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Autoimmune-related adverse effects may occur from monoclonal antibody medications though autoimmune encephalopathy is not a commonly reported reaction. Inhibiting the insulin-like growth factor 1 pathway has been shown to cause neurocognitive side effects. We report a case of a man in his early 60s who presented with neuropsychiatric changes after beginning teprotumumab for thyroid eye disease. He was diagnosed with teprotumumab-induced encephalopathy and ultimately treated with plasma exchange.