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 Vezzaniis 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 DEDICATIONACKNOWLEDGMENTS SECTION 1 - EVOLVING CONCEPTS1. 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 ChallengesCarolyn Houser 3. Cerebral Cortical Dysplasia or Dysgenesis: Keratan Sulfate Proteoglycan for Fetal Axonal Guidance and Excitatory/Inhibitory Synaptic Targets that Influence EpileptogenesisHarvey Sarnat and Laura Flores-Sarnat4. mTOR in Acquired and Genetic Models of EpilepsyMichael Wong, Angelique Bordey, and Steve C. Danzer5. Epilepsy Genomics: Disease Causing Sequence VariantsAntonio Delgado-Escueta SECTION 2 - SEIZURES, NETWORKS & SYSTEMSEditor: Massimo Avoli; Associate Editors: Christophe Bernard and Marco de Curtis IntroductionMassimo Avoli, Marco de Curtis, Christophe Bernard, and Ivan Soltesz6. GABAa-Receptor Signaling and Ionic Plasticity in the Generation and Spread of SeizuresKai Kaila, Andrew Trevelyan, Joseph Raimondo, Tommi Ala-Kurikka, Gilles Huberfeld, Massimo Avoli, and Marco de Curtis7. Connexins, Pannexins and EpilepsyLiang Zhang, Georg R. Zoidl, and Peter L. Carlen8. Mechanisms Leading to Initiation, Development and Termination of Focal SeizuresMarco de Curtis, Piotr Suffczynski, Maxime Lévesque, Laura Librizzi,Laura Uva, Paolo Scalmani, Vadym Gnatkovsky, and Massimo Avoli9. Transition to Seizure from Cellular, Network, and Dynamical PerspectivesWei-Chih Chang, Jan Kudlacek, Premysl Jiruska, and John G.R. Jefferys10. Role of the Subiculum in Focal EpilepsyAlesya Evstratova, Belén Diaz-Fernandez, Maxime Lévesque, Massimo Avoli, and Gand illes Huberfeld11. Optogenetic Modulation of Focal SeizuresMaxime Lévesque, Massimo Avoli, and Merab Kokaia 12. Balancing Seizure Control with Cognitive Side-EffectsSheela Tropani, Gene G Gurkoff, Kiarash Shahlaie, Fady Girgis, Ignacio Saez, Jeffrey Kennedy, and Karen A Moxon13. High Frequency OscillationsLiset Menendes de la Prida and Jean Gotman 14. Seizures and SleepBirgit Frauscher and Igor Timofeev 15. Cycles in epilepsyMaxime Baud, Vikram Rao, Christophe Bernard, and Philippa Karoly16. Human Single Unit Recordings in EpilepsyEdward Merricks and Catherine Schevon17. Role of Ion Concentration Dynamics in Epileptic SeizuresOscar C González, Igor Timofeev, and Maxim Bazhenov18. A Classification of Seizures Based on DynamicsHiba Sheheitli, Huifang Wang, Jean-Didier Lemarechal, Christophe Bernard, and Viktor K. Jirsa19. Seizures, Networks & Systems - Computational EEG Analysis of Human Epileptogenic NetworksVadim Gnatkovsky and Kaspar Schindler20. Excitation-Inhibition Balance in Absence Seizure IctogenesisMagor L. Lõrincz, Vincenzo Crunelli, and Francois David21. Cortical and Thalamic PV+ Interneuron Dysfunction in the Pathogenesis of Absence EpilepsyJochen Meyer and Atul Maheshwari22. Convergence of Thalamic Mechanisms in Genetic Epilepsies Frances Cho and Jeanne Paz Section 3 - EPILEPTOGENESIS: MOLECULAR MECHANISMS & TREATMENTSEditor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall IntroductionAnnamaria Vezzani and Helen Scharfman23. The Diverse Roles of Mossy Cells in the Normal Brain, Epileptogenesis, and Chronic EpilepsyHelen Scharfman24. Temporal Lobe Epileptogenesis; A Focus on Etiology, Neuron Loss, The Latent Period, and Dentate Granule Cell DisinhibitionRobert Sloviter25. Adult Neurogenesis in Epileptogenesis and ComorbiditiesKyung-Ok Cho and Jenny Hsieh 26. A Crucial Role for Astrocytes in Epileptogenesis: Gap Junctions and Glutamate ReceptorsPeter Bedner, Allison R. Peterson, DevinK.Binder, Christian Steinhäuser27. Adenosine Kinase: Cytoplasmic and Nuclear IsoformsMadhuvika Murugan and Detlev Boison28. Inflammatory Astrocytic TGFß- Signaling Induced by Blood-Brain Barrier