Ver el código de «Neuroleptic malignant syndrome»

==Background==
*Life threatening neurologic emergency associated with the use of neuroleptic agents<ref>Su YP, Chang CK, Hayes RD, Harrison S, Lee W, Broadbent M, et al. Retrospective chart review on exposure to psychotropic medications associated with neuroleptic malignant syndrome. Acta Psychiatr Scand. Nov 15 2013</ref><ref>Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009;23(6):477-92</ref>
**Can occur with single dose, increasing dose, or same dose as usual <ref>Dunkley, E. J. C., Isbister, G. K., Sibbritt, D., Dawson, A. H. and Whyte, I. M. (2003) ‘The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity’, QJM, 96(9), pp. 635–642. doi: 10.1093/qjmed/hcg109</ref>
**Most often seen with "typical" high potency antipsychotics ([[haloperidol]])
***also occurs with newer "atypicals" ([[risperidone]], [[olanzapine]])
***antiemetics ([[metoclopramide]], [[promethazine]]) 
***withdrawal of anti-Parkinson medication
*Develops over 1-3 days
*Majority of deaths occur from complications of muscle rigidity
*Mortality rates up to 5 to 20% <ref>Shalev A. Mortality from neuroleptic malignant syndrome. J Clin Psychiatry. 1989;50(1):18-25.</ref>

==Clinical Features==
[[File:PMC3703349 CRIM.DENTISTRY2013-542130.002.png|thumb|Patient exhibiting NMS symptoms: hyperthermia, significant extrapyramidal symptoms, various autonomic symptoms, and impaired consciousness.]]
*Develops over 1-3 days
*Tetrad of:<ref>Gurrera RJ, Velamoor V, Cernovsky ZZ. A Validation Study of the International Consensus Diagnostic Criteria for Neuroleptic Malignant Syndrome. J Clin Psychopharmacol. Aug 22 2013</ref>
**[[Altered mental status]] - [[agitated delirium]] progressing to stupor/[[coma]]
**Muscle rigidity - generalized, "lead pipe" rigidity
**[[Hyperthermia]] >38C (87%); >40C (40%)
**Autonomic instability - [[tachycardia]], [[hypertension]], diaphoresis

===Complications===
*[[Dehydration]]
*[[Electrolyte imbalance]]
*[[Acute renal failure]] ([[rhabdomyolysis]])
*[[Dysrhythmias ]]
*[[ACS]]
*[[Respiratory failure]]
**Chest wall rigidity, aspiration [[pneumonia]], [[PE]]
*[[DIC]]
*[[Seizure]] ([[hyperthermia]], [[electrolyte derangements]])
*[[Hepatic failure]]
*[[Sepsis]]

==Differential Diagnosis==
*[[Serotonin Syndrome]]
**Serotonin syndrome more likely to have hyperreflexia, myoclonus, ataxia, nausea and vomiting, diarrhea
**Rigidity and hyperthermia, if present, is less severe than in NMS; more commonly presents with clonus and hyperreflexia
*[[Malignant Hyperthermia]]
**Distinguish by clinical setting (use of inhalational anesthetics or sux)
**Hyperthermia, muscle rigidity, and dysautonomia is similar to NMS though more fulminant
*[[Anticholinergic Toxicity]]
**Diaphoresis, rigidity, elevated CK are absent
**Flushing, mydriasis, bladder distension are common
*[[Sympathomimetics]]
**Rigidity is not seen

{{Movement disorder DDX}}
{{AMS and fever DDX}}

==Evaluation==
*Total CK
**Typically >1000
**Correlates with degree of rigidity
*CBC
**[[leukocytosis|WBC >10K]] is typical
*Chemistry
**May show [[hypocalcemia]], [[hypomagnesemia]], [[hyperkalemia]], [[metabolic acidosis]]
*[[Urinalysis]]
**Myoglobinuria (from rhabdo)
*[[LFTs]]
**Transaminitis
*[[head CT|CT]]/[[LP]]
**CSF may have mildly elevated protein

{{Serotonin syndrome vs neuroleptic malignant syndrome}}

==Management==
*The causative agent should be stopped
*Discontinue all dopamine blocking agents
*If precipitant is a dopaminergic therapy (L-dopa or Carbidopa) it can be restarted later at lower doses as an outpatient

===Supportive Care===
*Agitation should be controlled with [[Benzodiazepines]] 
**Lorazepam 2 mg IV q5 min until agitation and muscle rigidity resolves
*[[Fluid resuscitation]]
*Cooling measures
*Intubation and paralysis for severe cases, chest wall rigidity or respiratory failure
**Use NON-DEPOLARIZING paralytic agent

===Directed Medical Therapy<ref>Addonizio G, Susman VL, Roth SD. Neuroleptic malignant syndrome: review and analysis of 115 cases. Biol Psychiatry. Aug 1987;22(8):1004-20 </ref>===
''Controversial with unclear and disputed efficacy''
*[[Dantrolene]] (skeletal muscle relaxant) - Consider only in patients with severe rigidity
**May cause hepatotoxicity in patients with liver disease
**0.25-2mg/kg IV q6-12hr, max dose 10mg/kg/day
*[[Bromocriptine]] (dopamine agonist)
**2.5mg PO q6-8hr, max dose 40mg/day
*[[Amantadine]] (alternative to bromocriptine)
**100mg PO initially; titrate up as needed to max dose 200mg q12hr

===Electroconvulsive Therapy===
*Limited case series suggest that ECT can be effective in NMS refractory to pharmacotherapy<ref>Morcos N et al., Electroconvulsive therapy for neuroleptic malignant syndrome: a case series. J ECT. 2019.</ref>

==Disposition==
*Admit, usually to ICU

==See Also==


==References==
<references/>

[[Category:Psychiatry]]
[[Category:Toxicology]]