Psychiatry · Year 2 · from Psychiatry

Case 2: Neuroleptic Malignant Syndrome

Patient Presentation

Demographics: 28-year-old male

Chief Complaint: "He's not responding and he's burning up."

History of Present Illness: A 28-year-old man with schizophrenia is brought to the emergency department by his group home staff. Over the past 2 days, he has become increasingly confused, less communicative, and has developed rigidity "all over his body." Today, his temperature was 103.5F at the group home, prompting emergent evaluation. Staff reports that 10 days ago, his antipsychotic was changed from risperidone 4 mg twice daily to haloperidol 10 mg twice daily due to insurance issues. Since then, he has been less active and has had difficulty swallowing. He has been eating and drinking less. Yesterday, staff noted he was "sweating a lot" and his clothes were soaked. This morning, he would not get out of bed and was minimally responsive.

Past Psychiatric History:

  • Schizophrenia diagnosed at age 22
  • Multiple hospitalizations for psychotic episodes
  • Previously stable on risperidone for 3 years prior to switch

Medications:

  • Haloperidol 10 mg BID (started 10 days ago)
  • Benztropine 1 mg BID
  • Metformin 1000 mg BID

Physical Examination:

  • Vital signs: T 40.2C (104.4F), BP 168/105 (labile - ranged 90/60 to 180/110), HR 118, RR 24
  • General: Diaphoretic, obtunded, not following commands
  • HEENT: Dry mucous membranes
  • Cardiac: Tachycardic, regular rhythm
  • Pulmonary: Clear, increased work of breathing
  • Neurological:
  • Mental status: Minimally responsive, confused, not oriented
  • Tone: Severe generalized rigidity - "lead-pipe" quality throughout all extremities
  • Reflexes: 1+ throughout, no clonus
  • Pupils: 4 mm, reactive

Mental Status Examination:

  • Unable to complete formal MSE due to altered consciousness
  • Minimally responsive to verbal stimuli
  • No purposeful movements

Workup:

  • CBC: WBC 18,500 (leukocytosis)
  • CMP: BUN 45, Cr 2.1 (AKI), K 5.8, glucose 142
  • CK: 24,000 U/L (markedly elevated - normal <200)
  • Urinalysis: Large blood, no RBCs (myoglobinuria)
  • LFTs: AST 180, ALT 145 (mild elevation)
  • Lactate: 4.2 (elevated - metabolic acidosis)
  • ABG: pH 7.28, pCO2 32, HCO3 18 (metabolic acidosis with respiratory compensation)
  • TSH: Normal
  • CT Head: No acute abnormality
  • LP: Normal (ruled out meningitis)
  • Urine toxicology: Negative
  • ECG: Sinus tachycardia, no arrhythmia

Diagnosis: Neuroleptic Malignant Syndrome (NMS)

Clinical Features Supporting Diagnosis:

  1. Hyperthermia (40.2C)
  2. Severe generalized lead-pipe rigidity
  3. Altered mental status (obtundation, confusion)
  4. Autonomic instability (labile BP, tachycardia, diaphoresis)
  5. Laboratory findings: Elevated CK with rhabdomyolysis, leukocytosis, metabolic acidosis, acute kidney injury
  6. Recent initiation/dose increase of dopamine-blocking agent (switch to high-potency haloperidol)
  7. Risk factors present: High-potency typical antipsychotic, rapid titration, dehydration

Treatment:

  • Immediate: Haloperidol STOPPED immediately
  • ICU admission for close monitoring
  • Supportive care:
  • Aggressive IV hydration (normal saline) - target urine output >1 mL/kg/hr to protect kidneys from myoglobin
  • Active cooling measures: cooling blanket, ice packs to axillae and groin
  • Continuous cardiac monitoring
  • Foley catheter placement
  • Pharmacotherapy:
  • Dantrolene 2 mg/kg IV, then 1 mg/kg q6h (muscle relaxant - decreases rigidity and heat production)
  • Bromocriptine 2.5 mg TID via NG tube (dopamine agonist)
  • Lorazepam 2 mg IV PRN for rigidity
  • Monitoring:
  • Serial CK, renal function, electrolytes
  • Temperature monitoring
  • Mental status checks
  • Hospital course:
  • Day 1: Continued hyperthermia (39.8C), CK peaked at 42,000
  • Day 2: Temperature improved to 38.5C, rigidity decreasing, more responsive
  • Day 3: Oriented to person, CK 18,000, creatinine improving (1.6)
  • Day 5: Fully oriented, rigidity resolved, CK 2,500
  • Day 7: Dantrolene and bromocriptine tapered
  • Day 10: Transferred to psychiatry floor
  • Day 14: Stable, started quetiapine 100 mg BID (low-risk atypical)
  • Discharged to group home with close monitoring

Clinical Pearl: NMS is a life-threatening emergency with a clinical tetrad: hyperthermia (often >40C), lead-pipe rigidity, altered mental status, and autonomic instability. CK is markedly elevated (often >1000, can reach >100,000) reflecting rhabdomyolysis. Higher-potency typical antipsychotics (haloperidol, fluphenazine) carry highest risk, but all antipsychotics can cause NMS. Risk factors include rapid titration, dehydration, and exhaustion. Treatment requires immediate cessation of the offending agent, aggressive supportive care (cooling, hydration), and specific therapy with dantrolene (muscle relaxant) and bromocriptine (dopamine agonist). Key differentiator from serotonin syndrome: NMS has lead-pipe rigidity with normal/decreased reflexes, develops over days-weeks, while serotonin syndrome has clonus/hyperreflexia and develops within hours. Untreated mortality is 10-20%.

Clinical Image

Image Description: Educational diagram illustrating the clinical tetrad of Neuroleptic Malignant Syndrome: (1) Hyperthermia - temperature often exceeding 40C/104F, (2) Lead-pipe muscular rigidity - generalized, distinct from the clonus of serotonin syndrome, (3) Altered mental status - ranging from confusion to coma, (4) Autonomic instability - tachycardia, labile blood pressure, and diaphoresis. Also highlights key laboratory findings (markedly elevated CK, leukocytosis) and treatment approach (stop offending agent, dantrolene, bromocriptine, supportive care).

Attribution: Educational diagram of Neuroleptic Malignant Syndrome clinical features. For clinical teaching purposes.

Image Source: Created for educational purposes illustrating NMS clinical presentation and management.

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