Dysfunction Drives EpileptogenesisLynn T. Yang, Giovanni Anthony, and Daniela Kaufer 29. Pericytes and Microglia: Neurovascular and Immune Regulatory Cells in Seizure DisordersNicola Marchi and Amy Brewster30. Neuroinflammation in Epilepsy: Cellular and Molecular MechanismsRay Dingledine, Nicholas Varvel, Teresa Ravizza, and Annamaria Vezzani31. Role of Reactive Oxygen Species in EpilepsyAshwini Sri Hari, Matthew C. Walker, and Manisha Patel32. BDNF/TrkB Signaling and EpileptogenesisStephen Harward, Yang Huang, and James McNamara33. Clinical Features and Molecular Mechanisms Underlying Autoantibody-Mediated SeizuresAlexander Mathy and Sarosh Irani34. Transcriptomic Alterations in Epileptogenesis: Transcription Factors in the SpotlightGary Brennan and Karen van Loo35. EpigeneticsKatja Kobow and Nadia Khan SECTION 4 - BIOMARKERS OF EPILEPTOGENESISEditor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall IntroductionAnnamaria Vezzani and David Henshall36. EEG Biomarkers of EpileptogenesisLyna Kamintsky, Dan Z Milikovsky, and Alon Friedman37. Blood Biomarkers: Noncoding RNAs and ProteinsDavid Henshall and Michele Simonato38. Behavioural Biomarkers of Epileptogenesis and Epilepsy SeverityIdrish Ali, Pablo Casillas-Espinosa, Nigel Jones, and Terence O'Brien39. Genetic and Imaging Biomarkers of EpileptogenesisMatthias Koepp, Simona Balestrini, Stefanie Dedurwaerdere, and William Theodore40. Machine-Learning Approach to Discover Novel Biomarkers for Post-Traumatic EpilepsyRobert Ciszek, Eppu Manninen, Olli Gröhn, Jussi Tohka, and Asla Pitkänen SECTION 5 - GENES AND NETWORK DEVELOPMENTEditors: Antonio Delgado Escueta and Jeffrey Noebels; Associate Editor: Elsa Rossignol IntroductionJeffrey Noebels41. Human Epilepsy Gene Discovery: The Next DecadeEmily Bonkowski and Heather Mefford42. Functional Exploration of Epilepsy Genes in Patint-Derived CellsMaria 'Carmen' Varela, Ranmal Samarasinghe, and Jack Parent 43. Brain mosaicism in Epileptogenic Cortical MalformationsThéo Ribierre and Stéphanie Baulac 44. Sodium Channelopathies in Human and Animal Models of Epilepsy and Neurodevelopmental DisordersKazuhiro Yamakawa, Miriam Meisler, and Lori Isom45. Potassium Channels in Genetic Epilepsy: a Functional PerspectiveMatthew Weston and Anastasios Tzingounis46. High Voltage Activated Calcium Channels in Epilepsy: Lessons from Humans and RodentsElsa Rossignol47. Transcription Factors Regulating Interneuron DevelopmentEmily Ling-Lin Pai, Daniel Vogt, Jia Sheng Hu, and John Rubenstein48. GABAA Receptors, Seizures and EpilepsyRichard Olsen, Martin Wallner, and Michael A. Rogawski49. Gene genome interactions - Understanding complex molecular traits in epilepsyKatja Kobow and John Mahoney SECTION - 6 PROGRESSIVE MYOCLONUS EPILEPSIESEditor: Antonio Delgado-Escueta; Associate Editor: Berge Minassian IntroductionA.V. Delgado-Escueta, Berge Minassian, Jose M Seratossa50. The Neuronal Ceroid LipofuscinosesSara Mole51. Progressive Myoclonus Epilepsy: Unverricht-Lundborg DiseaseSaara Tegelberg, Tarja Joensuu, and Anna-Elina Lehesjoki52. Strategies on Gene Therapy in Progressive Myoclonus EpilepsiesSaima Kayani, Emrah Gumusgoz, Berge Minassian, and Alison Dolce53. Therapeutic Window for the Treatment of Lafora DiseaseOlga Varea, Joan Guinovart, and Jordi Duran 54. Progressive Myoclonus Epilepsy of Lafora- Treatment with MetforminJose M. Seratossa, Daniel F. Burgos, Luis Zafra-Puerta, Nerea Iglesias-Cabeza, Pascual Sanz, and Marina P. Sánchez55. Treating Lafora Disease with an Antibody-Enzyme FusionMatthew Gentry, Kia H. Markussen, Ramon Sun, and Craig W. Vander Kooi56. Antisense Oligonucleotide Therapy for Progressive Myoclonus EpilepsiesSilvia Nitschke and Berge Minassian SECTION 7 - COMORBIDITIES OF EPILEPTIC