Brain Pathology最新文献

{"title":"Comments to the “Letter to the Editor” for the manuscript titled “Clinico-sero-pathological characteristics of anti-Ha antisynthetase syndrome”","authors":"Bing Zhao,&nbsp;Lining Zhang,&nbsp;Tingjun Dai","doi":"10.1111/bpa.70014","DOIUrl":"10.1111/bpa.70014","url":null,"abstract":"<p>Thank you very much for presenting this instructive case, which demonstrates classical features of anti-synthetase syndrome (ASS) through its clinical triad (arthritis, myositis, and interstitial lung disease) and characteristic muscle pathology (perifascicular necrosis with MHC-II overexpression). We would like to provide the following insights based on our experience:</p><p>In our previous studies, when anti-Ha antibodies were identified via immunoblotting, we further validated results using cell-based assays (CBA) and immunoprecipitation (IP). However, significant discrepancies were observed across these methods. For instance, some samples showed strong positivity in IP but weak reactivity in CBA, while others exhibited faint IP signals despite prominent immunoblot bands. We hypothesize that these inconsistencies may arise from: (1) variations in the conformational structure of the Ha-antigen complex across different platforms; (2) technical differences in antigen presentation and assay conditions. While IP remains the current gold standard, our findings highlight the need for harmonized protocols to improve cross-method reproducibility.</p><p>Although the classic ASS triad and perifascicular necrosis are well recognized, our cohort of anti-Ha-positive patients rarely presented with such prototypical features as described in this report by Marie-Thérèse Holzer et al. Potential explanations for this divergence include: (1) Selection bias: there might be some differences in patient referral patterns between neuromuscular centers (focused on myopathy subtypes) and rheumatology centers (prioritizing systemic manifestations); (2) Genetic predispositions: Population-specific HLA haplotypes or modifier genes may influence phenotypic expression.</p><p>We aim to publish our previous findings to raise awareness of anti-Ha-associated ASS heterogeneity and encourage multicenter collaborative efforts to validate these observations across diverse populations. Enhanced recognition of anti-Ha antibody cases through interdisciplinary collaboration will ultimately refine the clinicopathological profile of this rare ASS subtype and optimize therapeutic strategies.</p><p><b>Bing Zhao</b>: Writing—Original draft preparation. <b>Lining Zhang, Tingjun Dai</b>: Writing—Reviewing and Editing.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076081","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":"Correspondence to: Clinico-sero-pathological characteristics of anti-Ha antisynthetase syndrome","authors":"Marie-Therese Holzer,&nbsp;Robert Biesen,&nbsp;Sarah Tansley,&nbsp;Carsten Dittmayer,&nbsp;Werner Stenzel,&nbsp;Udo Schneider","doi":"10.1111/bpa.70015","DOIUrl":"10.1111/bpa.70015","url":null,"abstract":"&lt;p&gt;With great interest, we read the article on the clinico-sero-pathological characteristics of anti-Ha antisynthetase syndrome by Zhao et al. [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;The authors describe 12 patients with anti-Ha as a single myositis-specific antibody [&lt;span&gt;1&lt;/span&gt;]. In light of this manuscript, we would like to add a report and discuss an anti-Ha-positive patient (a 39-years-old female), who was diagnosed and treated at the university hospital Charité Berlin with severe antisynthetase syndrome (ASyS).