Objective: To report a case of adult-onset neuronal intranuclear inclusion disease (NIID) presenting with progressive gait instability, neurogenic bladder, and life-threatening gastrointestinal dysmotility.

Background: NIID is a progressive neurodegenerative disorder associated with GGC repeat expansions in the NOTCH2NLC gene. Its clinical presentation is highly heterogeneous, often involving cognitive decline, movement disorders, and autonomic dysfunction. While leukoencephalopathy is a hallmark, visceral involvement can lead to severe gastrointestinal complications that mimic acute primary GI disease, complicating the diagnostic trajectory.

Method: We performed a clinical and diagnostic review of a 68-year-old female who presented with a 2-year history of motor and autonomic symptoms. Data were collected from longitudinal clinical examinations, magnetic resonance imaging (MRI), histopathology from gastric biopsy, and genetic analysis.

Results: A 68-year-old female presented with a two-year history of insidious, progressive gait instability characterized by small steps and festination. Her medical history was notable for detrusor underactivity, and she later developed recurrent vomiting and diarrhea, leading to aspiration pneumonia and type 1 respiratory failure requiring mechanical ventilation. The clinical course was further complicated by hydronephrosis necessitating stenting, as well as cognitive decline with intermittent visual hallucinations. Physical examination revealed bilateral elbow rigidity and a UPDRS Part III (ON) score of 43. Brain MRI showed atrophy and confluent FLAIR hyperintensities within the deep and periventricular white matter. A gastric biopsy obtained via esophagogastroduodenoscopy revealed p62-positive intranuclear inclusions, and genetic testing confirmed a pathological GGC repeat expansion (122 repeats) in the NOTCH2NLC gene. Ultimately, refractory gastroparesis and impaired transit required the surgical placement of a decompressive gastrostomy and a feeding jejunostomy.

Conclusion: This case emphasizes that gastrointestinal dysmotility can be a dominant and life-threatening feature in addition to gait instability, leukoencephalopathy, and autonomic symptoms of NIID. Furthermore, gastric biopsy is a viable, minimally invasive alternative to skin biopsy for confirming the presence of characteristic intranuclear inclusions.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/severe-gastroparesis-and-atypical-parkinsonism-as-presenting-features-of-neuronal-intranuclear-inclusion-disease-niid/