Microglial activation visualized by 18F-DPA714 PET is a potential marker of severity and prognosis for Anti-LGI1 encephalitis

Title : Microglial activation visualized by 18F-DPA714 PET is a potential marker of severity and prognosis for Anti-LGI1 encephalitis

Abstract:

Background and Purpose: Whether microglial activation plays important role in the pathogenesis of autoimmune encephalitis (AE), such as anti-leucine-rich, glioma-inactivated-1 (LGI1) encephalitis, remains unknown.  ¹⁸F-DPA714 PET targeting the translocator protein (TSPO) is a novel method to detect neuroinflammation via visualizing activated microglia. In this study, we aimed to investigate the roles of ¹⁸F-DPA714 for severity evaluation and prognostic effect in anti-LGI1 encephalitis.

Methods: Patients with anti-LGI1 encephalitis underwent ¹⁸F-DPA714 PET scan from the Autoimmune Encephalitis Molecular Imaging Cohort in Huashan Hospital (HS-ATOMIC) were enrolled. Standardized uptake value ratios normalized to the cerebellum (SUVRc) in LGI1-AE patients were calculated for semi-quantitative analysis. Microglial activation marker, soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was measured in cerebrospinal fluid (CSF) in patients with anti-LGI1 encephalitis as well as in NIC group, and compared with SUVRc for demonstrating its correlation with ¹⁸F-DPA714 PET imaging and cognitive impairment. Logistic regression analysis was used to identify predictors of prognosis.

Results: Forty-six patients with anti-LGI1 encephalitis were included in this study. Increased TSPO uptake was identified in hippocampus, frontal cortex and caudate nucleus. MoCA score was significantly correlated with SUVRc in hippocampus (R²=0.13, P=0.034) and frontal cortex (R²=0.13, P=0.017). Overexpressed sTREM2 in CSF was correlated with SUVRc in hippocampus (R²=0.18, P=0.04). SUVRc in hippocampus significantly decreased after immunotherapy and associated with improvement of MoCA score (R²=0.54, P=0.023). Increased SUVRc in frontal cortex and hippocampus associated with unfavorable disability recovery (odds ratio [OR]=7.1, 95% CI 1.67-29.9, P=0.008) and persistent amnesia (OR=5.4, 95% CI 1.3-22.2, P=0.021) respectively.

Conclusion: LGI1-AE patients have increased TSPO uptake in distinct brain regions, which reflects their cognitive function and can be partially reversed after immunotherapy. Microglial activation visualized by ¹⁸F-DPA714 PET is associated with clinical features and may be used as a potential biomarker for therapeutic and prognostic evaluation.

Audience Take Away Notes:

• Distinct imaging pattern of ¹⁸F-DPA714 PET in anti-LGI1 encephalitis
• Relationship of regional microglial activation and cognitive impairment in LGI1-AE patients
• The follow-up changes of cerebral inflammation after immunotherapy visualized by ¹⁸F-DPA714 PET
• The role of ¹⁸F-DPA714 PET in prognosis of anti-LGI1 encephalitis
• Provide a novel insight to investigate the relationship between innate immunity and autoimmune encephalitis

Biography:

Mr. Jingguo studied Clinical Medicine at the Harbin Medical University and obtained his Master degree in 2021. He is a doctoral candidate under the supervision of Prof. Xiangjun Chen at Fudan University in Shanghai, China, and currently studying as a visiting researcher at Carl-Ludwig institute of Physiology, Leipzig University, Germany. He has published 9 research articles in SCI (E) journals.