Epilepsy is a neurological disorder that affects about 65 million people worldwide. Although antiepileptic drugs provide sufficient control of seizures in approximately 70% of patients with epilepsy, the remaining 30% are resistant to monotherapy. This means around 20 million people worldwide face significant adverse life-long consequences such as sudden unexpected death from epileptic seizures, increased risk of injuries, and learning and developmental disabilities at school age. That is why, a continuous search for drugs targeting novel antiseizure mechanisms and alternative ways of epilepsy management is going on. This book covers a number of valid issues aimed at understanding the etiology and pathophysiology of epilepsy, epilepsy genetics, current therapeutic challenges, and possible novel therapeutic targets. The authors point to a number of etiologic factors, which incorporate anatomic, acquired, genetic, metabolic, and immunologic aspects. The overlap between neurodevelopmental disorders and epilepsy, and the involvement of hippocampal sclerosis in the process of epileptogenesis are also elegantly described. The readers will also find a very detailed description of the contemporary management of status epilepticus. There are also clues on how to inhibit a very dangerous super refractory status epilepticus. Regarding precision medicine-based management of epilepsy, recent data on GABAA receptor variants and canonical transient receptor potential channels are provided, which can help develop novel strategies for epilepsy treatment. Ketogenic diet may be considered as a non-pharmacological option for children and adolescents suffering from drug-resistant epilepsy. The book, covering various aspects of epilepsy from receptor and genetic studies to therapeutic clues, will be of particular value to scientists and clinicians.

