Jiruska Modern Concepts of Focal Epileptic Networks

1. Auflage 2014
ISBN: 978-0-12-419957-6
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, Band 0, 364 Seiten

Reihe: International Review of Neurobiology

This volume ofÿInternational Review of Neurobiology concentrates on modern concepts of focal epileptic networks. The volume addresses specific topics such as seizures (including transition and termination), limbic networks, alteration of metabolism, and neocortical focus and malformation of cortical development, among others. Published since 1959, International Review of Neurobiology is a well-known series appealing to neuroscientists, clinicians, psychologists, physiologists, and pharmacologists. Led by an internationally renowned editorial board, this important serial publishes both eclectic volumes made up of timely reviews, and thematic volumes that focus on recent progress in a specific area of neurobiology research. - Our knowledge about the mechanisms involved in pathophysiology of epilepsy has rapidly expanded during last decade - This special volume brings overview about modern concepts of epileptic focus organization and about the altered neural network dynamics which results in propensity of the brain tissue to generate spontaneous and repeated seizures

Autoren/Hrsg.

Jiruska, Premysl

Inhaltsverzeichnis

1;Front Cover;1
2;Modern Concepts of Focal Epileptic Networks;4
3;Copyright;5
4;Contents;6
5;Contributors;10
6;Chapter One: Modern Concepts of Focal Epileptic Networks;14
6.1;Acknowledgments;18
6.2;References;18
7;Chapter Two: Neocortical Focus: Experimental View;22
7.1;1. Introduction;23
7.2;2. Neocortical Neuronal Activities During States of Vigilance;23
7.3;3. Neocortical Neuronal Activities During Seizures;28
7.4;4. Alterations of Synaptic and Intrinsic Excitability During Seizures;30
7.5;5. Unbalance of Excitatory and Inhibitory Influences Leading to Seizure Generation;31
7.6;6. Focus of Epilepsy Versus Seizure and Interaction of Epileptic Focus with Intact Cortex;33
7.7;7. Neuronal Plasticity Leading to Development of Epilepsy;35
7.8;8. Conclusions;38
7.9;Acknowledgments;39
7.10;References;39
8;Chapter Three: Malformations of Cortical Development and Neocortical Focus;48
8.1;1. Introduction;49
8.2;2. Normal and Abnormal Development of the Cerebral Cortex;50
8.2.1;2.1. Neurogenesis and apoptotic cell death;50
8.2.2;2.2. Gliogenesis and myelination;53
8.2.3;2.3. Neuronal migration;53
8.2.4;2.4. Transient neurons and transient circuits;55
8.2.5;2.5. The developmental excitatory–inhibitory shift of GABA;56
8.3;3. The (UN)identified Neocortical Focus;58
8.3.1;3.1. Molecular, structural, and functional alterations in an epileptic focus;59
8.3.1.1;3.1.1. Animal models;59
8.3.1.2;3.1.2. Experimental studies in human tissue;62
8.4;4. Removal of a Neocortical Focus;63
8.4.1;4.1. Concept of presurgical evaluation in neocortical epilepsies;63
8.4.2;4.2. Epilepsy surgery for cortical malformations;65
8.5;5. Conclusion;66
8.6;Acknowledgments;66
8.7;References;66
9;Chapter Four: Limbic Networks and Epileptiform Synchronization: The View from the Experimental Side;76
9.1;1. Background;77
9.2;2. Mechanisms Underlying Epileptiform Synchronization;79
9.2.1;2.1. Interictal spikes;80
9.2.2;2.2. High-frequency oscillations;82
9.2.3;2.3. Ictal discharges;83
9.3;3. Interactions Between Limbic Areas;86
9.4;4. Seizure-Onset Types;88
9.4.1;4.1. Human background;88
9.4.2;4.2. Experimental evidence in vitro;89
9.4.3;4.3. Chronic models of MTLE;90
9.5;5. Modulation of Epileptiform Synchronization by Neurosteroids;91
9.6;6. Conclusions;94
9.7;Acknowledgments;94
9.8;References;94
10;Chapter Five: Limbic Networks: Clinical Perspective;102
10.1;1. Introduction;103
10.2;2. Clinical Features of Limbic Epilepsy;104
10.3;3. Structural Networks in Limbic Epilepsy;108
10.3.1;3.1. MRI studies;108
10.3.2;3.2. DTI studies;109
10.4;4. Functional Networks in Limbic Epilepsy;110
10.4.1;4.1. Electro- and magnetoencephalographic studies;110
10.4.2;4.2. fMRI;118
10.5;5. Metabolic Networks in Limbic Epilepsy;122
10.6;6. Conclusions;124
10.7;References;125
11;Chapter Six: Modern Concepts of Seizure Modeling;134
11.1;1. Introduction;135
11.2;2. Detailed Biophysical Models;135
11.2.1;2.1. Role of potassium and other ion channels;136
11.2.1.1;2.1.1. Extracellular potassium;137
11.2.1.2;2.1.2. Sodium concentrations;139
11.2.1.3;2.1.3. Chloride;140
11.2.2;2.2. Gap junctions and VFOs;141
11.2.3;2.3. Posttraumatic epilepsy and homeostatic synaptic plasticity;142
11.2.4;2.4. Network topology;143
11.2.4.1;2.4.1. Topological changes in the hippocampus;143
11.2.4.2;2.4.2. Spatial propagation of seizure activity;146
11.2.5;2.5. Thalamocortical loop and absence seizures;148
11.3;3. Lumped Models;150
