Neuropathology最新文献

{"title":"An Autopsy Case With Fragile X-Associated Tremor/Ataxia Syndrome Presenting Intranuclear Inclusion Bodies Mainly in the Limbic System.","authors":"Ayako Shioya, Kazuhiro Ishii, Taiki Sato, Masayuki Noguchi, Akira Tamaoka, Yuko Saito","doi":"10.1111/neup.70053","DOIUrl":"10.1111/neup.70053","url":null,"abstract":"<p><p>Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder characterized by a late onset and slow progression caused by a premutation (55-200 CGG repeat) in the fragile X mental retardation (FMR1) gene. Here, we report the case of a Japanese patient with FXTAS which is the first case autopsied in Japan. The patient was a 74-year-old man with a family history of fragile X syndrome at the time of death. The clinical features included postural tremors, mild cognitive decline, and ataxia. Magnetic resonance imaging (MRI) showed a high-intensity lesion in the bilateral middle cerebellar peduncles and deep white matter around the ventricle on T2-weighted images. A gene analysis revealed that the patient had a pre-mutation of the CGG expansion (83 CGG repeats) in the FMR1 gene. Neuropathologically, ubiquitin- and p62-positive intranuclear inclusions were widely present, especially in the hippocampus. The middle cerebellar peduncle (MCP), where the \"MCP sign\" was seen on MRI, showed marked spongiosis with accompanied demyelination and axon loss, and a similar pathology was seen in the cerebral and cerebellar white matter. In an electron microscopy study, intranuclear inclusions were found to consist of a non-membrane-bound filamentous material. The clinical, MRI, and neuropathological findings were similar to those of neuronal intranuclear inclusion disease. Awareness of the disease is gradually increasing, and the number of autopsy cases is likely to increase, contributing to the elucidation of the pathology and development of treatments.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70053"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12993113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Attempt of a Staining Method to Clarify the Localization of Hematomas in Autopsy Cases of Intracerebral Hemorrhage: Application of Double Staining With Immunohistochemistry for Anti-Synaptophysin Antibody Using DAB-CoCl₂ and EA50.","authors":"Seiichi Hirata, Hitoshi Takahashi, Shigeki Takeda","doi":"10.1111/neup.70051","DOIUrl":"10.1111/neup.70051","url":null,"abstract":"<p><p>In order to prepare specimens to clarify the anatomical localization of intracerebral hematomas (ICHs), we examined 18 autopsy cases ranging from 1 day to 2.5 months after onset: Five cases of hypertensive ICH (two cases of putaminal hematoma, one case of thalamic hematoma, one case of mixed-type hematoma, and one case of cerebellar hematoma), two cases of subarachnoid hemorrhage with ICH, three cases of cerebral amyloid angiopathy-related hemorrhage, two cases of ICH associated with blood coagulation abnormalities, and six cases of brain death with ICH (brain death period: 10 h to 13 days). Paraffin blocks containing hematomas that have hardened and have poor formalin penetration can be easily sectioned at 6 μm thickness by using Histoheme, an ammonia-based softening reagent. By mounting the sections on MAS-coated glass slides or New Silan III-coated glass slides, we were able to minimize the peeling of hematomas from the slides. Conventional staining (Klüver-Barrera staining, Elastica-Masson Goldner staining) showed decreased staining of the brain tissue surrounding the hematoma due to the effects of edema, making the localization of the hematoma unclear. Synaptophysin (SYP) immunostaining was visualized with 3,3'-diaminobenzidine tetrahydrochloride (DAB)-CoCl₂ and double stained with eosin azur 50 (EA50) (DAB-CoCl₂ SYP + EA50). This method revealed gray matter as black and fresh to relatively recent hematoma as red, and clearly demonstrated the anatomical localization of the hematoma without any reduction in staining due to edema. In contrast, hematomas in cases more than 29 days after onset showed heterogeneous staining in red or green, and the boundary between the brain tissue and the hematoma was unclear. However, with double staining using DAB-CoCl₂ SYP and Masson Goldner staining, the hematoma stained dark red, and the boundary with the brain tissue was more clearly visible than with DAB-CoCl₂ SYP + EA50.