Epilepsy: A Comprehensive Textbook

 

Description:

Authoritative and updated, Epilepsy: A Comprehensive Textbook, 3rd Edition, contains 365 chapters that cover the full spectrum of relevant topics in biology, physiology, and clinical information, from molecular biology to public health concerns in developing countries. Written by world-renowned authorities and expertly edited by epileptologists Drs. Jerome Engel, Jr., Solomon L. Moshé, Aristea S. Galanopoulou, John M. Stern, Alexis Arzimanoglou, Jacqueline A. French, Renzo Guerrini, Andres M. Kanner, and Istvan Mody, this three-volume work includes detailed discussions of seizure types and epilepsy syndromes, relationships between physiology and clinical events, psychiatric and medical comorbidities, conditions that could be mistaken for epilepsy, and an increasing range of pharmacologic, surgical, and alternative therapies. 

 

Tab;e of Contents:

 

VOLUME I

SECTION 1 • Epidemiology and Pathology of Seizures and Epilepsy

CHAPTER 1. OVERVIEW: EPIDEMIOLOGY AND PATHOLOGY OF SEIZURES AND EPILEPSY

EPIDEMIOLOGY

PATHOLOGY

ACKNOWLEDGMENT

REFERENCES

CHAPTER 2. EPILEPSY: HISTORICAL PERSPECTIVES

PREHISTORIC TIMES AND ANCIENT HISTORY

THE MIDDLE AGES AND RENAISSANCE

FUNDAMENTS OF THE MODERN ERA

THE MODERN ERA OF EPILEPSY

1860–1910

1910–1945

1945–2000

REFERENCES

CHAPTER 3. INCIDENCE AND PREVALENCE OF SEIZURES AND EPILEPSY

INTRODUCTION

INCIDENCE OF EPILEPSY

Total Population Studies

Studies in Selected Age Groups

Age-Specific Incidence

Sex

Seizure Type

Race

Time Trends

Epileptic Syndromes

ETIOLOGY OF EPILEPSY IN INCIDENCE COHORTS

Classic Risk Factors

Risk Factors Identified in Epidemiologic Studies

Gender

Etiology

Race

Incidence and Prevalence of Epilepsy and the Global Burden of Disease

SUMMARY AND CONCLUSIONS

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 4. EPIDEMIOLOGY OF EPILEPSY IN LOW- AND MIDDLE-INCOME COUNTRIES

INTRODUCTION

METHODOLOGIC CONSIDERATIONS

Difficulties with Identification

Definition

The Diagnosis of Epilepsy

INCIDENCE OF EPILEPSY

PREVALENCE OF EPILEPSY

SEIZURE TYPE

THE CAUSES OF EPILEPSY

Identifying the Etiology

Family History of Epilepsy

Perinatal Brain Insults

Infections of CNS

Viral Infections

Human Immunodeficiency Virus

Traumatic Brain Injury

Cerebrovascular Disease

Tumors

MORTALITY

CONCLUSION

REFERENCES

CHAPTER 5. ETIOLOGY AND RISK FACTORS FOR SEIZURES AND EPILEPSY

INTRODUCTION

EPIDEMIOLOGIC STUDY DESIGNS

RISK FACTORS FOR CHILDHOOD EPILEPSY

Febrile and Acute Symptomatic Seizures

Prenatal and Perinatal Risk Factors

Postnatal Causes

Association of Different Risk Factors with Different Types of Epilepsy

RISK FACTORS FOR EPILEPSY IN ADULTS

Head Injury

Central Nervous System Infections

Central Nervous System Malignancies

Occlusive Cerebrovascular Disease

Dementia

Multiple Sclerosis

Depression and Treatment for Depression

Alcohol

Illicit Drugs

Acute Symptomatic Seizures

Migraines and Epilepsy

The Protective Effect of Diuretics

Socioeconomic Status

FUTURE RESEARCH

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 6. THE COMORBIDITIES IN EPILEPSY

COMORBIDITY AS AN EPIDEMIOLOGIC CONSTRUCT

BURDEN OF COMORBIDITY IN PEOPLE WITH EPILEPSY

CLINICAL APPROACH TO COMORBIDITIES IN PEOPLE WITH EPILEPSY

MECHANISMS OF ASSOCIATION

Chance and Artifactual Comorbidities

Causative and Resultant Mechanisms

Shared Risk Factors

Bidirectional Effects

CASE STUDY: CARDIOVASCULAR DISEASE AND EPILEPSY

CASE STUDY: EPILEPSY AND DIABETES

CASE STUDY: EPILEPSY AND DEPRESSION

CASE STUDY: MIGRAINE AND EPILEPSY

REFERENCES

CHAPTER 7. NATURAL HISTORY AND PROGNOSIS OF EPILEPSY

INTRODUCTION

METHODOLOGIC ISSUES

OVERALL PROGNOSIS OF EPILEPSY

Prognosis of a First Seizure

EARLY PROGNOSIS OF UNPROVOKED SEIZURES AND EPILEPSY

Prognosis after the First Unprovoked Seizure

Risk Factors for Recurrence after a First Unprovoked Seizure

Treatment, Risk of Recurrence, and Long-Term Prognosis of a First Seizure

PROGNOSIS OF UNTREATED EPILEPSY

PROGNOSIS OF NEWLY DIAGNOSED AND TREATED EPILEPSY

Principal Prognostic Indicators in Treated Epilepsy

Prognosis of Epilepsy Syndromes

Antiseizure Medications and Seizure Outcome

PROGNOSIS OF EPILEPSY AFTER TREATMENT WITHDRAWAL

Factors Predicting Seizure Relapse after Treatment Withdrawal

PSYCHOSOCIAL OUTCOME

SUMMARY AND CONCLUSIONS

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 8. EPIDEMIOLOGY OF ACUTE SYMPTOMATIC SEIZURES

INTRODUCTION

INCIDENCE OF ACUTE SYMPTOMATIC SEIZURES

Overall Incidence

Gender

Age

Seizure Type and Duration

CAUSES OF ACUTE SYMPTOMATIC SEIZURES

Acute Symptomatic Seizures Associated with Primary Brain Insults

Acute Symptomatic Seizures Associated with Systemic Disturbances

CUMULATIVE INCIDENCE OF ACUTE SYMPTOMATIC SEIZURES

PROGNOSIS OF ACUTE SYMPTOMATIC SEIZURES

SUMMARY AND CONCLUSIONS

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 9. SEIZURE PRECIPITANTS

INTRODUCTION

STRESS

SLEEP AND SLEEP LOSS

NONADHERENCE TO ASM TREATMENT

ALCOHOL

DRUGS AND STIMULANTS

FEVER

MENSTRUAL CYCLE

PHYSICAL EXERCISE

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 10. THE MORTALITY OF EPILEPSY

INTRODUCTION

OVERALL MORTALITY

ETIOLOGY OF EPILEPSY

AGE AND SEX

DURATION OF EPILEPSY

SEIZURE TYPE AND FREQUENCY

CAUSE-SPECIFIC MORTALITY IN PEOPLE WITH EPILEPSY

SUDDEN UNEXPECTED DEATH IN EPILEPSY

STATUS EPILEPTICUS

INJURIES AND ACCIDENT-RELATED DEATHS

SUICIDES

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 11. GENERAL NEUROPATHOLOGY OF EPILEPSY

NEUROPATHOLOGY REVISITED: ETIOLOGY MATTERS IN DIAGNOSIS AND TREATMENT

THE CONCEPT OF CELLULAR PATHOLOGY AS THE FOUNDATION OF MODERN MEDICINE

THE CONCEPT OF MOLECULAR PATHOLOGY AS THE FOUNDATION OF PERSONALIZED MEDICINE

THERE ARE UNIQUE MORPHOLOGIC SUBSTRATES THAT SUBSERVE INTRINSIC EPILEPTOGENCITY IN HUMAN NEOCORTEX

COMMON NEUROPATHOLOGIC CHANGES THAT RESULT FROM EPILEPSY

FUTURE DIRECTIONS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 12. NEUROPATHOLOGY OF HIPPOCAMPAL SCLEROSIS

ANATOMY OF THE HUMAN HIPPOCAMPUS

HIPPOCAMPAL SCLEROSIS IN TEMPORAL LOBE EPILEPSY

HISTOPATHOLOGIC CLASSIFICATION OF HIPPOCAMPAL SCLEROSIS

THE INTERNATIONAL LEAGUE AGAINST EPILEPSY CONSENSUS CLASSIFICATION OF HIPPOCAMPAL SCLEROSIS

HS ILAE Type 1

HS ILAE Type 2 (CA1 Predominant Neuronal Cell Loss and Gliosis)

HS ILAE Type 3 (CA4 Predominant Neuronal Cell Loss and Gliosis)

No Hippocampal Sclerosis, Gliosis Only (no HS)

DENTATE GYRUS PATHOLOGY

ASSOCIATED FOCAL CORTICAL DYSPLASIA TYPE 3A

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 13. NEUROPATHOLOGY OF DEVELOPMENTAL DISORDERS ASSOCIATED WITH EPILEPSY

INTRODUCTION

THE ENIGMA OF EPILEPSY OR NOT IN CEREBRAL MALFORMATIONS

CLINICOPATHOLOGIC FEATURES

NOSOLOGY

DEVELOPMENT OF THE NEOCORTEX

Overview of Neocortical Development

Radial Migration of Neuroblasts from the Subventricular Zone

Tangential Migration of GABAergic Interneurons from Ganglionic Eminence

Origin of Cajal–Retzius Cells and Their Biologic Significance

Origin of Superficial Granular Layer of Brun and Its Biologic Significance

Subplate Neurons as Pioneer Cells to Form Early Thalamocortical Projections

Neuropathology and Pathophysiologic Significance of MCD

PATHOGENESIS OF CORTICAL DYSPLASIAS

CONCLUSIONS

REFERENCES

CHAPTER 14. NEUROPATHOLOGY OF BRAIN TUMORS ASSOCIATED WITH EPILEPSY

INTRODUCTION

GLIONEURONAL TUMORS

Ganglioglioma

Dysembryoplastic Neuroepithelial Tumor

Papillary Glioneuronal Tumor

Rosette-Forming Glioneuronal Tumor

Diffuse Leptomeningeal Glioneuronal Tumor

Multinodular and Vacuolating Neuronal Tumor of the Cerebrum

Pilocytic Astrocytoma

Pleomorphic Xanthoastrocytoma

DIFFUSE ASTROCYTIC AND OLIGODENDROGLIAL TUMORS

Diffuse Astrocytoma

Oligodendroglioma

Angiocentric Gliomas

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 15. NEUROPATHOLOGY OF VASCULAR LESIONS ASSOCIATED WITH EPILEPSY

INTRODUCTION

NEUROPATHOLOGY OF POSTSTROKE EPILEPSY IN CEREBROVASCULAR DISEASES

EPILEPSY-ASSOCIATED VASCULAR MALFORMATIONS

Arteriovenous Malformation

Cerebral Cavernous Malformation or Cavernous Angioma

Developmental Venous Anomalies

Capillary Telangiectasia/Capillary Malformation

Leptomeningeal Angiomatosis of Sturge–Weber Syndrome

MENINGIOANGIOMATOSIS

OTHER EPILEPSY-ASSOCIATED VASCULAR LESIONS

Intracranial Unruptured Saccular (Berry) Aneurysm

Moyamoya Disease/Spontaneous Occlusion of the Circle of Willis

Systemic Autoimmune Disorders Causing Cerebrovascular Complications

Primary Angiitis of the Central Nervous System

SUMMARY AND CONCLUSIONS

REFERENCES

SECTION 2 • Genetics in Epilepsy

CHAPTER 16. OVERVIEW: GENETICS IN EPILEPSY

CHAPTER 17. GENETIC EPIDEMIOLOGY IN EPILEPSY

INTRODUCTION

FAMILIAL AGGREGATION STUDIES

Rationale and Importance

Methodologic Considerations

Major Findings of Family Aggregation Studies

TWIN STUDIES

Rationale, Assumptions, and Limitations

Methodologic Considerations

Major Findings of Twin Studies

Comparison of Twin Studies to Familial Aggregation Studies

EPIDEMIOLOGY AND THE MOLECULAR GENETICS OF THE EPILEPSIES

CONCLUSIONS

REFERENCES

CHAPTER 18. GENETIC ARCHITECTURE OF THE EPILEPSIES

INTRODUCTION

CONCEPTUAL ISSUES

How Much of Epilepsy Is Genetic?

Heritability of Epilepsy

Epilepsy Classification, Syndromes, and Genetics

OVERVIEW OF GENETIC ARCHITECTURE

Monogenic Epilepsies

Complex Epilepsies

UNCONVENTIONAL MECHANISMS

Mosaicism

Repeat Expansions

PHARMACOGENOMICS

FUTURE PERSPECTIVE

REFERENCES

CHAPTER 19. SINGLE GENE EPILEPSIES

REFERENCES

CHAPTER 20. HOW TO INTERPRET AND ACT ON CLINICAL EXOMES IN EPILEPSY

INTRODUCTION

EFFECTIVENESS OF EXOME ANALYSIS FOR EPILEPSY DIAGNOSIS

CLASSIFICATION AND NOMENCLATURE OF IDENTIFIED VARIANTS

FILTERING TO FIND PATHOGENIC VARIANTS

Allele Frequency

Prediction

Segregation

Previous Reports

Functional Assay

American College of Medical Genetics Guidelines

EXOME ANALYSIS PROCESS

PITFALLS OF EXOME ANALYSIS

Chromosomal Structural Abnormalities

Splicing and Gene-Regulation Variants

Mitochondrial Disorders

Gene-Panel or Exome Sequencing

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 21. FAMILIAL EPILEPSIES IN THE FIRST YEAR OF LIFE

INTRODUCTION

FAMILIAL EPILEPSIES IN THE FIRST YEAR OF LIFE

History and Terminology

Investigations

SELF-LIMITED FAMILIAL NEONATAL EPILEPSY

Epidemiology

Clinical Manifestation

Genetic Backgrounds and Molecular Mechanisms

Other KCNQ2-Related Disorders

Treatment

Outcome

SELF-LIMITED FAMILIAL NEONATAL–INFANTILE EPILEPSY

Clinical Manifestations

Genetic Backgrounds and Molecular Mechanisms

SELF-LIMITED FAMILIAL INFANTILE EPILEPSY

Clinical Manifestations

Genetic Backgrounds and Molecular Mechanisms

Treatment

Outcome

CONCLUSION

REFERENCES

CHAPTER 22. DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES

INTRODUCTION

DEES PRESENTING IN THE NEONATAL AND INFANCY PERIOD

Early Infantile Developmental and Epileptic Encephalopathy

Epilepsy of Infancy with Migrating Focal Seizures

Infantile Epileptic Spasms Syndrome

Dravet Syndrome

PCDH19-DEE

Epilepsy with Myoclonic Atonic Seizures

Lennox–Gastaut Syndrome

REFERENCES

CHAPTER 23. GENETIC GENERALIZED EPILEPSIES

DEFINITION OF THE PHENOTYPE

ABSENCE EPILEPSIES

Childhood Absence Epilepsy

Juvenile Absence Epilepsy

OTHER TYPES OF EPILEPSY WITH ABSENCES NOT CLASSICALLY CONSIDERED UNDER GGES

Epilepsy with Myoclonic Absences

Myoclonic Astatic Epilepsy

Other Possible Syndromes with Typical Absence Seizures

Juvenile Myoclonic Epilepsy

GGE with Generalized Tonic–Clonic Seizures Alone

Adult-Onset Genetic Generalized Epilepsy

Genetic Generalized Epilepsies: Discrete or Overlapping Entities?

Genetic Etiology

Sex-Related Effects

Anatomical Changes of Brain Architecture

Treatment

REFERENCES

CHAPTER 24. GENETIC ENCEPHALOPATHIES WITH EPILEPSY AS A MAIN FEATURE

INTRODUCTION

AICARDI SYNDROME

Diagnosis

Phenotype

Treatment

ANGELMAN SYNDROME

Diagnosis

Phenotype

Treatment

CORNELIA DE LANGE SYNDROME

Diagnosis

Phenotype

Treatment

KBG SYNDROME

Diagnosis

Phenotype

Treatment

KMT2E-RELATED NEURODEVELOPMENTAL DISORDER

Diagnosis

Phenotype

Treatment

MOWAT–WILSON SYNDROME

Diagnosis

Phenotype

Treatment

PITT–HOPKINS SYNDROME

Diagnosis

Phenotype

Treatment

RETT SYNDROME

Diagnosis

Phenotype

Treatment

REFERENCES

CHAPTER 25. GENETIC TESTING AND COUNSELING FOR THE EPILEPSIES

INTRODUCTION

CHANGING LANDSCAPE OF GENETICS OF EPILEPSY

IMPORTANCE OF GENETIC TESTING

REVIEW OF AVAILABLE DIAGNOSTIC TESTING OPTIONS

Molecular Genetic Tests

Chromosomal Genetic Tests

Biochemical Genetic Tests

WHICH PATIENTS WITH EPILEPSY SHOULD HAVE GENETIC TESTING?

APPROACH TO TEST SELECTION FOR PATIENTS WITH EPILEPSY

GENETIC COUNSELING FOR EPILEPSY

Informed Consent for Genetic Testing

Disclosure of Genetic Test Results

SUMMARY AND CONCLUSIONS

REFERENCES

SECTION 3 • Neurobiology of Epilepsy

CHAPTER 26. OVERVIEW: NEUROBIOLOGY OF EPILEPSY

CHAPTER 27. TRANSCRIPTIONAL CHANNELOPATHIES IN GENETIC AND ACQUIRED EPILEPSIES

TRANSCRIPTIONAL CHANNELOPATHIES

TRANSCRIPTIONAL REGULATION OF VOLTAGE-GATED ION CHANNELS LEADING TO GENETIC EPILEPSIES

Voltage-Gated K+ Channelopathies

Voltage-Gated Na+ Channelopathies

Voltage-Gated Ca2+ Channelopathies

HCN Ion Channelopathies

TRANSCRIPTIONAL REGULATION OF LIGAND-GATED ION CHANNELS LEADING TO GENETIC EPILEPSIES

NMDA Receptor Channelopathies

GABA Receptor Channelopathies

Nicotinic Acetylcholine Receptor Channelopathies

TRANSCRIPTIONAL CHANNELOPATHIES IN ACQUIRED EPILEPSIES

GABAA Receptor Alterations in Hippocampal Dentate Granule Cells in Multiple Experimental TLE Models

HCN Channel Alterations in Hippocampal CA1 Pyramidal Neurons in Multiple Experimental TLE Models

Cav3.2 Channel Upregulation in Hippocampal CA1 Pyramidal Neurons in an Experimental TLE Model

Potential for Therapy in Acquired Transcriptional Channelopathies

SUMMARY

REFERENCES

CHAPTER 28. PRINCIPAL CELL HETEROGENEITY IN MALFORMATIONS OF CORTICAL DEVELOPMENT AND ACQUIRED EPILEPSY

INTRODUCTION

CORTICAL DEVELOPMENT AND MALFORMATIONS

Mispositioning of Neurons

Abnormal Cellular Development

NONUNIFORM COMPUTATIONAL MODULES FOR PARALLEL PROCESSING AND PRINCIPAL CELL HETEROGENEITY: INSIGHTS FROM THE HIPPOCAMPUS

PYRAMIDAL CELL HETEROGENEITY AND LOCAL MICROCIRCUITS IN THE HIPPOCAMPUS

PRINCIPAL CELL HETEROGENEITY IN THE DG IN CHRONIC TEMPORAL LOBE EPILEPSY

CONCLUSIONS AND OUTLOOK

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 29. MECHANISMS OF NEURONAL EXCITATION LEADING TO SYNCHRONY

INTRODUCTION

MEASURING NEURAL SYNCHRONY: THE IMPORTANCE OF TECHNICAL LIMITATION AND PERSPECTIVE

SYNAPTIC MECHANISMS FOR SYNCHRONIZATION: RECURRENCE

SYNAPTIC MECHANISMS FOR SYNCHRONIZATION: DISINHIBITION

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: INTRINSIC PROPERTIES

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: EXTRACELLULAR COMPARTMENT

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: EPHAPTIC COUPLING

NONSYNAPTIC MECHANISMS FOR SYNCHRONIZATION: GAP JUNCTION COUPLING

FUTURE OUTLOOK

REFERENCES

CHAPTER 30. INTERNEURON DIVERSITY IN EPILEPSY: CHALLENGES AND PROGRESS

INTRODUCTION

OVERVIEW OF THE NORMAL DIVERSITY OF INTERNEURONS

Interneurons Innervating Principal Cell Soma or Axon Initial Segments

Interneurons Innervating Principal Cell Dendrites

Interneurons Innervating Other Interneurons

WHAT INTERNEURONS DEGENERATE IN ACQUIRED EPILEPSY?

WHAT ARE THE FUNCTIONAL CONSEQUENCES OF INTERNEURON LOSS?

HOW DO SURVIVING INTERNEURONS ADAPT IN THEIR STRUCTURE AND FUNCTION?

Functional Impairment of Surviving Interneurons

Overexpression of Neuropeptides and Glutamate Decarboxylases in Surviving Interneurons

Sprouting and Reorganization of Surviving Interneurons

WHAT ARE THE ROLES OF SURVIVING INTERNEURONS IN EPILEPSY?

Effects of Selectively Modulating Interneuron Activity

Monitoring Interneuron Activity Prior to and During Seizure Activity

WHAT IS THE POTENTIAL FOR INTERNEURON-BASED TREATMENT OF EPILEPSY?

Modulation of Interneurons for the Treatment of Epilepsy

Transplantation of Interneurons for the Treatment of Epilepsy

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 31. MECHANISMS OF NEURONAL INHIBITION LEADING TO SYNCHRONY

INTRODUCTION

AN OVERVIEW OF INTERNEURONAL CLASSES AND CONNECTIVITY IN CORTICAL NETWORKS

PHYSIOLOGIC SYNCHRONIZATION

DETERMINANTS OF GABA CURRENT: INTRA- AND EXTRACELLULAR CHLORIDE

DYNAMIC CHANGES IN GABAERGIC FUNCTION

GABAERGIC INFLUENCES IN EPILEPTIC DISCHARGES

CHARACTERISTICS OF CELLULAR RECRUITMENT TO SEIZURES

REFERENCES

CHAPTER 32. NEURONS AND CIRCUITS DURING BRAIN DEVELOPMENT

INTRODUCTION

DEVELOPMENTAL CHANGES IN NEURONAL PROPERTIES

GAP-JUNCTION CONNECTIONS

EXCITATORY SYNAPTIC CONNECTIONS

Local and Long-Range Connections

Functional Properties of Developing Excitatory Synapses

INHIBITORY CIRCUITS

Delayed Recruitment of Perisomatic Inhibition

Depolarizing Actions of GABA

Actions of GABA in Vivo

EARLY NETWORK ACTIVITY PATTERNS

Correlated Activity Mediated by Gap Junctions

Delta Waves

Early Gamma and Spindle-Burst Oscillations

CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 33. METABOLISM, REACTIVE OXYGEN SPECIES, AND EPILEPSY

INTRODUCTION

NEURONAL–GLIAL METABOLISM

REACTIVE OXYGEN SPECIES IN EPILEPSY

MITOCHONDRIA AS A SOURCE AND TARGET OF ROS IN EPILEPSY

NOX ENZYMES AS SOURCES OF ROS IN EPILEPSY

PHARMACOLOGIC REDOX-BASED APPROACHES FOR EPILEPSY AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 34. DENDRITIC MECHANISMS OF EXCITABILITY

INTRODUCTION

BASIC MECHANISMS OF DENDRITIC INTEGRATION

ALTERED DENDRITIC MORPHOLOGY AND PASSIVE MEMBRANE PROPERTIES IN EPILEPSY

ACTIVE MECHANISMS IN DENDRITES AFFECTING PROPAGATION OF VOLTAGE SIGNALS

Voltage- and Ca2+-Gated K+ Channels

Dendritic h-currents

Voltage-Gated Na+ Channels

ACTIVE MECHANISMS IN DENDRITES: DENDRITIC SPIKES

ALTERED DENDRITIC ELECTROPHYSIOLOGY IN EPILEPSY

Epilepsy-Related Changes in Dendritic Kv4.2 Channels

Epilepsy-Related Changes in Dendritic HCN Channels

Changes in Dendritic T-Type Currents Mediated by CaV3.2 Channels

Epilepsy-Related Changes in KCa3.1 Channels

Mechanisms of Dendritic Integration Across Species—Mouse to Human

ROLE OF ACTIVE DENDRITIC INTEGRATION IN VIVO

Outlook

REFERENCES

CHAPTER 35. THALAMOCORTICAL ORGANIZATION AND FUNCTION: NEW INSIGHTS AND IMPLICATIONS FOR EPILEPSY

INTRODUCTION

ANATOMICAL AND FUNCTIONAL OVERVIEW OF THE THALAMUS

SINGLE-CELL ANALYSES ESTABLISH A HIGH-RESOLUTION FRAMEWORK OF THE THALAMUS

Classification of TC Relay Nuclei

In Search of Molecular Markers for the nRT

MAPPING MOLECULAR PROPERTIES WITH CIRCUIT PROPERTIES REVEALS NEW PATHWAYS

Input–Output Connectivity of the nRT

Intra-nRT Connectivity

INSIGHTS FROM DISSECTING THE ROLE OF nRT IN SPINDLE OSCILLATIONS: CAN nRT SPINDLES ELUCIDATE SEIZURES?

NEW INSIGHTS ON THE ROLE OF nRT IN TC SEIZURE DYNAMICS

CONCLUDING REMARKS

Molecular Insights

Electrophysiologic Insights

Circuit Insights

REFERENCES

CHAPTER 36. MECHANISMS OF SEIZURE INITIATION AND PROPAGATION

INTRODUCTION

ELECTROPHYSIOLOGIC SIGNATURES OF FOCAL SEIZURES

Clinical EEG Assessment

Electrographic Seizure-Onset Patterns

High-Frequency Activity as a Biomarker of Seizure-Generating Sites

Infra-Slow Activity at Seizure Onset

NEURONAL ACTIVITY IN SEIZURE INITIATION AND MAINTENANCE

Ictal Neuronal Firing Patterns

Neuronal Cell-Type–Specific Activity

MECHANISMS UNDERLYING THE SEIZURE TRANSITION

Dysregulated Chloride Homeostasis

Interneuron Depolarization Block

Astrocyte-Mediated Excitation

SPATIAL STRUCTURE OF HUMAN SEIZURES

The Dual-Territory Hypothesis: Ictal Core and Penumbra

Cross-Scale Seizure Effects

Epileptic Networks

CONCLUDING REMARKS

REFERENCES

CHAPTER 37. SEIZURES AND NETWORKS IN THE HUMAN FOCAL EPILEPSIES: BEYOND THE ANIMAL MODELS

INTRODUCTION

FOCAL SEIZURE–ONSET PATTERNS

LESION-SPECIFIC ICTAL PATTERNS

REGION-SPECIFIC ICTAL PATTERNS

THE EPILEPTOGENIC NETWORKS

CONCLUSIONS

REFERENCES

CHAPTER 38. TEMPORAL COORDINATION: A KEY TO UNDERSTAND COGNITIVE AND BEHAVIORAL DEFICITS IN EPILEPSY

INTRODUCTION: LOSING THE BEAT

COGNITIVE AND BEHAVIORAL IMPAIRMENTS IN EPILEPSY

GENERAL CONTRIBUTORS OF COGNITIVE COMORBIDITIES

PHYSIOPATHOLOGIC FEATURES OF EPILEPSIES

The Case of TLE

The Case of Epilepsies of Genetic Origin

NETWORK MECHANISMS UNDERLYING COGNITIVE IMPAIRMENT IN EPILEPSY

Alterations of Neuronal Network Dynamics and Computation

Impact on High-Level Cognitive Representations

RHYTHMOPATHIES AND EPILEPSY

θ Oscillations and Epilepsy

γ Oscillations and Epilepsy

High-Frequency Oscillations in Epilepsy

FROM INTERNEUROPATHIES TO RHYTHMOPATHIES

CONCLUSIONS

REFERENCES

CHAPTER 39. EPILEPSY AND CONSCIOUSNESS

INTRODUCTION

THE DIMENSIONS OF CONSCIOUSNESS IN SEIZURES

ESTIMATION OF CONSCIOUSNESS DURING SEIZURES

IMPAIRED CONSCIOUSNESS IN GENERALIZED SEIZURES

Generalized Tonic–Clonic Seizures

Absence Seizures

IMPAIRED CONSCIOUSNESS IN FOCAL SEIZURES

Temporal Lobe Seizures

Extratemporal Lobe Seizures

Mechanisms

Insights from Animal Models

THERAPEUTIC APPROACHES

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 40. ACTIVATING AND RECORDING NEURONAL ENSEMBLES

INTRODUCTION

ACTIVATING NEURONAL ENSEMBLES

Electrical Stimulation

Optogenetic Stimulation

Chemogenetic Activation

RECORDING NEURONAL ENSEMBLES

EEG/LFP

Wireless Telemetry

Imaging Techniques

CONSIDERATIONS AND PERSPECTIVES

REFERENCES

CHAPTER 41. GENETICALLY ENCODED PROBES for OPTICAL MEASUREMENT of NEURONAL EXCITABILITY and SYNCHRONY

INTRODUCTION

ADVANCES IN FLUORESCENCE MICROSCOPY

The Impact of 2-Photon Excitation Microscopy

Miniaturized Epifluorescence Microscopy

GENETICALLY ENCODED PROBES FOR RECORDING NEURONAL EXCITABILITY

Calcium Indicators

Voltage Sensors

METHOD OF DELIVERY

Viruses

Transgenic Animals

Electroporation

RECORDING NEURAL EXCITABILITY AND SYNCHRONY WITH GENETICALLY ENCODED FLUORESCENT INDICATORS IN THE CONTEXT OF EPILEPSIES

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 42. FAST RHYTHMS IN EPILEPSIES

INTRODUCTION

DEFINITION/DESCRIPTION OF FAST RHYTHMS

FAST RHYTHMS IN THE NORMAL BRAIN

FAST RHYTHMS IN THE EPILEPTIC BRAIN

Pathologic Gamma Activity

Cellular and Network Mechanisms of Epileptic Ripples

Cellular and Network Mechanisms of Epileptic Fast Ripples

Mechanisms of Very-High HFOs

Regional Properties of Pathologic HFOs

SIGNIFICANCE OF FAST RHYTHMS

HFA and the Modern Concept of the Epileptic Focus

HFOs in Epileptogenesis

HFOs as a Marker of Seizure Susceptibility

FUTURE DIRECTIONS

REFERENCES

CHAPTER 43. Miniaturized Microscopy as a Tool to Track Neuronal Population Dynamics in Epilepsy Models

INTRODUCTION

BRIEF HISTORY OF IMAGING IN BEHAVING ANIMALS

MINIATURE MICROSCOPY

CURRENT TOOLS AND FEATURES

Electrowetting Lenses

Dual-Channel Microscopes

Optogenetics

Wide-Field Imaging

Neurovascular Coupling

Volumetric Imaging

Wireless and Wire-Free

Electrophysiology

Simultaneous Behavior Tracking/Readout

DATA ANALYSIS

FUTURE INNOVATION OF MINIATURE MICROSCOPY

Wireless Power Delivery and Data Transmission

Close-Loop Experiments

Fast Imaging of Voltage Sensors

Lensless Imaging

STUDYING EPILEPSY WITH MINISCOPES

SUMMARY

REFERENCES

CHAPTER 44. SEIZURE CONTROL THROUGH CLOSED-LOOP SYSTEMS

INTRODUCTION

CLOSED-LOOP INTERVENTIONS: AN OVERVIEW

Example Potential Signals for Seizure Detection

Closed-Loop Interventions Are Not Limited to Electrical Stimulation Approaches

Closed-Loop Approaches Are Not Limited to On-Demand Interventions

ADVANTAGES OF CLOSED-LOOP SYSTEMS

CURRENT CLOSED-LOOP INTERVENTIONS IN EPILEPSY

Responsive Neurostimulation System

On-Demand Stimulation of the Vagus Nerve

Biofeedback

CLOSED-LOOP INTERVENTIONS IN EPILEPSY: ANIMAL STUDIES PROVIDE INSIGHT AND INFORM POTENTIAL FUTURE APPROACHES

Closed-Loop Approaches in Absence Epilepsy Models

Closed-Loop Approaches in Temporal Lobe Epilepsy Models

Closed-Loop Gene Therapy via eGluCl

FUTURE DIRECTIONS

CONCLUSIONS

REFERENCES

CHAPTER 45. BIOMARKERS

INTRODUCTION

SUSCEPTIBILITY/RISK BIOMARKERS

Genetic Risk Biomarkers

Blood/CSF Risk Biomarkers

Neurophysiology Risk Biomarkers

Neuroimaging Risk Biomarkers

DIAGNOSTIC BIOMARKERS

Diagnostic Genetic Biomarkers

Diagnostic Blood/CSF Biomarkers

Diagnostic Neurophysiologic Biomarkers

Diagnostic Imaging Biomarkers

PROGNOSTIC BIOMARKERS

Prognostic Genetic Biomarkers

Prognostic Blood/CSF Biomarkers

Prognostic Neurophysiologic Biomarkers

Prognostic Imaging Biomarkers

MONITORING AND PREDICTIVE BIOMARKERS/SURROGATE ENDPOINTS

Predictive Genetic Biomarker

Predictive Blood/CSF Biomarkers

Predictive Neurophysiology Markers

Predictive Imaging Biomarkers

CONCLUSIONS

REFERENCES

CHAPTER 46. COMORBIDITIES AS PROGNOSTIC FACTORS FOR EPILEPTOGENESIS

INTRODUCTION

BEHAVIORAL AND COGNITIVE METHODS USED TO ASSESS COMORBIDITIES IN ANIMAL MODELS OF ACQUIRED EPILEPSY

COMORBIDITIES IN ANIMAL MODELS OF ACQUIRED EPILEPSY

COMORBIDITIES AND SEIZURE THRESHOLD AS PROGNOSTIC FACTORS FOR EPILEPTOGENESIS

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 47. USE OF HUMAN PLURIPOTENT STEM CELLS IN EPILEPSY RESEARCH

INTRODUCTION

iPSC METHODS RELEVANT TO EPILEPSY STUDIES

INVESTIGATION OF EPILEPSY PHENOTYPES IN 2D CULTURES

Brain Organoids for Epilepsy Research

Exploring SUDEP Mechanisms with iPSCs

CHALLENGES AND FUTURE DIRECTIONS

CONCLUSIONS

REFERENCES

CHAPTER 48. NOVEL ROLES OF MYELINATION IN NEURAL CIRCUIT PLASTICITY AND IMPLICATIONS FOR EPILEPSY

INTRODUCTION

ROLES OF MYELIN IN THE CENTRAL NERVOUS SYSTEM

Myelin Increases Neuronal Conduction Velocity

Role of Myelination in Regulating Timing of Neuronal Signals

DEVELOPMENTAL MYELINATION AND THE LIFE CYCLE OF THE OLIGODENDROCYTE

Oligodendrocyte Precursor Cells

Premyelinating Oligodendrocytes

Myelin Wrapping and Compaction

NEURONAL ACTIVITY IN THE REGULATION OF MYELINATION

Structural and Cellular Changes to Myelin in Response to Neuronal Activity

How Does Neuronal Activity Influence Myelination?

