[Neuronal intranuclear hyaline inclusion disease (NIHID): an update]

Neuronal intranuclear hyaline inclusion disease (NIHID) is a neurodegenerative disorder characterized by eosinophilic intranuclear inclusions in neuronal cells. Such inclusions are also found in non-neuronal cells. The clinical features and pathological findings in patients with NIHID are highly varied, and NIHID is therefore considered a heterogeneous disease entity. It can be categorized into three clinical subgroups based on disease onset and duration: the infantile, juvenile, and adult forms. The infantile and juvenile forms are generally associated with slowly progressive multiple-system degeneration. Recently, reports of patients with adult form NIHID have increased. Major symptoms in typical adult-onset cases are memory loss, cognitive dysfunction, and disorientation. Autonomic dysfunctions and peripheral neuropathy are also frequently observed. This type of adult-onset NIHID can be predicted by characteristic MRI findings-leukoencephalopathy with high intensity of the corticomedullary junction in diffusion-weighted imaging. Ante-mortem diagnosis of NIHID can be made by identification of intranuclear inclusions in skin or rectal biopsies. Intranuclear accumulation of abnormal proteins and/or dysfunction of protein degradation might underlie the pathogenesis of NIHID; however, the disease mechanisms remain largely unknown.