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

## TL;DR

A cancer patient developed autoimmune encephalitis after long-term treatment with nivolumab, even though antibody tests were negative.

## Contribution

This case highlights a late-onset, antibody-negative form of ICI-associated autoimmune encephalitis.

## Key findings

- The patient showed neurological symptoms and MRI changes consistent with autoimmune encephalitis.
- CSF analysis showed improvement with corticosteroids, IVIG, and rituximab.
- Antibody tests were negative, suggesting seronegative autoimmune encephalitis.

## Abstract

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.