Introduction to Epilepsy

Cover
Introduction to Epilepsy
Title
Copyright
Dedication
Contents
Contributors
Foreword by Dr Edward H. Reynolds
The Fund, the Centre and the Institute
The MSc Course in Epilepsy
Preface
Acknowledgements
Section 1 Basic principles
Chapter 1 History of epilepsy
Introduction
Ancient descriptions and concepts
Epilepsy as a brain disorder
Functional localization and unilateral seizures
Idiopathic and symptomatic epilepsy
Basic mechanisms: vascular and electromagnetic theories
The psychiatry of epilepsy
Epilepsy as a social disorder
Learning objective
Chapter 2 What is epilepsy?
Reference
Learning objectives
Chapter 3 Functional anatomy of the central nervous system
Cerebral hemispheres
Cerebral cortex
Regions of cortex
Topographic and contralateral organization of motor and sensory cortices
Connections of the cortex
Functional anatomy of speech function
Hemisphere specialization (asymmetries)
The limbic system and the physiology of emotions
Subcortical structures
Sleep
Recommended reading
Reference
Learning objectives
Chapter 4 Introduction to neurochemistry and receptor pharmacology
Neurons and glia
The cell membrane of the neurons
Basic anatomy of the neuron
Anatomy and physiology of the synapse
Membrane receptors
Agonists and antagonists
Cortical neurons
Layers of cortex
Surround inhibition
Neuromodulators
Learning objectives
Chapter 5 Cellular electrophysiology: membrane, synaptic and action potentials
Some key concepts about the physiology of cell membrane
Behaviour of the cell membrane at rest
Equilibrium potential
Excitable cells and postsynaptic potentials
Action potentials
Membrane channels and currents
Sodium channels
Calcium channels
Potassium channels
Sodium-potassium currents or hyperpolarizing inward rectification (Ih)
The paroxysmal depolarizing (or depolarization) shift (PDS)
Recommended reading
Learning objectives
Chapter 6 Techniques used to study epilepsy in the laboratory: experimental techniques in basic neurophysiology
Experimental models in vitro
Artificial membrane-channel preparations
Acutely isolated neuron
Chronically cultured neurons
Slice culture
Brain slices
Isolated brain
Experimental techniques in vitro
Single-channel patch clamp
Whole-cell patch clamp
Perforated patch clamp
Intracellular recordings (sharp electrode technique)
Current and voltage clamp recordings
Optical recording methods
Electrical extracellular stimulation
Experimental models and experimental techniques in vivo
Single-cell extracellular recordings
Intracranial EEG recordings
Local drug application
Microdialysis
Lesional models
Learning objective
Chapter 7 Techniques used to study epilepsy in the laborator
Handling of epilepsy surgical specimens
Histochemistry
Immunohistochemistry
Electron microscopy
Molecular and genetic techniques for diagnosis and research of epilepsy diagnosis
Recommended reading
Learning objective
Chapter 8 Functional anatomy and physiology of the hippocampus
Recommended reading
Learning objectives
Chapter 9 Neurotransmission and biochemistry of neurotransmitters in epilepsy
Glutamate and excitatory neurotransmission
AMPA and NMDA receptors
Kainate receptors
Glutamate metabotropic receptors
GABA and inhibitory neurotransmission
GABA transporters
GABAA receptors
Phasic inhibition and tonic inhibition
Genetic defects involving the GABAA receptor and epileptic syndromes
GABAB receptors
GABA-transaminase and the further metabolism of GABA
GABA-ergic circuitry is the basis of recurrent inhibition and surround inhibition
References
Learning objectives
Chapter 10 Experimental models of epilepsy
Drug screening
Basic mechanisms
Chronic models – focal epilepsy
Secondarily generalized seizures
Chronic models – idiopathic generalized epilepsies
Conclusions
Recommended reading
Learning objectives
Chapter 11 Epileptogenesis in vitro
Introduction
Types of epileptogenesis
Mechanisms of epileptogenesis
Stages of epileptogenesis
Seizure types
Reactive seizures and epileptogenesis
Epileptogenesis at molecular level
Epileptogenesis at cellular level
Epileptogenesis at the network level (slices)
The role of synchronization
The epileptic hippocampus
Conclusion
Recommended reading
Learning objective
Chapter 12 Epileptogenesis in vivo
In vivo animal models of epilepsy
Mechanisms of focal seizures in man
Mechanisms of generalized seizures in man
Cellular and synaptic mechanisms of generalized spike-wave
Recommended reading
References
Learning objectives
Chapter 13 Neuropathology of epilepsy
Introduction
Changes secondary to epilepsy
Status epilepticus
Chronic epileptic brain damage
Mesial temporal sclerosis (MTS)
Cerebellar atrophy
Diffuse neocortical atrophy
Traumatic injuries due to epileptic falls
Possible iatrogenic damage
Sudden unexpected death in epileptics (SUDEP)
Symptomatic epilepsy
Cerebral malformations
Cortical dysplasia
Mild malformation of cortical development (MCD)
Focal cortical dysplasia (FCD)
Tuberous sclerosis
Perinatal brain damage
Vascular malformations
Infections
Rasmussens encephalitis
Febrile convulsions
Trauma
Tumours
Ganglioglioma
Dysembryoplastic neuroepithelial tumour (DNT)
Myoclonic epilepsy
A. Progressive encephalopathy accompanied by myoclonic jerks
B. Myoclonus is a presenting symptom leading to progressive neurological deterioration
Lafora body disease (see also Chapter 30: `Progressive myoclonic epilepsies´)
Unverricht-Lundborg disease (Baltic myoclonus epilepsy)
Mitochondrial myopathy with ragged red fibres (MERRF)
Ramsay Hunt syndrome
Neurosurgery and neurosurgical pathology of epilepsy
Genetics of epilepsy
Recommended reading
Learning objective
Chapter 14 Introduction to the electroencephalogram (EEG)
The electroencephalogram (EEG)
How is an EEG recorded?
