Abstract
Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated 'dementia dominant group', followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated 'limb weakness group', followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and familial NIID cases presented with a decline in Mini-Mental State Examination and Frontal Assessment Battery scores. Based on these clinicopathological features, we proposed a diagnosis flow chart of adult-onset NIID. Our study suggested that the prevalence rate of adult-onset NIID may be higher than previously thought, and that NIID may be underdiagnosed. We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy.
Highlights
Neuronal intranuclear inclusion disease (NIID), known as neuronal intranuclear hyaline inclusion disease (NIHID) or intranuclear inclusion body disease (INIBD), is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central, peripheral and autonomic nervous system cells, and in visceral organs cells.The first case of NIID was reported in 1968 (Lindenberg et al, 1968)
Intranuclear inclusions in the skin biopsy samples were confirmed on 37 sporadic NIID cases and 15 familial NIID cases from six families studied in this study, including cases we reported previously (Sone et al, 2005; Kitagawa et al, 2014; Sone et al, 2014)
Of the sporadic NIID cases, Subject S-5 was diagnosed by autopsy, Subject S-31 was diagnosed by both autopsy and skin biopsy, and the others were diagnosed by skin biopsy
Summary
Neuronal intranuclear inclusion disease (NIID), known as neuronal intranuclear hyaline inclusion disease (NIHID) or intranuclear inclusion body disease (INIBD), is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central, peripheral and autonomic nervous system cells, and in visceral organs cells.The first case of NIID was reported in 1968 (Lindenberg et al, 1968). 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). A wide range of clinical manifestations has been reported: pyramidal and extrapyramidal symptoms, cerebellar ataxia, dementia, convulsions, neuropathy, and autonomic dysfunction. This wide range of clinical phenotypes makes ante-mortem diagnosis of NIID difficult, especially in adult-onset NIID cases. One of the reasons for this is surely the small chance of diagnosis of NIID, due to it being limited to post-mortem dissection
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