Molecularly targeted immunotherapy used to treat a novel overlap syndrome of pediatric

Objective: Overlap syndromes have been described between Methods: We describe a 9-year-old boy with new-onset seizures and worsening encephalopathy. Results: Initial evaluation was concerning for neurosarcoidosis, including elevated cerebrospinal fluid (CSF) and serum angiotensin-converting enzyme and leptomeningeal with multiple cranial nerve enhancement on magnetic resonance imaging. CSF and serum cytokine profiles were used to choose targeted empiric immunotherapy, and the boy's seizure burden and encephalopathy improved after treatment with tocilizumab. The NMDA receptor antibody titer was later found to be elevated, raising suspicion for a novel overlap syndrome. Interpretation: Our patient met the criteria for definite NMDARE and possible neurosarcoidosis. Given the mixed radiographic and serologic markers in this child, cytokine levels were used to direct the choice of empiric treatment, resulting in excellent clinical response. This case suggests that targeted immunotherapy informed by cytokine testing may be helpful in cases of high-acuity pediatric neuroinflammatory disease with limited diagnostic clarity.