Journal of Neuropathology and Experimental Neurology最新文献_第9页

Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death. 海马齿状回发育不良与意外猝死的风险

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae121

Douglas C Miller, Kristen M Scheitler, Jeffery Holloway, C Christopher Stacy

{"title":"Hippocampal dentate gyrus dysplasia and the risk of sudden unexpected death.","authors":"Douglas C Miller, Kristen M Scheitler, Jeffery Holloway, C Christopher Stacy","doi":"10.1093/jnen/nlae121","DOIUrl":"10.1093/jnen/nlae121","url":null,"abstract":"Hippocampal dentate gyral dysplasia is well-described in temporal lobe epilepsy and may be a risk factor for sudden, unexpected death in several populations: infants (sudden infant death syndrome [SIDS], sudden unexpected infant death [SUID]), toddlers (sudden unexpected death of a child [SUDC]), and epileptics (sudden unexpected death in epilepsy [SUDEP]). We examined reports and histopathological slides from autopsies performed at our institution from 2008 through 2016 to determine whether the presence or absence of any of the described forms of such dysplasias (duplications, hyperconvolutions, and granule cell dispersion, including bilamination), correlated with the causes of death. From well over 4000 autopsies, we identified 949 autopsies with a neuropathology examination by a neuropathologist. Of these, 205 cases (21.6%) had 1 or more of the described abnormalities of 1 or both dentate gyri; 87 (42.4%) of the individuals in this group of 205 autopsies had died suddenly and unexpectedly, including 29/90 (32.2%) cases of SUDEP, 17/31 (54.8%) cases of SUDC, and 51/104 (49.0%) cases of infants with SIDS or SUID. We conclude that these changes are readily recognizable by experienced neuropathologists and that because they are overrepresented in an autopsy population that died suddenly and unexpectedly, they may represent a risk factor for such outcomes.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"126-131"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A machine learning approach to automate microinfarct and microhemorrhage screening in hematoxylin and eosin-stained human brain tissues. 机器学习方法在苏木精和伊红染色的人脑组织中自动筛选微梗死和微出血。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae120

Luca Cerny Oliveira, Joohi Chauhan, Ajinkya Chaudhari, Sen-Ching S Cheung, Viharkumar Patel, Amparo C Villablanca, Lee-Way Jin, Charles DeCarli, Chen-Nee Chuah, Brittany N Dugger

{"title":"A machine learning approach to automate microinfarct and microhemorrhage screening in hematoxylin and eosin-stained human brain tissues.","authors":"Luca Cerny Oliveira, Joohi Chauhan, Ajinkya Chaudhari, Sen-Ching S Cheung, Viharkumar Patel, Amparo C Villablanca, Lee-Way Jin, Charles DeCarli, Chen-Nee Chuah, Brittany N Dugger","doi":"10.1093/jnen/nlae120","DOIUrl":"10.1093/jnen/nlae120","url":null,"abstract":"Microinfarcts and microhemorrhages are characteristic lesions of cerebrovascular disease. Although multiple studies have been published, there is no one universal standard criteria for the neuropathological assessment of cerebrovascular disease. In this study, we propose a novel application of machine learning in the automated screening of microinfarcts and microhemorrhages. Utilizing whole slide images (WSIs) from postmortem human brain samples, we adapted a patch-based pipeline with convolutional neural networks. Our cohort consisted of 22 cases from the University of California Davis Alzheimer's Disease Research Center brain bank with hematoxylin and eosin-stained formalin-fixed, paraffin-embedded sections across 3 anatomical areas: frontal, parietal, and occipital lobes (40 WSIs with microinfarcts and/or microhemorrhages, 26 without). We propose a multiple field-of-view prediction step to mitigate false positives. We report screening performance (ie, the ability to distinguish microinfarct/microhemorrhage-positive from microinfarct/microhemorrhage-negative WSIs), and detection performance (ie, the ability to localize the affected regions within a WSI). Our proposed approach improved detection precision and screening accuracy by reducing false positives thereby achieving 100% screening accuracy. Although this sample size is small, this pipeline provides a proof-of-concept for high efficacy in screening for characteristic brain changes of cerebrovascular disease to aid in screening of microinfarcts/microhemorrhages at the WSI level.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"114-125"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci. 基于甲基化数量性状位点的未知原发癌深度学习分类器。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-02-01 DOI: 10.1093/jnen/nlae123

Adam Walker, Camila S Fang, Chanel Schroff, Jonathan Serrano, Varshini Vasudevaraja, Yiying Yang, Sarra Belakhoua, Arline Faustin, Christopher M William, David Zagzag, Sarah Chiang, Andres Martin Acosta, Misha Movahed-Ezazi, Kyung Park, Andre L Moreira, Farbod Darvishian, Kristyn Galbraith, Matija Snuderl

