Treatment of Epilepsy (eBook)

Jr. Jerome Engel, Emilio Perucca, Simon Shorvon (Herausgeber)

eBook Download: PDF

2015 | 4. Auflage
Wiley (Verlag)
978-1-118-93698-6 (ISBN)

Infos

Highly Commended at the British Medical Association Book Awards 2016
The Treatment of Epilepsy, fourth edition, is a comprehensive reference and clinical guide to the pharmacological, medical and surgical options available in the treatment of epilepsy.

• The text is compiled by a group of internationally renowned editors and contributors and is now in full color and extensively illustrated
• The first two sections cover the background to, and principles of, treatment in different clinical situations
• Section three comprises a series of systematic reviews of contemporary drug therapy, devoting one chapter to each anti-epileptic drug and covering all clinically-relevant aspects
• Section four focuses on the surgical options, devoting individual chapters to each of the modalities of presurgical assessment and to each surgical operation or approach
• This 4th edition is extensively revised incorporating the many recent developments in therapy, and comprises 81 chapters from world experts from 18 countries

Simon Shorvon MA MB BChir MD FRCP
Professor in Clinical Neurology and Clinical SubDean, UCL Institute of Neurology, University College London and Consultant Neurologist, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK

Emilio Perucca MD PhD FRCP(Edin)
Professor of Medical Pharmacology, Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; and Director, Clinical Trial Center, C Mondino National Neurological Institute, Pavia, Italy

Jerome Engel Jr MD PhD
Director, Seizure Disorder Center, Jonathan Sinay Distinguished Professor, Neurology, Neurobiology, Psychiatry and Behavioural Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Inhalt

The Treatment of Epilepsy 3
Contents 5
List of Contributors 7
Preface to the Fourth Edition 11
Preface to the First Edition 13
Historical Introduction: The Drug Treatment of Epilepsy from 1857 to 2015 15
SECTION I Introduction 37
CHAPTER 1 Definition (Terminology) and Classification in Epilepsy: A Historical Survey and Current Formulation, with Special Reference to the ILAE 37
Definition 37
Epilepsy and epileptic seizures 37
Classification 38
ILAE classifications of epileptic seizures and epilepsies 38
The future of classification schemes of epilepsy 51
Classification by aetiology 51
Classification by semiology and anatomical site 52
Definition 54
Acute symptomatic seizures 54
Epilepsy in remission 55
Provoked epilepsy and reflex epilepsy 55
Definition and classification – status epilepticus 55
Afterthought 58
Acknowledgement 58
References 58
CHAPTER 2 Differential Diagnosis of Epilepsy 60
Introduction 60
General approach to the diagnosis of episodic disturbances 60
Syncope 64
Non-epileptic seizures 67
Panic disorder 68
Migraine 68
Sleep disorders 69
Vertigo 70
Movement disorders 70
Cerebral ischaemia 70
Endocrine and metabolic abnormalities 70
Transient global amnesia 71
References 71
CHAPTER 3 Mechanisms of Epileptogenesis 74
Membrane ion channels 75
Voltage-gated channels 75
Membrane ion channels as targets for antibodies in acquired autoimmune disorders 79
Channel and receptor trafficking and plasticity 79
Network and system involvement in epileptogenesis 80
Local circuits 80
Networks 81
Systems 82
Epileptogenesis as a process 83
Plastic changes in channels and receptors 83
New targets for antiepileptic and antiepileptogenic strategies 84
New strategies targeting AMPA and GABA receptors 84
Conclusions 85
References 85
CHAPTER 4 Antiepileptic Drug Discovery 88
Characteristics of the ideal model system 88
The current era of AED discovery 88
Anticonvulsant Screening Program 89
Early identification of antiepileptic activity 89
MES, scPTZ and 6-Hz tests 89
Differentiation of anticonvulsant activity 91
Pharmacological profile and potential clinical utility 92
Pharmacoresistant seizure models 93
Therapeutic index and toxicity assessment 93
Aetiologically relevant model systems 93
Beyond the seizure 94
Antiepileptogenesis and disease modification (see also Chapter 8) 94
Conclusions 94
Acknowledgement 95
References 95
CHAPTER 5 Antiepileptic Drug Development 97
Introduction 97
Overview on clinical studies and trials for drug development 98
Lessons learned after two decades of AED trials 98
Opportunities for developing better antiseizure AEDs 105
Development of epilepsy drugs beyond suppressing seizures 106
Conclusions 108
Acknowledgements 109
References 109
CHAPTER 6 Mechanisms of Antiepileptic Drug Action 111
Main targets 111
Sodium channels 111
Calcium channels 114
GABA and GABA receptors 115
Other targets 119
Glutamate and glutamate receptors 119
Potassium channels 120
Cyclic nucleotide-gated channels 121
Synaptic vesicle protein SV2A 121
Monoamines 121
Intracellular signalling pathways 123
References 124
CHAPTER 7 Mechanisms of Drug Resistance and Tolerance 128
Introduction 128
The concept of drug resistance in epilepsy 128
Disease-related mechanisms of drug resistance in epilepsy 129
Epilepsy syndrome associated with drug resistance 129
Severity and progression of epilepsy 129
Structural brain alterations and/or network changes 130
Alterations in drug targets 131
Multidrug transporter hypothesis 133
Drug-related mechanisms of drug resistance in epilepsy 134
Development of tolerance 135
Pharmacogenetic mechanisms of drug resistance in epilepsy 135
Proof-of-concept of drug resistance hypotheses 135
Conclusions 135
References 136
CHAPTER 8 Epilepsy Biomarkers 139
Introduction 139
Need for biomarkers 139
Mechanisms of epilepsy 140
Potential biomarkers 141
Electrophysiological biomarkers 142
Neuroimaging biomarkers 143
Molecular and cellular biomarkers 144
Behavioural biomarkers 144
Research to identify biomarkers 145
Acknowledgements 145
References 145
SECTION II Principles of Medical Management 146
CHAPTER 9 General Principles of Medical Management 146
Aims of treatment 146
Complete seizure control 146
Reduction of seizure severity 146
Avoidance of adverse effects 147
Suppression of subclinical epileptic activity 147
Reduction of seizure-related mortality and morbidity 147
Addressing comorbidities 147
Avoidance of adverse drug interactions 148
Avoidance of obstruction to patient’s life 148
Prevention of epileptogenesis 148
When should treatment be started? 148
Individuals with a history of a single seizure 148
Individuals with a history of two or more unprovoked seizures 149
Individuals with seizures precipitated by specific triggers 149
Other situations 149
Initiation of treatment and dose optimization 149
Choice of the most appropriate drug 149
Dose escalation 150
Initial target maintenance dosage 150
Frequency of administration 152
Choosing among different formulations (including generics) 153
Adjusting dosage in individuals not responding to the initial target dosage 154
Dose optimization in special situations 154
Assessing clinical response 154
What next when the initial treatment fails? – monotherapy and combination therapy 155
Alternative monotherapy 155
Combination therapy 156
Are some drug combinations more useful than others (‘rational polytherapy’)? 156
How long should treatment be continued? 157
References 157
CHAPTER 10 Pharmacokinetic Optimization of Therapy 160
Introduction 160
Basic pharmacokinetic principles 160
Why do individuals respond differently to the same drug concentration? 160
The concept of reference range 163
The concept of individual therapeutic concentrations and interpretation of serum concentrations in the clinical setting 164
Main indications for measuring serum antiepileptic drug concentrations 164
Practical aspects in the application of TDM 166
When should blood samples be taken? 166
Monitoring unbound drug concentrations 166
Measurement of saliva concentrations 166
Other biological matrices 167
Development and progress of analytical methods 167
Application of TDM to individual antiepileptic drugs 167
First generation antiepileptic drugs 167
Second generation antiepileptic drugs 169
Tailored therapy and future developments for TDM 172
Conclusions 172
References 172
CHAPTER 11 Management of Chronic Active Epilepsy in Adults 175
Prognosis and outcome of treatment of chronic active epilepsy 175
Heterogenity of epilepsy 176
Extent of response to therapy in chronic active epilepsy 176
The term ‘drug-resistant epilepsy’ 177
Clinical factors influencing prognosis in chronic epilepsy 177
Prediction of pharmacoresistance by pharmacogenomics 177
Provision of care 178
The epilepsy centre (CSAG model) 178
Treatment approach for chronic active epilepsy in adult patients 179
Assessment 179
Treatment 180
Epilepsy surgery 181
Limits on therapy 181
Counselling and information provision 182
Acknowledgement 182
References 182
CHAPTER 12 Management of Epilepsy in Remission 184
Introduction 184
Risk of relapse upon AED withdrawal 184
Medical Research Council Antiepileptic Drug Withdrawal Study 184
Akershus double-blind antiepileptic drug withdrawal study 184
Non-randomized controlled or uncontrolled studies 185
Early versus late withdrawal in children 185
Rapid versus slow withdrawal 186
Factors associated with seizure relapse after AED withdrawal 186
Syndromic classification 186
Seizure type 186
Age at onset 187
EEG findings 187
Severity of epilepsy and duration of seizure freedom 187
Influence of individual drugs 187
Models for prediction of relapse 187
Antiepileptic drug withdrawal after epilepsy surgery 188
Consequences of relapse 188
Seizure control after relapse 189
Risks associated with continuing AEDs (or benefits of withdrawal) 189
Patient attitudes 189
Clinical therapeutics 190
References 190
CHAPTER 13 Management of Epilepsy in Neonates and Infants 192
Introduction 192
Currently available drug therapies for neonates 194
Benzodiazepines 194
Bumetanide 197
Levetiracetam 197
Lidocaine 198
Phenobarbital 198
Phenytoin 198
Topiramate 198
Currently available drug therapies for infants 198
Hormonal treatments 198
Benzodiazepines 199
Carbamazepine 199
Levetiracetam 199
Lamotrigine 199
Oxcarbamazepine 199
Phenobarbital 199
Phenytoin 199
Rufinamide 199
Stiripentol 199
Topiramate 200
Valproic acid 200
Vigabatrin 200
Zonisamide 200
Polypharmacy 200
Ketogenic diet 200
Epilepsy surgery 200
Intravenous immunoglobulin 201
Treatment of acute neonatal seizures and neonatal status epilepticus 201
General guidelines 201
Treatment of neonatal status epilepticus 202
Treatment of focal seizures 202
Provoked seizures 202
Treatment of specific syndromes in the neonatal period 202
Benign familial neonatal seizures 202
Benign non-familial neonatal seizures 202
Early myoclonic encephalopathy 203
Early infantile encephalopathy with epilepsy or Ohtahara syndrome 203
KCNQ2 encephalopathy 203
Vitamin responsive seizures 203
Glucose transporter-1 deficiency 203
Glycine encephalopathy (neonatal non-ketotic hyperglycinaemia) 204
Treatment of specific syndromes in the infantile period 204
Malignant migrating partial seizures in infancy 204
West syndrome 204
Myoclonic epilepsy of infancy 204
Benign infantile epilepsy and benign familial infantile epilepsy 205
Dravet syndrome (severe myoclonic epilepsy in infancy) 205
Tuberous sclerosis complex 205
Sturge–Weber syndrome 205
Febrile seizures 206
Prognosis and complications of neonatal and infantile seizures 206
Acknowledgements 206
References 206
CHAPTER 14 Management of Childhood Epilepsy Syndromes 210
Introduction 210
Treatment of childhood epilepsy: the evidence base 210
Treatment of febrile seizures 210
Treatment of idiopathic generalized epilepsies 215
Treatment of idiopathic focal epilepsy syndromes of childhood 220
Treatment of epileptic encephalopathies 222
Lennox–Gastaut syndrome 223
Doose syndrome 224
Landau–Kleffner syndrome and the syndrome of continuous spikes and waves in slow sleep 225
Myoclonic absence epilepsy 225
References 225
CHAPTER 15 Management of Epilepsy in People with Intellectual Disabilities 229
The importance of the topic 229
Comprehensive epilepsy service 229
Multidisciplinary approach 229
Medical aspects 230
Psychological and cognitive aspects 230
Social and educational aspects 230
Antiepileptic drug treatment 231
Adherence 231
Older drugs 231
Newer drugs 232
Central nervous system side-effects 234
Paradoxical effects 234
Can the development of the disorder be influenced by treatment? 235
Influence of aetiology and disease mechanisms on epilepsy treatment 235
Non-pharmacological treatment 236
Epilepsy surgery 236
Vagus nerve stimulation 236
Ketogenic diet 236
Acute seizure treatment with benzodiazepines 236
Concomitant psychopharmacological treatment 237
Prognosis of epilepsy in intellectually disabled patients 237
Overall prognosis 237
Prognosis after withdrawal of AEDs 238
References 238
CHAPTER 16 Management of Epilepsy in the Elderly 241
Introduction 241
Epidemiology 241
Diagnosis 241
Clinical presentation of epilepsy in the elderly 245
Investigations 245
Electroencephalography 245
Neuroimaging 246
Risk of recurrence 246
Treatment of epilepsy in the elderly 246
Pharmacokinetic changes 246
Absorption 246
Protein binding 246
Hepatic clearance 246
Renal clearance 247
Pharmacodynamic changes 248
Antiepileptic drug choice 248
Older antiepileptic drugs 248
Newer antiepileptic drugs 249
Comorbid conditions and medication interactions 251
Epilepsy surgery 252
Aspects of the impact of epilepsy inold age 252
References 254
CHAPTER 17 Emergency Treatment of Seizures and Status Epilepticus 257
Status epilepticus 257
Epidemiology and causes 257
Status epilepticus and neuronal damage 261
Drug pharmacokinetics and pharmacodynamics 262
Acute drug pharmacokinetics 262
Peripheral and cerebral distribution of drugs during epileptic seizures 263
Development of resistance to AED action 263
Treatment of acute seizures and acute repetitive seizures 263
General (non-pharmaceutical) measures 263
Emergency drug therapy in acute repetitive seizures and prolonged seizures 263
Drugs used in the emergency therapy of acute repetitive seizures and prolonged seizures 264
Treatment of tonic–clonic status epilepticus 265
Diagnosis 265
Medical management and complications 265
Drug treatment of tonic–clonic status epilepticus 267
Protocol for the drug treatment of tonic–clonic status epilepticus (Table 17.4) 267
Treatment in the premonitory stage of tonic–clonic status epilepticus 268
Treatment in early status epilepticus 268
Treatment in established status epilepticus 269
Treatment in refractory and super-refractory status epilepticus 270
Treatment of common forms of non-convulsive status epilepticus 272
Diagnosis 272
Medical management 272
Summary of drug therapies most commonly used in status epilepticus 274
Diazepam 274
Fosphenytoin 274
Levetiracetam 274
Lorazepam 275
Midazolam 275
Phenobarbital 275
Phenytoin 275
Propofol 276
Thiopental/pentobarbital 276
Valproate 276
Acknowledgement 277
References 277
CHAPTER 18 Management of Medical Comorbidity Associated with Epilepsy 281
Introduction 281
Bone health in epilepsy 281
Overview of bone physiology and biochemistry 281
Fracture and osteoporosis risk in people with epilepsy 282
Screening for bone health in people with epilepsy 282
Prevention and treatment of bone loss in people with epilepsy 283
Organ dysfunction 284
Overview of AED pharmacokinetics and dosing in hepatic disorders 284
AED pharmacokinetics and dosing in renal disorders 285
Hepatic and renal impairment due to epilepsy and its treatment 286
Epilepsy and thyroid disease 288
Multiorgan dysfunction 288
Organ transplantation 288
Cancer and epilepsy 289
Infections and epilepsy 289
Human immunodeficiency virus infection and seizures 290
Cysticercosis and epilepsy 290
Connective tissue disorders 290
Pulmonary disease 291
Cardiac disease 291
Cardiac arrythmias 291
Ischaemic cardiovascular disease 292
References 292
CHAPTER 19 Psychiatric Features of Epilepsy and their Management 295
Anxiety and affective disorders 295
Prevalence of anxiety and affective disorders in epilepsy 295
‘Bidirectional relationship’ between epilepsy and depression 296
Diagnostic criteria 296
Atypical affective disorders in epilepsy 296
Interictal dysphoric disorder 296
Preictal, ictal and postictal depressive symptoms 297
Generalized anxiety disorder 297
Panic disorder 297
Obsessive–compulsive disorder 297
Suicide 298
FDA guidance on suicide risk associated with AEDs 298
Treatment of depression in epilepsy 299
Pharmacokinetic interactions between antidepressants and AEDs 301
Pharmacodynamic interactions 301
Cognitive behavioural therapy 301
Electroconvulsive therapy, transcranial magnetic stimulation and vagal nerve stimulation 301
Deep brain stimulation for treatment-resistant depression 302
Psychoses of epilepsy 302
Ictal delirium 302