&lt;/p&gt;&lt;p&gt;The patient initially presented in 2023 with arthralgia and scaly skin on her palms (see Figure 1A) and was diagnosed with psoriatic arthritis. In the following months, she developed a dry cough and myalgia, and subsequently, in early 2024, progressive dyspnoea and night sweats. Because of the existing prednisolone and TNF-inhibitor treatment for supposed psoriatic arthritis, an infection with &lt;i&gt;pneumocystis jirovecii&lt;/i&gt; was suspected. Following a thorough and negative infection screen, the patient was ultimately transferred to the intensive care unit of the Charité with acute respiratory distress syndrome (ARDS) and evaluated for possible lung transplantation (see Figure 1D). Because of progressive respiratory insufficiency, high-dose glucocorticosteroids as well as cyclophosphamide were initiated. The suspected diagnosis was revised to idiopathic inflammatory myopathy (IIM) based on the clinical presentation with arthritis, myalgia with elevated creatine kinase (CK, 939 U/L), scaly exanthema (retrospectively identified as mechanic hands) and rapidly progressive interstitial lung disease (RP-ILD). Immunofluorescence on HEp2 cells revealed a speckled cytoplasmic pattern with a titre of 1:640 (see Figure 1B). Despite repetitive testing of myositis-specific and myositis-associated antibodies with commercial line blots, only anti-Ro52 antibodies were identified. Therefore, after muscle MRI showing patchy oedema and fasciitis, a muscle biopsy of the M. quadriceps was performed. This revealed a histopathological pattern consistent with ASyS: A mild but typical pattern of perifascicular necrosis and atrophy, as well as positive MHC class I and II staining with a perifascicular pattern (particularly for MHC class II) (see Figure 2).&lt;/p&gt;&lt;p&gt;Combined, the clinical symptoms with a complete clinical triad (Arthritis, Myositis, ILD [&lt;span&gt;2, 3&lt;/span&gt;]) and the muscle biopsy consistent with ASyS led to the diagnosis of ASyS [&lt;span&gt;4&lt;/span&gt;]. Hence, treatment was expanded to include rituximab (RTX), as a good response to RTX in ASyS had been reported [&lt;span&gt;4, 5&lt;/span&gt;]. To search thoroughly for possible autoantibodies in this apparent myositis-specific antibody-negative case, radioimmunoprecipitation was performed at the University of Bath [&lt;span&gt;6&lt;/span&gt;] and anti-Ha-antibodies were identified (see Figure 1C). Following RTX therapy, the patient experienced significant improvement of her ILD (see early follow-up CT, Figure 1D). On subsequent outpatient","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970525","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":"Comparative pathology boards facilitate the translation of knowledge between canine and human cancer patients","authors":"Jessica A. Beck,&nbsp;Christina Mazcko,&nbsp;Sara Belluco,&nbsp;Mireille Bitar,&nbsp;Daniel Brat,&nbsp;Jonathan W. Bush,&nbsp;Rati Chkheidze,&nbsp;Kara N. Corps,&nbsp;Chad Frank,&nbsp;Caterina Giannini,&nbsp;Craig Horbinski,&nbsp;Jason T. Huse,&nbsp;Jennifer W. Koehler,&nbsp;Andrew D. Miller,&nbsp;C. Ryan Miller,&nbsp;M. Gerard O'Sullivan,&nbsp;Joanna J. Phillips,&nbsp;Daniel R. Rissi,&nbsp;Courtney R. Schott,&nbsp;Anat Stemmer-Rachamimov,&nbsp;Stephen Yip,&nbsp;Amy K. LeBlanc","doi":"10.1111/bpa.70013","DOIUrl":"10.1111/bpa.70013","url":null,"abstract":"<p>Comparative pathology boards bring together anatomic pathologists with expertise in canine and human histology to identify shared features, including immune or TME components, tumor subtypes, or prognostic tissue biomarkers. This article summarizes feedback to improve future initiatives and enhance the translational relevance of comparative oncology for human patients.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953795","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":"A pineal mass in a 39-year-old woman","authors":"Charlotte Paoli,&nbsp;Thibault Fabas,&nbsp;Lydiane Mondot,&nbsp;Catherine Godfraind,&nbsp;Bérengère Dadone-Montaudié,&nbsp;Fanny Burel-Vandenbos","doi":"10.1111/bpa.70012","DOIUrl":"10.1111/bpa.70012","url":null,"abstract":"<p>A 39-year-old woman, with no significant medical history, presented progressively worsening behavioral problems. Brain MRI revealed a nodular lesion in the pineal region, with a necrotic center, heterogeneous peripheral enhancement, and an ependymal spread to the floor of the third ventricle and posterior part of the bulb (Figure 1). Germ cell markers (HCG, AFP) in CSF were negative. Because of the development of obstructive hydrocephalus, a ventriculocisternostomy with endoscopic ventricular biopsy (three biopsies from 1 to 5 mm) was performed, followed by a resection 1 month later. The surgical specimen was composed of fragments with a total weight of 3 g (Box 1).