From the Guidelines
Neuroleptic Malignant Syndrome (NMS) is diagnosed based on a clinical diagnosis, with key criteria including exposure to dopamine antagonist or withdrawal of dopamine agonist, hyperthermia, rigidity, mental status alteration, and creatine kinase elevation, as assigned by a Delphi panel of international NMS experts 1. The diagnostic criteria for NMS are not strictly defined, but rather based on a constellation of symptoms and laboratory findings.
- Key symptoms include:
- Hyperthermia (>100.4°F oral on ≥2 occasions)
- Rigidity
- Mental status alteration
- Creatine kinase elevation (≥4 times upper limit of normal)
- Additional criteria, as assigned by the Delphi panel, include:
- Sympathetic nervous system lability (defined as 2 or more of the following: elevated or fluctuations in blood pressure, diaphoresis, or urinary incontinence)
- Hypermetabolism (defined as a heart rate increase ≥25% above baseline and respiratory rate ≥50% above baseline)
- Negative workup for infectious, toxic, metabolic, or neurologic causes The diagnosis of NMS requires a high index of suspicion in patients taking neuroleptic medications who develop fever and rigidity, and early recognition is crucial as NMS can be life-threatening 1.
- Laboratory findings supporting the diagnosis include:
- Elevated creatine kinase levels
- Leukocytosis
- Metabolic acidosis
- Elevated liver enzymes It is essential to differentiate NMS from other conditions with similar presentations, such as serotonin syndrome, malignant hyperthermia, and central nervous system infections 1.
From the FDA Drug Label
Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure
- Diagnostic criteria for NMS include:
- Hyperpyrexia
- Muscle rigidity
- Altered mental status
- Autonomic instability
- Elevated creatine phosphokinase
- Myoglobinuria
- Acute renal failure The diagnostic evaluation of patients with this syndrome is complicated, and it is essential to identify cases where the clinical presentation includes both serious medical illness and untreated or inadequately treated extrapyramidal signs and symptoms (EPS) 2.
- Key considerations in the differential diagnosis include:
- Central anticholinergic toxicity
- Heat stroke
- Drug fever
- Primary central nervous system pathology Similar diagnostic criteria for NMS are also described for risperidone 3.
From the Research
Diagnostic Criteria for Neuroleptic Malignant Syndrome (NMS)
The diagnostic criteria for NMS include:
- Exposure to dopamine-blocking agent 4
- Severe muscle rigidity 5, 6, 4, 7, 8
- Fever 5, 6, 4, 7, 8
- Altered mental status 5, 6, 4, 7, 8
- Autonomic dysfunction 5, 6, 4, 7, 8
- Elevated serum creatine kinase levels 5, 4, 8
- Diaphoresis 4
- Dysphagia 4
- Mutism 4
- Tremors 4, 8
- Tachycardia 4
- High or labile blood pressure 4
- Leukocytosis 4, 8
Differential Diagnosis
NMS should be considered in the differential diagnosis of any patient receiving a neuroleptic who develops a high fever or severe rigidity 8. Other conditions to be ruled out include: