Neuroleptic Malignant Syndrome Workup

Updated: Aug 08, 2022
  • Author: Theodore I Benzer, MD, PhD; Chief Editor: Gil Z Shlamovitz, MD, FACEP  more...
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Approach Considerations

No laboratory test result is diagnostic for neuroleptic malignant syndrome (NMS). However, the following laboratory studies may be indicated, to assess severity and complications or rule out other diagnostic possibilities:

  • Complete blood count (CBC)

  • Blood cultures

  • Liver function tests (LFTs)

  • Blood urea nitrogen (BUN) and creatinine levels

  • Calcium and phosphate levels

  • Creatine kinase (CK) level

  • Serum iron level

  • Urine myoglobin level

  • Arterial blood gas (ABG) levels

  • Coagulation studies

  • Serum and urine toxicologic screening (eg, salicylates, cocaine, amphetamines)

General laboratory features in neuroleptic malignant syndrome include leukocytosis, thrombocytosis, and evidence of dehydration. The serum iron concentration might be decreased. The cerebrospinal fluid (CSF) protein concentration might be elevated. [44]

The rigidity and hyperthermia in neuroleptic malignant syndrome contribute to muscle damage and necrosis, which is reflected in elevated blood levels of the following:

  • CK

  • LFTs (aspartate aminotransferase [AST], alanine aminotransferase [ALT])

  • Lactate dehydrogenase (LDH)

Muscle damage and necrosis can progress quickly to rhabdomyolysis with hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia. Elevated levels of myoglobin can be observed in blood and urine, and may ultimately lead to renal failure.

Assessment of the serum CK level is especially frequently used in psychiatric practice for diagnostic evaluation of rhabdomyolysis in patients with possible neuroleptic malignant syndrome. Other causes of CK elevation may include prescription drugs, alcohol, acute coronary syndrome, and other medical conditions.

Other causes of fever should be investigated, depending on the clinical scenario. This may include urinary tract, respiratory, and central nervous system (CNS) infections. Cultures from various sites may be indicated.

A summary of the laboratory abnormalities that may be found in neuroleptic malignant syndrome includes the following:

  • Increased LDH

  • Increased CK (50-100% of cases)

  • Increased AST and ALT

  • Increased alkaline phosphatase

  • Hyperuricemia

  • Hyperphosphatemia

  • Hyperkalemia

  • Myoglobinemia

  • Leukocytosis (70-98% of cases)

  • Thrombocytosis

  • Proteinuria

  • Decreased serum iron [2]

  • Increased CSF protein

  • Hypocalcemia

  • Myoglobinuria

  • Metabolic acidosis

If thromboembolic phenomenon or disseminated intravascular coagulation (DIC) is suspected, the following coagulation studies may be performed:

  • Platelet count

  • Prothrombin time (PT) and international normalized ratio (INR)

  • Activated partial thromboplastin time (aPTT)

Imaging studies do not yield any diagnostic information for neuroleptic malignant syndrome per se. However, computed tomography (CT) or magnetic resonance imaging of the brain may be performed to rule out other conditions, such as intracranial hemorrhage (ICH), trauma, or structural lesions. Chest radiography is indicated for suspected aspiration pneumonia.

A lumbar puncture (LP) is indicated to rule out meningitis as a cause of fever and altered mental status. No universal agreement exists on the absolute need for a head CT scan before performing an LP in patients without clinical evidence of a structural lesion of the brain; the decision is left to the individual practitioner.