Fatal Steroid-Refractory Autoimmune Encephalitis Following Sequential Immune Checkpoint Inhibitor Therapy in Squamous Non-Small Cell Lung Cancer

Immune checkpoint inhibitors (ICIs) have improved outcomes in advanced non-small cell lung cancer (NSCLC) but can cause severe immune-related adverse events. We report a fatal case of suspected steroid-refractory autoimmune encephalitis in a 71-year-old male with squamous NSCLC, occurring 14 months after sequential ICI therapy (toripalimab, then sintilimab, followed by anlotinib-sintilimab). He presented with acute behavioral decline. Brain MRI revealed non-enhancing T2/FLAIR hyperintensities in the cerebellum and frontal lobes, with low cerebrospinal fluid (CSF) opening pressure. Diagnostic workup was negative for infections and neuronal autoantibodies. Despite aggressive immunosuppression with high-dose corticosteroids, mycophenolate mofetil, and intravenous immunoglobulin, his condition progressed to coma with diffuse cerebral edema and hydrocephalus, leading to death within 14 days. This case highlights the lethal potential of ICI-induced encephalitis, the diagnostic challenges of seronegative presentations, and the urgent need for more effective treatment strategies.