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Case report on ribbon sign in NIID diagnosis with coincidental intracranial stenosisRibbon sign on brain scan points to rare disease in woman

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Key Takeaway
Consider the ribbon sign on neuroimaging and skin biopsy for NIID diagnosis when genetic testing is negative.

This is a single case report describing a 64-year-old woman with neuronal intranuclear inclusion disease (NIID) and coincidental intracranial atherosclerotic stenosis. The authors detail diagnostic imaging and tissue findings.

Brain MRI showed a new area of restricted diffusion in the right frontoparietal region and ipsilateral middle cerebral artery M2 segment stenosis greater than 50 percent. A linear hyperintensity along the corticomedullary junction, identified as the ribbon sign, was seen on diffusion-weighted imaging.

Skin biopsy with electron microscopy demonstrated characteristic non-membranous intranuclear inclusions. Genetic testing for NOTCH2NLC GGC repeat expansion was negative, so diagnosis relied on biopsy.

The authors note this is a single case report with limited generalizability. Genetic testing was negative, and diagnosis depended on tissue biopsy. They emphasize recognizing the ribbon sign on neuroimaging for NIID diagnosis, even with coincidental atherosclerosis, and using targeted biopsy when genetic testing is unrevealing.

Practice relevance is restrained to diagnostic consideration in similar presentations. No causal inference can be made from this case report.

A 64-year-old woman kept having sudden, temporary brain symptoms, but she had no typical risk factors like high blood pressure or diabetes. Doctors took a close look at her brain MRI and found a thin, bright line along the brain's surface, known as the ribbon sign. This sign can point to a rare condition called neuronal intranuclear inclusion disease (NIID). They also saw a narrowed artery in her brain, but that was likely a separate issue.

To confirm the diagnosis, doctors did a skin biopsy. Under an electron microscope, they saw the tiny, telltale inclusions inside cells that are the hallmark of NIID. A genetic test for the known NIID mutation was negative, so the biopsy was key.

This is just one person, so we can't generalize from it. But it shows how important it is for doctors to recognize the ribbon sign on an MRI, even if a patient also has a common problem like a narrowed brain artery. When genetic tests don't give a clear answer, a targeted tissue biopsy can be the next best step.

What this means for you:
A special brain scan sign can point to a rare disease, even when a genetic test is negative.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedMay 2026
View Original Abstract ↓
BackgroundNeuronal 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 presentationWe 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.ConclusionWe 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.
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