MOLECULAR MECHANISMS OF NEURONAL ACTIVITY-DEPENDENT MYELINATION

Neuronal Signals and Activity-Dependent Myelination

Translating Neuronal Signals Into OL Responses: Intracellular Calcium

Calcium-Regulation of OL Cell Biology: Mechanistic Insight Into Activity-Dependent Myelination

INTERNEURON MYELINATION

OPEN QUESTIONS

Structure and Function of Neuron-OPC Synapses

Molecular Mechanisms Regulating Activity-Dependent Myelination

Functional Relevance of Activity-Dependent Myelination in Regulating Neural Circuit Function and Behavior

Function of PV Myelin

ROLE OF MYELIN AND MYELIN PATHOLOGY TO EPILEPSY

CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 49. ROLE OF DYSFUNCTIONAL ASTROCYTES IN EPILEPTOGENESIS

INTRODUCTION

BASIC PHYSIOLOGY OF “NORMAL” ASTROCYTES

Membrane Physiology

Astrocyte Metabolism and Synaptic Activity

ASTROCYTE DYSFUNCTIONS CONTRIBUTE TO INITIATION AND PROGRESSION OF EPILEPSY

Reactive Astrocytes May Generate Seizure Activity

Altered K+ Channels and Water Channels in Epilepsy

Loss of Astroglial Gap-Junction Coupling as a Key Mechanism in Initiation and Progression of TLE

Altered Glutamate Homeostasis in Epilepsy

Astrocyte Ca2+ Signaling in Epilepsy

CONCLUSIONS AND PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 50. NEUROVASCULAR INFLAMMATION IN EPILEPSY

INTRODUCTION

EVIDENCE FOR PERSISTENT NEUROINFLAMMATION AND ITS DEFECTIVE RESOLUTION IN EPILEPSY

NEUROINFLAMMATORY SIGNALS IMPLICATED IN EXPERIMENTAL EPILEPSY

The IL-1β System

The Prostanoid Cascade: The Focus on MAGL and COX-2

Specialized Proresolving Molecules

MECHANISMS OF HYPEREXCITABILITY

CEREBROVASCULAR PERMEABILITY AND PERIVASCULAR INFLAMMATION DURING SEIZURES

PERIPHERAL INFLAMMATION AND EPILEPSY: HUMAN AND EXPERIMENTAL EVIDENCE

DOES PRE-EXISTING INFLAMMATION ENABLE SEIZURES?

CONCLUSIONS ON THERAPEUTIC PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 51. THE BLOOD–BRAIN BARRIER AND EPILEPSIES

INTRODUCTION

BBB DYSFUNCTION FOLLOWING BRAIN INSULTS

BBB DYSFUNCTION AND EPILEPSIES

BBB DYSFUNCTION AND MECHANISMS UNDERLYING EPILEPTOGENESIS

BBB-TARGETED THERAPIES: A NEW OPPORTUNITY IN THE PREVENTION AND TREATMENT OF EPILEPSY?

REFERENCES

CHAPTER 52. THE mTOR PATHWAY IN EPILEPTOGENESIS

INTRODUCTION

mTOR IN ANIMAL MODELS OF TSC

mTOR IN ANIMAL MODELS OF OTHER GENETIC AND ACQUIRED EPILEPSIES

CLINICAL TRANSLATION OF mTOR INHIBITORS IN EPILEPSY AND TSC

CONCLUSIONS AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 53. EPIGENETIC MECHANISMS IN EPILEPSY

INTRODUCTION

OVERVIEW: EPIGENETICS, GENE EXPRESSION, AND CHROMATIN STRUCTURE

Gene Expression and Protein Production

DNA Organization and Epigenetic Modifications

CORE EPIGENETIC MECHANISMS CONTROLLING GENE EXPRESSION

DNA Methylation

Histone Posttranslational Modifications and Histone Variants

Noncoding RNA

Other Mediators of Epigenetic Processes

EPIGENETIC MECHANISMS IN EPILEPSY

DNA Methylation in Epilepsy

Histone Modifications in Epilepsy

Noncoding RNAs in Epilepsy

EPILEPSY-ASSOCIATED GENES WITH EPIGENETIC FUNCTIONS

INTERACTIONS AND INTERDEPENDENCE IN EPIGENETICS: ADDING A LAYER OF COMPLEXITY

CELL SPECIFICITY IN EPIGENETICS: AN ONGOING CHALLENGE

How Do Epigenetic Processes Favor or Protect Against Neuronal Excitability and Seizures?

Metabolically Controlled Epigenetic Mechanisms in Epilepsy

DIAGNOSTIC IMPLICATIONS OF EPIGENETICS RESEARCH IN EPILEPSY

THERAPEUTIC IMPLICATIONS AND LIMITATIONS

CHAPTER SUMMARY: RESEARCH PROSPECTS AND CHALLENGES

REFERENCES

CHAPTER 54. PURINERGIC SIGNALING IN EPILEPSY

OVERVIEW: EVOLUTIONARY LOGIC OF PURINERGIC REGULATION. WHY IS IT SO DIFFERENT COMPARED TO ANTISEIZURE DRUGS?

ADENOSINE AND ATP METABOLISM

THE ADENOSINE KINASE HYPOTHESIS OF EPILEPTOGENESIS

THE RECEPTORS

DYSREGULATION OF THE PURINERGIC SYSTEM IN EPILEPSY

P1 Receptor Expression Changes

P2 Receptor Expression Changes

PURINERGIC TREATMENT OPTIONS

Targeting P1 Receptors

Targeting P2 Receptors

Targeting Adenosine Metabolism

Adenosine Augmentation Strategies

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 55. NEUROTROPHIC FACTORS IN EPILEPSY

INTRODUCTION

Seizures Themselves Can Both Cause and Worsen Temporal Lobe Epilepsy

Neurotrophic Factors: Molecular Effectors of Activity-Induced Plasticity

NEUROTROPHINS

Brain-Derived Neurotrophic Factor

Nerve Growth Factor

Neurotrophin 3 and Neurotrophin 4

GLIAL-DERIVED NEUROTROPHIC FACTORS

Glial Cell Line-Derived Neurotrophic Factor

FIBROBLAST GROWTH FACTORS

Fibroblast Growth Factor 2

PERSPECTIVE AND CONCLUDING REMARKS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 56. NEUROGENESIS IN EPILEPSY

INTRODUCTION

MECHANISMS OF ADULT HIPPOCAMPAL NEUROGENESIS IN RODENT HIPPOCAMPUS

EVIDENCE FOR ADULT HIPPOCAMPAL NEUROGENESIS IN HUMANS

ACTIVITY-DEPENDENT NEUROGENESIS IN PHYSIOLOGIC AND PATHOLOGIC CONTEXTS

A WIDE VARIETY OF EPILEPTOGENIC INSULTS DISRUPT NEUROGENESIS

FUNCTIONAL SIGNIFICANCE OF ABNORMAL HIPPOCAMPAL GRANULE CELLS

Pathologic Roles of Adult-Generated Granule Cells

Beneficial Roles of Adult-Generated Granule Cells

NEUROGENESIS IN THE DEVELOPMENT OF TEMPORAL LOBE EPILEPSY

Abnormal Granule Cells Are Sufficient to Cause Epilepsy

Ablating Adult-Generated Granule Cells Is Antiepileptogenic

TARGETING NEUROGENESIS AS A THERAPEUTIC STRATEGY TO TREAT EPILEPSY

Early Intervention

Late Intervention

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 57. SOMATIC MOSAICISM IN FOCAL MALFORMATIONS OF CORTICAL DEVELOPMENT

INTRODUCTION

CLINICAL AND NEUROPATHOLOGIC FEATURES OF FOCAL MCDS

BRAIN SOMATIC MOSAICISM

SOMATIC VARIANTS IN FOCAL MCDs

mMCD, MOGHE and FCD Type 1

FCD Type 2 and HME

EPIGENETIC SIGNATURES IN CORTICAL MALFORMATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 58. THE MICROBIOTA–GUT–BRAIN AXIS AND EPILEPSY

INTRODUCTION

THE MICROBIOTA–GUT–BRAIN AXIS

THE MICROBIOTA–GUT–BRAIN AXIS IN BRAIN DEVELOPMENT

THE GUT MICROBIOME IN EPILEPSY

THE GUT MICROBIOME AND THE KETOGENIC DIET IN EPILEPSY

THE IMPACT OF DRUG TREATMENT ON THE GUT MICROBIOTA

POTENTIAL MICROBIAL THERAPEUTIC TARGETS FOR EPILEPSY

CONCLUSIONS AND FUTURE PERSPECTIVES

ACKNOWLEDGMENTS

REFERENCES

SECTION 4 • Translational and Clinical Biology of Seizures and Epilepsy

CHAPTER 59. OVERVIEW: TRANSLATIONAL AND CLINICAL BIOLOGY OF SEIZURES AND EPILEPSY

CHAPTER 60. REFINEMENT OF RODENT MODELS OF SEIZURES AND EPILEPSY

GENERAL DESCRIPTION

BACKGROUND

The 3Rs

Legal Framework

NC3Rs REPORT ON IMPROVING WELFARE IN RODENT EPILEPSY MODELS

INTRINSIC FEATURES OF EPILEPSY MODELS

Seizures

Comorbidities

Assessing Harms and Well-Being

Incidental Harms

Housing and Husbandry

CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

CHAPTER 61. WHAT DO MODELS MODEL IN EPILEPSY?

ANIMAL MODELS OF VARIOUS SEIZURE TYPES

ANIMAL MODELS OF EPILEPSIES

REFERENCES

CHAPTER 62. TRANSLATIONAL EPILEPSY RESEARCH: PROGRESS, CHALLENGES, AND FUTURE

INTRODUCTION

THE FIRST INTERNATIONAL TRANSLATIONAL WORKSHOP TO OPTIMIZE EPILEPSY THERAPY DEVELOPMENT (LONDON, 2012)

THE ILAE/AES JOINT TRANSLATIONAL TASK FORCE

Harmonization of Video-Electroencephalography and Electrophysiologic Studies in Rodents (TASK1)

Systematic Reviews of Animal Model Data (TASK2)

Creation of Preclinical Common Data Elements for Epilepsy Research (TASK3)

Development of an Infrastructure for Multicenter Preclinical Studies (TASK4)

TRANSPARENCY IN REPORTING

TRANSLATIONAL INITIATIVES FOR ANTIEPILEPTOGENESIS AND DISEASE MODIFICATION

CONCLUSIONS AND FUTURE PERSPECTIVES

REFERENCES

CHAPTER 63. AGE AND SEX IN THE NEUROBIOLOGY OF EPILEPSIES IN ANIMAL MODELS

DEVELOPMENTAL STAGES OF RODENT BRAIN

INCREASED SEIZURE SUSCEPTIBILITY IN IMMATURE BRAIN

Developmental Changes in Neurotransmitter Systems

AGE-SPECIFIC CONSEQUENCES OF SEIZURES

SEX-SPECIFIC DIFFERENCES IN SEIZURES OF THE DEVELOPING BRAIN

Steroid Hormones Shape Sex Differences in the Developing Brain

Sex Differences in the Developing Brain

Sex Differences in GABA Signaling

Sex Differences in Seizures

SEX-SPECIFIC CONSEQUENCES OF EARLY LIFE SEIZURES

GABA Signaling

Subsequent Behavioral Comorbidities

Seizure Susceptibility and Epilepsy

SEX-SPECIFIC MATURATION OF THE BRAIN NETWORK MEDIATING SEIZURE CONTROL

SEX-SPECIFIC DIFFERENCES IN SEIZURES OF THE ADULT BRAIN

Chemically Induced Status Epilepticus

Response to GABA-Related Convulsants

Kindling

Rodent Spike-Wave Discharges

Sex Differences in Seizures of Adult Animals Due to Steroids

REFERENCES

CHAPTER 64. GENDER IN CLINICAL BIOLOGY OF EPILEPSY

INTRODUCTION

SEX HORMONES: EFFECTS ON EXCITABILITY AND SITES OF ACTION

SEX HORMONE EFFECTS ON SEIZURE PROVOCATION IN ACQUIRED EPILEPSIES

Direct Hormonal Effects

Indirect Hormonal Effects

GENERAL EFFECTS OF SEX

CONCLUSIONS

REFERENCES

CHAPTER 65. AGE AND CLINICAL BIOLOGY OF EPILEPSY: ADULTS

THE OLDER ADULT—AN INCREASING POPULATION

CLINICAL PRESENTATION OF SEIZURES IN OLDER ADULTS

DIAGNOSIS OF SEIZURES IN OLDER ADULTS

Diagnostic Delays

Etiology of Seizures in Older Adults

Differential Diagnosis

MANAGEMENT OF SEIZURES IN OLDER ADULTS

Epilepsy Treatment Considerations in Older Adults

Choosing Antiseizure Agents for Older Adults

Generic Antiseizure Medications for Older Adults

Practical Aspects of Antiseizure Medication Use in Older Adults

Surgery in Older Adults

CONCLUSION

REFERENCES

CHAPTER 66. AGE AND CLINICAL BIOLOGY OF EPILEPSY: INFANTS

INTRODUCTION

CLINICAL FEATURES OF FOCAL SEIZURES

Seizures Show More Elaborate, Distinctive, and Complex Motor Features with Age

Alteration of Consciousness Is Difficult to Determine in the Very Young and Auras Are not Usually Volunteered, Even in Young Children with Language

Focal Seizures in the Immature Sometimes Have “Generalized” Clinical Features

Focal Seizures in the Immature Do Not Tend to Go On to Orderly Secondary Generalization

ELECTROGRAPHIC FEATURES OF FOCAL EPILEPSIES

There Is a Posterior to Anterior Shift in the Focus of the Interictal Epileptiform Discharges in Patients with Focal Seizures and Self-Limited Epilepsies

Location Varies but the Electrographic Morphology of Focal Ictal Discharges Are Remarkably Similar Across the Age Range

GENERALIZED SEIZURES IN GENETIC GENERALIZED EPILEPSIES

Generalized Spike–Waves Show a Penetrance Pattern that Is Age-Dependent

The Semiology of Generalized Seizures Varies as a Function of Age

Interictal Epileptiform Activity Shows an Orderly Change in Frequency and Organization with Age

EPILEPSIES WITH ENCEPHALOPATHY AND MIXED SEIZURES

Seizure Types and EEG Features Vary as a Function of Age in the Epileptic Encephalopathies

OVERVIEW OF MANAGEMENT OF SEIZURES IN INFANTS AND CHILDREN

Antiseizure Medications

Dietary Therapy

Epilepsy Surgery

Neurostimulation

Emerging Novel Therapies

CONCLUSION

REFERENCES

CHAPTER 67. CHRONOBIOLOGY OF EPILEPSY

INTRODUCTION

HISTORICAL PERSPECTIVE

QUANTITATIVE METHODOLOGY

Tracking Seizures

Chronic EEG

Circular Statistics

KEY CONCEPTS

Pre- and Proictal States

Seizure Triggers

Reflex Seizures

Seizure Clusters

Tipping Points

LIFE CYCLE

Early Incidence

Changes During Childbearing Age

Late Incidence

SEASONAL CYCLE

Putative Mechanisms

MULTIDIEN CYCLES

About-Monthly Cycle

About-Weekly Cycle

Animal Data

Putative Mechanisms

CIRCADIAN AND SLEEP–WAKE CYCLE

Sleep–Wake Cycle

Sleep-Related Epilepsy Syndromes

Circadian Seizure Chronotypes

Seizure Timing and Seizure Focus

Sleep Homeostasis

Putative Mechanisms

ULTRADIAN CYCLES

NREM-REM Sleep cycles

ICTAL AND INTERICTAL EPILEPTIFORM ACTIVITY

IMPLICATIONS FOR RESEARCH

Refining Clinical Trials in Epilepsy

Seizure Forecasting

Chronotherapy

CONCLUSION

REFERENCES

CHAPTER 68. SLEEP AND EPILEPSY

INTRODUCTION

SEIZURES AND INTERICTAL DISCHARGES IN WAKEFULNESS, NONRAPID EYE MOVEMENT SLEEP, AND RAPID EYE MOVEMENT SLEEP

Clinical Findings

Basic Mechanisms

SLEEP ABNORMALITIES

Clinical Findings

Basic Mechanisms

ANTISEIZURE MEDICATIONS

Clinical Findings

Basic Mechanisms

SLEEP DEPRIVATION

Clinical Findings

Basic Mechanisms

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 69. BREATHING AND AUTONOMIC DISTURBANCES DURING SEIZURES

BREATHING DYSFUNCTION

Historical Overview of Breathing Dysfunction in Seizures

Historical Explorations of Cortical Breathing Control and Modulation

Modern Methods of Respiratory Monitoring

Peri-ictal Breathing Compromise: Types and Mechanisms of Dysfunction

Neuroanatomical Basis of Breathing Dysfunction

AUTONOMIC DYSFUNCTION

Historical Overview of Autonomic Dysfunction in Seizures

Methods of Monitoring Autonomic Dysfunction in Seizures

Types of Autonomic Dysfunction with Mechanisms

CONCLUSIONS: IMPLICATIONS FOR MORBIDITY AND MORTALITY

REFERENCES

CHAPTER 70. SUDDEN UNEXPECTED DEATH IN EPILEPSY (SUDEP)

INTRODUCTION

DEFINITIONS

CASE IDENTIFICATION

INCIDENCE

CLINICAL RISK FACTORS

OTHER INVESTIGATIONS (MRI, EEG, ECG, GENETIC)

MECHANISTIC HYPOTHESES

Dysautonomia

Direct Ictal

Indirect Ictal

Interictal

Asystole

Ventricular Fibrillation

Obstructive Apnea

Central Apnea

Cerebral Shutdown/Brainstem Depolarization

A Unification Theory for SUDEP Mechanism

PREVENTION

TALKING ABOUT SUDEP

POSTMORTEM EVALUATION IN EPILEPSY

CONCLUSION

REFERENCES

CHAPTER 71. STRESS AND EPILEPSY

INTRODUCTION

EFFECT OF STRESS HORMONES ON THE BRAIN

Stress Hormones and Their Receptors

Effect of Stress Hormones on Brain Activity: Preclinical Evidence

Chronic Stress across the Lifespan

Effect of Long-Lasting Occupational Stress on the Human Brain

STRESS AND EPILEPSY

A Susceptible Stress System and Susceptible Brain

Stress and Epilepsy in Rodents

Stress and Epilepsy in Humans

Some Individuals with Epilepsy Are More Stress-Susceptible Than Others

STRESS, EPILEPSY, AND GENDER

STRESS-REDUCING INTERVENTIONS

Mindfulness

Progressive Muscle Relaxation

CONCLUDING REMARKS

REFERENCES

CHAPTER 72. SEIZURES AND EPILEPSY IN GENERAL MEDICAL DISORDERS

INTRODUCTION

GENERAL PRINCIPLES

SEIZURES AND KIDNEY FAILURE

SEIZURES AND LIVER DISEASE

SEIZURES AND CONNECTIVE TISSUE DISEASES

EPILEPSY AND CARDIAC DISEASE

SEIZURES IN THE TRANSPLANT PATIENT

HUMAN IMMUNODEFICIENCY VIRUS AND SEIZURES

SEIZURES RELATED TO ALCOHOL AND DRUGS OF ABUSE

EPILEPSY AND PULMONARY DISEASE

METABOLIC CAUSES OF SEIZURES

Disorders of Glucose Metabolism

Hyponatremia

Hypernatremia

Hypocalcemia and Hypomagnesemia

Seizures Caused by Anoxic–Ischemic Encephalopathy

THYROID DISEASE AND EPILEPSY

SEIZURES ASSOCIATED WITH SYSTEMIC CANCER

CEREBROVASCULAR DISEASE

INFECTIOUS DISEASES

DEGENERATIVE DISEASES

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 73. MEDICAL CONDITIONS IN CHILDREN WITH EPILEPSY

INTRODUCTION

DEVELOPMENTAL AND MENTAL HEALTH COMORBIDITIES

Incidence

Cognitive Impairment

Depression and Anxiety

Psychosis

Autism

Psychosocial Consequences

Social Consequences

MEDICAL COMORBIDITIES

Migraine

Sleep

Endocrine

IMPACT OF SURGICAL TREATMENT ON COMORBID CONDITIONS

OUTCOME OF ADULTS WITH CHILDHOOD-ONSET SEIZURES

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 74. NEURODEGENERATIVE DISORDERS AND EPILEPTOGENESIS

INTRODUCTION

NEURODEGENERATIVE DISORDERS AND SEIZURES

Alzheimer’s Disease

Neurocognitive Disorder with Lewy Bodies

Neurocognitive Disorder Due to Parkinson’s Disease

Frontotemporal Neurocognitive Disorders

Early-Onset Huntington’s Disease

NEURODEGENERATION IN HUMAN EPILEPSIES AND EPILEPSY SYNDROMES

CROSSROADS BETWEEN EPILEPSIES AND NEURODEGENERATIVE DISORDERS: INSIGHTS FROM ANIMAL MODELS

Tauopathies

Amyloidoses

Alpha-Synucleinopathies

TDP-43 Proteinopathies

Preclinical Insights on Molecular Mechanisms Promoting Seizures and Epileptogenesis

Common Networks

CONCLUSIONS

REFERENCES

CHAPTER 75. ANESTHESIA FOR PROCEDURES IN PATIENTS WITH EPILEPSY

INTRODUCTION

PREANESTHESIA ASSESSMENT, PREPARATION, AND PLANNING

ANESTHESIA MANAGEMENT DURING PROCEDURES

Antiseizure Medication Interactions

Anesthetics

Inhaled Anesthetics

Intravenous Anesthetics, Sedatives, and Anxiolytics

Nonopiate Analgesics

Muscle Relaxants

Others

EMERGENCE, POSTANESTHESIA CARE, POSTPROCEDURE DISPOSITION, AND MANAGEMENT OF PROLONGED SEIZURES

CONSIDERATIONS FOR SELECTED PROCEDURES

Dental Procedures

Procedures for the Evaluation and Treatment of Epilepsy

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 76. HORMONE CHANGES IN EPILEPSY

INTRODUCTION

EFFECTS OF EPILEPSY AND SEIZURES ON HORMONES IN ANIMAL MODELS

Changes in Circulating Hormone Levels in Chronic Epilepsy and in Response to Acute Seizures

Reproductive Endocrine Dysfunction in Animal Models of Epilepsy

Dysregulation of Hypothalamic Neuroendocrine Circuits in Animal Models of Epilepsy

EFFECTS OF EPILEPSY AND SEIZURES ON HORMONES IN HUMANS

Acute Changes in Hormones Following Seizures: Prolactin, Follicle-Stimulating Hormone, and Luteinizing Hormone

Altered Pulsatile Secretion of Gonadotropins and Prolactin in Epilepsy

Epilepsy During Perimenopause and Menopause

Effects of Epilepsy on Sexuality in Men and Women

Stress Hormones in Epilepsy

SUMMARY AND CONCLUSIONS

Animal Studies

Clinical Studies

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 77. EFFECTS OF HORMONES ON SEIZURE EXPRESSION

INTRODUCTION

STRESS AS SEIZURE PRECIPITATOR

ADRENOCORTICOTROPIC HORMONE EFFECT ON SEIZURE EXPRESSION

Adrenocorticotropic Hormone

Corticosteroids

SEX HORMONES

Experimental Data on Excitability

Mechanisms within the Brain

Peripheral Neurosteroid Production

Steroid Distribution and Metabolism in the Central Nervous System

Central Nervous System Effects of Synthetic Steroids

CLINICAL CHANGES ACROSS REPRODUCTIVE LIFE

Puberty

Menstrual Cycle Linkages

Menopause

HORMONES AND EPILEPSY IN MEN

FUTURE PROSPECTS

Neurosteroids in Epilepsy Treatment

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 78. DISORDERS OF REPRODUCTION AND FERTILITY IN EPILEPSY

INTRODUCTION

DEFINITIONS AND RISKS OF REPRODUCTIVE DISORDERS IN WOMEN WITH EPILEPSY

Menstrual Disorders

Reproductive Endocrine Disorders

Infertility

ETIOLOGY AND PATHOPHYSIOLOGY OF REPRODUCTIVE ENDOCRINE DISORDERS IN WOMEN WITH EPILEPSY

Epilepsy

Antiseizure Medications

Epilepsy and Valproate Combination

TREATMENT OF REPRODUCTIVE ENDOCRINE DISORDERS IN WOMEN WITH EPILEPSY

DEFINITIONS AND RISKS OF REPRODUCTIVE DISORDERS IN MEN WITH EPILEPSY

Hypogonadism

Sexual Dysfunction

Infertility

Abnormal Semen Analysis

ETIOLOGY AND PATHOPHYSIOLOGY OF HYPOGONADISM IN MEN WITH EPILEPSY

Psychosocial Stress

Antiseizure Medications

Epilepsy

TREATMENT OF REPRODUCTIVE ENDOCRINE DISORDERS IN MEN WITH EPILEPSY

Antiseizure Medication Selection

Testosterone Supplement

Phosphodiesterase Inhibitor and Prostaglandin Treatment

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 79. SEXUALITY IN EPILEPSY

SEXUAL DYSFUNCTION IN EPILEPSY

SEXUAL DYSFUNCTION IN WOMEN

SEXUAL DYSFUNCTION IN MEN

ANTISEIZURE MEDICATIONS AND SEXUAL FUNCTION

TREATMENT

CONCLUSION

REFERENCES

CHAPTER 80. MATERNAL OUTCOMES DURING PREGNANCY IN WOMEN WITH EPILEPSY

INTRODUCTION

FECUNDITY AND INFERTILITY FOR WOMEN WITH EPILEPSY

MATERNAL RISKS OF SEIZURES

FACTORS IN SEIZURE CONTROL DURING PREGNANCY

OBSTETRIC COMPLICATIONS IN WOMEN WITH EPILEPSY

INTRAPARTUM AND POSTPARTUM DEPRESSION AND ANXIETY IN WOMEN WITH EPILEPSY

BREASTFEEDING CONSIDERATIONS FOR WOMEN WITH EPILEPSY

SUMMARY

REFERENCES

CHAPTER 81. CONSEQUENCES OF SEIZURES

INTRODUCTION

SEIZURES BEGET SEIZURES?

Kindling

Secondary Epileptogenesis

Developmental and Epileptic Encephalopathies

Acute Symptomatic Seizures and Acquired Epilepsy

Can Treatment of Early Seizures Affect Development of Chronic Seizures?

SEIZURES AND BRAIN STRUCTURE

Insights from the Animal Models

Is Neuronal Loss in Epilepsy Progressive?

Mossy Fiber Sprouting and Epilepsy

Seizure Preconditioning and Epileptic Tolerance

SEIZURES AND BEHAVIOR

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 82. DRUG RESISTANCE IN EPILEPSY

INTRODUCTION

IN VIVO AND IN VITRO MODELS OF DRUG RESISTANCE

CURRENT HYPOTHESES OF MECHANISMS OF DRUG RESISTANCE

Alteration of Drug Targets in the Brain

Alteration of Drug Uptake into the Brain

Alterations of Pharmacokinetics in the Periphery

Neural Network Hypothesis

Intrinsic Severity Hypothesis

Gene Variant Hypothesis

The Epigenetic Hypothesis

Potential Role of Neuroinflammation and Blood–Brain Barrier Dysfunction in Drug-Resistance Mechanisms

Other Potential Mechanisms of Drug Resistance

HOW TO OVERCOME DRUG RESISTANCE?

