Teaching NeuroImage: Neuronal Intranuclear Inclusion Disease Presenting With Both Macular and Higher Visual Dysfunction

A 68-year-old music teacher reported 6 years of progressive bilateral monocular diplopia and nyctalopia.Acuity was 6/18 on the right eye and 6/12 on the left eye; Ishihara 0/15 and 5/15, respectively.Fundus photography and optical coherence tomography showed macular mottling and ellipsoid-zone loss (Figure , A and B).Perimetry showed bilateral centrocecal scotomata (Figure , C). Electroretinography confirmed macular dysfunction.However, disability exceeded retinal findings: She read musical notes only when widely spaced, copied interlocking pentagons separately (Figure , D), and showed visuospatial executive deficits (Figure , E). MRI identified parieto-occipital atrophy and symmetrical U-fiber restricted diffusion (Figure, F), suggesting neuronal intranuclear inclusion disease (NIID).This was confirmed by whole-blood analysis showing a 134 GGC repeat expansion in NOTCH2NLC.NIID can cause retinopathy, 1 explaining her nyctalopia, miosis and macular dystrophy, and disrupt visual association cortex.2 We highlight that NIID often presents with a posterior cortical atrophy (PCA)-like phenotype.While PCA often arises from Alzheimer pathology, low plasma p-tau217 (0.266 pg/mL; <0.400 pg/mL), genetics, and neuroimaging made this less likely.