Free neuropathology最新文献

{"title":"A novel KDM2A::YAP1 fusion in a pediatric supratentorial CNS neoplasm resembling a tumor with BCOR internal tandem duplication.","authors":"Arnault Tauziède-Espariat, Alice Métais, Dorian Bochaton, Euphrasie Servant, Guillaume Chotard, Mégane Le Quang, Benjamin Bonhomme, Nathalène Truffaux, Volodia Dangouloff-Ros, Nathalie Boddaert, Lauren Hasty, Edouard Gimbert, Pascale Varlet","doi":"10.17879/freeneuropathology-2025-6152","DOIUrl":"10.17879/freeneuropathology-2025-6152","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preservation of cellular structure via immersion fixation in brain banking.","authors":"Macy Garrood, Emma L Thorn, Adam Goldstein, Allison Sowa, William Janssen, Alyssa Wilson, Claudia S López, Raakhee Shankar, Erin S Stempinski, Kurt Farrell, John F Crary, Andrew T McKenzie","doi":"10.17879/freeneuropathology-2025-6104","DOIUrl":"10.17879/freeneuropathology-2025-6104","url":null,"abstract":"<p><p>Immersing the brain in a solution containing formaldehyde is a commonly used method for preserving the structure of human brain tissue in brain banking. However, there are questions about the quality of preservation using this method, as formaldehyde takes a relatively long period of time to penetrate a large organ such as the human brain. As a result, there is a critical need to determine whether immersion fixation is an adequate initial preservation method. To address this, we present exploratory histologic findings from our brain bank following the immersion fixation of hemi-sectioned brain specimens under refrigeration. Using light microscopy, we found that there was no significant change in the size of pericellular or perivascular rarefaction areas based on the postmortem interval (PMI) or on the progression from the outer (frontal cortex) to the inner (striatum) brain regions. Additionally, we did not identify any significant number of ghost cells - a state of late-stage cellular necrosis - in the light micrographs analyzed. Using transmission electron microscopy of tissue from the frontal cortex, we found that synapses could still be visualized, but there was vacuolization and variable degrees of myelin disbanding identified. Using serial section transmission electron microscopy, we found that identified synapses could be traced from one section to the next. Using serial block face scanning electron microscopy, we also found that myelinated axons on 2D images can be traced with high fidelity from one image to the next, even at PMIs of up to 27 hours. Collectively, our data corroborate previous findings that immersion fixation is effective for prevention of cellular necrosis and for visualizing many ultrastructural features in at least the surface areas of the brain. However, how structural preservation quality should best be assessed in brain banking is an open question that depends on the intended research applications.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinsonism associated with prolonged unresponsive wakefulness syndrome after blunt head injury: a clinico-pathological study.","authors":"Kurt A Jellinger","doi":"10.17879/freeneuropathology-2025-5982","DOIUrl":"10.17879/freeneuropathology-2025-5982","url":null,"abstract":"<p><p><b>Objective:</b> Survival after traumatic brain injury (TBI) and posttraumatic parkinsonian-like symptoms is increasing, in particular in those patients developing during disease course an unresponsive wakefulness syndrome (UWS) previously termed persistent vegetative state. <b>Material & methods:</b> 100 patients with disorders of consciousness after a blunt TBI ranging from deep coma to defective states / minimal cognitive state survived between 12 and 900 days. 15 patients developed parkinsonian symptoms, which were correlated with their neuropathological changes. <b>Results:</b> The patients, surviving either UWS recovery (n = 10) or defective minimally conscious state (MCS) (n = 5), clinically presented with severe (n = 7), moderate (n = 5), or mild (n = 3) parkinsonian symptoms mainly comprising symmetrical rigidity, amimia, hypo- / akinesia and convergence disorder, which in six patients were associated with unilateral or bilateral resting tremor. Following levodopa treatment, 11 patients showed mild to moderate improvement and four patients almost complete improvement of UWS, parkinsonism or both. Neuropathology revealed in most cases supratentorial traumatic lesions such as contusions, cerebral hemorrhages and diffuse white matter lesions. In addition to lesions in the basal ganglia and hippocampus, all cases displayed older lesions in the dorsolateral or lateral parts of the pons and in lower midbrain with various involvement of substantia nigra. The periaqueductal gray and upper midbrain tegmentum were however preserved. The pattern of brainstem lesions correlated with the sequelae of transtentorial shifting due to increased intracranial pressure. <b>Conclusions:</b> These and other rare observations following blunt TBI confirm the importance of the pattern of secondary brainstem lesions for the development and prognosis of UWS and rare parkinson-like symptoms.