{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:56:50Z","timestamp":1771930610399,"version":"3.50.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008884","name":"Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JPJSBP 120217720"],"award-info":[{"award-number":["JPJSBP 120217720"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. We investigated a role of nonconvulsive status epilepticus (NCSE) in cognitive dysfunction in pathologically confirmed NIID. We also analyzed distinctive factors to differentiate NIID from Alzheimer\u2019s disease (AD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 63-year-old man presented with transient consciousness disturbance (Day 1). For previous 6\u202fyears he had been suffering from similar episodes and gradually progressive cognitive decline. Clinical characteristics and response to antiseizure medications (ASM) were analyzed with a narrative literature review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Neurological examination showed disorientation, memory disturbance, aphasia, agraphia, and impaired visuospatial ability. On Day 27, his MMSE scored 10. Diffusion-weighted MRI showed high intensity signal in the corticomedullary junction of the frontal lobe, which could not explain his neurological manifestations. EEG showed seizure patterns arising from the bilateral occipital areas. ASM improved MMSE score to 23. Skin biopsy confirmed his diagnosis as dementia-dominant sporadic NIID. He died on Day 77. Cognitive dysfunction in visuospatial execution, manifested by impaired pentagon drawing and agraphia of both kanji (Japanese morphograms) and kana (Japanese syllabograms), its fluctuating course, and reactivity to ASM were clear distinction from AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>NCSE can accelerate cognitive decline and ASM can improve cognitive function in NIID. Cognitive evaluation using pentagon drawing and handwriting of both morphograms and syllabograms can be useful to differentiate NIID from AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1734078","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:48:19Z","timestamp":1770187699000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Distinctive features of cognitive dysfunction and amelioration by antiseizure medication in neuronal intranuclear inclusion disease"],"prefix":"10.3389","volume":"20","author":[{"given":"Hiroya","family":"Ohara","sequence":"first","affiliation":[{"name":"Department of Neurology, Minaminara General Medical Center","place":["Yoshino, Nara, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masami","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Minaminara General Medical Center","place":["Yoshino, Nara, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumi","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Diagnostics, Nara Medical University School of Medicine","place":["Kashihara, Nara, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiko","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Minaminara General Medical Center","place":["Yoshino, Nara, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marisse Dy","family":"Dizon","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Behavioral Medicine, University of Santo Tomas Hospital","place":["Manila, Philippines"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay","family":"Elangovan","sequence":"additional","affiliation":[{"name":"Human Cytogenetics and Stem Cell Laboratory, Department of Zoology, Central University of Punjab","place":["Bathinda, Punjab, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harysh Winster Suresh","family":"Babu","sequence":"additional","affiliation":[{"name":"Human Cytogenetics and Stem Cell Laboratory, Department of Zoology, Central University of Punjab","place":["Bathinda, Punjab, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahalaxmi","family":"Iyer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Central University of Punjab","place":["Bathinda, Punjab, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balachandar","family":"Vellingiri","sequence":"additional","affiliation":[{"name":"Human Cytogenetics and Stem Cell Laboratory, Department of Zoology, Central University of Punjab","place":["Bathinda, Punjab, India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Hospital Organization Utano National Hospital","place":["Kyoto, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1001\/archneur.1992.00530270060019","article-title":"Lesion localization in apractic agraphia","volume":"49","author":"Alexander","year":"1992","journal-title":"Arch. Neurol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1111\/epi.14070","article-title":"Nonconvulsive status epilepticus in rats leads to brain pathology","volume":"59","author":"Avdic","year":"2018","journal-title":"Epilepsia"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"107174","DOI":"10.1016\/j.neuropsychologia.2019.107174","article-title":"Two distinct pathological substrates associated with MMSE-pentagons item deficit in DLB and AD","volume":"133","author":"Beretta","year":"2019","journal-title":"Neuropsychologia"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1111\/ene.12739","article-title":"The diagnostic accuracy of routine electroencephalography after a first unprovoked seizure","volume":"23","author":"Bouma","year":"2016","journal-title":"Eur. J. Neurol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3233\/BEN-120319","article-title":"The qualitative scoring MMSE pentagon test (QSPT): a new method for differentiating dementia with Lewy body from Alzheimer's disease","volume":"27","author":"Caffarra","year":"2013","journal-title":"Behav. Neurol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1684\/epd.2014.0709","article-title":"Non-convulsive status epilepticus in the elderly","volume":"16","author":"Cheng","year":"2014","journal-title":"Epileptic Disord."