Ictal psychosis (complex partial status epilepticus) 302
Postictal psychosis 302
Interictal psychosis 303
Definition 303
Prevalence 303
Duration and other clinical factors 303
Relationship to epilepsy subtype 303
‘Bidirectional relationship’ between epilepsy and schizophrenia 303
Psychopathology in interictal psychosis: comparison with schizophrenia 303
Therapy of psychosis in epilepsy 304
Postoperative psychiatric disorders 304
Forced normalization 305
Personality disorders in epilepsy 306
Epileptic personality 306
DSM-IV (Axis II) personality disorders 306
Mental and behavioural disorders secondary to AED use 307
References 307
CHAPTER 20 Prevention and Management of Side-effects of Antiepileptic Drugs 311
Types of adverse effects 313
Type A 313
Type B 315
Type C 316
Prevention and management of adverse effects 317
Analysis of risk factors 317
Strategies for prevention or minimization of adverse effects 319
Early identification 319
Treatment 320
References 321
CHAPTER 21 Ketogenic Diets 324
Introduction 324
Mechanisms of action 325
Seizure outcomes 325
Ketogenic diets and adults 327
Alternative ketogenic diets 327
Indications for the ketogenic diet 327
Calculation of the ketogenic diet 328
Initiation of the ketogenic diet 329
Handling increased seizures 330
Discontinuation of the ketogenic diet 330
Side-effects 331
Conclusions 332
Acknowledgements 332
References 332
CHAPTER 22 Complementary and Alternative Treatments for Epilepsy 334
Introduction 334
Importance of indirect benefits 334
The placebo effect 335
Stress and anxiety 335
Ancient medical traditions 336
Ayurvedic medicine 336
Traditional Chinese medicine 336
Herbal remedies 337
Bishop’s wort 338
Blue cohosh 338
Kava 338
Mistletoe 338
Itchweed 338
Mugwort 338
Ground holly 338
Skullcap 338
Cannabis 338
Homeopathy 339
Behavioural approaches 340
Comprehensive neurobehavioural approach 340
Neurofeedback 341
Aromatherapy 342
Music therapy 342
Meditation and hypnosis 343
Hypnosis 344
Conclusions 344
References 344
CHAPTER 23 Reproductive Aspects of Epilepsy Treatment 347
Fertility 347
Reproductive dysfunction 347
Birth control 348
Pregnancy in women with epilepsy 349
Effects of maternal seizures on the fetus 349
Maternal risks with uncontrolled seizures 349
Seizure control during pregnancy and delivery 350
Pharmacokinetics of antiepileptic drugs during pregnancy 350
Obstetric complications during pregnancy and delivery 350
Sensitive periods 353
Folate supplementation 354
Vitamin K supplementation and neonatal haemorrhage 354
Preconception counselling 354
Management during pregnancy 355
Labour and delivery 356
Puerperium 356
Implications for the treatment of women of child-bearing age 356
References 356
CHAPTER 24 Genetic Counselling in Epilepsy 359
Introduction 359
The pedigree as a diagnostic tool 359
Risk assessment 359
Genetic testing 360
Diagnostic tests 360
Carrier identification tests 360
Predictive tests 360
Susceptibility tests 361
Pharmacogenetics tests 361
Mode of inheritance of genetic disorders 361
Chromosomal inheritance 362
Mendelian inheritance 362
X-linked inheritance 364
Mitochondrial inheritance 365
Complex inheritance 365
Genetic counselling in epilepsy: approaching a heterogeneous disorder 365
Mendelian epilepsies 366
Complex epilepsies 368
Epileptic encephalopthies 370
Copy number variations and epilepsy 372
Genetic syndromes including epilepsy as an important clinical feature 372
Progressive myoclonus epilepsies 372
Conclusions 375
References 376
CHAPTER 25 Drug Interactions 380
Introduction 380
Mechanisms of drug interactions 380
Pharmacokinetic interactions 380
Absorption 381
Distribution 381
Metabolism 381
Clinically relevant pharmacokinetic druginteractions of AEDs 388
Pharmacodynamic interactions 392
Conclusions 393
References 394
CHAPTER 26 Medical Treatment of Epilepsy in Resource-Poor Countries 396
Introduction 396
Diagnosing epilepsy in LAMICS 396
Clinical history 396
Electroencephalogram 397
Neuroimaging 397
Blood investigations 397
Antiepileptic drug monitoring 397
Summary – the role of investigation 397
Treating epilepsy in LAMICs 398
Drug treatment of epilepsy 398
Stigmata of epilepsy in LAMICs 398
Non-pharmacological care of epilepsy 398
Epilepsy service organization in LAMICS 398
References 399
SECTION III Antiepileptic Drugs 401
CHAPTER 27 Introduction to the Choice of Antiepileptic Drugs 401
Spectrum of efficacy in relation to seizure types and epilepsy syndromes 402
Magnitude of efficacy in specific seizure types 403
Focal seizures 403
Generalized seizures 403
Adverse effect profile 404
Drug interaction potential 404
Impact on comorbidities 405
Other medication-related factors 405
Mechanisms of action 405
Availability of appropriate formulations 405
Dose escalation requirements 405
Monitoring requirements 406
Cost of treatment 406
Ease of use 406
Old or new drugs? 406
Approved versus off-label use 406
Importance of patient-related factors 407
Seizure types and epilepsy syndrome 407
Aetiology of epilepsy 407
Electroencephalographic features 407
Genotypes 407
Age and gender 408
Comorbidities and co-medications 408
Other patient-related factors 408
Conclusions 409
References 409
CHAPTER 28 Acetazolamide 412
Introduction 413
Chemistry 413
Mechanism of action and activity in animal models 413
Pharmacokinetics 414
Absorption 414
Distribution 414
Elimination 414
Drug interactions 414
Serum level monitoring 414
Efficacy 414
General overview of results of clinical trials 414
Absence seizures 418
Myoclonic seizures 418
Generalized tonic–clonic seizures 418
Focal seizures 418
Tolerance 419
Adverse effects 419
Idiosyncratic reactions 419
Common non-idiosyncratic adverse effects 420
Other adverse effects 420
Place in current therapy 421
Usefulness and limitations 421
Dosing recommendations 421
Precautions and contraindications 421
References 422
CHAPTER 29 Adrenocorticotropic Hormone and Corticosteroids 424
Introduction 425
Chemistry 426
Mechanisms of action 426
Pharmacokinetics 427
ACTH 427
Corticosteroids 427
Drug interactions 428
Serum level monitoring 428
Efficacy 428
Infantile spasms 428
Other epilepsy syndromes 430
Adverse effects 430
Current place in therapy 431
References 432
CHAPTER 30 Benzodiazepines Used in the Treatment of Epilepsy 434
Introduction 434
Chemistry 434
Mechanisms of action 434
Pharmacokinetics 434
Absorption 434
Distribution 435
Elimination 435
Drug interactions 440
Serum level monitoring 440
Efficacy 440
Clobazam 440
Clonazepam 441
Clorazepate 442
Diazepam 442
Lorazepam 443
Midazolam 444
Nitrazepam 445
Adverse effects 445
Clobazam 446
Clonazepam 446
Clorazepate 446
Diazepam 446
Lorazepam 448
Midazolam 448
Nitrazepam 448
Place of benzodiazepines in current therapy 448
Chronic epilepsy treatment 448
Emergency treatment 448
References 449
CHAPTER 31 Brivaracetam 454
Introduction 455
Chemistry 455
Pharmacology 455
Activity in experimental models of seizures and epilepsy 455
Evidence of activity in non-epilepsy indications 456
Mechanisms of action 456
Toxicology data 456
Studies conducted with the parent drug 456
Studies conducted with the inactive hydroxy acid metabolite 457
Pharmacokinetics 457
Absorption 457
Distribution 458
Elimination 458
Pharmacokinetics in special populations 458
Drug interactions 459
Effect of other drugs on brivaracetam pharmacokinetics 459
Effect of brivaracetam on the pharmacokinetics of other antiepileptic drugs 460
Effect of brivaracetam on the pharmacokinetics of other drugs 460
Serum level monitoring 460
Efficacy 460
Proof-of-concept study in photosensitive epilepsy 460
Randomized, placebo-controlled, adjunctive-therapy studies in uncontrolled focal epilepsy 460
Randomized flexible-dose adjunctive-therapy study in patients with focal or primarily generalized seizures 462
Other studies in patients with epilepsy 462
Studies in other indications 463
Adverse events 464
Place in current therapy 465
Acknowledgements 465
References 465
CHAPTER 32 Carbamazepine 467
Introduction 468
Chemistry 468
Pharmacology 468
Pharmacokinetics 468
Absorption 468
Distribution 469
Elimination 469
Relationship between serum concentration and dosage 469
Pharmacokinetics in special groups 469
Drug interactions 470
Interactions between carbamazepine and other AEDs 470
Interactions between carbamazepine and other drugs 471
Serum level monitoring 473
Efficacy 473
Focal seizures 473
Primary generalized tonic–clonic seizures 474