</p><p>Histologically, the lesion had a predominantly piloid morphology with some radial perivascular arrangements on an abundant myxoid background. Most cells showed an eosinophilic cytoplasm and bi- or multipolar extensions as well as round to angular nuclei with homogeneous chromatin. Floret-like multinucleated cells were present. In certain places, the glial cells were arranged in cords, giving the tumor a chordoid morphology. Cytonuclear atypia ranged from mild to pronounced. Mitotic index was 4 mitoses per 10 fields. Endothelial vascular proliferation and necrotic areas were present. No Rosenthal fibers or granular bodies were found. Tumor cells were immunopositive for GFAP and OLIG2 as well as focally for synaptophysin, but were negative for CD34, TTF1, EMA, NeuN, and Chromogranin A. ATRX, H3K27me3, INI1, and BRG1 expression was retained (Figure 2).</p><p>No mutation or gene rearrangement was detected by next-generation sequencing (NGS), RNA sequencing, or droplet digital PCR (FGFR1) in panel genes, including MAPK pathway genes (BRAF, KRAS, HRAS, and FGFR1-3). The DNA methylation array data, obtained using EPICv2 Beadchips, was analyzed using the DKFZ brain classifier v12.8 (https://www.molecularneuropathology.org/) and the resulting methylation profiles matched (calibrated score 0.99) with the methylation class of high-grade astrocytoma with piloid features (HGAP). The profiles were then clustered within the HGAP class using Uniform Manifold Approximation and Projection (UMAP). Copy number analysis showed homozygous deletion of the <i>CDKN2A</i>/<i>CDKN2B</i> loci (Figure 2).</p><p>High-grade astrocytoma with piloid features (HGAP).</p><p>Gliomas account for about 14%–22% of all pineal region tumors. They are mainly circumscribed low-grade astrocytomas, especially in children, and diffuse high-grade gliomas. The 2021 WHO classification has expanded the scope of circumscribed gliomas to include HGAP. This novel and rare glioma, mainly occurring in the adult cerebellum, has not been previously reported in the pineal region. This particular tumor, with a distinctive DNA methylation profile essential to the diagnosis, without specific histological or molecular hallmarks, may mimic other malignant or benign gliomas developing in the pineal region [<span>1</span>].</p><p>Before DN","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961698","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":"Stereological analysis of cholinergic neurons within bilateral pedunculopontine nuclei in health and when affected by Parkinson's disease","authors":"Puneet Kumar Sharma,&nbsp;Steve Gentleman,&nbsp;David Trevor Dexter,&nbsp;Ilse Sanet Pienaar","doi":"10.1111/bpa.70011","DOIUrl":"10.1111/bpa.70011","url":null,"abstract":"<p>During Parkinson's disease (PD), loss of brainstem-based pedunculopontine nucleus' (PPN) cholinergic neurons induces progressive postural-gait disability (PGD). PPN-deep brain stimulation inconsistently alleviates PGD, due to stereotactic targeting inaccuracies resulting from insufficiently detailed human PPN anatomical descriptions. Relatedly, rodent studies show rostro-caudal clustering of PPN-cholinergic neurons, reflecting functional sub-territories. We applied unbiased cerebro-bilateral 3-dimensional (3-D) stereology to post-mortem PPNs from PD versus neurological-control cases, to estimate total numbers of cholinergic neurons and describe their rostro-caudal distribution. Given ambiguous descriptions of the PPN's confines, we utilized two complimentary definitions of the PPN's anatomical