Contributor: Taylor Lynch, MD

Educational Pearls:

What is NMS?

• Neuroleptic Malignant Syndrome

• Caused by anti-dopamine medication or rapid withdrawal of pro-dopamenergic medications

• Mechanism is poorly understood

• Life threatening

What medications can cause it?

• Typical antipsychotics

• Haloperidol, chlorpromazine, prochlorperazine, fluphenazine, trifluoperazine

• Atypical antipsychotics

• Less risk

• Risperidone, clozapine, quetiapine, olanzapine, aripiprazole, ziprasidone

• Anti-emetic agents with anti dopamine activity

• Metoclopramide, promethazine, haloperidol

• Not ondansetron

• Abrupt withdrawal of levodopa

How does it present?

• Slowly over 1-3 days (unlike serotonin syndrome which has a more acute onset)

• Altered mental status, 82% of patients, typically agitated delirium with confusion

• Peripheral muscle rigidity and decreased reflexes. AKA lead pipe rigidity. (As opposed to clonus and hyperreflexia in serotonin syndrome)

• Hyperthermia (>38C seen in 87% of patients)

• Can also have tachycardia, labile blood pressures, tachypnea, and tremor

How is it diagnosed?

• Clinical diagnosis, focus on the timing of symptoms

• No confirmatory lab test but can see possible elevated CK levels and WBC of 10-40k with a left shift

What else might be on the differential?

• Sepsis

• CNS infections

• Heat stroke

• Agitated delirium

• Status eptilepticus

• Drug induced extrapyramidal symptoms

• Serotonin syndrome

• Malignant hyperthermia

What is the treatment?

• Start with ABC's

• Stop all anti-dopaminergic meds and restart pro-dopamine meds if recently stopped

• Maintain urine output with IV fluids if needed to avoid rhabdomyolysis

• Active or passive cooling if needed

• Benzodiazapines, such as lorazepam 1-2 mg IV q 4hrs

What are active medical therapies?

• Controversial treatments

• Bromocriptine, dopamine agonist

• Dantrolene, classically used for malignant hyperthermia

• Amantadine, increases dopamine release

• Use as a last resort

Dispo?

• Mortality is around 10% if not recognized and treated

• Most patients recover in 2-14 days

• Must wait 2 weeks before restarting any medications

References

• Oruch, R., Pryme, I. F., Engelsen, B. A., & Lund, A. (2017). Neuroleptic malignant syndrome: an easily overlooked neurologic emergency. Neuropsychiatric disease and treatment, 13, 161–175. https://doi.org/10.2147/NDT.S118438

• Tormoehlen, L. M., & Rusyniak, D. E. (2018). Neuroleptic malignant syndrome and serotonin syndrome. Handbook of clinical neurology, 157, 663–675. https://doi.org/10.1016/B978-0-444-64074-1.00039-2

• Velamoor, V. R., Norman, R. M., Caroff, S. N., Mann, S. C., Sullivan, K. A., & Antelo, R. E. (1994). Progression of symptoms in neuroleptic malignant syndrome. The Journal of nervous and mental disease, 182(3), 168–173. https://doi.org/10.1097/00005053-199403000-00007

• Ware, M. R., Feller, D. B., & Hall, K. L. (2018). Neuroleptic Malignant Syndrome: Diagnosis and Management. The primary care companion for CNS disorders, 20(1), 17r02185. https://doi.org/10.4088/PCC.17r02185

Summarized by Jeffrey Olson MS2 | Edited by Meg Joyce & Jorge Chalit, OMSIII