Clinical features and brain MRI volumetric changes in anti-mGluR5 encephalitis

Abstract

Background: Anti-metabotropic glutamate receptor 5 (mGluR5) encephalitis is a rare and under-recognized autoimmune encephalitis. This study is conducted to characterize its clinical and neuroimaging features.

Methods: Twenty-nine patients with anti-mGluR5 encephalitis (15 new cases identified in this study and 14 previously reported cases) were included in this study and their clinical features were characterized. Brain MRI volumetric analysis using FreeSurfer software was performed in 9 new patients and compared with 25 healthy controls at both early (≤6 months of onset) and chronic (>1 year of onset) disease stages.

Results: The common clinical manifestations of anti-mGluR5 encephalitis included cognitive deficits (n = 21, 72.4%), behavioral and mood disturbances (n = 20, 69%), seizures (n = 16, 55.2%), and sleep disorder (n = 13, 44.8%). Tumors were observed in 7 patients. Brain MRI T2/FLAIR signal hyperintensities were observed predominantly in mesiotemporal and subcortical regions in 75.9% patients. MRI volumetric analysis demonstrated significant amygdala enlargement in both early and chronic disease stages compared to healthy controls (P < 0.001). Twenty-six patients had complete or partial recovery, one remained stable, one died and one was lost to follow-up.

Conclusion: Our findings demonstrated that cognitive impairment, behavioral disturbance, seizures, and sleep disorder are the prominent clinical manifestations of anti-mGluR5 encephalitis. Most patients showed a good prognosis with full recovery, even in the paraneoplastic disease variants. The amygdala enlargement in the early and chronic disease stages is a distinct MRI feature, which exploratively offer a valuable perspective for the study of the disease processes.

Figure 1

(A) The distributions of patients by age, sex, and the presence or absence of tumors. (B) The outcome at the last follow‐up. (C) Comparison of mRS scores at peak of the disease with that at the last follow‐up in 27 patients with available information.

Figure 2

Neuroimaging features of routine MRI studies in anti‐mGLUR5 encephalitis. (A) T2/FLAIR hyperintensities in the bilateral medial temporal lobes including both amygdala and hippocampus. (B) T2/FLAIR hyperintensities in bilateral insular lobes. (C:) T2/FLAIR hyperintensity in left brachium pontis. (D) Mild enhancement in the right tentorium cerebelli. (E) Small punctuate white matter T2/FLAIR hyperintensity in the right frontal lobe in a 30‐year‐old patient. (F) Global atrophy in T1 sequence in a 46‐year‐old patient.

Figure 3

Schematic outline of MRI volumetric analysis. Nine patients (12 MRI studies) and 25 healthy subjects were included in the analysis. (A) Neuroimage pre‐processing including cortical reconstruction of T1‐MPRAGE images and co‐registration of T2 images. (B) Amygdala segmentation. (C) Schematics depicting the amygdala subnuclei with dark purple representing a statistically significant increase in subnuclei volumes compared with healthy controls (P < 0.001, uncorrected). ABN, accessory‐basal nucleus; AAA, anterior‐amygdaloid area; CAT, cortico‐amygdaloid transition.

Figure 4

Longitudinal MRI volumetric analysis. (A) Amygdala enlargement in early study (MRI group 1) in Patient 4. (B) Decreased amygdala volume in late study (MRI group 2) in Patient 4. (C) Longitudinal analysis of three patients showed a significant decrease in right amygdala volume in MRI 2 compared to MRI 1.