NETWORKSEditor: Jeffrey Noebels; Associate Editor: Peyman Golshani IntroductionJeffrey Noebels57. Dissecting Epileptic and Cognitive Network Dysfunction in EpilepsyPierre-Pascal Lenck-Santini and Greg Holmes58. Attention Deficit Disorders and EpilepsyAtul Maheshwari59. What Rodent Models Teach Us About the Association of Autism and EpilepsyPeyman Golshani60. Artificial Intelligence-Guided Behavioral Phenotyping in EpilepsyTilo Gschwind and Ivan Soltesz61. Mechanisms of Depression in the Epileptic BrainNigel Jones and Jamie Maguire62. Heterogeneous Mechanisms of Spreading Depolarization and SeizuresIsamu Aiba63. Genetic and Cellular Mechanisms Underlying SUDEP RiskJeffrey Noebels SECTION 8- EPILEPSY THERAPEUTICS Editor: Michael Rogawski; Associate Editors: Wolfgang Löscher & Steve White IntroductionMichael Rogawski64. New Models for Assessment of Antiseizure ActivityCameron Metcalf, Peter West, Sharon Edwards, and Karen Wilcox65. Disease Biology Factors Accounting for Epilepsy Severity: An Updated Conceptual Framework for New Drug DiscoveryStefanie Dedeurwaerdere, Vincenzo Marra, and Michael R Johnson66. Animal Models of Pharmacoresistant EpilepsyMichelle Guignet and H. Steve White67. Drug Combinations for AntiepileptogenesisWolfgang Löscher68. Prophylaxis of Epileptogenesis in Injury and Genetic Epilepsy ModelsDavid Prince and Feng Gu69. Management of Febrile Status Epilepticus: Past, Present and FutureMegan M. Garcia-Curran and Tallie Z. Baram 70. Excitatory Transmission in Status EpilepticusSuchitra Joshi and Jaideep Kapur71. Ionic Mechanisms of Ictogenic Disinhibition: All GABA Signaling is LocalKevin Staley72. Epileptogenic Channelopathies Guide Design of NBI-921352, a Highly Isoform-Selective Inhibitor of NaV1.6J.P. Johnson, Jr, Alison J Cutts, James R. Empfield, and Charles J. Cohen73. Purinergic Signaling in EpilepsyTobias Engel and Nicholas Dale74. Anti-Inflammatory Strategies for Disease Modification: Focus on Therapies Close to Clinical TranslationAnnamaria Vezzani, Silvia Balosso, Nicholas H. Varvel, and Ray Dingledine75. Targeted Augmentation of Nuclear Gene Output (TANGO)Lori Isom and Kelly G. Knupp76. Gene Therapy for EpilepsyKimberly Goodspeed, Dallas Armstrong, Andrea Boitnott, Alison Dolce, Qinglan Ling, and Steve Gray77. Gene Therapy for Refractory EpilepsyDimitri Kullmann78. Cell Therapy for Treatment of EpilepsySonja Bröer and Daniel Vogt79. Mechanisms of Ketogenic Diet ActionRobin Williams, Detlev Boison, Susan Masino, and Jong Rho

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 Vezzaniis 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 DEDICATIONACKNOWLEDGMENTS SECTION 1 - EVOLVING CONCEPTS1. 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 ChallengesCarolyn Houser 3. Cerebral Cortical Dysplasia or Dysgenesis: Keratan Sulfate Proteoglycan for Fetal Axonal Guidance and Excitatory/Inhibitory Synaptic Targets that Influence EpileptogenesisHarvey Sarnat and Laura Flores-Sarnat4. mTOR in Acquired and Genetic Models of EpilepsyMichael Wong, Angelique Bordey, and Steve C. Danzer5. Epilepsy Genomics: Disease Causing Sequence VariantsAntonio Delgado-Escueta SECTION 2 - SEIZURES, NETWORKS & SYSTEMSEditor: Massimo Avoli; Associate Editors: Christophe Bernard and Marco de Curtis IntroductionMassimo Avoli, Marco de Curtis, Christophe Bernard, and Ivan Soltesz6. GABAa-Receptor Signaling and Ionic Plasticity in the Generation and Spread of SeizuresKai Kaila, Andrew Trevelyan, Joseph Raimondo, Tommi Ala-Kurikka, Gilles Huberfeld, Massimo Avoli, and Marco de Curtis7. Connexins, Pannexins and EpilepsyLiang Zhang, Georg R. Zoidl, and Peter L. Carlen8. Mechanisms Leading to Initiation, Development and Termination of Focal SeizuresMarco de Curtis, Piotr Suffczynski, Maxime