Clinical Reasoning: A 9-Year-Old Girl With CNS Immune Dysregulation

A 9-year-old girl presented with encephalopathy, left upper extremity rhythmic shaking, and fever, after 1 month of intermittent headaches and 1 week of upper respiratory symptoms. EEG confirmed focal seizures, and brain MRI revealed polyfocal T2/fluid-attenuated inversion recovery hyperintensities involving both the white and gray matter. CSF analysis showed lymphocytic pleocytosis, elevated protein, and elevated opening pressure. She was diagnosed with acute disseminated encephalomyelitis and treated with IV corticosteroids, plasmapheresis, IV immunoglobulins, and antiseizure medications with improvement in encephalopathy and seizures, but persistence of focal deficits. Six weeks after symptom onset, she again became critically ill with encephalopathy and a brain MRI demonstrated worsening of the previous lesions. Paraneoplastic and autoimmune encephalopathy antibody testing was negative, cultures and PCR testing did not identify infection, there was no evidence of rheumatologic conditions, and no malignant cells were found in the spinal fluid. Brain biopsy demonstrated an inflammatory infiltrate, primarily composed of macrophages, T cells, and a few B cells and neutrophils. A CD107a degranulation assay demonstrated a defect in natural and cytotoxic T-cell function, and ultimately, genetic testing revealed the diagnosis. This case highlights the diagnostic challenges faced in cases of CNS immune dysregulation, including differential diagnoses, interpretation of functional assays, and genetic considerations.