Brain Pathology最新文献

{"title":"Society News","authors":"","doi":"10.1111/bpa.13093","DOIUrl":"https://doi.org/10.1111/bpa.13093","url":null,"abstract":"","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13093","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50124175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Honing in on magnetic resonance imaging predictors of multiple sclerosis pathology","authors":"Klaus Schmierer","doi":"10.1111/bpa.13209","DOIUrl":"10.1111/bpa.13209","url":null,"abstract":"<p>As our understanding of the mechanisms leading to tissue damage and repair in multiple sclerosis (MS) evolves, so does our desire to detect and monitor their structural and functional correlates in people with this chronic disease during life. Given the heterogeneous nature of the tissue injury in MS, in terms of severity and timing, this is of significant interest for (i) the management of people with MS (pwMS) in clinical practice and (ii) the selection of outcomes in clinical trials.</p><p>However, very few biopsies are being undertaken to confirm a tissue diagnosis of MS or to assess specific lesion stages, and despite significant progress in the field of fluid biomarkers [<span>1</span>], magnetic resonance imaging (MRI) retains its pivotal role translating histological findings into MRI signals that can be measured repeatedly, over a virtually infinite number of time points.</p><p>The desire to directly correlate changes identified using MRI with their microscopic substrate in MS is not new [<span>2</span>]. However, the technology of both histology and MRI has significantly evolved including advances in co-registration of the two modalities—MRI and histology—from mere visual like-for-like matching, through the use of a stereotaxic frame system [<span>3</span>] to current state-of-the-art 3D printing technology using whole brain cutting boxes [<span>4</span>].</p><p>In this issue of Brain Pathology two international teams are taking us another step towards non-invasively dissecting specific microstructural features in post mortem MS brain, ultimately serving the prospect that the severity of lesions, nature of inflammation and, in particular, the degree of (re-) myelination can be inferred from quantitative MRI (qMRI) indices.</p><p>Galbusera and co-workers focus on patterns of qMRI measures to (i) try and distinguish histological lesion types, and (ii) explore the relationship between those qMRI measures and quantitative histological indices of myelin, axons, and astrogliosis [<span>5</span>]. For this purpose, they employed a total of six different qMRI techniques including proton density-weighted, quantitative T1 (qT1), magnetisation transfer ratio (MTR), myelin water fraction (MWF), susceptibility mapping (QSM), and diffusion-derived metrics, such as fractional anisotropy (FA) and radial diffusivity (RD), on three whole post mortem brains from pwMS who had passed away with a relapsing (2) and secondary progressive (1) clinical phenotype, respectively. After scanning, regions of interest were defined on 3D echo-planar MRI, which then guided tissue block dissection for immuno-/histochemistry. Lesion classification included active, chronic-active, inactive and remyelinated.</p><p>QSM, qT1 and—with some reservation due confounding by crossing fibres—RD came out on top distinguishing (i) active and (ii) remyelinated lesions versus the other lesion types. None of the MRI techniques employed was effectively separating inactive from chronic ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid metabolism and oxidative stress in patients with Alzheimer's disease and amnestic mild cognitive impairment","authors":"Yuting Nie,&nbsp;Changbiao Chu,&nbsp;Qi Qin,&nbsp;Huixin Shen,&nbsp;Lulu Wen,&nbsp;Yi Tang,&nbsp;Miao Qu","doi":"10.1111/bpa.13202","DOIUrl":"10.1111/bpa.13202","url":null,"abstract":"<p>Lipid metabolism and oxidative stress are key mechanisms in Alzheimer's disease (AD). The link between plasma lipid metabolites and oxidative stress in AD patients is poorly understood. This study was to identify markers that distinguish AD and amnestic mild cognitive impairment (aMCI) from NC, and to reveal potential links between lipid metabolites and oxidative stress. We performed non-targeted lipid metabolism analysis of plasma from patients with AD, aMCI, and NC using LC–MS/MS. The plasma malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) levels