Recording and reviewing principles
How to interpret an EEG
Useful EEG terminology
Learning objectives
Chapter 15 Phenomenology of normal EEG: effects of age and state of awareness
Introduction
Normal background
Artefacts
Normal transients and benign variants
Effects of state and age
Recommended reading
References
Learning objectives
Chapter 16 Pathological EEG phenomena and their significance
Epilepsy
Brain tumours
EEG findings in intracranial tumours
Cerebrovascular disorders
EEG findings in cerebrovascular disorders
Hypoxic brain damage
Encephalitis
Herpes simplex encephalitis
Creutzfeldt–Jakob disease (CJD)
Subacute sclerosing panencephalitis
Hepatic encephalopathy
Status epilepticus (SE)
Cardiac arrhythmia
References
Learning objectives
Section 2 Classification and diagnosis of epilepsy
Chapter 17 Electroclinical classification of seizures and syndromes
International classifications
Classification of seizures
Focal seizures
Focal seizures with preserved consciousness ('simple partial seizures' according to the 1981 ILAE seizure classification)
Motor signs
Sensory symptoms
Autonomic symptoms and signs
Psychic symptoms
Focal seizures with impairment of consciousness
Manifestations of seizures with impaired consciousness
Other focal seizures
Classification of focal seizures according to the site of origin
Generalized seizures
EEG manifestations of seizures
Evolution of ILAE classifications of seizures
Classification of the epilepsies
Practical examples for epilepsy classification
Relevance of epilepsy classification
Future perspectives
Other classifications
References
Learning objectives
Chapter 18 Clinical use of EEG in epilepsy
The value of interictal EEG in epilepsy
Background activity
Paroxysmal abnormalities in epilepsy
Photoparoxysmal responses
Effects of hyperventilation
Summary on interpretation of the interictal EEG in epilepsy
Ictal EEG recordings
Indications of ictal recordings
EEG findings during ictal recordings
How to interpret ictal recordings
Common misconceptions about the EEG in epilepsy
Reference
Learning objectives
Chapter 19 General overview of epileptic syndromes in childhood and adolescence
Characteristics of epilepsy syndromes
Benign epilepsy of childhood with centrotemporal spikes (BECTS)
Seizure types
Interictal EEG findings
Course and prognosis
Early-onset benign occipital epilepsy (Panayiotopoulos syndrome)
Seizure types
EEG findings
Course and prognosis
Late-onset occipital epilepsy (Gastaut type)
Types of seizures
EEG findings
Course and prognosis
Idiopathic photosensitive occipital epilepsy
Chronic progressive epilepsia partialis continua of childhood (Kojewnikow syndrome) and Rasmussen´s syndrome
Childhood absence epilepsy
Seizure types
EEG findings
Course and prognosis
Juvenile absence epilepsy
Seizure types
EEG findings
Course and prognosis
Juvenile myoclonic epilepsy (Janz syndrome)
Seizure types
EEG findings
Course and prognosis
Lennox-Gastaut syndrome
Seizure types
Causes
EEG findings
Course and prognosis
Myoclonic-astatic epilepsy (MAE) (Doose syndrome)
Seizure types
EEG findings
Course and prognosis
Other myoclonic epilepsies
Landau-Kleffner syndrome (acquired epileptic aphasia)
Seizure types
EEG findings
Course, prognosis and treatment
Continuous spike-waves during slow-wave sleep (CSWS) syndrome
Seizure types
EEG findings
Conclusion
Recommended reading
Learning objective
Chapter 20 Neonatal seizures
Aetiology
Clinical manifestation and classification
Diagnosis
Treatment
Prognosis
References
Learning objectives
Chapter 21 Epileptic encephalopathies in the first year of life
Introduction
West syndrome or infantile spasms
Early epileptic encephalopathies with suppression-burst EEG
References
Learning objectives
Chapter 22 Epileptic encephalopathies in early childhood
Introduction
Lennox-Gastaut syndrome (LGS)
A strict (European) definition requires
Myoclonic-astatic epilepsy
Atypical benign partial epilepsy
Reference
Learning objectives
Chapter 23 Febrile convulsions/seizures and related epileptic syndromes
Introduction
Febrile seizures
Febrile convulsions
Dravet syndrome or severe myoclonic epilepsy of infancy (DS)
Generalized epilepsy with febrile seizures plus (GEFS+)
References
Learning objectives
Chapter 24 Idiopathic focal epilepsies
Introduction
Rolandic epilepsy
Panayiotopoulos syndrome
The idiopathic occipital lobe epilepsies
Investigations
Management
Other proposed benign focal epilepsies of childhood
Learning objectives
Questions
Chapter 25 The idiopathic generalized epilepsies
Seizure types
Typical absence seizures
Myoclonic seizures (myoclonic jerks)
Generalized tonic-clonic seizures (GTCS)
Syndromes of IGE
Benign myoclonic epilepsy of infancy
Childhood absence epilepsy (CAE)
Juvenile absence epilepsy (JAE)
