The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.

https://link.springer.com/content/pdf/10.1007%2Fs00401-007-0243-4.pdf

The 2007 WHO Classification of Tumours of the Central Nervous System

In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a "research framework" because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration [AT(N)]. This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.

/pdf/nia-aa-research-framework-toward-a-biological-definition-of-1sjt6cvmd3.pdf

NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease

Nobel Lecture: Prions

The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in ∼50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

/pdf/astrocytes-biology-and-pathology-2hq13zf0bo.pdf

Astrocytes: biology and pathology

https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2011.e991

Editorial: The European Response to BSE: A Success Story

Dysembryoplastic neuroectodermal tumor (DNT) is a rare brain neoplasm. Although the tumor pathology is relatively well charactererized, its full clinicopathological spectrum is still discussed, and ultrastructural data on it are very limited. Here, the authors describe detailed ultrastructural pathology of 7 cases of DNT. Each tumor consisted of 3 major elements: neoplastic cells (oligodendroglial-like cells, OLC), elongated processes forming neuropil-like structure, and expanded "mucoid" extracellular space, the latter giving an impression of cellular elements floating within it. Neoplastic cells had round, oval, or elongated nuclei, no discernible nucleoli, and a relatively narrow rim of cytoplasm. Some nuclei were irregular and invaginated, and pseudoinclusions (invaginations of cytoplasm penetrated into toroid-like nuclear formations) were observed. Part of the cytoplasm sequestrated within pseudoinclusions often appeared degenerated with large blebs and electron-lucent vesicles, and some of these con...

Dysembryoplastic neuroectodermal tumor: an ultrastructural study of six cases.

125th anniversary of the Institute of Neurology (Obersteiner Institute) in Vienna. "Germ Cell" of interdisciplinary neuroscience.

The Bovine Spongiform Encephalopathy (BSE) monitoring system implemented in the European Union (EU) has been reviewed in this opinion for twenty five Member States (MSs). For this revision, MSs were divided into three groups depending on the number of years during which they have implemented the EU monitoring regime, and/or on the similarities of their epidemiological situations. Key assumptions made include: (i) full past compliance (for at least 6 years) with EU regulatory requirements for the surveillance and control of cattle BSE, (ii) future continuity of the BSE controls, and (iii) perfect sensitivity of the rapid tests employed for BSE surveillance. Two methodologies were applied to these three groups of MSs using available EU BSE monitoring data. The first one looks at the age of detected cases in each calendar year, while the second looks at the number of cases in successive annual birth cohorts. For the first group of MSs, these methodologies were applied in order to estimate the number of Classical BSE cases that would be missed under three different scenarios: (i) an increase in the age for BSE testing in cattle; (ii) stopping testing in cattle born after a certain date, and (iii) stopping testing of healthy slaughter cattle after certain dates. In the second group of MSs, the epidemiological situation was at least equivalent to that of the first group, and thus the conclusion was that they can be considered together for any potential revision of the BSE monitoring system. For the third group of MSs, it was not possible to calculate detailed estimates as their particular epidemiological situation compromises the application of some of the methods used. Recommendations are made in order to overcome the limitations encountered, and to ensure fitness of the EU monitoring regime for the purposes for which it is currently used

Scientific Opinion on a second update on the risk for human and animal health related to the revision of the BSE monitoring regime in some Member States

Herbert Budka

Papers

Editorial: The European Response to BSE: A Success Story

Dysembryoplastic neuroectodermal tumor: an ultrastructural study of six cases.

125th anniversary of the Institute of Neurology (Obersteiner Institute) in Vienna. "Germ Cell" of interdisciplinary neuroscience.

Scientific Opinion on a second update on the risk for human and animal health related to the revision of the BSE monitoring regime in some Member States

32. Sporadic Creutzfeldt–Jakob Disease