Case report: Neuronal intranuclear inclusion disease presenting with acute encephalopathy

Abstract

Neuronal intranuclear inclusion disease (NIID), a neurodegenerative disease previously thought to be rare, is increasingly recognized despite heterogeneous clinical presentations. NIID is pathologically characterized by ubiquitin and p-62 positive intranuclear eosinophilic inclusions that affect multiple organ systems, including the brain, skin, and other tissues. Although the diagnosis of NIID is challenging due to phenotypic heterogeneity, a greater understanding of the clinical and imaging presentations can improve accurate and early diagnosis. Here, we present three cases of pathologically proven adult-onset NIID, all presenting with episodes of acute encephalopathy with protracted workups and lengthy time between symptom onset and diagnosis. Case 1 highlights challenges in the diagnosis of NIID when MRI does not reveal classic abnormalities and provides a striking example of hyperperfusion in the setting of acute encephalopathy, as well as unique pathology with neuronal central chromatolysis, which has not been previously described. Case 2 highlights the progression of MRI findings associated with multiple NIID-related encephalopathic episodes over an extended time period, as well as the utility of skin biopsy for antemortem diagnosis.

Keywords: arterial spin labeling; case report; chromatolysis; magnetic resonance imaging; neuronal intranuclear inclusion disease.

Figure 1

Axial FLAIR (A), T1 post-contrast (B), and ASL (C) demonstrate cortical edema, cortical and pial enhancement, and marked hyperperfusion involving the left temporal and occipital lobes. DWI (D) and ADC (E) show T2 shine-through but no definite restricted diffusion in the involved regions. Also noted is a chronic infarct in the right frontal lobe.

Figure 2

Pathologic features of NIID on biopsies from all three patients: Hematoxylin- and eosin-stained sections [(A–C); 400x magnification] from biopsies on all three patients showed prominent intranuclear eosinophilic inclusions (arrows), seen within neurons also exhibiting central chromatolysis in the brain biopsy from patient 1, the eccrine glandular epithelium on the skin biopsy from patient 2, and neurons and glia on brain biopsy from patient 3. All intranuclear inclusions were immunoreactive for ubiquitin [(D–F); arrowheads]. Electron microscopy on all three specimens confirmed the presence of intranuclear fibrillar inclusions (G–I).

Figure 3

DWI, ADC, and FLAIR from 2017 (A–C), 2019 (D–F), and 2021 (G–I) demonstrate progressive diffusion restriction at the corticomedullary junction of the bilateral frontal and parietal lobes, as well as diffuse confluent white matter FLAIR hyperintensity.

Figure 4

Axial FLAIR (A), T1 post-contrast (B), DWI (C), and ADC (D) demonstrate diffuse cortical edema and patchy cortical enhancement throughout the left cerebral hemisphere on a background of corticomedullary diffusion restriction involving the bilateral frontal and left parietal lobes as well as diffusion restriction in the corpus callosum.