Juvenile myoclonic epilepsy (JME)
Epilepsy with GTCS only
Epilepsy with myoclonic absences (EMyA)
Eyelid myoclonia with absences (EMAb)
Other syndromes and possible syndromes of IGE
Investigations
Treatment
Learning objectives
Questions
Chapter 26 Temporal lobe epilepsy
Epidemiology and etiology
Medial/mesial temporal lobe epilepsy
Semiology of seizures (Box 26.2 and Table 26.1)
Lateral temporal epilepsy
Investigations
EEG (Boxes 26.3 and 26.4)
MRI
Treatment
Medication
Surgery
Recommended reading
References
Learning objectives
Chapter 27 Frontal lobe epilepsy
Epidemiology and etiology
Manifestations
Management
Autosomal dominant frontal lobe epilepsy (ADFLE)
Epilepsia partialis continua
References
Learning objective
Chapter 28 Parietal and occipital focal symptomatic epilepsies
Parietal lobe epilepsy
Occipital lobe epilepsy
Investigations
Management
Learning objective
Chapter 29 Epilepsy and myoclonus
General characteristics of myoclonus
Physiological characteristics of epileptic myoclonus
Rhythmic myoclonus
Negative myoclonus
Cortical action-reflex myoclonus
Myoclonus in symptomatic generalized epileptic syndromes
Myoclonus in idiopathic generalized epilepsy syndromes
Epileptic syndromes with myoclonus of unclear neurophysiological characteristics
Reticular reflex myoclonus
Treatment of epileptic myoclonus
Recommended reading
References
Learning objectives
Chapter 30 Progressive myoclonic epilepsies
Lafora body disease
Unverricht-Lundborg disease
Dentato-rubro-pallido-luysian atrophy (DRPLA)
Sialidosis
Mitochondrial disease (myoclonic epilepsy with ragged red fibres syndrome or MERRF)
Late infantile NCL
Juvenile Gaucher disease
Progressive neuronal degeneration of childhood with liver disease (Alpers disease)
Treatment of PME
Recommended reading
Learning objectives
Chapter 31 Acute symptomatic seizures
Epileptic seizures without epilepsy
Characteristics of acute symptomatic seizures
Causes of acute symptomatic seizures
Incidence of acute symptomatic seizures
Cumulative incidence of acute symptomatic seizures
Prognosis of acute symptomatic seizures
References
Learning objectives
Chapter 32 EEG in neonates and children
Definitions
Normal neonatal EEG
Technique
Normal neonatal EEG
Full term
Pre-term EEG
Abnormal neonatal EEG
Dysmaturity
Subtle background changes asymmetry/asynchrony
Discontinuous EEG (periods of suppression 20 V, bursts 150 V)
Continuous low-voltage inactive EEG (CLV)
Burst-suppression pattern – stable or invariant for 2 weeks
Early infantile epileptic encephalopathy (EIEE or Ohtaharas syndrome)
Early (neonatal) myoclonic encephalopathy (EME)
Neonatal seizures
The EEG in childhood
The normal EEG in childhood
Epileptic encephalopathy in infancy and early childhood
Infantile spasms and West syndrome
Severe myoclonic epilepsy of infancy (Dravet syndrome)
Malignant migrating partial seizures of infancy
Lennox-Gastaut syndrome
Idiopathic generalized epilepsy syndromes
Childhood absence epilepsy
Benign myoclonus of infancy
Myoclonic-astatic epilepsy
Juvenile myoclonic epilepsy
Idiopathic focal epilepsy syndromes
Benign childhood epilepsy with centrotemporal spikes
Panayiotopoulos syndrome
References
Learning objectives
Chapter 33 Applications of EEG other than epilepsy
Brain disease
Dementia
Infections of the central nervous system
Encephalopathy
Space-occupying lesions (SOL)
Identification of syncope
Brainstem death
Learning objective
Chapter 34 Evoked potentials in epilepsy
Summary
Introduction
Basics of visual evoked cortical potentials (VEPs) and electroretinography (ERG)
The role of VEP and ERG in epilepsy
Basics of auditory evoked potentials (AEPs)
The role of AEPs in epilepsy
Basics of sensory evoked potentials (SEPs)
The role of SEPs in epilepsy
Conclusion
References
Learning objectives
Chapter 35 Introduction to neuroimaging and relevant anatomical landmarks
Learning objectives
Chapter 36 The role of structural imaging in the assessment of epilepsy
Conclusion
Recommended reading
Learning objectives
Chapter 37 Indications for neuroradiological investigation of epilepsy
New-onset seizures
Chronic epilepsy
Recommended reading
References
Learning objectives
Questions
Chapter 38 Volumetric MRI and MRI spectroscopy
Magnetic resonance imaging and spectroscopy
Basic principles of nuclear magnetic resonance
Nuclear spin
Hydrogen nuclei in a magnetic field
Precession
Excitation and resonance
Relaxation and detection of the MR signal
Magnetic resonance image formation
Magnetic field gradient
Slice selection
Encoding spatial information within a slice
Volumetric MRI
Magnetic resonance spectroscopy
References
Learning objective
Chapter 39 Functional MRI in epilepsy
Introduction
How does fMRI work? And why is the way it works a problem in patients?