Lévesque, Laura Librizzi,Laura Uva, Paolo Scalmani, Vadym Gnatkovsky, and Massimo Avoli9. Transition to Seizure from Cellular, Network, and Dynamical PerspectivesWei-Chih Chang, Jan Kudlacek, Premysl Jiruska, and John G.R. Jefferys10. Role of the Subiculum in Focal EpilepsyAlesya Evstratova, Belén Diaz-Fernandez, Maxime Lévesque, Massimo Avoli, and Gand illes Huberfeld11. Optogenetic Modulation of Focal SeizuresMaxime Lévesque, Massimo Avoli, and Merab Kokaia 12. Balancing Seizure Control with Cognitive Side-EffectsSheela Tropani, Gene G Gurkoff, Kiarash Shahlaie, Fady Girgis, Ignacio Saez, Jeffrey Kennedy, and Karen A Moxon13. High Frequency OscillationsLiset Menendes de la Prida and Jean Gotman 14. Seizures and SleepBirgit Frauscher and Igor Timofeev 15. Cycles in epilepsyMaxime Baud, Vikram Rao, Christophe Bernard, and Philippa Karoly16. Human Single Unit Recordings in EpilepsyEdward Merricks and Catherine Schevon17. Role of Ion Concentration Dynamics in Epileptic SeizuresOscar C González, Igor Timofeev, and Maxim Bazhenov18. A Classification of Seizures Based on DynamicsHiba Sheheitli, Huifang Wang, Jean-Didier Lemarechal, Christophe Bernard, and Viktor K. Jirsa19. Seizures, Networks & Systems - Computational EEG Analysis of Human Epileptogenic NetworksVadim Gnatkovsky and Kaspar Schindler20. Excitation-Inhibition Balance in Absence Seizure IctogenesisMagor L. Lõrincz, Vincenzo Crunelli, and Francois David21. Cortical and Thalamic PV+ Interneuron Dysfunction in the Pathogenesis of Absence EpilepsyJochen Meyer and Atul Maheshwari22. Convergence of Thalamic Mechanisms in Genetic Epilepsies Frances Cho and Jeanne Paz Section 3 - EPILEPTOGENESIS: MOLECULAR MECHANISMS & TREATMENTSEditor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall IntroductionAnnamaria Vezzani and Helen Scharfman23. The Diverse Roles of Mossy Cells in the Normal Brain, Epileptogenesis, and Chronic EpilepsyHelen Scharfman24. Temporal Lobe Epileptogenesis; A Focus on Etiology, Neuron Loss, The Latent Period, and Dentate Granule Cell DisinhibitionRobert Sloviter25. Adult Neurogenesis in Epileptogenesis and ComorbiditiesKyung-Ok Cho and Jenny Hsieh 26. A Crucial Role for Astrocytes in Epileptogenesis: Gap Junctions and Glutamate ReceptorsPeter Bedner, Allison R. Peterson, DevinK.Binder, Christian Steinhäuser27. Adenosine Kinase: Cytoplasmic and Nuclear IsoformsMadhuvika Murugan and Detlev Boison28. Inflammatory Astrocytic TGFß- Signaling Induced by Blood-Brain Barrier Dysfunction Drives EpileptogenesisLynn T. Yang, Giovanni Anthony, and Daniela Kaufer 29. Pericytes and Microglia: Neurovascular and Immune Regulatory Cells in Seizure DisordersNicola Marchi and Amy Brewster30. Neuroinflammation in Epilepsy: Cellular and Molecular MechanismsRay Dingledine, Nicholas Varvel, Teresa Ravizza, and Annamaria Vezzani31. Role of Reactive Oxygen Species in EpilepsyAshwini Sri Hari, Matthew C. Walker, and Manisha Patel32. BDNF/TrkB Signaling and EpileptogenesisStephen Harward, Yang Huang, and James McNamara33. Clinical Features and Molecular Mechanisms Underlying Autoantibody-Mediated SeizuresAlexander Mathy and Sarosh Irani34. Transcriptomic Alterations in Epileptogenesis: Transcription Factors in the SpotlightGary Brennan and Karen van Loo35. EpigeneticsKatja Kobow and Nadia Khan SECTION 4 - BIOMARKERS OF EPILEPTOGENESISEditor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall IntroductionAnnamaria Vezzani and David Henshall36. EEG Biomarkers of EpileptogenesisLyna Kamintsky, Dan Z Milikovsky, and Alon Friedman37. Blood Biomarkers: Noncoding RNAs and ProteinsDavid Henshall and Michele Simonato38. Behavioural Biomarkers of Epileptogenesis and Epilepsy SeverityIdrish Ali, Pablo Casillas-Espinosa, Nigel Jones, and