Imaging biomarkers in antibody-mediated autoimmune encephalitis

Abstract

Background: Imaging, particularly multimodal magnetic resonance imaging (MRI), serves as an essential auxiliary examination for diagnosing autoimmune encephalitis (AE). The diversity of autoantibodies complicates the imaging presentation of AE, exhibiting both common and individual features across different subtypes of AE. Currently, there is a lack of comprehensive studies on the imaging features of different subtypes of AE. The study aimed to explore imaging biomarkers for AE mediated by various subtypes of antibodies and clarify their significance in disease severity, treatment response, and prognosis.

Methods: The clinical and imaging data of 45 patients with AE at The First Affiliated Hospital of Dalian Medical University, collected from January 2013 to August 2022, were analyzed. Patients underwent multi-modal brain MRI. Lesion probability maps were generated, and regions of interest (ROIs) were selected based on lesion location and clinical-electroencephalographic features, for measurement of three-dimensional T1-weighted imaging (3D-T1WI), T2-weighted imaging (T2WI), T2 fluid-attenuated inversion recovery (T2 FLAIR), and apparent diffusion coefficient (ADC) sequences. These values were used for correlating with disease severity, antibody titers, response to treatment, and prognosis.

Results: The study included 45 AE patients: 18 with anti-leucine-rich glioma inactivated protein 1 (anti-LGI1), 11 with anti-N-methyl-D-aspartate receptor (anti-NMDAR), 5 with anti-gamma-aminobutyric acid receptor B (anti-GABA_BR), 4 with anti-myelin oligodendrocyte glycoprotein (MOG), 4 with anti-glutamate decarboxylase 65 (anti-GAD65), and 3 with anti-contactin-associated protein-like 2 (anti-Caspr2) encephalitis. MRI abnormalities were present in 62.2% of patients, lower than that of electroencephalography (EEG) (95.6%, P<0.05). Imaging typically showed common features across different AE subtypes, predominantly involving the limbic system or regions outside of it, manifesting as T1 hypointensity, T2 FLAIR hyperintensity or mild hyperintensity, and normal or mild hyperintensity on diffusion-weighted imaging (DWI). Different AE subtypes displayed specific imaging features: anti-LGI1 encephalitis often involved 2 locations: unilateral or bilateral hippocampus or basal ganglia; anti-NMDAR encephalitis showed a low rate of imaging abnormalities, with diffuse and unfixed cortical or subcortical T2 FLAIR hyperintensity. Anti-GABA_BR encephalitis primarily affected the temporal lobe or hippocampus. MOG antibody cortical encephalitis exhibited cortical swelling with T2 FLAIR hyperintensity in unilateral or bilateral hemispheres, particularly in the frontal lobe. Anti-GAD65 encephalitis involved the temporal lobe/hippocampus or pontocerebellar regions. The ADC value within the ROI positively correlated with both disease severity (r=0.6891, P<0.0001) and prognosis score (r=0.8102, P<0.0001). Further analysis using receiver operating characteristic (ROC) curve and binary logistic regression indicated that the ADC value was a risk factor for poor prognosis.

Conclusions: Imaging abnormalities are less frequent than those detected by EEG but exhibit distinct features by subtype. Functional imaging enhances diagnostic accuracy. ADC values can serve as a crucial prognostic indicator.

Keywords: Antibody-mediated autoimmune encephalitis (antibody-mediated AE); apparent diffusion coefficient value (ADC value); brain magnetic resonance imaging (brain MRI).

Figure 1

Lesion probability map for all subtypes of antibody-mediated AE (A) and different subtypes of AE (B). AE, autoimmune encephalitis; GABA_BR, gamma-aminobutyric acid receptor B; GAD, glutamate decarboxylase; LGI1, leucine-rich glioma inactivated protein 1; MOG, myelin oligodendrocyte glycoprotein; NMDAR, N-methyl-D-aspartate receptor.

Figure 2

Case 9, a 56-year-old male diagnosed with anti-LGI1 encephalitis, MTLE-like seizure group. (A-D) Brain MRI revealed T2 FLAIR hyperintensity in the left hippocampus 34 days post-onset and prior to immunotherapy. (E-H) Significant improvement in the abnormalities on brain MRI was observed 6 months after immunotherapy. anti-LGI1, anti-leucine-rich glioma inactivated protein 1; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; MTLE, mesial temporal lobe epilepsy.