Problem 1: it is not known whether the normal link between neuronal activity and BOLD is the same in pathological brain
Problem 2: fMRI images are often subject to distortion, low resolution, signal loss and movement artefact, giving rise to anatomical uncertainties
Problem 3: there is no consensus regarding `study design´ in clinical fMRI
Problem 4: what does brain activity mean? How should statistical thresholds be applied?
fMRI in epilepsy patients
Identification of primary sensorimotor cortex
Lateralization and localization of language
Mesial temporal (memory) function
References
Learning objectives
Questions
Chapter 40 SPECT in epilepsy
Background
Interictal studies
Ictal SPECT
Research
Other applications in epilepsy
References
Learning objectives
Questions
Chapter 41 PET in epilepsy
Introduction
Methodological considerations
The `old´ PET tracer: FDG and flumazenil
The new PET tracer
Opiate neurotransmission
Serotonergic neurotransmission
Glutamatergic neurotransmission
Malformations of cortical development
Tumours
`MRI-negatives´
Recommended reading
References
Learning objectives
Chapter 42 Advanced MRI sequences – diffusion tensor imaging
Introduction
Background
The biological and physical basis of diffusion-based imaging
From diffusion tensor imaging to tractography
Methods
Selecting a seed region
Tractography algorithms
Tract analysis
Results
Language – the superior longitudinal fasciculus
Memory – the parahippocampal gyrus
Preoperative planning – visual pathways
Future goals
Conclusion
Recommended reading
Learning objectives
Chapter 43 EEG-correlated fMRI in epilepsy
EEG and functional MRI
Combined EEG and fMRI experiments
References
Learning objectives
Chapter 44 Source localization methods
Other source identification techniques
References
Learning objectives
Chapter 45 Magnetoencephalography in epilepsy
Introduction
MEG signal
The MEG equipment
Relative merits
References
Learning objectives
Chapter 46
History-taking and physical examination in epilepsy
Introduction
Background factors in history-taking
History of the seizures
History of the patient
The physical examination in epilepsy
Interictal examination in patients with new seizure presentation
Interictal examination in patients with treated epilepsy
Ictal examination (examination during a seizure)
Recommended reading on history-taking
Recommended reading on physical examination
Learning objectives
Chapter 47
The role of video-EEG monitoring in epilepsy
Diagnosis of epilepsy
Diagnosis of psychogenic non-epileptic seizures
Classification of seizures in known epilepsy
Focus localization
Evaluation of clinical syndromes
Subtle seizures
Estimation of seizure frequency
Detection of precipitating factors
Recommended reading
References
Learning objectives
Chapter 48
Cardiovascular syndromes simulating epilepsy
Epilepsy syndromes
Cerebral perfusion
Syncope
Neurocardiogenic syncope
Autonomic failure
Treatment of syncope
Conclusion
Learning objectives
Chapter 49
Sleep disorders simulating epilepsy
Introduction
Attacks of unusual behaviour
Attacks associated with NREM sleep
Attacks associated with REM sleep
Attacks associated with narcolepsy
Other sleep conditions that may be mistaken for epilepsy
Reference
Learning objectives
Chapter 50
Psychiatric disorders mistaken for epilepsy
Introduction
Why might psychiatric disorders be confused with epilepsy?
Panic disorder
Psychosis
Other psychiatric disorders
Conclusion
Recommended reading
Learning objectives
Chapter 51
Differential diagnosis of epilepsy: migraine and movement disorders
Migraine
Clinical differences between migraine and epilepsy
Is there a link between migraine and epilepsy?
Movement disorders
Paroxysmal kinesigenic choreoathetosis
Paroxysmal non-kinesigenic choreoathetosis
Paroxysmal ataxia and tremor
Tonic spasms of multiple sclerosis
Hyperekplexia
References
Learning objectives
Chapter 52
Differential diagnosis of epilepsy in children
Differential diagnosis in childhood epilepsy
What else could it be?
Syncope and related disorders
Disorders of orthostatic control include:
Behavioural and psychiatric disorders
Neurological disorders
Sleep disorders
Recommended reading
Learning objectives
Chapter 53
Investigation of newly diagnosed and chronic epilepsy in adults
Assessment of acute symptomatic seizures
Cardiology assessment
Identification of new/progressive neurological disease
Identification of fixed static disease
Routine blood tests
Electroclinical classification of seizures
Indications for routine and specialist EEG investigations
Structural imaging
Functional imaging
Epilepsy with autoimmune disease, progressive deterioration or atypical features
Epilepsy and autoimmune disease
Rarer cases of seizures and epilepsy
Epilepsy and progressive cognitive decline
Recommended reading
Learning objective
Chapter 54
The role of investigations in the management of epilepsy in children
The role of neurophysiology
The EEG
Types of EEG and their use
Neuroimaging
Structural imaging
The role of functional imaging
Other investigations
Recommended reading
Learning objective
Chapter 55
Case scenarios in paediatric epilepsy
Samuel
Key learning points from this case
Rubi
Key learning points from this case scenario
Sadia
Key learning points from this case scenario
Teresa
Key learning points from this case scenario
Some of the key learning points from this case scenario
In summary
Reference
Learning objectives
Chapter 56
Psychogenic non-epileptic seizures: diagnostic approach
Misdiagnosis: facts and consequences
Definition, terminology and classification
Investigating for psychogenic non-epileptic seizures
Limitations and pitfalls of video-EEG telemetry
Video-telemetry modalities in the diagnosis of psychogenic non-epileptic seizures
Protocol for the `Activation Clinic´ at Kings College Hospital in London
How to make a diagnosis of non-epileptic seizures
References
Learning objectives
Chapter 57
Seminar: paediatric EEG reporting session
Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Answers
Recommended reading
Learning objective
Section 3 Epidemiology
Chapter 58 Epidemiology of epilepsy
What is epidemiology?
