Pharmacoresistance In Epilepsy

This new edition of Pharmacoresistance in Epilepsy addresses all issues relating to drug-resistance in epilepsy, including studies in patients as well in experimental models and presents the basis for an understanding of recent developments in the pathogenesis and treatment of this condition. Important issues associated with drug-resistant epilepsy are reviewed and updated, such as abnormalities in inhibitory mechanisms, neurotoxicity and changes the immune system associated with this disorder, and the development of drug-resistance as consequence of chronic exposure to antiseizure-medications. Considering that a major obstacle is that epilepsy associated with drug-resistance cannot be controlled with the traditional antiseizure medications, specific chapters describe therapeutic strategies to prevent or reduce the progression of the disease with complementary medical therapies, such as transcranial focal stimulation to promote neuroprotection. Pharmacoresistance in Epilepsy is a valuable resource for anyone working in the field, whether studying epilepsy in the lab or treating it in an office.

Although more than 10 new antiepileptic drugs have been developed in the past decade, epilepsy remains resistant to drug therapy in about one third of patients, many of whom struggle with the disease their entire lives. Managing these patients is a challenge and requires a structured multidisciplinary approach. The book includes chapters on all issues related to pharmacoresistance in epilepsy and describes recent developments in the pathogenesis and treatment of this disorder. It addresses abnormalities in inhibitory mechanisms, epilepsy-related changes to the immune system, development of pharmacoresistance caused by chronic exposure to antiepileptic drugs, and novel therapeutic strategies for preventing or slowing down the progression of the disease. Clinicians and basic scientists alike will find up-to-date information on the development of pharmacoesistance, as well as reviews of mechanisms associated with epilepsy that may help them consider novel strategies for preventing the development of pharmacoresistance in the first place. The book also features information on new therapeutic strategies for control of epilepsy, such as transcutaneous electrical stimulation and virtual screening of new antiepileptic drugs. Pharmacoresistance in Epilepsy: From Genes and Molecules to Promising Therapies is useful to anyone working in the field, whether they’re studying epilepsy in the lab or treating it in a doctor’s office.”

Over 12 million people with epilepsy have seizures that cannot be controlled by antiepileptic drugs. The term "drug-resistance" is abundantly used in the epilepsy literature but the definitions proposed differ considerably. It is used indifferently in a number of different settings: as a criterion for selection of patients eligible for new antiepileptic drug trials, for the selection of surgical candidates, for the design of epidemiological studies, for the design of studies on quality of life, for the definition of the epileptic encephalopathies (in comparison to more benign epilepsy syndromes), to mention but a few. As a result, available studies are usually not comparable and referral to epilepsy specialists is unacceptably delayed. The volume includes several focused chapters on all issues relating to drug-resistance and offers the basis for a consensus on a clinically meaningful core definition.

More than 12 million people with epilepsy have seizures that cannot be controlled by antiepileptic drugs. The term "drug-resistance" is abundantly used in the epilepsy literature but the definitions proposed differ considerably. It is used indifferently in a number of different settings: as a criterion for selection of patients eligible for new antiepileptic drug trials, for the selection of surgical candidates, for the design of epidemiological studies, for the design of studies on quality of life, for the definition of the epileptic encephalopathies (in comparison to more benign epilepsy syndromes), to mention but a few. As a result, available studies are usually not comparable and referral to epilepsy specialists is unacceptably delayed. The present volume of Progress in Epileptic Disorders includes several focused chapters on all issues relating to drug-resistance and offers the basis for a consensus on a clinically meaningful core definition.

About 20% of people with epilepsy have seizures which are resistant to anticonvulsant medications. These drug-resistant seizures are called `intractable', and the patients who have them - about 1 in 500 of the general population - present a major challenge to neurologists and epilepsy associations. The present volume describes the symptomatology of the major `intractable' syndromes, the most appropriate drugs for each, and the possibilities for surgical control. Research related to the causes and effects of unchecked seizures is presented, and new directions in prevention and therapy are discussed.

Epilepsy affects approximately 3% of the population, and is usually defined as a tendency to experience recurrent seizures arising from periodic neuronal hyperexcitability of unknown causes. Different genetic factors, through various mechanisms, can cause this abnormal neuronal behavior. The etiology of epilepsy is a major determinant of clinical course and prognosis. Many of the genes that have been implicated in idiopathic epilepsies code for ion channels, whereas a wide spectrum of syndromes where epilepsy is a main clinical feature are caused by mutated genes that are involved in functions as diverse as cortical development, brain malformations, mitochondrial function, and cell metabolism. Similarly, different conditions as hypoxia, trauma, infections, or metabolic unbalances can develop epileptic syndromes where upregulation of several genes could be related to the epileptogenic mechanisms. The most common human genetic epilepsies display a complex pattern of inheritance, and the susceptible genes are largely unknown. However, major advances have recently been made in our understanding of the genetic basis of monogenic inherited epilepsies. As we continue to unravel the molecular genetic basis for epilepsies, it will increasingly influence their classification and diagnosis. A majority of epileptic patients may control their crisis with anticonvulsant drugs, however 30%–40% became refractory to pharmacological therapies and require surgical treatment. The challenge of the molecular revolution will be the design of the best treatment protocols based on genetic profiles that include both the specific mechanistic etiology of the epilepsies, as well as their potential refractory behavior to current medications. This includes also the design of new therapeutic agents and targets, so as to reduce the number of cases with refractory epilepsy and epileptogenesis, and perhaps avoid the current surgical treatment (a procedure that was first described more than 4000 years ago) except as a last option.

Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.