Development of New Antiseizure Drugs by Using New Drug Screening Paradigms

Precision Medicine

Targeting of Transporter Function and Expression

Anti-Inflammatory Drugs and Strategies to Repair the BBB

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

SECTION 5 • Phenomenology of Seizures

CHAPTER 83. OVERVIEW: PHENOMENOLOGY OF SEIZURES

CHAPTER 84. CLASSIFICATION OF EPILEPTIC SEIZURES

INTRODUCTION

The Value of a Classification System

Historical Perspectives

CLASSIFICATION OF EPILEPTIC SEIZURES

1981 ILAE Classification of Epileptic Seizures

Early Attempts to Revise the 1981 Classification of Epileptic Seizures

The 2017 International League Against Epilepsy Seizure Classification

The Basic ILAE 2017 Classification of Seizures

The Expanded ILAE 2017 Classification of Seizures

Scope of the 2017 ILAE Classification

Summary of Seizure Types

Descriptors

HOW TO CLASSIFY A SEIZURE

ACCEPTANCE OF THE 2017 SEIZURE CLASSIFICATION

CONCLUSION

REFERENCES

CHAPTER 85. AWARENESS IN SEIZURES

INTRODUCTION

DEFINITIONS AND COMPONENTS

CLINICAL RELEVANCE

ASSESSMENT AND MEASURES OF IMPAIRED CONSCIOUSNESS

Patient and Observer Report

Objective Behavioral Testing

CONCLUSIONS AND FUTURE DIRECTIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 86. AUTOMATISMS IN SEIZURES

INTRODUCTION

PHYSIOLOGIC MECHANISMS AND NETWORKS INVOLVED IN THE GENERATION OF AUTOMATISMS

Hyperkinetic Automatisms

AUTOMATISMS AND THE RELEVANCE OF THEIR LOCALIZATION IN FOCAL SEIZURES

AUTOMATISMS IN GENERALIZED EPILEPSY

Perseverative versus De Novo Automatisms

Duration of Absences and Occurrence of Automatisms

Incidence of Automatisms in Absence Seizures

Automatisms in Generalized Seizures Other Than Classical Absences

Clinical Relevance

DIFFERENTIATION OF EPILEPTIC FROM NONEPILEPTIC AUTOMATISMS

Parasomnias: Somnambulism

Movement Disorders: Gilles-de-la-Tourette Syndrome

Automatisms in Brainstem Compression

REFERENCES

CHAPTER 87. HYPERKINETIC SEIZURES

INTRODUCTION AND HISTORICAL NOTES

PREDICTORS OF HYPERKINETIC SEIZURES

ANATOMOCLINICAL CORRELATIONS OF HYPERKINETIC SEIZURES

DISTINGUISHING FRONTAL FROM EXTRAFRONTAL HYPERKINETIC SEIZURES

REFERENCES

CHAPTER 88. AUTONOMIC AURAS AND SEIZURES

INTRODUCTION

DEFINITIONS

ANATOMIC PATHWAYS AND PATHOPHYSIOLOGY

CLASSIFICATION AND DESCRIPTION

Gastrointestinal Aura/Seizures

Cardiovascular

Secretory

Genitourinary

Cutaneous

Pupillary

CONCLUSIONS

REFERENCES

CHAPTER 89. COGNITIVE SEIZURES

INTRODUCTION

DYSMNESIC SEIZURES

ICTAL ILLUSIONS

STRUCTURED ICTAL HALLUCINATIONS

VISUAL HALLUCINATIONS AND ILLUSIONS

DISTORTIONS OF BODY IMAGE AND SOMATOSENSORY ILLUSIONS

Illusions of Movement

AUDITIVE HALLUCINATIONS AND ILLUSIONS

Illusions

Syndromatic Aspects

DISTORTIONS OF TIME SENSE

ICTAL DISORDERS OF LANGUAGE

Aphasia and Dysphasia

Speech Automatisms

Dyslexia

FORCED THINKING

STATUS OF COGNITIVE SEIZURES AND AURA CONTINUA

CONCLUSIONS

REFERENCES

CHAPTER 90. AFFECTIVE SEIZURES

INTRODUCTION

HISTORICAL PERSPECTIVES

CLASSIFICATION

ANXIETY WITH AUTONOMIC SYMPTOMS (FOCAL EMOTIONAL SEIZURES WITH FEAR/ANXIETY/PANIC): CASE 1

FOCAL EMOTIONAL SEIZURES WITH ANGER: CASE 2

ECSTATIC SEIZURES (FOCAL EMOTIONAL SEIZURE WITH PLEASURE): CASE 3

FOCAL EMOTIONAL SEIZURES WITH LAUGHTER (GELASTIC): CASE 4

FOCAL EMOTIONAL SEIZURES WITH CRYING (DACRYSTIC): CASE 5

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 91. NEOCORTICAL SENSORY SEIZURES

INTRODUCTION

DEFINITIONS

EPIDEMIOLOGY

ANATOMIC PATHWAYS AND PATHOPHYSIOLOGY

CLINICAL FEATURES

ELECTROENCEPHALOGRAPHIC FINDINGS AND CLINICAL CORRELATIONS

DIAGNOSTIC CONSIDERATIONS

DIFFERENTIAL DIAGNOSIS

SPECIFIC SYNDROMES INCORPORATING THE SEIZURE TYPE AS AN INTEGRAL FEATURE

RESPONSES TO TREATMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 92. TYPICAL ABSENCE SEIZURES

INTRODUCTION

EPIDEMIOLOGY

HISTORICAL PERSPECTIVE

Animal Models and Electrophysiologic Studies

State of the Art Nowadays: “Hot Spot Theory”

Other Anatomical Substrates

CLINICAL FEATURES

Impairment of Consciousness

Motor and Autonomic Manifestations

Induced Seizures

EEG FEATURES

ABSENCE STATUS EPILEPTICUS

DIAGNOSIS OF TAS

EPILEPSY SYNDROMES FEATURING TAS

TREATMENT OF TAS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 93. ATYPICAL ABSENCE SEIZURES

INTRODUCTION

DEFINITIONS

EPIDEMIOLOGY

ANATOMIC PATHWAYS AND PATHOPHYSIOLOGY

Neuronal Circuitry of AAS

Receptor Regulation of AAS

Mechanisms of Cognitive Impairment

Genetic Predisposition for AAS

CLINICAL FEATURES

EEG MANIFESTATIONS

DIAGNOSTIC CONSIDERATIONS

DIFFERENTIAL DIAGNOSIS

SPECIFIC SYNDROMES WITH AAS

TREATMENT

SUMMARY AND CONCLUSIONS

ACKNOWLEGMENTS

REFERENCES

CHAPTER 94. MYOCLONIC ABSENCE SEIZURES

INTRODUCTION

EPIDEMIOLOGY

SEIZURE SEMIOLOGY

ELECTROENCEPHALOGRAPHY AND POLYGRAPHIC FEATURES

NEUROIMAGING

TREATMENT

EPILEPSY WITH MYOCLONIC ABSENCES

REFERENCES

CHAPTER 95. SEIZURES WITH EYELID MYOCLONIA

INTRODUCTION

DEFINITIONS

EPIDEMIOLOGY

ANATOMIC PATHWAYS AND PATHOPHYSIOLOGY

CLINICAL FEATURES

Ictal

EEG MANIFESTATIONS AND CLINICAL CORRELATIONS

Interictal

Ictal

DIAGNOSTIC CONSIDERATIONS

SPECIFIC EPILEPSY SYNDROMES INCORPORATING EYELID MYOCLONIA AS AN INTEGRAL FEATURE

RESPONSES TO TREATMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 96. ATONIC SEIZURES

INTRODUCTION

DEFINITIONS

EPIDEMIOLOGY

ANATOMICAL PATHWAYS AND PATHOPHYSIOLOGY

ELECTROCLINICAL FEATURES

Generalized Atonic Seizures

Focal Atonic Seizures

DIAGNOSTIC CONSIDERATIONS

DIFFERENTIAL DIAGNOSIS

SPECIFIC SYNDROMES INCORPORATING ATONIC SEIZURES AS AN INTEGRAL FEATURE

RESPONSE TO TREATMENT

Medical Treatment

Surgical Treatment

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 97. CLONIC SEIZURES

INTRODUCTION

ANATOMIC BASIS

FOCAL ONSET CLONIC SEIZURES

GENERALIZED ONSET CLONIC SEIZURES

REFERENCES

CHAPTER 98. EPILEPTIC SPASMS

INTRODUCTION

DEFINITIONS

EPIDEMIOLOGY

ANATOMIC PATHWAYS AND PATHOPHYSIOLOGY

CLINICAL FEATURES

ELECTROENCEPHALOGRAPHIC FINDINGS

DIAGNOSTIC CONSIDERATIONS

SPECIFIC SYNDROMES

New Onset West Syndrome

Structural Brain Disorder

Developmental and Epileptic Encephalopathy

Epileptic Spasms Beyond the First Year of Life

RESPONSE TO TREATMENT

SUMMARY AND CONCLUSION

REFERENCES

CHAPTER 99. MYOCLONIC, MYOCLONIC–ATONIC, AND MYOCLONIC TONIC–CLONIC SEIZURES

INTRODUCTION

MYOCLONUS VERSUS MYOCLONIC SEIZURES

MYOCLONUS: DEFINITIONS AND CLASSIFICATIONS

Myoclonus in Relation to Epilepsy

Clinical Manifestations of Myoclonus

MYOCLONIC SEIZURES–CLASSIFICATION AND ELECTROCLINICAL FEATURES

Diagnostic Considerations and Relevance of Video-EEG-Polygraphy

MYOCLONIC EPILEPSIES

Early Myoclonic Encephalopathy

Myoclonic Encephalopathy in Nonprogressive Disorders

Myoclonic Epilepsy in Infants

Dravet Syndrome

Myoclonic-Atonic Epilepsy

Lennox–Gastaut Syndrome

Epilepsy With Myoclonic Absences

Juvenile Myoclonic Epilepsy

Benign Adult Familial Myoclonus Epilepsy

Progressive Myoclonus Epilepsies

MS in Symptomatic Epilepsies of Miscellaneous Etiology

PATHOPHYSIOLOY

Cortical Positive Myoclonus

Cortical Negative Myoclonus

Thalamocortical Myoclonus

Reticular Reflex Myoclonus

TREATMENT OF MYOCLONIC SEIZURES

Valproic Acid

Levetiracetam

Lamotrigine

Benzodiazepines

Zonisamide

Topiramate

Perampanel

Brivaracetam

Antiseizure Medications Potentially Aggravating MS

Treatment of Epileptic Negative Myoclonus

Ketogenic Diet

Vagus Nervus Stimulation

CONCLUSIONS

REFERENCES

CHAPTER 100. TONIC SEIZURES

HISTORICAL REVIEW

GENERALIZED TONIC SEIZURES

Summary of Generalized Tonic Seizures

Pathophysiology of Generalized Tonic Seizures

FOCAL TONIC SEIZURE

TREATMENTS

SUMMARY AND CONCLUSION

REFERENCES

CHAPTER 101. GENERALIZED TONIC–CLONIC SEIZURES

INTRODUCTION

DEFINITIONS AND CLASSIFICATION

EPIDEMIOLOGY

ANATOMIC PATHWAYS AND PATHOPHYSIOLOGY

CLINICAL FEATURES

Ictal

Postictal

EEG MANIFESTATIONS AND CLINICAL CORRELATIONS

Interictal

Ictal

Postictal

DIAGNOSTIC CONSIDERATIONS

DIFFERENTIAL DIAGNOSIS: NONEPILEPTIC CONDITIONS

RESPONSES TO TREATMENT

REFERENCES

CHAPTER 102. BEHAVIORAL ARREST IN SEIZURES

INTRODUCTION

PATHOPHYSIOLOGY

“BEHAVIORAL ARREST” AS A DESCRIPTOR IN THE NEW OPERATIONAL SEIZURE CLASSIFICATION

USE OF THE TERM “BEHAVIORAL ARREST” IN NEONATAL SEIZURE CLASSIFICATION

LATERALIZATION AND LOCALIZATION VALUE OF BEHAVIORAL ARREST AS A SEIZURE MANIFESTATION

Seizures of Temporal Lobe Origin

Seizures of Frontal Lobe Origin

Seizures of Occipital and Parietal Lobe Origin

BEHAVIORAL ARREST AS AN ICTAL MANIFESTATION OF FOCAL SEIZURES IN INFANTS AND YOUNG CHILDREN

CONCLUSION

REFERENCES

CHAPTER 103. NEONATAL SEIZURES

INTRODUCTION

EPIDEMIOLOGY AND RISK FACTORS

ETIOLOGIES

CHARACTERIZATION AND CLASSIFICATION

NEUROPHYSIOLOGY OF NEONATAL SEIZURES

APPLICATIONS OF CONTINUOUS EEG MONITORING IN DIAGNOSIS AND MANAGEMENT OF NEONATAL SEIZURES

THERAPEUTIC STRATEGIES

OUTCOME

SUMMARY

REFERENCES

CHAPTER 104. LOCALIZING AND LATERALIZING VALUE OF SEIZURE PHENOMENOLOGY

INTRODUCTION

UTILITY AND ACCURACY

SEMIOLOGY CLASSIFICATION

COGNITIVE

Somatosensory Auras

Visual Auras

Auditory Auras

Vertiginous Auras

Olfactory and Gustatory Auras

Autonomic Auras and Seizures

Other Auras

MOTOR SEIZURES

Simple Motor Seizures

Other Motor Seizures

POSTICTAL PHENOMENA

MESIAL VERSUS NEOCORTICAL TEMPORAL LOBE SEIZURES

FRONTAL LOBE SEIZURES

LIMITATIONS OF SEIZURE SEMIOLOGY

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 105. STATUS EPILEPTICUS: PHENOMENOLOGY AND PATHOPHYSIOLOGY

DEFINITION

EPIDEMIOLOGY, ETIOLOGY, AND PROGNOSIS

HUMAN PHENOMENOLOGY

MRI Findings

PATHOPHYSIOLOGY OF SE: STUDIES IN EXPERIMENTAL ANIMALS

Role of GABAergic Inhibition

Seizures Open the Dentate Gate by Breaking Down GABAergic Inhibition

Seizure Potentiates Excitatory Synaptic Transmission in CA1 Pyramidal Neurons

TREATMENT OF STATUS EPILEPTICUS

REFERENCES

VOLUME II

SECTION 6 • Diagnostic Evaluation of Seizures and Epilepsy

CHAPTER 106. OVERVIEW: DIAGNOSTIC EVALUATION IN EPILEPSY

INTRODUCTION

SUMMARY AND CONCLUSIONS

CHAPTER 107. HISTORY AND PHYSICAL EXAMINATION IN EPILEPSY

INTRODUCTION

HISTORY TAKING

Background

Past Medical History

The Person with Epilepsy

PHYSICAL EXAMINATION

Neurologic Examination

General Medical Examination

Brief Assessment of Cognitive, Social, and Behavioral Functioning

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 108. EPILEPSY INFORMATICS

INTRODUCTION

EPILEPSY AND THE ELECTRONIC HEALTH RECORD—CLINICAL CARE

Electronic Health Record Systems

EHR Content

Direct Patient Interactions with the EHR

Clinical Decision Support

Automated Review of Diagnostic Studies

Epilepsy and Telehealth

EPILEPSY AND THE ELECTRONIC HEALTH RECORD—FOUNDATIONS FOR POPULATION HEALTH

Common Data Elements

Computable Phenotypes

Ontologies

Individualized Predictions with EHR Data

Learning Health Care Systems

EPILEPSY AND THE INTERNET

Internet as Source of Information

Epilepsy and Social Media

EPILEPSY AND INTERNET-CONNECTED DEVICES

Introduction to Patient-Generated Data/Internet of Things

Electronic Seizure Diaries

Wearable Devices for Epilepsy

Seizure Detection Devices (Implanted)

Internet of Things

CONCLUSION

REFERENCES

CHAPTER 109. LABORATORY ETIOLOGICAL SCREENING FOR SEIZURES

INTRODUCTION

LABORATORY ETIOLOGIC INVESTIGATION FOR ACUTE SYMPTOMATIC SEIZURES

LABORATORY INVESTIGATION FOR THE ETIOLOGY OF EPILEPSY SYNDROMES: METABOLIC, INFLAMMATORY, OR INFECTIOUS CAUSES

Metabolic Screening

Immunologic Testing

Genetic Testing and Screening

Serum Concentration Measurements of Antiseizure Medications

Laboratory Monitoring of Toxicity

Pharmacogenetic Analyses

CONCLUSIONS

REFERENCES

CHAPTER 110. PHYSIOLOGICAL BASIS OF THE ELECTROENCEPHALOGRAM AND LOCAL FIELD POTENTIALS

INTRODUCTION

MEASURING EXTRACELLULAR CURRENT FLOW TO DERIVE NETWORK MECHANISMS: A TUTORIAL

Extracellular Potentials of an Individual Neuron

Extracellular Potentials of Neural Populations

Network Mechanisms of an Electrophysiologic Pattern: The Hippocampal Sharp Wave

ORIGIN OF EXTRACELLULAR CURRENTS

Fast (Na+) Action Potentials

Synaptic Activity

Calcium Spikes

Voltage-Dependent Intrinsic Oscillations

Intrinsic Spike Afterhyperpolarizations

Ephaptic Effects

Gap Junctions and Neuron–Glia Communication

EXTRACELLULAR BRAIN SIGNALS FOLLOW A POWER LAW

EXTRACELLULAR POTENTIALS ORGANIZE INTO A SYSTEM OF FUNCTIONAL OSCILLATIONS

BRAIN OSCILLATIONS INTERACT IN SPACE AND TIME

IMPLICATIONS FOR BRAIN DYNAMICS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 111. VIDEO-EEG TECHNOLOGIES, MONTAGES, AND POSTPROCESSING IN EPILEPSY

INTRODUCTION

EEG ELECTRODES AND RECORDING

Location and Securing Electrodes

Key Electrodes

Artifact Channels

Impedance Checks

EEG RECORDING SITES AND MONTAGES

Electrode Nomenclature

Additional Electrodes

Montages

Montage Reformatting

Depth Electrode Montages

EEG PROCESSING AND DISPLAYING

Digitization

ADC Resolution

Filtering

Postprocessing

PRUNING AND STORING

EEG Storage

Pruning and Archiving

VIDEO RECORDING

CABLE, RADIO, AND AMBULATORY RECORDING

Radio or Cable

Ambulatory Recording

REFERENCES

CHAPTER 112. INTERICTAL ELECTROENCEPHALOGRAPHY

INTRODUCTION

THE ROLE OF EEG IN THE DIAGNOSIS OF EPILEPSY

TYPES OF EEG

CRITERIA FOR INTERICTAL EPILEPTIFORM DISCHARGES (IEDs)

SENSITIVITY OF IEDs

SPECIFICITY OF IEDs

TYPES OF IEDs

Focal IEDs

Generalized IEDs

Photoparoxysmal Response

INTERICTAL EEG IN COMMON EPILEPSY SYNDROMES

Focal Epilepsy Syndromes

Generalized Epilepsy Syndromes

ROLE OF INTERICTAL EEG IN THE DECISION TO DISCONTINUE ANTISEIZURE MEDICATIONS

ROLE OF INTERICTAL EEG IN EVALUATING PATIENTS FOR EPILEPSY SURGERY

SUMMARY AND CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 113. ICTAL ELECTROENCEPHALOGRAPHY

INTRODUCTION

RATIONALE FOR RECORDING SEIZURES

Differential Diagnosis

Classification

Localization

Quantification

METHODS FOR RECORDING SEIZURES

Electrodes

EEG Recording

Limitations of EEG Recording

Enhancing Seizure Occurrence

FOCAL SEIZURES

Seizures Recorded With Scalp Electrodes

Seizures Recorded With Intracranial Electrodes

GENERALIZED SEIZURES

EARLY INFANTILE SEIZURES (NEONATAL SEIZURES)

Atonic Seizures

Behavioral Arrest (Hypomotor) Seizures

Clonic Seizures

Migratory Seizures

Myoclonic Seizures

Spasms

Tonic Seizures

LATE INFANCY

Myoclonic–Atonic Seizures

Myoclonic–Tonic or Spasm–Tonic Seizures

CHILDHOOD, ADOLESCENCE, AND ADULTHOOD

SUMMARY AND CONCLUSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 114. POLYGRAPHIC RECORDINGS IN EPILEPSY

INTRODUCTION

TECHNICAL ASPECTS

Currency

Methodology

Polysomnography in Patients with Epilepsy

POLYGRAPHIC STUDIES IN THE INVESTIGATION OF EPILEPTIC MOTOR MANIFESTATIONS

Analysis of Motor Phenomena

Analysis of Motor Patterns

Evolution of Motor Manifestations in Relation to Sleep–Wake Cycle

Unverricht–Lundborg Disease

Computer-Assisted Analysis of Polygraphic Signals

POLYGRAPHIC INVESTIGATIONS IN THE STUDY OF REFLEX EPILEPSY

POLYGRAPHY AS AN AID IN THE DIFFERENTIAL DIAGNOSIS OF EPILEPTIC AND NONEPILEPTIC EPISODES

Syncope and Cardiac Dysrhythmia

Psychogenic Nonepileptic Seizures

POLYGRAPHIC MONITORING OF THE EFFECTS OF ANTISEIZURE DRUGS

SEIZURE DETECTION AND PREDICTION WITH WEARABLE DEVICES RECORDING MULTIPLE BIOLOGIC SIGNALS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 115. HOME-VIDEO EEG MONITORING IN EPILEPSY

INTRODUCTION

EVOLUTION OF HOME VEEG TELEMETRY

INDICATIONS FOR HOME VEEG TELEMETRY

Seizure Capture and Characterization

Diagnosis of Psychogenic Nonepileptic Seizure

Assessment of Response to Medications

Assessment After Medication Discontinuation

ADVANTAGES OF HOME VEEG TELEMETRY

Increase Diagnostic Yield Over Routine EEG

Convenient

Cost Effective

DISADVANTAGES OF HOME VEEG TELEMETRY

Loss of Recording Integrity and Increased Artifacts

Inability to Decrease Medications

Unable to Examine Patient During Clinical Events

Unable to Use Provocation Techniques

CHALLENGES OF HOME VEEG TELEMETRY

Patient Selection

Video Recording Quality

Equipment Handling, Learning

HOME VEEG TELEMETRY BEYOND EPILEPSY AND SEIZURE-LIKE SPELLS

Future Directions

CONCLUSION

REFERENCES

CHAPTER 116. STANDARDIZED EEG REPORTING

BASIC INFORMATION ABOUT THE PATIENT AND THE RECORDING

Identification of the Patient

History and Referral Information

Recording Conditions and Technical Information

BACKGROUND ACTIVITY

ABNORMAL EEG PATTERNS

Name and Morphology of the Abnormality

Location of the Abnormality

Time-Related Features

Reason for Abnormality

PAROXYSMAL EVENTS

ILAE Classifications

ILAE Terminology for Semiology

Standardized Terminology for EEG Changes

NORMAL VARIANTS AND ARTIFACTS

POLYGRAPHIC RECORDINGS

SYNOPSIS

INTERPRETATION

Classification

Diagnostic Significance

Clinical Comments

CONCLUSION

REFERENCES

CHAPTER 117. ELECTROENCEPHALOGRAPHY IN THE INTENSIVE CARE UNIT

INTRODUCTION

INDICATIONS AND DURATION OF cEEG MONITORING

TECHNICAL ADVANCES

INTERICTAL EEG ABNORMALITIES

SEIZURES AND THE ICTAL–INTERICTAL CONTINUUM

BEYOND SEIZURE DETECTION

Delayed Cerebral Ischemia

Prognostication

SUMMARY

REFERENCES

CHAPTER 118. LONG-TERM MONITORING IN THE EPILEPSY MONITORING UNIT

INTRODUCTION

APPLICATIONS

Distinguishing Seizures from Nonepileptic Events

Characterization of Seizures or Epilepsy Syndrome

Quantification of Seizures

Identification of IEDs

Presurgical Evaluation

TECHNICAL ASPECTS

The Patient’s Room

Recording Techniques

Monitoring of Other Biologic Signals

Techniques to Increase the Yield of Seizures

Safety Considerations in the EMU

EMU GUIDELINES

ADVANTAGES AND DISADVANTAGES OF EMU MONITORING

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 119. DRUG WITHDRAWAL AND OTHER ACTIVATING TECHNIQUES IN EPILEPSY

INTRODUCTION

PHARMACOLOGIC TECHNIQUES OF ACTIVATION

Activation by Discontinuation of Antiseizure Medications

Potential Complications of ASM Withdrawal and Methods of Prevention

Procedure for Withdrawing Antiseizure Medications for Long-term Monitoring

Are Children Less at Risk?

Activation with Parenteral Drugs

OTHER ACTIVATION TECHNIQUES

Sleep Deprivation

Hyperventilation

Photic Stimulation

Electrical Stimulation of Intracranial Electrodes

ROLE OF ACTIVATION IN PSYCHOGENIC SEIZURES

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 120. ELECTROENCEPHALOGRAPHY AND MAGNETOENCEPHALOGRAPHY POSTPROCESSING IN EPILEPSY: MAPPING, SOURCE IMAGING, AND DYNAMIC ANALYSIS

VOLTAGE MAPS

FREQUENCY MAPS

MAGNETOENCEPHALOGRAPHY

SOURCE IMAGING

Forward and Inverse Solutions

Electrode Array and Head Models

Propagation of the Activity and Averaging of the Spikes

Analysis—Pipeline

Evidence for the Accuracy and Clinical Utility of SI in Presurgical Evaluation

Automated SI

DYNAMIC ANALYSIS

EEG Connectomes

Applications

Caveats and Future Perspectives

REFERENCES

CHAPTER 121. QUANTITATIVE EEG ANALYSIS AND AUTOMATIC EVENT DETECTION

QUANTITATIVE ANALYSIS OF EEG BACKGROUND

Filtering and Digitization of the EEG

Single Channel EEG Recording and Analysis

Methods of Analyzing the EEG Background

Sampling in Time and Space

Assessing Epileptic Neuronal Networks and Resting-State Brain Activity Using EEG

Mathematical Decomposition

AUTOMATIC SEIZURE DETECTION

Types of Seizure Detection

What Is a Seizure and Measuring Seizure Detection Performance

Seizure Detection Methods

Conclusion

AUTOMATIC SPIKE DETECTION

Conclusion

AUTOMATED DETECTION OF HFOS

Pathologic versus Physiologic HFOs

Data Selection

Artifacts

Data Preprocessing

HFO Detection

Classification, Semiautomated Review, and Validation

Detecting Interictal HFOs in Noninvasive EEG

Phase–Amplitude Coupling

Epileptogenicity Index

Conclusions

REFERENCES

CHAPTER 122. STRUCTURAL NEUROIMAGING IN EPILEPSY

INTRODUCTION

IN EPILEPSY, “NORMAL” AND “ABNORMAL” MRI ARE DIAGNOSES THAT REQUIRE CERTAINTY: “SUSPICIOUS” IS EQUALLY IMPORTANT

TECHNICAL ISSUES

An “Epilepsy Protocol” Is Essential

T1-Weighted Images

T2-Weighted Images

Fluid-Attenuated Inversion Recovery Images

Image Acquisition

Interpretation

Requests

Typical Imaging Sequences for an Optimized Epilepsy Protocol

Morphometry, Quantification of Volumes, and T2 Relaxometry in Epilepsy

Diffusion-Weighted Imaging

Advanced Analysis Techniques

MAJOR FINDINGS ON MAGNETIC RESONANCE IMAGING

Obvious Lesions

Hippocampal Sclerosis

Malformations of Cortical Development

SPECIAL CONSIDERATIONS FOR INFANTS AND CHILDREN

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 123. POSITRON EMISSION TOMOGRAPHY IN EPILEPSY

INTRODUCTION

PET METHODOLOGY

Principles of PET

Infrastructure Requirements: Cyclotrons, Radiochemistry, and Scanners

Isotopes Used Now or in Future

Acquisition Technique: Clinical PET

Acquisition Technique: Research PET

Interpretation of Clinical (FDG) PET

Role of Quantification

Clinical Indications for FDG PET

Expected Findings on FDG PET

TEMPORAL LOBE EPILEPSY

Lesional Temporal Lobe Epilepsy

Nonlesional Temporal Lobe Epilepsy

EXTRATEMPORAL LOBE EPILEPSY

FDG PET IN SOME SPECIFIC CONDITIONS

Childhood Epilepsy Syndromes

Developmental Abnormalities

Encephalitis

Status Epilepticus

Focal Hypermetabolism

FDG PET AND EPILEPSY SURGERY

Prediction of Postsurgical Outcome

Effects of Surgery

Effects of Neuromodulation

PET WITH NOVEL RADIOTRACERS

GABA-Ergic Neurotransmission in Focal Epilepsies

GABA-Ergic Neurotransmission in Genetic Epilepsies

Glutamatergic Neurotransmission

Opiate Receptors

Cannabinoids

Serotonergic Systems

Dopaminergic Neurotransmission

Cholinergic Neurotransmission

Inflammation

Multidrug Transporter Function

Imaging of Antiseizure Medications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 124. SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY IN EPILEPSY

INTRODUCTION

INTERICTAL BLOOD FLOW SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

PERI-ICTAL SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

Technique of Peri-Ictal Single Photon Emission Computed Tomography Injection

PERI-ICTAL SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY PERFUSION PATTERNS

TECHNIQUES IN SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY IMAGE ANALYSIS AND INTERPRETATION

Subtraction Single Photon Emission Computed Tomography with Magnetic Resonance Imaging Coregistration

Single Photon Emission Computed Tomography with Statistical Parametric Mapping Analysis

LIMITATIONS OF SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

RESEARCH APPLICATIONS IN SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 125. MAGNETIC RESONANCE SPECTROSCOPY IN EPILEPSY

INTRODUCTION

MR SPECTROSCOPY: PROTON SPECTRUM

MR SPECTROSCOPY (MRS) STUDIES IN HUMANS

NAA in Defined Lesions (Focal Cortical Dysplasias, Heterotopias, Polymicrogyrias, Hippocampal Sclerosis)

N-acetyl Aspartate Levels Depend on Epilepsy Duration in Temporal Lobe Epilepsy

Multimodal Studies in Human Epilepsy

Human Studies in Surgical Epilepsy for Classification

Glutamate and GABA in Epilepsy

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 126. FUNCTIONAL MAGNETIC RESONANCE IMAGING IN EPILEPSY

INTRODUCTION

THE PHYSICAL AND PHYSIOLOGIC BASES OF FUNCTIONAL MAGNETIC RESONANCE IMAGING

FUNCTIONAL MAGNETIC RESONANCE IMAGING

APPLICATIONS OF FUNCTIONAL MAGNETIC RESONANCE IMAGING TO EPILEPSY

Presurgical Planning

Newer Applications for fMRI in Epilepsy

EEG-fMRI

Resting-State fMRI

CONCLUSIONS

REFERENCES

CHAPTER 127. SEIZURE PREDICTION

INTRODUCTION

LESSONS LEARNED FROM HISTORY

OVERVIEW OF ANALYSIS TECHNIQUES USED TO PREDICT SEIZURES

STATISTICAL CONSIDERATIONS

DATABASES, DATA QUALITY, AND THEIR IMPLICATIONS

ANIMAL MODELS OF SEIZURES AND EPILEPSY

PATIENT-BASED SEIZURE PREDICTION

SEIZURE PREDICTION WITH MULTIMODAL NON-EEG DATA/WEARABLES

Preictal Changes in Cortical Excitability Following External Brain Stimulation

Preictal Alterations in Cortical Hemodynamics

Use of Wearables and Peripheral Non-EEG Characteristics for Seizure Prediction

OUTLOOK

REGULATORY ASPECTS

CHALLENGES

REFERENCES

CHAPTER 128. EEG- AND NON–EEG-BASED WEARABLE DEVICES FOR SEIZURE DETECTION

INTRODUCTION

NON–EEG-BASED WEARABLE DEVICES

SUBCUTANEOUS EEG WEARABLE DEVICES

REFERENCES

CHAPTER 129. TRANSCRANIAL MAGNETIC STIMULATION IN EPILEPSY

INTRODUCTION

ELECTROMAGNETIC INDUCTION AND TMS BASICS

Transcranial Magnetic Stimulation Coils

Site of Transcranial Magnetic Stimulation Activation

TMS Measures of Cortical Excitability

Altered TMS Metrics in Epilepsy

Studies Performed by Stimulating During the Seizures

EFFECTS OF ANTISEIZURE TREATMENT

TMS and ASMs

TMS and Nonpharmacologic Antiseizure Interventions

SEIZURE SUPPRESSION BY RTMS

rTMS in Status Epilepticus

Controlled rTMS Trials in Epilepsy

Considerations for Deep Foci

MAPPING MOTOR FUNCTION, LANGUAGE, AND MEMORY

Mapping the Primary Motor Cortex

Mapping Language

TMS SAFETY AND TOLERABILITY IN EPILEPSY

rTMS Safety

TMS in Patients With Prior Cranial Surgery

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 130. NEUROPSYCHOLOGICAL EVALUATION OF ADULTS WITH EPILEPSY

INTRODUCTION

MULTIFACTORIAL INFLUENCES

GENETIC EPILEPSIES

FOCAL SYMPTOMATIC EPILEPSY

Temporal Lobe Epilepsy

Frontal Lobe Epilepsy

Etiology

ANTISEIZURE MEDICATION EFFECTS

ACCELERATED LONG-TERM FORGETTING

NEWER SURGICAL EPILEPSY TREATMENTS

NEUROMODULATION

NEUROBEHAVIORAL PHENOTYPING

NEUROPSYCHOLOGICAL DIAGNOSTICS

Cognitive Screening

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 131. NEUROPSYCHOLOGICAL EVALUATION OF CHILDREN WITH EPILEPSY

INTRODUCTION

MODELS OF NEUROPSYCHOLOGICAL ASSESSMENT

DOMAINS COVERED IN THE NEUROPSYCHOLOGICAL ASSESSMENT

WHO SHOULD CONDUCT A NEUROPSYCHOLOGICAL ASSESSMENT?

WHO SHOULD UNDERGO A NEUROPSYCHOLOGICAL ASSESSMENT AND WHEN?