11.3.1;3.1. Abstract models;151
11.3.2;3.2. Neural mass and neural field models;153
11.3.3;3.3. Epileptor model;156
11.3.4;3.4. Large-scale models;156
11.4;4. Analogies;159
11.4.1;4.1. Stochastic models;159
11.4.2;4.2. Power-law behavior;159
11.5;5. Discussion;161
11.6;Acknowledgments;162
11.7;References;162
12;Chapter Seven: Mechanisms of Ictogenesis;168
12.1;1. Introduction;169
12.2;2. Recording the Brain and its Networks During the Transition to Seizures;172
12.2.1;2.1. Preictal dynamics;172
12.2.2;2.2. Transition to seizure;175
12.3;3. Cellular Substrates of Ictogenesis: Neurons and Neurotransmission;175
12.3.1;3.1. Neuronal behavior during ictogenesis;175
12.3.2;3.2. Pyramidal cells;177
12.3.3;3.3. Glutamatergic neurotransmission;178
12.3.4;3.4. Interneurons;178
12.3.5;3.5. GABAergic neurotransmission;180
12.4;4. The Environment of Neurons: Ions, Astrocytes, and the Extracellular Space;183
12.4.1;4.1. Potassium;183
12.4.2;4.2. Calcium;185
12.4.3;4.3. Extracellular space;185
12.4.4;4.4. Astrocytes;186
12.5;5. Conclusion;187
12.6;Acknowledgments;188
12.7;References;188
13;Chapter Eight: Seizure Termination;200
13.1;1. Introduction;201
13.2;2. Metabolic Mechanisms of Seizure Termination;202
13.2.1;2.1. Oxygen, glucose, and neurotransmitter depletion;202
13.2.2;2.2. Acidosis;203
13.2.3;2.3. Extracellular potassium concentration;204
13.2.4;2.4. Neuromodulators;205
13.3;3. Network Aspects of Seizure Termination;206
13.3.1;3.1. Synchronization;206
13.3.2;3.2. Graphs and functional networks;210
13.3.3;3.3. Seizure termination as a critical transition;212
13.4;4. Conclusions;215
13.5;References;216
14;Chapter Nine: Epileptic Focus and Alteration of Metabolism;222
14.1;1. Introduction;223
14.2;2. Acute Changes in Energy Metabolism During Seizures;225
14.3;3. Metabolic Dysfunction of Chronic Epileptic Tissue;229
14.3.1;3.1. Oxidative stress;230
14.3.2;3.2. Mitochondrial dysfunction;230
14.4;4. Alteration of Mitochondrial Genome in Chronic Epileptic Tissue;233
14.5;5. Changes in Blood Flow Regulation in Epileptic Tissue;237
14.6;6. Alteration of Blood Brain Barrier;241
14.6.1;6.1. Blood brain barrier breakdown: Cause or consequence of epilepsy?;241
14.6.2;6.2. Blood brain barrier: A site of pharmacoresistance in epilepsy?;244
14.7;7. Conclusions;245
14.8;Acknowledgments;246
14.9;References;246
15;Chapter Ten: Modern Techniques of Epileptic Focus Localization;258
15.1;1. Introduction;259
15.2;2. Structural Imaging, Volumetrics, and Morphometric Analysis;260
15.2.1;2.1. Image preprocessing;261
15.2.2;2.2. MRI volumetry;261
15.2.3;2.3. Voxel-based morphometry;263
15.2.4;2.4. Surface-based morphometry;264
15.2.5;2.5. Cortical morphometry;264
15.2.6;2.6. Diffusion tensor imaging;265
15.3;3. Functional Neuroimaging in Epilepsies Using PET;266
15.3.1;3.1. Interictal metabolic changes (FDG PET);267
15.3.1.1;3.1.1. Pathophysiology;267
15.3.1.2;3.1.2. Localization and extent of hypometabolism in TLE;268
15.3.1.3;3.1.3. Clinical implications in TLE;270
15.3.1.4;3.1.4. Clinical implications in extratemporal lobe epilepsy;270
15.3.1.5;3.1.5. Statistical parametric mapping;271
15.3.2;3.2. Flumazenil PET;271
15.3.3;3.3. Other tracers;272
15.3.3.1;3.3.1. 5-HT1A receptor antagonists;272
15.3.3.2;3.3.2. Tryptophan metabolism;272
15.3.3.3;3.3.3. Inflammatory changes;273
15.4;4. Ictal Perfusion;273
15.4.1;4.1. Preictal, ictal, and postictal changes (pathophysiology, hemodynamics);273
15.4.2;4.2. SPECT in epileptic seizures;274
15.4.2.1;4.2.1. Propagation pattern;275
15.4.2.2;4.2.2. Subtraction (SISCOM vs. STATISCOM);276
15.4.2.3;4.2.3. Clinical implications;277
15.5;5. Irritative Zone as Assessed by BOLD fMRI;278
15.5.1;5.1. Principles;279
15.5.2;5.2. Technical aspects;280
15.5.3;5.3. Methodological aspects;280
15.5.4;5.4. Clinical implications;282
15.6;6. Conclusions;284
15.7;Acknowledgments;284
15.8;References;284
16;Chapter Eleven: From Treatment to Cure: Stopping Seizures, Preventing Seizures, and Reducing Brain Propensity to Seize;292
16.1;1. From Anticonvulsant Therapy to Disease-Modifying Treatment;293
16.2;2. Seizure Prevention: Toward Personalized Medicine to Stop Seizures from Happening;293
16.3;3. Seizure Prevention: Stopping Epileptogenesis;295
16.4;4. Reducing Potential Adverse Effects by Treating Seizures in Real Time;296
16.5;5. Real-Time Seizure Treatments: What to Deliver?;296
16.6;6. Optogenetics;297
16.7;7. Chemical Genetics;300
16.8;8. What to Hit: Are Interneurons a Good Target for Interventions?;301
16.9;9. Gene Therapy: Introducing Genes to Selected Neurons;303
16.10;10. Treatments to Restore Excitability: Is there a Possibility of a Cure?;304
16.11;11. How Far to Cure(s)?;306
16.12;Acknowledgments;307
16.13;References;307
17;Index;314
18;Contents of Recent Volumes;320