{"title":"Deep learning-based classifier for carcinoma of unknown primary using methylation quantitative trait loci.","authors":"Adam Walker, Camila S Fang, Chanel Schroff, Jonathan Serrano, Varshini Vasudevaraja, Yiying Yang, Sarra Belakhoua, Arline Faustin, Christopher M William, David Zagzag, Sarah Chiang, Andres Martin Acosta, Misha Movahed-Ezazi, Kyung Park, Andre L Moreira, Farbod Darvishian, Kristyn Galbraith, Matija Snuderl","doi":"10.1093/jnen/nlae123","DOIUrl":"10.1093/jnen/nlae123","url":null,"abstract":"Cancer of unknown primary (CUP) constitutes between 2% and 5% of human malignancies and is among the most common causes of cancer death in the United States. Brain metastases are often the first clinical presentation of CUP; despite extensive pathological and imaging studies, 20%-45% of CUP are never assigned a primary site. DNA methylation array profiling is a reliable method for tumor classification but tumor-type-specific classifier development requires many reference samples. This is difficult to accomplish for CUP as many cases are never assigned a specific diagnosis. Recent studies identified subsets of methylation quantitative trait loci (mQTLs) unique to specific organs, which could help increase classifier accuracy while requiring fewer samples. We performed a retrospective genome-wide methylation analysis of 759 carcinoma samples from formalin-fixed paraffin-embedded tissue samples using Illumina EPIC array. Utilizing mQTL specific for breast, lung, ovarian/gynecologic, colon, kidney, or testis (BLOCKT) (185k total probes), we developed a deep learning-based methylation classifier that achieved 93.12% average accuracy and 93.04% average F1-score across a 10-fold validation for BLOCKT organs. Our findings indicate that our organ-based DNA methylation classifier can assist pathologists in identifying the site of origin, providing oncologists insight on a diagnosis to administer appropriate therapy, improving patient outcomes.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"147-154"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11747144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New criteria to predict LATE-NC in the clinical setting: Probable/Possible LATE and LANS. 在临床环境中预测 LATE-NC 的新标准：可能/可能的 LATE 和 LANS。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-01-01 DOI: 10.1093/jnen/nlae113

Peter T Nelson

引用次数: 0

Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature. 齿状回局灶性颗粒细胞淤积症--在人类各年龄段的发病率及文献综述。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-01-01 DOI: 10.1093/jnen/nlae109

Rita Machaalani, Michael Rodriguez, Arunnjah Vivekanandarajah

{"title":"Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature.","authors":"Rita Machaalani, Michael Rodriguez, Arunnjah Vivekanandarajah","doi":"10.1093/jnen/nlae109","DOIUrl":"10.1093/jnen/nlae109","url":null,"abstract":"The prevalence of focal granule cell bilamination (FGCB) in the hippocampal dentate gyrus varies from 0% to 44%, depending on age and study population. FGCB is commonly thought to be a specific feature of temporal lobe epilepsy (TLE) but its prevalence in cases without TLE is unclear. Using formalin-fixed, paraffin-embedded hippocampal sections, this retrospective postmortem study evaluated the prevalence of FGCB and other granule cell pathologies in infants (1-12 months of age, n = 16), children (4-10 years, n = 6), and adults (28-91 years, n = 15) with no known history of epilepsy or seizures. We found FGCB in 6% of infants, 17% of children, and 27% of adults. We then compared our findings with those in published reports of sudden unexpected deaths in infancy (SUDI), childhood (SUDC), and epilepsy (SUDEP), and in surgical specimens from patients with TLE. The reported prevalence of FGCB in those studies was 6%-19% in infants, 0%-17% in children, and 0%-2% in adults in non-seizure-related cases and 9% in children and 3%-25% in adults with TLE. Our findings highlight the presence of FGCB in individuals with no known epilepsy/seizure-related histories in proportions similar to those reported in individuals with clinical epilepsy.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"22-33"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multidimensional analysis of matched primary and recurrent glioblastoma identifies contributors to tumor recurrence influencing time to relapse. 对匹配的原发性和复发性胶质母细胞瘤进行多维分析，找出影响复发时间的肿瘤复发因素。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-01-01 DOI: 10.1093/jnen/nlae108

Tala Shekarian, Marie-Françoise Ritz, Sabrina Hogan, Tomás A Martins, Philip Schmassmann, Alexandra Gerber, Julien Roux, Deniz Kaymak, Célia Durano, Bettina Burger, Matthias Matter, Gregor Hutter