CHALLENGES FOR ASSESSING VERY YOUNG OR DEVELOPMENTALLY DELAYED CHILDREN

NEUROPSYCHOLOGICAL ASSESSMENT IN PEDIATRIC EPILEPSY SURGERY

Information About the Epileptogenic Focus

Risks of Surgery

Evaluating the Outcome of Surgery

TRANSITION PLANNING

FUTURE DIRECTIONS

CONCLUSION

REFERENCES

SECTION 7 • General Treatment Considerations in Epilepsy

CHAPTER 132. OVERVIEW: GENERAL APPROACHES TO MEDICAL TREATMENT FOR EPILEPSY

INTRODUCTION

LEVELS OF DIAGNOSIS

GENERAL CONSIDERATIONS OF MEDICAL TREATMENT ISSUES

PRINCIPLES OF DRUG TREATMENT

STRATEGIES FOR PHARMACOTHERAPY

SPECIAL THERAPEUTIC CONSIDERATIONS

ALTERNATIVE APPROACHES

SUMMARY AND CONCLUSIONS

CHAPTER 133. WHEN TO START ANTISEIZURE MEDICATION THERAPY

INTRODUCTION

ILLUSTRATIVE CASES

ELEMENTS OF THE DECISION-MAKING PROCESS: ASSESSING RISKS AND BENEFITS

Risk of Seizure Recurrence After a First Unprovoked Seizure

Type of Seizure

Timing of Seizures

Frequency of Seizures

Effects of Age on Consequences of Seizures

Environment

Consequences of Treatment

DECIDING WHETHER TO TREAT

Issues to Consider Prior to Initiating Antiseizure Medication Therapy

Acute Symptomatic and Provoked Seizures

Self-limited Epilepsy Syndromes and Childhood Epilepsy with Only a Few Solitary Seizures

Other Considerations

CONSIDERATION OF THE ILLUSTRATIVE CASES

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 134. MANAGEMENT OF ANTISEIZURE MEDICATION INITIATION

INTRODUCTION

SETTING AN INITIAL THERAPEUTIC GOAL

RATE OF ASM INITIATION

RASH: COUNSELING AND POTENTIAL MANAGEMENT

PATIENT COUNSELING

ASM Side Effects and Special Considerations

Adherence

Pregnancy, Contraception, Folic Acid

Medication Interactions

Seizure Safety

Alcohol and Other Drugs

Sudden Unexpected Death in Epilepsy

Driving

Resources for Patients

RESCUE THERAPY AND PLANNING FOR SEIZURE RECURRENCE

Rescue Therapy

Planning for Seizure Recurrence and Follow-Up

CONCLUSIONS

REFERENCES

CHAPTER 135. MATCHING ANTISEIZURE MEDICATIONS TO THE PATIENT

INTRODUCTION

GENERAL PRINCIPLES

MEDICAL–PHYSIOLOGIC FACTORS

Genetic Factors

Age

Sex

Comorbid Illness

NONMEDICAL PATIENT FACTORS

PHYSICIAN FACTORS

MEDICATION FACTORS

Route

Frequency of Dosing

Cost

Renal and/or Hepatic Clearance

Interactions

Speed of Onset

Side Effects

Habit-Forming and Ease of Withdrawal

Mechanism of Action

CONCLUSIONS

REFERENCES

CHAPTER 136. CHOICE OF ANTISEIZURE MEDICATIONS

INTRODUCTION

EPILEPSY CLASSIFICATION

EFFICACY

Newly Diagnosed

Add-on Therapy

SAFETY AND TOLERABILITY

DRUG INTERACTIONS

COMORBID CONDITIONS

TITRATION AND DOSE SELECTION

AVAILABILITY

STAGES OF DISEASE

Initial Monotherapy

When the First ASM Fails

Treatment-Resistant Patients

SPECIAL GROUPS

Children

Women

The Elderly

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 137. MEASURING TREATMENT RESPONSE IN THE EPILEPSY CLINIC

INTRODUCTION

TECHNIQUES TO MEASURE SEIZURE FREQUENCY, TYPE, AND INTENSITY

Paper Diaries

Electronic Diaries

Real-Time Tracking with Implanted Devices

SEIZURE FREQUENCY OVER TIME

THE FOLLOW-UP CLINIC VISIT

The Follow-Up Visit

Spontaneously Reported Symptoms

Checklist of Symptoms and Closed-Ended Questions

MEASURING PLASMA LEVELS AND SIDE EFFECTS OF ASMs

THE UTILITY OF ROUTINE AND LONG-TERM EEG MONITORING IN MEASURING TREATMENT RESPONSE

CONCLUSIONS

REFERENCES

CHAPTER 138. SELF-MANAGEMENT STRATEGIES IN EPILEPSY—BEYOND ANTISEIZURE MEDICATIONS

INTRODUCTION

COMPONENTS OF EPILEPSY SELF-MANAGEMENT

MAIN APPROACHES FOR EPILEPSY SELF-MANAGEMENT

Educational Approaches

Psychosocial Approaches

LOGISTICS OF EPILEPSY SELF-MANAGEMENT PROGRAM DELIVERY

A PROFESSIONAL AND RESEARCH COLLABORATION TO ADVANCE EPILEPSY SELF-MANAGEMENT

Special Populations

FUTURE CHALLENGES AND OPPORTUNITIES

CONCLUSIONS

REFERENCES

CHAPTER 139. PHARMACIST ROLES IN INTERPROFESSIONAL TEAM CARE OF PEOPLE WITH EPILEPSY AND APPROACH TO CARE

INTRODUCTION

PHARMACY SERVICES FOR THE CARE OF THE PATIENT WITH EPILEPSY IN SPECIALIZED CLINICS AND EPILEPSY CENTERS

PHARMACY SERVICES FOR THE CARE OF THE PATIENT WITH EPILEPSY IN THE PRIMARY CARE AND COMMUNITY SETTING

PHARMACY SERVICES IN EPILEPSY EDUCATION

PHARMACIST APPROACH TO CARE OF THE PATIENT WITH EPILEPSY

MOTIVATIONAL INTERVIEWING

REFERENCES

CHAPTER 140. PHARMACOKINETICS OF ANTISEIZURE MEDICATIONS

INTRODUCTION

ABSORPTION

Gastrointestinal Absorption

Rectal Absorption

Intramuscular Absorption

Buccal Absorption

Nasal Absorption

Absorption from Other Routes

DISTRIBUTION

Binding to Plasma Proteins

Tissue Binding

Tissue Blood Flow and Drug Distribution

Blood–Brain Barrier

Placental Barrier

Distribution into Breast Milk

ELIMINATION

Pharmacokinetic Concepts

Biotransformation

Factors Affecting Drug Metabolism

Renal Excretion

SINGLE-DOSE PHARMACOKINETICS

Intravenous Administration

Oral Administration

PHARMACOKINETICS DURING CONTINUOUS OR MULTIPLE DOSING

Continuous Dosing

Multiple Doses

NONLINEAR PHARMACOKINETICS

Dose-Dependent Kinetics

Dose-Dependent Absorption

Dose-Dependent Protein Binding

Dose-Dependent Metabolism: Enzyme Saturation

Time-Dependent Kinetics

POPULATION PHARMACOKINETICS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 141. PHARMACOKINETIC AND PHARMACODYNAMIC DRUG-DRUG INTERACTIONS IN EPILEPSY

INTRODUCTION

PHARMACODYNAMIC INTERACTIONS

PHARMACOKINETIC INTERACTIONS

Enzyme Induction and Inhibition

Other Pharmacokinetic Mechanisms

PHARMACOKINETIC INTERACTIONS BETWEEN ASMS

PHARMACOKINETIC INTERACTIONS BETWEEN ASMS AND OTHER DRUGS

CONCLUSION

REFERENCES

CHAPTER 142. THERAPEUTIC DRUG MONITORING IN EPILEPSY

INTRODUCTION

PRINCIPLES OF THERAPEUTIC DRUG MONITORING

FACTORS AFFECTING RESPONSE TO A GIVEN ANTISEIZURE MEDICATION LEVEL

Characteristics of the Seizure Disorder

Age

Duration of Treatment

Conditions Associated with Altered Drug Binding to Serum Proteins

Comorbidities

Drug Interactions

Confounding Effects of Pharmacologically Active Metabolites

THE CONCEPT OF THERAPEUTIC RANGE

The Individual Reference Concentration

ASSESSMENT OF THE IMPACT OF THERAPEUTIC DRUG MONITORING ON CLINICAL OUTCOME

USE OF THERAPEUTIC DRUG MONITORING IN VARIOUS CLINICAL SETTINGS

Settings in Which Clinical Assessment of Effects Is Particularly Difficult

Settings with Alterations in Pharmacokinetics

Settings with Unexpected Clinical Response

MISUSE OF ASM-LEVEL TESTING

Inappropriate ASM-Level Testing

Misinterpretation of ASM Levels

TIME OF SAMPLING

BIOLOGIC MATRIX

ANALYTICAL TECHNIQUES

Direct Measurement of Unbound Drug Concentrations

RELEVANCE AND APPLICATION OF THERAPEUTIC DRUG MONITORING IN RELATION TO INDIVIDUAL ANTISEIZURE MEDICATIONS

Older Antiseizure Medications

Newer Antiseizure Medications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 143. DOSE-RELATED SIDE EFFECTS OF ANTISEIZURE MEDICATIONS

INTRODUCTION

THE SCOPE OF DOSE-RELATED ADVERSE EFFECTS

DOSE-RELATED ADVERSE EFFECTS FOR ASMS

Cognitive Impairment and Fatigue

Rash

Teratogenicity

Peak Dose Effects

Tolerance to Dose-Related Adverse Effects

PATIENT GROUPS WITH AN INCREASED RISK FOR DOSE-RELATED ADVERSE EFFECTS

MANAGEMENT OF DOSE-RELATED ADVERSE EFFECTS

CONCLUSION

REFERENCES

CHAPTER 144. IDIOSYNCRATIC ADVERSE REACTIONS FROM ANTISEIZURE MEDICATIONS

INTRODUCTION

PATHOGENESIS OF IDIOSYNCRATIC ADVERSE REACTIONS TO ASMS

The Role of Reactive Metabolites

Mechanisms of Idiosyncratic Adverse Reactions to ASMs

GENETIC DETERMINANTS

RISK FACTORS

Age

Starting Dose and Titration Rate

Role of Diseases

Role of Concomitant Treatments

MOST COMMON ASM-INDUCED IDIOSYNCRATIC REACTIONS

Cutaneous Manifestations of Hypersensitivity

Hematologic Reactions

Hepatotoxicity

Pancreatitis

CNS Reactions

Ocular Reactions

Cardiac Effects

Miscellanea

PREVENTION, DIAGNOSIS, AND MANAGEMENT

Prevention

Diagnosis

Management

REFERENCES

CHAPTER 145. LONG-TERM ADVERSE EFFECTS OF ANTISEIZURE MEDICATIONS

INTRODUCTION

COSMETIC EFFECTS

REPRODUCTIVE HEALTH

SEXUAL DYSFUNCTION

BONE HEALTH

THYROID FUNCTION

PERIPHERAL NEUROPATHIES

CEREBELLAR ATROPHY

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 146. GENDER ISSUES FOR DRUG TREATMENT IN EPILEPSY

INTRODUCTION

REPRODUCTIVE DYSFUNCTION

Birth Rates

Fertility

Polycystic Ovary Syndrome, Epilepsy, and Valproate Use

Semen Quality, Epilepsy, and Antiseizure Medications

Sexuality

PERIMENOPAUSE, MENOPAUSE, AND BONE HEALTH

FAMILY PLANNING

FACTORS IN DRUG SELECTION IN WOMEN OF CHILDBEARING AGE

Traditional Drugs—Pros and Cons

Newer Drugs—Pros and Cons

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 147. MANAGING ANTISEIZURE MEDICATIONS THROUGH CONTRACEPTION AND PREGNANCY

INTRODUCTION

ASMs AND CONTRACEPTION

ASMS AND PREGNANCY

Absorption and Distribution

Hepatic Clearance

Renal Clearance

Therapeutic Drug Monitoring

CONCLUSIONS

REFERENCES

CHAPTER 148. ANTISEIZURE MEDICATIONS AND STRUCTURAL TERATOGENESIS

INTRODUCTION

MECHANISMS OF TERATOGENESIS

STRUCTURAL TERATOGENESIS AND SPECIFIC ANTISEIZURE MEDICATIONS

Valproate

Carbamazepine

Lamotrigine

Levetiracetam

Oxcarbazepine

Phenytoin

Phenobarbital

Topiramate

Zonisamide

Other ASMs

EFFECT OF ASM DOSE

POLYTHERAPY

ASMS AND OTHER MEDICATIONS

ASMS AND FETAL GROWTH

EPILEPSY SURGERY

OTHER THERAPIES

IMPLICATIONS FOR PATIENT CARE

Prepartum Counseling and Management

Folic Acid

Fetal Monitoring

CONCLUSION

REFERENCES

CHAPTER 149. NEURODEVELOPMENTAL EFFECTS OF ANTISEIZURE MEDICATIONS

INTRODUCTION

ANIMAL DATA

Behavioral Data for Individual Antiseizure Medications

Antiseizure Medication Effects on Neurodevelopment: Potential Mechanisms

HUMAN DATA FROM OFFSPRING OF MOTHERS WITH EPILEPSY

Confounding Factors

Fetal Antiseizure Medication Syndromes

Intelligence

Specific Cognitive Abilities

Behavior

The Effect of Folate

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 150. DRUG TREATMENT IN CHILDREN WITH EPILEPSY

INTRODUCTION

CLINICAL APPROACHES

Treatment by Seizure or Epilepsy Type

Treatment by Broad Syndrome Categories

Treatment by Etiology

GENERAL SIDE-EFFECT CONSIDERATIONS

PREGNANCY AND EPILEPSY

GENERAL PHARMACOKINETIC CONSIDERATIONS

MONITORING

WHEN AND HOW TO STOP

CREATING A UNIFORM WORLDWIDE PERSPECTIVE

REFERENCES

CHAPTER 151. DRUG TREATMENT IN ADOLESCENTS WITH EPILEPSY

INTRODUCTION

MEDICATIONS USED TO TREAT JUVENILE GENERALIZED EPILEPSIES

Juvenile Absence Epilepsy, Juvenile Myoclonic Epilepsy, and Epilepsy with Generalized Tonic–Clonic Seizures Alone

Refractory Generalized Epilepsy

Adolescent Onset Progressive Myoclonic Epilepsies: Lafora Disease, Unverricht–Lundborg Disease, and Neuronal Ceroid Lipofuscinosis

MEDICATIONS USED TO TREAT JUVENILE FOCAL EPILEPSIES

Medications for Refractory Focal Epilepsy

SPECIFIC CONSIDERATIONS THAT AFFECT THERAPY IN ADOLESCENCE

QUALITY OF LIFE, NEUROPSYCHOLOGICAL ABNORMALITIES, AND LEARNING DISORDERS

TRANSITION TO ADULT EPILEPSY CLINICS

DURATION OF THERAPY

CONCLUSIONS

REFERENCES

CHAPTER 152. TRANSITION FROM PEDIATRIC TO ADULT CARE FOR PEOPLE WITH EPILEPSY

OUTCOMES OF CHILDHOOD-ONSET EPILEPSIES

Comorbidities in Patients with Childhood-Onset Epilepsy Moving to Adult Care

Beyond the Seizures

TRANSITION IS MORE THAN HANDING OVER YOUNG ADULTS WITH SEIZURES

How Do Differences in the Adult System Affect Patients and Caregivers?

What Might Happen If Transition Is Poorly Managed?

MODELS OF TRANSITION PROGRAMS

WHAT ISSUES SHOULD BE ADDRESSED BY A TRANSITION PROGRAM?

Ages 12 to 15 Years: Introduce the Concept of Transition and Create a “Seizure Emergency Plan”

Ages 12 to 17 Years: Exploring Financial, Community, and Legal Support Available for the Young Adult with Epilepsy

Ages 16 to 17 Years: Determining the Transition Readiness of Patients with Epilepsy and Their Parents

Ages 12 to 19 Years: Identifying and Addressing Risk Factors for Unsuccessful Transition in Normally Developing Adolescents with Epilepsy

Ages 12 to 19 Years: Identifying and Addressing Risk Factors for Unsuccessful Transition in Adolescents with Epilepsy and Intellectual Disability

Ages 16 to 19 Years: Time to Rethink the Diagnosis

Ages 16 to 17 Years: Identify Obstacles for Continuation of Treatment of Drug-Resistant Epilepsies

PEDIATRIC DISCHARGE PACKAGE AND ROLE OF THE FAMILY DOCTOR

CONCLUSION

REFERENCES

CHAPTER 153. DIAGNOSIS AND TREATMENT OF EPILEPSY IN THE OLDER ADULT

INTRODUCTION

DEFINITION AND EPIDEMIOLOGY OF EPILEPSY IN OLDER ADULTS

OLDER ADULTS ARE NOT A HOMOGENOUS POPULATION

SEIZURE TYPES IN OLDER ADULTS

DIAGNOSIS

EEG AND MRI

COMMON CAUSES OF EPILEPSY IN OLDER ADULTS

Stroke

Neurodegenerative Disorders with Dementia

Brain Tumors

NURSING HOME USE OF ASMS

COMMUNITY USAGE OF ASMS

PHARMACOKINETICS AND PHARMACODYNAMICS

CLINICAL TRIALS IN THE ELDERLY

SPECIFIC ASMS

Carbamazepine

Eslicarbazepine

Felbamate

Gabapentin

Lacosamide

Lamotrigine

Levetiracetam

Oxcarbazepine

Perampanel

Phenytoin

Pregabalin

Topiramate

Valproic Acid

Zonisamide

DRUG INTERACTIONS

THERAPEUTIC DRUG MONITORING

TREATING A SINGLE SEIZURE

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 154. TREATMENT ADHERENCE IN EPILEPSY

INTRODUCTION

DEFINING ADHERENCE

SUBOPTIMAL ADHERENCE IMPACTS HEALTH OUTCOMES

MEASURING ADHERENCE IN EPILEPSY

Blood Serum Levels

Pharmacy Refill Data/Medication Possession Ratio

Electronic Monitors

SELF- OR PARENT-REPORT

Provider Estimates

ADHERENCE PREDICTORS

Sociodemographic Predictors

Medical Predictors

Individual and Family Predictors of Adherence

INTERVENTIONS TO IMPROVE ADHERENCE IN EPILEPSY

PRACTICAL STRATEGIES TO IMPROVE ADHERENCE IN CLINICAL PRACTICE

CONCLUSIONS AND FUTURE DIRECTIONS

REFERENCES

CHAPTER 155. DISCONTINUATION OF ANTISEIZURE MEDICATIONS

INTRODUCTION

WHEN TO CONSIDER TAPERING ASMs

RISK STRATIFICATION

SPECIAL SYNDROMES

POST-SURGERY WITHDRAWAL

DIAGNOSTIC TOOLS

HOW FAST TO TAPER

RELAPSE AFTER WITHDRAWAL

SUDDEN UNEXPLAINED DEATH IN EPILEPSY

CONCLUSION

REFERENCES

CHAPTER 156. ROUTINE MONITORING FOR SAFETY AND TOLERABILITY DURING CHRONIC TREATMENT WITH ANTISEIZURE MEDICATIONS

INTRODUCTION

ADVERSE EFFECTS

LABORATORY MONITORING DURING CHRONIC ANTISEIZURE MEDICATION TREATMENT

Indications for Routine Laboratory Testing

Common Laboratory Findings

SERIOUS IDIOSYNCRATIC REACTIONS

IDENTIFICATION OF HIGH-RISK PATIENTS AND MANAGEMENT OF SPECIAL POPULATIONS

MONITORING BLOOD LEVELS OF ANTISEIZURE MEDICATIONS

The Reference Range and the Therapeutic Range

Indications for Therapeutic Drug Monitoring of ASMs

Other Forms of Monitoring

Monitoring Strategies

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 157. COMBINATION PHARMACOTHERAPY IN EPILEPSY

INTRODUCTION

POTENTIAL DISADVANTAGES OF COMBINATION THERAPY

Increased Number or Intensity of Side Effects

Potentiation of Idiosyncratic or Dose-related Side Effects

Pharmacokinetic Interactions

Difficulty of Attributing a Response to a Given Drug

Possible Change in the Therapeutic Range of Plasma Levels

POTENTIAL ADVANTAGES OF COMBINATION THERAPY

Clinical Studies

CLINICAL APPROACH TO SELECTION OF ANTISEIZURE MEDICINE COMBINATIONS

Strategy for Adding or Replacing Drugs

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 158. TREATMENT OF SINGLE AND INFREQUENT SEIZURES

INTRODUCTION

DIAGNOSIS OF EPILEPTIC SEIZURES, FIRST UNPROVOKED SEIZURES, AND EPILEPSY

CHANGED VIEWS ON THE EARLY PROGNOSIS OF EPILEPSY AND THE EFFECTS OF EARLY TREATMENT

RISK OF RECURRENCE OF A FIRST SEIZURE

THE IMPACT OF TREATMENT ON THE RECURRENCE AFTER A FIRST SEIZURE AND ON THE LONG-TERM PROGNOSIS OF EPILEPSY

ADVERSE EFFECTS OF ANTISEIZURE MEDICATIONS, QUALITY OF LIFE, AND PATIENTS’ PREFERENCE

OTHER FACTORS

STARTING OR WITHHOLDING TREATMENT AFTER A FIRST SEIZURE

TREATMENT OF THE PATIENT WITH INFREQUENT SEIZURES

SUMMARY AND CONCLUSIONS

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 159. TREATMENT OF NEONATAL SEIZURES

INTRODUCTION

RATIONALE FOR TREATMENT

BASICS OF EVALUATION

EVALUATION OF SEMIOLOGY TO GUIDE TREATMENT

TREATMENT WITH ANTISEIZURE MEDICATION

FIRST-LINE TREATMENT

Phenobarbital

SECOND-LINE TREATMENT

Phenytoin/Fosphenytoin

Levetiracetam

Benzodiazepines

Lidocaine

EMERGING TREATMENTS

Bumetanide

Carbamazepine

Topiramate

Therapeutic Hypothermia

APPROACH TO MANAGEMENT OF NEONATAL SEIZURES

Acute Symptomatic Seizures

Neonatal-Onset Epilepsies

PROGNOSIS AND COMPLICATIONS

SUMMARY

REFERENCES

CHAPTER 160. FEBRILE SEIZURES AND FEVER-RELATED SEIZURES

INTRODUCTION

EPIDEMIOLOGY

DEFINITION

ETIOLOGY/PATHOPHYSIOLOGY

FEBRILE SEIZURES AFTER IMMUNIZATIONS

FEBRILE SEIZURE MODULATORS

IRON, ZINC, AND SELENIUM DEFICIENCY

PREDICTING THE DEVELOPMENT OF EPILEPSY

PROLONGED FEBRILE SEIZURES AND FEBRILE STATUS EPILEPTICUS

FEBRILE INFECTION–RELATED EPILEPSY SYNDROME

DIAGNOSTIC EVALUATION

Hematologic Evaluation

Lumbar Puncture

Neuroimaging

EEG

Genetic Tests

MANAGEMENT

PREVENTION OF SEIZURE RECURRENCE

Antipyretic Therapy and Other Measures of Prevention

LONG-TERM OUTCOME

REFERENCES

CHAPTER 161. STRATEGIES WHEN TREATMENTS FAIL IN PEOPLE WITH EPILEPSY

INTRODUCTION

SOMETHING OLD

SOMETHING NEW

SOMETHING BORROWED

Serotonergic Neurotransmission

Immunomodulation and Immunosuppression

Utilization of Medical Devices

Diets and Dietary Supplement

NOTHING BLUE (IN THREE STEPS)

REFERENCES

CHAPTER 162. MANAGING EPILEPSY IN PATIENTS WITH MEDICAL COMORBIDITIES

INTRODUCTION

KIDNEY DISEASE

Effect of Kidney Disease on Use of ASMs

Potential Deleterious Effects of ASMs on the Kidneys

Use of ASMs in the Setting of Renal Replacement Therapies

Comments on Specific ASMs in Context of Renal Disease

MENTAL HEALTH DISORDERS

Effect of Epilepsy Treatment on Mental Health Disorder

Effect of Psychotropic Medications on Epilepsy

Antidepressants

Antipsychotics

EPILEPSY AND ONCOLOGIC AND HEMATOLOGIC DISEASES

Hematologic and Oncologic Diseases

Does Hematologic Disease Impact Epilepsy?

General Recommendations

EPILEPSY AND CARDIAC DISEASES

Impact of Epilepsy Treatment on Cardiac Disease

Impact of Cardiac Disease Treatment on Epilepsy

Specific Medication Classes

Implanted Devices

OTHER SPECIFIC SITUATIONS

Patient With a History of Drug Rash

Liver Disease

Sexual Dysfunction

FINAL COMMENTS

REFERENCES

CHAPTER 163. PREVENTION AND TREATMENT OF PROVOKED SEIZURES

INTRODUCTION

EMOTIONAL FACTORS

FATIGUE AND SLEEP DEPRIVATION

ALCOHOL

DRUG-INDUCED SEIZURES

Psychotropic and Neuroleptic Drugs

Antidepressants

Antipsychotic Neuroleptics

Antiseizure Medications

Anesthetic Drugs

Drugs for Medical Disorders

Drugs of Abuse

SPECIFIC STIMULI

TREATMENT OF PROVOKED SEIZURES

People with Epilepsy

Persons Without Epilepsy

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 164. KETOGENIC DIETS FOR EPILEPSY

INTRODUCTION

HISTORY

CLINICAL ASPECTS OF KETOGENIC DIETS

Ketogenic Diet Foods and Composition

“Alternative” Ketogenic Diets

Indications

Adults

Initiation of the Classic KD

Maintenance

Side Effects

Discontinuation

HOW DOES THE KETOGENIC DIET WORK?

Overview of Brain Energy Metabolism

Direct Effects of Ketone Bodies

Neurotransmitters and Ion Channel Regulation

Bioenergetic and Mitochondrial Changes

Glycolytic Restriction/Diversion

Fatty Acid Oxidation and Polyunsaturated Fatty Acids

TCA Cycle Effects and Anaplerosis

Other Emerging Mechanisms

CONCLUDING REMARKS

REFERENCES

CHAPTER 165. REPRODUCTIVE HORMONAL TREATMENT FOR EPILEPSY

INTRODUCTION

REPRODUCTIVE HORMONE EFFECTS ON EPILEPSY

Estradiol

Progesterone

Testosterone

Dehydroepiandrosterone Sulfate

CATAMENIAL EPILEPSY

HORMONAL TREATMENT OF WOMEN WITH EPILEPSY

Progestogen Therapy

Allopregnanolone Analog Therapy

Gonadotrophin-Releasing Hormone Analog Therapy

HORMONAL TREATMENT OF MEN WITH EPILEPSY

Testosterone/Aromatase Inhibitor

Phosphodiesterase Inhibitor or Prostaglandin

CONCLUSIONS

REFERENCES

CHAPTER 166. PSYCHO-BEHAVIORAL THERAPIES IN EPILEPSY

INTRODUCTION

ARREST OF SEIZURES

History

MODERN ACCOUNTS

ANECDOTAL OBSERVATIONS

THEORETICAL CONCEPTS

CURATIVE EFFECT

PREVENTION OF SEIZURES

Specific Precipitating Factors

Nonspecific Precipitating Factors

Psychogenic Precipitants

Mind–Body Approaches for Seizure Prevention

BEHAVIOR MODIFICATION TODAY

THE APPLICATION OF PSYCHO-BEAHVIORAL THERAPIES ACROSS THE EPILEPSY SPECTRUM

Depressive Symptoms

Anxiety

Social and Family Problems and Stigma

Treatment Nonadherence

Cognitive Disturbances

TREATMENT DELIVERY AND RESEARCH CONSIDERATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 167. COMPLEMENTARY AND ALTERNATIVE MEDICAL THERAPIES FOR EPILEPSY

INTRODUCTION

SCOPE OF USE

Developed Countries

Developing Countries

CAM THERAPIES USED FOR EPILEPSY

Herbal Medicines and Other Dietary Supplements

Psychological Therapies and Mind–Body Techniques

REGULATORY ASPECTS OF HERBAL MEDICINES IN THE UNITED STATES

SAFETY ISSUES

OPPORTUNITIES FOR FURTHER RESEARCH

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

SECTION 8 • Antiseizure Medications

CHAPTER 168. OVERVIEW: ANTISEIZURE MEDICATIONS

INTRODUCTION

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 169. EPILEPSY PHARMACOGENETICS AND PHARMACOGENOMICS

INTRODUCTION AND DEFINITIONS

ADVANCES IN GENETIC TESTING TECHNOLOGY

PHARMACOKINETIC PHARMACOGENETICS

Variation in Cytochrome P450 Enzymes

Phenytoin

Carbamazepine

Valproate

Lamotrigine

PHARMACOGENOMICS OF BROAD DRUG RESPONSE

MDR1 Resistance

Recent Genetic Studies of Pharmacoresistance

Lamotrigine Resistance

Specific Drug Response

PHARMACOGENOMICS OF ADVERSE REACTIONS

Cutaneous Drug Reactions

GENETIC PREDICTORS OF ASD-INDUCED cADRs

ASD-Associated Weight Changes

Levetiracetam and Neurobehavioral Side Effects

Vigabatrin-Associated Visual Field Loss

CONCLUSION

REFERENCES

CHAPTER 170. SCREENING OF NEW COMPOUNDS AND THE ROLE OF THE PHARMACEUTICAL INDUSTRY IN EPILEPSY

INTRODUCTION

HISTORICAL PERSPECTIVE

ANIMAL MODELS FOR DRUG DISCOVERY

Screening for Efficacy: The Value of Animal Seizure Models

Focal Seizures: Kindling

PHARMACORESISTANT ANIMAL MODELS

Introduction

Defining Pharmacoresistance

Models of Drug-Resistant Seizures and Epilepsy

Antiseizure Medication–Resistant Kindled Rats

The Low-Frequency (6-Hz) Electroshock Seizure Model

Post–Status Epilepticus Models of Temporal Lobe Epilepsy

Summary

ROLE OF THE PHARMACEUTICAL INDUSTRY

The Role of the pharmaceutical industry: A Brief History of ASM Discovery and Development

The Roles of the Industry in ASM Discovery and Development

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 171. INVESTIGATIONAL DRUGS IN EPILEPSY

INTRODUCTION

GAMMA-AMINOBUTYRIC ACID–TARGETED THERAPIES

CVL-865 (Darigabat)

ETX-155

Ganaxolone

NRP2945

OV329

GLUTAMATERGIC TARGETED THERAPIES

AV-101

JNJ-40411813 (ADX71149)

ION CHANNEL MODULATORS

SMALL MOLECULE SODIUM CHANNEL MODULATORS (NBI-921352 AND PRAX-562)

NBI-921352 (Previously Xen901)

PRAX-562

KV7.2 ACTIVATORS (KB-3061, XEN496, AND XEN1101)

KB-3061 (BPN-25203)

XEN496 (Retigabine)

XEN1101

T-TYPE VOLTAGE GATED Ca2+ CHANNEL BLOCKERS (ACT-709478, CX-8998 AND NBI-827104)

ACT-709478

CX-8998

NBI-827104

NOVEL SEROTONERGIC DRUGS IN DEVELOPMENT (EPX-100, EPX-300, AND LORCASERIN)

EPX-100 (Clemizole)

Lorcaserin (EPX-200)

EPX-300 (Trazodone)

MECHANISTICALLY NOVEL ANTISEIZURE DRUGS IN DEVELOPMENT

Blacamesine (ANAVEX 2–73)

GAO-3-02

Soticlestat (TAK 935/OV935)

SPN817

GENE THERAPY TREATMENTS FOR EPILEPSY

Gene Therapy Products for Dravet Syndrome

Gene Therapy Products to Treat SLCA13A5 Deficiency

Gene Therapy Products for Angelman Syndrome

Gene Therapy Approaches for Focal Neocortical and Temporal Lobe Epilepsy

Cell Transplantation Approaches for Treating Focal Epilepsy

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 172. CLINICAL TRIALS OF ANTISEIZURE MEDICATIONS IN ADULTS AND CHILDREN

INTRODUCTION

PHASES OF TESTING IN HUMANS

EFFICACY TRIALS

TRIAL DESIGN

Need for Blinding and Control Groups

Active Versus Placebo Comparisons

Adjunctive Versus Monotherapy Trials

Parallel Versus Crossover Designs

PATIENT ISSUES

Epilepsy Syndrome Selection

Trials for Orphan Indications

Seizure Severity

Children

DRUG ISSUES

ANALYSIS OF RESULTS: STANDARD MEASURES

Choosing an Outcome Variable

Handling Seizure Data

Intent to Treat

Other Analysis Problems

Nonstandard Outcome Measures

SAFETY TRIALS

Safety Testing During Phase II Efficacy Trials

Safety Issues in Children

ETHICAL ISSUES

Ethical Issues in Children

APPLICABILITY OF TRIAL DATA TO CLINICAL PRACTICE

Efficacy Versus Effectiveness

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 173. SEIZURE RESCUE THERAPY

INTRODUCTION

SEIZURE ACTION PLAN

RESCUE MEDICATIONS

DIAZEPAM

Rectal Diazepam

Intranasal Diazepam

Intramuscular Diazepam

Oral/Buccal Diazepam

MIDAZOLAM

Intranasal Midazolam

Buccal Midazolam

OTHER BENZODIAZEPINES

Clonazepam

Lorazepam

OTHER TREATMENTS FOR ARS

Paraldehyde

Vagus Nerve Stimulation

REFERENCES

CHAPTER 174. ADRENOCORTICOTROPIC HORMONE AND STEROIDS IN EPILEPSY

INTRODUCTION

ACTH AND STEROIDS: STRUCTURE AND CHEMISTRY

MECHANISMS OF ACTION

PHARMACOKINETICS

Adrenocorticotropic Hormone

Steroids

Neurosteroids

DRUG INTERACTIONS

SERUM LEVEL MONITORING

TREATMENT OF SPECIFIC DISORDERS

Infantile Spasms/West Syndrome

Long-Term Studies

Other Epilepsy Syndromes

NEUROSTEROIDS

ADVERSE EFFECTS

CURRENT PLACE IN THERAPY

REFERENCES

CHAPTER 175. BRIVARACETAM

INTRODUCTION

STRUCTURE

FORMULATION

MECHANISM OF ACTION

EFFICACY IN ANIMAL MODELS

METABOLISM IN HUMANS (ABSORPTION, DISTRIBUTION, ELIMINATION)

INTERACTIONS

Interactions with Other ASMs

Interactions with Other Medications

EFFICACY IN HUMAN STUDIES

Efficacy Against Photosensitivity in a Proof-of-Principle Study

Efficacy as Adjunctive Therapy in Pivotal Trials

Conversion to Monotherapy Trials

Long-Term Follow-up Studies

TOLERABILITY AND SAFETY

Tolerability in Controlled Trials and Their Open-Label Extension

Tolerability of BRV versus LEV

Time Course of BRV Treatment-Emergent Adverse Effects

BRV Cognitive and Mood Effects

BRV Teratogenicity

INTRAVENOUS FORMULATION

POSTMARKETING EXPERIENCE

Efficacy

Patients with Intellectual Disability and Patients with Psychiatric Comorbidity

Pediatric Population

Potential Role of BRV in Other Epilepsies

Status Epilepticus and Acute Seizure Exacerbations

Potential Efficacy Advantages of BRV Over LEV

SUMMARY

REFERENCES

SUGGESTED READINGS

CHAPTER 176. CANNABIDIOL AND OTHER PHYTOCANNABINOIDS IN EPILEPSY

INTRODUCTION

CENTRAL NERVOUS SYSTEM TARGETS OF CANNABIDIOL

PRECLINICAL EFFICACY DATA

EARLY CLINICAL ANECDOTES

RANDOMIZED CONTROLLED CLINICAL TRIALS IN PATIENTS WITH DRAVET SYNDROME, LENNOX–GASTAUT SYNDROME, AND TUBEROUS SCLEROSIS–RELATED EPILEPSY

Efficacy

Safety

EFFICACY IN OTHER EPILEPSIES

CLINICAL PHARMACOLOGY

DRUG–DRUG INTERACTIONS

SAFETY AND TOLERABILITY

CONCLUSIONS

REFERENCES

CHAPTER 177. CARBAMAZEPINE

INTRODUCTION

CHEMICAL STRUCTURE, FORMULATION, AND MONITORING

Chemical Structure and Synthesis

Formulations

Methods for Determination in Body Fluids

PHARMACOLOGY

Activity in Experimental Models of Seizures/Epilepsy

Mechanism of Action

CLINICAL PHARMACOKINETICS

Absorption

Plasma Protein Binding and Distribution

Metabolism and Elimination

ROLE OF THERAPEUTIC DRUG MONITORING

EFFICACY

Use in Adults

Use in Children

Use in the Elderly

Limits of Use and Risk of Selective Seizure Aggravation

ADVERSE EFFECTS

Dose-Related, Nonidiosyncratic Reactions

Idiosyncratic Reactions

SECOND-GENERATION EFFECTS

DRUG INTERACTIONS

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Precautions

Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 178. CENOBAMATE

INTRODUCTION

CHEMICAL STRUCTURE

Formulations

PHARMACOLOGY

Mechanisms of Action

GABAA Modulation

Mechanism of Action Summary

CLINICAL PHARMACOKINETICS

Absorption, Plasma Protein Binding and Distribution, Metabolism, and Elimination

Effects of Renal and Hepatic Dysfunction

EFFICACY

Overview of Clinical Efficacy Trials in Humans

Proof-of-Principle Study

Adult with Focal Seizures

SAFETY

Dose-Related (Nonidiosyncratic) Adverse Effects

Idiosyncratic Adverse Reactions

Status Epilepticus

Teratogenicity

Suicidal Behavior and Ideation

Drug Interactions

Pharmacokinetics in Epilepsy Patients and Simulation Models of Cenobamate Monotherapy

Abuse Potential

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Precautions

Contraindications

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 179. CLOBAZAM AND OTHER BENZODIAZEPINES FOR CHRONIC USE

INTRODUCTION

CHEMICAL STRUCTURE, FORMULATION, AND MONITORING

Chemical Structure and Synthesis

Formulations

Methods for Determination in Body Fluids

PHARMACOLOGY

Activity in Experimental Models of Seizures/Epilepsy

Mechanism of Action

CLINICAL PHARMACOKINETICS

Absorption

Plasma Protein Binding and Distribution

Metabolism and Elimination

ROLE OF THERAPEUTIC DRUG MONITORING

EFFICACY

Clobazam

Clonazepam

Clorazepate

Nitrazepam

ADVERSE EFFECTS

Dose-Related, Nonidiosyncratic Adverse Effects

Idiosyncratic Reactions

REPRODUCTIVE EFFECTS

Clobazam

Clonazepam

Clorazepate

Nitrazepam

TOLERANCE TO THE ANTISEIZURE EFFECTS

DRUG INTERACTIONS

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Precautions

Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 180. ESLICARBAZEPINE ACETATE

