Case report: 10-year follow-up of a patient with neuronal intranuclear inclusion disease and a literature review

Abstract

Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disease with variable clinical manifestations. High signals on diffusion-weighted imaging (DWI) along the corticomedullary junction (CMJ) are a specific feature of NIID. Only a few reports have observed patients for a long period and demonstrated a relationship between magnetic resonance imaging (MRI) features and clinical manifestations. Herein, we present a case of a patient with NIID who underwent a 10-year brain MRI follow-up study and a literature review. A 78-year-old woman presented with severe cognitive dysfunction and disturbances of consciousness. Her brain MRI DWI signal intensity gradually increased over 10 years, and her cognitive function progressively declined. The DWI signal changes were related to the clinical manifestations in this case. In the literature review, we analyzed patients with NIID by classifying them into subgroups and found that high signals on fluid-attenuated inversion recovery (FLAIR) and DWI were related to dementia. Although high DWI signals along the CMJ are specific to NIID, many patients also show high signals on FLAIR in the deep subcortical white matter. In our literature review, dementia could have some correlation to MRI signals. In our case with longitudinal follow up, the DWI high intensity signal expansion could have correlation to cognitive decline. We found dementia and the dementia progression may have some relation to expansion of DWI with intensity signals from the CMJ to the deep subcortical white matter. Our report highlights that DWI signal changes are strongly correlated with the clinical manifestations of NIID.

Keywords: NOTCH2NLC; dementia; magnetic resonance imaging; neurodegenerative disease; neuronal intranuclear inclusion disease.

Figure 1

(A–C) Brain MRI images on DWI are shown. Each image was taken in 2014, 2018, and 2024. (A,B) DWI high-intensity signals were observed along CMJ, and they expanded to deep white matter. (C) DWI high-intensity signals were observed in cerebellar peduncles in 2024. (D–F) Brain MRI images on FLAIR are shown. Each image was taken in 2014, 2018, and 2024. (D,E) FLAIR high-intensity signals were observed in deep white matter in 2014, 2018, and 2024. (F) FLAIR high-intensity signals were observed in paravermis from 2014 to 2024. It was observed in bilateral cerebellar peduncles in 2024. (G) Schematic diagram of the timeline and clinical manifestation of our case. MRI, magnetic resonance imaging; DWI, diffusion-weighted imaging; FLAIR, fluid-attenuated inversion recovery; MoCA-J, Montreal Cognitive Assessment; MMSE, Mini-Mental State Examination.

Figure 2

(A) Electroencephalogram (EEG) of this case is shown. The EEG frequency indicated about 6–7 Hz, theta band oscillation (scale bar represents 1.0 s and 50 μV). (B) Results of the nerve conduction velocity study are shown. Motor nerve conduction velocity in the median, ulnar, and tibial nerves, as well as sensory nerve conduction velocity in the median nerve, ulnar, and sural nerves, are shown. The amplitude was slightly decreased, and the latency was slightly increased, suggesting axonal neuropathies existed. (C) Skin biopsy findings with anti-p62 antibody immunostaining of fibroblasts (scale bar represents 10 μm). (D) Skin biopsy findings with anti-p62 antibody immunostaining of dermal adipocyte (scale bar represents 10 μm). (E) Expansion of the GGC repeat on the NOTCH2NLC gene was detected by florescence amplicon analysis. (F) Control gene sequences of control by florescence amplicon analysis.

Figure 3

(A) Mean size ± standard deviation (SD) of onset age for each clinical manifestation is shown. No statistical differences were detected in the mean size ± SD of onset age along with clinical manifestation by the Kruskal–Wallis test (Total: N = 112, 58.03 ± 13.08; Dementia: N = 21, 56.71 ± 15.67; Movement disorder: N = 23, 51.78 ± 15.50; Autonomic failure: N = 29, 60.10 ± 10.42; Episodic symptom: N = 39, 60.87 ± 10.72). (B) Mean size ± SD of the GGC repeat number for each clinical manifestation is shown. No statistical differences were detected in the mean size ± SD of the GGC repeat number along with clinical manifestation by Kruskal–Wallis test (Total: N = 112, 110.2 ± 32.52; Dementia: N = 21, 106.2 ± 35.83; Movement disorder: N = 23, 119.2 ± 43.33; Autonomic failure: N = 29, 108.8 ± 28.51; Episodic symptom: N = 39, 108.1 ± 25.77). (C) Statistical analysis of the correlation between onset age and repeat number by simple linear regression (Y = 0.01862X + 55.97, R squared = 0.002146, Sy.x = 13.12, p = 0.6277).