Objectives of epidemiology with regard to epilepsy
Definition of epilepsy
Incidence of epilepsy
Total population studies
Age-specific incidence
Gender
Seizure types
Race
Time trends
Epilepsy syndromes
Cumulative incidence
Prevalence of epilepsy
Causes of epilepsy (etiology)
Epidemiological study designs to identify risk factors
Risk factors for epilepsy (Hesdorffer and Verity, 1997)
Other risk factors for epilepsy
Non-genetic risk factors of childhood epilepsy
Recommended reading
References
Learning objectives
Chapter 59 Prognosis of newly diagnosed and chronic epilepsy
Prognosis of epilepsy
Basic definitions
Prognosis after a single seizure
Risk factors for recurrence after a first seizure
Natural history of treated epilepsy
Natural history of untreated epilepsy
Spontaneous remission without treatment
Effects of early treatment on prognosis
Prognosis of specific syndromes
References
Learning objectives
Chapter 60 Single seizures
Good prognosis
Poorer prognosis
Investigations and management
Recommended reading
Learning objectives
Chapter 61 Epidemiology of epilepsy in childhood
Introduction to epilepsy in childhood
Epilepsy in infants
Febrile convulsions
Infantile spasms
Epilepsy in children
Commoner causes of non-febrile epilepsy in children
History-taking
Clinical observation
Main types of seizures in childhood
The type of epilepsy
Epilepsy emergencies
Non-epilepsy seizures
Recommended reading
Learning objectives
Chapter 62 Mortality in epilepsy
Summary
Background
Standardized mortality ratio (SMR) and proportional mortality
Causes of death in epilepsy
Suicides
Treatment of epilepsy
Seizure-related deaths
Accidental deaths
Status epilepticus
SUDEP – sudden unexpected (`unexplained´) death in epilepsy
Excess mortality in epilepsy: practical implications
Recommended reading
Learning objectives
Section 4 Genetics of epilepsy
Chapter 63 Introduction to modern molecular genetics: a genetics timeline
Learning objective
Chapter 64 Methods of molecular genetics
Strategies for identification of epilepsy genes
Mendelian epilepsies
Non-mendelian epilepsies
Learning objective
Chapter 65 Progress in the genetics of the epilepsies
Mendelian epilepsies
Non-mendelian epilepsies
Chromosomal epilepsies
The future
Recommended reading
Learning objective
Section 5 Management of epilepsy
Chapter 66 Neurochemistry of antiepileptic drug action
Introduction
AED action via voltage-gated ion channels
Voltage-gated sodium channels
Actions of AEDs on VG sodium channels
Voltage-gated calcium channels
Actions of AEDS on VG Ca2+ channels
Voltage-gated potassium channels
AED action via GABA-mediated inhibitory transmission
GABAA receptors and AEDs
Action of AEDs on GABA re-uptake and further metabolism
GABAB receptors and epilepsy
AED action via glutamatergic excitatory transmission
AMPA and kainate receptors
NMDA receptors
Glutamate metabotropic receptors
Actions of glutamate antagonists on epileptogenesis
Mechanism of AED action in relation to side effects
Conclusion
Recommended reading
Learning objectives
Chapter 67 Antiepileptic drug pharmacokinetics and therapeutic drug monitoring
Introduction
Pharmacokinetics
Therapeutic drug monitoring
Sampling time
Biological matrixes
Altered drug binding to plasma proteins
`Therapeutic ranges vs `reference ranges vs `individualized therapeutic concentrations
Carbamazepine
Eslicarbazepine acetate
Ethosuximide
Felbamate
Gabapentin
Lacosamide
Lamotrigine
Levetiracetam
Oxcarbazepine
Phenobarbital
Phenytoin
Pregabalin
Primidone
Rufinamide
Stiripentol
Tiagabine
Topiramate
Valproic acid
Vigabatrin
Zonisamide
Conclusions
Recommended reading
Learning objectives
Chapter 68 Antiepileptic drug trials and their methodology
Preclinical trials
Introduction
Drug discovery
Models and methods
The ADD program
Predicting clinical activity
Additional investigations
Future studies
Summary
Clinical trials
Introduction
Basic principles
Sample size
Inclusion/exclusion criteria
Randomization
Blinding
Control
Dose selection
Analysis
Trial designs
Cross-over studies (Figure 68.1)
Parallel-group studies (Figure 68.2)
Long-term extension studies
Phase I trials
Phase II trials
Phase III trials
Submission and approval
Phase IV studies
Monotherapy trials
Active control
Low-dose control
Novel designs
Summary
References
Learning objectives
Chapter 69 Treatment with traditional antiepileptic drugs
Principles of drug treatment
Toxicity
Advantages of traditional antiepileptic drugs
Disadvantages of traditional antiepileptic drugs
Chronic toxicity of barbiturates and hydantoins
Clinical use of phenobarbitone
Clinical use of phenytoin
Clinical use of carbamazepine
Clinical use of sodium valproate
Clinical use of lamotrigine
Clincial use of ethosuximide
Clinical use of benzodiazepines
Conclusions
Recommended reading
Learning objectives
Chapter 70 Treatment with `new´ antiepileptic drugs
Background
NICE and AEDs
Meta-analyses and Cochrane reviews
New-onset epilepsy
Intractable epilepsy
Where are we now?
Selected features of some of the new AEDs, listed alphabetically
References
Learning objectives
Chapter 71 Pharmacological interactions
Introduction
Mechanisms of drug interactions
Pharmacokinetic interactions
Interactions affecting drug absorption
Displacement from plasma protein binding
Metabolic drug interactions
Interactions affecting renal excretion
Pharmacodynamic interactions
Interactions between different AEDs
Carbamazepine
Eslicarbazepine acetate
Ethosuximide
Gabapentin
Lacosamide
Lamotrigine
Levetiracetam
Oxcarbazepine
Phenobarbital
Phenytoin
Pregabalin
Primidone
Rufinamide
Stiripentol
Tiagabine
Topiramate
Valproic acid
Vigabatrin
Zonisamide
Conclusions
Recommended reading
Learning objectives
Chapter 72 Monotherapy or polytherapy?
