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 an 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 application of [18F]-DPA714 PET in anti-LGI1 encephalitis. Methods: Patients with anti-LGI1 encephalitis and non-inflammatory controls (NIC) underwent [18F]-DPA714 PET scans were enrolled. Standardized uptake value ratios normalized to the cerebellum (SUVRc) in LGI1-AE patients were calculated for semi-quantitative analysis. The microglial activation marker, soluble triggering receptor expressed on myeloid cells 2 (sTREM2) was measured in cerebrospinal fluid (CSF) to demonstrate its correlation with [18F]-DPA714 PET imaging. Logistic regression analysis was used to identify potential predictors of prognosis. Results: Forty-six patients with anti-LGI1 encephalitis were included in this study. Increased TSPO uptake was identified in the hippocampus, frontal cortex, and caudate nucleus. Montreal Cognitive Assessment (MoCA) score was significantly correlated with SUVRc in the 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 the hippocampus (R2 = 0.18, p = 0.04). SUVRc in the hippocampus significantly decreased after immunotherapy and was associated with improvement of MoCA score (R2 = 0.54, p = 0.023). Increased SUVRc in the frontal cortex and hippocampus was 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: 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.