A 69-year-old man with metastatic clear-cell RCC on maintenance pembrolizumab and prior treatment with axitinib, presented with about 18 months of progressive changes in mentation with changes in his personality, hypersexuality, and visual and auditory hallucinations. His symptoms were masked by preserved cognition but at times would have non sequitur responses.

MRI brain showed bifrontal hygromas, and FLAIR changes in pons and periventricular that were nonspecific. EEG with mild diffuse slowing. Serum autoimmune encephalitis panel showed NIF IFA antibody with titer of 1:1920 and cerebrospinal fluid (CSF)autoimmune encephalitis panel ws positive for IgG NIF-IFA at 1:8 titers. His CSF profile showed WBC 1 µl, RBC 1 µl, protein 42 mg/dL, and glucose 49 mg/dL. Pembrolizumab was held.

IV methylprednisolone at 1g daily was initiated for 5 days, resulting in improvement in alertness and reduction in hallucinations.

NIF IFA antibodies can be seen as a paraneoplastic syndrome and have infrequently been described in RCC. To our knowledge, this is the first reported case of paraneoplastic encephalitis associated with clear cell RCC in the setting of pembrolizumab use. Symptoms were subtle and progressive suggesting a high level of suspicion is required to prevent further neurological decline.