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dopamine blocking agents (e.g., antipsychotic medications). The clinical presentation often comprises a constellation of fever, autonomic instability, leukocytosis, tremor, elevated enzymes, and rigidity. While NMS is a diagnosis of exclusion, laboratory studies to support the diagnosis may show elevated creatine kinase (CPK), myoglobinuria, leukocytosis, and metabolic acidosis. Numerous diagnostic criteria have been proposed, but their clinical utility is debated. Management includes discontinuation of the culprit medication, supportive measures, and, in some cases, pharmacotherapy (e.g, dantrolene, bromocriptine, lorazepam).(NMS) is a rare, life-threatening associated with
NMS is an associated with dopamine blocking agents.
- Causative agents 
Risk factors 
- A genetic predisposition is suspected.
- Possible pharmacological factors include high dosages and/or parenteral administration of causative agents. 
- The underlying mechanism is not well understood. A disruption of numerous neurotransmitter pathways is suspected.
- Central D2 receptor blockade in the nigrostriatal pathway and hypothalamus, resulting in movement disorders and impaired thermoregulation
- Increased sympathetic tone disrupts autonomic regulation and increases muscle tone and metabolism.
- Increased release of calcium from the SR of striated muscle cells, resulting in increased contractility and muscle breakdown
Symptom progression 
- Onset: insidious, within 2–4 weeks of initiation of medication
- Sequence: cognitive changes precede systemic manifestations
- Resolution: gradually, within 7–10 days of stopping the culprit medication
Typical presentation 
- Mental status changes (encephalopathy)
- Hyperthermia: High-grade fever is common. 
- Autonomic instability
- NMS is a diagnosis of exclusion.
- Obtain a focused clinical evaluation including a comprehensive medication history.
- Obtain diagnostic studies to support the diagnosis or identify an alternative cause.
- Consider the use of diagnostic criteria. 
The diagnosis of neuroleptic malignant syndrome is primarily clinical and based on typical signs and symptoms of NMS (e.g., hyperthermia, rigidity, autonomic dysfunction), supportive laboratory findings (e.g., elevated creatine kinase), and the exclusion of differential diagnoses.
Laboratory studies 
- Blood tests
- Urine studies: myoglobinuria
Additional studies 
Obtain as needed to rule out differential diagnoses of NMS.
- Toxic and pharmacological
- Other: heat stroke
The differential diagnoses listed here are not exhaustive.
- Discontinue suspected causative agent (e.g., antipsychotics).
- Initiate supportive measures for all patients.
- Consider admission to ICU for patients with:
- Consult psychiatry or neurology for guidance on pharmacotherapy.
- Consider electroconvulsive therapy for patients refractory to supportive care and pharmacotherapy.
Supportive measures 
- Facilitate heat dissipation.
- Keep the head of bed > 45 degrees to reduce the risk of aspiration. 
- Provide .
Evidence of the benefits of pharmacotherapy is primarily based on small, retrospective studies.
- (off-label) : for severe NMS 
- Dopamine agonists, e.g., bromocriptine (off-label) , amantadine (off-label) , or apomorphine: for moderate or severe NMS 
- Benzodiazepines, e.g., lorazepam (off-label) : can be used to treat mild symptoms of NMS and/or psychomotor agitation 
- Calcium-channel blockers: for hypertension