Visual Pathway Involvement in NMDA Receptor Encephalitis: A Clinical, Optical Coherence Tomography, and 18-Fluorodeoxyglucose PET/CT Approach

Supplemental Digital Content is Available in the Text. Background: Anti-NMDA receptor (NMDAR) encephalitis patients have been reported to exhibit visual dysfunction without retinal thinning. The objective of our study was to examine the involvement of the visual pathway structure and function in anti-NMDAR encephalitis by assessing postrecovery visual function and retinal structure, and acute-phase occipital cortex function. Methods: In this cross-sectional study, patients diagnosed with anti-NMDAR encephalitis per consensus criteria underwent postrecovery visual acuity (VA) testing and optical coherence tomography (OCT) with automated retinal layer segmentation. Clinical data and acute-phase brain 18F-fluorodeoxyglucose (FDG) PET/CT (performed within 90 days of symptom onset, assessed qualitatively and semi-quantitatively) were retrospectively analyzed. VA and OCT measures were compared between anti-NMDAR and age, sex, and race-matched healthy controls (HC). When available, FDG-PET/CT metabolism patterns were analyzed for correlations with VA, and OCT measures. Results: A total of 16 anti-NMDAR (32 eyes) and 32 HC (64 eyes) were included in the study. Anti-NMDAR exhibited lower low-contrast VA (2.5% contrast: −4.4 letters [95% CI; −8.5 to −0.3]; P = 0.04, 1.25% contrast: −6.8 letters [95%CI; −12 to −1.7]; P = 0.01) compared with HC, but no differences were found on OCT-derived retinal layer thicknesses. Acute-phase FDG-PET/CT medial occipital cortex metabolism did not correlate with follow-up low-contrast VA or ganglion cell/inner plexiform layer thickness (GCIPL) (n = 7, 2.5% contrast: r = −0.31; P = 0.50, 1.25% contrast: r = −0.34; P = 0.45, GCIPL: r = −0.04; P = 0.94). Conclusions: Although the visual system seems to be involved in anti-NMDAR encephalitis, no retinal structural or occipital cortex functional abnormalities seem to be responsible for the visual dysfunction. When detected acutely, occipital lobe hypometabolism in anti-NMDAR encephalitis does not seem to associate with subsequent retrograde trans-synaptic degenerative phenomena, potentially reflecting reversible neuronal/synaptic dysfunction in the acute phase of the illness rather than neuronal degeneration.