Clinical features of antibody-negative autoimmune encephalitis: A meta-analysis and literature review

Authors

  • Weiwei Gao Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Jingjing She Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Lijuan Cai Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Lihong Su Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Yifen Zhang Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Shuixian Li Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Xingyu Chen Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
  • Renjing Zhu Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University

DOI:

https://doi.org/10.54029/2025iwd

Keywords:

Autoimmune encephalitis, antibody-negative, seronegative, clinical features

Abstract

Objective: This study aimed to conduct a comprehensive literature review and meta-analysis of antibody-negative Autoimmune encephalitis (AE) and to quantitatively compare the clinical features of antibody-negative versus antibody-positive AE patients.

Methods: Systematic searches of the PubMed, Embase, Web of Science, and Chinese databases (China National Knowledge Infrastructure, Wanfang, and VIP) were conducted up to December 2023. Relevant articles including references and similar documents from retrieved papers, were further screened. Standardized mean differences (SMD) or odds ratios (OR) with 95% confidence intervals (CI) were calculated using fixed-effect or random-effect models for demographic characteristics, clinical manifestations, magnetic resonance imaging (MRI) and electroencephalogram (EEG) abnormalities, and cerebrospinal fluid (CSF) parameters. Subgroup analyses were performed to identify sources of heterogeneity.

Results: Six studies (one prospective and five retrospective case-control studies) detailing the clinical features of antibody-negative AE were included in the meta-analysis. Compared to patients with antibody-positive AE, those with antibody- negative AE had a significantly older age at onset (SMD = 0.26, 95% CI: 0.04, 0.49; P = 0.02), a lower incidence of concurrent tumors (OR = 0.57, 95% CI: 0.31, 1.07; P = 0.08), and a lower CSF pleocytosis rate (OR = 0.46, 95% CI: 0.27, 0.79; P = 0.01). No significant differences were observed in sex distribution, clinical manifestations, MRI or EEG abnormality rates, or CSF protein concentrations. Furthermore, subgroup analysis demonstrated a lower prevalence of epileptic seizures among Western populations with antibody-negative AE compared to their Asian counterparts (P = 0.03).

Conclusion: This meta-analysis revealed significant differences in age of onset, tumor comorbidity, and CSF pleocytosis rate between patients with antibody-negative and antibody-positive AE, contributing to a more nuanced understanding of antibody-negative AE among clinicians.

Published

2025-04-01

Issue

Vol. 30 No. 1 (2025)

Section

Original Article