Behavioral Change and Orofacial Dyskinesia in a 12-Year-Old
A 12-year-old girl is admitted with 10 days of behavioral change, insomnia, and odd orofacial movements. She has had two brief generalized seizures and episodes of hypertension and tachycardia. She is afebrile. Cerebrospinal fluid shows 30 white blood cells/µL (80% lymphocytes), protein 60 mg/dL, and normal glucose. Herpes simplex virus PCR is negative. MRI of the brain is normal. EEG shows diffuse slowing without epileptiform discharges. She has been treated empirically with acyclovir for 48 hours. The family asks whether this is psychiatric.
1. What test should be sent next, and how do you decide whether to continue acyclovir and start immunotherapy?
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I would send cerebrospinal fluid for NMDA receptor antibody testing, and serum as well, because CSF is more sensitive but serum can support the diagnosis. The phenotype is highly suggestive: psychiatric symptoms, insomnia, seizures, orofacial dyskinesia, autonomic instability, and CSF pleocytosis with a normal MRI. A normal MRI does not exclude anti-NMDA receptor encephalitis. I would continue acyclovir until herpes PCR is confirmed negative and the clinical picture is clear, because HSV encephalitis can mimic this presentation and is treatable. Once HSV is excluded and the antibody result is pending or positive, I would start first-line immunotherapy with IV methylprednisolone plus IVIG or plasma exchange. Delaying immunotherapy for a pending antibody result can worsen outcome.
2. What screening and treatment steps are required after the antibody result returns positive?
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After confirmation, I would screen for an underlying tumor, especially an ovarian teratoma, because tumor removal improves outcome and reduces relapse. Screening includes pelvic ultrasound or MRI and CT or MRI of the chest, abdomen, and pelvis; occasionally repeat imaging is needed because teratomas can be small. If a tumor is found, I would involve gynecology or surgery for resection. First-line immunotherapy should continue with corticosteroids, IVIG, or plasma exchange. I would monitor for seizures, autonomic instability, central hypoventilation, and catatonia, and use EEG rather than clinical movements alone to guide antiseizure therapy. The family should be told that this is an immune-mediated neurologic disorder, not a primary psychiatric illness, and that recovery is often slow over months.
3. At 4 weeks she has improved but still has choreoathetosis and impulsivity. What is the role of second-line therapy, and what determines it?
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Second-line therapy is considered when there is no meaningful improvement after 4 weeks of first-line immunotherapy or when relapses occur. The options are rituximab or cyclophosphamide, with the choice influenced by severity, infection risk, fertility concerns, and local expertise. In this child, improvement is occurring, so I would not automatically escalate; I would continue first-line treatment and rehabilitation while monitoring for relapse. Choreoathetosis and impulsivity can lag behind seizure and autonomic recovery by months. I would involve neuropsychology, physical and occupational therapy, and school reintegration. If she plateaued or worsened, I would start rituximab rather than continue indefinite steroids. The key judgment is distinguishing slow recovery from treatment failure.