Inflammation and Epilepsy: New Vistas


Book Description

This book provides comprehensive information, both for clinicians and scientists, on the basic mechanisms, clinical features, and therapeutic approaches to epilepsy as an inflammatory disease. Inflammation has been for many years considered as an etiologic player (and a therapeutic target) for a specific group of epilepsies. However, it turns out that this concept underestimated the impact of inflammation in seizure disorders. Many accepted therapies for non-inflammatory epilepsies act in part as an inflammatory drug. The CNS actively responds to acute immune challenges by altering body temperature, stimulating the HPA axis, as well as up- and down-regulating specific sympathetic pathways.




The chronic challenge - new vistas on long-term multisite contacts to the central nervous system


Book Description

Have you ever heard of a Hype-Cycle? It is a description that was put forward by an IT consultancy firm to describe certain phenomena that happen within the life cycle of new technology products. As Fenn and Raskino stated in their book (Fenn and Raskino 2008), a novel technology - a “Technology Trigger” - gives rise to a steep increase in interest, leading to the “Peak of Inflated Expectations”. Following an accumulation of more detailed knowledge on the technology and its short-comings, the stake holders may need to traverse a “Trough of Disillusionment”, which is followed by a shallower “Slope of Enlightenment”, before finally reaching the “Plateau of Productivity”. In spite of the limitations and criticisms levied on this over-simplified description of a technology’s life-cycle, it is nonetheless able to describe well the situation we are all experiencing within the brain-machine-interfacing community. Our technology trigger was the development of batch-processed multisite neuronal interfaces based on silicon during the 1980s and 1990s (Sangler and Wise 1990, Campbell, Jones et al. 1991, Wise and Najafi 1991, Rousche and Normann 1992, Nordhausen, Maynard et al. 1996). This gave rise to a seemingly exponential growth of knowledge within the neurosciences, leading to the expectation of thought-controlled devices and prostheses for handicapped people in the very near future (Chapin, Moxon et al. 1999, Wessberg, Stambaugh et al. 2000, Chapin and Moxon 2001, Serruya, Hatsopoulos et al. 2002). Unfortunately, whereas significant steps towards artificial robotic limbs could have been implemented during the last decade (Johannes, Bigelow et al. 2011, Oung, Pohl et al. 2012, Belter, Segil et al. 2013), direct invasive intracortical interfacing was not quite able to keep up with these expectations. Insofar, we are currently facing the challenging, but tedious walk through the Trough of Disillusionment. Undoubtedly, more than two decades of intense research on brain-machine-interfaces (BMI’s) have produced a tremendous wealth of information towards the ultimate goal: a clinically useful cortical prosthesis. Unfortunately even today - after huge fiscal efforts - the goal seems almost to be as far away as it was when it was originally put forward. At the very least, we have to state that one of the main challenges towards a clinical useful BMI has not been sufficiently answered yet: regarding the long term – or even truly chronic – stability of the neural cortical interface, as well as the signals it has to provide over a significant fraction of a human’s lifespan. Even the recently demonstrated advances in BMI’s in both humans and non-human primates have to deal with a severe decay of spiking activity that occurs over weeks and months (Chestek, Gilja et al. 2011, Hochberg, Bacher et al. 2012, Collinger, Kryger et al. 2014, Nuyujukian, Kao et al. 2014, Stavisky, Kao et al. 2014, Wodlinger, Downey et al. 2014) and resolve to simplified features to keep a brain-derived communication channel open (Christie, Tat et al. 2014).