were assessed. We found significant differences in lipid metabolism between patients with AD and aMCI compared to those in NC. AD severity is associated with lipid metabolites, especially TG (18:0_16:0_18:0) + NH4, TG (18:0_16:0_16:0) + NH4, LPC(16:1e)-CH3, and PE (20:0_20:4)-H. SPH (d16:0) + H, SPH (d18:1) + H, and SPH (d18:0) + H were high-performance markers to distinguish AD and aMCI from NC. The AUC of three SPHs combined to predict AD was 0.990, with specificity and sensitivity as 0.949 and 1, respectively; the AUC of three SPHs combined to predict aMCI was 0.934, with specificity and sensitivity as 0.900, 0.981, respectively. Plasma MDA concentrations were higher in the AD group than in the NC group (<i>p</i> = 0.003), whereas plasma SOD levels were lower in the AD (<i>p</i> &lt; 0.001) and aMCI (<i>p =</i> 0.045) groups than in NC, and GSH-Px activity were higher in the AD group than in the aMCI group (<i>p</i> = 0.007). In addition, lipid metabolites and oxidative stress are widely associated. In conclusion, this study distinguished serum lipid metabolism in AD, aMCI, and NC subjects, highlighting that the three SPHs can distinguish AD and aMCI from NC. Additionally, AD patients showed elevated oxidative stress, and there are complex interactions between lipid metabolites and oxidative stress.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10067178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased expression of human antiviral protein MxA in FUS proteinopathy in amyotrophic lateral sclerosis","authors":"Hiroyuki Honda,&nbsp;Kaoru Yagita,&nbsp;Hajime Arahata,&nbsp;Hideomi Hamasaki,&nbsp;Hideko Noguchi,&nbsp;Sachiko Koyama,&nbsp;Naokazu Sasagasako","doi":"10.1111/bpa.13191","DOIUrl":"10.1111/bpa.13191","url":null,"abstract":"<p>FUS mutations are one of the major mutations in familial amyotrophic lateral sclerosis (ALS). The pathological hallmark is FUS-positive neuronal cytoplasmic inclusions (FUS-NCI), known as FUS proteinopathy. Human myxovirus resistance protein 1 (MxA) is an IFN-induced dynamin-like GTPase that acts as antiviral factor. In this study, we examined the expression of MxA in neurons bearing FUS-NCI. We performed immunohistochemistry for FUS and MxA to examine the expression of MxA in two autopsy cases with different FUS gene mutations localized at the nuclear localization signal site (Case 1, H517P; Case 2, R521C). MxA. Most neurons bearing FUS-NCI have increased cytoplasmic MxA expression. Increased cytoplasmic MxA showed several distribution patterns in relation to FUS-NCIs such as the following: colocalization with NCI, distribution more widely than NCI, and different distribution peaks from NCI. Our results suggested that antiviral signaling IFNs are involved upstream in the formation of FUS-NCI in ALS-FUS patients.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10367809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myelin protein zero mutation-related hereditary neuropathies: Neuropathological insight from a new nerve biopsy cohort","authors":"Juliane Bremer,&nbsp;Axel Meinhardt,&nbsp;Istvan Katona,&nbsp;Jan Senderek,&nbsp;Elke K. Kämmerer-Gassler,&nbsp;Andreas Roos,&nbsp;Andreas Ferbert,&nbsp;J. Michael Schröder,&nbsp;Stefan Nikolin,&nbsp;Kay Nolte,&nbsp;Bernd Sellhaus,&nbsp;Klimentina Popzhelyazkova,&nbsp;Frank Tacke,&nbsp;Ulrike Schara-Schmidt,&nbsp;Eva Neuen-Jacob,&nbsp;Chantal Ceuterick de Groote,&nbsp;Peter de Jonghe,&nbsp;Vincent Timmerman,&nbsp;Jonathan Baets,&nbsp;Joachim Weis","doi":"10.1111/bpa.13200","DOIUrl":"10.1111/bpa.13200","url":null,"abstract":"<p>Myelin protein zero (MPZ/P0) is a major structural protein of peripheral nerve myelin. Disease-associated variants in the <i>MPZ</i> gene cause a wide phenotypic spectrum of inherited peripheral neuropathies. Previous nerve biopsy studies showed evidence for subtype-specific morphological features. Here, we aimed at enhancing the understanding of these subtype-specific features and pathophysiological aspects of <i>MPZ</i> neuropathies. We examined archival material from two Central European centers and systematically determined genetic, clinical, and neuropathological features of 21 patients with <i>MPZ</i> mutations compared to 16 controls. Cases were grouped based on nerve conduction data into congenital hypomyelinating neuropathy (CHN; <i>n</i> = 2), demyelinating Charcot–Marie-Tooth (CMT type 1; <i>n</i> = 11), intermediate (CMTi; <i>n</i> = 3), and axonal CMT (type 2; <i>n</i> = 5). Six cases had combined muscle and nerve biopsies and one underwent autopsy. We detected four <i>MPZ</i> gene variants not previously described in patients with neuropathy. Light and electron microscopy of nerve biopsies confirmed fewer myelinated fibers, more onion bulbs and reduced regeneration in demyelinating CMT1 compared to CMT2/CMTi. In addition, we observed significantly more denervated Schwann cells, more collagen pockets, fewer unmyelinated axons per Schwann cell unit and a higher density of Schwann cell nuclei in CMT1 compared to CMT2/CMTi. CHN was characterized by basal lamina onion bulb formation, a further increase in Schwann cell density and hypomyelination. Most late onset axonal neuropathy patients showed microangiopathy. In the autopsy case, we observed prominent neuromatous hyperinnervation of the spinal meninges. In four of the six muscle biopsies, we found marked structural mitochondrial abnormalities. These results show that <i>MPZ</i> alterations not only affect myelinated nerve fibers, leading to either primarily demyelinating or axonal changes, but also affect non-myelinated nerve fibers. The autopsy case offers insight into spinal nerve root pathology in <i>MPZ</i> neuropathy. Finally, our data suggest a peculiar association of MPZ mutations with mitochondrial alterations in muscle.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10001076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNγ protects motor neurons from oxidative stress via enhanced global protein synthesis in FUS-associated amyotrophic lateral sclerosis","authors":"Amanda Faria Assoni,&nbsp;Erika N. Guerrero,&nbsp;René Wardenaar,&nbsp;Danyllo Oliveira,&nbsp;Petra L. Bakker,&nbsp;Luciana M. Alves,&nbsp;Valdemir M. Carvalho,&nbsp;Oswaldo Keith Okamoto,&nbsp;Mayana Zatz,&nbsp;Floris Foijer","doi":"10.1111/bpa.13206","DOIUrl":"10.1111/bpa.13206","url":null,"abstract":"<p>Amyotrophic lateral sclerosis type 6 (ALS6) is a familial subtype of ALS linked to Fused in Sarcoma (FUS) gene mutation. FUS mutations lead to decreased global protein synthesis, but the mechanism that drives this has not been established. Here, we used ALS6 patient-derived induced pluripotent stem cells (hIPSCs) to study the effect of the ALS6 FUS^R521H mutation on the translation machinery in motor neurons (MNs). We find, in agreement with findings of others, that protein synthesis is decreased in FUS^R521H MNs. Furthermore, FUS^R521H MNs are more sensitive to oxidative stress and display reduced expression of TGF-β and mTORC gene pathways when stressed. Finally, we show that IFN<b>γ</b> treatment reduces apoptosis of FUS^R521H MNs exposed to oxidative stress and partially restores the translation rates in FUS^R521H MNs. Overall, these findings suggest that a functional IFN<b>γ</b> response is important for FUS-mediated protein synthesis, possibly by FUS nuclear translocation in ALS6.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10006779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploiting nanopore sequencing for characterization and grading of IDH-mutant gliomas","authors":"Thidathip Wongsurawat,&nbsp;Piroon Jenjaroenpun,&nbsp;Panatna Anekwiang,&nbsp;Tantip Arigul,&nbsp;Wichayapat Thongrattana,&nbsp;Azemat Jamshidi-Parsian,&nbsp;Gunnar Boysen,&nbsp;Prapat Suriyaphol,&nbsp;Bhoom Suktitipat,&nbsp;Prajak Srirabheebhat,&nbsp;Pornsuk Cheunsuchon,&nbsp;Jantima Tanboon,&nbsp;Intawat Nookaew,&nbsp;Sith Sathornsumetee","doi":"10.1111/bpa.13203","DOIUrl":"10.1111/bpa.13203","url":null,"abstract":"<p>The 2021 WHO Classification of Central Nervous System Tumors recommended evaluation of cyclin-dependent kinase inhibitor 2A/B (<i>CDKN2A/B</i>) deletion in addition to codeletion of 1p/19q to characterize <i>IDH-</i>mutant gliomas. Here, we demonstrated the use of a nanopore-based copy-number variation sequencing (nCNV-seq) approach to simultaneously identify deletions of <i>CDKN2A/B</i> and 1p/19q. The nCNV-seq approach was initially evaluated on three distinct glioma cell lines and then applied to 19 <i>IDH</i>-mutant gliomas (8 astrocytomas and 11 oligodendrogliomas) from patients. The whole-arm 1p/19q codeletion was detected in all oligodendrogliomas with high concordance among nCNV-seq, FISH, DNA methylation profiling, and whole-genome sequencing. For the <i>CDKN2A/B</i> deletion, nCNV-seq detected the loss in both astrocytoma and oligodendroglioma, with strong correlation with the CNV profiles derived from whole-genome sequencing (Pearson correlation (<i>r</i>) = 0.95, <i>P</i> &lt; 2.2 × 10⁻¹⁶ to <i>r</i> = 0.99, <i>P</i> &lt; 2.2 × 10⁻¹⁶) and methylome profiling. Furthermore, nCNV-seq can differentiate between homozygous and hemizygous deletions of <i>CDKN2A/B</i>. Taken together, nCNV-seq holds promise as a new, alternative approach for a rapid and simultaneous detection of the molecular signatures of <i>IDH</i>-mutant gliomas without capital expenditure for a sequencer.