Neuroleptic Malignant Syndrome: Clinical Presentation
Neuroleptic Malignant Syndrome (NMS) is characterized by four hallmark features: hyperthermia, altered mental status, muscle rigidity, and autonomic instability, which can be life-threatening if not promptly recognized and treated. 1
Clinical Presentation
Cardinal Features
Mental status changes: Often the first manifestation (82.3% of cases) 2
- Can range from agitation and delirium to mutism, stupor, and coma
Muscle rigidity: "Lead pipe" rigidity is characteristic
- May present simultaneously with or shortly after mental status changes
- Typically involves all muscle groups
Hyperthermia: Temperature can reach up to 41.1°C
- Usually develops after mental status changes and rigidity
Autonomic instability:
- Tachycardia
- Blood pressure fluctuations (often hypertension)
- Diaphoresis
- Sialorrhea (excessive salivation)
- Cardiac dysrhythmias
- Tachypnea
Additional Neurological Findings
- Tremors
- Involuntary movements
- Positive Babinski sign
- Chorea
- Seizures
- Opisthotonos
- Trismus
- Oculogyric crisis 1
Laboratory Findings
- Elevated creatine kinase (CK): Marker of muscle breakdown
- Leukocytosis
- Electrolyte disturbances
- Elevated liver enzymes
- Metabolic acidosis
- Myoglobinuria 1
Progression of Symptoms
The typical progression of NMS follows this sequence in 70.5% of cases 2:
- Mental status changes
- Muscle rigidity
- Hyperthermia
- Autonomic dysfunction
Risk Factors
Patient Factors
- Young adults
- Male gender (2:1 male-to-female ratio)
- Dehydration
- Physical exhaustion
- Preexisting organic brain disease 1
Medication Factors
- Concomitant use of multiple psychotropic agents
- Use of long-acting depot antipsychotics
- Abrupt discontinuation of dopaminergic agents
- Rapid dose escalation of antipsychotics 1, 3
Differential Diagnosis
NMS must be distinguished from other conditions with similar presentations:
| Condition | Distinguishing Features |
|---|---|
| Serotonin Syndrome | Hyperreflexia, clonus, diarrhea, earlier onset (hours vs. days) |
| Malignant Hyperthermia | Exposure to anesthetics, more rapid onset |
| Lethal Catatonia | May lack history of antipsychotic use |
| CNS Infections | Fever typically precedes other symptoms, CSF abnormalities |
| Heat Stroke | Environmental exposure, lack of rigidity |
| Anticholinergic Toxicity | Dry mucous membranes, mydriasis, urinary retention |
Diagnostic Approach
A point system recommended by international NMS experts includes:
- Exposure to dopamine antagonist or withdrawal of dopamine agonist
- Hyperthermia
- Rigidity
- Mental status alteration
- Creatine kinase elevation
- Sympathetic nervous system lability
- Hypermetabolism
- Negative workup for infectious, toxic, metabolic, or neurologic causes 1
Clinical Course
- Untreated, NMS can progress rapidly and be fatal
- With proper treatment, symptoms typically resolve within 7-10 days for oral antipsychotics 4
- Mortality has decreased from 76% in the 1960s to less than 15% currently 3, 1
Important Considerations
- Atypical presentations can occur, particularly with newer antipsychotics, where rigidity may be less prominent 5
- Regular monitoring of CK levels can aid in early diagnosis in suspected cases
- Patients with a history of NMS are at increased risk for recurrence 1
Early recognition of NMS is crucial as prompt discontinuation of the offending agent and supportive care can significantly reduce morbidity and mortality associated with this potentially life-threatening condition.