Antibody-Negative Nivolumab-Induced Autoimmune Encephalitis: A Case Report and Review of Seronegative Presentations

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but can provoke immune-related neurological complications, including autoimmune encephalitis (AIE). We report a 70-year-old woman who developed AIE after 11 months of adjuvant nivolumab for melanoma. Serial cerebrospinal fluid (CSF) studies revealed a lymphocytic pleocytosis and elevated protein that improved with corticosteroids, intravenous immunoglobulin (IVIG), and rituximab. Magnetic resonance imaging (MRI) showed evolving bilateral thalamic and periventricular T2/FLAIR (fluid-attenuated inversion recovery) hyperintensities. CSF and serum were negative for paraneoplastic and antineuronal antibodies. Altogether, this case illustrates a late-onset, antibody-negative form of ICI-associated AIE. We also provide a focused review of ICI-associated seronegative AIE presentations, including epidemiology, clinical features, diagnostic approach, management, and prognosis. This report underscores the need for sustained vigilance for AIE throughout the course of ICI therapy and highlights serial CSF cell counts as a useful biomarker for diagnostic support and treatment monitoring.