Epilepsy syndromes 475
Combination therapy 475
Efficacy in non-epilepsy conditions 475
Adverse effects 475
CNS effects 476
Cutaneous hypersensitivity reactions (including cutaneous reactions associated with systemic symptoms) 476
Haematological adverse effects 477
Hepatotoxicity 477
Endocrinological effects 477
Antidiuretic hormone and hyponatraemia 477
Thyroid hormones 477
Bone metabolism 478
Cardiac adverse effects 478
Teratogenic effects and postnatal development 478
Other adverse effects 478
Adverse effects and quality of life studies 478
Overdose 479
Place in current therapy 479
Mode of use 479
Dose and titration rates 479
Laboratory monitoring 479
References 480
CHAPTER 33 Eslicarbazepine Acetate 483
Introduction 484
Chemistry 484
Activity profile in animal models and mechanisms of action 484
Mechanisms of action and activity in experimental models [6] 484
Toxicology 485
Pharmacokinetics 485
Pharmacokinetics in healthy subjects and patients with epilepsy 485
Pharmacokinetics in special populations 486
Drug interactions 488
Effect of other drugs on ESL pharmacokinetics 488
Effect of ESL on other drugs pharmacokinetics 488
Serum drug level monitoring and pharmacokinetic–pharmacodynamic relationships 489
Efficacy 489
Randomized placebo-controlled trials 489
Open-label extensions studies 491
Adverse effects 491
Adverse events in adults with epilepsy 492
Adverse events in children with epilepsy 493
Other safety parameters 493
Place in current therapy 493
Acknowledgments 494
References 494
CHAPTER 34 Ethosuximide 496
Introduction 497
Chemistry 497
Pharmacology 497
Activity in experimental models of seizures and epilepsy 497
Activity in experimental models relevant to other indications 498
Mechanisms of action 498
Pharmacokinetics 498
Absorption 498
Distribution 498
Elimination 498
Pharmacokinetics in special populations 499
Drug interactions 499
Effects of other drugs on ethosuximide pharmacokinetics 499
Effect of ethosuximide on the pharmacokinetics of other drugs 499
Pharmacodynamic drug interactions 499
Serum level monitoring 499
Efficacy 500
Initial studies in patients with absence seizures 500
Double-blind comparison with valproic acid and lamotrigine in childhood absence epilepsy 500
Efficacy in specific syndromes other than childhood absence epilepsy 501
Adverse effects 501
Gastrointestinal effects 502
Neurological, behavioural and psychiatric effects 502
Other adverse effects, including idiosyncratic reactions 503
Manifestations of overdose 504
Place in current therapy 504
Indications 504
Dose and titration rates 504
Laboratory monitoring 504
References 505
CHAPTER 35 Felbamate 508
Introduction 509
Chemistry 509
Pharmacology 509
Activity in experimental models of seizures and epilepsy 509
Mechanisms of action 509
Pharmacokinetics 509
Absorption 509
Distribution 510
Elimination 510
Pharmacokinetics in special populations 510
Drug interactions 510
Serum level monitoring 510
Efficacy 511
Adverse effects 511
Place in current therapy 512
Update on risk–benefit ratio and indications 512
Dosing recommendations 513
Laboratory and clinical monitoring 513
Acknowledgement 513
References 513
CHAPTER 36 Gabapentin 515
Introduction 516
Chemistry 516
Pharmacology 516
Activity in experimental models 516
Mechanisms of action 516
Pharmacokinetics 516
Absorption 516
Distribution 517
Elimination 517
Pharmacokinetics in special groups 517
Drug interactions 517
Serum level monitoring 517
Efficacy 517
Adjunctive therapy in epilepsy 518
Monotherapy in epilepsy 519
Gabapentin in non-epilepsy indications 519
Adverse effects 520
General overview of the most common adverse effects 520
Serious, rare and long-term effects 521
Abuse and overdose 521
Use in pregnancy 521
Place in current therapy 522
Main indications 522
Administration and dosage 522
Acknowledgement 522
References 522
CHAPTER 37 Lacosamide 525
Introduction 526
Chemistry 526
Pharmacology 526
Activity profile in experimental models of seizures and epilepsy 526
Activity in models relevant to non-epilepsy indications 526
Mechanisms of action 526
Pharmacokinetics 527
Key pharmacokinetic features 527
Pharmacokinetics in special populations 527
Drug interactions 528
Effect of other drugs on the pharmacokinetics of lacosamide 528
Effects of lacosamide on the pharmacokinetics of other drugs 528
Pharmacodynamic drug interactions 528
Serum level monitoring 528
Efficacy 529
Placebo-controlled double-blind trials in focal seizures 529
Conversion to monotherapy double-blind trial in focal seizures 530
Open-label trials in patients with (mostly) focal seizures 530
Preliminary experience in the treatment of status epilepticus 530
Adverse effects 530
Most common adverse events reported in controlled trials 530
Special safety issues 531
Intravenous formulation 531
Place in current therapy 532
References 532
CHAPTER 38 Lamotrigine 534
Introduction 535
Chemistry 535
Pharmacology 535
Activity in animal models of seizures and epilepsy 535
Activity in other experimental models 536
Mechanism of action 536
Pharmacokinetics 536
Absorption 536
Distribution 536
Elimination 537
Factors (other than age and co-medication) that affect lamotrigine pharmacokinetics 537
Drug interactions 537
Effects of co-administered drugs on lamotrigine pharmacokinetics 537
Effects of lamotrigine on the pharmacokinetics of co-administered drugs 538
Pharmacodynamic interactions 538
Serum level monitoring 538
Efficacy 539
Adjunctive therapy studies in focal epilepsy 539
Conversion to monotherapy studies in refractory epilepsies 540
Monotherapy studies in newly diagnosed, predominantly focal, epilepsy 540
Adjunctive therapy studies in generalized epilepsies 542
Monotherapy studies in newly diagnosed generalized epilepsies 542
Other studies 543
Quality of life assessments 543
Risk of seizure aggravation 543
Use in non-epilepsy indications 543
Adverse effects 543
Overview of the most common adverse effects 543
Cognitive and psychomotor effects 544
Neurological and behavioural effects 544
Neuroendocrine effects 544
Child development 544
Idiosyncratic effects 545
Sudden unexpected death in epilepsy 545
Teratogenicity 546
Lamotrigine overdose 546
Place in current therapy 546
References 548
CHAPTER 39 Levetiracetam 552
Introduction 553
Chemistry 553
Pharmacology 553
Activity in experimental models of seizures and epilepsy 553
Mechanisms of action 553
Pharmacokinetics 554
Absorption 554
Distribution 554
Elimination 554
Pharmacokinetics in special populations 554
Drug interactions 555
Effect of other drugs on levetiracetam pharmacokinetics 556
Effect of levetiracetam on the pharmacokinetics of other drugs 556
Serum level monitoring 556
Efficacy 556
Adjunctive therapy trials in adults with refractory focal seizures 556
Adjunctive therapy trials in children with refractory focal seizures 558
Monotherapy trials in adults with focal seizures 558
Adjunctive therapy trials in adults and children with refractory generalized epilepsies 559
Monotherapy trials in patients with childhood and juvenile absence epilepsy 559
Studies in patients with myoclonus 560
Studies in patients with neonatal seizures 560
Studies in adults and children with status epilepticus 560
Studies in the palliative care setting 560
Studies in patients with traumatic brain injury 560
Studies on patient’s functioning and health-related quality of life in adults with epilepsy 560
Studies in non-epilepsy indications 561
Adverse effects 561
Safety and tolerability profile from clinical trials in adults 561
Safety and tolerability profile from clinical studies in children 561
Review of the comparative tolerability profile in adults and children 563
Behavioural adverse effects 563
Seizure aggravation 564
Tolerance 564
Cardiac effects 564
Idiosyncratic reactions 564
Tolerability and safety of the intravenous formulation 564
Teratogenicity 564
Overdosage 565
Place in current therapy 565
Acknowledgement 566
References 566
CHAPTER 40 Oxcarbazepine 569
Introduction 570
Chemistry 570
Pharmacology and mechanism of action 571
Pharmacokinetic properties 571
Absorption 571
Distribution 571
Biotransformation and elimination 571
Pharmacokinetics in special groups 572
Drug interactions 572
Serum level monitoring 573
Efficacy 573
Double-blind trials in comparison with carbamazepine 573
Double-blind trials in comparison with other AEDs 574
Randomized open-label trials in comparison with otherAEDs in new-onset seizures 574