boundaries. The first was based on the structure's gross anatomy, by considering the nucleus as a recognizable “channel” enclosed by distinct white matter fiber tracts (WMFT) encompassing the medial lemniscus, central tegmental tract and decussation of the superior cerebellar peduncle. Second, the PPN was recognized by its histological architecture, as a dense collection of cholinergic neurons (the “Ch5” group) that were immunoreactive for choline acetyltransferase (ChAT), the enzyme responsible for biosynthesis of the neurotransmitter acetylcholine. Many such ChAT-immunoreactive neurons were dispersed within the traversing tracks and hence the PPN's Ch5-based outlining method permitted their stereological capture while also allowing distinction between the PPN's two subnuclei, namely the pars compacta (PPNc) and pars dissipata (PPNd), based on subnuclei-specific cholinergic cytoarchitectural organization. We further reconstructed template data as 3-D renders, revealing gross morphological differences between control and PD-affected PPNs. PD brains revealed significant PPN cholinergic neuronal loss, particularly affecting the PPNd. Control cases showed bimodal clustering of cholinergic neurons, prominently affecting left-sided PPNs. Most PD cases revealed more severe cholinergic neuronal loss in right-sided PPNs, potentially driving symptom lateralization. Our study provides a comprehensive cholinergic cytoarchitectural atlas of the human PPN in health versus during PD.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954782","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":"Quantitative T1 is sensitive to cortical remyelination in multiple sclerosis: A postmortem MRI study","authors":"Riccardo Galbusera,&nbsp;Matthias Weigel,&nbsp;Erik Bahn,&nbsp;Sabine Schaedelin,&nbsp;Alessandro Cagol,&nbsp;Po-Jui Lu,&nbsp;Muhamed Barakovic,&nbsp;Lester Melie-Garcia,&nbsp;Jonas Franz,&nbsp;Peter Dechent,&nbsp;Govind Nair,&nbsp;Ludwig Kappos,&nbsp;Wolfgang Brück,&nbsp;Christine Stadelmann,&nbsp;Cristina Granziera","doi":"10.1111/bpa.70010","DOIUrl":"10.1111/bpa.70010","url":null,"abstract":"<p>Remyelination of cortical lesions in people with multiple sclerosis (pwMS) has been shown to be extensive. In this work, we aimed to assess whether postmortem quantitative MRI (qMRI) can help detect those areas. We imaged six fixed whole brains of deceased pwMS by 3T-MRI using magnetization transfer ratio (MTR, 570 μm isotropic), myelin water fraction (MWF, 1000 μm isotropic), quantitative T1 (qT1, 670 μm isotropic), quantitative susceptibility mapping (QSM, 330 μm isotropic) and radial diffusivity (RD, 1300 or 1400 μm isotropic) maps. Immunohistochemistry for myelin proteins was performed in 129 tissue blocks including the cortex and enabled the detection of cortical demyelination (DM), cortical remyelination (RM), and normal-appearing cortex (NAC). We identified 25 DM, 25 RM, and for each of these areas, a corresponding NAC near the lesion. Wilcoxon paired tests showed that: (a) qT1 and RD were higher and QSM lower in DM versus NAC (all <i>p</i> &lt; 0.001), whereas RD was higher and QSM lower in RM versus NAC (<i>p</i> = 0.048 and <i>p</i> &lt; 0.01 respectively); (b) mean qT1 in RM did not differ from mean qT1 in NAC (<i>p</i> = 0.074); (c) MWF and MTR were not different between DM and RM. We compared the delta between DM versus NAC (∆DM) and the delta between RM versus NAC (∆RM) using a Mann–Whitney test, in which RM showed a partial recovery of qT1 only (∆qT1 DM &gt; ∆qT1 RM, <i>p</i> = 0.045). Mixed-effect models confirmed the findings obtained using univariate analyses. qT1 and QSM, but not RD, correlated with MBP intensity (<i>r</i> = −0.28, <i>p</i> &lt; 0.01 and <i>r</i> = 0.29, <i>p</i> &lt; 0.01 respectively). A Bonferroni correction was performed for multiple testing. Our data show that qT1 is altered in demyelinated but not in remyelinated cortical areas, while QSM and RD are affected by any cortical abnormalities. Accordingly, qT1 might be considered a potential imaging biomarker of cortical RM.