INTRODUCTION

CHEMICAL STRUCTURE

MECHANISM OF ACTION

PRECLINICAL EFFICACY ASSESSMENT

PRECLINICAL TOXICOLOGY

PHARMACOKINETICS

DRUG INTERACTIONS

THERAPEUTIC MONITORING

CLINICAL EFFICACY, TOLERABILITY, AND SAFETY OF ADJUNCTIVE ESL

Randomized Controlled Studies

Open-Label Extension and Real-World Studies

Studies in Pediatric Population

CLINICAL EFFICACY, TOLERABILITY, AND SAFETY OF ESL AS MONOTHERAPY

Approved Indications in United States and European Union

Potential Nonapproved Indication

Dosing Considerations

SWITCHING FROM ESL TO CARBAMAZEPINE AND OXCARBAZEPINE

Fertility, Pregnancy, and Lactation

ELDERLY POPULATION

Contraindications, Warnings, and Precautions for Use

CONCLUSIONS

REFERENCES

CHAPTER 181. ETHOSUXIMIDE

INTRODUCTION

CHEMICAL STRUCTURE, FORMULATIONS, AND METHODS FOR DETERMINATION IN BODY FLUIDS

PHARMACOLOGY

Activity in Experimental Models of Seizures/Epilepsy

Activity in Other Models

Mechanisms of Action

CLINICAL PHARMACOKINETICS

Absorption

Plasma Protein Binding and Distribution

Metabolism and Excretion

Relationship Between Plasma Concentrations and Antiseizure Effects

EFFICACY

ADVERSE EFFECTS

Dose-Related Effects

Idiosyncratic Reactions

Teratogenicity

DRUG INTERACTIONS

INDICATIONS

DOSING RECOMMENDATIONS

PRECAUTIONS

CONTRAINDICATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 182. EVEROLIMUS IN EPILEPSY

INTRODUCTION

CHEMICAL STRUCTURE

MECHANISM OF ACTION

PRECLINICAL EFFICACY ASSESSMENT

PRECLINICAL TOXICITY

CLINICAL EFFICACY

POTENTIAL NONAPPROVED INDICATIONS

TOXICITY

DOSE-RELATED SIDE EFFECTS

IDIOSYNCRATIC SIDE EFFECTS

LONG-TERM SIDE EFFECTS

SPECIFIC PEDIATRIC TOXICITY

SEIZURE AGGRAVATION

CONTRAINDICATIONS

PHARMACODYNAMICS/PHARMACOKINETICS/DRUG INTERACTIONS

THERAPEUTIC MONITORING

LABORATORY TEST MONITORING

THE MANAGEMENT OF ADVERSE EVENTS

CONCLUSIONS

REFERENCES

CHAPTER 183. FELBAMATE

INTRODUCTION

CHEMICAL STRUCTURE

Methods for Determination in Body Fluids

PHARMACOLOGY

Activity in Experimental Models of Seizures/Epilepsy

Mechanisms of Action

Activity in Other Models

Toxicity Models

CLINICAL PHARMACOKINETICS

Formulations

Absorption

Plasma Protein Binding and Distribution

Metabolism and Elimination

Drug Interactions

Relationship Between Plasma Concentration and Effects: Value of Therapeutic Drug Monitoring

ADVERSE EFFECTS

Dose-Related Effects

Idiosyncratic

Teratogenic Effects

Effects Related to Drug Interactions

EFFICACY

Localization-Related Epilepsies

Generalized Epilepsies

Activity in Other Indications

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Precautions and Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 184. FENFLURAMINE

INTRODUCTION

CHEMICAL STRUCTURE AND METHODS FOR DETERMINATION IN BODY FLUIDS

MECHANISM OF ACTION

PRECLINICAL EFFICACY ASSESSMENT

PHARMACOKINETICS/DRUG INTERACTIONS

Absorption

Plasma Protein Binding and Distribution

Metabolism

Elimination

Pharmacokinetics in Special Populations

DRUG INTERACTIONS

Stiripentol, Clobazam, and Valproate

Cannabidiol

CLINICAL EFFICACY

Efficacy in Dravet Syndrome

History and Initial Observations

Phase 3 Randomized, Double-Blind Placebo-Controlled Trials

Potential Nonapproved Indications

DOSING CONSIDERATIONS

TOXICITY

Dose-Related Side Effects

Long-Term Side Effects

CONTRAINDICATIONS

SUMMARY AND CONCLUSION

REFERENCES

CHAPTER 185. IMMUNOTHERAPY IN EPILEPSY

INTRODUCTION

THE IMMUNE SYSTEM AND EPILEPSY

IMMUNOLOGIC ALTERATIONS AND BIOMARKERS OF THE EPILEPSIES

THE USE OF IMMUNOTHERAPY IN HUMAN EPILEPSIES

Immunomodulatory Treatments

Immunosuppressive Treatments

SPECIFIC EPILEPTIC DISORDERS TREATED WITH IMMUNOTHERAPY

West Syndrome

Lennox–Gastaut Syndrome

Landau–Kleffner Syndrome

Rasmussen Encephalitis

Tuberous Sclerosis Complex

Autoimmune Encephalopathies

THE USE OF IMMUNOTHERAPY IN STATUS EPILEPTICUS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 186. LACOSAMIDE

INTRODUCTION

CHEMICAL STRUCTURE, FORMULATIONS, AND METHODS FOR DETERMINATION IN BODY FLUIDS

PHARMACOLOGY

Seizure Models

Pain Models

Mechanisms of Action

CLINICAL PHARMACOKINETICS

CLINICAL EFFICACY

Focal Seizures

Primary Generalized Tonic–Clonic Seizures

Drug Interactions

HOW TO USE LACOSAMIDE

CLINICAL SAFETY

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 187. LAMOTRIGINE

INTRODUCTION

CHEMICAL STRUCTURE

MECHANISM OF ACTION

PRECLINICAL SEIZURE MODELS

CLINICAL PHARMACOKINETICS

THERAPEUTIC MONITORING

PHARMACOKINETIC INTERACTIONS

CLINICAL EFFICACY

ADJUNCTIVE TREATMENT OF FOCAL SEIZURES

Conversion to Monotherapy

Conversion to Extended-Release Lamotrigine

MONOTHERAPY IN NEWLY DIAGNOSED PATIENTS

Lamotrigine Versus Phenytoin (In Focal and Generalized Tonic–Clonic Seizures)

Lamotrigine versus Pregabalin (In Focal Seizures)

Comparison with Carbamazepine, Oxcarbazepine, Topiramate, and Gabapentin (in Focal Seizures)

Lamotrigine versus Gabapentin (Focal and Generalized Seizures)

Lamotrigine versus Levetiracetam (Focal and Generalized Epilepsy)

EVIDENCE IN OLDER ADULTS

Lamotrigine versus Sustained-Release Carbamazepine

Lamotrigine versus Other ASMs in Older Individuals

EVIDENCE IN CHILDREN WITH FOCAL SEIZURES

Lamotrigine versus Oxcarbazepine

EVIDENCE IN IDIOPATHIC GENERALIZED EPILEPSY

CHILDHOOD ABSENCE EPILEPSY

Comparison with Valproate and Topiramate (in Generalized and Unclassifiable Epilepsy)

LENNOX–GASTAUT SYNDROME

INDICATIONS OTHER THAN EPILEPSY

ADVERSE EFFECTS

Toxicity in Children

Dose Related Nonidiosyncratic Adverse Effects

Idiosyncratic Reactions

ADDITIONAL SAFETY ISSUES

Use in Pregnancy

Aggravation of Seizures

DOSING RECOMMENDATIONS

PRECAUTIONS

Cardiac Concerns

CONCLUSIONS

REFERENCES

CHAPTER 188. LEVETIRACETAM

INTRODUCTION

PHARMACOLOGY

CLINICAL PHARMACOKINETICS

Absorption

Plasma Protein Binding and Distribution

Metabolism and Elimination

Therapeutic Drug Monitoring

Intravenous Formulation

EFFICACY

Efficacy as Adjunctive Treatment in Focal Seizures

Efficacy as Monotherapy

Efficacy in Generalized Seizures

Efficacy in Pediatric Epilepsy

Efficacy in the Elderly

Efficacy in Status Epilepticus

Efficacy in Nonepilepsy Indications

ADVERSE EFFECTS

Pregnancy and Lactation

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Available Formulations

Precautions

Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 189. OXCARBAZEPINE

INTRODUCTION

MECHANISM OF ACTION

REGULATORY STATUS

Human Monotherapy Trials

Adjunctive Therapy Trials

Double-Blind Randomized Placebo-Controlled Trials

Extended-Release Oxcarbazepine

ADVERSE EVENTS

Dose-Related Side Effects

Idiosyncratic Side Effects

CLINICAL PHARMACOKINETICS

Drug Interactions

Teratogenicity

DOSING

Use in Pregnancy

THERAPEUTIC MONITORING

SUMMARY

REFERENCES

CHAPTER 190. PERAMPANEL

INTRODUCTION

CHEMICAL STRUCTURE

MECHANISM OF ACTION

PRECLINICAL EFFICACY ASSESSMENT

PHARMACOKINETIC PROPERTIES

RENAL AND HEPATIC IMPAIRMENT

DRUG–DRUG INTERACTION

Effect of Coadministered Drugs on PER

Effect of PER on Coadministered Drugs

CLINICAL EFFICACY

Approved Indications in the United States and the European Union

Randomized Control Trials

Open-Label Extension Studies

Monotherapy

Pediatrics and Adolescents

Other Populations without Regulatory Approval

DOSAGE INFORMATION

TOXICITY

Dose-Related Side Effects

Most Relevant Adverse Events

Idiosyncratic Side Effects

Long-Term Side Effects

Teratogenicity

Specific Pediatric and Adolescent Toxicity

Seizure Aggravation

THERAPEUTIC DRUG MONITORING

CONCLUSION

REFERENCES

CHAPTER 191. PHENOBARBITAL AND BARBITURATE PRODRUGS

INTRODUCTION

CHEMISTRY, FORMULATIONS, ASSAY

Chemistry

Formulations

Assay

PHARMACOLOGY

Seizure Models

Mechanism of Action

CLINICAL PHARMACOLOGY

Absorption

Distribution

Metabolism

Elimination

Concentration–Effect Relationships

EFFICACY

ADVERSE EFFECTS

Dose-Related Effects

Idiosyncratic Reactions

Second-Generation Effects

DRUG INTERACTIONS

Effects of Phenobarbital on Other Drugs

Effects of Other Drugs and Therapies on Phenobarbital

Effects of Other Drugs on Primidone

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Precautions

Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 192. PHENYTOIN, FOSPHENYTOIN, AND OTHER HYDANTOINS

INTRODUCTION

PHENYTOIN

Chemistry

Pharmacology

Clinical Pharmacokinetics

Efficacy

Adverse Effects

Drug Interactions

Indications

Dosing Recommendations

Loading Dose

FOSPHENYTOIN

Chemistry

Pharmacology

Clinical Pharmacokinetics

Efficacy

Adverse Effects

Role in Epilepsy Treatment

ETHOTOIN

Chemistry

Pharmacology

Clinical Pharmacokinetics

Efficacy

Adverse Effects

Role in Epilepsy Treatment

MEPHENYTOIN

Chemistry

Pharmacology

Clinical Pharmacokinetics

Efficacy

Adverse Effects

Drug Interactions

Role in Epilepsy Treatment

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 193. PREGABALIN

INTRODUCTION

CHEMICAL STRUCTURE, FORMULATIONS, AND METHODS FOR DETERMINATION IN BODY FLUIDS

PHARMACOLOGY

Mechanism of Action

Activity in Experimental Models of Epilepsy

CLINICAL PHARMACOKINETICS/PHARMACODYNAMICS

Adults

Pediatrics

EFFICACY

Adults

Pediatrics

ADVERSE EFFECTS

Dose-Related, Nonidiosyncratic Adverse Effects

Weight Gain

Idiosyncratic Reactions

Teratogenicity

Carcinogenicity

Controlled Substance Classification

Overdosage

DRUG INTERACTIONS

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Effects on Mood

Cognitive Function

Precautions and Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 194. RETIGABINE/EZOGABINE

INTRODUCTION

CHEMICAL STRUCTURE OF RTG

MECHANISM OF ACTION

PRECLINICAL EFFICACY ASSESSMENT

Animal Models

Preclinical Toxicology

CLINICAL EFFICACY

Phase I Studies and Clinical Pharmacology

Phase II Studies

Phase III Studies

Long-Term Open-Label Extension Trials

RENAL IMPAIRMENT

LIVER IMPAIRMENT

APPROVED INDICATIONS: US AND EUROPE

Potential Nonapproved Indications

DOSING CONSIDERATIONS

Tolerability

PHARMACOKINETICS

Sex and Age

INTERACTIONS

With Other Anticonvulsants

With Other Medications

Ethanol

CONCLUSIONS

REFERENCES

CHAPTER 195. RUFINAMIDE

INTRODUCTION

CHEMISTRY

PHARMACOLOGY

Activity in Experimental Models of Seizures/Epilepsy

MECHANISM OF ACTION

CLINICAL PHARMACOKINETICS

Absorption

Plasma Protein Binding and Distribution

Metabolism and Elimination

Influence of Age on Pharmacokinetics

Influence of Sex on Pharmacokinetics

Influence of Renal Impairment on Pharmacokinetics

Pharmacokinetics in Epilepsy Patients

EFFICACY

Proof-of-Principle Study

Overview of Clinical Efficacy Trials in Humans

Adults with Focal-Onset Seizures: Adjunctive Therapy

Children with Focal-Onset Seizures: Adjunctive Therapy

Adults with Focal-Onset Seizures: Monotherapy

Adults with Primary Generalized Tonic–Clonic Seizures

Lennox–Gastaut Syndrome

Specific Epileptic Seizures or Syndromes

ADVERSE EVENTS

Dose-Related, Nonidiosyncratic Adverse Effects

Idiosyncratic Reactions

Status Epilepticus

Pregnancy and Teratogenicity

DRUG INTERACTIONS

DOSING RECOMMENDATIONS

Precautions

Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 196. STIRIPENTOL

INTRODUCTION

CHEMICAL CONSIDERATIONS

Chemical Structure

Formulations

MECHANISMS OF ACTION

GABAergic Mechanism

Inhibition of Lactate Dehydrogenase

Neuroprotection

ACTIVITY IN EXPERIMENTAL MODELS

CLINICAL EFFICACY

RCTs in Dravet Syndrome

Long-Term Studies in Dravet Syndrome

Studies in Adults With Dravet Syndrome

APPROVED INDICATION

POTENTIAL NONAPPROVED INDICATIONS

Drug-Resistant Focal Epilepsy

Super-Refractory Status Epilepticus

PCDH19

Malignant Migrating Partial Seizures in Infancy

SAFETY IN DRAVET SYNDROME

CLINICAL PHARMACOKINETICS

DRUG INTERACTIONS AND DOSES OF COMEDICATIONS

Interactions With the ASMs Used in Dravet Syndrome

Interactions With other ASMs

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Therapeutic Monitoring

Precautions and Contraindications

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 197. TIAGABINE

INTRODUCTION

Mechanism of Action

EXPERIMENTAL STUDIES

PHARMACOKINETICS

CLINICAL EFFICACY

Evidence From Randomized Controlled Trials

Evidence From Other Studies

Efficacy as Monotherapy

Efficacy in Pediatric Patients

CLINICAL SAFETY

ROLE IN EPILEPSY TREATMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 198. TOPIRAMATE

INTRODUCTION

CHEMISTRY

PHARMACOLOGY

Activity in Experimental Models of Seizures/Epilepsy

Mechanisms of Action

CLINICAL PHARMACOKINETICS

Absorption

Distribution and Binding

Metabolism and Elimination

Serum Concentrations

EFFICACY IN ADULTS AND CHILDREN

Focal-Onset Seizures in Adults: Adjunctive Therapy

Focal-Onset Seizures in Children: Adjunctive Therapy

Focal- and Generalized-Onset Seizures: Monotherapy

Generalized Tonic–Clonic Seizures of Nonfocal Origin

Lennox–Gastaut Syndrome

Infantile Spasms (West Syndrome)

Severe Myoclonic Epilepsy of Infancy (Dravet Syndrome)

Other Epilepsy Syndromes

Long-Term and Open-Label Treatment

Use in Refractory Status Epilepticus

COMORBIDITIES

ADVERSE EFFECTS

Dose-Related Adverse Effects

Non–Dose-Related Adverse Effects

DRUG INTERACTIONS

Effects of TPM on Other Drugs

Effects of Other Drugs on TPM

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

Precautions

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 199. TRIMETHADIONE, PARALDEHYDE, PHENACEMIDE, BROMIDES, SULTHIAME, ACETAZOLAMIDE, AND METHSUXIMIDE

INTRODUCTION

TRIMETHADIONE

Structure and Chemistry

Basic Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

Drug Interactions

The Role of the Drug

How to Use the Drug

PARALDEHYDE

Structure and Chemistry

Basic Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

Overdosage

Side Effects

Role of the Drug

Alcohol Withdrawal Syndrome and Delirium Tremens

Other Indications

How to Use the Drug

PHENACEMIDE

Structure and Chemistry

Basic Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

Teratogenicity

The Role of the Drug

How to Use the Drug

BROMIDES

Structure and Chemistry

Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

Drug Interactions

The Role of the Drug

How to Use the Drug

SULTHIAME

Structure and Chemistry

Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

Drug Interactions

The Role of the Drug

How to Use the Drug

ACETAZOLAMIDE

Structure and Chemistry

Basic Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

The Role of the Drug

How to Use the Drug

METHSUXIMIDE

Structure

Basic Mechanism of Action

Pharmacologic Fundamentals

Adverse Effects

Role of the Drug

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 200. VALPROIC ACID

INTRODUCTION

CHEMICAL STRUCTURE AND FORMULATIONS

PHARMACOLOGY

Activity in Experimental Models and Mechanisms of Action

Clinical Pharmacokinetics/Pharmacodynamics

EFFICACY

Idiopathic Generalized and Unclassifiable Epilepsy

Absence Seizures

Juvenile Myoclonic Epilepsy

Focal-Onset Seizures and Bilateral Tonic–Clonic Seizures

Developmental and Epileptic Encephalopathies

Febrile Seizures

Status Epilepticus

ADVERSE EFFECTS

Neurologic

Gastrointestinal

Reproductive

Hematologic

Other Side Effects

Teratogenicity and Neurodevelopmental Effects

DRUG INTERACTIONS

Effects of Valproate on Other Drugs

Effects of Other Drugs on VPA

ROLE IN EPILEPSY TREATMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 201. VIGABATRIN

INTRODUCTION

CHEMICAL CONSIDERATIONS AND MECHANISMS OF ACTION

Chemical Characteristics

Formulations

ACTIVITY IN EXPERIMENTAL MODELS OF SEIZURES/EPILEPSY

Mechanisms of Action

CLINICAL PHARMACOKINETICS

Methods of Determination in Body Fluids

Absorption

Plasma Protein Binding and Distribution

Metabolism and Elimination

Drug Interactions

EFFICACY IN ADULTS

Adjunctive Therapy

Long-Term Efficacy

Monotherapy

EFFICACY IN CHILDREN

Focal Seizures

Other Seizure Types (Excluding Spasms)

Infantile Spasms

ADVERSE EFFECTS

Visual Field Defects

Psychiatric Adverse Effects

Intramyelinic Edema and Brain MRI Abnormalities

Other Dose-Related, Nonidiosyncratic Reactions

Idiosyncratic Reactions

Teratogenic Effects

ROLE IN EPILEPSY TREATMENT

Indications

Dosing Recommendations

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 202. ZONISAMIDE

INTRODUCTION

STRUCTURE AND CHEMISTRY

MECHANISMS OF ACTION

PHARMACOLOGIC FUNDAMENTALS

Absorption and Routes of Administration

Distribution and Protein Binding

Metabolism

Elimination

DRUG INTERACTIONS

CLINICAL INDICATIONS

Indications

Zonisamide Monotherapy

Standard and New Antiepileptic Drugs (SANAD) II Study

Pediatric Population

ADVERSE EFFECTS

Dose-Related Adverse Effects

Idiosyncratic

Teratogenicity

LICENSING INFORMATION

CONTRAINDICATIONS

HOW TO USE THE DRUG

Dosage Formulations and Strengths

Starting Doses

Maintenance Doses, Dosing Frequency, and Maximum Dose

Discontinuing the Drug

SUMMARY AND CONCLUSIONS

REFERENCES

VOLUME III

SECTION 9 • Surgical Therapy for Epilepsy

CHAPTER 203. OVERVIEW: SURGICAL THERAPY FOR EPILEPSY

INTRODUCTION

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 204. A BRIEF HISTORY OF EPILEPSY SURGERY

INTRODUCTION

THE FIRST SURGERIES

LOCALIZATION OF FUNCTION

LESION-DIRECTED SURGERY

THE ROLE OF EEG

TEMPORAL LOBE RESECTIONS

INVASIVE RECORDING

NEUROIMAGING

BEHAVIOR

THE PALM DESERT CONFERENCES

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 205. INDICATIONS AND CRITERIA FOR EPILEPSY SURGERY IN CHILDREN

INTRODUCTION

Demographics: Epilepsy Surgery Unmet Need

The Range of Candidacy in Children

Criteria for Referral for Presurgical Evaluation and for Epilepsy Surgery

Noninvasive Overview: Concordance

Invasive Overview

ELECTROENCEPHALOGRAM

Semiology

Scalp EEG

Ictal Video EEG

Interictal Video EEG

NEUROIMAGING

Structural MRI

Functional MRI (in Older Children)

Diffusion-Weighted MRI

Nuclear Imaging

MAGNETOENCEPHALOGRAPHY

NEUROPSYCHOLOGICAL EVALUATION

NEUROPSYCHIATRIC ASSESSMENT

INVASIVE EEG MONITORING

Grids and Strips

Stereoelectroencephalography

PERIOPERATIVE ELECTRICAL STIMULATION

RADIOFREQUENCY THERMOCOAGULATION

CONCLUSION

REFERENCES

CHAPTER 206. INDICATIONS AND CRITERIA FOR EPILEPSY SURGERY IN ADULTS

INTRODUCTION

WHO IS A CANDIDATE FOR EPILEPSY SURGERY?

RATIONALE FOR SURGICAL INTERVENTION

CRITERIA FOR SURGICAL CANDIDACY

Medication-Resistant Seizures

Identification of a Surgically Remediable Focal Epilepsy

Loss of Quality of Life

ROLE OF EARLY INTERVENTION

GOALS OF SURGERY

TYPES OF SURGICAL TREATMENT

Mesial Temporal Lobe Epilepsy

Lesional Neocortical Epilepsy

“Nonlesional” Neocortical Epilepsy

Hemispheric Epilepsy Syndromes

Generalized Epilepsies

CONTRAINDICATIONS TO EPILEPSY SURGERY

COST-EFFECTIVENESS AS A CRITERION FOR SURGERY

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 207. PATTERNS OF EPILEPSY SURGERY REFERRALS AND EPILEPSY SURGICAL CENTER CHARACTERISTICS

PATTERNS OF REFERRAL

HISTORY OF EPILEPSY CENTERS

MODERN EPILEPSY CENTERS

WORLDWIDE EPILEPSY SURGERY CENTERS AND PEDIATRIC CONSIDERATIONS

REFERENCES

CHAPTER 208. PRESURGICAL EVALUATION FOR EPILEPSY: GENERAL PRINCIPLES AND METHODS

INTRODUCTION

TIMING OF REFERRAL FOR PRESURGICAL EVALUATION

GOALS AND TYPES OF SURGICAL CONSIDERATIONS

THE CONCEPTUAL APPROACH TO DEFINING EPILEPTOGENESIS

Epileptogenic Zone

Irritative Zone

Ictal-Onset Zone

Epileptogenic Lesion

Functional Deficit Zone

Symptomatogenic Zone

OVERVIEW OF PRESURGICAL METHODS

Noninvasive Investigation

Invasive Tests

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 209. INTRAOPERATIVE ELECTROCORTICOGRAPHY IN EPILEPSY

INTRODUCTION

INDICATIONS

Identification of the Epileptogenic Zone

Functional Mapping

TECHNIQUE

Electrodes and Instrumentation

Recording and Electrical Stimulation

Activation and Effects of Anesthesia

Interpretation

High Frequency Oscillations on Electrocorticography

Electrocorticography in Cortical Disconnection Surgeries

ADVANTAGES AND LIMITATIONS OF INTRAOPERATIVE ELECTROCORTICOGRAPHY

Advantages

Limitations

COMPLICATIONS

FUTURE DIRECTIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 210. INTRAOPERATIVE FUNCTIONAL MAPPING IN EPILEPSY

INTRODUCTION

INDICATIONS

TECHNIQUE36,40,41

COMPARISON TO OTHER APPROACHES

FUNCTIONAL MAGNETIC RESONANCE IMAGING AND ELECTRICAL STIMULATION MAPPING

FUTURE DIRECTIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 211. EXTRAOPERATIVE PROCEDURES WITH INVASIVE ELECTRODES IN EPILEPSY

INTRODUCTION

INDICATIONS FOR INTRACRANIAL ELECTRODES

DEPTH ELECTRODES

Construction

Insertion

Recording

Risks

Interpretation

Advantages and Limitations

Yield and Accuracy

Cost

SUBDURAL ELECTRODE STRIPS

Construction

Insertion

Recording

Risks

Interpretation

Advantages and Limitations

Yield and Accuracy

Costs

SUBDURAL GRIDS

Construction

Insertion

Recording

Risks

Interpretation

Advantages and Limitations

Yield and Accuracy

Costs

COMBINED STUDIES

SPECIAL CONSIDERATIONS IN INFANTS AND YOUNG CHILDREN

Indications

Surgical Aspects

Nursing Aspects

Interpretive Aspects

COMPARATIVE ASSESSMENTS

Depth/SEEG Versus Subdural Strip Electrodes

Depth/SEEG or Subdural Strips Versus Grids

Depth/SEEG or Subdural Strip Versus Scalp Electrodes

Depth/SEEG or Subdural Electrodes Versus Pegs

Depth/SEEG or Subdural Electrodes Versus Foramen Ovale Electrodes

Chronic Depth/SEEG or Subdural Electrodes Versus Electrocorticography

Grid Versus Scalp

SYNTHESIS

General Indications

Distinctions Among Techniques

Techniques for Specific Situations

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 212. INTRA-ARTERIAL ANESTHETIC PROCEDURES IN EPILEPSY

INTRODUCTION

INDICATIONS

Language

Memory

TECHNIQUES

Testing Paradigms

Selective Procedures

Surveys on IAP

Alternative Techniques

Alternative Drugs

INTERPRETATION

Implications

APPLICATION TO CHILDREN

Language

Memory

ADVANTAGES

LIMITATIONS

COMPLICATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 213. EEG BIOMARKERS OF EPILEPTOGENIC REGION

INTRODUCTION

EEG SIGNAL ANALYSIS AND BIOMARKERS

PITFALLS OF SIGNAL ANALYSIS

High-Frequency Artifacts in Surface EEG

NONINVASIVE BIOMARKERS OF THE EPILEPTIC ZONE

Interictal and Ictal Activity

High-Frequency Oscillations

Nonepileptiform HFOs in the EEG

Other scalp biomarkers in surface EEG

Source Modeling: From Surface into the Deep

COMBINING NONINVASIVE METHODS

Combined EEG-fMRI

Combined TMS-EEG

OUTLOOK AND CONCLUSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 214. INVASIVE MONITORING RESEARCH TECHNIQUES IN EPILEPSY

INTRODUCTION

RESEARCH IN EPILEPSY SURGERY PATIENTS

INVASIVE ELECTROPHYSIOLOGY SIGNALS

TYPES OF RESEARCH DEVICES APPROVED FOR HUMAN USE

Informed Consent and Ethical Considerations of Invasive Implants

Behnke–Fried Hybrid Depth Arrays

Microdialysis Probes

Utah Intracortical Electrode Array

“All-in-One” Macro- and Microelectrode Arrays

EXPERIMENTAL DEVICES

Laminar Multielectrode Arrays

Flexible Biofilm Dense Arrays

RESEARCH UTILIZING ELECTROCORTICAL STIMULATION

MICROELECTRODE DATA ACQUISITION

Data Acquisition Systems for Combined Clinical and Research Purposes

Recording Methods

Recording Environment

Maintenance of Microelectrode Recordings

Data Storage and Access

Personnel Considerations

RESEARCH USE OF CHRONICALLY IMPLANTED CLINICAL DEVICES

CONCLUSIONS

REFERENCES

CHAPTER 215. ANESTHESIA FOR EPILEPSY SURGERY

INTRODUCTION

PREANESTHESIA EVALUATION AND PREPARATION

ANESTHESIA MANAGEMENT IN PATIENTS WITH MEDICALLY REFRACTORY EPILEPSY

ELECTROCORTICOGRAPHY AND PHARMACOACTIVATION

ANESTHESIA CARE FOR PROCEDURES FOR THE INVESTIGATION OF SEIZURES

ANESTHESIA FOR SURGICAL PROCEDURES FOR THE TREATMENT OF EPILEPSY: RESECTION AND ABLATION

ANESTHESIA FOR SURGICAL PROCEDURES FOR THE TREATMENT OF EPILEPSY: DISCONNECTION

ANESTHESIA FOR SURGICAL PROCEDURES FOR THE TREATMENT OF EPILEPSY: NEUROMODULATION

SUMMARY

REFERENCES

CHAPTER 216. ANTERIOR MEDIAL TEMPORAL RESECTION FOR EPILEPSY

INTRODUCTION

Historical Perspective

Early Role of Pathology

Impact of Early Electrophysiology Studies

Impact of Neuroimaging

Frequency of Use

INDICATIONS

Principal Candidates

Evaluation Criteria

Novel Approaches to Surgical Planning Using Epilepsy Network Theory

Goals of Surgery

SURGICAL APPROACHES

Medial Temporal Lobe Epilepsy

Lesional Temporal Lobe Epilepsy: Developmental Abnormalities, Neoplasms, Vascular Anomalies, and Encephaloceles

Cryptogenic Temporal Lobe Epilepsy: No Image Substrate

NEUROMODULATION AS AN ALTERNATIVE TO RESECTION

Responsive Neurostimulation

Deep Brain Stimulation for MTLE

OUTCOME AND PREDICTORS OF SUCCESS

Success

Surgical Failures and Their Pathoetiology

Neuropsychological and Neurologic Sequelae

Surgical Complications

Transient Deficits

Permanent Deficits

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 217. NEOCORTICAL RESECTIONS FOR EPILEPSY

INTRODUCTION

GENERAL PRINCIPLES

Epileptogenic Zone Definition

Noninvasive Presurgical Workup

Invasive Presurgical Workup

Specifics for Children

SURGICAL TREATMENT

Presurgical Planning

Eloquent Cortex

Anesthetic Considerations

Surgical Technique

Resection

Disconnection

Minimally Invasive Ablations

Frontal Lobe Surgery

Posterior Quadrant Surgery

Temporal Neocortical Surgery

Surgical Technique

POSTOPERATIVE CONDUCT

RESULTS

PATHOLOGY

COMPLICATIONS

OUTCOME ON SEIZURES

CONCLUSION

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 218. INSULAR RESECTIONS FOR EPILEPSY

HISTORICAL BACKGROUND

INSULAR EPILEPSY SURGERY: IN WHICH CASES?

INSULAR EPILEPSY SURGERY: HOW CAN IT BE DONE?

INSULAR EPILEPSY SURGERY: WHAT RESULT CAN BE EXPECTED?

