Top ten discoveries of the year

 
 
Hans Lassmann
Free Neuropathol 2: 1 (2021)
Key requirements for the validity of a neuropathological study are the inclusion of large numbers of biopsy or autopsy cases and proper controls, the rigorous classification of the basic neuropathology and the selection of the most suitable technologies for investigation. Whether the studies are performed with the fanciest, new, and state of the art technology or with rather conventional methodology is of minor importance. Following these criteria, a spectrum of neuropathological studies has been published in 2020, which provides new insights on important questions related to neurological disease. They include the pathological substrate of brain disease in COVID-19 infected patients, the nature of the adaptive and innate inflammatory response, or the type and mechanisms of tissue injury and repair in multiple sclerosis, and diagnostically relevant or mechanistic new insights into antibody-mediated diseases of the central nervous system. Other studies describe in detail the dynamic changes of brain inflammation in patients with trisomy 21 as a disease model for Alzheimer’s disease, or the presence and consequences of vascular comorbidities in a chronic inflammatory disease, such as multiple sclerosis. All these contributions have provided important, highly relevant clues for basic and translational neuroscience.
 
 

 
 
 
John F. Crary
Free Neuropathol 1: 12 (2020)
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.
 
John F. Crary
Free Neuropathol 1: 12 (2020)
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.
 
Daniel P. Perl
Free Neuropathol 1: 10 (2020)
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 pathophysiology 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 neurotrauma. These studies can be broken down into three separate categories, namely, the importance of neurotrauma-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 traumatic 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 neurotrauma each year as well as those currently suffering from its long-term effects.
 
Pieter Wesseling
Free Neuropathol 1: 8 (2020)
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 cen-tral 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.
 
Anna Maria Planas
Free Neuropathol 1: 5 (2020)
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 cerebrovascular 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 malformations, 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 endothelial 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 diseases are strongly associated with inflammation. Beyond pathogenic roles of specific components of the inflammatory response, new discoveries showed interesting interactions between inflammatory molecules and regulators of vascular function. Clinical investigation on cerebrovascular diseases has progressed by combining advanced 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 dysfunction 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.
 
Marta Margeta
Free Neuropathol 1: 4 (2020)
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, POPDC3-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.
 
Hans Lassmann
Free Neuropathol 1: 3 (2020)
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.