So bored, I tested for lead-pipe rigidity – Is it really Neuroleptic Malignant Syndrome??

After doing your 24th neurological exam on your off-service neurology rotation, and realizing that you’re almost too good at them now and not even using a list anymore to make sure you don’t forget the finger to nose, heel to shin, and rapid alternating movements test, you are given a patient to follow that reminds you of being back in the Emergency Department. You go crazy thanking the neurologists and buy them all donuts and coffee for reminding you of life downstairs.

A 23-year-old male with an unknown psychiatric history is brought in by EMS for altered mental status. On exam, he is febrile to 104 F,  diaphoretic, pale, bradyreflexic, and he has severe, “lead-pipe” rigidity.


What is the differential diagnosis?


Serotonin syndrome, CNS infections, sepsis, drug-induced hyperthermic syndromes, anticholinergic poisoning, sympathomimetic toxicity, malignant hyperthermia, neuroleptic malignant syndrome


What is neuroleptic malignant syndrome (NMS)?

    • NMS is a  complication of antipsychotic drug therapy that usually occurs within the first two weeks of starting the medication, but  can occur at any time, including after dose adjustments
    • It can occur with all the typical antipsychotics like haloperidol or chlorpromazine, and most of the atypical antipsychotics, including aripiprazole, olanzapine, and risperidone

True or False? The antipsychotic serum concentration is usually outside the therapeutic range in setting of NMS?

False. It is usually within the therapeutic range


What is the incidence of NMS?

1 to 2 cases per 10,000 patients who are treated with antipsychotics


What are the clinical manifestations of NMS?

The presentation involves a tetrad of fever, muscular rigidity (“lead-pipe” and “cogwheel rigidity”), autonomic dysfunction, and altered mental status (including lethargy, agitation, mutism, or coma) that develop over a period of 1 to 3 days


What are common laboratory abnormalities associated with NMS?

Elevated CK, leukocytosis, transaminitis, hypernatremia or hyponatremia, metabolic acidosis, myoglobinuria, elevated BUN and Cr, and low iron level


Don’t be fooled!

  • Serotonin Syndrome and NMS commonly present similarly, and in setting of polypharmacy, differentiating them can be very difficult. Both can present with elevated CK and increased tone. It is best to avoid ALL neuroleptics, including haloperidol for agitated patients if there is ANY doubt regarding your diagnosis
    • Serotonin Syndrome usually presents within 24 hours of starting the serotonergic medication; NMS has a variable timeline of presentation
    • Serotonin syndrome may involve myoclonus, hyperreflexia, mydriasis, hyperactive bowel sounds; whereas in NMS, there may be hyporeflexia, normal pupils, normal/decreased bowel sounds

How do you treat NMS?

  • ABCs first!
    • Some patients may need intubation for airway protection. Also consider paralysis and intubation for hyperthermia and rigidity, as paralysis reduces muscle contraction and lowers temperature.
  • Supportive treatment primarily
    • Discontinue all antipsychotics immediately and drugs that can make NMS worse including anticholinergics, antihistamines, or lithium.
    • Reduce the patient’s temperature with external cooling measures.
    • Consider using a benzodiazepine like lorazepam to reduce agitation and sympathetic activity.
  • Reduce muscle rigidity with dantrolene 1-2.5 mg/kg IV loading dose then 1 mg/kg IV q6h or bromocriptine 2.5-5 mg PO BID or TID


What are the potential complications of NMS?

Rhabdomyolysis, renal failure, respiratory failure, DIC, cardiovascular collapse, and death



Dosi R, et al. “Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary.” BMJ Case Rep. 2014 Jun 23;2014.


Kateon, H. “Differentiating serotonin syndrome and neuroleptic malignant syndrome.” Mental Health Clinician: September 2013, Vol. 3, No. 3, pp. 129-133.


Tintinalli, J, et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 8th Edition. 2016.


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PGY2 clinical monster in training/EMIM resident/improviser

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