Neuroleptic Malignant Syndrome
Pediatric Neuroleptic Malignant Syndrome (NMS)
Neuroleptic malignant syndrome (NMS) is a rare but serious neurological emergency associated with the use of antipsychotic or neuroleptic medications. It is characterized by fever, muscle rigidity, autonomic instability, and altered mental status.
Key Points
- Rare complication, affecting 0.01-0.02% of patients treated with antipsychotics
- Higher incidence in children and adolescents compared to adults
- Mortality rate can be as high as 10-20% if not recognized and treated promptly
- Early recognition and intervention is critical for favorable outcomes
Causes and Risk Factors
Underlying Causes
- Blockade of dopamine D2 receptors in the brain
- Disruption of the thermoregulatory system
- Dysregulation of the sympathetic nervous system
Precipitating Factors
- Initiation or sudden increase in dose of antipsychotic medications
- Abrupt discontinuation of dopamine agonists
- Use of multiple antipsychotics or antidepressants concurrently
- Dehydration, infections, or other physiological stressors
High-Risk Populations
- Children and adolescents with psychiatric or neurological disorders
- Patients with underlying medical conditions (e.g., cardiovascular disease, renal impairment)
- Individuals with a personal or family history of NMS
- Those with genetic predisposition or polymorphisms in dopamine receptor genes
Clinical Presentation
Cardinal Features
- Fever (>38°C or 100.4°F)
- Muscle rigidity (often described as "lead-pipe" rigidity)
- Altered mental status (ranging from agitation to coma)
- Autonomic instability (tachycardia, labile blood pressure, diaphoresis, etc.)
Other Symptoms
- Rhabdomyolysis and elevated creatine kinase (CK) levels
- Leukocytosis with neutrophil predominance
- Acute kidney injury due to myoglobinuria
- Dysarthria, dysphagia, and respiratory distress
- Seizures and other neurological complications
Symptoms typically develop within the first 2 weeks of initiating or increasing the dose of an antipsychotic medication.
Diagnosis
Diagnostic Criteria
- Exposure to a dopamine antagonist (antipsychotic) within the past 72 hours
- Fever (>38°C or 100.4°F)
- Muscle rigidity
- At least two of the following:
- Diaphoresis
- Dysphagia
- Tremor
- Incontinence
- Altered consciousness
- Mutism
- Tachycardia
- Elevated or labile blood pressure
- Elevated creatine kinase (CK) levels
- No other obvious cause of the syndrome
Diagnostic Workup
- Complete blood count with differential
- Comprehensive metabolic panel (including renal and liver function tests)
- Creatine kinase (CK) levels
- Urinalysis and urine toxicology screen
- Electrocardiogram (ECG)
- Brain imaging (CT or MRI) to rule out other neurological causes
Management
Initial Emergency Care
- Immediate discontinuation of the offending antipsychotic medication
- Supportive care:
- Temperature control (cooling blankets, ice packs)
- Hydration and electrolyte management
- Respiratory support as needed
- Pharmacological intervention:
- Dantrolene sodium (muscle relaxant)
- Bromocriptine (dopamine agonist)
- Benzodiazepines for agitation and muscle rigidity
- Intensive monitoring in an ICU setting
Long-Term Management
- Gradual reintroduction of antipsychotics, if necessary, under close supervision
- Psychotherapy and behavioral interventions for underlying psychiatric conditions
- Avoidance of triggers (dehydration, infections, etc.)
- Patient and family education on NMS risk factors and prevention
Prognosis
Mortality and Complications
- Mortality rate can be as high as 10-20% if not recognized and treated promptly
- Complications include:
- Acute renal failure
- Cardiac arrhythmias
- Respiratory failure
- Disseminated intravascular coagulation (DIC)
Factors Affecting Prognosis
- Early recognition and initiation of appropriate treatment
- Severity of presenting symptoms and organ dysfunction
- Underlying medical conditions and comorbidities
- Prompt discontinuation of the offending antipsychotic medication
With prompt and appropriate management, the majority of patients can recover fully without long-term sequelae.