Structure-Based Drug Design for Diagnosis and Treatment of Neurological Diseases


Book Description

European Cooperation in Science and Technology (COST) supports the collaboration of nationally-funded science and technology research through the creation of networks. COST is the longest-running European framework enhancing cooperation among researchers, engineers and scholars across Europe. The COST Action CM1103 “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain” is a good example of the advances possible through interdisciplinary collaboration on difficult problems. COST Action CM1103 brought together 28 research groups from 18 countries to collaborate for four years on multi-target drug design for complex neuropathologies. The interdisciplinary expertise of the members is spans the range from computational enzymology to human studies, providing outstanding opportunities for the interdisciplinary development of trainees, and is reflected in the articles in this e-book. This Research Topic covers progress in multi-target drug design for the complex neuropathologies of the monoamine system that are apparent, for example, in Alzheimer’s disease. After a mini-review to introduce the topic of multi-target drug design, the other articles review the Research topic from their own perspective, two from computational approaches, three from medicinal chemistry, two from molecular pharmacology, and two from studies in whole brain. This multi-faceted approach describes new compounds, new methodology, and advances in the basic science of understanding the brain. This Ebook is based upon work from COST Action (CM1103 “Structure-based drug design for diagnosis and treatment of neurological diseases: dissecting and modulating complex function in the monoaminergic systems of the brain"), supported by COST (European Cooperation in Science and Technology). COST (European Cooperation in Science and Technology) is a pan-European intergovernmental framework. Its mission is to enable break-through scientific and technological developments leading to new concepts and products and thereby contribute to strengthening Europe’s research and innovation capacities. It allows researchers, engineers and scholars to jointly develop their own ideas and take new initiatives across all fields of science and technology, while promoting multi- and interdisciplinary approaches. COST aims at fostering a better integration of less research intensive countries to the knowledge hubs of the European Research Area. The COST Association, an International not-for-profit Association under Belgian Law, integrates all management, governing and administrative functions necessary for the operation of the framework. The COST Association has currently 36 Member Countries. www.cost.eu




Stress and Inflammation in Disorders


Book Description

Stress and Inflammation in Disorders, Volume 108, the newest volume in this ongoing series, brings forth new information on protocols and analysis of proteins. This volume covers the latest on Oxidative Stress: Love and Hate History in the Central Nervous System, Neuroinflammation in Alzheimer's Disease: The Preventive and Therapeutic Potential of Polyphenolic Nutraceuticals, Inflammation in Epileptic Encephalopathies, A Computational Approach to Identify the Biophysical and Structural Aspect of Methylenetetrahydrofolate Reductase (MTHFR) Mutations (A222V, E429A and R594Q) Leading to Schizophrenia, and Analyzing the Effect of V66M Mutation in BDNF in Causing MOOD Disorders- A Computational Approach. Each release in the Advances in Protein Chemistry and Structural Biology series is an essential resource for protein chemists, with each thematically organized volume guest edited by leading experts in a broad range of protein-related topics. - Provides cutting-edge developments in protein chemistry and structural biology - Features new information about protocols and analysis of proteins - Contains chapters written by authorities in their respective fields - Targeted to a wide audience of researchers, specialists, and students




Pathological Potential of Neuroglia


Book Description

Pathophysiological states, neurological and psychiatric diseases are almost universally considered from the neurocentric point of view, with neurons being the principal cellular element of pathological process. The brain homeostasis, which lies at the fulcrum of healthy brain function, the compromise of which invariably results in dysfunction/disease, however, is entirely controlled by neuroglia. It is becoming clear that neuroglial cells are involved in various aspects of initiation, progression and resolution of neuropathology. In this book we aim to integrate the body of information that has accumulated in recent years revealing the active role of glia in such pathophysiological processes. Understanding roles of glial cells in pathology will provide new targets for medical intervention and aide the development of much needed therapeutics. This book will be particularly useful for researchers, students, physicians and psychotherapists working in the field of neurobiology, neurology and psychiatry.