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9990380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Announcing the Asian Oceanian Society of Neuropathology guidelines for Adapting Diagnostic Approaches for Practical Taxonomy in Resource-Restrained Regions (AOSNP-ADAPTR)","authors":"M. E. Buckland,&nbsp;C. Sarkar,&nbsp;V. Santosh,&nbsp;M. Al-Hussaini,&nbsp;S. H. Park,&nbsp;T. Tihan,&nbsp;H. K. Ng,&nbsp;T. Komori","doi":"10.1111/bpa.13201","DOIUrl":"10.1111/bpa.13201","url":null,"abstract":"<p>In 2023, molecular evaluation contributes significantly to classifying many central nervous system (CNS) tumors and offers prognostic and predictive information [<span>1</span>]. Following the WHO 2016 [<span>2</span>], the 2021 WHO classification (WHO CNS5) further advanced the integration of molecular diagnostics into CNS tumor diagnosis and grading [<span>3</span>]. Methylation profiling is now also recognized as a powerful molecular diagnostic technique for CNS tumors, which can aid in diagnosing challenging cases and defining some tumor types and subtypes/subgroups [<span>4</span>].</p><p>The increasing impact of molecular approaches in diagnosing CNS tumors has created significant practical challenges in implementing WHO CNS5, especially in low- and middle-income countries, including those in the Asian Oceanian region. This is mainly attributable to the restricted availability of molecular testing facilities in these resource-restrained regions, owing to the high cost combined with a lack of technological infrastructure facilities and skilled technical human resources. Another challenge in implementing the current WHO classification is the shortage of trained neuropathologists.</p><p>Further, the relevance and real added value of several molecular markers in clinical management are unclear at the current stage. Thus, the available therapeutic options for many CNS tumors still remain limited, and very few molecular advances have translated to therapeutic molecular targets in CNS tumors, such as BRAF inhibitors for <i>BRAF</i> mutations and TRK inhibitors for <i>NTRK</i> fusions [<span>5</span>]. Adults diagnosed with high-grade gliomas, the most common primary CNS tumor, typically undergo maximal surgical tumor removal, followed by radiotherapy and chemotherapy as the standard treatment [<span>6</span>]. The recently announced results of a phase III study of vorasidenib in IDH-mutant grade 2 gliomas [<span>7</span>] give hope that more targeted therapies will emerge in the future.</p><p>The above challenges have mandated the generation of practical and economical guidelines for diagnosing CNS tumors in resource-restrained regions. Pathologists in various countries have proposed practical adaptations of the previous WHO 2016 classification to address this issue in the past [<span>8, 9</span>]. The present initiative termed ADAPTR (pronounced Adapter), spearheaded by the Asian Oceanian Society of Neuropathology (AOSNP), aims to adapt the current WHO CNS5 classification to make it suitable for routine diagnostic practices in resource-limited settings, with a specific focus on the Asian-Oceanian region. The ultimate objective is to benefit all patients with brain tumors worldwide with varying resource restraints. ADAPTR does not seek to alter the definition of tumor types or diagnostic criteria outlined in the WHO CNS5. Instead, its purpose is to offer practical information that can be effectively utilized in patient care and treatment within","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13201","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10362181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postmortem neuropathology in COVID-19: An update","authors":"David S. Younger","doi":"10.1111/bpa.13204","DOIUrl":"10.1111/bpa.13204","url":null,"abstract":"<p>Between 2020 and 2021, Younger [<span>1, 2</span>] described the neuropathology of 144 decedents due to severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) at the height of the 2019 coronavirus-2 (COVID-19) pandemic. The present study concerns an updated later cohort adding 150 new cases [<span>3-20</span>]. There was a modest demographic shift in the updated later cohort. The study population comprised 12 children and 138 adults in a 2.6:1 ratio of males to females, of age range (7 months to 97 years) with 72% ≥50 years, compared to the earlier cohort in whom all were adults of older ages (&gt;age 65 years in 79%). Serum cytokine and procoagulant levels were elevated in the vast majority of patients in life in both cohorts indicative of a cytokine storm, who were managed in an intensive care unit in 86% of cases (equally compared to the earlier cohort of 88%) until the time of death that occurred in a ratio of ≤10 days or more (0.78:1). There were seven children with COVID-19 associated multisystem inflammatory syndrome (MIS-C) (six patients) in the later cohort including one with angiographically negative small vessel childhood primary angiitis of the central nervous system (AN-SV-cPACNS) [<span>15</span>]. There was also a modest increase in several neuropathological aspects in the updated later cohort compared to the initial early cohort that included: Interstitial brainstem inflammation and neuronal loss (25% vs. 8%), focal or diffuse perivascular parenchymal T-cells (17% vs. 7%), acute hemorrhagic or ischemic infarcts (25% and 11% vs. 2% and 7%), and hypoxic–ischemic changes and neuronal loss (25% vs. 19%). Positive detection of SARS-CoV-2 ribonucleic acid (RNA) by quantitative real-time polymerase chain reaction (qRT-PCR) decreased, while negative findings increased respectively (17% and 44% vs. 9% and 22%). Investigations applying commercially available antisense nucleocapsid and spike gene probes to formalin-fixed paraffin-embedded tissue with amplification of in situ hybridization (ISH) signals employing RNAscope™ [<span>21</span>], counterstained by hematoxylin and eosin with comparison to control antisense probes, failed to show positivity in parenchymal brainstem tissues but did show positivity in the adventitia of a meningeal vessel outside of the medulla [<span>20</span>]. Brain microglia activation so noted in 21% of cases, although rarely mentioned in the earlier cohort.</p><p>Several salient findings characterize the morbid features of COVID-19 neurological illness. Elevated serum cytokines and procoagulant levels due to a cytokine storm likely contribute to critical illness, acute hemorrhagic, and thrombotic infarcts. Hypoxic–ischemic changes seen in up to a quarter of cases may not account for the myriad of neuropathological changes particularly indolent interstitial parenchymal cerebral or brainstem inflammation mediated predominantly by infiltrating CD8 T-cells. Despite the overall generally favorable prognosis, ","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13204","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the performance of large language models: ChatGPT and Google Bard in generating differential diagnoses in clinicopathological conferences of neurodegenerative disorders","authors":"Shunsuke Koga,&nbsp;Nicholas B. Martin,&nbsp;Dennis W. Dickson","doi":"10.1111/bpa.13207","DOIUrl":"10.1111/bpa.13207","url":null,"abstract":"<p>This study explores the utility of the large language models (LLMs), specifically ChatGPT and Google Bard, in predicting neuropathologic diagnoses from clinical summaries. A total of 25 cases of neurodegenerative disorders presented at Mayo Clinic brain bank Clinico-Pathological Conferences were analyzed. The LLMs provided multiple pathologic diagnoses and their rationales, which were compared with the final clinical diagnoses made by physicians. ChatGPT-3.5, ChatGPT-4, and Google Bard correctly made primary diagnoses in 32%, 52%, and 40% of cases, respectively, while correct diagnoses were included in 76%, 84%, and 76% of cases, respectively. These findings highlight the potential of artificial intelligence tools like ChatGPT in neuropathology, suggesting they may facilitate more comprehensive discussions in clinicopathological conferences.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.13207","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10316573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}