There is a paucity of biomarkers predicting clinical outcomes in NMDAR-IgG AE. The role of neuroimaging in NMDAR-IgG AE is incompletely understood.

To characterize quantitative features of brain 18-fluorodeoxyglucose (FDG)-PET at disease onset in N-methyl-D-aspartate receptor-IgG autoimmune encephalitis (NMDAR-IgG AE) and their association with acute and long-term outcomes.

This is an observational cohort study of adult patients with NMDAR-IgG AE (CSF-positive) with early brain FDG-PET (<3 months from onset). Clinical characteristics, including modified Rankin Scale (mRS) and clinical assessment scale in autoimmune encephalitis (CASE), were obtained at baseline (+/-10 days of FDG-PET), and late (>1 year) among a subset of patients. Brain region mean z-scores with a 95% confidence interval (CI) with a lower bound >1 were considered hypermetabolic, and those with an upper bound <-1 were considered hypometabolic. Spearman’s rank correlated FDG-PET measures with clinical outcomes.

Sixteen patients were included (mean age=29 years [interquartile range [IQR]=23-33]; 13 [81%] female). FDG-PET was performed at a median of 5.1 weeks (IQR=3.6-7.1) post-symptom onset. Of 70 brain regions analyzed, 17- predominantly orbitofrontal/temporal- were hypermetabolic; 12- predominantly occipital- were hypometabolic. Hypometabolic regions exhibited the strongest correlation with cross sectional disability and severity, including lingual gyrus (mRS: ρ=-0.78 [95%CI=-0.92,-0.47]; CASE: ρ=-0.77 [95%CI=-0.92,-0.45]) and primary visual cortex (mRS: ρ=-0.71 [95%CI=-0.89,-0.33]; CASE: ρ=-0.81 [95%CI=-0.93,-0.53]). Among 12 patients with follow-up assessments >1 year later, these hypometabolic regions at baseline FDG-PET continued to show strong correlation with late mRS (lingual gyrus: ρ=-0.73 [95%CI=-0.92,-0.27]; primary visual cortex: ρ=-0.89 [95%CI=-0.97,-0.64]), and modest correlation with late CASE (lingual gyrus: ρ=-0.47 [95%CI=-0.82,0.14]; primary visual cortex: ρ=-0.48 [95%CI=-0.83,0.13]).

This study observed frequent orbitofrontal/temporal hypermetabolism and occipital hypometabolism on baseline FDG-PET, characteristic of NMDAR-IgG AE. Specifically, degree of occipital hypometabolism correlated with disability and severity at baseline and follow-up, suggesting a potential role of FDG-PET in predicting outcomes in NMDAR-IgG AE.