Free Neuropathology 2020-04-03T16:09:31+02:00 Werner Paulus 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> 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 <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## 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 Keith Anthony Josephs Wen-lang Lin Dennis W Dickson <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## 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 Naomi P. Visanji Selma Hönigschnabl Angelika Reiner Peter Fischer Anthony Lang Herbert Budka Gabor G. Kovacs <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## Dementia with Lewy bodies – a clinicopathological update 2020-03-11T14:31:44+01:00 János Bencze Woosung Seo Abdul Hye Dag Aarsland Tibor Hortobágyi <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## Top ten discoveries of the year: Neurotrauma 2020-03-30T16:06:35+02:00 Daniel P Perl <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## Top ten discoveries of the year: Neurooncology 2020-03-11T14:34:45+01:00 Pieter Wesseling <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## 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## Top ten discoveries of the year: Neuromuscular disease 2020-03-11T14:21:17+01:00 Marta Margeta <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## Top ten discoveries of the year: Neuroinflammation 2020-03-11T14:15:02+01:00 Hans Lassmann <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## Neuropathologists play a key role in establishing the extent of COVID-19 in human patients 2020-04-03T16:09:31+02:00 Jose Javier Otero <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## The “neuroepithelial tumor”: Exchanging our trash can for an industrial size dumpster? 2019-12-20T11:45:48+01:00 Arie Perry <p>The “neuroepithelial tumor”: Exchanging our trash can for an industrial size dumpster?</p> 2020-01-01T00:00:00+01:00 ##submission.copyrightStatement##