Serostatus-Specific Prognostic Profiles and Phenotype-Dependent Therapeutic Windows in Autoimmune Encephalitis: A Multicenter Cohort Study.
16 affiliations
- 1Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
- 2Department of Neurology, People's Hospital of Hongze District, Huaian, China.
- 3Department of Medical Records, Nanjing Brain Hospital, Nanjing, China.
- 4Department of Neurology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China.
- 5Department of Neurology, Xuzhou Central Hospital, Xuzhou, China.
- 6Department of Neurology, The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
- 7Department of Neurology, Yancheng First People's Hospital, Yancheng, China.
- 8Department of Neurology, The Fourth Affiliated Hospital of Soochow University, Suzhou, China.
- 9Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
- 10Department of Geriatric Medicine, Nanjing Brain Hospital, Nanjing, China.
- 11Department of Neurology, Xuzhou Mining Group General Hospital, Xuzhou, China.
- 12Department of Neurology, Yancheng Third People's Hospital, Yancheng, China.
- 13Department of Neurology, First People's Hospital of Xuzhou, Xuzhou, China.
- 14Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
- 15School of Public Health, Xuzhou Medical University, Xuzhou, China.
- 16Department of Neurology, The First Clinical College, Xuzhou Medical University, Xuzhou, China.
Abstract
Background
While autoimmune encephalitis (AE) outcomes vary, serostatus-specific prognostic determinants and institutional clustering effects remain poorly characterized. We aimed to delineate the distinct prognostic architecture of AE, identifying serostatus-specific risk factors and potential therapeutic windows.Methods
This multicenter, retrospective cohort study (2016-2024) included 498 patients (382 antibody-positive [Ab+], 116 antibody-negative [Ab-]) across 11 tertiary centers. The primary endpoint was 1-year poor functional outcome (mRS > 2). We utilized Least Absolute Shrinkage and Selection Operator (LASSO) regression and generalized linear mixed models (GLMM) to adjust for institutional clustering, alongside phenotype-treatment interaction analyses.Results
Poor outcomes occurred in 12.9% of patients. GLMM analysis demonstrated negligible institutional heterogeneity. Prognostic architectures diverged by serostatus: Ab+ outcomes were dictated by failure to achieve early functional remission (discharge mRS: OR = 3.74; CASE: OR = 1.56; both p < 0.01) and age ≥ 65 years (OR = 5.78, p = 0.040). Conversely, Ab- outcomes were independent of discharge severity metrics, driven by baseline demographic and phenotypic features: age ≥ 65 and atypical presentation. Crucially, clinical phenotype modified the therapeutic response (pinteraction = 0.025). Delayed immunotherapy (≥ 30 days) significantly increased poor outcome risk in atypical presentations (OR = 9.16, p = 0.025) but not in canonical phenotypes. A derived prognostic nomogram yielded excellent discrimination (AUC = 0.909).Discussion
Long-term AE outcomes are dictated by patient-level clinical severity and phenotype, with negligible influence from institutional variations. These findings advocate for a serostatus- and phenotype-stratified management strategy. Crucially, atypical presentations exhibit a highly time-dependent therapeutic window requiring rapid immunotherapy, while elderly patients warrant prioritized intervention to mitigate inherent baseline risks.
Related
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- Case report: When encephalitis is not an infection: two cases of autoimmune GFAP astrocytopathy mimicking infectious encephalitis
BibTeX
@article{tang2026serostatusspecific,
title = {{Serostatus-Specific Prognostic Profiles and Phenotype-Dependent Therapeutic Windows in Autoimmune Encephalitis: A Multicenter Cohort Study.}},
author = {Xiaohong Tang and Jingxian Wang and Kaixin Zhu and Zhen Zhang and Liao Wu and Wei Wang and Chang Li and Qingyun Li and Hao Li and Jinghua Chen and Zhangxu Lian and Bin Liu and Tengfei Liu and Chunmei Wen and Nuan Wang and Sen Qun and Lishun Xiao and Qingwei Lai},
journal = {Annals of clinical and translational neurology},
year = {2026},
month = oct,
doi = {10.1002/acn3.70571},
url = {https://europepmc.org/article/MED/42951877},
note = {CC BY},
}
RIS
TY - JOUR
TI - Serostatus-Specific Prognostic Profiles and Phenotype-Dependent Therapeutic Windows in Autoimmune Encephalitis: A Multicenter Cohort Study.
AU - Xiaohong Tang
AU - Jingxian Wang
AU - Kaixin Zhu
AU - Zhen Zhang
AU - Liao Wu
AU - Wei Wang
AU - Chang Li
AU - Qingyun Li
AU - Hao Li
AU - Jinghua Chen
AU - Zhangxu Lian
AU - Bin Liu
AU - Tengfei Liu
AU - Chunmei Wen
AU - Nuan Wang
AU - Sen Qun
AU - Lishun Xiao
AU - Qingwei Lai
PY - 2026
DA - 2026/10/28
JO - Annals of clinical and translational neurology
DO - 10.1002/acn3.70571
UR - https://europepmc.org/article/MED/42951877
AB - Background While autoimmune encephalitis (AE) outcomes vary, serostatus-specific prognostic determinants and institutional clustering effects remain poorly characterized. We aimed to delineate the distinct prognostic architecture of AE, identifying serostatus-specific risk factors and potential therapeutic windows.Methods This multicenter, retrospective cohort study (2016-2024) included 498 patients (382 antibody-positive [Ab+], 116 antibody-negative [Ab-]) across 11 tertiary centers. The primary endpoint was 1-year poor functional outcome (mRS > 2). We utilized Least Absolute Shrinkage and Selection Operator (LASSO) regression and generalized linear mixed models (GLMM) to adjust for institutional clustering, alongside phenotype-treatment interaction analyses.Results Poor outcomes occurred in 12.9% of patients. GLMM analysis demonstrated negligible institutional heterogeneity. Prognostic architectures diverged by serostatus: Ab+ outcomes were dictated by failure to achieve early functional remission (discharge mRS: OR = 3.74; CASE: OR = 1.56; both p < 0.01) and age ≥ 65 years (OR = 5.78, p = 0.040). Conversely, Ab- outcomes were independent of discharge severity metrics, driven by baseline demographic and phenotypic features: age ≥ 65 and atypical presentation. Crucially, clinical phenotype modified the therapeutic response (pinteraction = 0.025). Delayed immunotherapy (≥ 30 days) significantly increased poor outcome risk in atypical presentations (OR = 9.16, p = 0.025) but not in canonical phenotypes. A derived prognostic nomogram yielded excellent discrimination (AUC = 0.909).Discussion Long-term AE outcomes are dictated by patient-level clinical severity and phenotype, with negligible influence from institutional variations. These findings advocate for a serostatus- and phenotype-stratified management strategy. Crucially, atypical presentations exhibit a highly time-dependent therapeutic window requiring rapid immunotherapy, while elderly patients warrant prioritized intervention to mitigate inherent baseline risks.
SN - 2328-9503
ER -