First case of adult onset neuronal intranuclear inclusion disease with both typical radiological signs and NOTCH2NLC repeat expansions in a Caucasian individual

Eur J Neurol. 2023 Sep;30(9):2854-2858. doi: 10.1111/ene.15905. Epub 2023 Jun 11.

Abstract

Background and purpose: Adult onset neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disorder with a heterogeneous clinical presentation that can mimic stroke and various forms of dementia. To date, it has been described almost exclusively in Asian individuals.

Methods: This case presentation includes magnetic resonance imaging (MRI) of the neurocranium, histology by skin biopsy, and long-read genome sequencing.

Results: A 75-year-old Caucasian female presented with paroxysmal encephalopathy twice within a 14-month period. Brain MRI revealed high-intensity signals at the cerebral corticomedullary junction (diffusion-weighted imaging) and the paravermal area (fluid-attenuated inversion recovery), a typical distribution observed in adult onset NIID. The diagnosis was corroborated by skin biopsy, which demonstrated eosinophilic intranuclear inclusion bodies, and confirmed by long-read genome sequencing, showing an expansion of the GGC repeat in exon 1 of NOTCH2NLC.

Conclusions: Our case proves adult onset NOTCH2NLC-GGC-positive NIID with typical findings on MRI and histology in a Caucasian patient and underscores the need to consider this diagnosis in non-Asian individuals.

Keywords: neurogenetics; neuronal intranuclear inclusion disease; neuroradiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain / diagnostic imaging
  • Brain / pathology
  • Female
  • Humans
  • Intranuclear Inclusion Bodies* / genetics
  • Intranuclear Inclusion Bodies* / pathology
  • Magnetic Resonance Imaging
  • Neurodegenerative Diseases* / diagnostic imaging
  • Neurodegenerative Diseases* / genetics

Supplementary concepts

  • Neuronal intranuclear inclusion disease