https://www.uni-muenster.de/Ejournals/index.php/fnp/issue/feed Free Neuropathology 2020-06-05T16:41:29+02:00 Werner Paulus werner.paulus@uni-muenster.de Open Journal Systems <p><em>Free Neuropathology</em> is a non-commercial journal that is run by Neuropathologists and other Neuroscientists and publishes papers on Human and Experimental Neuropathology. It is free for authors, free for readers, free from publishers, free from excessive formalities, and it encourages exchange of free opinions.</p> <p><em>Free Neuropathology</em> is not just another open-access online journal. It is a new type of journal edited and published by scientists working in the field. We do not have any financial interests, and we strongly feel that the huge amount of money currently spent for increasing the profit of publishers should be better invested into science. We believe that the usual activities of publishers such as copyediting, layout, hosting of articles, maintenance of the website and promotion could and should be overtaken by scientists in order to restitute scientific freedom. There is no article processing fee and no paywall -- the journal is free for everyone ("Diamond Open Access"). We try to reduce technicalities to a minimum. This grassroots development is managed by enthusiastic neuroscientists and it may be the future of publishing.</p> https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2610 Free for authors, free for readers, free from publisher, free formatting and free opinion: This is Free Neuropathology 2019-12-20T11:45:49+01:00 Werner Paulus werner.paulus@uni-muenster.de <p>Free for authors, free for readers, free from publisher, free formatting and free opinion: This is Free Neuropathology</p> 2020-01-01T00:00:00+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2639 Neuronal intermediate filament inclusion disease may be incorrectly classified as a subtype of FTLD-FUS 2020-03-11T15:58:29+01:00 Kevin F Bieniek bieniek@uthscsa.edu Keith Anthony Josephs josephs.keith@mayo.edu Wen-lang Lin lin.wenglang@mayo.edu Dennis W Dickson dickson.dennis@mayo.edu <p><strong>Background</strong>: The majority of cases of frontotemporal lobar degeneration (FTLD) are characterized by focal cortical atrophy with an underlying tau or TDP-43 proteinopathy. A subset of FTLD cases, however, lack tau and TDP-43 immunoreactivity, but have neuronal inclusions positive for ubiquitin, referred to as atypical FTLD (aFTLD-U). Studies have demonstrated that ubiquitin-positive inclusions in aFTLD-U are immunoreactive for fused in sarcoma (FUS). As such, the current nosology for this entity is FTLD-FUS, which is thought to include not only aFTLD-U but also neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease.</p> <p><strong>Objective</strong>: To compare pathological features of cases of aFTLD-U and NIFID.</p> <p><strong>Methods</strong>: We reviewed the neuropathology of 15 patients (10 males and 5 females; average age at death 54 years (range 41-69 years)) with an antemortem clinical diagnosis of a frontotemporal dementia and pathological diagnosis of aFTLD-U (n=8) or NIFID (n=7). Sections were processed for immunohistochemistry and immunoelectron microscopy with FUS, TDP-43, and α-internexin (αINX) antibodies.</p> <p><strong>Results</strong>: Eight cases had pathologic features consistent with FTLD-FUS, with severe striatal atrophy (7/8 cases), as well as FUS-positive neuronal cytoplasmic and vermiform intranuclear inclusions, but no αINX immunoreactivity. Five cases had features consistent with NIFID, with neuronal inclusions positive for both FUS and αINX. Striatal atrophy was present in only two of the NIFID cases. Two cases had αINX-positive neuronal inclusions consistent with NIFID, but both lacked striatal atrophy and FUS immunoreactivity. Surprisingly, one of these two NIFID cases had lesions immunoreactive for TDP-43.</p> <p><strong>Discussion</strong>: While FUS pathology remains a prominent feature of aFTLD-U, there is pathologic heterogeneity, including rare cases of NIFID with TDP-43- rather than FUS-positive inclusions.</p> 2020-03-11T13:04:06+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2616 Deposits of disease-associated alpha-synuclein may be present in the dura mater in Lewy body disorders: implications for potential inadvertent transmission by surgery 2020-03-11T14:25:43+01:00 Ellen Gelpi ellen.gelpi@gmail.com Naomi P. Visanji Naomi.Visanji@uhnresearch.ca Selma Hönigschnabl selma.hoenigschnabl@wienkav.at Angelika Reiner angelika.reiner@icloud.com Peter Fischer Peter.Fischer2@wienkav.at Anthony Lang Anthony.Lang@uhnresearch.ca Herbert Budka Herbert.Budka@meduniwien.ac.at Gabor G. Kovacs Gabor.Kovacs@uhnresearch.ca <p>Deposition of alpha-synuclein in the brain is a hallmark of Lewy body disorders. Alpha-synuclein has been considered to show prion-like properties. Prion diseases can be transmitted by the transplantation of cadaveric dura mater causing iatrogenic Creutzfeldt-Jakob disease. Recent observations of amyloid-β deposition in dural grafts support the seeding properties of amyloid-β. Here we assessed the presence of alpha-synuclein in dura mater samples as a potential transmissible seed source. We immunostained 32 <em>postmortem</em> dura mater samples; 16 cases with Lewy-body disorder (LBD) showing different pathology stages and 16 non-LBD cases for phosphorylated (Ser129) and disease-associated (5G4) alpha-synuclein. Disease-associated alpha-synuclein aggregates were identified in intradural nerve fibres and associated with a vessel in a single LBD-Braak stage 4 case. We conclude that alpha-synuclein is detectable, although rarely, in dura mater samples in patients with LBD. The risk of potential transmissibility of dural alpha-synuclein deserves assessment by complementary experimental studies.