CONCLUSIONS AND PERSPECTIVES

REFERENCES

CHAPTER 219. HEMISPHERECTOMY/HEMISPHEROTOMY AND MULTILOBAR RESECTIONS/DISCONNECTIONS FOR EPILEPSY

INTRODUCTION

HEMISPHERECTOMY/HEMISPHEROTOMY

Historical Perspective

Pathology

Role of Functional Localization

Electrophysiologic Studies

Neuroimaging

Indications

Seizure Semiology

Neurologic Examination

Language and Motor Function Evaluation

Electroencephalography and Imaging Findings

Etiology, Natural History, and Timing of Surgery

Goals of Surgery

Surgical Approaches

Endoscopic Hemispherotomy

Robotic Thermocoagulative Hemispherotomy

Outcomes and Complications of Hemispherotomy

MULTILOBAR RESECTIONS AND DISCONNECTIONS

Introduction

Underlying Pathologies

Presurgical Evaluation

Structural and Functional Imaging

Surgery

Multilobar Resection for Epilepsy: Published Series

Surgical Outcomes

Complications

CONCLUSIONS

REFERENCES

CHAPTER 220. ELOQUENT CORTEX SURGERY FOR EPILEPSY

INTRODUCTION

NEUROANATOMY OF THE ELOQUENT CORTEX

Motor Cortex

Somatosensory Cortex

Secondary Cortices and Areas

SEIZURE DISORDERS INVOLVING THE EC

Benign Childhood Epilepsy With Centrotemporal Spikes

Malignant Rolandic-Sylvian Epilepsy

MANAGEMENT PARADIGM

NONINVASIVE MAPPING

Functional MRI

Diffusion Tensor Imaging

Magnetoencephalography

Transcranial Magnetic Stimulation

INVASIVE MAPPING

Intraoperative Electrocorticography

Extraoperative Electrical Stimulation

Awake Craniotomy With Direct Cortical Stimulation

SURGICAL OPTIONS

Focal Resection

Multiple Subpial Transections

Neuromodulation

FUTURE DIRECTIONS

REFERENCES

CHAPTER 221. CORPUS CALLOSOTOMY FOR EPILEPSY

INTRODUCTION

HISTORY

RATIONALE FOR ANTISEIZURE EFFECTS

INDICATIONS

Seizure Type

EEGs

Epilepsy Syndrome

Pathology and Other Factors

SURGICAL ISSUES

Extent of Callosal Section

Surgical Techniques

OUTCOMES

Drop Attacks

Other Seizures

Epilepsy Syndrome

Cognitive and Behavioral Changes

Comparison with VNS

ADVERSE EFFECT AND COMPLICATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 222. ELECTRICAL STIMULATION TREATMENTS FOR EPILEPSY

VAGUS NERVE STIMULATION

Relevant Anatomy

Mechanisms of Action

Short-Term Efficacy

Long-Term Efficacy

Efficacy in Other Seizure Types and in Children

Effects on Other Comorbid Conditions

Safety and Tolerability of Vagus Nerve Stimulation in Patients with Epilepsy

Clinical Use

Summary and Conclusions

DEEP BRAIN STIMULATION

Rationale

Electrode Placement

Seizure Reduction

Adverse Effects

Ancillary Observations

RESPONSIVE NEUROSTIMULATION

Description of Stimulator System

Seizure Outcomes

Neuropsychologic and Quality-of-Life Outcomes

Effect on Sudden Unexplained Death in Epilepsy Incidence

Clinical and Scientific Insights from Chronic Ambulatory Intracranial EEG

REFERENCES

CHAPTER 223. ABLATIVE PROCEDURES FOR EPILEPSY: LASER ABLATION, STEREOTACTIC RADIOSURGERY, AND RADIOFREQUENCY ABLATION

THE RISE OF ABLATIVE PROCEDURES IN EPILEPSY SURGERY

MR-GUIDED LITT

Outcomes: General Considerations

MRg-LITT Surgical Approach and Target in MTLE

Extratemporal Lobe Epilepsy

LITT for Specific Pathologic Lesions

MRg-LITT for Disconnection Surgery: Laser Callosotomy and Hemispherotomy

STEREOTACTIC RADIOSURGERY

RADIOFREQUENCY ABLATION

Stereotactic Radiofrequency Amygdalohippocampotomy

Hypothalamic Hamartomas

RFA Through SEEG Electrodes for Malformations of Cortical Development and Other Lesions

CONCLUSIONS

REFERENCES

CHAPTER 224. EPILEPSY SURGERY FOR LOW-GRADE EPILEPSY ASSOCIATED TUMORS

INTRODUCTION

NEUROPATHOLOGIC CLASSIFICATION OF LEAT

Molecular Neuropathology

Histopathologic Classification

MRI IN LEAT

Glioneuronal Tumors

Glial Tumors

Lesion Localization

Differential Diagnosis

Follow-up Evaluation

EPILEPTOGENICITY IN LEAT

MEDICAL TREATMENT IN LEAT

SURGICAL TREATMENT IN LEAT

Malignant progression in LEAT

Tumor Surgery versus Epilepsy Surgery

Lesionectomy Versus Tailored Resection

CONCLUSION

REFERENCES

CHAPTER 225. EPILEPSY SURGERY FOR MALFORMATIONS OF CORTICAL DEVELOPMENT

INTRODUCTION

CLASS I

Focal Cortical Dysplasia Type II

Hemimegalencephaly

Cortical Dysplasias with Abnormal Cells

Tuberous Sclerosis Complex

CLASS II: PERIVENTRICULAR NODULAR HETEROTOPIA

CLASS III

Focal Cortical Dysplasia Type I

Focal Cortical Dysplasia Type III

Polymicrogyria

Mild Malformations of Cortical Development

OVERARCHING CONTROVERSIES

Outcome Assessment

Timing of Presurgical Assessment

Reoperation

The Network Perspective

Underutilization and Inequity of Access to Epilepsy Surgery

REFERENCES

CHAPTER 226. EPILEPSY SURGERY FOR VASCULAR LESIONS

INTRODUCTION

CEREBRAL CAVERNOUS HEMANGIOMA AND EPILEPSY

Epidemiology, Natural History, Pathophysiology, and Genetics

Concepts and Definition of Cavernoma-Related Epilepsy

Risk factors for CRE in patients with CCMs

Presurgical Evaluation

Surgical Techniques

Postsurgical Seizure Outcome and Its Predictors

Conclusions

AVMS AND EPILEPSY

Epidemiology, Natural History, Management

Clinical Presentation

Diagnostic Evaluation

Treatment Approaches

Conclusions

STURGE–WEBER SYNDROME AND EPILEPSY

Epidemiology, Natural History, and Genetics

Clinical Presentation

Diagnostic Evaluation

Medical and Surgical Treatment

CONCLUSIONS

REFERENCES

CHAPTER 227. RESULTS OF SURGERY FOR POSTTRAUMATIC EPILEPSY

INTRODUCTION

RISK FACTORS

Severity

Mechanism of Injury

Age Dependent: Pediatric and Elderly

Location of Injury

Comorbidities

Early Posttraumatic Seizure

Family History

Genetic Predisposition

PATHOPHYSIOLOGY

DIAGNOSIS

History

Examination

Metabolic Parameters

Imaging and Biomarkers

EEG and Biomarkers

ROLE OF ANTISEIZURE MEDICATIONS

Duration of ASM Usage

Choice of ASM

Other Therapies

ROLE OF SURGERY

Presurgical Work-up

Resective Surgery

Neuromodulation

CASE SERIES

ILLUSTRATIVE CASES

Case 1

Case 2

NEW AREAS OF RESEARCH

CONCLUSION

KEY POINTS

REFERENCES

CHAPTER 228. RESULTS OF EPILEPSY SURGERY IN PATIENTS WITH NON-LESIONAL MRI

MRI-NEGATIVE OR NON-LESIONAL EPILEPSY?

MRI is the Driving Force in Epilepsy Surgery

What Does “MRI-Negative” Mean?

N-MRI Epilepsy: Lesional Versus Genetic Epilepsy

HOW TO PROCEED IN N-MRI EPILEPSY SURGERY CANDIDATES

Presurgical Evaluation in N-MRI Epilepsies

Role of Other Than MRI Investigations

Combined Noninvasive Diagnostic Work-Up

Invasive Recordings

Outcomes in N-MRI Epilepsies

CONCLUSION

REFERENCES

CHAPTER 229. SURGERY FOR CEREBRAL INFECTIOUS AND POST-ENCEPHALITIC EPILEPSY

CEREBRAL INFECTIVE LESIONS

NEUROSURGERY FOR SEIZURES ASSOCIATED WITH BRAIN ABSCESS

Direct Spread

Hematogenous Spread

Postoperative Abscess

Trauma

Computed Tomography

Magnetic Resonance Imaging

Magnetic Resonance Spectroscopy

Diffusion-Weighted Imaging

NEUROSURGERY AND SEIZURES ASSOCIATED WITH NEUROCYSTICERCOSIS

NEUROSURGERY FOR SEIZURES ASSOCIATED WITH TUBERCULOSIS

NEUROSURGERY FOR SEIZURES ASSOCIATED WITH PARASITIC INFECTIONS

OUTCOMES OF NEUROSURGICAL RESECTION FOR EPILEPSY ASSOCIATED WITH ENCEPHALITIS

SUMMARY

REFERENCES

CHAPTER 230. SURGERY FOR RASMUSSEN ENCEPHALITIS

INTRODUCTION

CLINICAL MANIFESTATIONS

Presentation and Course

Clinical Vignette

ETIOLOGY AND PATHOGENESIS

DIAGNOSIS

Differential Diagnosis

Radiographic Features

Electrophysiologic Characteristics

Pathologic Diagnosis

Laboratory Tests

TREATMENT OPTIONS

Immune Agents

Antiseizure Medications

Epilepsy Surgery

TREATMENT OUTCOMES

REFERENCES

CHAPTER 231. EPILEPSY SURGERY FOR HYPOTHALAMIC HAMARTOMAS

INTRODUCTION

OPEN CRANIOTOMY

ENDOSCOPIC SURGERY

STEREOTACTIC RADIOSURGERY

STEREOTACTIC RADIOFREQUENCY THERMOCOAGULATION

STEREOTACTIC LASER ABLATION

COMPARISONS OF SURGICAL OUTCOMES

LONG-TERM PROGNOSIS

REFERENCES

CHAPTER 232. MEASURING EPILEPSY SURGERY OUTCOMES

INTRODUCTION

WHAT TO MEASURE AND HOW TO MEASURE

Common Data Elements

Core Outcome Sets

Selecting Specific Outcome Measurement Instruments to Address COS

SEIZURE OUTCOMES

Seizure Frequency

Postoperative Seizure Outcome Scales

Surgical Adverse Events

Neuropsychological Outcomes

Psychiatric and Behavioral Outcomes

PATIENT REPORTED OUTCOME MEASURES

MEASURING WHAT MATTERS: A PARENT’S PERSPECTIVE

REFERENCES

CHAPTER 233. ADVERSE EFFECTS OF EPILEPSY SURGERY

INTRODUCTION

Complications and Expected Adverse Effects

Classification of Complications

ADVERSE EFFECTS OF INVASIVE INVESTIGATIONS

Invasive EEG Procedures

ADVERSE EFFECTS OF EPILEPSY SURGERY

Mortality

Surgical Complications

Neurologic Adverse Effects

Seizure Worsening

Cognition

Psychiatric Adverse Effects

CONCLUSION

ACKNOWLEDGEMENT

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 234. PRE- AND POSTOPERATIVE REHABILITATION IN EPILEPSY SURGERY

INTRODUCTION

PSYCHOSOCIAL OUTCOMES IN EPILEPSY SURGERY

Cognitive/Neuropsychological Outcomes

Psychiatric Outcomes

Quality of Life

Burden of Normality

Social/Functional Outcomes

Surgical Expectations/Satisfaction

PRE- AND POSTSURGICAL ASSESSMENT

Psychosocial Assessment and the Burden of Normality Paradigm

Neuropsychological Evaluation

Psychiatric Evaluation

COMPREHENSIVE REHABILITATION

Prehabilitation

Postoperative Rehabilitation

CONCLUSION

REFERENCES

CHAPTER 235. ANTISEIZURE MEDICATION WITHDRAWAL AFTER EPILEPSY SURGERY

WHAT IS CURRENT PRACTICE?

WHAT ARE THE BENEFITS OF DRUG WITHDRAWAL?

WHAT ARE THE RISKS FOR SEIZURE RECURRENCE AFTER DRUG WITHDRAWAL?

WHAT IS THE IDEAL TIMING OF DRUG WITHDRAWAL?

CAN WE PREDICT SUCCESSFUL DRUG WITHDRAWAL IN THE INDIVIDUAL PATIENT?

CONCLUSION

REFERENCES

CHAPTER 236. REOPERATION FOR EPILEPSY

INTRODUCTION

EPILEPSY SURGERY: RATIONALE AND RESULTS

REOPERATION FOR EPILEPSY: REPORTED EXPERIENCES

Reoperation for DRE in Adults

Reoperation for DRE in Children

REOPERATION FOR EPILEPSY: LESSONS LEARNED

Role of Adjunctive Studies in Reoperation

Factors Favoring Reoperation

Complication Avoidance

CONCLUSIONS

REFERENCES

SECTION 10 • Psychiatric Issues in Epilepsy

CHAPTER 237. OVERVIEW: PSYCHIATRIC ISSUES IN EPILEPSY

REFERENCES

CHAPTER 238. WHAT IS A PSYCHIATRIC SYMPTOM IN PATIENTS WITH EPILEPSY?

INTRODUCTION

INTERICTAL DISORDERS

PERI-ICTAL EPISODES

PARAICTAL EPISODES

IATROGENIC PSYCHIATRIC SYMPTOMS AND EPISODES

CONCLUDING REMARKS

REFERENCES

CHAPTER 239. EPIDEMIOLOGIC ASPECTS OF PSYCHIATRIC COMORBIDITIES IN EPILEPSY

OVERVIEW

WHAT IS PREVALENCE?

WHO HAS A PSYCHIATRIC DISORDER?

DEPRESSION

ANXIETY

PSYCHOSIS

PERSONALITY DISORDERS

POST-TRAUMATIC STRESS DISORDER

ALCOHOL CONSUMPTION

SUICIDE

ATTENTION-DEFICIT HYPERACTIVE DISORDER

INTELLECTUAL DISABILITY

AUTISM SPECTRUM DISORDER

BIDIRECTIONAL RELATIONSHIP BETWEEN EPILEPSY AND PSYCHIATRIC DISORDERS

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 240. WHY SHOULD NEUROLOGISTS CARE ABOUT PSYCHIATRIC COMORBIDITIES IN PATIENTS WITH EPILEPSY AND THE OBSTACLES FOR THEIR CARE?

INTRODUCTION

WHY SHOULD NEUROLOGISTS CARE?

Impact of Psychiatric History on the Seizure Disorder

Impact of Psychiatric Comorbidities on the Life of PWE

OBSTACLES IN THE TREATMENT OF PSYCHIATRIC COMORBIDITIES IN EPILEPSY

Obstacles Caused by Physicians

Obstacles Caused by Patients

Obstacles Caused by the Medical Establishment

CONCLUDING REMARKS

REFERENCES

CHAPTER 241. NEUROBIOLOGICAL ASPECTS OF EPILEPTIC COMORBIDITIES: A REVIEW OF THE EXPERIMENTAL DATA

INTRODUCTION

RESEARCH DOMAIN CRITERIA: CLOSING THE GAP BETWEEN CLINICAL AND BASIC RESEARCH OF MENTAL DISORDERS

RDoC AND PRECLINICAL COMMON DATA ELEMENTS FOR EPILEPSY RESEARCH

MAJOR DEPRESSIVE DISORDER COMORBIDITY WITH EPILEPSY AND THE DYSFUNCTION OF MONOAMINERGIC CIRCUITRIES

Negative Valence, Construct of Loss

ATTENTION DEFICIT/HYPERACTIVITY DISORDER

A UNIFIED HYPOTHESIS OF EPILEPSY-ASSOCIATED DEPRESSION AND ADHD

COGNITIVE DYSFUNCTION

ANIMAL MODELS

EARLY-LIFE SEIZURES

DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHIES

The Role of Epileptiform Activities in Neurobehavioral Deficits

Acquired Mechanisms Underlying Neurobehavioral Mechanisms

Structural Lesions and Network Dysfunction

CONCLUSIONS

REFERENCES

CHAPTER 242. MOOD DISORDERS IN ADULTS WITH EPILEPSY

INTRODUCTION

EPIDEMIOLOGIC DATA

CLINICAL PRESENTATIONS

Interictal Depressive Disorders

Comorbid Psychiatric Disorders

Atypical Manifestations of Depression in Epilepsy

Interictal Dysphoric Disorder

Peri-ictal Symptoms

Ictal Symptoms of Depression

Preictal Symptoms

Postictal Symptoms

Suicidality as an Expression of Depression in Epilepsy

IMPACT ON QUALITY OF LIFE

COMMON PATHOGENIC MECHANISMS IN EPILEPSY AND DEPRESSION

Abnormal Secretion of Neurotransmitters

Functional Neuroimaging Studies in Epilepsy and Primary Depression

ENDOCRINE DISTURBANCES: HYPERACTIVE HYPOTHALAMIC–PITUITARY–ADRENAL AXIS AND INFLAMMATORY MECHANISMS

Hyperactive Hypothalamic–Pituitary–Adrenal Axis

Structural Changes in Temporal Lobes

Structural Changes in Frontal Lobes

Neuroinflammatory Mechanisms

OTHER PATHOGENIC MECHANISMS OF DEPRESSION

Psychosocial Causes of Depression

Depression as an Iatrogenic Process

Depression Following Epilepsy Surgery

A Genetic Predisposition

TREATMENT

Some Preliminary Basic Concepts

Selection of Antidepressant Pharmacotherapy

Choice of Antidepressant Drug

Pharmacokinetic Interactions Between Antidepressants and Antiseizure Medications

Pharmacodynamic Effects of Antidepressant Drugs to Watch for in People with Epilepsy

Antipsychotics

Mood-stabilizing Agents

Electroshock Therapy

Vagus Nerve Stimulation

When Should Patients Be Referred for Psychological Treatment?

CONCLUSIONS

REFERENCES

CHAPTER 243. SUICIDALITY AND EPILEPSY

INTRODUCTION

TOWARD A CLASSIFICATION OF SUICIDE

The Nomenclature of Suicide

SUICIDE IN THE GENERAL POPULATION

Epidemiology

Risk Factors for Suicide

SUICIDE IN EPILEPSY

Epidemiology

Bidirectionality of Suicide and Epilepsy

Epilepsy-Specific Risk Factors for Suicide

IDENTIFYING SUICIDALITY IN EPILEPSY

SUICIDE PREVENTION

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 244. AGGRESSIVE DISORDERS IN EPILEPSY

INTRODUCTION

CLASSIFYING AGGRESSION

AGGRESSIVE BEHAVIOR IN CLINICAL PRACTICE

PHENOMENOLOGY OF IED

EPIDEMIOLOGY OF IED

NEUROBIOLOGY OF IED

Clinical Studies

EEG and Imaging Studies

NEUROBIOLOGY OF AGGRESSION IN GENERAL AND IED IN PARTICULAR

Dual-Brain Pathology in Patients with Episodic Dyscontrol

IED—Is It Epilepsy?

Social and Psychological Aspects of Aggression in Epilepsy

THERAPY OF AGGRESSION AND EPISODIC DYSCONTROL

CONCLUSION

REFERENCES

CHAPTER 245. ANXIETY DISORDERS IN ADULTS WITH EPILEPSY

INTRODUCTION

ANXIETY SYMPTOMS AS A NORMAL REACTIVE PROCESS VERSUS AN EXPRESSION OF PSYCHOPATHOLOGY

EPIDEMIOLOGY

Prevalence of Anxiety Symptoms

CLINICAL MANIFESTATIONS

Interictal Anxiety Disorders

Peri-Ictal Symptoms of Anxiety

Comorbid Occurrence of Anxiety and Depression Disorders

Screening of Anxiety Symptoms in the Clinic

The Use of Screening Instruments in Research: A Cautionary Note

IMPACT OF ANXIETY DISORDERS ON QUALITY OF LIFE

IMPACT OF ANXIETY ON SUICIDALITY

PATHOGENIC MECHANISMS

Psychosocial Factors

Endogenous Changes of Anxiety in Epilepsy

Iatrogenic Mechanisms

Treatment

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 246. PSYCHOTIC DISORDERS IN EPILEPSY

INTRODUCTION

DEFINITIONS AND PHENOMENOLOGY

HISTORICAL BACKGROUND

EPIDEMIOLOGY

CLASSIFICATION

SYNDROMES OF PSYCHOSES IN RELATION TO SEIZURE ACTIVITY

Postictal Psychoses

Preictal Psychosis

Interictal Psychoses

RISK FACTORS

Genetic Predisposition

Sex Distribution

Duration of Epilepsy

Type of Epilepsy

Type of Seizures

Severity of Epilepsy

Laterality

Structural Lesions

FORCED NORMALIZATION

PSYCHOSIS FOLLOWING SURGERY

DIAGNOSIS

TREATMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 247. PERSONALITY AND PERSONALITY DISORDERS IN EPILEPSY

INTRODUCTION

THE SETTING

PERSONALITY

Normal versus Abnormal Personality

Assessing Normal Personality

The Big Five Personality Traits

Studies of Neuroticism in Epilepsy

Studies of Extraversion in Epilepsy

Studies of Other Traits

Implications

PERSONALITY DISORDERS

The DSM Approach

Limitations and Future Directions

REFERENCES

CHAPTER 248. INTELLECTUAL DISABILITIES IN EPILEPSY

INTRODUCTION

CLASSIFICATION AND TERMINOLOGY OF INTELLECTUAL DISABILITY

Definition of Intellectual Disability

THE NATURE AND IMPACT OF EPILEPSY IN PEOPLE WITH INTELLECTUAL DISABILITY

Epidemiology

Etiologic Issues

The Impact of Epilepsy on Development and Learning

Mortality

THERAPEUTIC INTERVENTIONS

Recognition of the Need of Intervention

Choosing an Intervention

Quality Evidence

Learning from the Evidence

Special Interventions

THE CONTEXT OF CARE

Health Advocacy

Barriers and Safety

Quality of Care

Specialist Provision

Epilepsy Management

Communication Skills: Management by Proxy

The Family

Coordinating Multiagency Care Delivery

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 249. AUTISM AND EPILEPSY

INTRODUCTION

PREVALENCE

RISK MARKERS

Age

Intellectual Functioning

Sex

Underlying Etiologies

EPILEPSY FEATURES

EEG FINDINGS

Epileptiform EEGs

Future Risk for Epilepsy?

REGRESSION

NEUROBEHAVIORAL CORRELATES/AUTISM SEVERITY

INDIVIDUALS WITH ASD WHO DEVELOP EPILEPSY MAY BE A DISTINCT SUBSET

CONCLUSION

REFERENCES

CHAPTER 250. MOOD AND ANXIETY DISORDERS IN PEDIATRIC PATIENTS WITH EPILEPSY

INTRODUCTION

HISTORY OF DEPRESSION AND ANXIETY OVERLAP WITH EPILEPSY

ROLE OF THE HPA AXIS AND TEMPORAL LOBE IN ANXIETY, DEPRESSION, AND EPILEPSY

ANXIETY AND MOOD DISORDERS VERSUS SYMPTOMS

EPIDEMIOLOGY OF ANXIETY AND MOOD DISORDER IN PEDIATRIC PATIENTS WITH EPILEPSY

Internalizing Disorders Are More Common in Pediatric Epilepsy

Association of Anxiety and Mood Disorder Subtypes to Epilepsy Subtypes

Seizure Variables

Gender Variability

Age of Epilepsy Onset

Duration of Epilepsy

Timing of Symptom Presentation

Social Factors

TREATMENT

Nonpharmacologic Strategies

Pharmacologic Strategies

CONCLUSION

REFERENCES

CHAPTER 251. ATTENTION DEFICIT HYPERACTIVITY DISORDER AND EPILEPSY

INTRODUCTION

BACKGROUND OF ADHD

Definitions of ADHD

Dimensional Approach

THE PRESENCE OF ADHD IN EPILEPSY

Most Common Comorbidity in Pediatric Epilepsy

Gender Equivalence

Epilepsy Subtypes Associated with ADHD

Network Connectivity

Familial Overlap

Differential with Absence Epilepsy

Differentiation from Other Conditions

BIDIRECTIONALITY

Electrographic Abnormalities in ADHD without Epilepsy

ADHD SYMPTOMS RESULTING FROM ANTICONVULSANT MEDICINE

USE OF STIMULANT MEDICINE IN ADHD AND EPILEPSY

Risks of Stimulants in Epilepsy

FUTURE RESEARCH STUDIES

CONCLUSION

REFERENCES

CHAPTER 252. PSYCHIATRIC SYMPTOMS OF ANTISEIZURE MEDICATIONS

INTRODUCTION

ADVERSE PSYCHIATRIC EFFECTS OF SPECIFIC ASMs

First-Generation Drugs

Second-Generation ASMs

POSITIVE PSYCHOTROPIC EFFECTS OF ASMs

RISK FACTORS FOR PSYCHIATRIC ADVERSE EVENTS

MECHANISMS

FORCED NORMALIZATION

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 253. PSYCHIATRIC IATROGENIC EFFECTS OF EPILEPSY SURGERY

INTRODUCTION

DEPRESSION

PSYCHOSIS

PERSONALITY DISORDERS

Studies on Postoperative Stability of Personality Traits

PD as an Obstacle to Successful Postoperative Adaptation

Impact of PD on Seizure Outcome

Conclusion on PD in the context of ES

PNES AFTER EPILEPSY SURGERY

The Nature of PNES

Patients with PNES after Surgery

New-Onset PNES after Surgery

Conclusion on PNES and epilepsy surgery

INFLUENCE OF PSYCHIATRIC DISORDERS ON QOL

The Effects of Good Preoperative Coping Styles for Postoperative Improvement of QOL

Conclusion on Psychiatric Influence on QOL

CONCLUSIONS

REFERENCES

CHAPTER 254. THERAPEUTIC EFFECTS OF EPILEPSY SURGERY ON PRESURGICAL PSYCHIATRIC COMORBIDITIES

INTRODUCTION

ANXIETY AND DEPRESSION

DE NOVO CONDITIONS

SUICIDE AND EPILEPSY SURGERY

PSYCHOSIS

BIPOLAR AFFECTIVE DISORDERS

RISK FACTORS RELATED WITH EPILEPSY SURGERY

CHILDREN AND EPILEPSY SURGERY

LIMITATIONS OF THE SCIENTIFIC EVIDENCE IN THIS FIELD

CONCLUSIONS

REFERENCES

CHAPTER 255. DO PSYCHIATRIC COMORBID DISORDERS HAVE AN IMPACT ON POSTSURGICAL SEIZURE OUTCOME?

INTRODUCTION

PSYCHIATRIC DISEASE IS A RISK FACTOR FOR POOR OUTCOMES AFTER ATL

PSYCHIATRIC DISEASE IS NOT A RISK FACTOR OF POOR SEIZURE OUTCOMES AFTER ATL

CONCLUDING REMARKS: HOW CAN WE MAKE SENSE OF THESE DATA?

REFERENCES

CHAPTER 256. COGNITIVE ADVERSE EFFECTS OF ANTISEIZURE MEDICATIONS

INTRODUCTION

THE STUDY OF COGNITIVE SIDE EFFECT OF ASMs

Methodologic Concerns and Constraints

ANTISEIZURE MEDICATIONS

Phenobarbital

Phenytoin

Ethosuximide

Valproate

Carbamazepine

Lamotrigine

Gabapentin

Topiramate

Tiagabine

Oxcarbazepine

Levetiracetam

Zonisamide

Rufinamide

Lacosamide

Perampanel

Eslicarbazepine Acetate

Brivaracetam

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 257. PHARMACOLOGIC TREATMENT OF PSYCHIATRIC DISORDERS IN EPILEPSY: BASIC CONCEPTS

INTRODUCTION

DEPRESSION

Antidepressant Drugs in Epilepsy

Antiseizure Medications for Depression in Epilepsy

ANXIETY DISORDERS

PSYCHOSES

Antipsychotic Drugs

Treatment Issues in Patients with Epilepsy and Psychoses

Benzodiazepines in Epilepsy and Psychoses

The Use of Lithium in Epilepsy

CONCLUSIONS

REFERENCES

CHAPTER 258. PSYCHOTHERAPY IN EPILEPSY

INTRODUCTION

GENERAL OVERVIEW OF PSYCHOTHERAPIES

Classification of Psychological Interventions

THE UTILITY OF PSYCHOMETRIC MEASURES IN THE PSYCHOTHERAPEUTIC PROCESS

Measures of Mood and Affect Symptoms

Measures of Anxiety Symptoms

Quality of Life in Epilepsy (QOLIE-31) and (QOLIE-89)

PSYCHOTHERAPEUTIC TREATMENT TARGETS IN EPILEPSY

WHAT TYPES OF PSYCHOTHERAPY CAN BE USEFUL IN THE TREATMENT OF PWE

CONCLUSION

REFERENCES

CHAPTER 259. THE USE OF ELECTROSHOCK THERAPY AND TRANSCRANIAL MAGNETIC STIMULATION IN PATIENTS WITH EPILEPSY: SAFETY AND THERAPEUTIC CONSIDERATIONS

ELECTROCONVULSIVE THERAPY

Overview of ECT

ECT Special Treatment Parameters for Patients with Epilepsy

ECT Side Effects and Safety Considerations in Patients with Epilepsy

ECT Potential Indications in Patients with Epilepsy

TRANSCRANIAL MAGNETIC STIMULATION

Overview of TMS

rTMS Mechanism

rTMS Side Effects and Safety Considerations in Patients with Epilepsy

rTMS Dosing and Treatment Parameters

rTMS Potential Indications in Patients with Epilepsy

Psychogenic Nonepileptic Seizures and Other Promising Future Areas of Study

REFERENCES

CHAPTER 260. PSYCHIATRY AND RESIDENTIAL CARE IN EPILEPSY

OVERVIEW

HISTORY: A BRIEF OUTLINE OF THE RISE AND FALL OF CONFINEMENT

Development of Institutions

Colonies for People with Epilepsy: Their Role and Development

CURRENT RESIDENTIAL CENTERS

Residential Education for Children

Residential Assessment for Children and Adults

Long-Stay Provision and Rehabilitation for Adults

New Areas of Business

CURRENT TRENDS AND PURPOSES IN EPILEPSY INSTITUTIONS

Discharge of People with Epilepsy into the Community

Coassessment of Intellectual Disability (Learning Disability/Mental Handicap)

Outcome on Discharge from Special Schools, Centers, and Hospitals

CURRENT INTERNATIONAL SITUATION

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 261. OVERVIEW: SOCIAL ISSUES IN EPILEPSY

INTRODUCTION

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 262. SOCIAL ASPECTS IN EPILEPSY: EPILEPSY STIGMA AND QUALITY OF LIFE

INTRODUCTION

EPILEPSY AS A SOCIAL LABEL

THEORIES OF STIGMA IN THE CONTEXT OF EPILEPSY

VIEWS ABOUT EPILEPSY AS A SOCIAL LABEL

Views of People with Epilepsy

Views of Other Groups

ROLE OF STIGMA IN QUALITY OF LIFE

MANAGING EPILEPSY STIGMA

Helping People with Epilepsy to Manage a Negative Social Label

Changing Negative Public Attitudes

SUMMARY AND CONCLUSIONS

DEDICATION

REFERENCES

CHAPTER 263. QUALITY OF LIFE IN CHILDREN WITH EPILEPSY

DEFINITION

ASSESSMENT AND MEASUREMENT ISSUES

Health Utility Approaches

Generic Measures

Disease-Specific Measures

BENEFIT OF MEASURING HRQOL IN CLINICAL PRACTICE

METHODOLOGIC ISSUES IN HRQOL MEASUREMENT

Clinically Meaningful Benchmarks

Clinical Cut-offs

Parent/Caregiver-Proxy Reporting

RISK AND RESILIENCE FACTORS

Medical Factors

Demographic Factors

Psychological and Neurocognitive Comorbidities

Family Factors

INTERVENTIONS TO IMPROVE HRQOL IN EPILEPSY

CONCLUSIONS AND FUTURE DIRECTIONS

REFERENCES

CHAPTER 264. QUALITY OF LIFE IN ADULTS WITH EPILEPSY

INTRODUCTION: OVERVIEW OF QUALITY OF LIFE IN ADULTS WITH EPILEPSY

MENTAL HEALTH AND COGNITION

Health Care Costs

Seizure Control

PSYCHOSOCIAL

Employment

Driving and Independence

Social Support

Marriage

DEVICE TREATMENT OF EPILEPSY

CONCLUSION

REFERENCES

CHAPTER 265. SELF/FAMILY MANAGEMENT IN PEDIATRIC EPILEPSY: OVERVIEW AND UTILITY IN ROUTINE PEDIATRIC EPILEPSY CARE

INTRODUCTION: SCOPE OF THE CHAPTER AND DEFINITION

ASSESSMENT: WHY IS IT IMPORTANT TO ASSESS PEDIATRIC EPILEPSY SELF/FAMILY MANAGEMENT?

INTERVENTION

Current Evidence-Based Recommendations for Psychological Treatments

TRANSITION

Developmental Considerations

INTEGRATING SELF AND FAMILY MANAGEMENT INTO THE CLINIC VISIT

CONCLUSION

REFERENCES

CHAPTER 266. SELF-MANAGEMENT PROGRAMS FOR ADULTS WITH EPILEPSY

INTRODUCTION

LITERATURE REVIEW

Assessment

SELF-MANAGEMENT PROGRAMS

WebEase

UPLIFT

HOBSCOTCH

PACES

TIME

SMART

MINDSET

PAUSE

Implementation of Self-Management Programs

BARRIERS TO IMPLEMENTATION

REFERENCES

CHAPTER 267. PSYCHOSOCIAL CARE NEEDS AND COMMUNITY RESOURCES FOR PEOPLE WITH EPILEPSY

INTRODUCTION

PSYCHOSOCIAL CARE

ASSESSMENT OF PSYCHOSOCIAL CARE NEEDS

PSYCHOSOCIAL CARE NEEDS ACROSS THE LIFESPAN

Children and Adolescents

Parents

Adults and Older Adults

STRATEGIES FOR MEETING PSYCHOSOCIAL CARE NEEDS

SOCIAL DETERMINANTS OF HEALTH

Risk Factors in People with Epilepsy

How SDH Can Influence Psychosocial Care Needs

RESOURCES TO ADDRESS PSYCHOSOCIAL CARE NEEDS

Resources in Health Care (Clinical) Setting

Resources in the Community Setting

Epilepsy Foundation—National and Local

Online Resources

Resources to Address SDH

CONCLUSION

REFERENCES

CHAPTER 268. THE RANGE OF NEEDS AND SERVICES IN VOCATIONAL REHABILITATION IN PEOPLE WITH EPILEPSY

INTRODUCTION

POSTSECONDARY SCHOOL VOCATIONAL ASSESSMENT

Vocational Interests/Work Values

Pattern of Abilities

Epilepsy-related Restrictions and Limitations

Behavioral Problems and Social Skills Deficits Associated with Epilepsy

SERVICES

Prevocational Intervention (Work Preparatory Courses, Social Rehabilitation)

Vocational Assessment and Its Components

Vocational Training Courses for Young Adults with Epilepsy

School-to-Work Transition

Subgroups of the Unemployed and Underemployed

Seizures and Unemployment

Neuropsychological Deficits and Employability

Interactions with Employers and Colleagues

Seizure Disclosure to Employers

Predictors of Long-term Employment Success

VOCATIONAL SERVICES

Programs for Assessment and Short-term Rehabilitation

Retraining Centers for Adults

Training and Placement Services

Postplacement Services

WORKPLACE ACCOMMODATIONS

Birgit’s Case

Harry’s Case

NATIONAL LEGISLATION AFFECTING JOB ACCESS

Germany

Americans with Disabilities Act

SHELTERED EMPLOYMENT VERSUS EMPLOYMENT OF PERSONS WITH EPILEPSY IN THE OPEN LABOR MARKET

NEW SERVICES

Models to Change Sheltered Employment

Models of Supported Employment Placement

Individualized Placement Programs

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

CHAPTER 269. EPILEPSY AND TRANSITION OF CARE

WHAT IS TRANSITION AND HOW IS IT DIFFERENT FROM TRANSFER?

