Is a patient with fever, tremors, chills, muscle pain, and a history of chest and abdominal pain while on Risperidone (risperidone), with mildly elevated creatine kinase (CK) levels, still at risk for Neuroleptic Malignant Syndrome (NMS)?

Mildly Elevated CK Does NOT Rule Out Neuroleptic Malignant Syndrome

Your patient with fever, tremors, chills, muscle pain on risperidone with CK 152 U/L (mildly elevated) remains at significant risk for NMS and requires immediate clinical evaluation and management based on the complete clinical picture, not CK levels alone. 1, 2

Why CK Levels Can Be Misleading in NMS

NMS is a clinical diagnosis—laboratory values support but do not define it. 1, 3

• While elevated CK (≥4 times upper limit of normal) is common in NMS and worth 10 points in diagnostic scoring systems, over 90% of NMS cases show elevation but some confirmed cases present with normal CK levels 3, 4
• A fatal case of confirmed NMS has been documented with completely normal CK levels measured three times during the syndrome's course 3
• Conversely, risperidone-induced NMS can present with exceptionally high CK levels (>250-fold elevation), demonstrating the wide variability 5
• Your patient's CK of 152 U/L represents mild elevation that could be early NMS, incomplete presentation, or measurement timing issues 3, 6

Clinical Diagnosis Takes Priority Over Laboratory Values

The American Academy of Pediatrics diagnostic point system requires ≥76 points for probable NMS, with clinical features weighted more heavily than CK: 1

• Dopamine antagonist exposure (risperidone) within 3 days: 20 points 1
• Hyperthermia (>100.4°F on ≥2 occasions): 18 points 1
• Rigidity: 17 points 1
• Mental status alteration: 13 points 1
• CK elevation (≥4× normal): 10 points 1
• Autonomic instability: 10 points 1

Your patient already has fever, tremors, and muscle pain on risperidone—this clinical constellation demands immediate action regardless of CK level. 2

Immediate Clinical Assessment Required

Evaluate for the complete NMS tetrad immediately: 7, 2

• Mental status changes: Look for delirium, alert mutism, agitation, stupor, or confusion 1
• Muscle rigidity: Assess for "lead pipe" rigidity (most common), though tremor, akinesia, or dyskinesia may occur instead 1
• Autonomic dysfunction: Check for tachycardia, blood pressure fluctuations, diaphoresis, sialorrhea, dysphagia—these often precede other symptoms 1
• Fever progression: Document temperature trends; hyperthermia can reach >41°C in severe cases 1

Critical Laboratory Workup Beyond CK

Order comprehensive testing to assess severity and rule out alternative diagnoses: 1, 4

• Complete blood count (leukocytosis 15,000-30,000 cells/mm³ expected) 1
• Electrolytes (dehydration pattern common) 1
• Renal function (acute renal failure from rhabdomyolysis) 1
• Liver enzymes (elevation expected) 1
• Arterial blood gases (metabolic acidosis) 1
• Urinalysis (myoglobinuria from muscle breakdown) 2

Immediate Management Protocol

If clinical suspicion for NMS exists, act immediately—do not wait for CK to rise further: 1, 2

1. Discontinue risperidone immediately 1, 2

2. Initiate aggressive supportive care: 1

   • External cooling measures for fever 1
   • IV fluids for dehydration and to prevent renal failure from rhabdomyolysis 1
   • Benzodiazepines for agitation 1
   • Normalize vital signs and monitor autonomic instability 1

3. Monitor for life-threatening complications: 1

   • Rhabdomyolysis progression (repeat CK serially) 1
   • Renal failure 1
   • Seizures 1
   • Disseminated intravascular coagulation 1
   • Respiratory failure 3

4. Consider ICU admission (required in approximately 25% of NMS cases) 1

Critical Pitfalls to Avoid

Waiting for "classic" laboratory findings delays treatment and increases mortality: 3, 6

• The case fatality rate has decreased from 76% to <10-15% specifically because of early recognition and prompt intervention 1
• Atypical or "silent" NMS presentations with only altered mental status and mildly elevated CK have been documented with risperidone 6
• Physical restraints must be avoided as they worsen isometric muscle contractions, hyperthermia, and lactic acidosis 1

The FDA explicitly warns that risperidone can cause NMS with elevated CPK as an additional sign, not a required diagnostic criterion 2