{"title":"Multidimensional analysis of matched primary and recurrent glioblastoma identifies contributors to tumor recurrence influencing time to relapse.","authors":"Tala Shekarian, Marie-Françoise Ritz, Sabrina Hogan, Tomás A Martins, Philip Schmassmann, Alexandra Gerber, Julien Roux, Deniz Kaymak, Célia Durano, Bettina Burger, Matthias Matter, Gregor Hutter","doi":"10.1093/jnen/nlae108","DOIUrl":"10.1093/jnen/nlae108","url":null,"abstract":"Glioblastoma (GBM) is a lethal brain tumor without effective treatment options. This study aimed to characterize longitudinal tumor changes in order to find potentially actionable targets to prevent GBM relapse. We extracted RNA and proteins from fresh frozen tumor samples from patient-matched IDHwt WHO grade 4 primary (pGBM) and recurrent (rGBM) tumors for transcriptomics and proteomics analysis. A tissue microarray containing paired tumor samples was processed for spatial transcriptomics analysis. Differentially expressed genes and proteins between pGBM and rGBM were involved in synapse development and myelination. By categorizing patients into short (STTR) and long (LTTR) time-to-lapse, we identified genes/proteins whose expression levels positively or negatively correlated with TTR. In rGBM, expressions of Fcγ receptors (FCGRs) and complement system genes were negatively correlated with TTR, whereas expression of genes involved in DNA methylation was positively correlated with TTR. Spatial transcriptomics of the tumor cells showed enrichment of oligodendrocytes in rGBM. Besides, we observed changes in the myeloid compartment such as a switch from quiescent to activated microglia and an enrichment in B and T cells in rGBM with STTR. Our results uncover a role for activated microglia/macrophages in GBM recurrence and suggest that interfering with these cells may hinder GBM relapse.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"45-58"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A case of a (not so) diffuse leptomeningeal glioneuronal tumor with an unusual clinical history. 一例临床病史不寻常的弥漫性脑膜胶质细胞瘤。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2025-01-01 DOI: 10.1093/jnen/nlae087

Christina Abi Faraj, Ian E McCutcheon, Donald F Schomer, Kenneth Aldape, Martha Quezado, Zied Abdullaev, Maria A Gubbiotti

引用次数: 0

Cytoplasmic vacuolization and ectopic formation of perineuronal nets are characteristic pathologies of cytomegalic neurons in tuberous sclerosis. 细胞质空泡化和神经元周围网的异位形成是结节性硬化症中巨细胞神经元的特征性病变。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-12-01 DOI: 10.1093/jnen/nlae079

Alexander A Sosunov, Guy McKhann Ii, Guomei Tang, James E Goldman

{"title":"Cytoplasmic vacuolization and ectopic formation of perineuronal nets are characteristic pathologies of cytomegalic neurons in tuberous sclerosis.","authors":"Alexander A Sosunov, Guy McKhann Ii, Guomei Tang, James E Goldman","doi":"10.1093/jnen/nlae079","DOIUrl":"10.1093/jnen/nlae079","url":null,"abstract":"Cytomegalic neurons, characterized by increased size and a hyperactive mechanistic target of rapamycin complex 1 (mTORC1), are pathognomonic for tuberous sclerosis complex (TSC). To model these neurons, we recently generated a murine Tsc1 conditional knockout model in which Tsc1 deletion in late embryonic radial glia results in neuronal hypertrophy of a subset of isocortical pyramidal neurons. In the current study, we compared the cellular pathology of these cytomegalic neurons to those of the enlarged neurons in human cortical tubers. Neurons from the mice showed unique features, such as cytoplasmic vacuoles associated with Golgi complexes and the ectopic formation of perineuronal nets (PNNs), a feature of inhibitory neurons, rarely present in excitatory cortical neurons. The membranes of these vacuoles were enriched for the plasma membrane proteins CD44, KCC2, and Na+/K+ ATPase, suggesting deficits in Golgi membrane trafficking. These aberrant features in the mouse appeared only after the onset of seizures, probably due to the prolonged seizure activity in the context of constitutive mTORC1 activation. Similar PNNs and cytoplasmic vacuoles were present in the cytomegalic neurons of human cortical tubers. Our findings reveal novel pathological features of Golgi complexes and PNNs in the cytomegalic neurons in TSC.","PeriodicalId":16682,"journal":{"name":"Journal of Neuropathology and Experimental Neurology","volume":" ","pages":"1047-1059"},"PeriodicalIF":3.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CTDSP2::GLI1 fusion in glioblastoma: A diagnostic challenge through tumor heterogeneity. 胶质母细胞瘤中的 CTDSP2::GLI1 融合：肿瘤异质性带来的诊断挑战。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-12-01 DOI: 10.1093/jnen/nlae073

Manita Kanathanavanich, Shunsuke Koga, Sara Lynn Stone, Jacquelyn Roth, Zied Abdullaev, Donald M O'Rourke, Stephen Bagley, Robert M Kurtz, Michelle Alonso-Basanta, Kenneth Aldape, MacLean P Nasrallah, Guang Yang

引用次数: 0

Accumulation of TMEM106B C-terminal fragments in Niemann-Pick type C disease. 尼曼-皮克型 C 疾病中 TMEM106B C 端片段的累积。

IF 3.2 3区医学

Journal of Neuropathology and Experimental Neurology Pub Date : 2024-11-01 DOI: 10.1093/jnen/nlae072

Ruth D Azaria, Sean P Ferris, Randy S Tashjian, Jolien Perneel, Marleen Van den Broeck, Ian R Mackenzie, Elizabeth Berry-Kravis, Rosa Rademakers, Andrew P Lieberman

引用次数: 0