Neurological syndrome with CSF anti-Hu positivity during serplulimab therapy in extensive-stage small-cell lung cancer: a case report
- 1Department of Medical Oncology, China-Japan Union Hospital of Jilin University
- 2Second Ward, Department of Medical Oncology, Xinyang Central Hospital
Abstract
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.
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BibTeX
@article{wang2026neurological,
title = {{Neurological syndrome with CSF anti-Hu positivity during serplulimab therapy in extensive-stage small-cell lung cancer: a case report}},
author = {Linjing Wang and Yanan Zhao and Bo Fan and Shang Sang and Xinying Li and Jia Yu and Yuansong Bai},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1974779},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1974779/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neurological syndrome with CSF anti-Hu positivity during serplulimab therapy in extensive-stage small-cell lung cancer: a case report
AU - Linjing Wang
AU - Yanan Zhao
AU - Bo Fan
AU - Shang Sang
AU - Xinying Li
AU - Jia Yu
AU - Yuansong Bai
PY - 2026
DA - 2026/10/26
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1974779
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1974779/full
AB - 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.
SN - 2234-943X
ER -