Terence O'Brien39. Genetic and Imaging Biomarkers of EpileptogenesisMatthias Koepp, Simona Balestrini, Stefanie Dedurwaerdere, and William Theodore40. Machine-Learning Approach to Discover Novel Biomarkers for Post-Traumatic EpilepsyRobert Ciszek, Eppu Manninen, Olli Gröhn, Jussi Tohka, and Asla Pitkänen SECTION 5 - GENES AND NETWORK DEVELOPMENTEditors: Antonio Delgado Escueta and Jeffrey Noebels; Associate Editor: Elsa Rossignol IntroductionJeffrey Noebels41. Human Epilepsy Gene Discovery: The Next DecadeEmily Bonkowski and Heather Mefford42. Functional Exploration of Epilepsy Genes in Patint-Derived CellsMaria 'Carmen' Varela, Ranmal Samarasinghe, and Jack Parent 43. Brain mosaicism in Epileptogenic Cortical MalformationsThéo Ribierre and Stéphanie Baulac 44. Sodium Channelopathies in Human and Animal Models of Epilepsy and Neurodevelopmental DisordersKazuhiro Yamakawa, Miriam Meisler, and Lori Isom45. Potassium Channels in Genetic Epilepsy: a Functional PerspectiveMatthew Weston and Anastasios Tzingounis46. High Voltage Activated Calcium Channels in Epilepsy: Lessons from Humans and RodentsElsa Rossignol47. Transcription Factors Regulating Interneuron DevelopmentEmily Ling-Lin Pai, Daniel Vogt, Jia Sheng Hu, and John Rubenstein48. GABAA Receptors, Seizures and EpilepsyRichard Olsen, Martin Wallner, and Michael A. Rogawski49. Gene genome interactions - Understanding complex molecular traits in epilepsyKatja Kobow and John Mahoney SECTION - 6 PROGRESSIVE MYOCLONUS EPILEPSIESEditor: Antonio Delgado-Escueta; Associate Editor: Berge Minassian IntroductionA.V. Delgado-Escueta, Berge Minassian, Jose M Seratossa50. The Neuronal Ceroid LipofuscinosesSara Mole51. Progressive Myoclonus Epilepsy: Unverricht-Lundborg DiseaseSaara Tegelberg, Tarja Joensuu, and Anna-Elina Lehesjoki52. Strategies on Gene Therapy in Progressive Myoclonus EpilepsiesSaima Kayani, Emrah Gumusgoz, Berge Minassian, and Alison Dolce53. Therapeutic Window for the Treatment of Lafora DiseaseOlga Varea, Joan Guinovart, and Jordi Duran 54. Progressive Myoclonus Epilepsy of Lafora- Treatment with MetforminJose M. Seratossa, Daniel F. Burgos, Luis Zafra-Puerta, Nerea Iglesias-Cabeza, Pascual Sanz, and Marina P. Sánchez55. Treating Lafora Disease with an Antibody-Enzyme FusionMatthew Gentry, Kia H. Markussen, Ramon Sun, and Craig W. Vander Kooi56. Antisense Oligonucleotide Therapy for Progressive Myoclonus EpilepsiesSilvia Nitschke and Berge Minassian SECTION 7 - COMORBIDITIES OF EPILEPTIC NETWORKSEditor: Jeffrey Noebels; Associate Editor: Peyman Golshani IntroductionJeffrey Noebels57. Dissecting Epileptic and Cognitive Network Dysfunction in EpilepsyPierre-Pascal Lenck-Santini and Greg Holmes58. Attention Deficit Disorders and EpilepsyAtul Maheshwari59. What Rodent Models Teach Us About the Association of Autism and EpilepsyPeyman Golshani60. Artificial Intelligence-Guided Behavioral Phenotyping in EpilepsyTilo Gschwind and Ivan Soltesz61. Mechanisms of Depression in the Epileptic BrainNigel Jones and Jamie Maguire62. Heterogeneous Mechanisms of Spreading Depolarization and SeizuresIsamu Aiba63. Genetic and Cellular Mechanisms Underlying SUDEP RiskJeffrey Noebels SECTION 8- EPILEPSY THERAPEUTICS Editor: Michael Rogawski; Associate Editors: Wolfgang Löscher & Steve White IntroductionMichael Rogawski64. New Models for Assessment of Antiseizure ActivityCameron Metcalf, Peter West, Sharon Edwards, and Karen Wilcox65. Disease Biology Factors Accounting for Epilepsy Severity: An Updated Conceptual Framework for New Drug DiscoveryStefanie Dedeurwaerdere, Vincenzo Marra, and Michael R Johnson66. Animal Models of Pharmacoresistant EpilepsyMichelle Guignet and H. Steve White67. Drug Combinations for AntiepileptogenesisWolfgang