Short-term double-blind monotherapy trials in comparison with placebo or low-dose active control 574
Double-blind adjunctive-therapy trials in comparison with placebo or low-dose active control 575
Uncontrolled studies 576
Use in non-epilepsy indications 576
Adverse effects 576
Worsening of seizures and/or EEG features 576
Other central nervous system adverse effects 576
Gastrointestinal effects 577
Rash and serious idiosyncratic reactions 577
Hyponatraemia 577
Other systemic effects and special populations 577
Teratogenicity 578
Adverse effects, seizures and quality of life 578
Mode of use 578
Dose initiation 578
Conversion from carbamazepine 578
Maintenance treatment 579
Monitoring serum sodium 579
Withdrawal 579
Current place in therapy 579
References 580
CHAPTER 41 Perampanel 582
Introduction 583
Chemistry 583
Pharmacology 583
Pharmacokinetics 583
Drug interactions 584
Effects of other drugs on the pharmacokinetics of perampanel 584
Effect of perampanel on the pharmacokinetics of other drugs 584
Serum level monitoring 585
Efficacy 585
Randomized placebo-controlled adjunctive therapy studies in focal epilepsy 585
Extension open label studies and additional observational studies 588
Randomized placebo-controlled adjunctive therapy study in primary generalized tonic-clonic seizures 588
Adverse effects 588
Overview of the tolerability and safety profile 588
Psychiatric adverse events 589
Place in current therapy 590
References 590
CHAPTER 42 Phenobarbital, Primidone and Other Barbiturates 591
Introduction 593
Phenobarbital 593
Chemistry 593
Activity in animal models and mechanisms of action 593
Pharmacokinetics 594
Drug interactions 596
Serum level monitoring 596
Efficacy 597
Adverse effects 599
Place in current therapy 603
Primidone 603
Chemistry 603
Activity in animal models and mechanisms of action 604
Pharmacokinetics 604
Drug interactions 604
Serum level monitoring 605
Efficacy 605
Adverse effects 605
Overdose 605
Place in current therapy 606
Other barbiturates 606
Barbexaclone 606
Metharbital 606
Methylphenobarbital (or mephobarbital) 606
References 607
CHAPTER 43 Phenytoin 610
Introduction 611
Chemistry 611
Pharmacology 611
Anticonvulsant activity in experimental models 611
Mechanisms of action 611
Pharmacokinetics 612
Absorption 612
Distribution 612
Elimination 612
Drug interactions 614
Interactions affecting phenytoin absorption 614
Interactions affecting phenytoin distribution 614
Interactions altering phenytoin metabolism 616
Phenytoin affecting other substances 616
Serum level monitoring 616
Efficacy 617
Adverse effects 618
Effects on the nervous system 618
Effects on the skin 618
Effects on the gums 618
Effects on bone 620
Effects on lymphoid tissue 620
Effects on folates 620
Cardiovascular effects 620
Other effects 620
Teratogenicity 620
Place in current therapy 621
References 622
CHAPTER 44 Piracetam 625
Introduction 626
Chemistry and mechanism of action 627
Pharmacokinetics 627
Absorption 627
Distribution 627
Metabolism and excretion 627
Drug interactions 628
Serum level monitoring 628
Efficacy 628
Adverse effects 629
Place in current therapy 629
References 630
CHAPTER 45 Pregabalin 631
Introduction 632
Chemistry 632
Pharmacology 632
Pharmacokinetics 632
Absorption 632
Distribution and elimination 632
Pharmacokinetics in special groups 632
Drug interactions 632
Serum level monitoring 633
Efficacy 633
Double-blind adjunctive-therapy trials versus placebo in focal epilepsy 633
Double-blind adjunctive-therapy trials in focal epilepsy in comparison with other antiepileptic drugs 636
Open-label uncontrolled studies of adjunctive use in focal epilepsy 636
Preliminary uncontrolled studies of adjunctive use in pediatric epilepsies 637
Conversion to monotherapy in patients with refractory focal epilepsy 637
Double-blind randomized comparison with lamotrigine in newly diagnosed focal epilepsy 637
Controlled studies on epilepsy comorbidities 638
Adverse effects 638
Adverse events in double-blind adjunctive-therapy trials 638
Adverse events reported in long-term studies and in routine clinical use 639
Potential for abuse 639
Teratogenicity 640
Place in current therapy 640
References 640
CHAPTER 46 Retigabine 642
Introduction 643
Chemistry 643
Pharmacology 643
Activity in experimental models of seizures and epilepsy 643
Activity in experimental models relevant for non-epilepsy indications 643
Mechanisms of action 644
Toxicology data 645
Pharmacokinetics 645
Absorption 645
Distribution 646
Metabolism and elimination 646
Pharmacokinetics in special populations 646
Drug interactions 646
Effect of other drugs on retigabine pharmacokinetics 646
Effect of retigabine on pharmacokinetics of other drugs 646
Serum level monitoring 647
Clinical efficacy 647
Phase 2 studies 647
Phase 3 studies 647
Long-term open label extension trials 647
Studies in patients with other disorders 648
Adverse effects 648
Current place in therapy 650
References 650
CHAPTER 47 Rufinamide 653
Introduction 654
Chemistry 654
Pharmacology 654
Activity in experimental models of seizures and epilepsy 654
Mechanism of action 655
Pharmacokinetics 655
Absorption and bioavailability 655
Distribution 655
Elimination and metabolism 655
Pharmacokinetics in special populations 656
Drug interactions 656
Effect of other drugs on rufinamide pharmacokinetics 656
Effect of rufinamide on the pharmacokinetics of other drugs 657
Serum level monitoring 657
Efficacy 657
Monotherapy studies in patients with focal seizures 657
Adjunctive therapy studies in patients with focalseizures 658
Adjunctive therapy studies in patients with generaliz edepilepsies 659
Open-label studies in various epileptic syndromes 660
General overview of efficacy data in epilepsy 660
Studies in other indications 660
Adverse effects 660
Overall safety profile 660
Effect on cognitive functions 661
Current place in therapy 661
Acknowledgement 662
References 662
CHAPTER 48 Stiripentol 664
Introduction 665
Chemistry 665
Pharmacology 665
Pharmacokinetics 665
Drug interactions 666
Serum level monitoring 666
Efficacy 666
Adverse effects 667
Current place in therapy 667
References 667
CHAPTER 49 Tiagabine 669
Introduction 670
Chemistry 670
Pharmacology 670
Activity in animal models of seizures and epilepsy 670
Mechanism of action 670
Pharmacokinetics 670
Key pharmacokinetic features 670
Pharmacokinetics in special populations 671
Drug interactions 671
Serum level monitoring 671
Efficacy 671
Randomized trials in adults with focal epilepsy 671
Other studies in (predominantly) adult patients with focal epilepsy 673
Studies in children 673
Efficacy as monotherapy 673
Adverse effects 674
Most common CNS adverse effects 674
Other CNS adverse effects 674
Visual field investigations 675
Idiosyncratic reactions 675
Teratogenicity 675
Place in current therapy 676
References 676
CHAPTER 50 Topiramate 678
Introduction 679
Chemistry 679
Pharmacology 679
Pharmacokinetics 679
Overall pharmacokinetic features 679
Pharmacokinetics in special populations 680
Drug interactions 680
Serum level monitoring 680
Efficacy 681
Monotherapy 681
Adjunctive therapy 682
Studies in other paediatric epilepsy syndromes 683
Special epilepsy populations 683
Elderly populations 683
Non-epilepsy indications 683
Adverse effects 684
Central nervous system adverse effects 684
Metabolic acidosis, bone effects and renal calculi 684
Weight loss 685
Ophthalmological adverse effects 685
Hepatic adverse effects 685
Adverse effects in children 685
Adverse effects during pregnancy/puerperium 685
Place in current therapy 685
References 686
CHAPTER 51 Valproate 688
Introduction 689
Chemistry 689
Pharmacology 689
Activity in animal models of seizures and epilepsy 689
Mechanisms of action 690
Pharmacokinetics 690
Rate and extent of absorption 690
Distribution 690
Elimination 691
Pharmacokinetics in special groups 691
Drug interactions 692
Effect of other drugs on valproic acid pharmacokinetics 692
Effect of valproic acid on the pharmacokinetics of other drugs 692
Pharmacodynamic drug interactions 693
Serum level monitoring 693
Efficacy 693
Absence seizures 693
Generalized tonic–clonic seizures 694
Myoclonic seizures 695
Infantile spasms and Lennox–Gastaut syndrome 695
Focal seizures 695
Status epilepticus 695
Other seizure disorders 696
Non-epilepsy indications 696
Adverse effects 696
Teratogenic effects (including effects on postnatal cognitive development after prenatal exposure) 697
