Rare and Misdiagnosed Case Reports: Analysis of Five Cases of Neuronal Intranuclear Inclusion Disease

Introduction: Neuronal intranuclear inclusion disease (NIID) is an uncommon, progressive degenerative neurological condition that poses diagnostic challenges, largely because its clinical features vary widely and it often resembles other, more frequently encountered diseases. This study investigates the application of imaging clues in its diagnostic pathway to reduce misdiagnosis and improve diagnostic precision. Case presentation: We retrospectively analyzed five patients with NIID, with one core case undergoing detailed observation. Among the five patients, four were female and one male, with ages ranging from 53 to 69 years. Clinical presentations were diverse: dizziness (5/5), cognitive impairment (4/5), tremor (3/5), urinary difficulty (2/5), psychiatric symptoms (1/5), hydrocephalus (1/5), nephritis (1/5), Hypoproteinemia(1/5). Magnetic Resonance Imaging (MRI) in all cases demonstrated cerebral atrophy and white matter lesions to differing extents, with symmetric signal hyperintensities chiefly affecting the subcortical white matter, periventricular region, and frontal and parietal lobes. Patient 5, the core case, had acute dizziness together with a long-standing tremor and urinary difficulty. The diagnosis of NIID was suggested by these typical MRI findings and later confirmed by a skin biopsy plus an expanded GGC repeat in the NOTCH2NLC gene. Conclusion: As an essential imaging hallmark of NIID, characteristic hyperintensity at the corticomedullary junction enables early suspicion of the disease in patients with multisystem symptoms such as dizziness, tremor and autonomic dysfunction; meanwhile, timely implementation of skin biopsy and genetic testing is necessary to reach a definitive diagnosis, with neuroimaging acting as an effective screening indicator and genetic testing serving as a powerful diagnostic approach.