THE IMPORTANCE OF CARE TRANSITIONS

TYPES OF TRANSITION PROGRAMS FOR ADOLESCENTS AND YOUNG ADULTS

GUIDANCE

BEST PRACTICE AND QUALITY MEASURES

MEASURING OUTCOMES

LIFE TRANSITIONS IN ADOLESCENTS AND YOUNG ADULTS WITH EPILEPSY: THE IMPORTANCE OF EPILEPSY SELF-MANAGEMENT

FRAMEWORKS FOR EPILEPSY CARE DURING TRANSITION PROCESS

EPILEPSY SELF-MANAGEMENT TRANSITION SKILLS

Medication Management, Adherence, and Self-Monitoring

Staying Safe: Using Seizure Action Plans

Staying Safe: Driving and Transportation

Reproductive Health

General Health and Wellness

Emotional Health

Educational and Vocational Needs

Independent Living

TRANSITION RESOURCES

SUMMARY

REFERENCES

CHAPTER 270. ENHANCING SCHOOL FUNCTIONING AND THE SCHOOL-TO-WORK TRANSITION IN CHILDREN WITH EPILEPSY

SCHOOL PERFORMANCE OF YOUTH WITH EPILEPSY

ICF Model and Epilepsy

Body Structures and Functions

Activity and Participation

Personal Factors

Environmental Factors

SCHOOL-TO-WORK TRANSITION

ISSUES RELATED TO TRANSITION

The ICF Model as a Conceptual Framework for Transition Planning

Keys to Success: Early and Transdisciplinary Transition Planning

Transdisciplinary Assessment for Transition Planning

Evidence Based Practices and Predictors for Transition Planning

Special Consideration: Differentiating between Entitlement and Eligibility

Special Consideration: Understanding Pre-Employment Transition Services

Evaluation of Transition Outcomes

CONCLUSION

REFERENCES

CHAPTER 271. ISSUES IN HEALTH OUTCOMES ASSESSMENT IN EPILEPSY

INTRODUCTION

THE CONCEPT OF HEALTH-RELATED QUALITY OF LIFE IN EPILEPSY

SEIZURE FREQUENCY AND HEALTH-RELATED QUALITY OF LIFE

SURGERY AND HEALTH-RELATED QUALITY OF LIFE

MEDICATIONS AND HEALTH-RELATED QUALITY OF LIFE

PSYCHIATRIC COMORBIDITY AND HEALTH-RELATED QUALITY OF LIFE

OTHER COMORBIDITIES

SLEEP

EXERCISE

MIGRAINE

ISSUES SPECIFIC TO CHILDREN

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 272. LEGAL CONCERNS AND EFFECTIVE ADVOCACY STRATEGIES IN EPILEPSY

INTRODUCTION

DEFINING DISABILITY

EMPLOYMENT DISCRIMINATION

Qualified

Application and Interview Process

Reasonable Accommodation Process

What Kind of Documentation Should I Provide?

Family and Medical Leave Act

ADA/FMLA Interplay

Enforcing Employment Nondiscrimination Rights in Employment

TITLES II AND III OF THE ADA

Title II

Title III

Enforcing of Nondiscrimination Rights under Title II and III of the ADA

EDUCATION

IDEA and Section 504 of the Rehab Act

IDEA

Section 504

Title II and III of the ADA

Administration of Rescue Medications in Schools

DRIVING

OTHER CRITICAL AREAS OF ADVOCACY

EFFECTIVE ADVOCACY STRATEGIES

CONCLUSION

REFERENCES

SECTION 11 • Epilepsy Syndromes

CHAPTER 273. OVERVIEW: INTRODUCTION TO EPILEPSY SYNDROMES

REFERENCES

CHAPTER 274. INTRODUCTION TO THE CLASSIFICATION OF EPILEPSY

HISTORICAL PERSPECTIVES

DEFINITIONS OF EPILEPSY

CLASSIFICATIONS OF EPILEPSY

THE 2017 CLASSIFICATION

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 275. SELF-LIMITED (FAMILIAL) NEONATAL EPILEPSY

INTRODUCTION

HISTORICAL PERSPECTIVES: FROM THE EARLY DAYS TO GENE IDENTIFICATION

GENETIC MECHANISMS AND GENOTYPE–PHENOTYPE CORRELATIONS

Functional Studies and Genotype–Phenotype Correlations

EPIDEMIOLOGY

CLINICAL PRESENTATION

DIAGNOSTIC EVALUATION

Interictal and Ictal EEG

Neuroimaging

TREATMENT

PROGNOSIS

DIFFERENTIAL DIAGNOSIS

SUMMARY

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 276. EARLY MYOCLONIC ENCEPHALOPATHY

INTRODUCTION

EPIDEMIOLOGY

ETIOLOGY

CLINICAL PRESENTATION/SEIZURE CHARACTERISTICS

EEG Features

Imaging

Other Laboratory Investigations

Developmental Course

Pathophysiologic Basis

DIFFERENTIAL DIAGNOSIS

TREATMENT

CONCLUSION

REFERENCES

CHAPTER 277. OHTAHARA SYNDROME

INTRODUCTION

HISTORICAL PERSPECTIVE

DEFINITIONS

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

DIAGNOSTIC EVALUATION

Electroencephalographic Findings

Neuroimaging and Other Laboratory Examinations

DIFFERENTIAL DIAGNOSIS

Ohtahara Syndrome and West Syndrome

Ohtahara Syndrome and Early Myoclonic Encephalopathy

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 278. SELF-LIMITED (FAMILIAL) INFANTILE EPILEPSY

INTRODUCTION

HISTORICAL PERSPECTIVE

DEFINITION

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

Self-Limited (Familial) Infantile Epilepsy

Self-Limited Familial Neonatal-Infantile Epilepsy

Self-Limited Infantile Seizures Associated With Mild Gastroenteritis

DIAGNOSTIC EVALUATION

ELECTROENCEPHALOGRAPHIC FINDINGS

NEUROIMAGING AND LABORATORY ASSESSMENT

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 279. EPILEPSY OF INFANCY WITH MIGRATING FOCAL SEIZURES

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITIONS

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

DIAGNOSTIC EVALUATION

Electroencephalographic Findings

Neuroimaging and Laboratory Examinations

Genetic Testing

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 280. INFANTILE EPILEPTIC SPASMS SYNDROME

INTRODUCTION

EPIDEMIOLOGY

ETIOLOGY

Structural

Metabolic

Infectious and immune

Genetic

BASIC MECHANISMS

CLINICAL PRESENTATION

Seizures

Development

DIAGNOSTIC EVALUATION

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 281. DRAVET SYNDROME

DEFINITION AND EPIDEMIOLOGY

CLINICAL AND EEG FEATURES

Clinical Presentation

Triggering Factors

Neurologic Signs

COGNITIVE AND BEHAVIORAL DEVELOPMENT

NEUROIMAGING AND NEUROPATHOLOGY

GENETICS

DIFFERENTIAL DIAGNOSIS

TREATMENT AND MANAGEMENT

Emergency Treatments and Protocols

Treatment Algorithm

Future Perspectives

LONG-TERM OUTCOME

CONCLUSIONS

REFERENCES

CHAPTER 282. MYOCLONIC EPILEPSIES IN INFANCY AND EARLY CHILDHOOD

INTRODUCTION

General Characteristics of Myoclonic Epilepsies

Definition of Epileptic Myoclonus

Clinical and EEG Features Common to the Myoclonic Seizures

DIFFERENTIAL DIAGNOSIS OF MYOCLONIC SEIZURES

ETIOLOGY OF THE MYOCLONIC EPILEPSIES

IDIOPATHIC MYOCLONIC EPILEPSY IN INFANCY

Historical Note and Nomenclature

Epidemiology

Genetics

Personal History

Clinical and EEG Manifestations

Treatment

Long-Term Outcome and Prognosis

IMEI WITH REFLEX SEIZURES

Diagnostic Criteria

Nosologic Place

EPILEPSY WITH MYOCLONIC-ATONIC SEIZURES

Nosologic Aspects

Etiology and Epidemiologic Data

Clinical and EEG Presentation

Course and Outcome

Treatment

REFERENCES

CHAPTER 283. HEMICONVULSION-HEMIPLEGIA-EPILEPSY SYNDROME

INTRODUCTION

HISTORICAL PERSPECTIVES AND DEFINITIONS

AGE AT ONSET

CLINICAL PRESENTATION AND DIAGNOSTIC EVALUATION

ETIOLOGY

PATHOPHYSIOLOGY

MANAGEMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 284. SELF-LIMITED EPILEPSY WITH CENTROTEMPORAL SPIKES

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITIONS

EPIDEMIOLOGY

GENETICS AND BASIC MECHANISMS

CLINICAL PRESENTATION

DIAGNOSTIC EVALUATION

Electroencephalographic Findings

Neuroimaging and Other Laboratory Examinations

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

CHAPTER 285. CHILDHOOD OCCIPITAL VISUAL EPILEPSY AND SELF-LIMITED EPILEPSY WITH AUTONOMIC SEIZURES

INTRODUCTION

HISTORICAL PERSPECTIVES

Self-Limited Epilepsy with Autonomic Seizures

Childhood Occipital Visual Epilepsy

DEFINITIONS

SeLEAS

COVE

EPIDEMIOLOGY

SeLEAS

COVE

ETIOLOGY AND BASIC MECHANISMS

SeLEAS

COVE

CLINICAL PRESENTATION

SeLEAS

COVE

Core Clinical Features in SeLEAS

Frequent Features of Seizures

Less Frequent, but Not Rare, Symptoms

DIAGNOSTIC EVALUATION

Core Clinical Features in COVE

Neuroimaging and Other Laboratory Examinations in SeLEAS and COVE

Electroencephalographic Findings

Other Neurophysiologic Studies in SeLEAS and COVE

DIFFERENTIAL DIAGNOSIS IN SELEAS AND COVE

TREATMENT AND OUTCOME

SeLEAS

COVE

LONG-TERM PROGNOSIS IN SELEAS AND COVE

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

CHAPTER 286. CHILDHOOD AND JUVENILE ABSENCE EPILEPSIES

INTRODUCTION

HISTORICAL PERSPECTIVES

EPIDEMIOLOGY

Childhood Absence Epilepsy

Juvenile Absence Epilepsy

ETIOLOGY

Genetic Factors

Childhood Absence Epilepsy

Juvenile Absence Epilepsy

Acquired Factors

CLINICAL PRESENTATION

Childhood Absence Epilepsy

Juvenile Absence Epilepsy

Cognitive and Psychiatric Comorbidity

DIAGNOSTIC EVALUATION

Electroencephalographic Findings

Neuroimaging

DIFFERENTIAL DIAGNOSIS

Within Generalized Genetic Epilepsies

From Focal Epilepsies

TREATMENT

SAFETY: PARTICIPATION IN SPORTS AND DRIVING

OUTCOME

Childhood Absence Epilepsy

Juvenile Absence Epilepsy

Social Prognosis of CAE/JAE

REFERENCES

CHAPTER 287. EPILEPSY WITH MYOCLONIC ABSENCES

INTRODUCTION

CLINICAL DATA

General Remarks

Myoclonic Absences

Seizures Other Than Myoclonic Absences

Neurologic and Neuropsychologic Examination

NEUROPHYSIOLOGIC DATA

Interictal EEG

Ictal EEG

Sleep EEG

EVOLUTION

DIAGNOSIS

TREATMENT

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 288. LENNOX–GASTAUT SYNDROME

INTRODUCTION

HISTORICAL PERSPECTIVE

DEFINITIONS

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

Interictal EEG

Seizures

Clinical Variants

DIAGNOSTIC EVALUATION

DIFFERENTIAL DIAGNOSIS

Infantile Epileptic Spasms Syndrome (IESS)

Dravet Syndrome

Epilepsy with Myoclonic Atonic Seizures

Developmental and/or Epileptic Encephalopathy with Spike-Wave Activation in Sleep

Focal Motor Seizures

Metabolic Disorders

Drug-Related Exacerbation of Epilepsy Etiologies

Specific Genetic Etiologies

TREATMENT

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 289. ENCEPHALOPATHY RELATED TO STATUS EPILEPTICUS DURING SLOW SLEEP (ESES) INCLUDING LANDAU KLEFFNER SYNDROME

INTRODUCTION

EPIDEMIOLOGY

ETIOLOGY

Personal Antecedents

Genetics

CLINICAL AND NEUROPHYSIOLOGIC FEATURES

Epilepsy

Encephalopathy

EEG

Auditory Evoked Potentials

PHYSIOPATHOGICAL MECHANISMS

The Mechanism Generating SES

Role of Sleep in Cognition in the Developmental Age and Interference by Sleep-Related Epileptiform EEG Activities

DIFFERENTIAL DIAGNOSIS

TREATMENT

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 290. RASMUSSEN SYNDROME

INTRODUCTION

HISTORICAL PERSPECTIVE

EPIDEMIOLOGY

ETIOLOGY AND PATHOGENESIS OF RASMUSSEN ENCEPHALITIS

CLINICAL PRESENTATIONS

Typical Course of the Disease

Clinical Variants of Rasmussen Encephalitis

DIAGNOSIS

Electroencephalographic Findings

Structural Imaging

Functional Imaging

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

Antiseizure Medication Therapy

Antiviral Therapy

Immune Therapy

Microglia-Activation–Mediated Neurodegeneration

Interferon-α

Steroids

Immunoglobulins

Plasmapheresis and Selective IgG Immunoadsorption

Immunosuppressive Therapy

Future Evolving Medical Therapies: Immunosuppressive or Immunomodulatory Treatment

Surgery

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 291. JUVENILE MYOCLONIC EPILEPSY

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITIONS

EPIDEMIOLOGY

Prevalence

Sex Ratio

Age of Onset

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

DIAGNOSTIC EVALUATION

Electroencephalographic Findings

Neuroimaging

Biochemical Studies

Genetic Studies

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 292. GENERALIZED TONIC–CLONIC SEIZURES ALONE AND EPILEPSY WITH GENERALIZED TONIC–CLONIC SEIZURES ON AWAKENING

GENERALIZED TONIC–CLONIC SEIZURES ALONE

EPILEPSY WITH GTCS ON AWAKENING

Preamble

Historical Perspective

Definitions

Etiology and Basic Mechanisms

Clinical Presentation

Diagnostic Evaluation

Differential Diagnosis

Treatment and Outcome

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 293. MESIAL TEMPORAL LOBE EPILEPSY WITH HIPPOCAMPAL SCLEROSIS

INTRODUCTION

DEFINITIONS

HISTORICAL PERSPECTIVES AND PREVIOUS TERMS

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

Evidence for Progression

Clinical Seizure Characteristics

Nonictal Manifestations of Temporal Lobe Epilepsy

DIAGNOSTIC EVALUATION

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 294. FAMILIAL TEMPORAL LOBE EPILEPSIES

INTRODUCTION

HISTORICAL PERSPECTIVE

DEFINITIONS

Familial Mesial Temporal Lobe Epilepsy

Familial Temporal Lobe Epilepsy With Auditory Features

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

Familial Mesial Temporal Lobe Epilepsy

Familial Temporal Lobe Epilepsy With Auditory Features

DIAGNOSTIC EVALUATION

Electroencephalographic Findings

Neuroimaging and Other Laboratory Examinations

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 295. FAMILIAL FRONTAL LOBE EPILEPSIES AND FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI

INTRODUCTION

FAMILIAL FRONTAL LOBE EPILEPSIES

Historical Perspectives

Definitions

Epidemiology

Etiology and Basic Mechanisms

Clinical Presentation

Diagnostic Evaluation

Differential Diagnosis

Treatment and Outcome

Long-term Prognosis

Summary and Conclusions

FAMILIAL FOCAL EPILEPSY WITH VARIABLE FOCI

Historical Perspectives

Definitions

Epidemiology

Etiology and Basic Mechanisms

Clinical Presentation

Diagnostic Evaluation

Differential Diagnosis

Treatment and Outcome

Long-Term Prognosis

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 296. GELASTIC SEIZURES AND HYPOTHALAMIC HAMARTOMAS

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITIONS

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

DIAGNOSTIC EVALUATION

EEG Findings

MRI

PET and SPECT Imaging

DIFFERENTIAL DIAGNOSIS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 297. PROGRESSIVE MYOCLONUS EPILEPSIES

THE PME SYNDROME AND ITS PHENOTYPIC LIMITS

GENETIC AND CLINICAL PHENOTYPIC FEATURES

Unverricht–Lundborg Disease

Lafora Disease

Neuronal Ceroid Lipofuscinoses

Myoclonic Epilepsy with Ragged Red Fibers

Action Myoclonus Renal Failure

Myoclonic Epilepsy and Ataxia Due to Potassium Channel Mutation

GOSR2 “North Sea” PME

Sialidosis

Dentatorubropallidoluysian Atrophy

KCTD7-Related PME

Gaucher Disease

Spinal Muscular Atrophy–Progressive Myoclonus Epilepsy

Neuroserpinopathy

RARE AND EMERGING CAUSES OF PME

TREATMENT STRATEGIES IN PME

Dietary Modification

Neuromodulatory Therapies

Immunomodulatory Therapies

Enzyme-Replacement Therapies

Gene Therapies

REFERENCES

CHAPTER 298. POSTTRAUMATIC SEIZURES

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITIONS

EPIDEMIOLOGY

Traumatic Brain Injury

Epidemiologic Studies of Seizures After Traumatic Brain Injury

Characterization and Background of Impact Convulsions

Immediate and Early Seizures

Early Posttraumatic Seizures and Secondary Brain Injury

Late Seizures

Seizure Type of Late Seizures

Seizure Recurrence

Prevalence of Posttraumatic Epilepsy

Association of TBI and PTE With Cognitive and Psychiatric Comorbidities

Modalities of Traumatic Brain Injury and Posttraumatic Epilepsy

Posttraumatic Epilepsy Is Mechanistically Heterogeneous

Multiple Pathophysiologic Mechanisms May Contribute to Posttraumatic Epilepsy

RISK FACTORS FOR POSTTRAUMATIC EPILEPSY

Suggested Pathophysiologic Risk Factors for Posttraumatic Epilepsy

Possible Electrophysiologic Biomarkers for PTE

CLINICAL CONSIDERATIONS FOR SEIZURES AND EPILEPSY AFTER TBI

Clinical Presentation

Acute Seizures, Ictal–Interictal Continuum, and Secondary Brain Injury

DIAGNOSTIC EVALUATIONS

Electroencephalographic Findings

Neuroimaging and Other Laboratory Examinations

DIFFERENTIAL DIAGNOSIS

Nonepileptic Seizures After TBI

TREATMENT AND OUTCOMES

Management of Posttraumatic Seizures

TREATMENT OF POSTTRAUMATIC EPILEPSY

Efficacy of Surgical Therapy for Posttraumatic Epilepsy in Selected Cases

Failure of Clinical Trials in TBI

SUPPORTIVE THERAPY

LONG-TERM PROGNOSIS

REFERENCES

CHAPTER 299. ISOLATED SEIZURES

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITIONS AND NOSOLOGIC PLACE

EPIDEMIOLOGY

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

RISK FOR RELAPSE

PROVOCATION OF ISOLATED SEIZURES

HOW EPILEPSY EVOLVES FROM A FIRST SEIZURE

DIAGNOSTIC EVALUATION

DIFFERENTIAL DIAGNOSIS

TREATMENT AND OUTCOME

LONG-TERM PROGNOSIS

CONCLUSION

REFERENCES

CHAPTER 300. GENETIC EPILEPSY WITH FEBRILE SEIZURES PLUS

INTRODUCTION

HISTORICAL PERSPECTIVES

DEFINITION AND EPIDEMIOLOGY OF GENETIC EPILEPSY WITH FEBRILE SEIZURES PLUS

ETIOLOGY AND BASIC MECHANISMS

CLINICAL PRESENTATION

Febrile Seizures

Febrile Seizures Plus

Febrile Seizures or Febrile Seizures Plus with Other Seizure Type

Epilepsy with Myoclonic-Atonic Seizures

Dravet Syndrome

Focal Epilepsies

DIAGNOSTIC EVALUATION

DIFFERENTIAL DIAGNOSIS

TREATMENT

LONG-TERM PROGNOSIS

Febrile Seizures

Febrile Seizures or Febrile Seizures Plus with Other Seizure Type

Doose Syndrome

GENETIC COUNSELING

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 301. REFLEX EPILEPSIES

DEFINITIONS

PHOTOSENSITIVITY

HOT WATER OR BATHING EPILEPSY

MUSICOGENIC EPILEPSY

THINKING (NOOGENIC) EPILEPSY

EPILEPSY WITH SOMATOSENSORY-STIMULATION–INDUCED SEIZURES

EPILEPSY WITH PROPRIOCEPTION-INDUCED SEIZURES

EATING EPILEPSY

READING EPILEPSY

SEXUAL/ORGASMIC EPILEPSY

EPILEPSY WITH PRAXIS-INDUCED REFLEX SEIZURES

SUMMARY

REFERENCES

CHAPTER 302. MALFORMATIONS OF CORTICAL DEVELOPMENT IN EPILEPSY

MALFORMATIONS RELATED TO ABNORMAL PROLIFERATION OF NEURONS AND GLIA

Megalencephaly, Hemimegalencephaly, Focal Cortical Dysplasia

MALFORMATIONS DUE TO ABNORMAL NEURONAL MIGRATION

Gray Matter Heterotopia

Periventricular Nodular Heterotopia

Lissencephaly and Subcortical Band Heterotopia (Agyria–Pachygyria-Band Spectrum)

Other Rare Genetic Causes of Lissencephaly or SBH

Tubulinopathies and Related Disorders

MALFORMATIONS RELATED TO ABNORMAL CORTICAL ORGANIZATION

Polymicrogyria

REFERENCES

CHAPTER 303. CHROMOSOMAL ABNORMALITIES IN EPILEPSY

INTRODUCTION

CYTOGENETIC AND MOLECULAR TECHNIQUES FOR DIAGNOSTICS

MAIN, RECURRENT, CHROMOSOMAL ABNORMALITIES, AND CNVS ASSOCIATED WITH EPILEPSY

Epilepsy in Syndromic Patients With Numeric Chromosomal Aberrations and Microdeletions

Other Recognizable and Rare Chromosomal Anomalies in Patients with Epilepsy

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 304. INHERITED METABOLIC DISORDERS AND EPILEPSY

INTRODUCTION

METABOLIC DISORDERS OF THE NEONATAL PERIOD

Aminoacidurias

Organic Acidurias

Dihydropyrimidine Dehydrogenase Deficiency (#274270)

Peroxisomal Diseases

Mitochondrial Disorders

Disorders of the Urea Cycle

Disorders of Carbohydrate Metabolism

Disorders of Vitamin Metabolism

METABOLIC DISORDERS OF EARLY INFANCY

Aminoacidurias

Lysosomal Disorders

Disorders of Vitamin Metabolism

Glucose Transporter Type 1 Deficiency Syndrome

Congenital Disorders of Glycosylation

Organic Acidurias

Defects of the Urea Cycle

Disorders of γ-Aminobutyric Acid Metabolism

Menkes Disease (#309400)

METABOLIC DISORDERS OF LATE INFANCY

Metachromatic Leukodystrophy

Mucopolysaccharidoses

Neuronal Ceroid Lipofuscinoses

METABOLIC DISORDERS OF CHILDHOOD AND ADOLESCENCE

Homocystinuria

Adrenoleukodystrophy

Lysosomal Disorders

Progressive Myoclonus Epilepsies

DIAGNOSTIC INVESTIGATION

TREATMENT

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 305. MITOCHONDRIAL DISEASES AND EPILEPSY

INTRODUCTION

CLINICAL DESCRIPTION

Mitochondrial Encephalomyopathies Associated With mtDNA Mutations

Mitochondrial Encephalomyopathies Associated With Nuclear Mutations

EPILEPTIC SEIZURES

Kearns–Sayre Syndrome

Myoclonus Epilepsy With Ragged-Red Fibers

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

Other Mitochondrial Encephalomyopathies With Epilepsy Due to mtDNA Point Mutations

Mitochondrial Encephalomyopathies Associated With Nuclear Mutations

DIAGNOSTIC INVESTIGATION

Clinical Issues

Clinical Laboratory Tests

Special Laboratory Tests

TREATMENT

Symptom Management

Metabolic Therapy

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 306. SEIZURES IN NEONATAL HYPOXIC–ISCHEMIC ENCEPHALOPATHY

INTRODUCTION

DEFINITIONS

CLINICAL DIAGNOSIS OF HIE

Contributing Factors and Diagnostic Considerations

Criteria for Treatment With Therapeutic Hypothermia

PATHOPHYSIOLOGY OF HIE

Experimental Models

Evolution of Injury in Hypoxia–Ischemia

Mechanisms of Neuroprotection With Therapeutic Hypothermia

ACUTE SYMPTOMATIC SEIZURES IN HIE

Incidence of Seizures in Clinical HIE

Pathophysiology of Increased Seizure Susceptibility of the Neonatal Brain

Diagnosis of Seizures in Clinical HIE

Treatment of Neonatal Seizures Due to HIE

DEVELOPMENT OF EPILEPSY AFTER HIE

Epileptogenesis in the Developing Brain

Risk Factors for Epilepsy Following HIE

CONCLUSIONS

REFERENCES

CHAPTER 307. CENTRAL NERVOUS SYSTEM TUMORS AND SEIZURES: EPIDEMIOLOGY, DIAGNOSIS, AND MANAGEMENT

NEOPLASTIC DISEASES: INTRODUCTION

HISTORICAL PERSPECTIVES

EPIDEMIOLOGY

The Influence of Tumor Location and Growth Rate on Seizure Frequency

Biologic Factors

Epilepsy in Glioneuronal Tumors and Gliomas

Epilepsy in Meningiomas and Brain Metastases

CLINICAL PRESENTATION

Seizure Types in Tumor-Associated Epilepsies

Status Epilepticus in Patients With Brain Tumor

DIFFERENTIAL DIAGNOSIS

DIAGNOSTIC EVALUATION

Neuroimaging

Laboratory Investigations

Neurophysiologic Studies

The Role of Neuropsychological Evaluation

ANTISEIZURE MEDICATION THERAPY

Pharmacotherapeutic Aspects of Tumor-Associated Epilepsy

Potential Synergistic Antitumor Effects of ASM With Concurrent Chemotherapy or Radiation

Prophylactic ASM Use

Withdrawal of ASM Therapy in Brain Tumor Patients With Seizures

SURGICAL THERAPY

Lesionectomy Versus More Extensive Surgery

Electrocorticography in Tumor Surgery

RADIATION THERAPY AND CHEMOTHERAPY

Seizures as Prognostic Indicator in Gliomas

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 308. INFECTIOUS DISEASES AND SEIZURES OR EPILEPSY

PARASITIC INFECTIONS

Neurocysticercosis

Cerebral Malaria

Other Parasitic Diseases of the CNS

BACTERIAL INFECTIONS

Pyogenic Meningitis

Brain Abscess

Empyemas

Tuberculosis of the CNS

VIRAL INFECTIONS

Viral Encephalitis

Acquired Immunodeficiency Syndrome

REFERENCES

CHAPTER 309. ACUTE SYMPTOMATIC SEIZURES SECONDARY TO AUTOIMMUNE ENCEPHALITIS AND AUTOIMMUNE-ASSOCIATED EPILEPSIES

INTRODUCTION

DEFINITIONS

ACUTE SYMPTOMATIC SEIZURES SECONDARY TO AUTOIMMUNE ENCEPHALITIS

Clinical and Paraclinical Features of Seizures Secondary to Autoimmune Encephalitis

Specific Antibody Syndromes

AUTOIMMUNE-ASSOCIATED EPILEPSIES

Clinical and Paraclinical Features of Autoimmune Associated Epilepsies

Frequency of Autoantibody Positivity in Epilepsy Cohorts

Specific Antibodies in Autoimmune-Associated Epilepsy

Postencephalitic Epilepsy

DIAGNOSTIC APPROACH

Antibody Testing

Clinical and Paraclinical Investigations

Malignancy Screening

TREATMENT APPROACH AND OUTCOMES

General Treatment Approach

Outcomes

Predictive Outcome Scales

Clinical Trials

CONCLUSIONS

REFERENCES

CHAPTER 310. ELECTROLYTE, SPORADIC METABOLIC, AND ENDOCRINE DISORDERS IN EPILEPSY

INTRODUCTION

ELECTROLYTE DISORDERS

Sodium Electrolyte Disorders: Hyponatremia

Magnesium Electrolyte Disorders: Hypomagnesemia

RENAL FAILURE

Uremic Encephalopathy

Aluminum Encephalopathy Syndrome in Infancy and Childhood

Dialysis Disequilibrium Syndrome

Dialysis Encephalopathy Syndrome

ENDOCRINE DISORDERS

Hypothalamic–Pituitary Disorders

Thyroid Disorders

Parathyroid Disorders

Pancreas Disorders

Reproductive Endocrine Disorders

DISEASES OF THE GASTROINTESTINAL SYSTEM

Celiac Disease

Other Gastrointestinal Diseases and Epilepsy

Hepatic Disorders

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 311. THE RELATIONSHIP OF ALCOHOL AND SUBSTANCE MISUSE/ABUSE TO SEIZURES AND EPILEPSY

INTRODUCTION

ALCOHOL

Direct Alcohol Effects

Indirect Effects of Alcohol

Treatment of Alcohol Withdrawal Syndrome and Alcohol-Related Seizures

Alcohol Withdrawal Syndrome

Advice Concerning Drinking Alcohol in People With Epilepsy

SEDATIVE AND HYPNOTIC WITHDRAWAL SEIZURES

RECREATIONAL (ABUSED) DRUGS (CANNABINOIDS, COCAINE, PSYCHOSTIMULANTS)

Amphetamines

Cannabinoids

Cocaine

Dextromethorphan

Dissociative Anesthetics

Hallucinogens

Opioids

Summary of Illicit Substances

PRESCRIBED (LEGAL) STIMULANTS

Prescribed or Illicit Use of ASM

MANAGEMENT ISSUES

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 312. DISORDERS OF PREGNANCY IN EPILEPSY

INTRODUCTION

CARE IN CHILDHOOD AND ADOLESCENCE

CARE DURING CHILDBEARING YEARS

MANAGEMENT OF EPILEPSY DURING PREGNANCY

POSTPREGNANCY CONCERNS

ASM Dose Adjustments

Breastfeeding

Postpartum Depression

ECLAMPSIA

SEIZURE OCCURRENCE DURING PREGNANCY

SUMMARY

REFERENCES

CHAPTER 313. NEW-ONSET REFRACTORY STATUS EPILEPTICUS AND FEBRILE INFECTION-RELATED EPILEPSY SYNDROME

DEFINITION OF NORSE AND FIRES

HISTORY

EPIDEMIOLOGY OF NORSE AND FIRES

CLINICAL FEATURES OF NORSE AND FIRES

DIFFERENTIAL DIAGNOSIS AND MOST FREQUENTLY IDENTIFIED ETIOLOGIES

PATHOPHYSIOLOGY OF CRYPTOGENIC CASES

DIAGNOSTIC WORKUP OF NORSE AND FIRES

Laboratory

Electroencephalogram

Neuroimaging

TREATMENT OF NORSE AND FIRES

OUTCOME OF NORSE AND FIRES

CONCLUSION

REFERENCES

SECTION 12 • Disorders That Can Resemble Epilepsy

CHAPTER 314. OVERVIEW: DISORDERS THAT CAN RESEMBLE EPILEPSY

IMITATORS OF SEIZURES OF ORGANIC TYPE

Medical Disorders

Neurologic Disorders

Imitators of Seizures of Psychogenic Type

CONCLUDING REMARKS

REFERENCES

CHAPTER 315. SYNCOPE RESEMBLING SEIZURES

DEFINITIONS

INCIDENCE, PROGNOSIS, AND COST

CLINICAL DESCRIPTION

Classic Symptoms

Syncopal Convulsions/Syncopal Myoclonus

EEG Appearance

DIFFERENTIAL DIAGNOSIS

Disorders of Orthostatic Intolerance

Primary Cardiac Dysfunction

Metabolic Disorders

Psychiatric Disorders

Epilepsy and Other Neurologic Disorders

DIAGNOSTIC EVALUATION

History

Physical Examination

EKG/Cardiac Monitoring

Echocardiography

Tilt-Table Testing

EEG

Neuroimaging

Wearable Technology

TREATMENT

SUMMARY

REFERENCES

CHAPTER 316. METABOLIC AND ENDOCRINE DISORDERS RESEMBLING SEIZURES

INTRODUCTION

GENERAL COMMENTS REGARDING PATIENT HISTORY

SPECIFIC METABOLIC AND ENDOCRINE DISORDERS

Conditions That Can Mimic Seizures

Conditions That Can Cause or Mimic Seizures

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 317. NONEPILEPTIC NEUROLOGIC PAROXYSMAL DISORDERS AND EPISODIC SYMPTOMS IN INFANTS

