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

Ten years of EC-funded concerted actions on the neuropathology of prion disease: report on the final scientific meeting (31 October-2 November 2003, Baden near Vienna, Austria).

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/bpa.12101

ISN Information Days at the University of Witwatersrand Medical School, Johannesburg (South Africa) on September 23rd–24th, 2013

Very long chain fatty acids (VLFA;≥C24) were first reported to accumulate in cholesterol esters (CE) of brain white matter of patients suffering from X-linked adrenoleukodystrophy (X-ALD; 1). Later on, increased concentrations of VLFA, predominantly of hexacosanoic acid (C26:0) were also found in peripheral tissues (2,3) and blood lipids (4–6) of X-ALD patients due to a specific genetic defect in the peroxisomal oxidation of VLFA (7).

Very Long Chain Fatty Acids and Phytanic Acid in Genetic Peroxisomal Diseases

Project Secretary Dr Homa Adle-Biassette Inserm U676, Université Paris Diderot Hôpital Robert Debré 48 Bd Sérurier 75019 Paris France Fax: +33-1-40031995 E-mail: homa.adle@inserm.fr Dear Reader, I write this after returning from an Advocacy Workshop in Brussels, Belgium, that was jointly organized by the Federation of European Neuroscience Societies (FENS) and the Society for Neuroscience (SfN) (see http://www.sfn.org/index.aspx?pagename=FENS_ Advocacy_Workshop). I participated on behalf of Euro-CNS, the European Confederation of Neuropathological Societies. The main aim of the workshop was to work on strategies for national neuroscience societies to promote the importance of neuroscience research with policy makers in order to obtain financial support at times of globally shrinking resources. This is more than pertinent also for national societies of neuropathology and the ISN. It was fascinating to learn about the many facets of approaches to advocacy in science and biomedicine. FENS, with an extremely well organized administrative framework, is still exploring future strategies, while the SfN has already established its approach, utilizing dedicated staff that are well experienced in productively lobbying legislators and other policy makers. The Canadian Association for Neuroscience has been particularly successful in teaming up with top-notch industrial representatives, the British Neuroscience Association has listed advocacy at the top of its wish list, and the European Brain Council solicits partnerships between biomedical researchers, clinicians, industry, patients and their families. In a nutshell, successful strategies seemingly rely on two very simple but pivotal factors—1) formation of alliances, and 2) being active, both re-active and pro-active. As alliances are essential, neuropathology has to do more, MUCH more, to partner with basic and clinical neurosciences. Soberingly, neuropathologists seem to be poorly represented within the large scientific societies mentioned above, and our representation in influential clinical bodies seems to be no better. Among no less that 193 contributing experts of the “Consensus Document on European Brain Research” (Di Luca et al, Europ J Neurosci 2011; 33: 768–818) that deals with all aspects of neurological disorders, I could find only ONE neuropathologist. Aren’t WE THE experts on neurological diseases (together with others)? So, if we want to increase support, we must come out of our ivory towers and become much more visible to our partners and the public. Being active, re-active and pro-active, is an obvious recipe for almost everything in life, but is not that easy to translate into reality. It demands our minds, hearts, time and dedication. The ISN has already started some promising activity in advocacy: in order to foster local development and support of neuropathology, “ISN Information Days” have been organized to show to local basic and clinical neuroscientists what up-to-date neuropathology can offer them in clinical service, research and teaching. The ISN Subcommitte on Training and Education, with its Chairperson Prof. Francesco Scaravilli, has supported local hosts in organizing successful annual events in Sofia, Bulgaria (2009) and Istanbul, Turkey (2010). This year another ISN Information Day will be held in Surabaya, Java, Indonesia (Sept. 17–18, 2011). The ISN invites everybody who might be interested in hosting such a future event to contact Prof. Scaravilli or myself. Thus, it’s time to act and join forces if we want to steer our beloved discipline into a promising future. The ISN is willing to lead in this, but it is up to you as individual neuropathologists to follow suit and make a difference by your personal engagement.

Advocacy for Neuropathology

established by him. Thus, numerous brains of autopsied cases could be examined in the institute. The collection of autopsy cases with full neuropathological examination now numbers 15 000. Shortly after the end of World War II the institute was visited by two Japanese doctors, Prof. Yushi Uchimura and Prof. Masayuki Namba (Department of Psychiatry, University of Tokyo). The major scientific research fields of Dr Seitelberger, infantile neuroaxonal dystrophy and Pelizaeus–Merzbacher disease, are well known. His research output, however, was enlarged by cooperation with Dr Kurt Jellinger, for example, to metabolic disturbances, inflammatory diseases, vaccination disorders, alcoholic encephalopathies, astroglial pathology, brain trauma and multiple sclerosis. In 1959 Prof. Seitelberger was nominated as Director of the Neurological Institute, and he has subsequently expanded and rearranged the Institute by creating additional sections such as neurophysiology in 1960 (Prof. Hellmuth Petsche), a section for peripheral nerve and muscle in 1962 (Prof. Elfriede Sluga), neurochemistry in 1966 (Prof. Hans Bernheimer), pathology of the autonomic nervous system (Prof. Gustav Lassmann), neurological disorders in aphasia (Prof. Karl Gloning) in 1967, and experimental neuropathology in 1975 (Prof. Hans Lassmann) on the basis of his conviction that interdisciplinary collaboration is absolutely necessary for development of the neurological sciences. As is well known, he founded Acta Neuropathologica (Berlin) in 1961, and was managing editor until Dr K. Jellinger succeeded him in 1986. Moreover, he was Rector of the University of Vienna between 1975 and 1977, and retired in 1987. Prof. Seitelberger is intimate with Japanese eminent neuropathologists (Prof. Hirotsugu Shiraki, Prof. Takeshi Yonezawa, Prof. Fusahiro Ikuta, Dr Koshiro Fujisawa), psychiatrists (Prof.Tadashi Inose, Prof. Susumu Yokoi) and neurosurgeons (Prof. Naoki Kageyama and Prof. Eiichi Tani), and was decorated with the second Order of Merit from the Japanese Government for his distinguished Neuropathology 2000; 20, S124–S126

Herbert Budka

Papers

Ten years of EC-funded concerted actions on the neuropathology of prion disease: report on the final scientific meeting (31 October-2 November 2003, Baden near Vienna, Austria).

ISN Information Days at the University of Witwatersrand Medical School, Johannesburg (South Africa) on September 23rd–24th, 2013

Very Long Chain Fatty Acids and Phytanic Acid in Genetic Peroxisomal Diseases

Advocacy for Neuropathology

Neuropathological relationships between Austria and Japan.