The predominance of "astrocytic" intranuclear inclusions in neuronal intranuclear inclusion disease manifesting encephalopathy-like symptoms: A case series with brain biopsy.

Autor: Ishizawa K; Department of Pathology, Saitama Medical University, Saitama, Japan.; Department of Neurology, Saitama Medical University, Saitama, Japan.; Department of Laboratory Medicine, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan., Komori T; Department of Laboratory Medicine, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan., Homma T; Department of Laboratory Medicine, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.; Department of Diagnostic Pathology, Saitama Medical University International Medical Center, Saitama, Japan., Sone J; Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan., Nakata Y; Department of Neuroradiology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan., Nakazato Y; Department of Neurology, Saitama Medical University, Saitama, Japan., Takahashi K; Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan., Yamamoto T; Department of Neurology, Saitama Medical University, Saitama, Japan., Sasaki A; Department of Pathology, Saitama Medical University, Saitama, Japan.
Jazyk: angličtina
Zdroj: Neuropathology : official journal of the Japanese Society of Neuropathology [Neuropathology] 2024 Oct; Vol. 44 (5), pp. 351-365. Date of Electronic Publication: 2024 Mar 13.
DOI: 10.1111/neup.12971
Abstrakt: Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder represented by eosinophilic intranuclear inclusions (EIIs) and GGC/CGG repeat expansion in the NOTCH2NLC gene. We report here two adult cases of NIID, genetically confirmed, with manifestation of encephalopathy-like symptoms and address the histopathologic findings obtained by brain biopsies, with a focus on "astrocytic" intranuclear inclusions (AIIs). Case 1 presented with paroxysmal restlessness, vertigo, or fever and was later involved in severe dementia and tetraparesis. Case 2 presented with forgetfulness and then with paroxysmal fever and headache. In both cases, delimited areas with gadolinium enhancement on magnetic resonance imaging and corresponding hyperperfusion were detected, leading to brain biopsies of the cortex. On histology, Case 1 showed an abnormal lamination, where the thickness of layers was different from usual. Both neurons and astrocytes showed some dysmorphologic features. Notably, astrocytes rather than neurons harbored EIIs. Case 2 showed a cortex, where neurons tended to be arrayed in a columnar fashion. Astrocytes showed some dysmorphologic features. Notably, much more astrocytes than neurons harbored EIIs. By a double-labeling immunofluorescence study for p62/NeuN and p62/glial fibrillary acidic protein, the predominance of AIIs was confirmed in both cases. Considering the physiological functions of astrocytes for the development and maintenance of the cortex, the encephalopathy-like symptoms, dynamic change of cerebral blood flow, and cortical dysmorphology can reasonably be explained by the dysfunction of EII-bearing astrocytes rather than EII-bearing neurons. This study suggests the presence of a subtype of NIID where AIIs rather than "neuronal" intranuclear inclusions are likely a key player in the pathogenesis of NIID, particularly in cases with encephalopathy-like symptoms. The importance of AIIs ("gliopathy") should be more appreciated in future studies of NIID.
(© 2024 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Neuropathology.)
Databáze: MEDLINE
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