MRI Characteristics of Autoimmune Encephalitis With Autoantibodies to GABAA Receptor: A Case Series

Abstract

Background and objectives: To characterize the clinical and neuroimaging phenotypes of patients with autoantibodies to γ-aminobutyric acid type A receptor (GABA_AR).

Methods: Ten patients with autoantibodies against GABA_AR from Huashan Hospital Autoimmune Encephalitis cohort were identified. We used MRI assessments and clinical examinations to summarize major clinical profile and visualize and quantify lesion distribution features. The relationship between clinical features, neuroimaging phenotypes, and topology of GABA_AR expression were further investigated.

Results: The median age at onset of 10 patients (8 male patients and 2 female patients) with anti-GABA_AR encephalitis was 41.5 years (range: 17-73 years). All patients had prominent seizures and multifocal spotted or confluent lesions involved in limbic, frontal, and temporal lobes on brain MRI. Bilateral but asymmetric lesions in cingulate gyri were observed in all patients. These involved lesions could change dynamically with immunotherapies and relapse. Distribution of patients' brain MRI lesions was positively correlated with gene expression level of β3 subunit-containing GABA_AR (Spearman ρ = 0.864, p = 0.001), the main target of autoantibodies. According to topology of lesions, patients with anti-GABA_AR encephalitis could be classified into 2 clinical-radiological types: confluent type with bilateral confluent lesions involved in almost all limbic, frontal, and temporal lobes and spotted type with multiple scattered small-to-medium patchy lesions. Patients with confluent type exhibited worse clinical presentations and outcomes when compared with those with spotted type (maximum modified Rankin scale [mRS]: 5 [5-5] vs 3.5 [3-4], respectively, p = 0.008; follow-up mRS: 4 [2-6] vs 0.5 [0-1], respectively, p = 0.016).

Discussion: Anti-GABA_AR encephalitis has distinctive neuroimaging phenotype. Cingulate gyri were frequently involved in this disorder. The topology of lesions might be associated with the distribution of β3 subunit-containing GABA_AR and reflected patients' disease severity and outcomes.

Figure 1. Characteristics of Brain MRI in Anti-GABA_AR Encephalitis

Note that multiple cortical and subcortical lesions show hyperintense signal on FLAIR imaging (A.a), hypointense signal on T1-weighted imaging without evident mass effect and gadolinium enhancement (A.b, A.c), and no significant restricted diffusion on diffusion-weighted imaging and apparent diffusion coefficient maps (A.d, A.e). Long-term follow-up FLAIR scans in 1 representative patient (patient 1) show confluent lesions predominantly involved bilateral frontal and temporal lobes at the acute stage (B.a, B.b). Some lesions disappeared, but new multifocal lesions emerged 1.5 months later (C.a, C.b). Seven months after onset, most intracranial lesions at acute stage resolved, but signs of cortical atrophy and enlarged lateral ventricles appeared (D.a, D.b). Three years after onset, this patient had stable clinical symptoms without any lesion but dilated lateral ventricles (red circle) and brain atrophy predominantly involved in temporal and frontal lobes (red arrow) (E.a, E.b). Of note, the FLAIR scans at the follow-ups were registered in the native FLAIR space at baseline to ensure that the scans from 4 time points were comparable anatomically with a side-by-side inspection. FLAIR = fluid-attenuated inversion recovery; GABA_AR = γ-aminobutyric acid type A receptor.

Figure 2. Two Types of Representative Lesion Distribution Patterns in Anti-GABA_AR Encephalitis

Type 1: confluent type (A); type 2: spotted type (B). Note that patients with both types had bilateral but asymmetric lesion involvement in cingulate gyri (red arrow). GABA_AR = γ-aminobutyric acid type A receptor.

Figure 3. Lesion Probability Map of Anti-GABA_AR Encephalitis

Note that limbic (especially bilateral anterior cingulate gyri, white arrow), frontal, and temporal lobes were dominantly involved. GABA_AR = γ-aminobutyric acid type A receptor.

Figure 4. Lateral and Medial Views of GABRA1, GABRB3, andGABRR2 Gene Expression Data Projected Onto the FreeSurfer Cortical Regions

Expression level was log2 transformed. Note the high expression of GABAB3 in limbic, frontal, and temporal lobes but a relative low expression in parietal and occipital lobes.