Introduction
Reasons for polytherapy (Box 72.1)
Problems associated with polytherapy (Box 72.2)
Unnecessary polytherapy
Monotherapy in newly diagnosed patients
Conclusions
References
Learning objective
Chapter 73 Antiepileptic drugs currently under development
Introduction
Brivaracetam
Mechanism of action
Pharmacokinetics
Drug interactions
2-Deoxy-D-glucose
Mechanism of action
Pharmacokinetics
Drug interactions
Fluorofelbamate
Mechanism of action
Pharmacokinetics
Drug interactions
Ganaxolone
Mechanism of action
Pharmacokinetics
Drug interactions
JZP-4
Mechanism of action
Pharmacokinetics
Drug interactions
Retigabine (D-23129)
Mechanism of action
Pharmacokinetics
Drug interactions
Safinamide (FCE 26743; PNU-151774E; NW-1015)
Mechanism of action
Pharmacokinetics
Drug interactions
Seletracetam (ucb 44212)
Mechanism of action
Pharmacokinetics
Drug interactions
T2000
Mechanism of action
Pharmacokinetics
Drug interactions
Talampanel (LY300164; GIKY 53773)
Mechanism of action
Pharmacokinetics
Drug interactions
Tonabersat (SB-220453)
Mechanism of action
Pharmacokinetics
Drug interactions
Valrocemide (N-valproyl-glycinamide; TV 1901)
Mechanism of action
Pharmacokinetics
Drug interactions
YKP3089
Mechanism of action
Pharmacokinetics
Drug interactions
Conclusions
Recommended reading
Learning objective
Chapter 74 Antiepileptic drug withdrawal
Background
Clinical practice
Recommended reading
Learning objective
Chapter 75 Behavioural effects of antiepileptic drugs
Introduction
Confounding factors affecting behaviour
Older drugs
Well-established drugs
Newer drugs
Vigabatrin
Lamotrigine
Gabapentin
Topiramate
Tiagabine
Oxcarbazepine
Levetiracetam
Zonisamide
Pregabalin, rufinamide, lacosamide, stiripentol and eslicarbazepine
Felbamate
Conclusions
References
Learning objectives
Chapter 76 Epilepsy emergency treatment
Non-medical management of seizures, by Gonzalo Alarcón
What to do during a convulsive seizure (patient unresponsive, stiff or jerking)
What to do during a complex partial seizure or prolonged epileptic absence (patient vacant or confused, unresponsive or partially responsive, and may have automatisms)
What to do during very brief seizures (absence seizures, myoclonic jerks, atonic and some tonic seizures)
What to do during a simple partial seizure (patient fully conscious)
Once the seizure has stopped
If the seizure is not stopping
Emergency treatment of prolonged seizures, by Frank Besag
Conclusions
Recommended reading and references
Learning objectives
Chapter 77 Clinical neuropsychological evaluation
References
Learning objectives
Chapter 78 Neuropsychological effects of antiepileptic drugs
Introduction
Evaluating the evidence
Neuropsychological effects of AEDs
Older AEDs
Newer AEDs
Further considerations
Conclusion
References
Learning objectives
Chapter 79
The Wada test (intra-arterial amobarbital procedure)
Introduction
The procedure
Interpretation
Lateralizing language function
Left and right brain support for memory
Controversies about use and alternatives
Recommended reading
Learning objectives
Chapter 80 General principles of surgical treatment
Resective surgery
Who is a potential surgical candidate?
Defining the focus
Defining the risks of surgery
Functional surgery
Multiple subpial transactions (MST)
Corpus callosotomy
Learning objectives
Chapter 81 Preoperative assessment
Who can be operated on and when to suggest surgery
Surgical strategies
Purpose of presurgical assessment
Clinical contraindications to surgery for epilepsy
Presurgical assessment
Medical history
Seizure semiology
Neuropsychiatric assessment
Neuroimaging
Quantification of MR images (hippocampal volume, hippocampal T2 measurements)
Positron emission tomography (PET)
Single proton emission tomography (SPECT)
Neuropsychology
Interictal scalp EEG
Magnetoencephalography
Ictal scalp EEG
The amytal test (carotid amobarbital test, Wada test)
Intracranial EEG recordings
Foramen ovale electrodes
Subdural electrodes
Depth (intracerebral) electrodes
Epidural peg electrodes
Indications for implantation of intracranial electrodes
Complications of intracranial electrodes
Interpretation of intracranial recordings
Functional mapping
Phased evaluation
Misconceptions about presurgical assessment in epilepsy surgery
References
Learning objectives
Chapter 82 Surgical techniques
Surgery for mesial temporal sclerosis
Lesionectomy
Hemisphere procedures
Learning objective
Chapter 83 Outcome of surgery
Resective surgery
Functional surgery
Conclusions
References
Learning objectives
Chapter 84 Epilepsy surgery in children
Outcome
Conclusions
References
Learning objectives
Chapter 85 Vagus nerve stimulation
Learning objective
Chapter 86 Brain stimulation for the treatment of epilepsy
Recommended reading
Reference
Learning objective
Chapter 87 Diagnosis and treatment of hypothalamic hamartomas
Diagnosis
Management
Medical treatment
Resective surgical treatment
Non-resective surgical treatment
References
Learning objective
Chapter 88 Intraoperative (acute) electrocorticography (ECoG)
Effects of general anaesthesia on discharges
Value of activation procedures
Is excision of all discharging areas necessary?
