Jasper's Basic Mechanisms of the Epilepsies

Jeffrey L. Noebels is Cullen Chair in Neurogenetics and Professor of Neurology, Neuroscience, and Molecular and Human Genetics at Baylor College of Medicine. His major research focus is to identify genes and molecular targets for the treatment of epilepsy and its comorbidities. Massimo Avoli is Professor in the Departments of Neurology & Neurosurgery and Physiology at McGill University, and a member of the Neural Circuits Research Group at the Montreal Neurological Institute-Hospital. His laboratory employs electrophysiological, pharmacological and molecular approaches to analyze the mechanisms of neuronal network excitability and seizure generation. Michael A. Rogawski is Distinguished Professor of Neurology and Pharmacology at the University of California, Davis School of Medicine. His research encompasses the cellular neurophysiology of ion channels, the mechanisms of action of antiseizure medications, and epilepsy therapy discovery and development. Annamaria Vezzani is head of the Laboratory of Experimental Neurology, Department of Neuroscience at the Istituto di Ricerche Farmacologiche Mario Negri IRCCS. Her main research focus is on mechanisms of seizures and epileptogenesis, with the aim of identifying biomarkers and developing new epilepsy treatments. Antonio V. Delgado-Escueta is Professor Emeritus in Neurology at the David Geffen School of Medicine at UCLA. He studies the mechanisms of genetic epilepsies, including Lafora progressive myoclonus epilepsy and the genetic generalized epilepsies, like Juvenile Myoclonic Epilepsies and Childhood Absence Epilepsies.

PREFACE
DEDICATION
ACKNOWLEDGMENTS

SECTION 1 - EVOLVING CONCEPTS
1. The Paroxysmal Depolarizing Shift (PDS): The First Cellular Marker of Focal Epileptogenesis
David Prince and Massimo Avoli
2. Hippocampal Sclerosis in Temporal Lobe Epilepsy: New Views and Challenges
Carolyn Houser
3. Cerebral Cortical Dysplasia or Dysgenesis: Keratan Sulfate Proteoglycan for Fetal Axonal Guidance and Excitatory/Inhibitory Synaptic Targets that Influence Epileptogenesis
Harvey Sarnat and Laura Flores-Sarnat
4. mTOR in Acquired and Genetic Models of Epilepsy
Michael Wong, Angelique Bordey, and Steve C. Danzer
5. Epilepsy Genomics: Disease Causing Sequence Variants
Antonio Delgado-Escueta

SECTION 2 - SEIZURES, NETWORKS & SYSTEMS
Editor: Massimo Avoli; Associate Editors: Christophe Bernard and Marco de Curtis

Introduction
Massimo Avoli, Marco de Curtis, Christophe Bernard, and Ivan Soltesz
6. GABAa-Receptor Signaling and Ionic Plasticity in the Generation and Spread of Seizures
Kai Kaila, Andrew Trevelyan, Joseph Raimondo, Tommi Ala-Kurikka, Gilles Huberfeld, Massimo Avoli, and Marco de Curtis
7. Connexins, Pannexins and Epilepsy
Liang Zhang, Georg R. Zoidl, and Peter L. Carlen
8. Mechanisms Leading to Initiation, Development and Termination of Focal Seizures
Marco de Curtis, Piotr Suffczynski, Maxime Lévesque, Laura Librizzi,Laura Uva, Paolo Scalmani, Vadym Gnatkovsky, and Massimo Avoli
9. Transition to Seizure from Cellular, Network, and Dynamical Perspectives
Wei-Chih Chang, Jan Kudlacek, Premysl Jiruska, and John G.R. Jefferys
10. Role of the Subiculum in Focal Epilepsy
Alesya Evstratova, Belén Diaz-Fernandez, Maxime Lévesque, Massimo Avoli, and Gand illes Huberfeld
11. Optogenetic Modulation of Focal Seizures
Maxime Lévesque, Massimo Avoli, and Merab Kokaia
12. Balancing Seizure Control with Cognitive Side-Effects
Sheela Tropani, Gene G Gurkoff, Kiarash Shahlaie, Fady Girgis, Ignacio Saez, Jeffrey Kennedy, and Karen A Moxon
13. High Frequency Oscillations
Liset Menendes de la Prida and Jean Gotman
14. Seizures and Sleep
Birgit Frauscher and Igor Timofeev
15. Cycles in epilepsy
Maxime Baud, Vikram Rao, Christophe Bernard, and Philippa Karoly
16. Human Single Unit Recordings in Epilepsy
Edward Merricks and Catherine Schevon
17. Role of Ion Concentration Dynamics in Epileptic Seizures
Oscar C González, Igor Timofeev, and Maxim Bazhenov
18. A Classification of Seizures Based on Dynamics
Hiba Sheheitli, Huifang Wang, Jean-Didier Lemarechal, Christophe Bernard, and Viktor K. Jirsa
19. Seizures, Networks & Systems - Computational EEG Analysis of Human Epileptogenic Networks
Vadim Gnatkovsky and Kaspar Schindler
20. Excitation-Inhibition Balance in Absence Seizure Ictogenesis
Magor L. Lõrincz, Vincenzo Crunelli, and Francois David
21. Cortical and Thalamic PV+ Interneuron Dysfunction in the Pathogenesis of Absence Epilepsy
Jochen Meyer and Atul Maheshwari
22. Convergence of Thalamic Mechanisms in Genetic Epilepsies
Frances Cho and Jeanne Paz