Pellock's Pediatric Epilepsy


Book Description

Now in its fourth edition, Pellock’s Pediatric Epilepsy: Diagnosis and Therapy remains the gold standard for diagnosis, treatment, classification, and management of childhood epilepsies. With over 100 distinguished contributors from world-leading epilepsy programs, the long-awaited new edition maintains the breadth and scope the book is known for while significantly updating the science, practice, and therapeutic strategies that continue to move the field forward. At the center of this new edition is the totally reorganized and expanded section on age-related syndromes. There is a major emphasis on new genetic-based classifications and the clinical implications for identifying and managing the various subtypes. New chapters devoted exclusively to Panayiotopoulos syndrome, myoclonic status epilepticus, and autosomal dominant focal epilepsies, among others, cover even more ground than the last edition. Brand-new chapters in the drug and diet section cover perampanel, ezogabine, and lacosamide, while the existing chapters on major medical treatments have been comprehensively updated to reflect the latest trials and studies. Other sections contain new chapters on genetics, non-invasive functional mapping, sleep issues for pediatric epilepsy patients, and more. With more than 80 chapters, Pellock’s Pediatric Epilepsy now contains a full discussion of the spectrum of epilepsy disorders, not just seizures. From basic mechanisms and epidemiology, through diagnosis and therapy, to quality of life issues, the new edition of this established reference covers every aspect of childhood epilepsy and will continue to be the definitive core text for all professionals involved in the field. New to the Fourth Edition: Every chapter thoroughly reviewed, revised, and updated Section on age-related syndromes completely reconfigured to align with new ILAE terminology and organization in classifying seizures and forms of epilepsy Major update on disease mechanisms and all treatments for epilepsy, including drugs Increased attention to special populations, including a heavily-updated chapter on the female epilepsy patient New final section covers the epilepsy spectrum, with new chapters on epilepsy and sleep, co-morbidities of childhood, behavioral influence of AEDs, and transitioning to adulthood







Histiocytic Disorders


Book Description

This volume provides a comprehensive and world-class review of the field of histiocytic neoplasms and hemophagocytic lymphohistiocytosis (HLH). It reviews all the advances in the field of histiocytoses during the last ten years, particularly with regards to the genomic findings in LCH and other histiocytic neoplasms and the new suggested classification of the histiocytic disorders. Additionally, it features a state-of-the art update on the most recent treatment strategies for LCH, including the results of the last LCH-III international trial, salvage therapies such as reduced-intensity conditioning (RIC) stem cell transplant (SCT), and targeted therapies with BRAF and MEK inhibitors, as well as the challenging cases of CNS-neurodegenerative LCH and its therapeutic perspectives. For primary and secondary HLH the book updates the most recent genetic and pathophysiological findings, including macrophage-activation syndrome (MAS), and includes a special chapter on HLH in adults. Treatment chapters encompass therapy for newly diagnosed HLH and refractory disease as well as stem-cell transplantation and novel therapies. The text also highlights the most recent advances in the treatment of the uncommon histiocytic disorders, such as Erdheim-Chester disease (ECD), Juvenile xanthogranuloma (JXG) and JXG-like conditions, Rosai-Dorfman disease (RDD), and the very rare malignant histiocytoses. Written by international experts in the field, Histiocytic Disorders is a valuable resource for clinicians, researchers, fellows and residents who are interested in or manage histiocytic disorders in children and adults.




Models of Seizures and Epilepsy


Book Description

Models of Seizures and Epilepsy, Second Edition, is a valuable, practical reference for investigators who are searching for the most appropriate laboratory models to address key questions in the field. The book also provides an important background for physicians, fellows, and students, offering insight into the potential for advances in epilepsy research as well as R&D drug development. Contents include the current spectrum of models available to model different epilepsy syndromes, epilepsy in transgenic animals, comorbidities in models of epilepsy, and novel technologies to study seizures and epilepsies in animals. - Provides a comprehensive reference detailing animal models of epilepsy and seizure - Offers insights on the use of novel technologies that can be applied in experimental epilepsy research - Edited by leading experts in the field that provide not only technical reviews of these models but also conceptual critiques - Comments on the strengths and limitations of various models, including their relationship to clinical phenomenology and their value in developing better understanding and treatments