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70051"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypertensive Bilateral Thalamic Hemorrhage: Distribution of Ruptured Blood Vessels and Hematoma and Considerations on the Mechanism of Vascular Rupture.","authors":"Shigeki Takeda, Hitoshi Takahashi, Seiichi Hirata, Teruo Miyakawa, Kazunori Yamazaki","doi":"10.1111/neup.70050","DOIUrl":"10.1111/neup.70050","url":null,"abstract":"<p><p>The ruptured blood vessels of a 57-year-old Japanese man who had died 5 days after bilateral hypertensive thalamic hemorrhage (HTH) were investigated by preparing 9 paraffin-embedded tissue blocks, all containing the hematomas. Each block was cut serially into 6-μm-thick sections. The first of every 18 sections was stained with Victoria blue and hematoxylin-eosin, the second with elastica-Goldner, and the third with phosphotungstic acid-hematoxylin. Several additional stainings, including immunostaining for α-smooth muscle actin and synaptophysin, were performed as necessary. In the large hematoma on the right, 18 cross-sections of ruptured blood vessels, comprising 12 arteries and 6 veins, were observed in the area supplied by the thalamoperforate arteries, thalamogeniculate arteries, and some of the posterior choroidal arteries. With an anteroposterior distribution, these ruptured vessels were observed in the middle third to posterior third of the thalamus, with arteries especially concentrated in the middle third. The small hematoma on the left was distributed mainly in the internal capsule. Two cross-sections of ruptured arteries, one of which had ruptured on the internal capsule side, were observed in the lateral part of the ventral posterolateral nucleus of the thalamus. In the hematomas, degeneration of medial smooth muscle cells due to arteriolosclerosis was observed in 14 cross-sections of ruptured arteries encountered, one of which showed a ruptured dissecting aneurysm. Microaneurysm or lipohyalinosis was not evident in any of them as well as the other non-ruptured arteries within the hematomas. The arteries surrounding the hematomas showed fibrinoid degeneration, lipohyalinosis, disruption of the internal elastic lamina, and degeneration and loss of smooth muscle cells in the media. Even though serial sections were examined at the rupture sites, no aneurysm-like structure was found. We concluded that HTH essentially arises from arterial wall fragility due to hypertension, and that aneurysm formation may not be essential.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70050"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary CNS Neuroblastoma, FOXR2-Activated: Clinicopathological Study of Two Cases With Immunohistochemical Characterization and Literature Review.","authors":"Sumanta Das, Sunita Ahlawat, Komal Agrawal, Salman Shaikh, Rakesh Kumar Gupta, Suman S Karanth, Sandeep Vaishya, Rana Patir, Mehar Chand Sharma","doi":"10.1111/neup.70049","DOIUrl":"10.1111/neup.70049","url":null,"abstract":"<p><p>Primary central nervous system (CNS) neuroblastoma, FOXR2-activated (CNS-NB-FOXR2), is a rare embryonal tumor characterized by neuroblastic differentiation and structural rearrangement of the FOXR2 gene. Previously grouped under CNS primitive neuroectodermal tumors (PNET), this entity has been reclassified based on genome-wide DNA methylation profiling. In this study, we present the detailed clinicopathological and immunohistochemical features of two pediatric cases diagnosed at our center. The first case involved a six-year-old with a left frontal mass; the second was a one-year-old with a large bifrontal lesion. Radiologically, both cases mimicked other embryonal tumors or high-grade gliomas. Histologically, tumors displayed small round blue cell morphology with neuroblastic features, including Homer-Wright rosettes and ganglionic differentiation. Immunohistochemistry demonstrated diffuse positivity for OLIG2, synaptophysin, and L1CAM, with negative expression for GFAP, EMA, and IDH1 R132H. FOXR2 showed nuclear positivity in both cases, supporting the diagnosis. Both cases exhibited diffuse L1CAM positivity-a rare finding with limited evidence in the existing literature. Although DNA methylation profiling could not be performed, the diagnosis was supported by characteristic morphology and immunohistochemistry profile. This report highlights key diagnostic features and potential mimics of CNS neuroblastoma, FOXR2-activated, and underscores the utility of immunohistochemistry in low-resource settings. Recognizing this entity is essential for accurate classification and appropriate therapeutic planning. Further studies are warranted to explore targeted therapies, including MEK inhibitors, which may hold promise based on emerging molecular data.