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Background Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative condition characterised by pathologic eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system. Heterogenous clinical manifestations present a challenge for antemortem diagnosis.Methods We describe two cases of NIID mimicking hemiplegic migraine and conducted a literature review identifying similar NIID cases.Results Both cases reported a past history of presumed hemiplegic migraine. The first case was an East Asian male in his 20s presenting with episodic headache, encephalopathy, and intermittent focal symptoms including dysphasia and left-sided hemiplegia. MRI revealed subcortical white matter T2/FLAIR hyperintensity, and focal cortical oedema accompanying episodes of severe encephalopathy. The second case was a Māori male in his 60s with two prolonged episodes of encephalopathy with fever and right-sided hemiplegia. MRI showed hemispheric cortical oedema and FLAIR hyperintensity with subsequent regional brain atrophy. In both patients, severe hemiplegic migraine was the initial diagnosis however genetic testing was negative. Recurrent encephalopathy and progressive cognitive impairment prompted consideration of alternative causes. NIID was confirmed by long-read nanopore sequencing showing GGC repeat expansion in NOTCH2NLC in the first case, and skin biopsy showing p62-positive intranuclear inclusions in the second. Most NIID cases are reported in East Asian and Polynesian populations. Several case reports describe progression from episodic migraine-like attacks to encephalopathic episodes, similar to our cases.Conclusion Recurrent migraine-like attacks with encephalopathy, where more common differential diagnoses are excluded, should raise suspicion for NIID, especially with progressive deficits, characteristic imaging changes, and East Asian or Polynesian ancestry.