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"6 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryopreservation of brain cell structure: a review.","authors":"Andrew T McKenzie, Emma L Thorn, Oge Nnadi, Borys Wróbel, Emil Kendziorra, Kurt Farrell, John F Crary","doi":"10.17879/freeneuropathology-2024-5883","DOIUrl":"10.17879/freeneuropathology-2024-5883","url":null,"abstract":"<p><p>Cryopreservation, the preservation of tissues at subzero temperatures, is a mainstay of brain banking that allows for the storage of brain tissue without the use of chemical fixatives. This is particularly important for molecular studies that are incompatible with tissue fixation. However, brain tissue is vulnerable to various forms of damage during the cryopreservation process, in particular due to the phase transition of water from a liquid to a solid state with the formation of ice crystals, which can disrupt cellular morphology. There is a critical need to characterize the effects of cryopreservation on brain cell structure at the microscopic level. In this review, we conducted a comprehensive literature search, identifying 97 studies that yielded 146 distinct observations of the effects of cryopreservation on neurohistology. We classified the reviewed studies into three main categories: cryofixation, freezing, and cryopreservation with cryoprotectants. Cryofixation techniques enable vitrification and excellent ultrastructural preservation of thin tissue samples but are limited in terms of the depth of tissue that can be preserved without ice artifacts. Freezing methods, particularly when applied to brain slices, can achieve rapid cooling rates that result in minimal ice artifacts detectable by light microscopy. Cryoprotectant-based approaches have the potential to reduce ice damage and achieve vitrification. For thin tissue samples, immersion in cryoprotectants has been found to be effective for structural preservation. However, for larger samples or the entire brain, perfusion of cryoprotectants is necessary to perform rapid distribution, and this has a more limited evidence base. In conclusion, while current cryopreservation methods can provide sufficient quality for some downstream applications, there is a need for improved techniques that enable the cryopreservation of larger brain tissue samples while maintaining excellent structural preservation.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"35"},"PeriodicalIF":0.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel FUS::BEND2 fusion expanding the molecular spectrum of astroblastomas.","authors":"Arnault Tauziède-Espariat, Benjamin Bonhomme, Nathalène Truffaux, Volodia Dangouloff-Ros, Nathalie Boddaert, Kévin Beccaria, Lauren Hasty, Alice Métais, Pascale Varlet","doi":"10.17879/freeneuropathology-2024-5983","DOIUrl":"10.17879/freeneuropathology-2024-5983","url":null,"abstract":"","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult glioblastoma with Lynch syndrome-associated mismatch repair deficiency forms a distinct high-risk molecular subgroup.","authors":"Maria-Magdalena Georgescu","doi":"10.17879/freeneuropathology-2024-5892","DOIUrl":"10.17879/freeneuropathology-2024-5892","url":null,"abstract":"<p><p>Glioblastoma is the most frequent and malignant primary brain tumor. Although the survival is generally dismal for glioblastoma patients, risk stratification and the identification of high-risk subgroups is important for prompt and aggressive management. The G1-G7 molecular subgroup classification based on the MAPK pathway activation has offered for the first time a non-redundant, all-inclusive classification of adult glioblastoma. Five patients from the large, 218-patient, prospective cohort showed germline mutations in mismatch repair (MMR) genes (Lynch syndrome) and a significantly worse median survival of 3.25 months post-surgery than those from the G1/EGFR and G3/NF1 major subgroups, or from the rest of the cohort adjusted for age. These rare tumors were assigned to a new subgroup, G3/MMR, a G3/NF1 subgroup spin-off, as they generally show genomic alterations leading to RAS activation, such as <i>NF1</i> and <i>PTPN11</i> mutations. An integrated clinical, histologic and molecular analysis of the G3/MMR tumors showed distinct characteristics as compared to other glioblastomas, including those with iatrogenic high tumor mutation burden (TMB), warranting a separate subgroup. Prior history of cancer, midline location or multifocality, presence of multinucleated giant cells (MGCs), positive p53 and MMR immunohistochemistry, and specific molecular characteristics, including high TMB, <i>MSH2</i>/<i>MSH6</i> alterations, biallelic <i>TP53</i> Arg mutations and co-occurring <i>PIK3CA</i> p.R88Q and <i>PTEN</i> alterations, alert to this high-risk G3/MMR subgroup. The MGCs and p53 immunohistochemistry analysis in G1-G7 subgroups showed that one in 7 tumors with these characteristics is a G3/MMR glioblastoma. The FDA-approved first-line therapy for many advanced solid tumors consists of nivolumab-ipilimumab immune checkpoint inhibitors. One G3/MMR patient received this regimen and survived much longer than the rest, setting a proof-of-principle example for the treatment of these very aggressive G3/MMR glioblastomas.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"32"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11745196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathology in 1984: a deadly shot into the heart of Europe.","authors":"Herbert Budka","doi":"10.17879/freeneuropathology-2024-5976","DOIUrl":"10.17879/freeneuropathology-2024-5976","url":null,"abstract":"<p><p>Just 40 years ago, Europe was divided into the Eastern communist bloc, which included the Czechoslovak Socialist Republic (ČSSR) and was dominated by the now historical Soviet Union, and the Western bloc comprising democracies such as Austria. The Iron Curtain, a heavily guarded and deadly border zone, separated the two blocs and constrained, in prison style, the populations of the Eastern bloc. The present neuropathological article relates the sad fate of František Faktor, a 33 years-old Czech who was shot by ČSSR border guards when attempting to flee to Austria at the border between <i>Česke Velenice</i> and <i>Gmünd</i>. František Faktor was found dead on November 5^th, 1984, on Austrian soil some 500 meters from the border. ČSSR authorities claimed that he was shot when still within their territory, then ran some 900 meters to the other side of the border and died there. Neuropathology demonstrated a gunshot injury of the spinal canal, with transverse lesioning of the spinal cord predominating at Th10 that must have resulted in immediate paraplegia. This finding proved that ČSSR border guards had shot on Austrian territory, resulting in a major diplomatic <i>éclat</i> between both countries. After the implosion of the communist governments of the Eastern bloc in 1989, relations between Czechia and Austria started to normalise. By now, the <i>Gmünd/Česke Velenice</i> region has developed an exemplary good local neighbourhood and the former border has become virtually irrelevant. Attempts to bring justice have started in Czechia as well as other countries behind the past Iron Curtain, and some former Czechoslovak officials held responsible for border killings were legally prosecuted. The present article demonstrates how a small medico-scientific discipline such as neuropathology can contribute to assess critical political events in our world. \"Who controls the past controls the future:who controls the present controls the past.\"- George Orwell (1903-1950), Nineteen Eighty-Four (1984) [1].</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurodegeneration: 2024 update.","authors":"John F Crary","doi":"10.17879/freeneuropathology-2024-5848","DOIUrl":"10.17879/freeneuropathology-2024-5848","url":null,"abstract":"<p><p>This review highlights a collection of both diverse and highly impactful studies published in the previous year selected by the author from the neurodegenerative neuropathology literature. As with previous reviews in this series, the focus is, to the best of my ability, to highlight human tissue-based experimentation most relevant to experimental and clinical neuropathologists. A concerted effort was made to balance the selected studies across neurodegenerative disease categories, approaches, and methodologies to capture the breadth of the research landscape. These studies employ a range of classical and state-of-the-art methodologies ranging from clinical pathoanatomical correlative studies to single-cell RNA sequencing, artificial intelligence, and patient-derived human induced pluripotent stem cell models. Key studies include demonstration of the earliest pathological changes in young patients with repetitive head impacts (RHI), elucidation of the longitudinal trajectory of extrapyramidal symptoms in Lewy body disease subtypes, mapping of cell-type specific polygenic risk in Alzheimer's disease to neuropathology, a novel measure of histological brain age acceleration using artificial intelligence, trends in cerebrovascular pathologies over 25 years, associations between RHI and TDP-43 / hippocampal sclerosis, microglia / T-cell interaction in neurodegeneration, the impact of viral exposures on neurodegenerative disease risk, and polyglutamine repeat expansion disorders. This sampling of the literature collectively displays the breadth of the progress being made in the neuropathology of neurodegenerative diseases.