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979056","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":"A 23-year-old woman with a headache and imbalance","authors":"Lukas Marcelis,&nbsp;Andrew Folpe,&nbsp;Sounak Gupta,&nbsp;Cinthya J Zepeda Mendoza","doi":"10.1111/bpa.70008","DOIUrl":"10.1111/bpa.70008","url":null,"abstract":"&lt;p&gt;A 23-year-old woman presented to the emergency department with headaches and imbalance. Computer tomography imaging was obtained first and showed the presence of a hemorrhagic lesion in the left cerebellum (not shown). Subsequent magnetic resonance imaging showed a heterogeneously enhancing mass in the left cerebellum measuring 3.4 × 2.1 × 2.4 cm with peripheral blood products (Figure 1). There was associated vasogenic edema in the left cerebellum with mass effect on the posterior lateral brainstem and encroachment upon the 4th ventricle without hydrocephalus. An operative resection of the lesion was then pursued.&lt;/p&gt;&lt;p&gt;H&amp;E-stained section revealed a highly cellular spindle cell neoplasm with a prominently fascicular growth pattern and no readily identifiable stroma (Figure 2A and Box 1). The tumor had very high mitotic activity (up to 10 mitotic figures in a single high-powered field) (Figure 2B). The spindle cells were monomorphic with oval to elongated nuclei and inapparent nucleoli (Figure 2B).&lt;/p&gt;&lt;p&gt;The immunophenotype of the tumor did not reveal a clear line of origin, with negative staining for GFAP, OLIG2, S100 protein, SOX10, desmin (Figure 2C), pankeratin, synaptophysin, and only focally positive vimentin. Delicate pericellular reticulin deposition was noted, supporting the hypothesis of a sarcomatous neoplasm. The proliferation index (Ki-67) was over 80% in accordance with the high mitotic activity. Subsequent staining for H3K27me3 showed loss of nuclear expression (Figure 2D); beta-catenin staining was exclusively cytoplasmic, and SS18-SSX fusion antibody staining was negative (Figure 2E), but SSX-C terminus antibody staining was strongly and diffusely positive (Figure 2F).&lt;/p&gt;&lt;p&gt;DNA next-generation sequencing (NGS) mutation analysis with a neuro-oncology gene panel was performed and showed three clinically relevant mutations, one in &lt;i&gt;TP53&lt;/i&gt; (c.493C &gt; T (Exon 5)) and two mutations in &lt;i&gt;DICER1&lt;/i&gt; (c.4405_4406del (Exon 23) and c.5425G &gt; A (Exon 25)). RNA NGS gene fusion analysis with a sarcoma gene panel did not reveal any gene fusions. Chromosome microarray (CMA) analysis was performed (Applied Biosystems (Affymetrix) OncoScan) and was consistent with a clonal neoplastic process with chromosomal complexity including heterozygous deletion of 9p (encompassing &lt;i&gt;CDKN2A/B&lt;/i&gt;) and chromosome Xq chromothripsis, among others (Figure 2G).&lt;/p&gt;&lt;p&gt;Primary intracranial sarcoma, DICER1-mutant.&lt;/p&gt;&lt;p&gt;This was a difficult to diagnose as a high-grade spindle cell neoplasm without specific morphological or immunohistochemical features. The initial differential diagnosis based on imaging included medulloblastoma given the anatomical location and the patient's age. The morphologic presentation of a sarcomatous, monomorphic spindle cell proliferation raised a broad differential diagnosis including malignant peripheral nerve sheath tumor (MPNST), primary intracranial sarcoma, DICER1-mutant, and synovial sarcoma (SS). Subsequent targete","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751206","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":"Herpes simplex virus-1 infection alters microtubule-associated protein Tau splicing and promotes Tau pathology in neural models of Alzheimer's disease","authors":"Emmanuel C. Ijezie,&nbsp;Michael J. Miller,&nbsp;Celine Hardy,&nbsp;Ava R. Jarvis,&nbsp;Timothy F. Czajka,&nbsp;Lianna D'Brant,&nbsp;Natasha Rugenstein,&nbsp;Adam Waickman,&nbsp;Eain Murphy,&nbsp;David