A 34-year-old man comes to the hospital due to several hours of difficulty swallowing, dry mouth, and blurred vision. The patient has a history of major depression. Examination shows mydriasis and poorly reactive pupils. Electrodiagnostic studies reveal normal nerve conduction velocity but decreased compound muscle action potential (CMAP). Rapid, repetitive nerve stimulation leads to facilitation of CMAP. Further review of this patient's medical history would most likely reveal which of the following?

Question

A 34-year-old man comes to the hospital due to several hours of difficulty swallowing, dry mouth, and blurred vision.  The patient has a history of major depression.  Examination shows mydriasis and poorly reactive pupils.  Electrodiagnostic studies reveal normal nerve conduction velocity but decreased compound muscle action potential (CMAP).  Rapid, repetitive nerve stimulation leads to facilitation of CMAP.  Further review of this patient's medical history would most likely reveal which of the following?

Quizplus · Accepted Answer

The combination of nicotinic (eg, diplopia, dysphagia) and muscarinic blockade (eg, dry mouth) is strongly suggestive of food poisoning with Clostridium botulinum toxin, a highly potent preformed neurotoxin. The toxin inhibits acetylcholine release from presynaptic nerve terminals at the neuromuscular junction (NMJ), thereby preventing muscular contraction. This effect can be seen on electromyography as a decrease in the compound muscle action potential (CMAP, or electrical response of the muscle) following stimulation of a motor nerve. High-rate, repetitive nerve stimulation improves the deficit as the rapid depolarization rate increases calcium concentration in the presynaptic nerve terminal, helping mobilize additional acetylcholine vesicles. The anaerobic environment within canned foods contaminated by C botulinum spores allows for germination and growth of the organism. The toxin (produced by vegetative bacteria) is not actively secreted, remaining intracellular until autolysis causes its release into food. The toxin is readily destroyed by heat; however, if food containing the toxin is not cooked properly, the classic diplopia, dysphagia, and dysphonia ("3 Ds") can develop within 12-36 hours of consumption. (Choice B) Guillain-Barré syndrome can develop following Campylobacter jejuni infection and is characterized by absent reflexes and progressive symmetric weakness, typically starting from the lower extremities (unlike botulism, which commonly causes descending paralysis starting from the cranial nerves). (Choice C) Myasthenia gravis (autoimmune attack against postsynaptic nicotinic receptors) is characterized by episodic diplopia and ptosis. However, muscarinic symptoms (eg, dry mouth, mydriasis) are not characteristic, and CMAP does not improve with rapid, repetitive nerve stimulation. In contrast, Lambert-Eaton syndrome (autoantibodies against presynaptic voltage-gated calcium channels) can present with muscarinic symptoms and improved CMAP with rapid nerve stimulation, but the initial weakness typically involves the proximal extremities (particularly legs). (Choice D) Poisoning due to organophosphates (acetylcholinesterase inhibitors) used in insecticides reflects depolarizing blockade (muscle weakness, fasciculations, paralysis), central nervous system effects (lethargy, seizures), and muscarinic overstimulation (miosis, bradycardia, increased lacrimation and salivation). (Choice E) Tetrodotoxin poisoning (due to contaminated puffer fish ingestion) leads to inhibition of sodium influx into nerve cells. Manifestations include weakness, paresthesias (face, extremities), loss of reflexes, and sometimes severe hypotension. Patients commonly remain conscious, although paralyzed. (Choice F) Anticholinergic toxicity is one of the manifestations of tricyclic antidepressant overdose. However, this produces muscarinic (not nicotinic) blockade with no effect on the NMJ (ie, no alterations in CMAP). Educational objective: Botulinum neurotoxin produced by Clostridium botulinum prevents the release of acetylcholine from presynaptic nerve terminals. The toxin impairs peripheral muscarinic and nicotinic neurotransmission, causing both autonomic symptoms (eg, fixed pupillary dilation, dry mouth) and skeletal muscle weakness (eg, diplopia, dysphagia, respiratory depression). Its effects at the neuromuscular junction can be seen on electromyography as a decrease in muscle response following stimulation of a motor nerve.

A 34-Year-Old Man Comes to the Hospital Due to Several