INTRODUCTION

ENHANCED NORMAL PHENOMENA AND OTHER PAROXYSMAL EPISODES

Sporadic Myoclonic Jerks During Sleep or Physiologic Sleep Myoclonus

Localized Myoclonus during Wakefulness

Startle Responses

Bruxism

Nonepileptic Apnea

TRANSIENT OR BENIGN MOVEMENT DISORDERS

Benign Neonatal Sleep Myoclonus

Tonic Reflex Seizures of Early Infancy

Head Atonic Attacks in Infancy

Benign Myoclonus of Early Infancy or Fejerman Syndrome

Benign Paroxysmal Tonic Upward Gaze

Transient Paroxysmal Dystonia

Benign Paroxysmal Torticollis

Adverse Reactions to Exogenous Agents

HABIT-TYPE MOVEMENT AND SELF-GRATIFICATION EPISODES

Head Banging, Head Rolling, Rocking, and Other Stereotypic Movements

Masturbation-Like Episodes

SYMPTOMATIC ABNORMAL MOVEMENTS

Neonatal Posturing and Other Nonepileptic Episodes

Opsoclonus–Myoclonus Syndrome

Bobble-head Doll Syndrome

Encephalopathic Nonepileptic Myoclonus

OTHER NEUROLOGIC CONDITIONS WITH EPISODIC SYMPTOMS

Hyperekplexia

Cogan Oculomotor Apraxia

Benign Paroxysmal Vertigo

Spasmus Nutans

Alternating Hemiplegia of Childhood

Paroxysmal Dystonia and Choreoathetosis

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 318. MIGRAINE RESEMBLING SEIZURES

INTRODUCTION

CLASSIFICATION

Migraine

Aura

Mechanisms of Aura

Headache Phase

Postdrome or Postictal Phase

FORMAL INTERNATIONAL CLASSIFICATION OF HEADACHE DISORDERS-3 CLASSIFICATION

Migraine without Aura (Common Migraine)

Migraine With Aura (Classic Migraine)

MIGRAINE SUBTYPES

Migraine With Brainstem Aura (Formerly Basilar-Type Migraine)

Benign Paroxysmal Vertigo of Childhood (ICHD-3 1.6.2)

Aura without Headache (ICHD-3 1.2.1.2)

Migraine Aura–Triggered Seizure (ICHD-3 1.4.4)

EPIDEMIOLOGIC CONNECTIONS BETWEEN MIGRAINE AND EPILEPSY

INTERRELATIONSHIPS BETWEEN HEADACHE AND EPILEPSY

Headache as a Consequence of Seizures

Migraine–Epilepsy Syndromes

DIFFERENTIAL DIAGNOSIS AND CONCOMITANT DIAGNOSIS OF MIGRAINE AND EPILEPSY: CLINICAL AND ELECTROENCEPHALOGRAPHIC FEATURES

TREATMENT CONSIDERATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 319. CEREBROVASCULAR DISORDERS RESEMBLING SEIZURES

INTRODUCTION

EPIDEMIOLOGY

TREATMENT

NOSOLOGY OF TRANSIENT ISCHEMIC ATTACKS

PREVALENCE AND INCIDENCE OF TRANSIENT ISCHEMIC ATTACKS

NATURAL HISTORY OF TRANSIENT ISCHEMIC ATTACKS

DIAGNOSTIC DIFFICULTY

TYPICAL TRANSIENT ISCHEMIC ATTACK SYMPTOMS

TYPICAL TIME COURSE OF TRANSIENT ISCHEMIC ATTACKS

ATYPICAL TRANSIENT ISCHEMIC ATTACK PRESENTATIONS

Limb-shaking Carotid Transient Ischemic Attacks

Unilateral Asterixis

Episodic Dyskinesia

Pure Sensory Spells

Speech Arrest

Visual Inversion

Visual Hallucinations

Brainstem Auditory Hallucinosis

Auditory Aprosodia

Transient Anosognosia

Akinetic Mutism

Drop Attacks

Moyamoya Disease

SUMMARY AND CONCLUSIONS

ADDITIONAL INFORMATION

REFERENCES

CHAPTER 320. SLEEP AND EPILEPSY: SEIZURE MIMICS AND SLEEP

EPILEPSY AND BIOLOGIC RHYTHMS

Circadian Rhythm

Ultradian Rhythm

Antiseizure Influence on Ultradian Rhythm and Sleepiness

Multidien Rhythm

SLEEP DISORDER MIMICS OF EPILEPSY

Sleep Disorders in Epilepsy

Nocturnal Frontal Lobe Epilepsy/Sleep-Related Hypermotor Epilepsy

Disorders of Central Hypersomnolence

Sleep-Related Movement Disorders

CONCLUSIONS

REFERENCES

CHAPTER 321. MYOCLONUS AND MYOCLONIC SYNDROMES

INTRODUCTION

CLINICAL DESCRIPTION

CLASSIFICATION

EPILEPTIC MYOCLONUS

Progressive Myoclonus Epilepsies

Dementias

Viral Encephalopathies

Metabolic Encephalopathies Including Endocrine Disorders

Autoimmune Disorders

Toxic Encephalopathies Including Drug Side Effects

Physical Encephalopathies Including Hypoxia

Focal Brain Damage

NONEPILEPTIC MYOCLONUS

Dystonic Myoclonus and Fragments of Other Involuntary Movement Disorders

Essential Myoclonus

Exaggerated Startle

Periodic Movements in Sleep

Segmental Myoclonus Including Spinal Myoclonus and Palatal Myoclonus

Asterixis

Functional (Psychogenic) Myoclonus

DIAGNOSTIC INVESTIGATION

TREATMENT

Epileptic Myoclonus

Essential Myoclonus

Exaggerated Startle

Periodic Movements in Sleep

Segmental Myoclonus

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 322. MOVEMENT DISORDERS RESEMBLING SEIZURES

INTRODUCTION

INFANTS

Myoclonus

Tremor and Oscillatory Movements

Dystonia

CHILDREN

Stereotypies and Tics

Paroxysmal Disorders

ADULTS

Functional Movement Disorders

Autoimmune Movement Disorders

Cortical Tremor

Staring Episodes in Lewy Body Dementia

Hemifacial Spasm

REFERENCES

CHAPTER 323. MOVEMENT DISORDERS: DYSKINESIAS

INTRODUCTION

PAROXYSMAL DYSKINESIAS—HISTORY

PAROXYSMAL KINESIGENIC DYSKINESIA

Clinical Features

Idiopathic Paroxysmal Dyskinesias

Symptomatic Paroxysmal Dyskinesias

PAROXYSMAL NONKINESIGENIC DYSKINESIA

Clinical Features

Idiopathic Nonkinesigenic Dyskinesias

Symptomatic Paroxysmal Nonkinesigenic Dyskinesia

PAROXYSMAL EXERTIONAL DYSKINESIA

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

CHAPTER 324. SENSORY DISORDERS RESEMBLING SEIZURES

INTRODUCTION

DISORDERS OF OLFACTION

DISORDERS OF VISION

DISORDERS OF HEARING

DISORDERS OF THE VESTIBULAR SYSTEM

DISORDERS OF THE SOMATOSENSORY SYSTEM

DISORDERS OF THE AUTONOMIC (VISCERAL) SENSORY SYSTEM

PSYCHOGENIC SENSORY SYMPTOMS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 325. OTHER NEUROLOGIC EVENTS RESEMBLING EPILEPTIC SEIZURES

INTRODUCTION

TRANSIENT GLOBAL AMNESIA AND ITS DIFFERENTIATION FROM TRANSIENT EPILEPTIC AMNESIA

MOVEMENTS THAT MAY MIMIC SEIZURE ACTIVITY IN THE COMATOSE PATIENT

Decorticate and Decerebrate Posturing

Paroxysmal Sympathetic Hyperactivity Following Acquired Brain Injury

Involuntary Focal and Segmental Movements

DEMYELINATION AND PAROXYSMAL DYSKINESIA AS A POTENTIAL SEIZURE MIMIC

CONCLUSION

REFERENCES

CHAPTER 326. OVERVIEW: PSYCHIATRIC DISTURBANCES

INTRODUCTION

HISTORICAL PERSPECTIVE

CURRENT CHALLENGES

THE PROBLEM WITH SEIZURE MISDIAGNOSIS

WHAT CAN WE DO BETTER?

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 327. PSYCHOGENIC NONEPILEPTIC SEIZURES IN ADULTS

INTRODUCTION

NOMENCLATURE

EPIDEMIOLOGY OF PSYCHOGENIC NONEPILEPTIC SEIZURES

DIAGNOSIS OF PNES

ETIOLOGY

Stressors (Trauma, Abuse, and Stressful Life Events)

Acute and Persistent Stress

Dysfunctional Relationships and Attachment

Illness Beliefs

PSYCHIATRIC COMORBIDITY

Dissociative and Functional Disorders

Posttraumatic Stress Disorder

Personality Disorder

Depression and Anxiety

Factitious Disorder

Malingering

MEDICAL AND NEUROLOGIC COMORBIDITY

Epilepsy and Epilepsy Surgery

Traumatic Brain Injury

Cognitive Complaints

Chronic Pain

Migraine

Asthma

TREATMENT

SUMMARY AND CONCLUSION

REFERENCES

CHAPTER 328. PSYCHOGENIC NONEPILEPTIC SEIZURES IN PEDIATRIC PATIENTS

INTRODUCTION

RISK FACTORS

ASSESSMENT AND DIAGNOSIS

CLINICAL PNES CHARACTERISTICS AND COMORBIDITIES

TREATMENT

OUTCOME

SUMMARY

REFERENCES

CHAPTER 329. DISORDERS OF IMPULSE CONTROL IN EPILEPSY

INTRODUCTION

IMPULSIVE AGGRESSION IN EPILEPSY

TREATMENT OF AGGRESSION IN EPILEPSY

EPILEPSY AND OTHER DISORDERS OF IMPULSE CONTROL

CONCLUSION

REFERENCES

CHAPTER 330. DISSOCIATIVE DISORDERS

INTRODUCTION

THE CONCEPT OF DISSOCIATION: A HISTORICAL BACKGROUND

Origins of Dissociation

Division of Consciousness: Dissociation as Seen in Hysteria

Psychoanalytic Theories

Modern Theories

EPIDEMIOLOGY OF DISSOCIATIVE DISORDERS

PHENOMENOLOGY OF DISSOCIATION AND NOSOLOGIC CLASSIFICATION OF DISSOCIATIVE DISORDERS

Specific DSM-5 Dissociative Disorders

NEUROBIOLOGIC MECHANISMS OF DISSOCIATIVE DISORDERS

MEASURES OF DISSOCIATION

DIFFERENTIAL DIAGNOSIS

TREATMENT OF DISSOCIATIVE DISORDERS

Psychotherapy

Pharmacologic Treatment and Neuromodulation

CONCLUSIONS

REFERENCES

CHAPTER 331. PANIC DISORDER AND HYPERVENTILATION SYNDROME

INTRODUCTION

PANIC ATTACKS AND PANIC DISORDER

Epidemiologic Aspects

Clinical Manifestations

Localization of Ictal Fear

Differential Diagnosis

Diagnostic Evaluations

Treatment Strategies

HYPERVENTILATION SYNDROME

Historical Aspects

Clinical Manifestations

Physiopathologic Aspects

Differential Diagnosis

Treatment of HVS

HV-Induced Epileptic Seizures

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 332. OBSESSIVE-COMPULSIVE BEHAVIOR

INTRODUCTION

CLINICAL PRESENTATION

Obsessive-Compulsive Disorder

Obsessive-Compulsive–Related Disorders

The Neuroanatomy of Obsessive-Compulsive Behavior—Results of Neuroimaging Studies in Obsessive-Compulsive Disorder

Putative Neuroanatomic Model

DIFFERENTIAL DIAGNOSIS

INVESTIGATIONS

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 333. PSYCHOTIC SYMPTOMS MIMICKING EPILEPTIC SEIZURES

INTRODUCTION

PSYCHOTIC SYMPTOMS AS AN EXPRESSION OF EPILEPTIC SEIZURES

Ictal Psychotic Symptoms and Episodes

PSYCHOTIC SYMPTOMS AS AN EXPRESSION OF NONCONVULSIVE STATUS EPILEPTICUS

Psychiatric Manifestations of Absence Status Epilepticus

POSTICTAL PSYCHOTIC SYMPTOMS

FORCED NORMALIZATION OR ALTERNATIVE PSYCHOSIS

SUMMARY AND CONCLUSION

REFERENCES

SECTION 13 • Delivery of Health Care in People with Epilepsy

CHAPTER 334. OVERVIEW: DELIVERY OF HEALTH CARE AND SOCIOECONOMIC ISSUES IN PEOPLE WITH EPILEPSY

INTRODUCTION

LEVELS OF CARE

Primary Care

Secondary Care

Tertiary Care

Specialized Centers or Fourth-level Care

Stepped Model of Epilepsy Care

SOCIOECONOMIC CONSIDERATIONS

Government versus Private Bureaucracy

Gap in Epilepsy Care With Private Health Care

DEVELOPMENT OF EPILEPSY CARE

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENT

REFERENCES

CHAPTER 335. EPILEPSY IN AFRICA

EPIDEMIOLOGY

PREVALENCE AND BURDEN OF DISEASE

Risk Factors (Secondary Causes)

Health Care Services for People with Epilepsy in SSA

CONCLUSION

REFERENCES

CHAPTER 336. EPILEPSY IN ARGENTINA

INTRODUCTION

THE ARGENTINE HEALTH CARE SYSTEM

LEVELS OF MEDICAL CARE

NEUROLOGISTS AND CHILD NEUROLOGISTS

DATA ON EPILEPSY

ANTISEIZURE MEDICATIONS

PSYCHOSOCIAL ASPECTS

NEUROLOGY AND EPILEPSY TRAINING AND RESEARCH

SCIENTIFIC SOCIETIES

ADVOCACY AND PARENT ASSOCIATIONS

THE LAW ON EPILEPSY

NATIONAL PROGRAM

TELEMEDICINE IN EPILEPSY

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 337. EPILEPSY IN ASIA

INTRODUCTION

SOCIOECONOMIC BACKGROUND

EPIDEMIOLOGY

CAUSES

EPILEPSY CARE

Low Number of Neurologists in South and South East Asia

Antiseizure Medications

Neuroimaging, EEG, and Epilepsy Surgery

Treatment Gap

PSYCHO-CULTURAL ISSUES AND STIGMA

SOUTH EAST ASIA

Epidemiology

Aetiology

Status Epilepticus

Alternative Medicine

Compliance to Medication

Psychiatric Comorbidities

PAKISTAN, BANGLADESH, NEPAL, SRI LANKA

Pakistan

Bangladesh

Nepal

Sri Lanka

NORTH EAST ASIA OTHER THAN CHINA, JAPAN, AND SOUTH KOREA

North Korea

Taiwan

Hong Kong

Mongolia

THE PACIFIC ISLANDS

EPILEPSY ORGANIZATIONS

RESEARCH

REGIONAL NETWORKING

REFERENCES

CHAPTER 338. EPILEPSY IN BRAZIL

INTRODUCTION

GENERAL DATA ON THE HEALTH SYSTEM

EPILEPSY DATA

ANTISEIZURE MEDICATIONS

Clinicians and Neurologists

Drug Consumption and Treatment

THE SISTEMA ÚNICO DE SAúDE: A WORLD REFERENCE HEALTH SYSTEM

EPILEPSY IN BRAZIL

Types of Seizures and Epilepsy

Etiologies

Psychosocial Aspects

THE ROLE OF SOCIETIES

Brazilian Societies

Lay-People Associations and the National Demonstration Project on Epilepsy

HIGHLIGHTS OF BRAZILIAN SCIENTIFIC CONTRIBUTIONS TO EPILEPTOLOGY

Paulo Niemeyer Soares and the Transventricular Amygdalohippocampectomy

Esper Abrão Cavalheiro and the Pilocarpine Epilepsy Model

The Brazilian Program for Epilepsy Surgery

The Scientific Contribution of Brazilian Epilepsy Centers

Latin American Summer School on Epilepsy

International Summer School for Neuropathology and Epilepsy Surgery

Pediatric Epilepsy Training

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 339. EPILEPSY IN CANADA

HEALTH CARE IN CANADA

EPIDEMIOLOGY OF EPILEPSY IN CANADA

EPILEPSY RESOURCES

Antiseizure Medications and Devices

An Example of Organized Epilepsy Care: The Ontario Provincial Strategy

National Epilepsy Associations

CONCLUSIONS

REFERENCES

CHAPTER 340. EPILEPSY IN THE CARIBBEAN

INTRODUCTION

HEALTH STATISTICS OF THE ENGLISH-SPEAKING CARIBBEAN

EPILEPSY CARE IN THE CARIBBEAN: BEFORE THE JAMAICAN LEAGUE AGAINST EPILEPSY

EPILEPSY CARE IN THE CARIBBEAN: SINCE THE FORMATION OF THE JAMAICAN LEAGUE AGAINST EPILEPSY

ORGANIZATION OF HEALTH CARE SYSTEMS IN THE ENGLISH-SPEAKING CARIBBEAN

Jamaica

Barbados

Trinidad and Tobago

French Caribbean

THE CRITICAL IMPORTANCE OF RELATIONSHIPS IN CREATING CHANGE

ACHIEVEMENTS AND FAILURES

SUMMARY AND CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 341. EPILEPSY IN CHILE

INTRODUCTION

CHILEAN HEALTH SYSTEM

EPILEPSY IN CHILE AS “NONTRANSMISSIBLE CHRONIC DISEASE”

STAGES IN THE PROGRESS OF EPILEPSY MANAGEMENT IN THE MINISTRY OF HEALTH IN CHILE

IMPLEMENTATION OF THE EXPLICIT HEALTH GUARANTEE PLAN

EPILEPSY PROGRAM IN CHILE AND MINISTRY OF HEALTH: FOUNDATION OF THE EPILEPSY PROGRAM, OBJECTIVES, STRATEGIES, AND RESULTS

CHILEAN LEAGUE AGAINST EPILEPSY

Volunteering

Medication Banks

Boards of Directors

Present

Roles and Responsibilities

ANLICHE: National Association of Chilean Leagues Against Epilepsy

LICHE as PAHO/WHO Collaborating Center

CONCLUSIONS

REFERENCES

CHAPTER 342. EPILEPSY IN CHINA

INTRODUCTION

EPIDEMIOLOGY

Prevalence, Incidence, and Treatment Gap

Mortality and Sudden Unexpected Death in Epilepsy

Etiology

Prognosis

DIAGNOSIS AND TREATMENT

Preface

Diagnosis

ASM Treatments

Epilepsy Surgery and Presurgical Evaluation

Neuromodulation

Dietary Therapy

TCM and Epilepsy

PEDIATRIC EPILEPSY

EPILEPSY IN PUBLIC HEALTH ASPECTS

Stigma and Psychosocial Aspects

Public Health Projects for Epilepsy Control in China

“Going West” Project

Awareness, Publicities, and Education

Networking

EPILEPSY RESEARCH

CONCLUSION

REFERENCES

CHAPTER 343. EPILEPSY IN CUBA

THE CUBAN HEALTH SYSTEM

EPIDEMIOLOGY OF EPILEPSY IN CUBA

MANAGEMENT OF EPILEPSY AT PRIMARY HEALTH LEVEL

TRAINING OF HUMAN RESOURCES

STUDIES IN EXPERIMENTAL MODELS OF EPILEPSY

PSYCHOSOCIAL ASPECTS

COST OF EPILEPSY IN CUBA

A COMPREHENSIVE EPILEPSY PROGRAM FOR THE ASSESSMENT AND SURGICAL TREATMENT OF PHARMACORRESISTENT EPILEPSIES IN CUBA

Presurgical Evaluation in Pharmacoresistant Epilepsy of the Temporal and Extratemporal Lobe

Intraoperative Electrocorticographic Monitoring in Epilepsy Surgery: Relationship with the Neuropathologic Substrate

Surgical Treatment of Pharmacoresistant Epilepsies of the Temporal and Extratemporal Lobe: Electroclinical, Neuropsychological, Sensory, and Immunologic Longitudinal Follow-up

CONCLUSIONS

REFERENCES

CHAPTER 344. EPILEPSY IN THE CZECH REPUBLIC

INTRODUCTION

THE ORGANIZATION OF THE HEALTH CARE SYSTEM

EPILEPSY-SPECIFIC HEALTH CARE RESOURCES

ANTISEIZURE MEDICATION

NATIONAL EPILEPSY ORGANIZATION

EPILEPSY AWARENESS IN THE CZECH REPUBLIC

CONCLUSION

REFERENCES

CHAPTER 345. EPILEPSY IN GERMANY

INTRODUCTION

THE GERMAN SOCIAL WELFARE SYSTEM

Health Insurance

ORGANIZATION OF HEALTH SERVICES

EPILEPSY-SPECIFIC HEALTH CARE RESOURCES

Structure of Epilepsy-Specific Care in Germany

Cost of Epilepsy-Specific Care in Germany

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 346. EPILEPSY IN INDIA

TREATMENT GAP

National Epilepsy Program

Rural Medical Camps and Home-Based Care for Epilepsy

SPECIAL SYNDROMES

Pharmacogenetics

MANAGEMENT OF EPILEPSY

EPIDEMIOLOGY

NCC

Hot Water Epilepsy

Excess Mortality and SUDEP

SPECIAL ISSUES

Women with Epilepsy

Children

DISABILITY OF EPILEPSY

ECONOMIC BURDEN

MEDICOLEGAL

CONCLUSION

REFERENCES

CHAPTER 347. EPILEPSY IN IRAN

INTRODUCTION

HEALTH CARE IN IRAN

HISTORICAL BACKGROUND

EPIDEMIOLOGY

CAUSES OF EPILEPSY

PROVISION OF CARE FOR PEOPLE WITH EPILEPSY

DIAGNOSIS

PRESURGICAL EVALUATION

EPILEPSY SURGERY

SOCIAL SUPPORT

EPILEPSY RESEARCH

EFFECTS OF ECONOMIC SANCTIONS ON THE HEALTH CARE OF EPILEPTIC PATIENTS

CHALLENGES

CONCLUSION

REFERENCES

CHAPTER 348. EPILEPSY IN IRAQ

PREMODERN HISTORY

MODERN HISTORY

IRAQI HEALTH CARE

Education and Training

Health Services and Capacity

Cost of Care

Barriers to Services

CONCLUSION

REFERENCES

CHAPTER 349. EPILEPSY IN LATIN AMERICA

INTRODUCTION

MEDICAL CARE

DATA ON EPILEPSY

EPILEPSY CARE

Specialized Centers, Neurologists, and Epileptologists

Antiseizure Medications

Diagnostic Studies

Epilepsy Surgery

Ketogenic Diet

Vagus Nerve Stimulation

Traditional Medicine

THE TREATMENT GAP

PSYCHOSOCIAL ASPECTS AND STIGMA

EPILEPSY TRAINING IN PRIMARY HEALTH CARE

NEUROLOGY AND EPILEPSY TRAINING

RESEARCH IN EPILEPSY

SCIENTIFIC SOCIETIES

Advocacy and Parent Associations

The Laws on Epilepsy and National Programs

Telemedicine in Epilepsy

Plan of Action and Strategy for Epilepsy

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 350. EPIDEMIOLOGY OF EPILEPSY IN LATIN AMERICA

INTRODUCTION

PREVALENCE STUDIES

INCIDENCE STUDIES IN LATIN AMERICA

TREATMENT GAP

MORTALITY

CONCLUSION

REFERENCES

CHAPTER 351. EPILEPSY IN MEXICO

EPIDEMIOLOGY

CLASSIFICATION AND RISK FACTORS FOR EPILEPSY IN MEXICO

THERAPEUTIC EPILEPSY GUIDELINES PUBLISHED IN MEXICO

Guides of the National Center of Technological Excellence in Health (CENETEC)

Priority Epilepsy Program Guidelines

REPORTS ON EPILEPSY SURGERY IN MEXICO

Vagus Nerve Stimulation

Intracranial Neuromodulation

MEXICAN RESEARCH ARTICLES ON EPILEPSY

NEUROPSYCHIATRIC STUDIES OF EPILEPSY IN MEXICO

SOCIAL AND ECONOMIC IMPACT OF EPILEPSY IN MEXICO

EPILEPSY AT THE NATIONAL INSTITUTE OF NEUROLOGY AND NEUROSURGERY “MANUEL VELASCO SUáREZ” AND THE COMPREHENSIVE CARE CENTER 1 OF THE PRIORITY EPILEPSY PROGRAM IN MEXICO

EPILEPSY TRAINING IN MEXICO

Undergraduate Education in Epilepsy

Postgraduate Education in Mexico

CONCLUSIONS

REFERENCES

CHAPTER 352. EPILEPSY IN THE NETHERLANDS

EPIDEMIOLOGY

HEALTH CARE FACILITIES

HEALTH CARE PROVIDERS

Knowledge Transfer

Health Care Finances and Reimbursements

MORTALITY IN EPILEPSY

EPILEPSY DIAGNOSIS

SEIZURE DETECTION

EPILEPSY CLASSIFICATION AND DIAGNOSTIC FACILITIES

EPILEPSY TREATMENT

COLLABORATION IN CARE AND RESEARCH

REFERENCES

CHAPTER 353. EPILEPSY IN NIGERIA

GENERAL BACKGROUND OF NIGERIA

HEALTH CARE FACILITIES IN NIGERIA

HEALTH CARE HUMAN RESOURCES (MEDICAL DOCTORS)

EPIDEMIOLOGY OF EPILEPSY

Etiology

Antenatal Care, Birth Injury, Birth Asphyxia

Infectious Disease

Brain Injury and Stroke

TREATMENT OF EPILEPSY

Inadequate Manpower

Antiseizure Medications

Treatment Gap

Outcome

Quality of Life Measures

PSYCHIATRIC MORBIDITY IN EPILEPSY

CULTURAL CONTEXT OF EPILEPSY

INJURIES

HEALTH EDUCATION

REFERENCES

CHAPTER 354. EPILEPSY IN THE RUSSIAN FEDERATION

INTRODUCTION

HISTORY OF EPILEPTOLOGY IN RUSSIA

The Founders of Russian Epileptology

The Soviet Period

Epileptology in the Russian Federation

EPIDEMIOLOGY

ORGANIZATION OF CARE

EDUCATION

CONCLUSION

REFERENCES

CHAPTER 355. EPILEPSY IN SAUDI ARABIA

INTRODUCTION

EPIDEMIOLOGY OF EPILEPSY

CAUSES OF EPILEPSY

Epilepsy Management in the Kingdom of Saudi Arabia

Specialist Care

Developing Epilepsy Patients’ Medical Registers Program

Diagnostic Devices

Manpower for Epilepsy Management in KSA

Epilepsy Surgery Program in KSA

CLINICAL EPILEPSY RESEARCH IN THE KINGDOM OF SAUDI ARABIA

PUBLIC AWARENESS AND ATTITUDES

EPILEPSY HEALTH CARE SYSTEM IN KSA

CONCLUSIONS

REFERENCES

CHAPTER 356. EPILEPSY IN SCANDINAVIA

DEMOGRAPHY

CENTRAL REGISTERS FOR SURVEILLANCE AND RESEARCH

EPILEPSY CARE IN SWEDEN

Short History of Epilepsy Care in Sweden

Levels of Epilepsy Care in Sweden Today and Referral System

Specialized Epilepsy Care, Tertiary Centers

National Guidelines

Planned Improvements of Epilepsy Care

EPILEPSY CARE IN DENMARK

Organization of Health care in Denmark

Organization of Epilepsy Care in Denmark

Investigational Procedures

The Danish Epilepsy Hospital “Filadelfia”

EPILEPSY CARE IN NORWAY

Primary Health Care

Specialist Health Care

National Centre for Epilepsy

EpilepsiNETT

Norwegian Guidelines for Care and Treatment of Epilepsy

SIMILARITIES AND DIFFERENCES BETWEEN THE SCANDINAVIAN COUNTRIES

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 357. EPILEPSY IN SENEGAL

INTRODUCTION

OVERVIEW OF THE COUNTRY

GENERAL DATA ON THE HEALTH SYSTEM

Health Organization and General Data

Health Financing

Health Personnel

Neurologists

EPILEPSY IN SENEGAL

Epidemiology

The Etiologic Factors

Sociocultural Representation

Available Antiseizure Medications and Diagnostic Facilities in Senegal

The Role of the Senegalese League Against Epilepsy

SUMMARY AND CONCLUSION

ACKNOWLEDGMENT

REFERENCES

CHAPTER 358. EPILEPSY IN SOUTH AFRICA

INTRODUCTION, DEMOGRAPHICS, AND HEALTH CHALLENGES

Health Challenges

Social Support

History of the SA Health System

Present Day Access to Health Care

Epidemiology

ACUTE CARE

SPECIFIC CONDITIONS AND COMORBIDITIES

Neurocysticercosis

HIV and Epilepsy

Bone Health

Epileptic Spasms

Dravet Syndrome

Hemiconvulsion-Hemiplegia-Epilepsy Syndrome

EEG Utility

Psychogenic Nonepileptic Seizures

Social Stigma

Traditional and Faith Healers

Nongovernment Organizations for Epilepsy

TRAINING AND EDUCATION OPPORTUNITIES

NATIONAL BODIES

ILAE SA Chapter

Neuroscience Research in South Africa: Basic Science Activity

UNIQUE DIRECTIONS FOR SOUTH AFRICA

CONCLUSIONS

REFERENCES

CHAPTER 359. EPILEPSY IN SOUTH KOREA

TRADITIONAL ORIENTAL MEDICINE

ERA OF WESTERN MEDICINE

MEDICAL TREATMENT OF EPILEPSY

HEALTH CARE SYSTEM IN KOREA

EPILEPSY SURGERY

SIGNIFICANT ACHIEVEMENTS FOR THE EPILEPSY CARE IN KOREA

Driving Privileges

National Disability Enactment

New Name of Epilepsy

Prescription of SSRI and SSSNRI in Patients with Epilepsy

Life Insurance for Patients with Epilepsy

National Epilepsy Support Program

REFERENCES

CHAPTER 360. EPILEPSY IN TUNISIA

INTRODUCTION

GENERAL DATA ON THE HEALTH SYSTEM

Organization of the Health Care System in Tunisia

Health Care Professionals

Technical Resources for Epilepsy Diagnosis

Antiseizure Medications

HEALTH CARE FINANCING AND HEALTH INSURANCE

Health Care Financing

Health Insurance

EPIDEMIOLOGY OF EPILEPSY IN TUNISIA

EDUCATION ON EPILEPSY IN TUNISIA

RESEARCH IN EPILEPSY IN TUNISIA

THE ROLE OF SCIENTIFIC AND SOCIAL SOCIETIES

REFERENCES

CHAPTER 361. EPILEPSY IN TURKEY

BRIEF HISTORY OF THE TURKISH HEALTH CARE SYSTEM

SOCIAL SECURITY INSTITUTION

ORGANIZATION OF THE HEALTH CARE SERVICES IN TURKEY

Preventive Health Services

Therapeutic Health Services

Rehabilitation Services

MEDICAL CARE FOR PERSONS WITH EPILEPSY IN TURKEY

CONCLUSION

REFERENCES

CHAPTER 362. EPILEPSY IN THE UNITED KINGDOM

INTRODUCTION

MEDICAL DEVELOPMENTS

The Organisation of Paediatric Epilepsy Networks in the United Kingdom

Examples of Notable UK Epilepsy Studies

The Cochrane Collaboration

Genomics England, 100,000 Genome Project

Autoimmune Epilepsy

SURGICAL DEVELOPMENTS

Epilepsy Surgery in the United Kingdom

The Children’s Epilepsy Surgery Service (CESS)

GUIDELINES

NICE

SIGN

Entitlement to Drive

AUDITS

The National Sentinel Clinical Audit of Epilepsy-Related Death

Epilepsy12

National Audit of Seizure Management in Hospitals

Public Health England Mortality Audit

CHARITIES

Epilepsy Research UK

Epilepsy Action

SUDEP Action

Matthew’s Friends

CONCLUSIONS

ACKNOWLEDGMENTS

REFERENCES

CHAPTER 363. EPILEPSY IN THE UNITED STATES OF AMERICA

HEALTH CARE PROVIDERS

EPILEPSY CARE

HEALTH INSURANCE

Public Health Insurance

Private Health Insurance

SUMMARY AND CONCLUSIONS

REFERENCES

CHAPTER 364. IMPLEMENTATION SCIENCE FOR EPILEPSY

GENERAL BACKGROUND

IMPLEMENTATION SCIENCE AND THE RESEARCH PIPELINE

IMPLEMENTATION SCIENCE HAS A ROLE DISTINCT FROM HEALTH SERVICES RESEARCH AND QUALITY IMPROVEMENT

IMPLEMENTATION SCIENCE FRAMEWORKS

HYBRID MODELS

EPILEPSY IS A LATE ADAPTER TO IMPLEMENTATION SCIENCE

IMPLEMENTATION SCIENCE EMERGENCE WITHIN EPILEPSY RESEARCH AND CLINICAL CARE

REFERENCES

CHAPTER 365. SOCIAL MEDIA TO ENHANCE HEALTH CARE DELIVERY AND EDUCATION IN EPILEPSY

BACKGROUND

PUBLIC AWARENESS CAMPAIGNS IN THE EARLY NAUGHTS (2000–2009) AND THE USE OF SOCIAL MEDIA

USE OF SOCIAL MEDIA IN EPILEPSY CARE AND EDUCATION

Presence of Epilepsy Community and Groups on Social Media

Social Networking as Method for Peer-Support in Epilepsy

Community Education

Patient Care and Physician Engagement

Reaching Underserved Groups

Professional Networking

DANGERS OF SOCIAL MEDIA

Does Stigmatization of Epilepsy Exist in Social Media?

When GIFs and Social Media Posts Attack

Poor-Quality Information

Professionalism

Ethical Concerns with Patient Privacy, Data Security, and the Online Patient–Clinician Relationship

ISSUES WITH ONLINE HEALTH EDUCATION MATERIALS

SUMMARY

REFERENCES

Index

 

An aparitie	25 noi 2023
Autor	Jerome Engel, Jr., Solomon L. Moshe
Dimensiuni	213 x 276 mm
Editura	LWW
Format	Hardcover
ISBN	9781975105525
Limba	Engleza
Nr pag	3998
Versiune digitala	DA