The treatment of epilepsy PDF
Preview The treatment of epilepsy
The Treatment of Epilepsy Fourth Edition Edited by Simon Shorvon MA MB BChir MD FRCP Professor in Clinical Neurology and Consultant Neurologist UCL Institute of Neurology, University College London National Hospital for Neurology and Neurosurgery London, UK Emilio Perucca MD PhD FRCP(Edin) Professor of Medical Pharmacology Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics University of Pavia and Director, Clinical Trial Center C. Mondino National Neurological Institute Pavia, Italy Jerome Engel, Jr. MD PhD Jonathan Sinay Distinguished Professor of Neurology Neurobiology, and Psychiatry and Biobehavioral Sciences Director UCLA Seizure Disorder Center David Geffen School of Medicine at University of California Los Angeles, USA This edition first published 2016 © 2016 by John Wiley & Sons, Ltd. 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Contents List of Contributors Preface to the Fourth Edition Preface to the First Edition Historical Introduction The Drug Treatment of Epilepsy from 1857 to 2015 Commentary Acknowledgement References Section I Introduction 1 Definition (Terminology) and Classification in Epilepsy: A Historical Survey and Current Formulation, with Special Reference to the ILAE Definition Classification The future of classification schemes of epilepsy Definition Definition and classification – status epilepticus Afterthought Acknowledgement References 2 Differential Diagnosis of Epilepsy Introduction General approach to the diagnosis of episodic disturbances Syncope Non-epileptic seizures Panic disorder Migraine Sleep disorders Vertigo Movement disorders Cerebral ischaemia Endocrine and metabolic abnormalities Transient global amnesia References 3 Mechanisms of Epileptogenesis Membrane ion channels Membrane ion channels as targets for antibodies in acquired autoimmune disorders Network and system involvement in epileptogenesis Epileptogenesis as a process New targets for antiepileptic and antiepileptogenic strategies Conclusions References 4 Antiepileptic Drug Discovery Characteristics of the ideal model system The current era of AED discovery Anticonvulsant Screening Program Early identification of antiepileptic activity MES, scPTZ and 6-Hz tests Differentiation of anticonvulsant activity Pharmacological profile and potential clinical utility Pharmacoresistant seizure models Therapeutic index and toxicity assessment Aetiologically relevant model systems Beyond the seizure Antiepileptogenesis and disease modification (see also Chapter 8) Conclusions Acknowledgement References 5 Antiepileptic Drug Development Introduction Overview on clinical studies and trials for drug development Opportunities for developing better antiseizure AEDs Development of epilepsy drugs beyond suppressing seizures Conclusions Acknowledgements References 6 Mechanisms of Antiepileptic Drug Action Main targets Other targets References 7 Mechanisms of Drug Resistance and Tolerance Introduction The concept of drug resistance in epilepsy Disease-related mechanisms of drug resistance in epilepsy Drug-related mechanisms of drug resistance in epilepsy Pharmacogenetic mechanisms of drug resistance in epilepsy Proof-of-concept of drug resistance hypotheses Conclusions References 8 Epilepsy Biomarkers Introduction Need for biomarkers Mechanisms of epilepsy Potential biomarkers Research to identify biomarkers Acknowledgements References Section II Principles of Medical Management 9 General Principles of Medical Management Aims of treatment When should treatment be started? Initiation of treatment and dose optimization Assessing clinical response What next when the initial treatment fails? – monotherapy and combination therapy How long should treatment be continued? References 10 Pharmacokinetic Optimization of Therapy Introduction Basic pharmacokinetic principles Why do individuals respond differently to the same drug concentration? The concept of reference range The concept of individual therapeutic concentrations and interpretation of serum concentrations in the clinical setting Practical aspects in the application of TDM Tailored therapy and future developments for TDM Conclusions References 11 Management of Chronic Active Epilepsy in Adults Prognosis and outcome of treatment of chronic active epilepsy Provision of care Treatment approach for chronic active epilepsy in adult patients Acknowledgement References 12 Management of Epilepsy in Remission Introduction Risk of relapse upon AED withdrawal Factors associated with seizure relapse after AED withdrawal Antiepileptic drug withdrawal after epilepsy surgery Consequences of relapse Risks associated with continuing AEDs (or benefits of withdrawal) Patient attitudes Clinical therapeutics References 13 Management of Epilepsy in Neonates and Infants Introduction Currently available drug therapies for neonates Currently available drug therapies for infants Treatment of acute neonatal seizures and neonatal status epilepticus Treatment of specific syndromes in the neonatal period Treatment of specific syndromes in the infantile period Prognosis and complications of neonatal and infantile seizures Acknowledgements References 14 Management of Childhood Epilepsy Syndromes Introduction Treatment of childhood epilepsy: the evidence base References 15 Management of Epilepsy in People with Intellectual Disabilities The importance of the topic Comprehensive epilepsy service Antiepileptic drug treatment Influence of aetiology and disease mechanisms on epilepsy treatment Non-pharmacological treatment Acute seizure treatment with benzodiazepines Concomitant psychopharmacological treatment Prognosis of epilepsy in intellectually disabled patients References 16 Management of Epilepsy in the Elderly Introduction Epidemiology Diagnosis Clinical presentation of epilepsy in the elderly Investigations Electroencephalography Neuroimaging Risk of recurrence Treatment of epilepsy in the elderly Pharmacokinetic changes Pharmacodynamic changes Antiepileptic drug choice Older antiepileptic drugs Newer antiepileptic drugs Comorbid conditions and medication interactions Epilepsy surgery Aspects of the impact of epilepsy in old age References 17 Emergency Treatment of Seizures and Status Epilepticus Status epilepticus Drug pharmacokinetics and pharmacodynamics Treatment of acute seizures and acute repetitive seizures Treatment of tonic–clonic status epilepticus Drug treatment of tonic–clonic status epilepticus Treatment of common forms of non-convulsive status epilepticus Summary of drug therapies most commonly used in status epilepticus Acknowledgement References 18 Management of Medical Comorbidity Associated with Epilepsy Introduction Bone health in epilepsy Organ dysfunction Cancer and epilepsy Infections and epilepsy Connective tissue disorders Pulmonary disease Cardiac disease References 19 Psychiatric Features of Epilepsy and their Management Anxiety and affective disorders Prevalence of anxiety and affective disorders in epilepsy ‘Bidirectional relationship’ between epilepsy and depression Diagnostic criteria Atypical affective disorders in epilepsy Generalized anxiety disorder Panic disorder Obsessive–compulsive disorder Suicide Treatment of depression in epilepsy Pharmacokinetic interactions between antidepressants and AEDs Pharmacodynamic interactions Cognitive behavioural therapy Electroconvulsive therapy, transcranial magnetic stimulation and vagal nerve stimulation Deep brain stimulation for treatment-resistant depression Psychoses of epilepsy
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