Clinical characteristics of anti-neuronal antibody positive paraneoplastic neurological syndrome related to immune checkpoint inhibitors

Objective To analyze the clinical characteristics of anti - neuronal antibody positive paraneoplastic neurological syndrome related to immune checkpoint inhibitors (ICI - PNS). Methods and Results A total of 5 patients with anti - neuronal antibody positive ICI - PNS in Peking Union Medical College Hospital from January 2012 to March 2024 were included. Tumor types included small cell lung cancer (2 cases), malignant melanoma (one case), Hodgkin lymphoma (one case) and cervical cancer (one case). Immune checkpoint inhibitors (ICIs) included programmed death 1 (PD - 1) inhibitors (3 cases), programmed cell death ligand 1 (PD-L1) inhibitors (one case) and bispecific PD-1/cytotoxic T lymphocyte- associated antigen 4 (CTLA -4) inhibitors (one case). All 5 patients presented with high -risk neurologic phenotypes of paraneoplastic neurological syndrome (PNS), of which 4 presented with limbic encephalitis and one presented with rapidly progressive cerebellar syndrome. Anti - neuronal antibodies detected in serum and/or cerebrospinal fluid of patients included anti - Hu, γ - aminobutyric acid receptor type B (GABABR), sex-determining region of Y chromosome-related high mobility group box 1 (SOX1), metabotropic glutamate receptor 5 (mGluR5) and Yo antibodies. Neurological syndromes occurred within 2 weeks after receiving ICIs in 4 patients. The modified Rankin Score (mRS) of 4 patients was 3 at peak of illness, and one patient was 5 at peak of illness. The Common Terminology Criteria for Adverse Events (CTCAE) was grade 3 in all 5 patients. After withdrawal of ICIs and treatment with glucocorticoids and intravenous immunoglobulin (IVIg), the neurological symptoms of the patients were improved. Conclusions High/ intermediate - risk anti - neuronal antibodies are diagnostic markers of ICI - PNS. Evaluation of ICI - PNS clinical phenotypes and CTCAE grading are important for immunotherapy. Discontinuation of ICIs, administration of glucocorticoids and IVIg can improve the prognosis of patients.