{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:06:53Z","timestamp":1777565213702,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,7,4]],"date-time":"2021-07-04T00:00:00Z","timestamp":1625356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease; transactivation response DNA\u2010binding protein of 43\u2009kDa (TDP\u201043) and iron accumulation are supposed to play a crucial role in the pathomechanism of the disease. Here, we report an unusual case of a patient with ALS who presented with speech apraxia as an initial symptom and upper motor neuron deficiencies. In the early clinical stages, single\u2010photon emission computed tomography visualized focal hypoperfusion of the right frontal operculum, and magnetic resonance imaging identified a hypointense area along the frontal lobe on T2\u2010weighted images. Neuropathological examination revealed that neuronophagia of Betz cells, gliosis, appearance of phosphorylated TDP\u201043 (p\u2010TDP\u201043)\u2010positive glial and neuronal inclusions, and prominent iron accumulation were frequently visible in the precentral gyrus. TDP\u201043 pathology and focal iron accumulation were also visible in the frontal operculum, but only a mild neuronal loss and a few p\u2010TDP\u201043\u2010positive neuronal and glial inclusions were found in the hypoglossal nucleus of the medulla oblongata and anterior horn of the spinal cord. Immunoblot analysis revealed an atypical band pattern for ALS. In our case, abnormal TDP\u201043 and iron accumulation might possibly have caused neurodegeneration of the frontal operculum, in tandem or independently; it might then have spread into the primary motor area. Our results suggest a causative association between TDP\u201043 and iron accumulation in the pathomechanisms of ALS presenting with upper motor neuron signs.<\/jats:p>","DOI":"10.1111\/neup.12763","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T02:51:58Z","timestamp":1625453518000},"page":"324-331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Amyotrophic lateral sclerosis with speech apraxia, predominant upper motor neuron signs, and prominent iron accumulation in the frontal operculum and precentral gyrus"],"prefix":"10.1111","volume":"41","author":[{"given":"Tomoki T.","family":"Mitani","sequence":"first","affiliation":[{"name":"Department of Neurology Osaka University Graduate School of Medicine  Suita 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