# Case Report: Distinctive features of cognitive dysfunction and amelioration by antiseizure medication in neuronal intranuclear inclusion disease **Authors:** Hiroya Ohara, Masami Yamanaka, Fumi Okada, Aiko Okazaki, Marisse Dy Dizon, Ajay Elangovan, Harysh Winster Suresh Babu, Mahalaxmi Iyer, Balachandar Vellingiri, Masako Kinoshita PMC · DOI: 10.3389/fnins.2026.1734078 · Frontiers in Neuroscience · 2026-02-04 ## TL;DR This case report explores how cognitive dysfunction in a rare neurodegenerative disease called NIID can be improved with antiseizure medication and how it differs from Alzheimer's disease. ## Contribution The study identifies distinctive cognitive features and treatment response in NIID that differentiate it from Alzheimer’s disease. ## Key findings - Cognitive dysfunction in NIID showed improvement with antiseizure medication. - Pentagon drawing and handwriting of morphograms and syllabograms can help distinguish NIID from Alzheimer’s disease. - Nonconvulsive status epilepticus may accelerate cognitive decline in NIID. ## Abstract 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’s disease (AD). A 63-year-old man presented with transient consciousness disturbance (Day 1). For previous 6 years 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. 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. 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. ## Linked entities - **Diseases:** Neuronal intranuclear inclusion disease (MONDO:0011327), Alzheimer’s disease (MONDO:0004975) ## Full-text entities - **Genes:** FANCB (FA complementation group B) [NCBI Gene 2187] {aka FA2, FAAP90, FAAP95, FAB, FACB}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120] {aka ASM, ASM1, BWS, D11S813E, GMRSP, LINC00008}, NUP62 (nucleoporin 62) [NCBI Gene 23636] {aka IBSN, SNDI, p62}, NOTCH2 (notch receptor 2) [NCBI Gene 4853] {aka AGS2, HJCYS, hN2} - **Diseases:** stroke (MESH:D020521), confusion (MESH:D003221), nausea (MESH:D009325), autoimmune diseases (MESH:D001327), brain edema (MESH:D001929), apraxia (MESH:D001072), leukoencephalopathy (MESH:D056784), encephalitic (MESH:D010301), agraphia (MESH:D000381), vomiting (MESH:D014839), NCSE (MESH:D013226), Paraneoplastic neuronal syndrome (MESH:D010257), fever (MESH:D005334), neurological disorders (MESH:D009461), hemi-spatial neglect (MESH:C565524), dyscalculia (MESH:D060705), convulsion (MESH:D012640), femoral bone fracture (MESH:D050723), autoimmune encephalitis (MESH:D020274), hyperlipidemia (MESH:D006949), neurodegenerative disease (MESH:D019636), alexia (MESH:D004410), headache (MESH:D006261), edema of (MESH:D004487), DLB (MESH:D020961), atrophy (MESH:D001284), diabetes mellitus (MESH:D003920), malignant tumors (MESH:D009369), psychiatric (MESH:D001523), loss of consciousness (MESH:D014474), AD (MESH:D000544), NIID (MESH:C537395), amyloid (MESH:C000718787), dementia (MESH:D003704), cortical damage (MESH:D054220), epileptiform discharge (MESH:D019522), executive dysfunction (MESH:D006331), visuospatial dysfunction (MESH:D000377), disturbance of visuospatial perception (MESH:D012001), neuronal death (MESH:D009410), disturbance of spatial construction (MESH:D008569), Cognitive impairment (MESH:D003072), damage of the occipital cortex (MESH:D001480), postural tremor (MESH:D014202), retrograde amnesia (MESH:D000648), subcortical lesions (MESH:D015140), consciousness disturbance (MESH:D003244), hypertension (MESH:D006973), brain abnormalities (MESH:D001927), gliosis (MESH:D005911), Epileptic seizures (MESH:D004827), cerebellar ataxia (MESH:D002524), aphasia (MESH:D001037), impaired visuospatial ability (OMIM:313000), right hemisphere dysfunction (MESH:D002544), encephalitis (MESH:D004660) - **Chemicals:** B12 (MESH:C034730), ammonia (MESH:D000641), steroid (MESH:D013256), gadolinium (MESH:D005682), folate (MESH:D005492), levetiracetam (MESH:D000077287), glucose (MESH:D005947), alcohol (MESH:D000438), H&E (MESH:D006371), ASM (-), FDG (MESH:D019788), vitamin B1 (MESH:D013831) - **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12913443/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12913443/full.md ## References 51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12913443/full.md --- Source: https://tomesphere.com/paper/PMC12913443