Neurological adverse effects 697
Gastrointestinal adverse effects, including weight gain 697
Hepatic and pancreatic toxicity 698
Haematological adverse effects 698
Metabolic, endocrine and reproductive disorders 698
Miscellaneous adverse effects 699
Place in current therapy 699
Acknowledgement 700
References 700
CHAPTER 52 Vigabatrin 703
Introduction 704
Chemistry 704
Pharmacology and toxicology 704
Activity in experimental models of seizures and epilepsy 704
Animal toxicology data 704
Mechanism of action 705
Pharmacokinetics 705
Adults 705
Infants and children 705
Disease states 705
Drug interactions 705
Serum level monitoring 706
Efficacy 706
Infantile spasms (West syndrome) 706
Focal seizures 708
Generalized epilepsies 709
Adverse effects 709
Visual field constriction 709
MRI abnormalities 712
Place in current therapy 712
References 713
CHAPTER 53 Zonisamide 716
Introduction 717
Chemistry 717
Pharmacology 717
Activity in animal models 717
Mechanisms of action 718
Pharmacokinetics 718
Pharmacokinetics in special groups 718
Drug interactions 718
Serum level monitoring 719
Efficacy 719
Randomized controlled trials 719
Other studies 720
Adverse effects 721
Common adverse effects 721
Less common but potentially serious adverse effects 721
Teratogenicity 722
Place in current therapy 722
Acknowledgement 723
References 723
CHAPTER 54 Other Less Commonly Used Antiepileptic Drugs 725
Introduction 725
Bromide 725
Chemistry 726
Mechanisms of action and activity in experimental models of seizures and epilepsy 726
Clinical pharmacokinetics 726
Drug interactions 726
Clinical efficacy 726
Adverse effects 728
Place in current therapy 728
Lidocaine 728
Chemistry 729
Mechanism of action 729
Clinical pharmacokinetics 729
Drug interactions 729
Clinical efficacy 729
Adverse effects 729
Place in current therapy 729
Methsuximide 730
Chemistry 730
Mechanism of action 730
Clinical pharmacokinetics 730
Drug interactions 730
Clinical efficacy 730
Adverse effects 731
Place in current therapy 731
Paraldehyde 731
Chemistry 732
Mechanism of action 732
Clinical pharmacokinetics 732
Drug interactions 732
Clinical efficacy 732
Adverse effects 733
Place in current therapy 733
Sulthiame 733
Chemistry 734
Mechanism of action 734
Clinical pharmacokinetics 734
Drug interactions 734
Clinical efficacy 734
Adverse effects 734
Place in current therapy 735
Acknowledgement 735
References 735
CHAPTER 55 Drugs in Clinical Development 737
Introduction 737
Allopregnanolone (SAGE-547 Injection) 737
Chemistry 737
Activity in animal models and mechanism of action 737
Pharmacokinetics 737
Drug interactions 737
Efficacy 738
Adverse effects 738
Cannabinoids 738
Chemistry 738
Activity in animal models and mechanism of action 738
Pharmacokinetics 738
Drug interactions 738
Efficacy 738
Adverse effects 738
2-Deoxy-d-glucose 738
Activity in animal models and mechanism of action 738
Pharmacokinetics and drug interactions 738
Efficacy and adverse effects 739
Everolimus 739
Chemistry 739
Activity in animal models and mechanism of action 739
Pharmacokinetics 739
Drug interactions 739
Efficacy 739
Adverse effects 739
Ganaxolone 739
Activity in animal models and mechanism of action 739
Pharmacokinetics 739
Drug interactions 739
Efficacy 739
Adverse effects 739
Huperzine A (INS-001) 740
Activity in animal models and mechanism of action 740
Pharmacokinetics 740
Drug interactions 740
Efficacy and adverse effects 740
NAX 810-2 740
Activity in animal models and mechanism of action 740
Preclinical pharmacokinetics and drug interactions 740
Pitolisant 740
Activity in animal models and mechanism of action 740
Pharmacokinetics and drug interactions 741
Efficacy 741
Adverse effects 741
PRX-00023 (naluzotan) 741
Activity in animal models and mechanism of action 741
Pharmacokinetics 741
Drug interactions 741
Efficacy and adverse effects 741
Selurampanel 741
Activity in animal models 741
Pharmacokinetics and drug interactions 741
Efficacy and adverse effects 741
Tonabersat 741
Activity in animal models and mechanism of action 742
Pharmacokinetics 742
Drug interactions 742
Efficacy and adverse effects 742
YKP3089 742
Activity in animal models and mechanism of action 742
Pharmacokinetics 742
Efficacy 742
Adverse effects 742
Precision therapeutics and the promise of genomics 742
Conclusions 743
References 743
SECTION IV Presurgical assessment and epilepsy surgery 745
CHAPTER 56 Overview of surgical treatment for epilepsy 745
Introduction 745
Historical perspective 746
Epileptic disorders 747
The progressive nature of epilepsy 747
The concept of surgically remediable epilepsies 747
Types of surgical treatment for epilepsy 748
Standardized resections 749
Tailored resections 749
Disconnection surgery 749
Stereotactic ablative surgery and stimulation 750
Presurgical evaluation 750
Definition of terms 750
Candidate selection 751
Strategy for presurgical evaluation 753
Outcome 753
Outcome with respect to seizures 753
Quality of life, cognitive and social outcomes 755
Surgical complications 755
Acknowledgements 756
References 756
CHAPTER 57 Scalp EEG in the epilepsy surgery evaluation 759
Introduction 759
Technical considerations 759
Electrode locations 759
Types of scalp EEG recording 760
Interictal EEG 760
Unilateral focal temporal interictal epileptiform discharges 761
Bilateral independent interictal epileptiform discharges 761
Extratemporal interictal epileptiform discharges 761
Interictal non-epileptiform changes 761
Interictal epileptiform discharges that may preclude resective epilepsy surgery 762
Ictal scalp EEG 762
Ictal patterns 762
Postictal EEG changes 762
Inter-rater reliability of ictal EEG 762
Limitations of scalp ictal EEG 762
False lateralization: mesial temporal lobe epilepsy 763
False lateralization: lesional epilepsy 763
Late-appearing scalp ictal EEG 763
Bilateral independent temporal ictal EEG 763
Scalp ictal EEG in non-lesional MRI 763
Ictal behaviour: the role of video 764
Psychogenic non-epileptic seizures 764
Seizure activation during video-EEG monitoring 765
Antiepileptic drug withdrawal 765
Sleep deprivation 765
Hyperventilation 766
Photic stimulation 766
Potential complications 766
Conclusion 766
References 766
CHAPTER 58 Invasive EEG in presurgical evaluation of epilepsy 769
Introduction 769
Indications for intracranial EEG monitoring 769
Non-lesional extratemporal epilepsies 769
Neocortical temporal lobe epilepsy 770
Lesional epilepsy 770
Dual pathology 770
Mesial temporal lobe epilepsy 771
Special situations in MTLE often requiring invasive monitoring 771
Invasive monitoring and responsive neurostimulation 772
Identifying networks on intracranial EEG 773
Technical aspects in intracranial EEG 774
Specific intracranial electrode techniques 775
Technical aspects 776
Advantages 777
Disadvantages 777
Interpretation of invasive EEG recordings 778
Recording sessions 778
General comments 779
Background 779
Filter settings 779
Non-epileptiform findings 779
Interictal EEG 779
Ictal EEG 780
Functional cortical mapping and advanced electrophysiological techniques 786
General comments 786
Electrical cortical stimulation 786
Electrocorticography-based gamma mapping 787
Corticocortical evoked potentials 787
Electrocorticography (ECoG) 787
High-frequency oscillations 787
Ictal onset baseline shifts and infraslow activity (ISA) 788
References 788
CHAPTER 59 MEG in epilepsy surgery evaluation 792
Introduction 792
Method 793
Applications of magnetic source imaging in epileptic patients 793
Evoked activity 793
Spontaneous epileptic activity 794
MEG in presurgical evaluation 795
Acknowledgement 797
References 797
CHAPTER 60 MRI in presurgical evaluation 800
Introduction 800
When to use MR imaging and where to perform it 800
General MRI protocol 800
Common epileptogenic lesions 801
Class A: easy candidates 802
Class B: moderately difficult cases 807
Class C: very difficult surgical cases 807
Class D: palliative surgery candidates 807
Class E: non-surgical candidates 807
Specific MRI protocols 807
Diffusion-based imaging and tractography 807
Functional MRI 808
MR spectroscopy 809
Postprocessing 809
References 809
CHAPTER 61 PET and SPECT in presurgical evaluation of epilepsy 811
PET and SPECT in presurgical evaluation of patients with refractory partial epilepsy 811
PET 811
Methodology 811
FDG-PET and ictal onset zone in refractory focal epilepsy 812
FDG-PET hypometabolism in areas remote from the ictal onset zone 814