Löscher68. Prophylaxis of Epileptogenesis in Injury and Genetic Epilepsy ModelsDavid Prince and Feng Gu69. Management of Febrile Status Epilepticus: Past, Present and FutureMegan M. Garcia-Curran and Tallie Z. Baram 70. Excitatory Transmission in Status EpilepticusSuchitra Joshi and Jaideep Kapur71. Ionic Mechanisms of Ictogenic Disinhibition: All GABA Signaling is LocalKevin Staley72. Epileptogenic Channelopathies Guide Design of NBI-921352, a Highly Isoform-Selective Inhibitor of NaV1.6J.P. Johnson, Jr, Alison J Cutts, James R. Empfield, and Charles J. Cohen73. Purinergic Signaling in EpilepsyTobias Engel and Nicholas Dale74. Anti-Inflammatory Strategies for Disease Modification: Focus on Therapies Close to Clinical TranslationAnnamaria Vezzani, Silvia Balosso, Nicholas H. Varvel, and Ray Dingledine75. Targeted Augmentation of Nuclear Gene Output (TANGO)Lori Isom and Kelly G. Knupp76. Gene Therapy for EpilepsyKimberly Goodspeed, Dallas Armstrong, Andrea Boitnott, Alison Dolce, Qinglan Ling, and Steve Gray77. Gene Therapy for Refractory EpilepsyDimitri Kullmann78. Cell Therapy for Treatment of EpilepsySonja Bröer and Daniel Vogt79. Mechanisms of Ketogenic Diet ActionRobin Williams, Detlev Boison, Susan Masino, and Jong Rho

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 Vezzaniis 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 DEDICATIONACKNOWLEDGMENTS SECTION 1 - EVOLVING CONCEPTS1. 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 ChallengesCarolyn Houser 3. Cerebral Cortical Dysplasia or Dysgenesis: Keratan Sulfate Proteoglycan for Fetal Axonal Guidance and Excitatory/Inhibitory Synaptic Targets that Influence EpileptogenesisHarvey Sarnat and Laura Flores-Sarnat4. mTOR in Acquired and Genetic Models of EpilepsyMichael Wong, Angelique Bordey, and Steve C. Danzer5. Epilepsy Genomics: Disease Causing Sequence VariantsAntonio Delgado-Escueta SECTION 2 - SEIZURES, NETWORKS & SYSTEMSEditor: Massimo Avoli; Associate Editors: Christophe Bernard and Marco de Curtis IntroductionMassimo Avoli, Marco de Curtis, Christophe Bernard, and Ivan Soltesz6. GABAa-Receptor Signaling and Ionic Plasticity in the Generation and Spread of SeizuresKai Kaila, Andrew Trevelyan, Joseph Raimondo, Tommi Ala-Kurikka, Gilles Huberfeld, Massimo Avoli, and Marco de Curtis7. Connexins, Pannexins and EpilepsyLiang Zhang, Georg R. Zoidl, and Peter L. Carlen8. Mechanisms Leading to Initiation, Development and Termination of Focal SeizuresMarco de Curtis, Piotr Suffczynski, Maxime Lévesque, Laura Librizzi,Laura Uva, Paolo Scalmani, Vadym Gnatkovsky, and Massimo Avoli9. Transition to Seizure from Cellular, Network, and Dynamical PerspectivesWei-Chih Chang, Jan Kudlacek, Premysl Jiruska, and John G.R. Jefferys10. Role of the Subiculum in Focal EpilepsyAlesya Evstratova, Belén Diaz-Fernandez, Maxime Lévesque, Massimo Avoli, and Gand illes Huberfeld11. Optogenetic Modulation of Focal SeizuresMaxime Lévesque, Massimo Avoli, and Merab Kokaia 12. Balancing Seizure Control with Cognitive Side-EffectsSheela Tropani, Gene G Gurkoff, Kiarash Shahlaie, Fady Girgis, Ignacio Saez, Jeffrey Kennedy, and Karen A Moxon13. High Frequency OscillationsLiset Menendes de la Prida and Jean Gotman 14. Seizures and SleepBirgit Frauscher and Igor Timofeev 15. Cycles in epilepsyMaxime Baud, Vikram Rao, Christophe Bernard, and Philippa Karoly16. Human Single Unit Recordings in EpilepsyEdward Merricks and Catherine Schevon17. Role of Ion Concentration Dynamics in Epileptic SeizuresOscar C González, Igor Timofeev, and Maxim Bazhenov18. A Classification of Seizures Based on DynamicsHiba Sheheitli, Huifang Wang, Jean-Didier Lemarechal, Christophe Bernard, and Viktor K. Jirsa19. Seizures, Networks & Systems - Computational EEG Analysis of