Leseproben

Chapter One

Modern Concepts of Focal Epileptic Networks

Premysl Jiruska*,†,1; Marco de Curtis‡; John G.R. Jefferys§,¶    * Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of Czech Republic, Prague, Czech Republic
† Department of Neurology, 2nd Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic
‡ Department of Epileptology and Experimental Neurophysiology, Fondazione IRCCS, Istituto Neurologico C Besta, Milan, Italy
§ Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, United Kingdom
¶ Department of Pharmacology, University of Oxford, Oxford, United Kingdom
1 Corresponding author: email address: [e-mail]

Early experiments with topical application of convulsants and with local cortical lesions suggested that epileptic activity and seizures can be generated within a highly restricted cortical region, defined as the epileptic focus. Such foci were thought to contain populations of abnormally behaving cells (neurons and glia) that sustain a range of hyperexcitable phenomena including seizures, interictal epileptiform discharges, and pathological network oscillations. This concept was further supported by pioneering recordings and surgical resections from human brain during the early days of epilepsy surgery by Penfield and Jasper (1954). Seizures originating from the epileptic focus were termed focal seizures and the corresponding epilepsy was classified as focal epilepsy (Commission on Classification and Terminology of the International League Against Epilepsy, 1981). Focal seizures can propagate outside the focus to secondarily involve regions that are not functionally altered but are recruited by the epileptiform discharge. When discharge propagation is widespread and also involves subcortical areas, secondary generalization occurs. Altered network dynamics at the focus and local/distant effects of epileptiform activity can disrupt ongoing physiological processes and may result in neurological and cognitive deficits observed in some patients with epilepsy.

Neurobiological research in the field of epilepsy aims to identify specific structural, functional, or genetic abnormalities that can reliably explain how focal epilepsy develops (the study of epileptogenesis) and what are the main mechanisms responsible for seizure initiation (the study of ictogenesis). Advances in experimental and clinical studies brought novel insights into the cellular dynamics and network organization of the epileptic brain that question the concept of the epileptic focus. Specifically, experience from surgical treatment has shown that the concept of a restricted focus is not optimal for planning of epilepsy surgery and could be responsible for failure to achieve seizure freedom in a substantial population of patients who underwent resection. Intracranial recordings demonstrate that the region involved in the generation of seizures and interictal events often includes nonlesional areas and involves spatially distant regions within the same or different lobes. The concept of the epileptic focus was, therefore, redefined and replaced by the identification and the definition of overlapping pathological and pathophysiological zones that generate epileptiform activities: the seizure-onset zone, the irritative zone (the region that generates interictal discharges), the epileptogenic lesion, and the epileptogenic zone, the resection or disconnection of which is necessary and sufficient for seizure freedom (Kahane, Landre, Minotti, Francione, & Ryvlin, 2006; Rosenow & Luders, 2001). The importance of altered network organization in focal epilepsies was stressed by Spencer (2002) and the new classification proposal of epilepsies insists on the concept of the networks when focal epilepsies are discussed (Berg et al., 2010). More recently, the concept of “system epilepsy” was introduced (Avanzini et al., 2012) that suggests that specific networks are prone to generate seizures, possibly only when a part of the network is damaged or functionally altered. The existence of system-specific susceptibility to seizures is also supported by the demonstration that systemic applications of proconvulsive drugs selectively alter specific networks and induce interictal and ictal epileptiform patterns segregated into specific cortical systems (Boido, Jesuthasan, de Curtis, & Uva, 2014; Carriero et al., 2012).