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/0093-934x(88)90128-9","article-title":"Letter imagery deficits in a case of pure apraxic agraphia","volume":"34","author":"Crary","year":"1988","journal-title":"Brain Lang."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/s0301-0082(00)00026-5","article-title":"Interictal spikes in focal epileptogenesis","volume":"63","author":"de Curtis","year":"2001","journal-title":"Prog. Neurobiol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2514","DOI":"10.1111\/j.1528-1167.2009.02249.x","article-title":"Reevaluating the mechanisms of focal ictogenesis: the role of low-voltage fast activity","volume":"50","author":"de Curtis","year":"2009","journal-title":"Epilepsia"},{"key":"ref10","first-page":"197","article-title":"Sur un cas de c\u00e9cit\u00e9 verbale avec agraphie, suivie d'autopsie","volume":"3","author":"Dejerine","year":"1891","journal-title":"Compt. Rend. S\u00e9ances M\u00e9m. Soc. Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.3233\/JAD-170392","article-title":"Adult-onset epilepsy in presymptomatic Alzheimer's disease: a retrospective study","volume":"60","author":"DiFrancesco","year":"2017","journal-title":"J Alzheimer's Dis"},{"key":"ref12","volume-title":"Epilepsy and other chronic convulsive diseases: Their causes, symptoms & treatment","author":"Gowers","year":"1885"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","article-title":"A clinical approach to diagnosis of autoimmune encephalitis","volume":"15","author":"Graus","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e1014","DOI":"10.1212\/NXI.0000000000001014","article-title":"Updated diagnostic criteria for paraneoplastic neurologic syndromes","volume":"8","author":"Graus","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/WNP.0000000000000806","article-title":"American clinical neurophysiology society's standardized critical care EEG terminology: 2021 version","volume":"38","author":"Hirsch","year":"2021","journal-title":"J. Clin. Neurophysiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1111\/epi.14016","article-title":"Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions","volume":"59","author":"Hirsch","year":"2018","journal-title":"Epilepsia"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.1111\/j.1528-1167.2009.02097.x","article-title":"Negative motor seizure arising from the negative motor area: is it ictal apraxia?","volume":"50","author":"Ikeda","year":"2009","journal-title":"Epilepsia"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/S0166-2236(84)80198-8","article-title":"Kanji vs kana: neuropsychological correlates of the Japanese writing system","volume":"7","author":"Iwata","year":"1984","journal-title":"Trends Neurosci."},{"key":"ref19","first-page":"16","article-title":"Localization and symptomatology of pure alexia, pure agraphia and alexia with agraphia","volume":"6","author":"Kawamura","year":"1990","journal-title":"Jpn. J. Neuropsychol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nm.4330","article-title":"Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease","volume":"23","author":"Lam","year":"2017","journal-title":"Nat. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1161\/STROKEAHA.122.041848","article-title":"NOTCH2NLC GGC repeat expansion in patients with vascular leukoencephalopathy","volume":"54","author":"Liao","year":"2023","journal-title":"Stroke"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1007\/BF00690510","article-title":"A light and electron microscopy study of an unusual widespread nuclear inclusion body disease. A possible residuum of an old herpesvirus infection","volume":"10","author":"Lindenberg","year":"1968","journal-title":"Acta Neuropathol."},{"key":"ref23","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"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"CD011922","DOI":"10.1002\/14651858.CD011922.pub3","article-title":"Treatment of epilepsy for people with Alzheimer's disease","volume":"12","author":"Liu","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"791","DOI":"10.2165\/00002512-200320110-00001","article-title":"Seizures in elderly patients with dementia: epidemiology and management","volume":"20","author":"Mendez","year":"2003","journal-title":"Drugs Aging"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"823","DOI":"10.3233\/JAD-131403","article-title":"The new qualitative scoring MMSE pentagon test (QSPT) as a valid screening tool between autopsy-confirmed dementia with Lewy bodies and Alzheimer's disease","volume":"39","author":"Mitolo","year":"2014","journal-title":"J Alzheimer's Dis"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1528-1167.2010.02909.x","article-title":"A perfect storm: converging paths of epilepsy and Alzheimer's dementia intersect in the hippocampal formation","volume":"52","author":"Noebels","year":"2011","journal-title":"Epilepsia"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1002\/ana.25586","article-title":"GGC repeat expansion of NOTCH2NLC in adult patients with leukoencephalopathy","volume":"86","author":"Okubo","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3389\/fnbeh.2020.00149","article-title":"Time-dependent impairment