Inclusion-positive cell types in adult-onset intranuclear inclusion body disease: implications for clinical diagnosis

Abstract

The distribution of inclusions in adult-onset type intranuclear inclusion body disease (INIBD) has not been fully described. We analyzed the clinical and pathological changes of three autopsy cases of adult type INIBD and provide a detailed description of the distribution of inclusions in nervous system and visceral organs. Although patients showed cognitive decline and autonomic dysfunction, there were no specific symptoms related to general organs. The neuropathological changes responsible for cognitive decline and autonomic dysfunction were considered to be white matter changes in the cerebral hemispheres and inclusions in the autonomic nervous system, e.g., in the sympathetic ganglia and myenteric plexus. Alterations of spongiosis with both myelin and axon loss in the cerebral white matter seemed to be related to dysfunction of astrocytes with intranuclear inclusions. In visceral organs, the inclusions were much more widely distributed than previously appreciated and included renal mesangial cells, adrenal sustentacular cells, fibrocytes, Kupffer cells, pancreatic centroacinar and ductal epithelial cells. Since skeletal muscle cells, Schwann cells and smooth muscle cells were also inclusion positive, we propose that biopsy of muscle, peripheral nerve or rectum may prove useful for the clinical diagnosis of INIBD.

Clinicopathological features of adult-onset neuronal intranuclear inclusion disease

“…However, considering the systemic-wide distribution of intranuclear inclusion and neuronal loss in reported NIID cases (Lindenberg et al , 1968; Patel et al , 1985; Funata et al , 1990; Takahashi-Fujigasaki, 2003; Woulfe, 2007; Liu et al , 2008), we should be aware of the possibility of another phenotype of NIID (neither dementia nor weakness) and accumulate histopathologically-diagnosed NIID cases to refine the whole NIID clinical picture.…”

“…Since then, many NIID cases have been reported after post-mortem examination (Schuffler et al , 1978; Michaud and Gilbert, 1981; Patel et al , 1985; Munoz-Garcia and Ludwin, 1986; Oyer et al , 1991; Weidenheim and Dickson, 1995; Takahashi-Fujigasaki, 2003; Liu et al , 2008). The onset of disease varies from infancy to the sixties, but two-thirds of them were infantile or juvenile cases (Funata et al , 1990; Zannolli et al , 2002; Takahashi-Fujigasaki, 2003).…”

FUS immunoreactivity of neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

“…Immunohistochemically, INIBs in INIBD are positive for ubiquitin and ubiquitin‐related proteins (NUB1, SUMO‐1 and p62) [8,9,23] and a proportion of INIBs are immunolabelled with anti‐polyQ antibody 1C2 [8,9]. Recently, Woulfe et al .…”

“…The vast majority of inclusion‐bearing glial cells are astrocytic and others may be oligodendrocytes [6,9]. Based on these findings, the dysfunction of astrocytes with INIBs may cause secondary damage to both myelin and axons in the cerebral white matter, which is a cardinal neuropathological feature in adult‐onset INIBD [8,9].…”

Ubiquitin‐related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

“…Clinically, INIBD is divided into three categories concerning the age at onset: infantile, juvenile and adult forms 3–5 . In adult‐onset INIBD, INI are more frequently observed in glial cells than in neurons 2,6,7 . Most cases reported as INIBD are sporadic, but some familial cases have been recognized 8 .…”