CASPR2 antibody-associated neurological syndrome after PD-1 inhibitor treatment (tislelizumab) in a patient with lung adenocarcinoma: A case report and literature review.

Immune checkpoint inhibitors (ICIs) have significantly improved survival in patients with advanced lung cancer. However, they can induce immune-related adverse events (irAEs), including neurological complications such as protein-like 2 (CASPR2) antibody-associated neurological syndromes. This form of autoimmune neuroimmunological disease is associated with antibodies against contactin-associated CASPR2 and typically presents as limbic encephalitis, Morvan's syndrome, or peripheral nerve hyperexcitability. Clinical phenotypes often include cognitive impairment, memory deficits, dysautonomia, and may include cerebellar ataxia as an expanded phenotypic feature. While CASPR2 antibody-associated neurological syndromes presents with typical clinical features, it lacks a single specific manifestation. Furthermore, reported cases secondary to ICI therapy are extremely rare, and its symptoms overlap with those of lung cancer brain metastasis-collectively rendering diagnosis challenging. We report the case of a 46-year-old woman with advanced non-small cell lung cancer (NSCLC) who developed cerebellar syndrome accompanied by cognitive and autonomic symptoms manifesting after one week after the 2nd cycle of tislelizumab (the 4th total cycle of PD-1 inhibitor therapy). Serum testing revealed CASPR2 antibodies at a titer of 1:30 (cell-based assay), while cerebrospinal fluid (CSF) CASPR2 antibodies were negative and brain MRI showed no typical inflammatory changes. The patient's neurological symptoms resolved completely within 1 week after high-dose methylprednisolone and intravenous immunoglobulin treatment, But immune checkpoint inhibitor (ICI) therapy was permanently discontinued, and the patient subsequently died at home. The exact cause of death remains unclear, though it is presumed to be related to disease progression. A systematic literature review conducted upon submission identified only one previously reported peer-reviewed case of ICI-induced CASPR2 encephalitis, which also responded to corticosteroids. To our knowledge, this report describes the second documented case globally and the first associated with tislelizumab exposure. This case underscores that anti-PD-1 therapy can trigger this rare yet serious autoimmune neurological subtype.