Clinical correlations of resolution of FDG hypometabolism in areas remote from the ictal onset zone after seizure remission 817
AMT-PET in refractory focal epilepsy 817
SPECT 817
Methodology 817
Ictal SPECT in presurgical evaluation 818
Multimodality imaging 819
References 821
CHAPTER 62 Special neurophysiological techniques 823
Introduction 823
Source imaging of interictal spikes: methodology and validation 823
Equivalent current dipole modelling of interictal spikes 823
Imaging of the spiking volume 826
Distributed sources models 826
Volumetric imaging of epileptic spikes 827
Accuracy of spiking volume localization 827
Limitation of spiking volume imaging 828
Validation studies of interictal spikes source imaging 828
Intracranial recordings 828
Source imaging of interictal spikes and MRI lesions 830
Source imaging of interictal spikes and metabolic abnormalities 831
Clinical relevance of spikes source imaging in presurgical evaluation of epilepsy 833
Does source imaging help to lateralize the focus in TLE with bilateral interictal spikes? 833
Is spike source imaging helpful to predict epilepsy surgery outcome? 834
Diagnostic yield of magnetic source imaging of spikes in MRI-negative patients 834
Is spike source imaging helpful to guide intracranial recordings? 834
The modelling of ictal discharges 835
Functional connectivity studies 835
Overview of the methods aimed at characterizing epileptic networks 835
What have we learned from studying epileptogenic networks? 836
Outstanding questions 836
Conclusions 836
References 837
CHAPTER 63 Neuropsychological testing in presurgical evaluation 840
Introduction 840
Determination of site of dysfunction 840
Potential pitfalls in presurgical evaluation 841
Temporal neocortex 841
Medial temporal lobe function: memory assessment 842
Traditional memory tests 842
Matched verbal and non-verbal learning and memory tests 843
Other verbal learning and memory tests 844
Non-verbal learning and memory tests 844
Accelerated long-term forgetting 845
Evaluation of frontal lobe function 845
Complex problem solving: Wisconsin Card Sorting Test 845
Generation of novel responses: word and design fluency 845
Susceptibility to interference (cognitive inhibition) 846
Planning: the Tower of London test 846
Motor tasks: strength, dexterity and coordination 846
Parietal lobes 846
Occipital lobes 847
Computer-assisted batteries 847
Summary 847
Intracarotid anaesthetic procedures 847
Description of the procedure 848
Interpretation of intracarotid anaesthetic procedure results: language dominance 848
Interpretation of intracarotid anaesthetic procedure results: memory 848
Controversial issues in the IAP 848
Non-invasive lateralization procedures 849
Conclusion 850
Acknowledgments 850
References 850
CHAPTER 64 Presurgical psychiatric evaluation 853
Introduction 853
The case for a presurgical psychiatric evaluation in every surgical candidate 853
High prevalence of psychiatric comorbidities in surgical candidates: can it get in the way of the presurgical evaluation? 853
Postsurgical psychiatric complications 854
Epilepsy surgery has a positive impact on presurgical psychiatric disorders 857
Anxiety and depressive disorders 857
Obsessive compulsive disorders 857
Psychotic disorders 857
Impact of presurgical psychiatric history on postsurgical psychosocial outcome 858
Gainful employment 858
Family dynamics 858
Impact of presurgical psychiatric illness on postsurgical seizure outcome 858
Psychiatric aspects of paediatric epilepsy surgery 859
Presurgical psychiatric protocols 859
The obstacles to perform presurgical psychiatric evaluation 859
Can epileptologists and neuropsychologists rely on a patient’s self-report of past or concurrent psychiatric history? 859
Suggested protocols 860
Presurgical evaluations in research 860
Disclosure of postsurgical psychiatric complications 862
Conclusions and future directions 862
References 862
CHAPTER 65 Mesial temporal lobe surgery and other lobar resections 865
Introduction 865
Current practices of medial temporal lobe surgery 865
Extratemporal resections and temporal lobe resections outside the medial temporal lobe 866
Frontal lobe surgery 866
Occipital lobe surgery 867
Parietal lobe surgery 867
Insular epilepsy 867
Multilobar resections 867
Lobar epilepsy surgery evaluation 868
Positron emission tomography 868
Single photon emission computed tomography 868
Other magnetic resonance imaging methods: magnetic resonance spectroscopy, diffusion tensor imaging, high field MRI 868
Magnetoencephalography or magnetic source imaging 869
Functional magnetic resonance imaging 869
Neurocognitive evaluation 869
‘Wada test’ in select cases 869
Transcranial magnetic stimulation 869
Intracranial studies 869
Epilepsy surgery outcomes 870
Epilepsy surgery complications 873
New therapies and future directions 874
Conclusion 874
Acknowledgement 875
References 875
CHAPTER 66 Resective surgery of neoplasms 878
Introduction 878
Focal or localization-related epilepsy 878
Mechanism of epileptogenesis associated with structural mass lesions 879
Pathology: neoplastic lesions 879
Brain tumour as a cause of chronic epilepsy 880
Gangliogliomas 880
Dysembryoplastic neuroepithelial tumours 881
Presurgical evaluation 882
Duration of epilepsy 882
Clinical seizure characteristics 882
History and examination 883
Age at onset of seizures 883
Routine electroencephalogram recording 883
Long-term video-electroencephalogram monitoring 883
Neuroimaging 883
Neuropsychological assessment 885
Intracranial electroencephalogram monitoring 886
Diffusion weighted imaging and diffusion tensor imaging 886
Magnetic resonance spectroscopy 886
Functional magnetic resonance imaging 886
Single photon emission computed tomography 886
Positron emission tomography 887
Invasive cortical mapping 887
Electrocorticography 887
Treatment 887
Indications for surgery 887
Patients with medically intractable epilepsy 887
Surgical methods 887
Outcome 888
Seizure outcome 888
Pathology 888
Completeness of lesion resection 888
Completeness of epileptic focus resection 888
Functional outcome 888
Psychological outcome 889
References 889
CHAPTER 67 Resective surgery of vascular and infective lesions for epilepsy 894
Introduction 894
Vascular lesions 894
Arteriovenous malformations 894
Cavernous haemangioma (cavernoma) 897
Intracranial aneurysms 899
Venous malformations 899
Capillary telangectasias 899
Infective lesions 900
Pyogenic cerebral abscess 900
Neurocysticercosis 904
Cerebral tuberculoma 906
Hydatid disease 908
References 909
CHAPTER 68 Surgery of developmental anomalies causing epilepsy 914
Introduction 914
Epidemiology 914
Selection of surgical candidates 914
Presurgical evaluation: to determine the extent of the epileptogenic zone 915
History, physical examination and seizure semiology 915
Role of imaging 915
Role of electrophysiology 916
Surgical outcome 917
Surgical outcome in grey matter heterotopia 917
Surgical outcome in lissencephaly 918
Surgical outcome in hemimegalencephaly 918
Surgical outcome in polymicrogyria and schizencephaly 918
Surgical outcome in porencephaly 918
Surgical outcome in focal cortical dysplasia 918
Conclusion 919
References 920
CHAPTER 69 Hemispheric operations for epilepsy 923
Introduction 923
Indications 923
Diagnostic evaluations 924
Special considerations in Rasmussen encephalitis 925
Evolution of the surgical techniques 925
Functional hemispherectomy 925
Vertical parasagittal hemispherotomy 926
Seizure outcome 928
Postoperative seizures 928
Early and late complications 928
Conclusion 929
References 929
CHAPTER 70 Corpus callosum operations 931
Introduction 931
Indications 931
Surgical technique 932
Conclusion 935
References 935
CHAPTER 71 Hypothalamic hamartoma 939
Introduction 939
Clinical features 939
Gelastic seizures 939
Intrinsic epileptogenesis 940
Other seizure types 940
Secondary epileptogenesis 941
Cognition and behaviour 941
Aetiology 941
Pallister–Hall syndrome 941
Somatic mutation of GLI3 941
Treatment 941
Antiepilepsy drugs 941
Vagus nerve stimulation 942
Ketogenic diet 942
Corpus callosotomy 942
Deep brain stimulation 942
Surgical treatment 942
Hypothalamic hamartoma classification and surgical anatomy 942
Pterional approach to hypothalamic hamartoma lesions 943
Transcallosal resection 943
Endoscopic resection and disconnection 944
Interstitial radiosurgery 947