Human Epileptogenic NetworksVadim Gnatkovsky and Kaspar Schindler20. Excitation-Inhibition Balance in Absence Seizure IctogenesisMagor L. Lõrincz, Vincenzo Crunelli, and Francois David21. Cortical and Thalamic PV+ Interneuron Dysfunction in the Pathogenesis of Absence EpilepsyJochen Meyer and Atul Maheshwari22. Convergence of Thalamic Mechanisms in Genetic Epilepsies Frances Cho and Jeanne Paz Section 3 - EPILEPTOGENESIS: MOLECULAR MECHANISMS & TREATMENTSEditor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall IntroductionAnnamaria Vezzani and Helen Scharfman23. The Diverse Roles of Mossy Cells in the Normal Brain, Epileptogenesis, and Chronic EpilepsyHelen Scharfman24. Temporal Lobe Epileptogenesis; A Focus on Etiology, Neuron Loss, The Latent Period, and Dentate Granule Cell DisinhibitionRobert Sloviter25. Adult Neurogenesis in Epileptogenesis and ComorbiditiesKyung-Ok Cho and Jenny Hsieh 26. A Crucial Role for Astrocytes in Epileptogenesis: Gap Junctions and Glutamate ReceptorsPeter Bedner, Allison R. Peterson, DevinK.Binder, Christian Steinhäuser27. Adenosine Kinase: Cytoplasmic and Nuclear IsoformsMadhuvika Murugan and Detlev Boison28. Inflammatory Astrocytic TGFß- Signaling Induced by Blood-Brain Barrier Dysfunction Drives EpileptogenesisLynn T. Yang, Giovanni Anthony, and Daniela Kaufer 29. Pericytes and Microglia: Neurovascular and Immune Regulatory Cells in Seizure DisordersNicola Marchi and Amy Brewster30. Neuroinflammation in Epilepsy: Cellular and Molecular MechanismsRay Dingledine, Nicholas Varvel, Teresa Ravizza, and Annamaria Vezzani31. Role of Reactive Oxygen Species in EpilepsyAshwini Sri Hari, Matthew C. Walker, and Manisha Patel32. BDNF/TrkB Signaling and EpileptogenesisStephen Harward, Yang Huang, and James McNamara33. Clinical Features and Molecular Mechanisms Underlying Autoantibody-Mediated SeizuresAlexander Mathy and Sarosh Irani34. Transcriptomic Alterations in Epileptogenesis: Transcription Factors in the SpotlightGary Brennan and Karen van Loo35. EpigeneticsKatja Kobow and Nadia Khan SECTION 4 - BIOMARKERS OF EPILEPTOGENESISEditor: Annamaria Vezzani; Associate Editors: Helen Scharfman and David Henshall IntroductionAnnamaria Vezzani and David Henshall36. EEG Biomarkers of EpileptogenesisLyna Kamintsky, Dan Z Milikovsky, and Alon Friedman37. Blood Biomarkers: Noncoding RNAs and ProteinsDavid Henshall and Michele Simonato38. Behavioural Biomarkers of Epileptogenesis and Epilepsy SeverityIdrish Ali, Pablo Casillas-Espinosa, Nigel Jones, and Terence O'Brien39. Genetic and Imaging Biomarkers of EpileptogenesisMatthias Koepp, Simona Balestrini, Stefanie Dedurwaerdere, and William Theodore40. Machine-Learning Approach to Discover Novel Biomarkers for Post-Traumatic EpilepsyRobert Ciszek, Eppu Manninen, Olli Gröhn, Jussi Tohka, and Asla Pitkänen SECTION 5 - GENES AND NETWORK DEVELOPMENTEditors: Antonio Delgado Escueta and Jeffrey Noebels; Associate Editor: Elsa Rossignol IntroductionJeffrey Noebels41. Human Epilepsy Gene Discovery: The Next DecadeEmily Bonkowski and Heather Mefford42. Functional Exploration of Epilepsy Genes in Patint-Derived CellsMaria 'Carmen' Varela, Ranmal Samarasinghe, and Jack Parent 43. Brain mosaicism in Epileptogenic Cortical MalformationsThéo Ribierre and Stéphanie Baulac 44. Sodium Channelopathies in Human and Animal Models of Epilepsy and Neurodevelopmental DisordersKazuhiro Yamakawa, Miriam Meisler, and Lori Isom45. Potassium Channels in Genetic Epilepsy: a Functional PerspectiveMatthew Weston and Anastasios Tzingounis46. High Voltage Activated Calcium Channels in Epilepsy: Lessons from Humans and RodentsElsa Rossignol47. Transcription Factors Regulating Interneuron DevelopmentEmily Ling-Lin Pai, Daniel Vogt, Jia Sheng Hu, and