C. Butler","doi":"10.1111/bpa.70006","DOIUrl":"10.1111/bpa.70006","url":null,"abstract":"<p>Herpes simplex virus 1 (HSV-1) infection alters critical markers of Alzheimer's disease (AD) in neurons. One key marker of AD is the hyperphosphorylation of Tau, accompanied by altered levels of Tau isoforms. However, an imbalance in these Tau splice variants, specifically resulting from altered 3R to 4R <i>MAPT</i> splicing of exon 10, has yet to be directly associated with HSV-1 infection. To this end, we infected 2D and 3D human neural models with HSV-1 and monitored <i>MAPT</i> splicing and Tau phosphorylation. Further, we transduced SH-SY5Y neurons with HSV-1 ICP27, which alters RNA splicing, to analyze if ICP27 alone is sufficient to induce altered <i>MAPT</i> exon 10 splicing. We show that HSV-1 infection induces altered splicing of <i>MAPT</i> exon 10, increasing 4R-Tau protein levels, Tau hyperphosphorylation, and Tau oligomerization. Our experiments reveal a novel link between HSV-1 infection and the development of cytopathic phenotypes linked with AD progression.</p>","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 5","pages":""},"PeriodicalIF":6.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718007","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":"Multiple intracranial hemorrhages in a postmenopausal female","authors":"Xinhua Lu,&nbsp;Xinya Xu,&nbsp;Xiaopeng Zhang","doi":"10.1111/bpa.70007","DOIUrl":"10.1111/bpa.70007","url":null,"abstract":"&lt;p&gt;A 53-year-old postmenopausal female presented to the neurology clinic with acute onset of right arm weakness for 1 week. Neurologic examination was notable for 4/5 strength in the right upper extremity. Computed tomography revealed multiple hematomas with mass effect in the left frontal lobe and basal ganglia (Figure 1A; Box 1). Magnetic resonance imaging with gadolinium showed multiple heterogeneously enhancing lesions associated with surrounding edema, mass effect, and midline shift (Figure 1B). Given the absence of an overt primary source for the hemorrhagic mass with elevated intracranial pressure and neurologic deficits, surgical excision of the left frontal lobe lesion was performed. Intraoperatively, the mass showed evidence of prior hemorrhage and was noted to encase a relatively large vessel. Postoperative CT imaging showed gross total resection of the frontal lesion and found a new lesion adjacent to the left lateral ventricle (Figure 1A inset). Of notice in the past medical history, the patient had undergone hysterectomy 3 years earlier. After a final diagnosis was reached, adjuvant treatment was performed with stereotactic radiosurgery (SRS) and chemotherapy. At 10 months of follow-up, the patient's symptoms have resolved.&lt;/p&gt;&lt;p&gt;Hematoxylin–eosin stain showed that several pieces of tissue mingled together with a lot of blood. There was no normal brain parenchyma found. Small clusters of atypical cells made up of uninucleate and multinucleated cells were embedded in the hemorrhagic material. These were big cells with clumped chromatin, noticeable nucleoli, uneven nuclear outlines and nuclear-cytoplasmic ratios, and a modest proportion of amphophilic cytoplasm. Eosinophilic hyaline globules were seen in a large number of the cells. Mitoses were present (Figure 2A,B). Moreover, we saw atypical cells infiltrating relatively large vessels (Figure 2A) and some small vessels. Looking carefully into the previous history of hysterectomy, we found the diagnosis of complete hydatidiform mole, which led us to consider the possibility of metastatic gestational trophoblastic neoplasia (GTN). The atypical cells were strongly and diffusely positive for CK7 (Figure 2C) and β-HCG (Figure 2D), slightly immunopositive for SALL-4 (Figure 2E) on immunohistochemical examination. Ki-67 displayed a high proliferative index (approximately 60%, Figure 2F).&lt;/p&gt;&lt;p&gt;Metastatic gestational choriocarcinoma following complete hydatidiform mole.