Section 3 - EPILEPTOGENESIS: MOLECULAR MECHANISMS & TREATMENTS
Editor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall

Introduction
Annamaria Vezzani and Helen Scharfman
23. The Diverse Roles of Mossy Cells in the Normal Brain, Epileptogenesis, and Chronic Epilepsy
Helen Scharfman
24. Temporal Lobe Epileptogenesis; A Focus on Etiology, Neuron Loss, The Latent Period, and Dentate Granule Cell Disinhibition
Robert Sloviter
25. Adult Neurogenesis in Epileptogenesis and Comorbidities
Kyung-Ok Cho and Jenny Hsieh
26. A Crucial Role for Astrocytes in Epileptogenesis: Gap Junctions and Glutamate Receptors
Peter Bedner, Allison R. Peterson, DevinK.Binder, Christian Steinhäuser
27. Adenosine Kinase: Cytoplasmic and Nuclear Isoforms
Madhuvika Murugan and Detlev Boison
28. Inflammatory Astrocytic TGFß- Signaling Induced by Blood-Brain Barrier Dysfunction Drives Epileptogenesis
Lynn T. Yang, Giovanni Anthony, and Daniela Kaufer
29. Pericytes and Microglia: Neurovascular and Immune Regulatory Cells in Seizure Disorders
Nicola Marchi and Amy Brewster
30. Neuroinflammation in Epilepsy: Cellular and Molecular Mechanisms
Ray Dingledine, Nicholas Varvel, Teresa Ravizza, and Annamaria Vezzani
31. Role of Reactive Oxygen Species in Epilepsy
Ashwini Sri Hari, Matthew C. Walker, and Manisha Patel
32. BDNF/TrkB Signaling and Epileptogenesis
Stephen Harward, Yang Huang, and James McNamara
33. Clinical Features and Molecular Mechanisms Underlying Autoantibody-Mediated Seizures
Alexander Mathy and Sarosh Irani
34. Transcriptomic Alterations in Epileptogenesis: Transcription Factors in the Spotlight
Gary Brennan and Karen van Loo
35. Epigenetics
Katja Kobow and Nadia Khan

SECTION 4 - BIOMARKERS OF EPILEPTOGENESIS
Editor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall

Introduction
Annamaria Vezzani and David Henshall
36. EEG Biomarkers of Epileptogenesis
Lyna Kamintsky, Dan Z Milikovsky, and Alon Friedman
37. Blood Biomarkers: Noncoding RNAs and Proteins
David Henshall and Michele Simonato
38. Behavioural Biomarkers of Epileptogenesis and Epilepsy Severity
Idrish Ali, Pablo Casillas-Espinosa, Nigel Jones, and Terence O'Brien
39. Genetic and Imaging Biomarkers of Epileptogenesis
Matthias Koepp, Simona Balestrini, Stefanie Dedurwaerdere, and William Theodore
40. Machine-Learning Approach to Discover Novel Biomarkers for Post-Traumatic Epilepsy
Robert Ciszek, Eppu Manninen, Olli Gröhn, Jussi Tohka, and Asla Pitkänen

SECTION 5 - GENES AND NETWORK DEVELOPMENT
Editors: Antonio Delgado Escueta and Jeffrey Noebels; Associate Editor: Elsa Rossignol

Introduction
Jeffrey Noebels
41. Human Epilepsy Gene Discovery: The Next Decade
Emily Bonkowski and Heather Mefford
42. Functional Exploration of Epilepsy Genes in Patint-Derived Cells
Maria 'Carmen' Varela, Ranmal Samarasinghe, and Jack Parent
43. Brain mosaicism in Epileptogenic Cortical Malformations
Théo Ribierre and Stéphanie Baulac
44. Sodium Channelopathies in Human and Animal Models of Epilepsy and Neurodevelopmental Disorders
Kazuhiro Yamakawa, Miriam Meisler, and Lori Isom
45. Potassium Channels in Genetic Epilepsy: a Functional Perspective
Matthew Weston and Anastasios Tzingounis
46. High Voltage Activated Calcium Channels in Epilepsy: Lessons from Humans and Rodents
Elsa Rossignol
47. Transcription Factors Regulating Interneuron Development
Emily Ling-Lin Pai, Daniel Vogt, Jia Sheng Hu, and John Rubenstein
48. GABAA Receptors, Seizures and Epilepsy
Richard Olsen, Martin Wallner, and Michael A. Rogawski
49. Gene genome interactions - Understanding complex molecular traits in epilepsy
Katja Kobow and John Mahoney