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Northern Lights Neuroscience Symposium 2024: Expanding Spectrum of Common Dementia Disorders.","authors":"","doi":"10.17879/freeneuropathology-2024-6108","DOIUrl":"10.17879/freeneuropathology-2024-6108","url":null,"abstract":"<p><p>The Northern Lights Neuroscience Symposium 2024 \"Expanding Spectrum of Common Dementia Disorders\" was held in Hanasaari, Helsinki (Espoo), Finland on September 26-27, 2024. The meeting was jointly organised by the Scandinavian Neuropathological Society (chair Olivera Casar-Borota) and University of Helsinki. Drs. Liisa Myllykangas (chair), Olli Tynninen, Maria Gardberg and Tuomas Rauramaa made up the organising committee. The event brought together neuropathologists, clinicians and neuroscientists from nine different counties. In total, 91 people had registered for the meeting, and there were 29 abstracts. The keynote lectures on neuropathological and clinical aspects of new dementia entities such as LATE and PART as well as subtypes of AD and LBD, vascular and mixed patologies, were given by Irina Alafuzoff, Peter Nelson, David Wolk, Gabor Kovacs, Melissa Murray, Jacob Vogel, Liisa Myllykangas, Per Borghammer, Johannes Attems and Masafumi Ihara. The Patrick Sourander lecture \"Investigating choroid plexus and cerebrospinal fluid roles and functions in neurologic disease\" was presented by Maria Lehtinen from Harvard Medical School. Seven additional oral presentations (selected from submitted abstracts) were also given. The participants were highly appreciative of the meeting's top level scientific content and of the networking event, which included a Finnish sauna, a cruise in the Helsinki archipelago and a dinner in the center of Helsinki.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"30"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"35th Australian and New Zealand Society for Neuropathology (ANZSNP) Scientific Meeting 2024: Saturday 31 August - Sunday 1 September 2024, Hotel Crowne Plaza, Queenstown, New Zealand.","authors":"","doi":"10.17879/freeneuropathology-2024-5984","DOIUrl":"10.17879/freeneuropathology-2024-5984","url":null,"abstract":"<p><p>The ANZSNP scientific meeting 2024 was held in the scenic city of Queenstown, New Zealand on 31 August and September 1. Dr Fouzia Ziad, President of the ANZSNP and Dr Laveniya Satgunaseelan, Secretary /Treasurer of the ANZSNP were the convenors of the meeting. The meeting was co-badged with the Australasian Winter Conference on Brain Research (AWCBR) 2024. There were 55 registrants from Australia, New Zealand, USA, Europe and Asia. The academic program covered a wide range of neuropathology topics ranging from neuro-trauma to neuro-oncology. The neuro-oncology sessions featured a series of lectures on updates in the classification and diagnosis of various CNS tumours delivered by keynote speaker Prof Arie Perry, UCSF. Dr Thomas Robertson presented an approach to frozen sections in surgical neuropathology. An interactive session on the RCPA Neuropathology Quality Assurance Program (QAP) was organised with the QAP convenor, Dr Barbara Koszyca. Prof David Capper delivered the plenary lecture on \"<i>DNA methylation profiling and its practical implications</i>\" during the combined session with AWCBR attendees. Combined sessions also featured presentations on non-neoplastic conditions such as neurotrauma and neurodegeneration, comprising of presentations from invited faculty including Prof Michael Buckland, Dr Helen Murray and Prof Glenda Halliday. Four scientific research papers and 3 interesting cases were selected for oral presentation by the scientific committee. The meeting concluded with a plenary lecture delivered by Prof Arie Perry on \"<i>Biomarkers in Neuro-oncology</i>\". Two of the research paper presentations were eligible for the Bill Evans Memorial award for postgraduate students or trainees. The prize was awarded to Dr Monish Maharaj for his presentation \"<i>DNA Methylation Profiling to categorise meningioma recurrence risk: optimisation of resource allocation for patient selection</i>\". The feedback from the participants suggested that the meeting was well organized and appreciated for its educational content.</p>","PeriodicalId":73056,"journal":{"name":"Free neuropathology","volume":"5 ","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}