The clinical and neuropathological picture of adult neuronal intranuclear inclusion disease with no radiological abnormality

In typical adult neuronal intranuclear inclusion disease (NIID) with predilection for the basal ganglia or cerebral cortex, not only neurons but also glial cells harbor intranuclear inclusions. In addition, these inclusions are present in the peripheral autonomic nervous system, visceral organs and skin. In NIID cases with an expansion of GGC repeats in the 5 '-untranslated region (5 '-UTR) of the Notch 2 N-terminal like C (NOTCH2NLC) gene, these repeats are located in an upstream open reading frame (uN2C) and result in the production of a polyglycine-containing protein called uN2CpolyG. Typically, patients with adult NIID show high-intensity signals at the corticomedullary junction on diffusion-weighted brain magnetic resonance imaging. We report a case of adult NIID in a 78-year-old Japanese male, who suffered from mild, non-progressive tremor during life but showed no radiographic abnormalities suggestive of adult NIID. Pathologically, ubiquitin-, p62- and uN2CpolyG-positive neuronal intranuclear inclusions were particularly frequent in the hippocampal formation, but were also seen in the enteric plexuses, kidney and cardiac muscles. By contrast, glial intranuclear inclusions were barely evident in the affected regions. The present case also had an immunohistochemical profile differing from that of typical adult NIID. The findings in this case suggest that adult NIID can show clinical, radiographic and pathological heterogeneity.

Automated summary

In adult neuronal intranuclear inclusion disease (NIID), both neurons and glial cells harbor intranuclear inclusions, which can also be found in the peripheral autonomic nervous system, visceral organs, and skin. This study reports a case of NIID in a 78-year-old Japanese male who exhibited mild tremors but did not show typical radiographic abnormalities. Pathological analysis revealed that neuronal intranuclear inclusions were particularly frequent in the hippocampal formation, while glial intranuclear inclusions were barely evident in the affected regions. The case also had an immunohistochemical profile differing from that of typical adult NIID.