</p> 2020-02-12T09:52:19+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2613 Dementia with Lewy bodies – a clinicopathological update 2020-03-11T14:31:44+01:00 János Bencze bencze.janos@med.unideb.hu Woosung Seo wooah.seo@gmail.com Abdul Hye abdul.1.hye@kcl.ac.uk Dag Aarsland dag.aarsland@kcl.ac.uk Tibor Hortobágyi tibor.hortobagyi@kcl.ac.uk <p>Dementia is one of the major burdens of our aging society. According to certain predictions, the number of patients will double every 20 years. Although Alzheimer’s disease (AD), as the most frequent neurodegenerative dementia, has been extensively analysed, less is known about dementia with Lewy bodies (DLB). Neuropathological hallmarks of DLB are the deposition of intracellular Lewy bodies (LB) and Lewy neurites (LN). DLB belongs to the α-synucleinopathies, as the major component of these inclusions is pathologically aggregated α-synuclein. Depending on the localization of LBs and LNs in the central nervous system cognitive and motor symptoms can occur. In our work, we will systematically review the possible etiology and epidemiology, pathological (both macroscopic and microscopic) features, structural and functional imaging findings, with a special emphasis on the clinico-pathological correlations. Finally, we summarize the latest clinical symptoms-based diagnostic criteria and the novel therapeutic approaches. Since DLB is frequently accompanied with AD pathology, highlighting possible differential diagnostic approaches is an integral part of our paper. Although our present knowledge is insufficient, the rapid development of diagnostic and research methods provide hope for better diagnosis and more efficient treatment, contributing to a better quality of life.</p> 2020-02-18T11:16:50+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2672 Top ten discoveries of the year: Neurodevelopmental disorders 2020-04-16T16:18:13+02:00 Mara Dierssen mara.dierssen@crg.es <p>Developmental brain disorders, a highly heterogeneous group of disorders with a prevalence of around 3% of worldwide population, represent a growing medical challenge. They are characterized by impaired neurodevelopmental processes leading to deficits in cognition, social interaction, behavior and motor functioning as a result of abnormal development of brain. This can include developmental brain dysfunction, which can manifest as neuropsychiatric problems or impaired motor function, learning, language or non-verbal communication. Several of these phenotypes can often co-exist in the same patient and characterize the same disorder. Here I discuss some contributions in 2019 that are shaking our basic understanding of the pathogenesis of neurodevelopmental disorders. Recent developments in sophisticated <em>in-utero</em> imaging diagnostic tools have raised the possibility of imaging the fetal human brain growth, providing insights into the developing anatomy and improving diagnostics but also allowing a better understanding of antenatal pathology. On the other hand, advances in our understanding of the pathogenetic mechanisms reveal a remarkably complex molecular neuropathology involving a myriad of genetic architectures and regulatory elements that will help establish more rigorous genotype-phenotype correlations.</p> 2020-04-15T17:00:59+02:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2634 Top ten discoveries of the year: Neurodegeneration 2020-04-09T16:14:26+02:00 John Fonda Crary jfcrary@me.com <p>As we embark on a new year of scientific inquiry in neurodegenerative disease research, it is helpful to take a look back and consider the contributions in the field with the potential to be the most impactful. The purpose of this review is to highlight recent advances in 2019 which have the potential to be transformative in the field of neurodegenerative neuropathology. Substantive scientific progress rarely occurs as a “eureka moment”, and when possible, we opted to highlight collaborative efforts and research trends. We also included groundbreaking methodologies and tools. The generous increases in federal funding in the United States and elsewhere have massively expanded the total number of active programs researching Alzheimer’s disease. This exacerbates an imbalance, and an effort was made to highlight innovations across disease categories, and not to permit dementia to crowd out movement disorders, motor neuron disease, ataxias, etc. Thus, our overall goal was to highlight some of the most important discoveries, tools or methods that we feel will most likely directly enhance our ability to understand and diagnose neurodegenerative brain diseases. Given space limitations and the targeted readership of this journal, we selected ten topics most relevant to neuropathologists and clinical neuroscientists: 1. A new neurodegenerative disease category, 2. A new approach to probing gene expression on the single cell level, 3. A new approach merging histology and gene expression profiling, 4. A new computational approach using deep machine learning and computer vision, 5. A neuropathological substrate for sleep disturbance in Alzheimer’s disease, 6. A candidate pathogenic agent for Alzheimer’s disease, 7. A comprehensive approach to morphometric analysis of cerebellar neurodegeneration, 8. The strongest evidence yet linking neurodegeneration to contact sports, 9. Mounting evidence for gut to central nervous system transmission in Parkinson’s disease, and 10. A spotlight on glia in Huntington’s disease.