The discovery of immune checkpoint proteins and the subsequent development of their inhibitors have made significant advances in available treatment options for cancer therapy. Immune checkpoint inhibitors potentiate the host’s own immune response by targeting anti-CTLA-4 and anti-PD-1/PD-L1 antibodies. Ipilimumab was the first antibody directed against cytotoxic T-lymphocyte-associated-antigen 4 (CTLA-4) that was used to activate latent T-cells directed at cancer cells. Nivolumab potentiates the activity of T cells on tumor cells as an antibody against the programed-cell death protein-1. Compared to standard chemotherapy-based treatment, these immune checkpoint inhibitors have provided positive treatment outcomes towards progression free and overall survival. However, these immune checkpoint inhibitors also have a wide spectrum of toxic effects including central and peripheral neurologic complications.
We describe a 36-year-old woman who presented to the Neuro-Onocology clinic with severe short term memory loss after her third dose of Ipilimumab and Nivolumab that was being administered as part of an ongoing clinical trial for her metastatic neuroendocrine disease. She had a Montreal Cognitive Assessment (MoCA) test wherein she had deficits in delayed recall, attention and orientation (score of 22). No focal neurologic deficits on exam. A MRI demonstrated increased FLAIR changes of the right mesial temporal lobe. EEG demonstrated bi-temporal slowing of delta frequency. Lumbar puncture had normal opening pressure with elevated glutamic acid decarboxylase 65 receptor antibodies (1244 nmol/L; reference <0.02 nmol/L). She was given IVIG (1g/kg) for two days with no objective improvement. Two months later she was treated with five cycles of plasma exchange with improvement back to neurologic baseline (MoCA score of 30), repeat anti-GAD65 level of 8.8 nmol/L, normalized EEG and improved MRI findings.