Is a patient with leukocytosis, elevated CRP, and elevated CK, on neuroleptic medications, at risk for Neuroleptic Malignant Syndrome (NMS)?

Diagnostic Assessment for Possible Neuroleptic Malignant Syndrome

These laboratory values alone are insufficient to diagnose NMS, but they are concerning in a patient on neuroleptic medications and warrant immediate clinical evaluation for fever, muscle rigidity, and altered mental status. 1, 2

Understanding the Laboratory Values

Your laboratory results show:

• WBC 12.36 × 10⁹/L (mild leukocytosis) 2
• CRP 9 mg/L (mildly elevated) 3
• CK 212 IU/L (mildly elevated, reference range typically 39-162 IU/L) 4

These values are suggestive but not diagnostic of NMS. Classic NMS typically presents with much higher CK levels (often >1000 IU/L and can exceed 15,000 IU/L), more pronounced leukocytosis (often >15,000/μL), and marked clinical symptoms. 2, 4, 5

Critical Clinical Features Required for NMS Diagnosis

You must immediately assess for the following clinical signs 1, 2:

• Fever: Temperature >38°C (though NMS can initially present without fever, as delayed fever onset has been documented with risperidone) 4
• Muscle rigidity: "Lead-pipe" rigidity is classic, though atypical presentations with newer antipsychotics may have minimal or absent rigidity 4
• Altered mental status: Confusion, disorientation, mutism, or decreased level of consciousness 2, 4, 5
• Autonomic instability: Tachycardia, labile blood pressure, diaphoresis, tachypnea 2, 5

Important caveat: Atypical antipsychotics like risperidone can cause atypical NMS presentations where fever and rigidity may be delayed or less pronounced. 4 One documented case showed fever not appearing until hospital day 2, with maximum temperature only 38.6°C and CK peaking at 1991 IU/L. 4

Immediate Differential Diagnoses to Exclude

Before confirming NMS, you must rule out infectious causes 1:

1. Infection workup (perform immediately):

   • Blood cultures (obtain before antibiotics) 1
   • Urinalysis and urine culture 1
   • Chest X-ray if any respiratory symptoms 1
   • Stool studies if diarrhea present 1

2. Other causes of elevated CK and inflammatory markers:

   • Rhabdomyolysis from other causes (trauma, seizures, strenuous exercise) 2
   • Sepsis (can present with similar laboratory abnormalities) 1
   • Drug-induced fever (typically resolves 1-3 days after drug discontinuation, average lag time 21 days from drug initiation) 1
   • Inflammatory myopathies (typically present with symmetric proximal weakness and CK >10× upper limit of normal) 1

Management Algorithm

If NMS is suspected based on clinical presentation 1, 2:

1. Discontinue the neuroleptic immediately (do not wait for confirmatory tests) 1, 2, 4

2. Initiate aggressive supportive care 2:

   • Intensive monitoring in appropriate care setting
   • Aggressive hydration (2.5-3 liters/m²/day) 6
   • Cooling measures if febrile
   • Monitor for complications: acute renal failure from rhabdomyolysis, respiratory failure, cardiac arrhythmias 2

3. Specific pharmacologic treatment (if diagnosis confirmed) 2, 4, 5:

   • Bromocriptine (dopamine agonist): 2.5-10 mg three times daily 2, 4, 5
   • Dantrolene (muscle relaxant): 1-2.5 mg/kg IV every 6 hours 2, 4
   • Benzodiazepines (diazepam or lorazepam) for agitation and muscle rigidity 4

4. Do not delay empiric antibiotics if sepsis is suspected - treat infection and NMS concurrently 1

Critical Pitfalls to Avoid

• Do not dismiss NMS based on "normal" or only mildly elevated laboratory values - atypical presentations with newer antipsychotics are well-documented 4
• Do not wait for fever to develop - consider NMS in afebrile patients with diaphoresis, altered consciousness, tremors, tachycardia, leukocytosis, and elevated CK on neuroleptics 4
• Do not assume infection is excluded - perform complete infectious workup as infection can coexist with or mimic NMS 1
• Do not restart neuroleptics too early after an NMS episode - premature reintroduction (within 10 days) has caused recurrent NMS 5

Prognosis and Long-term Considerations

Most patients recover without neurologic sequelae with early recognition and treatment, though mortality can occur without prompt intervention. 2, 7 Brain MRI changes, if present, may be reversible but do not always correlate with neurologic prognosis. 7 Risk factors for NMS include dehydration, parenteral antipsychotics, high-potency agents, and potentially low serum iron. 8