Objective:

To describe immune checkpoint inhibitor (ICI)-related central nervous system (CNS) demyelination in a patient with metastatic melanoma whose imaging initially suggested multiple sclerosis (MS) or metastatic disease.

Background:

Opdualag (nivolumab, a PD-1 inhibitor, plus relatlimab, a LAG-3 inhibitor) is an emerging dual-checkpoint immunotherapy for melanoma. While effective, ICIs can trigger immune-related adverse events, including rare but serious CNS demyelination that may mimic MS or metastasis radiographically.

Design/Methods:

Single-patient case report with literature review.

Results:

A 49-year-old woman with metastatic melanoma received 13 cycles of Opdualag. During the last infusions, she developed progressive headaches; initial brain MRI was unremarkable. Two months later she presented with blurred vision and diplopia. Exam revealed bilateral optic disc edema. MRI showed innumerable tiny periventricular and diffuse leptomeningeal enhancing foci, initially interpreted as leptomeningeal metastases. Dexamethasone led to clinical improvement. Follow-up MRI one month later revealed new periventricular T2 hyperintensities with an MS-like pattern. CSF analysis demonstrated elevated kappa free light chains (0.1520), total protein 97 mg/dL, and 16 nucleated cells (89% lymphocytes) but no malignant cells or oligoclonal bands. Despite radiographic MS-like lesions, the atypical course, steroid resistance, and CSF profile argued against true MS. Serial MRIs over subsequent months showed resolution of prior lesions and emergence of scattered new white-matter hyperintensities, consistent with ICI-related CNS demyelination.

Conclusions:

Dual immune checkpoint blockade with nivolumab/relatlimab can induce demyelinating CNS injury that radiographically mimics MS or metastatic spread. Awareness of this toxicity is critical to avoid misdiagnosis and to guide management of immune-related neurotoxicity.