SECTION - 6 PROGRESSIVE MYOCLONUS EPILEPSIES
Editor: Antonio Delgado-Escueta; Associate Editor: Berge Minassian

Introduction
A.V. Delgado-Escueta, Berge Minassian, Jose M Seratossa
50. The Neuronal Ceroid Lipofuscinoses
Sara Mole
51. Progressive Myoclonus Epilepsy: Unverricht-Lundborg Disease
Saara Tegelberg, Tarja Joensuu, and Anna-Elina Lehesjoki
52. Strategies on Gene Therapy in Progressive Myoclonus Epilepsies
Saima Kayani, Emrah Gumusgoz, Berge Minassian, and Alison Dolce
53. Therapeutic Window for the Treatment of Lafora Disease
Olga Varea, Joan Guinovart, and Jordi Duran
54. Progressive Myoclonus Epilepsy of Lafora- Treatment with Metformin
Jose M. Seratossa, Daniel F. Burgos, Luis Zafra-Puerta, Nerea Iglesias-Cabeza, Pascual Sanz, and Marina P. Sánchez
55. Treating Lafora Disease with an Antibody-Enzyme Fusion
Matthew Gentry, Kia H. Markussen, Ramon Sun, and Craig W. Vander Kooi
56. Antisense Oligonucleotide Therapy for Progressive Myoclonus Epilepsies
Silvia Nitschke and Berge Minassian

SECTION 7 - COMORBIDITIES OF EPILEPTIC NETWORKS
Editor: Jeffrey Noebels; Associate Editor: Peyman Golshani

Introduction
Jeffrey Noebels
57. Dissecting Epileptic and Cognitive Network Dysfunction in Epilepsy
Pierre-Pascal Lenck-Santini and Greg Holmes
58. Attention Deficit Disorders and Epilepsy
Atul Maheshwari
59. What Rodent Models Teach Us About the Association of Autism and Epilepsy
Peyman Golshani
60. Artificial Intelligence-Guided Behavioral Phenotyping in Epilepsy
Tilo Gschwind and Ivan Soltesz
61. Mechanisms of Depression in the Epileptic Brain
Nigel Jones and Jamie Maguire
62. Heterogeneous Mechanisms of Spreading Depolarization and Seizures
Isamu Aiba
63. Genetic and Cellular Mechanisms Underlying SUDEP Risk
Jeffrey Noebels

SECTION 8- EPILEPSY THERAPEUTICS

Editor: Michael Rogawski; Associate Editors: Wolfgang Löscher & Steve White

Introduction
Michael Rogawski
64. New Models for Assessment of Antiseizure Activity
Cameron Metcalf, Peter West, Sharon Edwards, and Karen Wilcox
65. Disease Biology Factors Accounting for Epilepsy Severity: An Updated Conceptual Framework for New Drug Discovery
Stefanie Dedeurwaerdere, Vincenzo Marra, and Michael R Johnson
66. Animal Models of Pharmacoresistant Epilepsy
Michelle Guignet and H. Steve White
67. Drug Combinations for Antiepileptogenesis
Wolfgang Löscher
68. Prophylaxis of Epileptogenesis in Injury and Genetic Epilepsy Models
David Prince and Feng Gu
69. Management of Febrile Status Epilepticus: Past, Present and Future
Megan M. Garcia-Curran and Tallie Z. Baram
70. Excitatory Transmission in Status Epilepticus
Suchitra Joshi and Jaideep Kapur
71. Ionic Mechanisms of Ictogenic Disinhibition: All GABA Signaling is Local
Kevin Staley
72. Epileptogenic Channelopathies Guide Design of NBI-921352, a Highly Isoform-Selective Inhibitor of NaV1.6
J.P. Johnson, Jr, Alison J Cutts, James R. Empfield, and Charles J. Cohen
73. Purinergic Signaling in Epilepsy
Tobias Engel and Nicholas Dale
74. Anti-Inflammatory Strategies for Disease Modification: Focus on Therapies Close to Clinical Translation
Annamaria Vezzani, Silvia Balosso, Nicholas H. Varvel, and Ray Dingledine
75. Targeted Augmentation of Nuclear Gene Output (TANGO)
Lori Isom and Kelly G. Knupp
76. Gene Therapy for Epilepsy
Kimberly Goodspeed, Dallas Armstrong, Andrea Boitnott, Alison Dolce, Qinglan Ling, and Steve Gray
77. Gene Therapy for Refractory Epilepsy
Dimitri Kullmann
78. Cell Therapy for Treatment of Epilepsy
Sonja Bröer and Daniel Vogt
79. Mechanisms of Ketogenic Diet Action
Robin Williams, Detlev Boison, Susan Masino, and Jong Rho