{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:43:39Z","timestamp":1792597419013,"version":"4.5.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Neuronal Intranuclear Inclusion Disease (NIID) is a neurodegenerative disorder characterized by the formation of eosinophilic inclusions in the neurons, visceral and skin cells. The cause is associated with the GGC nucleotide repeat expansion in the NOTCH2NLC gene. The imaging hallmark of NIID is hyperintensities on diffusion-weighted imaging (DWI) at the corticomedullary junction. Clinical manifestations of NIID are highly heterogeneous. Here, we report a case of NIID presenting with acute-onset dementia and cortical edema.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>We describe an elderly male patient who presented with sudden dementia within a day. Considering the abrupt onset and the stroke history, we initially diagnosed vascular disease. However, further imaging revealed cortical edema in the temporo-parieto-occipital lobes. Blood and cerebrospinal fluid tests ruled out immunological, metabolic, infectious, or neoplastic etiologies. Genetic testing ultimately confirmed the diagnosis of NIID. Intravenous immunoglobulin (IVIG) therapy did not improve the patient\u2019s symptoms; However, about 1\u2009month after treatment, spontaneous improvement was observed. It is noteworthy that 22\u2009months before the onset of cognitive impairment, the patient\u2019s MRI for headaches already exhibited the typical imaging lesions of this disease in the cerebellum paravermal region.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with encephalopathy syndrome exhibiting imaging features resembling mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome or Creutzfeldt-Jakob disease should consider the NIID as differential diagnosis. Chronic headaches and symmetric lesions in the cerebellar paravermal region on MRI may be noteworthy indicators of NIID during non-episodic phases.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1464991","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:47:16Z","timestamp":1730090836000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuronal Intranuclear Inclusion Disease Presenting with Acute-Onset Dementia and Cortical Edema: A Case Report"],"prefix":"10.3389","volume":"15","author":[{"given":"Xiao","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1093\/brain\/aww249","article-title":"Clinicopathological features of adult-onset neuronal intranuclear inclusion disease","volume":"139","author":"Sone","year":"2016","journal-title":"Brain"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/s41588-019-0459-y","article-title":"Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease","volume":"51","author":"Sone","year":"2019","journal-title":"Nat Genet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1046\/j.1440-1789.2003.00524.x","article-title":"Neuronal intranuclear hyaline inclusion disease","volume":"23","author":"Takahashi-Fujigasaki","year":"2003","journal-title":"Neuropathology"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3760\/cma.j.issn.0253-2727.2019.01.010","article-title":"Study of clinical outcome and prognosis in pediatric core binding factor-acute myeloid leukemia","volume":"40","author":"Wu","year":"2019","journal-title":"Zhonghua Xue Ye Xue Za Zhi"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1136\/jnnp-2022-329772","article-title":"Clinical features of NOTCH2NLC-related neuronal intranuclear inclusion disease","volume":"93","author":"Tian","year":"2022","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2100","DOI":"10.3174\/ajnr.A5336","article-title":"MR imaging features of the cerebellum in adult-onset neuronal Intranuclear inclusion disease: 8 cases","volume":"38","author":"Sugiyama","year":"2017","journal-title":"AJNR Am J Neuroradiol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.3390\/life11111111","article-title":"Clinical characteristics of mitochondrial Encephalomyopathy, lactic acidosis, and stroke-like episodes","volume":"11","author":"Fan","year":"2021","journal-title":"Life (Basel)"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e12787","DOI":"10.1111\/nan.12787","article-title":"Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy","volume":"48","author":"Ogasawara","year":"2022","journal-title":"Neuropathol Appl Neurobiol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1186\/s12883-021-02425-z","article-title":"FXTAS is difficult to differentiate from neuronal intranuclear inclusion disease through skin biopsy: a case report","volume":"21","author":"Toko","year":"2021","journal-title":"BMC Neurol"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awae274","article-title":"GGC repeat expansions in NOTCH2NLC cause uN2CpolyG cerebral amyloid angiopathy","author":"Bao","year":"2024","journal-title":"Brain"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"934725","DOI":"10.3389\/fnagi.2022.934725","article-title":"Clinical and mechanism advances of neuronal intranuclear inclusion disease","volume":"14","author":"Liu","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s40478-022-01383-y","article-title":"The polyG diseases: a new disease entity","volume":"10","author":"Liufu","year":"2022","journal-title":"Acta Neuropathol Commun"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e200132","DOI":"10.1212\/nxg.0000000000200132","article-title":"Review of phenotypic heterogeneity of neuronal Intranuclear inclusion disease and NOTCH2NLC-related GGC repeat expansion disorders","volume":"10","author":"Zhang","year":"2024","journal-title":"Neurol Genet"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1007\/s10072-023-06677-0","article-title":"Current advances in neuronal intranuclear inclusion disease","volume":"44","author":"Bao","year":"2023","journal-title":"Neurol Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"21","DOI":"10.3390\/ijms21124391","article-title":"Fragile X-associated tremor\/Ataxia syndrome (FXTAS): pathophysiology and clinical implications","volume":"21","author":"Cabal-Herrera","year":"2020","journal-title":"Int J Mol Sci"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.2169\/internalmedicine.0156-22","article-title":"Acute reversible encephalopathy with neuronal Intranuclear inclusion disease diagnosed by a brain biopsy: inferring the mechanism of encephalopathy from radiological and histological findings","volume":"62","author":"Orihara","year":"2023","journal-title":"Intern Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1212\/wnl.0000000000200984","article-title":"Teaching NeuroImage: Paravermal lesions in neuronal Intranuclear inclusion disease","volume":"99","author":"Sugiyama","year":"2022","journal-title":"Neurology"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1111\/head.13687","article-title":"Interrelated pathogenesis? Neuronal Intranuclear inclusion disease combining with hemiplegic migraine","volume":"60","author":"Wang","year":"2020","journal-title":"Headache"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1186\/s12883-021-02367-6","article-title":"Neuronal intranuclear inclusion disease presented with recurrent vestibular migraine-like attack: a case presentation","volume":"21","author":"Zhao","year":"2021","journal-title":"BMC Neurol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00702-021-02313-3","article-title":"Neuronal intranuclear inclusion disease: recognition and update","volume":"128","author":"Lu","year":"2021","journal-title":"J Neural Transm (Vienna)"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1093\/brain\/awac135","article-title":"Neuronal intranuclear inclusion disease in patients with adult-onset non-vascular leukoencephalopathy","volume":"145","author":"Liu","year":"2022","journal-title":"Brain"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1464991\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:47:18Z","timestamp":1730090838000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2024.1464991\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,28]]},"references-count":21,"alternative-id":["10.3389\/fneur.2024.1464991"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2024.1464991","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,28]]},"article-number":"1464991"}}