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70049"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147290614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferrin Receptor 1 Overexpression Drives Proliferation and Ferroptosis Sensitivity in Glioblastoma: A Potential Therapeutic Vulnerability.","authors":"Minakshi M Behera, Suvendu Purkait, Amit Ghosh, Mukund N Sable, Rabi Narayan Sahu, Gaurav Chhabra","doi":"10.1111/neup.70056","DOIUrl":"10.1111/neup.70056","url":null,"abstract":"<p><p>Glioblastoma (GBM) is an aggressive CNS malignancy with extensive tumor growth and invasion. Highly proliferating cells require an increased intracellular iron concentration to maintain cell metabolism. We assessed the expression of transferrin receptor 1 (TFR1), the principal iron transporter, in GBM and ascertained its clinicopathological significance, implication in pathobiology, and therapeutic potential. Ninety-four cases of adult-type hemispheric GBM were included, along with 60 cases of IDH-mutant astrocytic and oligodendroglial tumors (grade 2-4) for comparison. The protein and mRNA expression were assessed by immunohistochemistry and qRT-PCR, respectively. We used U87MG and LN229 cell lines for in vitro analysis. TFR1 expression was significantly higher in GBM than in other IDH-mutant/lower-grade diffuse gliomas at mRNA and protein level. The non-tumor brain was negative on immunohistochemistry, and strong immunoreactivity was present only in GBM, indicating its diagnostic significance. SiRNA-mediated knockdown of TFR1 was associated with reduced cell survival, proliferation, migration, invasion, and increased apoptosis in vitro. Ferroptosis induction by RSL3/FIN56 led to increased TFR1 expression and ROS generation. The pro-ferroptotic effect of these drugs could be reversed by TFR1 knockdown. Hence, TFR1 appears to be crucially implicated in the cell survival and proliferation and ferroptosis sensitivity of malignant cells. Temozolomide in combination with siRNA-mediated gene silencing showed a significantly higher antitumor effect than the drug or silencing alone. This may be one of the important therapeutic vulnerabilities of GBM. High TFR1 expression was associated with shorter overall survival in all gliomas together but not in GBM separately.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70056"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of IDH-Mutant Astrocytoma Harboring an IDH2 R172_H173delinsSN Variant.","authors":"Thomas Auen, Jie Chen, Nicole Shonka, Sahara Cathcart","doi":"10.1111/neup.70048","DOIUrl":"10.1111/neup.70048","url":null,"abstract":"<p><p>IDH-mutant gliomas most commonly harbor the canonical IDH1 p.R132H mutation, followed by less common mutations involving IDH1 p.R132 or IDH2 p.R172 codons. We present a case of a 32-year-old male found to have a left temporal brain tumor with regional enhancement on brain MRI, for which he underwent resection. Histologic sections showed an infiltrating astrocytic tumor with increased mitotic activity and elevated Ki67 (MIB1) labeling. The tumor was negative for IDH1 p.R132H mutant protein expression with retained ATRX expression. 1p/19q was intact by FISH analysis, and next-generation sequencing identified a previously unreported IDH2 (p.R172_H173delinsSN) likely pathogenic variant. A diagnosis of astrocytoma, IDH-mutant, CNS WHO grade 3 was rendered. Subsequent tumor methylation profiling performed at the National Institutes of Health matched with high confidence to the class \"IDH glioma, subclass astrocytoma\" and confirmed lack of MGMT promoter hypermethylation. He received adjuvant concurrent radiation and temozolomide. Surveillance brain MRI at 32 months post resection demonstrated no evidence of interval tumor progression. We present a case of IDH-mutant astrocytoma with a somewhat atypical molecular presentation, including a previously uncharacterized IDH2 mutation, retained ATRX expression, and lack of MGMT promoter hypermethylation. Though it has not been biochemically or functionally validated, tumor methylation profiling is supportive of this previously uncharacterized IDH2 variant as tumorigenic.