Seronegative demyelinating disease within the neuromyelitis optica/MOG antibody-associated disease spectrum following nivolumab and ipilimumab: A case report and literature review.

Immune checkpoint inhibitors (ICIs) are increasingly used in the treatment of advanced malignancies and have been associated with a broad spectrum of immune-related adverse events (irAEs). We present the case of a 65-year-old woman who developed a series of neurological complications, including autoimmune encephalitis, myelitis, and optic neuritis, following treatment with nivolumab and ipilimumab for non-small-cell lung cancer. The clinical and radiological findings supported a diagnosis within the seronegative neuromyelitis optica spectrum disorder/myelin oligodendrocyte glycoprotein antibody-associated disease (NMOSD/MOGAD) spectrum. The patient was treated with high-dose corticosteroids followed by intravenous immunoglobulin (IVIG) as first-line therapy and rituximab as maintenance treatment, resulting in sustained clinical and radiological remission over 30 months of follow-up. To our knowledge, this represents one of the few reported cases of a seronegative central nervous system demyelinating disorder associated with ICIs and among the first to demonstrate a favorable response to IVIG in the acute setting. This case highlights the potential for ICIs to trigger or unmask autoimmune demyelinating syndromes, even in antibody-negative patients, and suggests a potential role for IVIG as an alternative to plasma exchange in selected cases.