</p> 2020-04-08T16:41:51+02:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2662 Top ten discoveries of the year: Neurotrauma 2020-03-30T16:06:35+02:00 Daniel P Perl daniel.perl@usuhs.edu <p>Neurotrauma represents a major public health problem and is one of the leading causes of death and disability worldwide. Despite its high prevalence, there are major gaps in our understanding of the underlying patho-physiology leading to the substantial morbidity and mortality associated with this problem. Here, ten studies published in 2019 are reviewed that addressed issues related to the acute and long-term effects of neurotrau-ma. These studies can be broken down into three separate categories, namely, the importance of neurotrau-ma-based damage to the cerebrovascular unit, white matter damage following neurotrauma, and research related to the long-term neurodegenerative consequences of repeated head trauma, especially chronic trau-matic encephalopathy. The advances highlighted here indicate that progress has been made. However, major gaps in knowledge remain which will require additional neuropathologic studies of clinical specimens, as well as the development and investigation of a wide range of relevant pre-clinical models. Further efforts in this field are clearly needed if there are to emerge better clinical outcomes for the numerous patients that suffer neuro-trauma each year as well as those currently suffering from its long-term effects.</p> 2020-03-30T15:08:29+02:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2671 Top ten discoveries of the year: Neurooncology 2020-03-11T14:34:45+01:00 Pieter Wesseling p.wesseling@amsterdamumc.nl <p>This article briefly discusses 10 topics that were selected by the author as top 10 discoveries published in 2019 in the broader field of neuro-oncological pathology (so including neurosciences as well as clinical neuro-oncology but with implications for neuro-oncological pathology). Some topics concern new information on immunohistochemical and molecular markers that enable improved diagnosis of particular tumors of the central nervous system (CNS) and information on a refined classification of medulloblastomas. Subsequently, several papers are discussed that further elucidate some pathobiological aspects of especially medulloblastomas (histogenesis, molecular evolution) and diffuse gliomas (mechanisms involved in CNS infiltration, role of cancer stem(-like) cells, longitudinal molecular evolution). The remaining topics concern progress made in vaccination therapy for glioblastomas and in using cerebrospinal fluid for liquid biopsy diagnosis of gliomas. Clearly, substantial, and sometimes even amazing progress has been made in increasing our understanding in several areas of neuro-oncological pathology. At the same time, almost every finding raises new questions, and translation of new insights in improving the outcome for patients suffering from CNS tumors remains a huge challenge.</p> 2020-02-26T11:27:59+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2615 Top ten discoveries of the year: Neurovascular disease 2020-01-30T13:23:01+01:00 Anna Maria Planas anna.planas@IIBB.CSIC.ES <p>The aim of this review is to highlight novel findings in 2019 in the area of neurovascular disease. Experimental studies have provided insight into disease development, molecular determinants of pathology, and putative novel therapeutic targets. Studies in genetic experimental models as well as monogenic forms of human cere-brovascular diseases identified pathogenic molecules that may also be relevant to sporadic cases. There have been advances in understanding the development of cerebral cavernous angiomas and arteriovenous malfor-mations, and putative curative treatments have been suggested from experimental models. Key pathogenic pathways involved in vessel calcification and stiffness have also been identified. At the cellular level, studies showed that proper function of endothelial and mural cells, particularly pericytes, is crucial to ensure full endo-thelial differentiation and blood-brain barrier integrity. Moreover, recent discoveries support the existence of a homeostatic crosstalk between vascular cells and other neural cells, including neurons. Cerebrovascular diseas-es are strongly associated with inflammation. Beyond pathogenic roles of specific components of the inflam-matory response, new discoveries showed interesting interactions between inflammatory molecules and regu-lators of vascular function. Clinical investigation on cerebrovascular diseases has progressed by combining ad-vanced imaging and genome-wide association studies. Finally, vascular cognitive impairment and dementia are receiving increasing attention. Recent findings suggest that high-salt intake may cause cerebrovascular dys-function and cognitive impairment independent of hypoperfusion and hypertension. These and other recent reports will surely inspire further research in the field of cerebrovascular disease that will hopefully contribute to improved prevention and treatment.