Value of residual discharges
ECoG in temporal lobe surgery
ECoG in frontal lobe surgery
New developments
Learning objectives
Chapter 89 Single-pulse electrical stimulation
Conclusion
References
Learning objectives
Chapter 90 Ketogenic diet in the management of childhood epilepsy
Recommended reading
Learning objective
Section 6 Epilepsy in specific circumstances.
Chapter 91 Reflex epilepsies
The stimulus
The response
References
Learning objective
Chapter 92 Photosensitive and language-induced seizures and epilepsies
Photosensitive epilepsy
Definition
Laboratory (EEG) and clinical photosensitivity
Prevalence
Precipitants
Pure photosensitive epilepsy
Photosensitivity and epilepsy syndromes
Visual stimuli
Video game (VG) sensitive seizures
Pattern-sensitive epilepsy
Fixation-off sensitive epilepsies
Idiopathic photosensitive occipital seizures (IPOS) and epilepsy (IPOE)
Treatment
References
Learning objective
Chapter 93 Audiogenic epilepsies
Startle epilepsy
Musicogenic epilepsy
Conditions that may be mistaken for audiogenic epilepsy
Audiogenic epilepsy models in rodents
Recommended reading
Learning objective
Chapter 94 Reading epilepsy
Description
Prevalence
Ictal semiology
Treatment
Reference
Learning objective
Chapter 95 Status epilepticus: classification and pathophysiology
Introduction
Epidemiology
Classification
Status epilepticus as a staged phenomenon
Conclusion
Recommended reading
Learning objectives
Chapter 96 Status epilepticus: diagnosis and management
Diagnosis
Principles underlying treatment
Randomized clinical trials in status epilepticus
Drug treatment of convulsive status epilepticus
Premonitory phase
Established status epilepticus
Refractory status epilepticus
Drug treatment of non-convulsive status epilepticus
Conclusion
Learning objectives
Chapter 97 Management of epilepsy in women
Learning objectives
Chapter 98 Catamenial seizures
Management
Reference
Learning objective
Chapter 99 The management of epilepsy in children
References
Learning objectives
Chapter 100 Learning and educational issues in epilepsy
Epidemiology
Learning disability
Risk factors for learning difficulties
Epilepsy syndromes
Seizures
Behavioural problems
Antiepilepsy medication
Types of learning difficulties and neurophysiological mechanisms
Management
References
Learning objectives
Chapter 101 Epilepsy in old age
Seizures in the elderly
Impact of seizures in old age
Diagnosis of seizures in old age
Causes of seizures in old age
Investigation of epilepsy in the elderly
Frequently asked questions
Starting treatment in the elderly
Choice of drugs in the elderly
Carbamazepine
Phenytoin
Valproate
Levetiracetam
Lamotrigine
Gabapentin
Important considerations to determine the dose of AEDs in the elderly
Complications of epilepsy in old age
References
Learning objectives
Chapter 102 Epilepsy and learning
Prevalence
Relationships between epilepsy and learning disability
Conclusions
References
Learning objectives
Chapter 103 Epilepsy in chromosomal and related disorders
Angelman syndrome (AS)
Rett syndrome
Down syndrome
Ring chromosome 20
Recommended reading
Recommended websites
Learning objective
Chapter 104 Epilepsy and cerebral trauma
Conclusion
References
Learning objectives
Questions
Chapter 105 Epilepsy after cerebral tumours, hamartomas and neurosurgery
Conclusions
References
Learning objectives
Questions
Chapter 106 Epilepsy and cerebrovascular disease
Factors in relationship between CVD and epilepsy
Types of CVD
Mechanisms for ischaemia
Mechanisms for haemorrhage
Epidemiology of CVD
Risk factors for stroke
Relationship between CVD and epilepsy
Types of seizures
Role of the EEG
Treatment strategies
Prognosis
Recommended reading
Learning objectives
Chapter 107 Abnormalities of neuronal migration
Lissencephaly/band heterotopia
Cobblestone complex
Grey matter heterotopia
Recommended reading
Learning objectives
Chapter 108 Malformations of cortical development
Conclusions
References
Learning objectives
Questions
Chapter 109 Rasmussens disease and epilepsia partialis continua
Chronic (Rasmussens) encephalitis
Conclusions
References
Learning objectives
Questions
Chapter 110 Behavioural treatment of epilepsy
Recommended reading
Learning objective
Section 7 Psychiatric, social and legal aspects
Chapter 111 Affective disorders and epilepsy
Introduction
Depression in epilepsy
Ictal depression
Peri-ictal depression
Treatment of ictal and peri-ictal depression
Interictal depression
Treatment of interictal depression
Use of antidepressants in epilepsy
Bipolar mood disorder in epilepsy
Recommended reading
Learning objectives
Chapter 112 Anxiety disorders and epilepsy
References
Learning objectives
Chapter 113 Personality and epilepsy
References and recommended reading
Learning objective
Chapter 114 The psychoses of epilepsy
Pre-ictal states
Minor status
Conclusion
Reference
Learning objective
Chapter 115 Epilepsy and aggression
References and recommended reading
Learning objective
Chapter 116 Epilepsy in childhood: effects on behaviour and mental health
Introduction
Behavioural disorders
Causes of behavioural problems
The epilepsy itself
The treatment of the epilepsy
The reactions to the epilepsy
Associated brain damage
Coincidental causes
Assessment
Management
Recommended reading
Learning objectives
Chapter 117 Psychogenic non-epileptic (dissociative) seizures: psychiatric aspects
What are dissociative seizures?