Contents

• Foreword
• Preface
• List of Contributors
• 1. Pathophysiological Mechanisms Underlying the Etiologies of Seizures and Epilepsy
  Alejandro Vera-González.
  • INTRODUCTION
  • ETIOLOGY OF EPILEPSY AND PATHOPHYSIOLOGICAL MECHANISMS
  • CURRENT EPILEPSY TREATMENT
  • FUTURE DIRECTIONS
  • CONCLUSION
  • REFERENCES
• 2. The Anatomical Basis of Seizures
  Pradip Chauhan, Shalom Elsy Philip, Girish Chauhan, and Simmi Mehra.
  • INTRODUCTION
  • THE HIPPOCAMPUS AND EPILEPSY
  • THE TEMPORAL LOBE, THALAMUS, AMYGDALA AND EPILEPSY
  • OLFACTORY CORTEX AND EPILEPSY
  • FRONTAL CORTEX AND EPILEPSY
  • CEREBELLUM AND EPILEPSY
  • DENDRITIC PATHOLOGY AND EPILEPSY
  • CONCLUSION
  • REFERENCES
• 3. Epilepsy Genetics: Advancements in the Field and Impact on Clinical Practice
  Senyene E. Hunter, Elizabeth Jalazo, Thomas R. Felton, Erin L. Heinzen, and Yael Shiloh-Malawsky.
  • INTRODUCTION
  • OVERVIEW
  • EPIDEMIOLOGY
  • METHODS AND TECHNOLOGY PROGRESS – FROM BENCH TO BEDSIDE
  • PARADIGM SHIFT IN THE FIELD
  • IMPLICATIONS AND IMPACT ON PATIENT CARE
  • EVALUATION PATHWAY
  • CHALLENGES IN GENETIC EVALUATIONS AND TEST INTERPRETATION
  • SUGGESTED CLINICAL PRACTICE MODEL
  • CONCLUSION
  • REFERENCES
• 4. Overlap Between Epilepsy and Neurodevelopmental Disorders: Insights from Clinical and Genetic Studies
  Hitomi Shimizu, Yoshiro Morimoto, Naoki Yamamoto, Tatsuyuki Tayama, Hiroki Ozawa, and Akira Imamura.
  • INTRODUCTION
  • THE GENETIC BACKGROUNDS OF NEURODEVELOPMENTAL DISORDERS AND EPILEPSY
  • MODELS OF OVERLAP BETWEEN EPILEPSY AND NEURODEVELOPMENTAL DISORDERS
  • CONCLUSION
  • REFERENCES
• 5. Modern Treatment of Status Epilepticus in Adults
  Kjell Heuser, Ketil Berg Olsen, Line Bédos Ulvin, Leif Gjerstad, and Erik Taubøll.
  • INTRODUCTION
  • EARLY-STAGE STATUS EPILEPTICUS
  • ESTABLISHED STATUS EPILEPTICUS
  • REFRACTORY STATUS EPILEPTICUS
  • SUPER-REFRACTORY STATUS EPILEPTICUS
  • NON-ANTISEIZURE MEDICATIONS USED IN THE TREATMENT OF STATUS EPILEPTICUS
  • OTHER TREATMENT OPTIONS
  • CONCLUSION
  • REFERENCES
• 6. Canonical Transient Receptor Potential Channels as Novel Targets for Antiepileptic Drugs
  Fang Zheng.
  • INTRODUCTION
  • TRPC: SUBUNIT COMPOSITION, STRUCTURE, AND GATING
  • CONCLUSION
  • REFERENCES
• 7. GABA_A Receptor Variants in Epilepsy
  Xu Fu, Ya-Juan Wang, Jing-Qiong Kang, and Ting-Wei Mu.
  • INTRODUCTION
  • STRUCTURE OF GABA_ARECEPTORS
  • EPILEPSY-ASSOCIATED VARIANTS IN THE α1 SUBUNIT
  • EPILEPSY-ASSOCIATED VARIANTS IN THE β2/β3 SUBUNIT
  • EPILEPSY-ASSOCIATED VARIANTS IN THE γ2 SUBUNIT
  • VARIANTS WITH MODERATE SEVERITY OF EPILEPSY SYNDROMES
  • VARIANTS WITH SEVERE EPILEPSY SYNDROMES
  • CONCLUSION
  • REFERENCES
• 8. The Role of Milk Nutrition and Ketogenic Diet in Epileptic Disorders
  Maria Giovanna Ciliberti, Antonella Santillo, Rita Polito, Giovanni Messina, and Marzia Albenzio.
  • INTRODUCTION
  • THE GUT-BRAIN AXIS IN CHILDHOOD EPILEPSY DISORDER
  • THE ROLE OF KETOGENIC DIET IN EPILEPSY TREATMENT
  • COW’S MILK ALLERGY AND EPILEPTIC EVENTS
  • CONCLUSION
  • REFERENCES

Professor Stanislaw J. Czuczwar, MD, PhD, graduated from the Medical Faculty of Lublin Medical University, Poland, in 1975. Currently, he is the Head of Department of Pathophysiology at the Lublin Medical University. His area of research is mainly focused on experimental epilepsy and antiepileptic drugs. With his research team, he characterized, using isobolographic analysis, several synergistic combinations of antiepileptic drugs, which may be of importance for the management of drug-resistant epilepsy. During his time in the Department of Experimental Neurology, University of London, UK, he tested newly synthesized antagonists of N-methyl-D-aspartate receptors as potential anticonvulsant agents. His research continued at the Free University of West Berlin, Germany, where he evaluated ligands of various receptors in the search of anticonvulsants. In the 1990s of the former century, he stayed as a visiting professor at the Department of Neurology of Vanderbilt University (Nashville, TN, USA). He has published more than 450 papers, mainly devoted to interactions of antiepileptic drugs with drugs affecting various receptors or channels, delineating promising combined treatments from the preclinical point of view.

Epilepsy

ISBN: 978-0-6453320-4-9

DOI: https://doi.org/10.36255/exon-publications-epilepsy

Edited by

Stanislaw J. Czuczwar, MD, PHD, Department of Pathophysiology, Medical University of Lublin, Lublin, Poland

Published by

Exon Publications, Brisbane, Australia

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First Published in April 2022

Printed in Australia