Neurological syndrome with CSF anti-Hu positivity during serplulimab therapy in extensive-stage small-cell lung cancer: a case report

Background Immune checkpoint inhibitors (ICIs) have improved outcomes in extensive-stage small-cell lung cancer (ES-SCLC), but neurological immune-related adverse events (n-irAEs) can be severe and disabling. Small-cell lung cancer (SCLC) is also strongly associated with anti-Hu-associated paraneoplastic neurological syndromes (PNSs). Neurological syndromes emerging or worsening after ICI exposure may therefore represent post-ICI PNS, in which paraneoplastic autoimmunity and ICI-related neurotoxicity overlap clinically. Case presentation A 52-year-old woman with stage IV ES-SCLC received four cycles of serplulimab plus etoposide and carboplatin, followed by five cycles of serplulimab maintenance. During maintenance therapy, she developed anorexia, weight loss, and alternating constipation and diarrhea, followed by progressive memory impairment, somnolence, cognitive dysfunction, and gait instability. Cerebrospinal fluid (CSF) examination showed mild mononuclear pleocytosis, and CSF anti-Hu antibody was detected by a cell-based assay at a titer of 1:100; no residual specimen was available for independent confirmatory testing. Brain magnetic resonance imaging (MRI) demonstrated newly developed bilateral paramedian thalamic abnormalities, whereas diffusion-weighted imaging and apparent diffusion coefficient mapping showed no evidence of acute cerebral infarction. The neurological presentation was classified as an intermediate-risk phenotype under the 2021 PNS-Care criteria. If the reported CSF anti-Hu result is accepted, the recalculated PNS-Care score would be 9, corresponding to the definite PNS category, although interpretation is limited by the absence of orthogonal antibody confirmation. Serplulimab was permanently discontinued, and corticosteroids plus intravenous immunoglobulin (IVIG), followed by individualized IVIG maintenance, resulted in substantial but incomplete neurological recovery. MoCA, MMSE, and mRS improved from 11/30, 12/30, and 3 to 24/30, 22/30, and 2, respectively, although residual cognitive impairment persisted. Separately, a complete response was first documented on July 20, 2021, and radiological CR remained confirmed through May 2023, with no subsequently documented clinical tumor progression before death in January 2025. In 2024, intestinal pseudo-obstruction required segmental colectomy, and histopathology demonstrated lymphocytic inflammation surrounding the myenteric plexus. Conclusion This case illustrates the diagnostic overlap between paraneoplastic neurological autoimmunity and ICI-related neurological toxicity in a patient with CSF anti-Hu positivity. The later gastrointestinal episode raised the possibility of enteric nervous system involvement, but its etiology remained uncertain.