We present a case of teprotumumab-induced encephalopathy responsive to plasmapheresis, further supporting the need for early recognition of this potential adverse effect.

Teprotumumab is a monoclonal antibody (mAb) inhibitor of the insulin-like growth factor-1 receptor (IGF-1R) and is indicated for treatment of thyroid eye disease.  Other mAbs have been noted to cause autoimmune adverse effects due to targeted modulation of immune pathways, but there is little reported neurologic involvement with teprotumumab use.

A 61-year-old man presented with memory difficulty, emotional lability, and fatigue for approximately one month following initiation of teprotumumab infusions four months prior. His cognitive difficulties were characterized by poor concentration and short-term recall along with mania.

Diagnostic evaluation included an MRI brain study that was unremarkable for cortical atrophy or acute inflammatory changes.  CSF findings revealed a lymphocytic pleocytosis with total nucleated cells of 17/cmm and protein of 81 mg/dL His thyroid peroxidase antibody was negative. Therefore, with the proximity of his symptoms to the start of teprotumumab, we concluded the most likely explanation was a medication-induced encephalopathy. His mental status improved after starting plasmapheresis for total of five sessions. At follow-up one month after discharge, he has sustained improvement.  

Teprotumumab- induced acute autoimmune encephalopathy is a rare side effect of the novel therapeutic teprotumumab used for thyroid eye disease. Our case is the third described in the literature with improvement after plasmapheresis. Early recognition and prompt treatment of this potential side effect may help mitigate cognitive decline.