CSF is an invaluable diagnostic tool in clinical neurological research, and development of new disease biomarkers depends on basic CSF research. While there are books on CSF in clinical context, there is currently a lack in literature focused on a research based perspective. To that end, this volume is split into two parts. The first will provide a brief overview on current use of CSF in clinical routine, the physiology of CSF, and its usefulness and potential as a biomarker. The second part addresses the main purpose of the volume, which is to look at CSF from a research perspective in context with the most important diagnostic entities in neurology. Many neurological diseases are poorly understood in terms of etiology and pathophysiology, and CSF reflects the biochemistry of normal and pathological procedures in the nervous system. The authors provide insight into the current understanding of CSF changes in these various conditions and what it tells us about the nature of neurological diseases. Furthermore, methodological aspects are discussed as well as shortcomings that need to be addressed in the future. Finally, we provide an outlook for potential directions that might be explored to improve all these various aspects of CSF research with the ultimate goal of being incorporated in clinical practice.
CSF is an invaluable diagnostic tool in clinical neurological research, and development of new disease biomarkers depends on basic CSF research. While there are books on CSF in clinical context, there is currently a lack in literature focused on a research based perspective. To that end, this volume is split into two parts. The first will provide a brief overview on current use of CSF in clinical routine, the physiology of CSF, and its usefulness and potential as a biomarker. The second part addresses the main purpose of the volume, which is to look at CSF from a research perspective in context with the most important diagnostic entities in neurology. Many neurological diseases are poorly understood in terms of etiology and pathophysiology, and CSF reflects the biochemistry of normal and pathological procedures in the nervous system. The authors provide insight into the current understanding of CSF changes in these various conditions and what it tells us about the nature of neurological diseases. Furthermore, methodological aspects are discussed as well as shortcomings that need to be addressed in the future. Finally, we provide an outlook for potential directions that might be explored to improve all these various aspects of CSF research with the ultimate goal of being incorporated in clinical practice.
Section I. General Aspects
1. The use of cerebrospinal fluid in biomarker studies
2. The cerebrospinal fluid and barriers – anatomical and
physiological considerations
3. More than a drainage fluid: the role of CSF in signalling in the
brain and other effects on brain tissue
4. Dosing, collection and quality control issues in cerebrospinal
fluid research using animal models
Section II. CSF Research in Particular Disease Entities and its
Clinical Context
5. Multiple sclerosis, and other demyelinating and autoimmune
inflammatory diseases of the central nervous system
6. Cerebrospinal fluid in the dementias
7. Biomarkers in cerebrospinal fluid for synucleinopathies,
tauopathies, and other neurodegenerative disorders
8. Cerebrospinal fluid in Creutzfeld-Jakob disease
9. Cerebrospinal fluid findings in Guillain-Barré syndrome and
chronic inflammatory demyelinating polyneuropathies
10. Cerebrospinal fluid biomarkers of malignancies located in the
central nervous system
11. Impaired cerebrospinal fluid pressure
12. Cerebrospinal fluid in acute and chronic infectious
diseases
13. Vascular diseases and bleedings
14. Cerebrospinal fluid and brain extracellular fluid in severe
brain trauma
15. Epilepsy
16. Primary headaches
17. Psychiatric syndromes other than dementia
The only book on the market geared specifically for neurological researchers, providing coverage of how this important reflects the biochemistry of normal and pathological procedures in the nervous system
Florian Deisenhammer is presently Professor of Neurology at the
University of Innsbruck in Austria. After graduating in 1989 from
the University of Vienna Medical School, he finished training in
clinical Neurology at Innsbruck Medical University in 1996 and
became senior staff member since then. He is director of the
neuroimmunological laboratory and his clinical work focuses on
stroke and neuroimmunology, particularly multiple sclerosis. His
main scientific interest is MS therapy monitoring, specifically
antibodies against interferons and other biomarkers in CSF and
blood. He issued guideline papers on CSF and led a workpackage in
an EU project on interferon antibodies (NABINMS) and he is
currently involved in a broader EU project on immunogenicity of
biopharmaceuticals in general (ABIRISK). He received several prices
for his scientific work. He is a member of various international
and national societies including the Austrian Medical Society, the
International Society of Neuroimmunology, the EFNS task force on
beta interferon neutralizing antibodies, board member of the German
society of neurochemistry and CSF diagnostics, the task force on
CSF, and member of the editorial board of the Journal Multiple
Sclerosis and Related Disorders (MSARD). Charlotte Teunissen’s
research mission is to cure dementia disorders through development
of body fluid biomarkers. The studies of her research group cover
the entire spectrum of biomarker development. The studies start
with biomarker identification, hypothesis based as well as by mass
spectrometry based proteomics method, including mass spectrometry
and aptamer-based proteomics technologies. The group puts strong
effort in analytical validation of the most promising biomarkers by
available immunoassays, which we also develop ourselves. In the
next step, extensive internal and external clinical validation are
performed and the last type of studies are aimed at implementation
of novel biomarkers in clinical practice. The lab possesses state
of the art technologies, such as SOMAscan, Quanterix ultrasensitive
SimOA technology, Mesoscale technology and in vitro technologies
for clinical routine lab analysis. These studies are all based on
the availability of a well-characterised biobank, headed by me, of
>4000 paired CSF and serum samples of dementia patients (a.o.
Alzheimer, Frontotemporal, Lewy Bodies) and controls with
subjective complaints, that visit the Alzheimer Center Amsterdam
outpatient clinic. To ensure the quality of biosamples, Teunissen
performs scientific studies to detect e.g. sentinel biomarkers, and
take the lead in guideline development for CSF biomarker study
methodology. Teunissen has always collaborated strongly in the
field, as this is a prerequisite for performing high quality
biomarker studies, visible in her lead in the BioMS network, the
Society for Neurochemistry and routine CSF analysis, and the
Alzheimer Association-global biomarker standardization consortium.
Dr. Tumani received his medical degree from the University of
Göttingen/Germany in 1991. He received Board certification in
Neurology in 1999, and completed his professorship thesis in 2001
on the topic “physiology and clinical relevance of brain-specific
proteins in CSF.
Dr. Tumani is Professor of Neurology and Director of Multiple
Sclerosis Center at the Dept. of Neurology of the University School
of Medicine, in Ulm/Germany. He is also the Director of the CSF
laboratory, and past President of the “German Society of CSF
analysis and clinical neurochemistry (DGLN). Since 2015, he is
also Chief of the Clinic of Neurology Dietenbronn in
Schwendi/Germany specialized for diagnostics and treatment of
neuroinflammatory and neurodegenerative disorders.
Dr. Tumani has published over 200 peer-reviewed original papers and
over 20 book chapters, and he is a reviewer for several journals
and research funding agencies. His scientific areas of interest
include diagnostic and prognostic biomarkers in neuroinflammatory
as well as neurodegenerative diseases. Dr. Tumani has served as
principal investigator on several multi-center clinical trials.
Dr. Tumani’s research has been funded by the Hertie-Foundation,
German Research Foundation (DFG), Federal Ministry of Education and
Research (BMBF), Faculty of University of Ulm,
Polyradikulitis-Stiftung, and the pharmaceutical industry.
Affiliations and Expertise: Department of Neurology, University of
Ulm, Germany
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