Clinical features of dissociative seizures
Clinical semiology
Ictal observation/examination
Psychiatric co-morbidity
Management
Recommended reading
Learning objectives
Chapter 118 Psychiatric effects of surgical treatment for epilepsy
Learning objective
Chapter 119 Use of psychotropics in people with epilepsy
Special considerations for use of psychotropic drugs in epilepsy
Effects on seizure threshold
Pharmacokinetic interactions
General rules to use psychotropics in people with epilepsy
References
Learning objectives
Chapter 120 Time-limited psychodynamic counselling for people with epilepsy
Conclusion
Recommended reading
References
Learning objective
Chapter 121 Evaluation of quality of life in epilepsy
Generic
Disease-specific
Physical and psychological impact of seizures and treatment and their impact on QOL
Psychological impact of the diagnosis and seizures
Seizure type and severity
Antiepileptic drug therapy
Measuring QOL in children and adolescents
Cultural and ethnic considerations
Applications of HRQOL scales in epilepsy
Clinical drug trials
Interventions and epilepsy surgery
Clinical practice and monitoring treatment
Practical advice: improving peoples quality of life
The most commonly used HRQOL tools in epilepsy
Quality Of life In Epilepsy Instruments (QOLIE 31, QOLIE 89 and QOLIE 10)
Epilepsy Surgery Inventory-55 (ESI-55)
Liverpool Quality Battery
Repertory Grid Assessments
References and recommended reading
Learning objectives
Chapter 122 Cultural aspects of epilepsy: stigma, prejudice, self-image
Internalized stigma
Interpersonal stigma
Institutional stigma
Real stigma
Perceived stigma
References
Learning objectives
Chapter 123 Epilepsy, marriage and the family
Epilepsy and marriage
Impact of epilepsy on relationships and marriage
Sexuality and epilepsy
Fertility
Practical advice
Recommended reading
Epilepsy and the family
If a child develops epilepsy
School performance
If the parent has a diagnosis of epilepsy
References and recommended reading
Learning objectives
Chapter 124 Epilepsy and employment
Epilepsy and employment: a historical context
Epilepsy and employment: what are the issues now?
Overview of barriers to, and concerns about, employment
The Equality Act 2010
The Equality Act 2010 and employment
`Equal´ versus `the same´
Justifiable reasons
Reasonable adjustments
The Equality Act 2010 and epilepsy
What can employers do to help?
Disclosing a disability
Employers obligations
Learning objectives
Chapter 125 Drivers and pilots licences
Ordinary (Group 1) driving licences
Group 2 – Heavy goods vehicles or public service vehicle licences: HGV/PSV
Withdrawal of antiepileptic drugs in a person who is seizure-free
Informing the police or DVLA that a patient is driving
Pilots licences
Learning objectives
Chapter 126 Treatment with limited pharmacopoeia
Introduction
What limits drug choices?
What drugs are available?
The role of phenobarbital in the twenty-first century
Recommended reading
Learning objectives
Chapter 127 The role of primary care in the management of epilepsy
Background
The UK NHS provision of health care in primary care
References
Learning objectives
Questions
Chapter 128 Residential care and special centres for epilepsy
History
Concept and role
Longer-term placement for those with severe epilepsy, particularly with a high risk of status epilepticus
Severe co-morbidity that is difficult to manage
Short-term assessment to clarify diagnostic uncertainty
Short-to-medium-term management of complex antiepileptic medication changes
Presurgical assessment
The future of residential epilepsy centres
Reference
Learning objectives
Chapter 129 Main UK charities supporting epilepsy
National Society for Epilepsy (NSE)
Epilepsy Action (until 2002: British Epilepsy Association – BEA)
Epilepsy Bereaved (EB)
Joint Epilepsy Council (JEC)
Learning objective
Chapter 130 Public education and resources
To whom is the campaigning addressed, and who are the public?
What needs to be addressed in the educational message?
How may the message be delivered?
References and recommended reading
Learning objectives
Chapter 131 Organizations and support services for people with epilepsy
Mandate
Consumer-led
Professional-led
Patronage
Function
Care provider
Information, support and training
Fundraising for research, and awarding research grants
Seeking to influence
Locus of action
Disability legislation in the UK
Disabling aspects of epilepsy
Politicizing disability
Final thoughts
References
Learning objectives
Chapter 132 Can a joined-up primary-secondary care approach help people with epilepsy?
Introduction
New-onset epilepsy
Long-term epilepsy
Linking primary and specialist services to tackle inequalities
References
Learning objective
Chapter 133 Support groups and their role in care in the community
Support for sufferers, families, friends and carers
Support groups can help the epileptologists, too
General comments
Learning objectives
Chapter 134 The International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)
Foundation and history
Objectives
The International Bureau for Epilepsy (IBE)
The ILAE/IBE/WHO Global Campaign against Epilepsy
References
Learning objective
Chapter 135 Health economics and epilepsy
Introduction
Resource use
Unit costs
Sources of information about unit costs
Different types of economic study
Budget impact and cost-of-illness study
Cost-effectiveness study
Sensitivity analysis
Conclusions
References
Learning objectives
Chapter 136 Epilepsy, crime and legal responsibility
The medical definition of automatism
References and recommended reading
Learning objective
Chapter 137 The law and its consequences for people with epilepsy
The Disability Discrimination Act
The Health and Safety at Work Act
References
Learning objective
Chapter 138 Epilepsy and lifestyle issues
Independence, risks and death
Death
Sex, drugs and rock and roll
Sex
Drugs
Rock and roll
Conclusions
References
Learning objectives
Chapter 139 Bereavement, SUDEP and Epilepsy Bereaved
Support and enablement
Raising awareness and informing of ways to reduce risks
Prevention of deaths
References
Learning objective
Index