John Rubenstein48. GABAA Receptors, Seizures and EpilepsyRichard Olsen, Martin Wallner, and Michael A. Rogawski49. Gene genome interactions - Understanding complex molecular traits in epilepsyKatja Kobow and John Mahoney SECTION - 6 PROGRESSIVE MYOCLONUS EPILEPSIESEditor: Antonio Delgado-Escueta; Associate Editor: Berge Minassian IntroductionA.V. Delgado-Escueta, Berge Minassian, Jose M Seratossa50. The Neuronal Ceroid LipofuscinosesSara Mole51. Progressive Myoclonus Epilepsy: Unverricht-Lundborg DiseaseSaara Tegelberg, Tarja Joensuu, and Anna-Elina Lehesjoki52. Strategies on Gene Therapy in Progressive Myoclonus EpilepsiesSaima Kayani, Emrah Gumusgoz, Berge Minassian, and Alison Dolce53. Therapeutic Window for the Treatment of Lafora DiseaseOlga Varea, Joan Guinovart, and Jordi Duran 54. Progressive Myoclonus Epilepsy of Lafora- Treatment with MetforminJose M. Seratossa, Daniel F. Burgos, Luis Zafra-Puerta, Nerea Iglesias-Cabeza, Pascual Sanz, and Marina P. Sánchez55. Treating Lafora Disease with an Antibody-Enzyme FusionMatthew Gentry, Kia H. Markussen, Ramon Sun, and Craig W. Vander Kooi56. Antisense Oligonucleotide Therapy for Progressive Myoclonus EpilepsiesSilvia Nitschke and Berge Minassian SECTION 7 - COMORBIDITIES OF EPILEPTIC NETWORKSEditor: Jeffrey Noebels; Associate Editor: Peyman Golshani IntroductionJeffrey Noebels57. Dissecting Epileptic and Cognitive Network Dysfunction in EpilepsyPierre-Pascal Lenck-Santini and Greg Holmes58. Attention Deficit Disorders and EpilepsyAtul Maheshwari59. What Rodent Models Teach Us About the Association of Autism and EpilepsyPeyman Golshani60. Artificial Intelligence-Guided Behavioral Phenotyping in EpilepsyTilo Gschwind and Ivan Soltesz61. Mechanisms of Depression in the Epileptic BrainNigel Jones and Jamie Maguire62. Heterogeneous Mechanisms of Spreading Depolarization and SeizuresIsamu Aiba63. Genetic and Cellular Mechanisms Underlying SUDEP RiskJeffrey Noebels SECTION 8- EPILEPSY THERAPEUTICS Editor: Michael Rogawski; Associate Editors: Wolfgang Löscher & Steve White IntroductionMichael Rogawski64. New Models for Assessment of Antiseizure ActivityCameron Metcalf, Peter West, Sharon Edwards, and Karen Wilcox65. Disease Biology Factors Accounting for Epilepsy Severity: An Updated Conceptual Framework for New Drug DiscoveryStefanie Dedeurwaerdere, Vincenzo Marra, and Michael R Johnson66. Animal Models of Pharmacoresistant EpilepsyMichelle Guignet and H. Steve White67. Drug Combinations for AntiepileptogenesisWolfgang Löscher68. Prophylaxis of Epileptogenesis in Injury and Genetic Epilepsy ModelsDavid Prince and Feng Gu69. Management of Febrile Status Epilepticus: Past, Present and FutureMegan M. Garcia-Curran and Tallie Z. Baram 70. Excitatory Transmission in Status EpilepticusSuchitra Joshi and Jaideep Kapur71. Ionic Mechanisms of Ictogenic Disinhibition: All GABA Signaling is LocalKevin Staley72. Epileptogenic Channelopathies Guide Design of NBI-921352, a Highly Isoform-Selective Inhibitor of NaV1.6J.P. Johnson, Jr, Alison J Cutts, James R. Empfield, and Charles J. Cohen73. Purinergic Signaling in EpilepsyTobias Engel and Nicholas Dale74. Anti-Inflammatory Strategies for Disease Modification: Focus on Therapies Close to Clinical TranslationAnnamaria Vezzani, Silvia Balosso, Nicholas H. Varvel, and Ray Dingledine75. Targeted Augmentation of Nuclear Gene Output (TANGO)Lori Isom and Kelly G. Knupp76. Gene Therapy for EpilepsyKimberly Goodspeed, Dallas Armstrong, Andrea Boitnott, Alison Dolce, Qinglan Ling, and Steve Gray77. Gene Therapy for Refractory EpilepsyDimitri Kullmann78. Cell Therapy for Treatment of EpilepsySonja Bröer and Daniel Vogt79. Mechanisms of Ketogenic Diet ActionRobin Williams, Detlev Boison, Susan Masino, and Jong Rho