | 60 mm Hg |
Which of the following is most likely abnormal in this patient?
Show Explanatory Sources
Myasthenia gravis (MG) is an acquired autoimmune disorder characterized by fatigable, fluctuating weakness of the skeletal muscles. The most commonly affected muscles include ocular (diplopia, ptosis), bulbar (dysarthria, fatigable chewing), facial (loss of smile), and proximal (neck/shoulder weakness) muscles. However, respiratory failure (↓ pH, ↑ pCO2, ↓ O2) can also occur due to diaphragmatic weakness (ie, myasthenic crisis), and may be the presenting symptom in some patients.
MG is caused by an autoantibody-mediated, T cell–dependent attack on the acetylcholine receptors (AChRs) of the postsynaptic neuromuscular junction. Antibody-mediated blockade of the active site of AChRs prevents acetylcholine from binding and also triggers endocytosis of AChRs (receptor internalization) as well as complement-mediated membrane damage. Over time, these changes result in reduced numbers of AChRs and impaired neuromuscular transmission.
(Choice A) Botulinum toxin irreversibly blocks acetylcholine release from presynaptic membranes of neuromuscular junctions. After exposure to the toxin, patients may develop cranial nerve abnormalities (including ptosis and facial weakness), symmetric descending weakness, and respiratory failure. However, autonomic abnormalities are common, and symptoms are rapidly progressive (hours rather than weeks) and do not worsen with repetition.
(Choices B and E) The action of acetylcholine at the postsynaptic membrane is terminated by acetylcholinesterase, not by acetylcholine reuptake. Organophosphates (eg, pesticides, sarin gas) irreversibly inactivate acetylcholinesterase, causing cholinergic toxicity (eg, increased glandular secretions, widespread smooth muscle activation). Muscle weakness, including respiratory failure, can occur due to depolarizing blockade at the neuromuscular junction; however, other symptoms (eg, diarrhea, urination, miosis, bradycardia, emesis, salivation) would be expected.
(Choice C) Lambert-Eaton myasthenic syndrome is due to autoantibodies directed against the voltage-gated calcium channels on presynaptic nerve terminals, leading to reduced calcium entry and impaired acetylcholine release. This syndrome commonly occurs in association with malignancy, particularly small cell lung cancer (which would be atypical in this young female), and generally causes proximal extremity weakness that is worse in the mornings and improves with repetition. Autonomic findings (eg, dry mouth, erectile dysfunction in males) are frequently seen and can be an important clue to diagnosis.
Educational objective:
Myasthenia gravis is caused by an autoantibody-mediated attack on the acetylcholine receptors of the postsynaptic neuromuscular junction, leading to a reduced number of acetylcholine receptors. It is characterized by fatigable weakness of the skeletal muscles; respiratory failure can occur due to diaphragmatic weakness.