From the Guidelines
Diagnosing Neuroleptic Malignant Syndrome (NMS) requires a clinical diagnosis based on a combination of symptoms, including exposure to dopamine antagonist or withdrawal of dopamine agonist, hyperthermia, rigidity, mental status alteration, and creatine kinase elevation, as proposed by a Delphi panel of international NMS experts 1. The diagnostic criteria for NMS are not strictly defined, but a recent study suggests that a combination of the following symptoms can guide diagnosis:
- Exposure to dopamine antagonist or withdrawal of dopamine agonist within 3 days
- Hyperthermia (>100.4°F oral on ≥2 occasions)
- Rigidity
- Mental status alteration
- Creatine kinase elevation (≥4 times upper limit of normal)
- 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 These criteria were proposed by a Delphi panel of international NMS experts and can be used to guide diagnosis 1. Some laboratory findings that support the diagnosis of NMS include:
- Elevated creatine kinase
- Leukocytosis
- Elevated liver enzymes
- Electrolyte findings consistent with dehydration It is essential to note that NMS can be life-threatening, with mortality rates of 5-20% if untreated, and early recognition is crucial to improve outcomes 1. The pathophysiology of NMS involves dopamine blockade in the hypothalamus and nigrostriatal pathways, leading to thermoregulatory dysfunction and muscle rigidity. In clinical practice, it is crucial to be aware of the potential for NMS in patients taking antipsychotic medications, particularly high-potency typical antipsychotics like haloperidol, and to monitor for symptoms of NMS, such as fever, rigidity, and altered mental status 1.
From the Research
Diagnostic Criteria for Neuroleptic Malignant Syndrome (NMS)
The diagnostic criteria for NMS include:
- Hyperthermia 2, 3, 4, 5
- Muscular rigidity 2, 3, 4, 5
- Altered consciousness 2, 3, 4
- Autonomic dysfunction 2, 3, 4 Other symptoms that may arouse suspicion of NMS include:
- Unexpected changes in mental status 3
- New-onset catatonia 3
- Episodic tachycardia, tachypnea, hypertension 3
- Dysarthria, dysphagia, diaphoresis, sialorrhea, incontinence 3
- Low-grade temperature elevations 3
- Rigidity 3
- Elevated infectious disease markers and creatine kinase as well as signs of rhabdomyolysis 5
Differential Diagnosis
Differential diagnosis should include:
Importance of Early Diagnosis
Early diagnosis and treatment of NMS are crucial to prevent significant morbidity and death 4. A high degree of suspicion and the discontinuation of antipsychotic agents even if the diagnosis is not established are essential for the safety of the patient 3.