Neuronal intranuclear inclusion disease

Neuronal intranuclear inclusion disease (NIID), also known as neuronal intranuclear hyaline inclusion disease (NIHID), is a rare, slowly progressive neurodegenerative disorder characterized by the presence of eosinophilic hyaline intranuclear inclusions in neurons and other cell types throughout the central and peripheral nervous systems, as well as in visceral organs. The disease affects multiple body systems, primarily the nervous system, and presents with a highly variable clinical picture depending on the age of onset. In the infantile form, patients may present with growth retardation, intellectual disability, and progressive motor dysfunction. In juvenile and adult-onset forms, the clinical features can include progressive cognitive decline and dementia, cerebellar ataxia, peripheral neuropathy, autonomic dysfunction (such as bladder disturbances and orthostatic hypotension), movement disorders (tremor, parkinsonism, chorea), seizures, and leukoencephalopathy visible on brain MRI. A characteristic MRI finding is high-intensity signal along the corticomedullary junction on diffusion-weighted imaging (DWI), which is considered a hallmark diagnostic feature. NIID has been linked to GGC repeat expansions in the 5' untranslated region of the NOTCH2NLC gene, a discovery that has significantly improved diagnostic capabilities. The disease can present sporadically or in a familial pattern. Diagnosis is supported by skin biopsy, which can reveal intranuclear inclusions in dermal cells (adipocytes, fibroblasts, and sweat gland cells), providing a less invasive alternative to brain biopsy. There is currently no cure or disease-modifying treatment for NIID. Management is supportive and symptomatic, focusing on addressing specific neurological symptoms such as seizures, movement disorders, and autonomic dysfunction. The prognosis varies considerably depending on the age of onset and the rate of disease progression, with infantile forms generally having a more severe course.

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