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Abstract

Abstract Background Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy generally responds well to corticosteroid therapy, but an extremely small subset of patients is refractory to first-line immunotherapy with high-dose corticosteroids combined with intravenous immunoglobulin (IVIG); the underlying mechanisms remain unclear. We report an EBV-DNA-negative patient with first-line immunotherapy-resistant GFAP astrocytopathy and analyze the pretreatment cerebrospinal fluid (CSF) cytokine profile to explore its possible association with treatment resistance. Case presentation: A 55-year-old male presented with fever, headache, meningeal signs, urinary retention, and long-segment spinal cord lesions. CSF GFAP-IgG was positive (1:32) and CSF EBV-DNA was negative. He received intravenous methylprednisolone 500 mg/d (days 3–5), 250 mg/d (days 6–8), and 125 mg/d (days 9–11) combined with IVIG 0.4 g/kg/d for 5 days as first-line immunotherapy, but showed no meaningful clinical improvement. Pretreatment CSF cytokine analysis revealed markedly elevated IFN-γ (160.73 pg/mL), MIG (68,534.15 pg/mL), IP-10 (54,682.19 pg/mL), IL-6 (319.53 pg/mL), IL-8 (626.08 pg/mL), and IL-10 (18.20 pg/mL), with MIG exceeding IP-10 and IFN-γ markedly higher than IFN-α. At discharge, he required tracheostomy with mechanical ventilation and showed no motor response to painful stimulation. Conclusions The pretreatment CSF Th1/Tc1-polarized profile in this case suggests CD8⁺ cytotoxic T cell-mediated CNS injury that may be relatively resistant to first-line corticosteroids and IVIG. For refractory GFAP astrocytopathy, early escalation to second-line immunotherapy may be considered; this hypothesis requires validation in prospective cohorts.