Pathophysiology
Clinical meaning
The Hunter Serotonin Toxicity Criteria (HSTC) is the most accurate clinical decision tool for diagnosing serotonin syndrome, with 84% sensitivity and 97% specificity. The criteria require exposure to a serotonergic agent PLUS at least one of: (1) spontaneous clonus, (2) inducible clonus PLUS agitation or diaphoresis, (3) ocular clonus PLUS agitation or diaphoresis, (4) tremor PLUS hyperreflexia, or (5) hypertonia PLUS temperature >38ยฐC PLUS ocular clonus or inducible clonus. Clonus is the cardinal distinguishing feature โ it is defined as involuntary rhythmic muscular contractions and relaxations. Lower extremity clonus is more prominent than upper extremity. Ocular clonus presents as slow, continuous, horizontal eye movements. The pathophysiology centers on excessive stimulation of postsynaptic 5-HT1A and 5-HT2A receptors in the brainstem and spinal cord. 5-HT1A activation contributes to altered mental status, autonomic instability, and myoclonus. 5-HT2A activation drives hyperthermia, agitation, and neuromuscular hyperactivity. The severity spectrum ranges from mild (tremor, hyperreflexia) to moderate (clonus, agitation, diaphoresis) to severe (hyperthermia >41.1ยฐC, rigidity, rhabdomyolysis, DIC, multi-organ failure). The NP must distinguish serotonin syndrome from neuroleptic malignant syndrome (NMS): serotonin syndrome develops within HOURS with...