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Difficulty: HardFormulating a Differential Diagnosis

Campus security brings a 21-year-old female university student to the emergency department due to extreme agitation, paranoia, and auditory hallucinations that began three days ago. Her roommate reports that two weeks prior, the patient experienced a mild febrile illness with a headache and rhinorrhea, which resolved with supportive care. Medical history is significant for generalized anxiety disorder and migraine headaches. Home medications include citalopram and sumatriptan. In the emergency department, she is administered a dose of intramuscular haloperidol for severe agitation. Vital signs show a temperature of 38.4°C (101.1°F), pulse of 126/min, and blood pressure of 148/92 mmHg. Physical examination reveals a diaphoretic, restless patient who intermittently exhibits repetitive lip-smacking and facial grimacing movements. Tone is slightly increased in the upper extremities, and deep tendon reflexes are 3+ bilaterally without sustained clonus. Laboratory studies show a leukocyte count of 11,500/mm³ and an antinuclear antibody (ANA) titer of 1:40. A urine toxicology screen is negative. Which of the following is the most likely diagnosis?

  1. Anti-N-methyl-D-aspartate receptor encephalitisAnswer
  2. B
    Serotonin syndrome
  3. C
    Neuroleptic malignant syndrome
  4. D
    Systemic lupus erythematosus cerebritis
  5. E
    Brief psychotic disorder

Answer

The most likely diagnosis is anti-N-methyl-D-aspartate (NMDA) receptor encephalitis.
The correct diagnosis is anti-NMDA receptor encephalitis. This autoimmune condition frequently affects young women and classically presents with a multi-stage clinical course. It typically begins with a flu-like viral prodrome, followed a few weeks later by severe psychiatric manifestations (agitation, hallucinations, paranoia) that can easily be mistaken for a primary psychotic break. As the disease progresses, autonomic instability (tachycardia, hypertension, diaphoresis, hyperthermia) and distinct neurological symptoms emerge. The most characteristic movement disorders are orofacial dyskinesias, such as repetitive lip-smacking, chewing, and facial grimacing. The patient's presentation perfectly aligns with this progression, making it the most likely diagnosis.

Step-by-Step Solution

1
Analyze the timeline and progression of symptoms.
The patient had a non-specific viral prodrome 2 weeks ago, followed by a rapid onset of severe psychiatric symptoms.
Establishing the sequence of events helps distinguish between primary psychiatric illnesses and medical conditions mimicking psychiatric disease.
2
Evaluate the objective physical examination and vital sign abnormalities.
The patient has autonomic instability (fever, tachycardia, hypertension, diaphoresis) and characteristic neurologic signs (orofacial dyskinesias, hyperreflexia).
These objective findings rule out a primary psychiatric diagnosis like a brief psychotic disorder and point towards an acute organic encephalopathy.
3
Synthesize the findings to formulate a differential diagnosis and identify the most cohesive condition.
The triad of a viral prodrome, acute psychosis, and characteristic movement disorders (lip-smacking/grimacing) in a young woman strongly points to anti-NMDA receptor encephalitis.
While drug-induced syndromes (Serotonin syndrome, NMS) are on the differential due to her medication history and ED treatment, they lack the full spectrum of specific findings seen in this patient.

Key Concept

Formulating a Differential Diagnosis for Acute Encephalopathy and Psychosis
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Topics

Formulating a Differential Diagnosis

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