The seeming contradiction between the concepts of epileptic focus and of epileptic networks can be reconciled when time is considered. In hypothetical terms, very localized, focal changes in excitability could in principle develop after an acute injury and the evolution of the acute damage, together with the occurrence of seizure-like discharges, may establish the later development of network changes. Acute recordings in patients with hemorrhagic strokes show that seizure patterns recorded during the acute stage differ from late seizures (Dreier et al., 2012).

The importance of the network concept was substantially bolstered by introduction into epilepsy research of approaches from the fields of complex dynamics of networks and graph theory (Chapter 6; Bullmore & Sporns, 2009; van Diessen, Diederen, Braun, Jansen, & Stam, 2013). This new and rapidly expanding mathematical field has a substantial impact on epilepsy research, and on neuroscience in general. It further demonstrates how important connectivity is for understanding the abnormal behavior generated within epileptic networks and how structural and functional connectivity can shape the epileptic phenomena (Stefan & Lopes da Silva, 2013; Wendling, Chauvel, Biraben, & Bartolomei, 2010). Experimental and clinical findings, together with the advanced use of mathematical and physical approaches in epilepsy research, revealed that epilepsy and seizures are very complex dynamical phenomena and that understanding these processes requires integrating together information from different spatial and temporal domains (Jiruska et al., 2013; Chapter 8). The importance of complexity is well demonstrated by genetic studies. Several genes have been identified within families in which epilepsy occurred across several generations (Lerche et al., 2013). However, people within families sharing the same mutations were identified but some of them did not develop epileptic phenotypes (Lerche et al., 2013). The twentieth century reductionist approach to identify specific genes responsible for diseases proved disappointing in many types of epilepsy, and it is now widely accepted that the epileptic phenotype is the result of complex interactions between genes and cellular networks within the organism, and environmental factors. In addition, development of antiepileptic drugs targeting specific mechanisms implicated in seizure initiation failed to live up to expectations and raised the possibility of much more complex mechanisms being responsible for seizures (Brodie et al., 2011). It is equally necessary to consider multiple factors and complex interactions for understanding how seizures are generated. It is well known that seizure (network) patterns observed in vivo are poorly reproduced in slices, suggesting that wider networks and more complex interactions are required to generate specific patterns of seizures.

On the local (cellular) scale, epileptiform phenomena are the result of the complex interaction between multiple neuronal subtypes. It is well known that behavior of isolated cells may substantially change when the cells are mutually connected; the pattern of connection determines the population behavior. One of the best examples comes from interneurons which, if connected into networks, generate spontaneous oscillations in the gamma band (Whittington, Traub, & Jefferys, 1995). In epilepsy, for a long time it was assumed that epileptic seizures are caused mainly by altered dynamics within the network of epileptic pyramidal neurons; this excitatory theory dominated the field of epilepsy research for decades. Traditionally, epilepsy is described as an imbalance between excitation and inhibition (Westbrook, 1991). Molecular reorganization of pyramidal cells, changes in intrinsic properties increasing neuronal excitability and newly developed pathological communication between pyramidal cells were seen as the main causes of this imbalance. The second factor of this imbalance represented weakened inhibition due to loss of specific interneurons, loss of excitatory drive onto interneurons, etc. (Pavlov, Kaila, Kullmann, & Miles, 2013; Sloviter, 1987; Vreugdenhil, Hack, Draguhn, & Jefferys, 2002). For many years, the shift of the balance between excitation and inhibition toward enhanced excitation dominated the theories on the interictal behavior within the focus and on the mechanisms responsible for initiation of seizures. Contemporary research implicates interneurons in playing more causal roles in seizure initiation and, paradoxically, has shown that intense activity of interneurons may induce complex changes that alter potassium and chloride homeostasis resulting in increased excitability, depolarization, and synchronization of principal cells and a shift brain dynamics toward the seizure (Chapter 7;...