Stereotactic radiosurgery (gamma knife radiosurgery) 947
Stereotactic thermoablation 947
Staged procedures for giant hypothalamic hamartoma 948
Reoperation after subtotal surgical treatment 948
References 948
CHAPTER 72 Multiple subpial transection 952
Introduction 952
Planning for multiple subpial transection 952
Cortical surgical anatomy 953
Operative procedure 953
Transections 953
Outcome 953
Indications for multiple subpial transection 954
Mesial temporal lobe epilepsy 954
Landau–Kleffner syndrome 955
Multifocal epilepsy 955
Super-refractory status epilepticus 955
Surgical morbidity 956
Acute postoperative morbidity 956
Chronic morbidity 956
Conclusions 956
Acknowledgment 957
References 957
CHAPTER 73 Awake surgery for epilepsy 958
Introduction 958
Preoperative and intraoperative functional assessments 959
Anaesthesia for awake craniotomy 960
Indications for awake tailored resection for medically refractory epilepsy versus anatomically guided resections 961
Technical aspects of temporal lobe resection tailored to intraoperative recording and stimulation 962
Preoperative preparation 962
Anaesthetic technique 962
Premedication and positioning 962
Local anaesthesia 963
Craniotomy 963
Intraoperative electrocorticography 963
Electrode placement and ECoG#1 963
Stimulation parameters 964
Motor and sensory mapping 964
Language mapping 964
Lateral cortical resection, ECoG#2 and hippocampal removal 964
References 965
CHAPTER 74 Epilepsy surgery in children 967
Introduction 967
Therapy-resistant epilepsy and the rationale for early seizure control 967
Which children are surgical candidates? 967
Risks of uncontrolled epilepsy 968
Why is it critical to control seizures as soon as possible in infants and children even if that means resective surgery? 968
Symptomatic substrates in surgically treated children 968
Pre-evaluation in paediatric epilepsy surgery 971
Surgical interventions for epilepsy in children 972
Anaesthesia and perioperative considerations 973
Outcomes in paediatric epilepsy surgery: seizure remission and cognitive/psychosocial results 974
Conclusion 974
Acknowledgement 974
References 975
CHAPTER 75 Complications of epilepsy surgery 977
Introduction 977
Complications of invasive procedures for presurgical assessment 977
Carotid amytal test 977
Invasive procedures for placing electrodes 977
Minor invasive techniques 977
Major invasive techniques 978
Summary 979
Therapeutic procedures 979
Introduction 979
Intracranial resective surgery 979
Reoperation 982
Functional surgery 982
Risk management 983
Conclusion 984
References 984
CHAPTER 76 Anaesthesia for epilepsy surgery 988
Overview 988
Preanaesthetic evaluation for epilepsy surgery 988
Anaesthesia and antiepileptic therapy 988
Anticonvulsant and proconvulsant effects of anaesthetics 989
Anaesthesia and intraoperative electrocorticography 990
Anaesthesia for diagnostic procedures prior to epilepsy surgery 990
General anaesthesia for epilepsy surgery 990
Anaesthesia for epilepsy surgery with awake intraoperative functional brain mapping 991
Anaesthesia for vagal nerve stimulator placement 992
Anaesthesia for epilepsy surgery in infants and children 992
Anaesthesia for stereotactic MRI-guided laser ablation of epileptogenic foci 992
Conclusion 992
References 992
CHAPTER 77 Vagus and trigeminal nerve stimulation 995
Introduction 995
Practical aspects of vagus nerve stimulation 995
Actions of vagus nerve stimulation and efficacy in animal models of epilepsy 995
Anatomy 995
Mechanism(s) of action of vagus nerve stimulation 996
Animal studies of vagus nerve stimulation 996
Efficacy studies of vagus nerve stimulation 996
The E03 and E05 studies 996
Long-term efficacy 997
Other efficacy studies 997
Safety and tolerability of vagus nerve stimulation 998
The E03 and E05 studies 998
Long-term safety and tolerability 998
Clinical use of vagus nerve stimulation for epilepsy 999
Emerging technologies for vagus nerve stimulation 1000
Trigeminal nerve stimulation for epilepsy 1000
Conclusion 1000
References 1001
CHAPTER 78 Brain stimulation for epilepsy 1003
Introduction 1003
Concept and requirements for programmed or chronic stimulation 1004
Concept of responsive neurostimulation 1004
Previous studies of chronic or programmed central neurostimulation 1005
Stimulation of the cerebellum 1005
Chronic stimulation of the thalamus 1006
Chronic stimulation of the subthalamic region 1008
Chronic stimulation of the hippocampus 1008
Clinical studies of responsive neurostimulation 1009
Unresolved questions 1011
Conclusion 1013
References 1013
CHAPTER 79 Non-resective approaches for medically intractable epilepsy 1016
Introduction 1016
Preclinical evidence 1016
Mesial temporal lobe epilepsy 1017
Hypothalamic hamartoma-associated gelastic epilepsy 1018
Arteriovenous malformations 1019
Cavernous malformations 1019
Long-term radiosurgical complications 1020
Antiepileptic mechanisms of radiosurgery 1020
Laser ablation 1020
Focused ultrasound 1020
References 1021
CHAPTER 80 Future focal treatment approaches to epilepsy 1023
Introduction 1023
Focal treatment principles 1023
Focal drug delivery 1023
The epileptic focus 1023
The trigger site 1025
Propagation pathways 1025
Other focal drug delivery approaches 1025
Seizure-stimulated drug release 1026
Focal cooling 1026
Genetic approaches to treatment 1026
Viral vectors 1026
Neuronal grafting 1027
Transplantation of genetically engineered cells 1028
New therapeutic approaches for focal epilepsy 1029
Optogenetics 1029
Chemical genetic attenuation 1031
Conclusion 1032
Acknowledgements 1032
References 1032
CHAPTER 81 Epilepsy surgery in countries with limited resources 1035
Introduction 1035
The need for epilepsy surgery in countries with limited resources 1036
Challenges to implement epilepsy surgery programmes 1036
Simplification of presurgical evaluation protocols in surgically remediable epilepsies: conceptual advances and the impact on epilepsy surgery in countries with limited resources 1037
Patients with MTLE-HS can be evaluated non-invasively, and often without the need for ictal recordings 1037
Lesionectomy plus electrocorticography-guided corticectomy can successfully treat most medically refractory epilepsies due to neocortical and limbic tumours 1037
Surgical decisions in children with severe epilepsies associated with large unilateral lesions are usually straightforward 1038
The stepwise approach and the minimal requirements for epilepsy surgery 1038
Present state of epilepsy surgery in resource-limited countries 1039
The Brazilian experience 1039
Epilepsy surgery in other countries in Latin America 1039
Epilepsy surgery in resource-limited countries in Asia 1039
Epilepsy surgery in Africa 1039
Surgical treatment gap 1039
Temporal trends in epilepsy surgery in resource-limited countries 1040
Surgical outcome in resource-limited countries 1040
Is epilepsy surgery cost-effective in resource-limited countries? 1040
Are minimum requirements for performing epilepsy surgery changing? 1041
A final word on education, early identification of refractory seizures and the value of epilepsy surgery 1041
Conclusions 1041
References 1041
Index 1044
EULA 1075

Produkt-Details

• Erscheint lt. Verlag: 15.9.2015
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Allgemeines / Lexika
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
• Schlagworte: acetazolamide • Adrenocorticotropic hormone and corticosteroids • Adult epilepsy • AEDs • American Academy of Neurology • American Epilepsy Society • anti-epileptic drugs • barbiturates • Benzodiaze-pines used in epilepsy • Biowissenschaften • Brivaracetam • Carbamazepine • Childhood Epilepsy • Emilio Perucca • Epilepsie • Epilepsy • epilepsy syndromes • Eslicarbazepine acetate • Ethosuximide • Felbamate • Gabapentin • iagabine • International Epilepsy Conference • International League of Epilepsy • Jerome Engel Jr • Lacosamide • Lamotrigine • Levetiracetam • Life Sciences • Medical Science • Medizin • Neurological • Neurologie • Neurology • Neuroscience • neurosurgery • Neurowissenschaften • Oxcarbazepine • pediatric dosing • Perampanel • Pharmacokinetic • Phenobarbital • Phenytoin • piracetam • Pregabalin • primidone • Retigabine • Rufinamide • Simon Shorvon • Stiripentol • The Treatment of Epilepsy • Topiramate • Valproate • Vigabatrin • Zonisamide
• ISBN-10: 1-118-93698-1 / 1118936981
• ISBN-13: 978-1-118-93698-6 / 9781118936986