Immune Checkpoint Inhibitor-Related Cerebellar Toxicity: Clinical Features and Comparison with Paraneoplastic...

Area of Science:

• Neuro-oncology
• Immunology
• Neurology

Background:

• Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but can cause immune-related adverse events (irAEs).
• Cerebellar irAEs are not well-defined, and their distinction from paraneoplastic cerebellar ataxia (PCA) is unclear.

Purpose of the Study:

• To characterize cerebellar irAEs.
• To compare cerebellar irAEs with PCA.

Main Methods:

• Multicenter, retrospective cohort study of patients with ICI-induced cerebellar dysfunction.
• Systematic review following PRISMA guidelines.
• Comparison of cerebellar irAE cases with PCA patients.

Main Results:

• 35 patients with cerebellar irAEs were analyzed; 48% had neuronal antibodies, and 83% showed inflammatory cerebrospinal fluid.
• Cerebellar irAEs were associated with male sex, non-small cell lung cancer, and showed a better outcome compared to PCA.
• ICI treatment led to improvement in most patients, though residual disability was common.

Conclusions:

• Cerebellar irAEs are a distinct clinical entity with specific associations and outcomes.
• Differences in tumor association, clinical features, and prognosis exist between cerebellar irAEs and PCA.
• The clinical presentation-antibody-tumor triad in ICI-related cerebellar dysfunction only partially mirrors paraneoplastic disorders.