&lt;/p&gt;&lt;p&gt;Multiple intracranial hemorrhages can be due to a variety of causes, including hypertension, cerebral amyloid angiopathy (CAA), primary or secondary CNS vasculitis, hematologic disorders, anticoagulant use, sinus thrombosis, and brain tumors, most frequently metastatic. In this patient, normotensive, young for CAA, and overall only apparently without a significant past medical history, multiple hemorrhagic lesions on MRI led to the suspicion of brain metastases. Once discovered, the previous diagnosis of complete hydat","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699670","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":"SOCIETY NEWS","authors":"Audrey Rousseau","doi":"10.1111/bpa.70009","DOIUrl":"https://doi.org/10.1111/bpa.70009","url":null,"abstract":"<p><b>The ISN is looking for a group of young motivated neuropathologists</b> to promote the specialty via the ISN website. If you are interested in participating, please contact Audrey Rousseau (<span>[email protected]</span>) or Monika Hofer (<span>[email protected]</span>).</p><p><b>The International Congress of Neuropathology (ICN)</b> will be held in Edinburgh, Scotland, in 2027 (ICN27). The Congress President will be Prof Colin Smith and the ICN27 will be hosted by the British Neuropathological Society (BNS).</p><p>“On behalf of the British Neuropathological Society I am delighted to extend a warm invitation to all our colleagues across the world to join us in Edinburgh for the International Congress of Neuropathology 2027. Edinburgh is an easily accessible centre, surrounded by 1000 years of living history. We will develop a strong academic programme covering all aspects of neuropathology with world leading plenary speakers, supported by a social programme highlighting some of Edinburgh's historic charms. For those wishing to explore further, Edinburgh offers access to many of Scotland's highlights, be it touring the Highlands, sampling our famous whisky or golfing on some of our picturesque courses. I do hope you will be able to join us for what I am sure will be a memorable meeting showcasing the best in international neuropathology.</p><p>Colin Smith</p><p>Congress President ISN 2027”</p><p>Summary report for ICN23 Berlin (our most recent International Congress of Neuropathology, September 2023) now available in the Society's journal Brain Pathology (see link: https://doi.org/10.1111/bpa.13249).</p><p>We are delighted to start the bidding process for holding the <b>2031 XXII International Congress of Neuropathology (ICN)</b>. As you know, the 2027 XXI ICN Congress will be in Edinburgh and we now need to think ahead to 2031 and find a new home for our much-loved congress.</p><p>The Invitation Letter calling for bids and outlining the process can be found on the ISN website (www.intsocneuropathol.com). Please note that the deadline is the <b>31st August 2025</b>.</p><p>The <b>7th Quadrennial Meeting of the World Federation of Neuro-Oncology Societies</b> will be held in conjunction with the 30th Annual Meeting &amp; Education Day of the Society for Neuro-Oncology <b>November 19-23, 2025</b> in Honolulu, Hawaii.</p><p><b><i>Brain Pathology has joined Wiley's Open Access</i></b> portfolio as of January 2021. As a result, all submissions are subject to an Article Publication Charge (APC) if accepted and published in the journal. ISN members are eligible for a 10% discount off the Open Access APC. For more information on the fees, please click here.</p><p><b>Free resource: digital microscopy platform for neurodegenerative diseases curated in Munich</b>. Prof Jochen Herms and his team have been setting up a digital microscopy platform for neurodegenerative diseases in their department in Munich. Registration is free. ISN members and interested","PeriodicalId":9290,"journal":{"name":"Brain Pathology","volume":"35 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bpa.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750004","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}