SHUTARO SUMIYOSHI, TAKESHI KUBOTA, HIROYUKI INOUE, Kazuya Takabatake, Keiji Nishibeppu, T Kosuga, H. Konishi, HITOSHI FUJIWARA, Atsushi Shiozaki
Background/Aim: Immune checkpoint inhibitors (ICIs), including nivolumab, have markedly improved gastric cancer (GC) outcomes. However, immune-related adverse events involving the central nervous system are rare and potentially life-threatening. Limbic encephalitis is an exceptionally uncommon manifestation, and its clinical course remains poorly understood. We conducted a literature review of ICI-induced encephalitis specifically in patients with gastrointestinal cancers to clarify its clinical characteristics and management. Case Report: We describe the case of an 83-year-old man with unresectable advanced GC who received multiple lines of chemotherapy, including nivolumab as third-line therapy. After more than 40 cycles of nivolumab treatment, the patient developed progressive cognitive decline. Brain magnetic resonance imaging (MRI) revealed fluid attenuated inversion recovery hyperintensity in the right hippocampus, consistent with limbic encephalitis. Nivolumab was discontinued without corticosteroid administration, leading to gradual cognitive recovery. Follow-up MRI demonstrated resolution of hippocampal abnormalities. Conclusion: This case highlights an exceptionally rare instance of nivolumab-induced limbic encephalitis in a patient with GC. While our patient recovered spontaneously after drug discontinuation without corticosteroids, the key clinical implication is that new-onset cognitive decline in elderly patients receiving ICIs should not be misattributed to dementia progression. Early recognition of neurological immune-related adverse events is essential, as continued ICI therapy in unrecognized cases may result in irreversible or even fatal outcomes.