Case Report: immune checkpoint inhibitor-associated aseptic meningitis in lung cancer: two cases illustrating an exclusion-based diagnosis approach and stepwise immunosuppressive treatment.

Background: Immune checkpoint inhibitor (ICI)-associated aseptic meningitis is uncommon neurological immune-related adverse event that can cause substantial morbidity if appropriate immunosuppressive therapy is delayed while excluding infectious meningitis or leptomeningeal carcinomatosis is being evaluated. We report two lung adenocarcinoma cases illustrating an exclusion-based diagnostic process and stepwise immunosuppressive treatment of suspected ICI-associated aseptic meningitis. Case description: Case 1: A 66-year-old woman experienced fever, neck stiffness, and altered mental status 13 days after initiating adjuvant atezolizumab. Cerebrospinal fluid (CSF) analysis showed pleocytosis and marked protein elevation, whereas neuroimaging remained unremarkable. After alternative diagnoses were excluded, high-dose intravenous methylprednisolone was administered, resulting in prompt improvement in consciousness and neurological symptoms, followed by oral corticosteroid tapering without recurrence. Case 2: A 75-year-old man receiving carboplatin/nab-paclitaxel with durvalumab plus tremelimumab experienced ICI-associated colitis followed by Common Terminology Criteria for Adverse Events grade 3 meningitis with impaired consciousness. CSF multiplex polymerase chain reaction, cytological analysis, and further investigations supported early consideration that common infections and leptomeningeal carcinomatosis were unlikely, enabling timely immunosuppression for suspected ICI-associated aseptic meningitis. However, neurological deterioration continued despite high-dose corticosteroids and intravenous immunoglobulin. Consequently, tocilizumab was administered as rescue therapy, following which, both clinical outcomes and CSF parameters improved. Conclusion: These two cases illustrated a practical clinical approach to suspected ICI-associated aseptic meningitis based on rapid exclusion of alternative diagnoses and stepwise immunosuppressive treatment. High-dose corticosteroids remain the cornerstone of initial therapy, whereas additional immunomodulatory treatment might be considered in select refractory cases. CSF multiplex polymerase chain reaction might serve as an adjunctive tool in some patients by helping exclude common treatable infections during early diagnostic evaluation.