</p> 2020-01-30T12:54:30+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2627 Top ten discoveries of the year: Neuromuscular disease 2020-03-11T14:21:17+01:00 Marta Margeta marta.margeta@ucsf.edu <p>This review highlights ten important advances in the neuromuscular disease field that either were first reported in 2019, or have reached a broad consensus during that year. The overarching topics include (i) new / emerging diseases; (ii) advances in understanding of disease etiology and pathogenesis; (iii) diagnostic advances; and (iv) therapeutic advances. Within this broad framework, the individual disease entities that are discussed in more detail include myoglobinopathy, <em>POPDC3</em>-mutated limb-girdle muscular dystrophy, neuromuscular adverse events associated with the immune checkpoint inhibition therapy, neuroglial stem cell-derived inflammatory pseudotumor of the spinal cord and spinal cord roots, acute flaccid myelitis, congenital myopathies, idiopathic inflammatory myopathies (with particular emphasis on immune-mediated necrotizing myopathies and sporadic inclusion body myositis), spinal muscular atrophy, and Duchenne muscular dystrophy. In addition, the review highlights several diagnostic advances (such as diagnostic RNA sequencing and development of digital diagnostic tools) that will likely have a significant impact on the overall neuromuscular disease field going forward.</p> 2020-01-23T12:13:32+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2612 Top ten discoveries of the year: Neuroinflammation 2020-03-11T14:15:02+01:00 Hans Lassmann hans.lassmann@meduniwien.ac.at <p>Ten neuropathological studies, published in 2019, are discussed, which address important aspects of neuroimmunology and inflammatory brain disease. They include topics related to new mechanisms of inflammation and immune mediated neurodegeneration, which are relevant for multiple sclerosis (publications 1 to 4) and discuss the role of specific autoantibodies against myelin oligodendrocyte glycoprotein or aquaporin 4 in neuromyelitis optica spectrum disorders (publications 5 and 6). Other studies highlight the discovery of new virus induced diseases of the nervous system and their relevance for clinical neurology and diagnostic neuropathology (publications 7 and 8). Finally, very interesting studies are discussed dealing with microglia and immune mechanisms in neurodegeneration (publication 9) and the neuropathological long-term outcome of Aß vaccination in Alzheimer’s disease (publication 10). All these studies highlight the central role of neuropathology in neurological disease research.</p> 2020-01-10T10:50:03+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2749 Optimizing filter trap assay for the detection of aggregated alpha-synuclein in brain samples 2020-04-28T16:24:00+02:00 Thibauld Oullier thibauld.oullier@univ-nantes.fr Alice Prigent prigent.alice@gmail.com Guillaume Chapelet guillaume.chapelet@chu-nantes.fr Michel Neunlist michel.neunlist@univ-nantes.fr Franck Letournel franck.letournel@univ-angers.fr Pascal Derkinderen derkinderenp@yahoo.fr 2020-04-28T10:49:46+02:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2818 Studies on inflammation and stroke provide clues to pathomechanism of central nervous system involvement in COVID-19 2020-06-05T16:41:29+02:00 Adám Dénes, Dr denesa@koki.hu Stuart M Allan, Prof. stuart.allan@manchester.ac.uk Tibor Hortobágyi, Prof. tibor.hortobagyi@kcl.ac.uk Craig J Smith, Prof. Craig.Smith-2@manchester.ac.uk 2020-06-05T11:48:09+02:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2736 Neuropathologists play a key role in establishing the extent of COVID-19 in human patients 2020-04-06T12:48:57+02:00 Lokman Cevik cevik.5@osu.edu Michele Joana Alves Michele.Alves@osumc.edu Jose Javier Otero jose.otero@osumc.edu <p>SARS-CoV2 infection causes COVID-19, &nbsp;and represents the most emergent health care crisis of our generation. Ample evidence in the scientific literature suggests that SARS-CoV, MERS-CoV, and endemic human coronaviruses infect brain cells.&nbsp; We delineate a rationale for encouraging evaluation of the brain, and in particular the brainstem, in COVID-19 so that potential neuropathological mechanisms can be delineated.</p> 2020-04-02T16:51:08+02:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2611 The “neuroepithelial tumor”: Exchanging our trash can for an industrial size dumpster? 2019-12-20T11:45:48+01:00 Arie Perry Arie.Perry@ucsf.edu <p>The “neuroepithelial tumor”: Exchanging our trash can for an industrial size dumpster?</p> 2020-01-01T00:00:00+01:00 ##submission.copyrightStatement## https://www.uni-muenster.de/Ejournals/index.php/fnp/article/view/2817 Neuropathology through the ages – personal reflections 2020-06-04T16:40:55+02:00 Herbert Budka herbert.budka@meduniwien.ac.at 2020-06-04T15:34:11+02:00 ##submission.copyrightStatement##