Neuronal intranuclear hyaline inclusion disease

Neuronal intranuclear hyaline inclusion disease (NIHID) is a rare childhood neurodegenerative disease, usually with unremarkable imaging. 

Typically NIHID presents in childhood (3-12 years of age) 2-3 although adult onset has also been described 3. Hereditary cases have been described, and an autosomal recessive pattern of inheritance is suspected 1-2.

The clinical presentation of patients with NIHID can be varied and includes 1-3:

  • pyramidal tract signs
  • extrapyramidal sings including parkinsonism
  • abnormal ocular movements and oculogyric crises
  • generalized cognitive degeneration and behavioral changes
  • peripheral neuropathy
    • severe muscle atrophy and weakness
    • sensory impairment in the distal limbs
    • dysphagia
  • autonomic neuropathy
    • episodic intestinal pseudoobstruction
    • urinary and fecal incontinence
  • cardiomyopathy: reported but uncommon
  • epilepsy: reported but uncommon

The diagnosis can be made using peripheral nerve biopsy (e.g. sural nerve) 1 or myenteric plexus biopsy (e.g. rectal biopsy)2-3

NIHID is characterized by accumulation of eosinophilic intranuclear inclusions which can be found widely within both the central and peripheral nervous system including sympathetic and myenteric ganglion neurons, dorsal root ganglion neurons, and spinal motor neurons 1-3

It is believed to be due to abnormal proteolysis, although the exact mechanism has as yet not been established 2-3.

The intranuclear inclusions fluoresce under ultraviolet light and are composed of uniform, fine straight filaments haphazardly arranged 3

Usually imaging is non-contributory 3 and its primary role is to exclude other entities which may mimic the condition clinically (see below).

Severe cerebellar cortical atrophy has been reported, particularly involving the vermis 3

Neuronal intranuclear hyaline inclusion disease (NIHID) is slowly progressive and has no proven therapy. Death usually occurs before the age of 30 years 3

Clinically the differential diagnosis includes 3:

  • juvenile parkinsonism
  • spinocerebellar degneration
  • GM2 gangliosidosis
  • infantile neuroaxonal dystrophy
Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.

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rID: 13122
Synonyms or Alternate Spellings:
  • Neuronal intranuclear hyaline inclusion disease (NIHID)
  • Neuronal intranuclear inclusion disease
  • Neuronal intranuclear inclusion disease (NIID)
  • NIID

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