Figure 3

Case 12, a 63-year-old female diagnosed with anti-LGI1 encephalitis, FBDS group. (A-D) Brain MRI showed high T1/T2 FLAIR signal in the left basal ganglia 19 days post-onset and prior to immunotherapy. (E-H) Significant improvement in the high T1/T2 FLAIR signal of the left basal ganglia was observed on brain MRI 10 days after immunotherapy. anti-LGI1, anti-leucine-rich glioma inactivated protein 1; FBDS, faciobrachial dystonic seizure; MRI, magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery.

Figure 4

Two cases who were diagnosed with anti-NMDAR encephalitis. (A,B) Case 29, a 14-year-old female diagnosed with anti-NMDAR encephalitis. Brain MRI showed T2 FLAIR hyperintensity in the left frontal and insula lobe 1 month after onset and before immunotherapy. (C,D) Case 27, a 47-year-old male diagnosed with anti-NMDAR encephalitis. Brain MRI revealed multiple and patchy T2 FLAIR hyperintensities involving bilateral frontotemporal parietal regions, thalamus and brainstem, 4 months post-onset and prior to immunotherapy. anti-NMDAR, anti-N-methyl-D-aspartate receptor; MRI, magnetic resonance imaging; FLAIR, fluid-attenuated inversion recovery.

Figure 5

Two cases who were diagnosed with anti-GABA_BR encephalitis. (A-D) Case 30, a 64-year-old male diagnosed with anti-GABA_BR encephalitis. Brain MRI revealed left hippocampus swelling and T2 FLAIR hyperintensity in the bilateral hippocampi 21 days post-onset and prior to immunotherapy. (E,F) Case 31, a 46-year-old male diagnosed with anti-GABA_BR encephalitis. ASL scanning showed decreased CBF within the right temporal region 4 years post-onset and before immunotherapy. anti-GABA_BR, anti-gamma-aminobutyric acid receptor B; ASL, arterial spin labeling; CBF, cerebral blood flow; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.

Figure 6

Case 37, a 33-year-old male diagnosed with MOG antibody cortical encephalitis. Twenty-three days post-onset and prior to immunotherapy, brain MRI revealed bilateral frontal lobe and cingulate gyrus cortical swelling and T2 FLAIR hyperintensity (A-D), DWI mild hyperintensity (E), with contrast enhancement on the bilateral frontal pia meninges (F); CBF (G) and CBV (H) showed decreased blood flow in the bilateral frontal lobe and cingulate gyrus (white arrows); MRS (I) showed decreased NAA peak and increased Cho peak. CBF, cerebral blood flow; CBV, cerebral blood volume; Cho, choline-containing compounds; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; MOG, myelin oligodendrocyte glycoprotein; MRS, magnetic resonance spectroscopy; MRI, magnetic resonance imaging; NAA, N-acetyl aspartate.

Figure 7

Two cases who were diagnosed with anti-GAD65 encephalitis. (A-D) Case 40, a 32-year-old female diagnosed with anti-GAD65 encephalitis. Brain MRI exhibited DWI mild hyperintensity and T2 FLAIR hyperintensity involving the left cerebellar hemisphere near the cerebellopontine crus and the right brachium pontine 1 month after onset of disease and before initiation of immunotherapy. (E,F) Case 39, a 52-year-old female diagnosed with anti-GAD65 encephalitis. Brain MRI displayed swelling of bilateral hippocampus with T2 FLAIR hyperintensity 3 months post-onset and before immunotherapy. anti-GAD65, anti-glutamate decarboxylase 65; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging.

Figure 8

Correlation analysis between the ADC value within ROI on brain MRI and clinical outcomes in patients with antibody-mediated AE. (A,B) The ADC value within ROI positively correlated with disease severity (r=0.6891, P<0.0001) (A) and prognosis score (r=0.8102, P<0.0001) (B). (C) ROC curve of the ADC value within ROI and prognosis in patients with antibody-mediated AE. The AUC was 0.836 (P<0.001), which was statistically significant, indicating that the ADC value is a significant predictor of prognosis in antibody-mediated AE. ****, P<0.0001. ADC, apparent diffusion coefficient; AE, autoimmune encephalitis; AUC, area under the curve; MRI, magnetic resonance imaging; ROC, receiver operating characteristic; ROI, region of interest; CI, confidence interval.