Case Report: Neuronal intranuclear inclusion disease mimicking recurrent stroke in the setting of intracranial stenosis.

Background: Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder that can present with stroke-like episodes, posing a significant diagnostic challenge. This difficulty is compounded when it coincides with intracranial atherosclerotic stenosis, a common cause of recurrent stroke. Case presentation: We report the case of a 64-years-old woman without conventional vascular risk factors who presented with a recurrent acute focal neurological deficit-her sixth similar episode over 8 years, each previously diagnosed as cerebral infarction. Brain magnetic resonance imaging (MRI) revealed a new area of restricted diffusion in the right frontoparietal region and an ipsilateral middle cerebral artery (MCA) M2 segment stenosis (>50%). Crucially, a systematic review of the diffusion-weighted imaging (DWI) sequences identified the pathognomonic linear hyperintensity along the corticomedullary junction, known as the "ribbon sign," which is highly suggestive of NIID. Despite a negative genetic test for the NOTCH2NLC GGC repeat expansion, the diagnosis was confirmed by a minimally invasive skin biopsy, which demonstrated characteristic non-membranous intranuclear inclusions on electron microscopy. Conclusion: We highlight the imperative to recognize this specific and pathognomonic neuroimaging pattern even in the presence of coincidental atherosclerosis. Furthermore, we detail the systematic diagnostic approach when genetic testing is unrevealing, emphasizing the pivotal role of targeted tissue biopsy in achieving a definitive diagnosis. This report underscores the key learning points in evaluating acute stroke mimics with atypical evolution.