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70048"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12933006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of MGMT Methylation Status in Malignant Gliomas With and Without Therapeutic Intervention: Significance of Two-Dimensional Immunohistochemical Analysis and Evaluation of Recurrent Specimens.","authors":"Kenichiro Asano, Toshio Fumoto, Akihisa Kamataki, Akira Kurose","doi":"10.1111/neup.70047","DOIUrl":"10.1111/neup.70047","url":null,"abstract":"<p><p>We investigated changes in O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in 21 patients with malignant gliomas who underwent two or more surgeries. Tumor specimens from multiple surgeries were analyzed using methylation-specific polymerase chain reaction (MS-PCR) and immunohistochemistry (IHC) for MGMT. Patients were divided into two groups: Group A (13 recurrent cases with therapeutic intervention) and Group B (8 cases of recurrence without therapeutic intervention or planned two-stage surgeries). MGMT methylation status was compared between initial and recurrent specimens, and in Group A, progression-free survival (PFS) and overall survival (OS) were analyzed according to MGMT methylation status at both initial and recurrent surgeries. By MS-PCR, changes in Group A were as follows: methylated to unmethylated in 23.1%, unchanged in 61.5%, and unmethylated to methylated in 15.4%. In Group B, changes were methylated to unmethylated in 12.5%, unchanged in 87.5%, and no cases of unmethylated to methylated. The difference in proportions between the groups was not significant (p = 0.13). By IHC, changes in Group A were methylated to unmethylated in 7.7%, unchanged in 53.8%, and unmethylated to methylated in 38.5%. In Group B, changes were methylated to unmethylated in 12.5%, unchanged in 87.5%, and no cases of unmethylated to methylated. The difference in proportions between the groups was significant (p = 0.034). Excluding one grade 3 case, in the 12 patients of Group A, median OS from treatment initiation differed by MGMT status assessed by immunohistochemistry in recurrent specimens (26.5 vs. 90.0 months, p = 0.043). These findings suggest that immunohistochemical assessment may capture spatial heterogeneity of MGMT status that is not readily detected by MS-PCR, and that therapeutic intervention may be associated with dynamic changes in MGMT methylation status. Furthermore, MGMT status assessed by IHC in recurrent specimens was associated with overall survival, indicating its potential prognostic relevance.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70047"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T Cells Inhibit Hippocampal Regeneration in Mice Following Trimethyltin-Induced Neurodegeneration.","authors":"Masashi Sakurai, Nao Aoki, Mika Sasamoto, Hinata Ariyoshi, Yusuke Sakai, Kyoko Yoshizaki, Masahiro Morimoto","doi":"10.1111/neup.70054","DOIUrl":"10.1111/neup.70054","url":null,"abstract":"<p><p>Although the regenerative capacity of the mammalian brain is quite weak, internal neural stem/progenitor cells (NSPCs) in the brain can provide new neurons into the brain lesions. Leukocytes, particularly T cells, infiltrate injured brain tissue and participate in immune reactions and have a large impact on the progress of the lesion. However, the effect of T cells on the regeneration of brain tissue remains unclear. Trimethyltin (TMT) is an organotin that has selective neurotoxicity on granule neurons in the hippocampal dentate gyrus. TMT-induced hippocampal lesion is mostly regenerated because adjacent NSPCs can provide new granule neurons. In this study, using TMT-injected mice as a model of brain tissue regeneration, the influence of T cells on hippocampal tissue regeneration was investigated. When TMT was injected into nude mice lacking T cells, they exhibited shortened immobility time in the tail suspension test, indicating improved functional outcomes. Immunohistochemical analysis revealed improved granule neuron replenishment and enhanced survival and differentiation of new neurons in nude mice. Microglial reaction characterized by phagocytosis and astrocytic reaction with brain-derived neurotrophic factor (BDNF) expression were enhanced in nude mice. Hippocampal tissue regeneration was impaired when nude mice were repopulated with total lymphocytes or with CD4- or CD8-positive cells. Repopulations of T cells altered microglial reactions; however, changes in astrocytes were not reproduced. These results suggest that both helper and cytotoxic T cells inhibit hippocampal tissue regeneration by preventing neuronal replenishment. T cells also affect lesion clearance by microglia and astrocytic BDNF expression; however, their effect is stronger on microglia. These findings provide novel insights into the immune regulation of brain tissue regeneration.