of fear conditioning and associated brain regions after pilocarpine-induced status epilepticus","volume":"14","author":"Qiu","year":"2020","journal-title":"Front. Behav. Neurosci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/0013-4694(91)90013-t","article-title":"Periodic lateralized epileptiform discharges with transitional rhythmic discharges: association with seizures","volume":"78","author":"Reiher","year":"1991","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"567","DOI":"10.5692\/clinicalneurol.51.567","article-title":"Lesion localization of non-aphasic alexia and agraphia","volume":"51","author":"Sakurai","year":"2011","journal-title":"Rinsho Shinkeigaku"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jns.2009.10.015","article-title":"Alexia and agraphia with lesions of the angular and supramarginal gyri: evidence for the disruption of sequential processing","volume":"288","author":"Sakurai","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1155\/2008\/393912","article-title":"Agraphia for kanji resulting from a left posterior middle temporal gyrus lesion","volume":"19","author":"Sakurai","year":"2008","journal-title":"Behav. Neurol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1155\/2007\/906417","article-title":"Parietal dysgraphia: characterization of abnormal writing stroke sequences, character formation and character recall","volume":"18","author":"Sakurai","year":"2007","journal-title":"Behav. Neurol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/s0022-510x(00)00363-4","article-title":"Alexia caused by a fusiform or posterior inferior temporal lesion","volume":"178","author":"Sakurai","year":"2000","journal-title":"J. Neurol. Sci."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1093\/brain\/awy022","article-title":"Cognition and dementia in older patients with epilepsy","volume":"141","author":"Sen","year":"2018","journal-title":"Brain"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1150496","DOI":"10.3389\/fneur.2023.1150496","article-title":"A practical approach to in-hospital management of new-onset refractory status epilepticus\/febrile infection related epilepsy syndrome","volume":"14","author":"Sheikh","year":"2023","journal-title":"Front. Neurol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"4501","DOI":"10.1007\/s10072-024-07492-x","article-title":"Encephalitis-like episodes with cortical edema and enhancement in patients with neuronal intranuclear inclusion disease","volume":"45","author":"Shen","year":"2024","journal-title":"Neurol. Sci."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ebcr.2019.01.007","article-title":"Non-convulsive status epilepticus associated with neuronal intranuclear inclusion disease: a case report and literature review","volume":"11","author":"Shindo","year":"2019","journal-title":"Epilepsy Behav. Case Rep."},{"key":"ref40","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":"ref41","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":"ref42","doi-asserted-by":"publisher","first-page":"1372","DOI":"10.1212\/WNL.0b013e3182166e13","article-title":"Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease","volume":"76","author":"Sone","year":"2011","journal-title":"Neurology"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1111\/ncn3.12016","article-title":"Neuronal intranuclear inclusion disease manifesting with new-onset epilepsy in the elderly","volume":"3","author":"Toyota","year":"2015","journal-title":"Neurol. Clin. Neurosci."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e23252","DOI":"10.1096\/fj.202300837R","article-title":"Acute inhibition of AMPA receptors by perampanel reduces amyloid beta-protein levels by suppressing beta-cleavage of APP in Alzheimer's disease models","volume":"37","author":"Ueda","year":"2023","journal-title":"FASEB J."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1016\/s1388-2457(03)00163-9","article-title":"Scalp-recorded slow EEG responses generated in response to hemodynamic changes in the human brain","volume":"114","author":"Vanhatalo","year":"2003","journal-title":"Clin. Neurophysiol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1159\/000106956","article-title":"Effect of seizures on progression of dementia of the Alzheimer type","volume":"6","author":"Volicer","year":"1995","journal-title":"Dementia"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/ana.24794","article-title":"Incidence and impact of subclinical epileptiform activity in Alzheimer's disease","volume":"80","author":"Vossel","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.neulet.2016.12.044","article-title":"Pathophysiology of status epilepticus","volume":"667","author":"Walker","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"425","DOI":"10.5692\/clinicalneurol.cn-001264","article-title":"Neuronal intranuclear inclusion disease with prolonged impaired consciousness and status epilepticus: a case report","volume":"59","author":"Yamanaka","year":"2019","journal-title":"Rinsho Shinkeigaku"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"841711","DOI":"10.3389\/fnagi.2022.841711","article-title":"Cognitive dysfunction in repeat expansion diseases: a review","volume":"14","author":"Zhang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1056261","DOI":"10.3389\/fnins.2022.1056261","article-title":"Clinical characteristics of two patients with neuronal intranuclear inclusion disease and literature review","volume":"16","author":"Zhao","year":"2022","journal-title":"Front. 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