A 5-year-old boy presents to the emergency department with a 3-day history of jaw stiffness, difficulty opening his mouth, and a characteristic "sardonic smile." His mother reports he sustained a puncture wound to his foot from a rusty nail 10 days ago. On examination, the structure marked **A** in the diagram is evident. Which of the following best explains the pathophysiological mechanism underlying this clinical sign?

Explanation

## Why option 1 is correct Risus sardonicus (the characteristic "sardonic smile" or fixed grin marked **A**) results from sustained spasm of the facial and masseter muscles in tetanus. The pathophysiology is well-established: Clostridium tetani produces tetanospasmin, a metalloprotease that cleaves synaptobrevin (a SNARE protein) at inhibitory interneurons (particularly Renshaw cells) in the spinal cord. This blockade prevents the release of inhibitory neurotransmitters—GABA and glycine—leading to unopposed (disinhibited) motor neuron firing and characteristic spastic paralysis. This mechanism explains why risus sardonicus appears early in tetanus, often alongside trismus (lockjaw), as the facial muscles are among the first to be affected. (Park 26e Ch 5; Murray 9e) ## Why each distractor is wrong - **Option 2**: While tetanospasmin does affect spinal cord neurons, it does not directly depolarize motor neurons. Rather, it acts presynaptically at inhibitory synapses to block neurotransmitter release. Direct depolarization is not the mechanism. - **Option 3**: Tetanospasmin does not inhibit acetylcholine release; this describes the mechanism of botulinum toxin (another clostridial toxin). Tetanus is a disease of unopposed excitation, not neuromuscular blockade. - **Option 4**: Tetanospasmin does not bind to nicotinic receptors on muscle. The primary site of action is the spinal cord inhibitory interneurons, not the neuromuscular junction or muscle membrane. **High-Yield:** Tetanus = loss of inhibition (blocked GABA/glycine) → spastic paralysis; Botulism = loss of acetylcholine → flaccid paralysis. Risus sardonicus is pathognomonic for tetanus and reflects facial muscle rigidity from disinhibited motor neurons. [cite: Park 26e Ch 5; Murray 9e]