## NMS vs Serotonin Syndrome: The Clonus Distinction ### Why Absence of Clonus Favors NMS **Key Point:** Clonus is a REQUIRED or near-required feature of serotonin syndrome (Hunter Criteria include clonus in 4 of 5 diagnostic branches). Its absence in a patient with severe rigidity and hyperreflexia strongly argues against serotonin syndrome and supports NMS. ### Comparative Neurological Findings | Neurological Sign | Serotonin Syndrome | NMS | |-------------------|-------------------|-----| | **Clonus** | Present (spontaneous or inducible) | Absent or minimal | | **Hyperreflexia** | ✓ Common | ✗ Absent or normal | | **Rigidity type** | Lower limb predominant | Uniform (lead pipe) | | **Tremor** | Fine, rapid | Coarse or absent | | **Babinski sign** | May be present | Usually absent | ### Clinical Context in This Case **High-Yield:** The patient is on an antipsychotic (haloperidol = D2 antagonist), not a serotonergic agent. NMS is the expected diagnosis. The absence of clonus—a hallmark of serotonin syndrome—further confirms NMS. In NMS, dopamine blockade in the basal ganglia produces rigidity without the motor hyperexcitability that generates clonus. ### Mnemonic: SEROTONIN vs NMS **Mnemonic:** **SEROTONIN** = **S**peed (rapid onset), **E**xcitability (hyperreflexia, clonus), **R**igidity (lower limb), **O**cular clonus, **T**remor (fine), **O**nset (hours), **N**ot antipsychotics, **I**ncreased reflexes, **N**o uniform lead-pipe rigidity. **NMS** = **N**eeds antipsychotics, **M**assive CK, **S**low onset (24–72 h), uniform rigidity, NO clonus. ### Clinical Pearl **Clinical Pearl:** In a patient on an antipsychotic with fever, rigidity, and altered mental status, the ABSENCE of clonus is reassuring for NMS (expected) and argues strongly against concurrent serotonin syndrome (which would require clonus). [cite:Harrison 21e Ch 398; American Psychiatric Association DSM-5] 
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