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70054"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Virus Detection in Olfactory Neuroblastomas Using Targeted Enrichment NGS.","authors":"Maria K Jauhiainen, Outi I Mielonen, Aaro Haapaniemi, Maria Söderlund-Venermo, Jaana Hagström, Maria F Perdomo, Saku T Sinkkonen, Antti A Mäkitie","doi":"10.1111/neup.70055","DOIUrl":"10.1111/neup.70055","url":null,"abstract":"<p><p>A variety of malignancies can be found in the sinonasal tract including the nasal cavity, paranasal sinuses, and skull base. Many of these are attributed to viruses, for example, carcinomas with the presence of transcriptionally active high-risk human papillomavirus, as well as Epstein-Barr virus associated malignant lymphoepithelial carcinoma and haematolymphoid neoplasias. Olfactory neuroblastoma (ONB) is a rare malignant tumor of the olfactory fossa with an unknown etiology. We present the first comprehensive virus study of ONB. By targeted next-generation sequencing for 41 DNA viruses, we investigated the presence of papillomaviruses, herpesviruses, polyomaviruses, and parvoviruses, among others, in 12 ONBs. In addition, herpesvirus presence was evaluated by qPCR. Low-risk HPV6 was detected in one sample. Human endogenous retroviruses were positive in all samples, supporting successful library preparation and sequencing, considered as an internal quality control. No other virus findings were observed. The present broad-scale virus study did not reveal abundant presence of viral DNA in ONB suggesting a limited viral role in its etiology. Nevertheless, our cohort exhibited a finding of low-risk HPV, which has been associated with increased risk of cancer progression of inverted sinonasal papilloma in the same anatomic site advocating for further research. Trial Registration: §31/07.03.2019.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70055"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13011989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Autopsy Case of a Patient With Corticobasal Degeneration and a History of Acute Restlessness and Stupor.","authors":"Saori Shimizu, Yuji Saitoh, Masashi Mizutani, Terunori Sano, Naoko Satake, Noriko Sato, Masaki Takao","doi":"10.1111/neup.70057","DOIUrl":"10.1111/neup.70057","url":null,"abstract":"<p><p>Some patients with corticobasal degeneration (CBD) present with neuropsychiatric symptoms, including frontal lobe symptoms. However, stupor is rarely reported. Here, we report a case of acute restlessness at onset, which was clinically diagnosed as frontotemporal dementia (FTD) but was found to be CBD at autopsy. A 71-year-old woman with COVID-19 presented to our hospital. At the age of 62, she had suddenly become restless and confused without any preceding motor or psychiatric symptoms. She was treated with psychotropic drugs but subsequently entered stupor and was admitted to a psychiatric hospital. Magnetic resonance imaging showed mild atrophy of the frontal lobe. Single-photon emission computed tomography showed decreased blood flow in the frontal lobe, and the patient was clinically diagnosed with FTD. At the age of 71, she was transferred to our hospital from a psychiatric hospital for COVID-19 treatment. Upon transfer to our hospital, the patient presented with akinetic mutism. The patient died of respiratory failure 10 days after the onset of COVID-19. Immunostaining with AT8 and RD4 antibodies revealed astrocytic plaques, pretangles, coiled bodies, and threads, predominantly in the frontal lobes and basal ganglia. Other pathologies include accumulation of pTDP43 in the basal ganglia, thalamus, and frontal lobes. Argyrophilic grains were observed in the amygdala and the hippocampus, which corresponded to Saito stage 2. Other neurodegenerative proteins, such as amyloid β or α-synuclein, were not observed. The patient was pathologically diagnosed with CBD. We present a rare autopsy case involving a patient with CBD who presented with acute psychiatric symptoms and stupor. The psychiatric symptoms were characterized by agitation and fear-related behavior, which differ from the disinhibition and antisocial behavior typically associated with frontal lobe symptoms. Further autopsies are needed to examine the extent of tau pathology spread and accumulation to better understand the psychiatric symptoms of CBD.</p>","PeriodicalId":19204,"journal":{"name":"Neuropathology","volume":"46 2","pages":"e70057"},"PeriodicalIF":1.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}