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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5203_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Preface
- •Acknowledgments
- •Contents
- •Contributors
- •1.4.3.1 Electrical Stimulation Kindling Model
- •1.4.2 Acute Epilepsy Models
- •1.4.2.1 Maximal Electroshock Seizure Model
- •1.4.2.3 Acute Pentylenetetrazol-Induced Seizure Model
- •1.4.2.4 Local Penicillin Model
- •1.4.3 Chronic Epilepsy Models
- •1.4.3.2 Kindling Model
- •1.4.3.3 Optogenetic Kindling Model
- •1.4.4 Poststatus Epilepticus Models
- •1.4.5 Genetic Models
- •1.4.5.1 Rodent Animal Models
- •Absence Seizure Models
- •1.4.5.2 Nonrodent Animal Models
- •Baboon Photosensitive Epilepsy Model
- •1.4.6.1 Posttraumatic Epilepsy Models
- •Fluid Percussion Injury Model
- •Controlled Cortical Impact Model
- •Impact Acceleration Model
- •1.4.6.2 Poststroke Epilepsy Models
- •1.4.6.3 Postinfection Epilepsy Models
- •1.5.1 Voltage-Gated Ion Channel Modulation Mechanism
- •1.5.1.1 Blocking Voltage-Gated Sodium Channels
- •1.5.1.2 Blocking Voltage-Gated Calcium Channels
- •1.5.1.3 Voltage-Gated Potassium Channel Enhancement
- •1.5.2 Blocking Excitatory Neurotransmission
- •1.5.4 Improving Neuronal GABAergic Inhibitory Function
- •1.5.4.3 Carbonic Anhydrase Inhibitors
- •1.5.5 Other Mechanisms
- •1.5.6 Conclusion
- •References
- •2.1 Commonly Used Antiseizure Medications
- •2.1.1 First-Generation Antiseizure Medications (ASMs)
- •2.1.1.1 Carbamazepine
- •Drug Characteristics
- •2.1.1.2 Clonazepam
- •Drug Characteristics
- •Other Studies
- •2.1.1.3 Ethosuximide
- •Drug Characteristics
- •Other Studies
- •2.1.1.4 Phenobarbital
- •Drug Characterization
- •2.1.1.5 Primidone
- •Drug Characteristics
- •2.1.1.6 Valproic Acid
- •Drug Characteristics
- •Mental Illness
- •Migraine Prevention
- •Ischemic Stroke
- •Tumors
- •Others
- •Hepatic Impairment
- •Hyperammonemia (HA)
- •Dyskinesia
- •Others
- •Summary
- •2.1.1.7 Phenytoin Sodium
- •Drug Characteristics
- •Other Research
- •2.1.1.8 Nitrazepam
- •Drug Characteristics
- •Other Studies
- •2.1.2 Second-Generation Antiseizure Drugs
- •2.1.2.1 Lamotrigine
- •General Characteristics
- •Historical Evolution
- •Adverse Effects
- •Cutaneous Adverse Effects
- •Hematological Adverse Effects
- •Cardiovascular Adverse Effects
- •Miscellaneous
- •Fundamental Research
- •2.1.2.2 Levetiracetam
- •Drug Characteristics
- •Preclinical Research
- •2.1.2.3 Topiramate
- •Topiramate-Related Adverse Reactions
- •2.1.2.4 Gabapentin
- •Drug Characteristics
- •Preclinical Research
- •2.1.2.5 Pregabalin
- •Drug Characteristics
- •2.1.2.6 Clobazam
- •Drug Characteristics
- •2.1.2.7 Felbamate
- •Drug Characteristics
- •Evidence-Based Medical Research Regarding Felbamate
- •Other Studies Involving Felbamate
- •2.1.2.8 Vigabatrin
- •Drug Characteristics
- •Historical Evolution
- •Evidence-Based Medical Research
- •Side Effects
- •Basic Research
- •Other Research
- •2.1.2.9 Zonisamide
- •Drug Characteristics
- •2.1.3 Third-Generation Antiseizure Medications
- •2.1.3.1 Lacosamide
- •Medicinal Features
- •Recent Fundamental Research
- •Adverse Effects
- •Serum Concentrations
- •2.1.3.2 Perampanel
- •Other Studies
- •2.1.3.3 Brivaracetam
- •Evidence-Based Medical Research
- •Drug Characteristics
- •Historical Development
- •Evidence-Based Medical Research
- •Basic Research
- •Other Research
- •2.1.3.5 Tiagabine (TGB)
- •Drug Characteristics
- •Historical Development
- •Evidence-Based Medical Research
- •Side Effects
- •Basic Research
- •Other Research
- •2.2 New Antiseizure Medications under Study
- •2.2.1 Cannabidiol
- •2.2.1.1 Drug Characteristics
- •References
- •3.1.4 Discontinue Anti-Seizure Medications
- •3.3.6 Pharmacokinetic Changes
- •3.4.1.1 Physiological Stage
- •3.4.1.2 Hypothalamic-Pituitary-Ovarian Axis
- •3.4.1.3 Menstrual Cycle
- •3.5.1 Introduction
- •3.5.5 Conclusions
- •3.6 Acute Symptomatic Epileptic Seizures
- •3.6.2 Historical Evolution
- •3.6.4 Epidemiological Investigation
- •3.6.5 Clinical Manifestations
- •3.6.6 Predictor
- •3.7.4.2 Serotonin Transferrin
- •3.7.4.3 Night Monitoring
- •3.7.4.4 Others
- •References
- •4.1.1.1 Focal Onset Seizures
- •4.1.1.2 Generalized-Onset Seizures
- •Generalized-Onset Tonic, Clonic, or Atonic Seizures
- •Generalized-Onset Myoclonic Seizures
- •Myoclonic-Atonic Seizures
- •Epileptic Spasms
- •Absence Seizures
- •4.2.3.1 Pretreatment Assessment
- •4.2.3.4 First-Line Anti-seizure Medications
- •4.3.1.2 Epidemiology
- •4.3.1.5 Drug Selection
- •4.3.2.2 Epidemiology
- •4.3.3.1 Epidemiology
- •4.3.3.2 Pathophysiological Mechanism
- •4.3.4.2 Pathologic Typing
- •Historical Evolution
- •Molecular Pathological Characterization
- •4.3.4.4 Pathogenic Mechanisms
- •Glial Cell Dysfunction
- •Extrasynaptic Mechanisms
- •4.3.4.5 Treatment
- •Other Medications
- •4.3.5.1 Epidemiological Information.
- •4.3.5.2 Pathogenesis
- •4.3.5.3 Clinical Manifestations
- •4.3.5.4 Anti-seizure Medications
- •4.3.6.1 Rasmussen Encephalitis
- •4.3.6.2 Anti-GAD65-Associated Epilepsy
- •4.3.6.3 Paraneoplastic Antibody-Associated Epilepsy
- •4.3.7.1 Hypoxic-Ischemic Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.7.2 Metabolic Encephalopathy
- •Hepatic Encephalopathy
- •4.3.7.3 Uremic Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.7.4 Pulmonary Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.7.5 Autoimmune-Related Encephalopathy
- •Hashimoto’s Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •Lupus Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.7.6 Toxic Encephalopathy
- •Carbon Monoxide Poisoning
- •Pathogenic Mechanisms
- •Treatment
- •Chronic Alcoholic Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.7.7 Heroin-Induced Spongiform Leukoencephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.7.8 Radiation Encephalopathy
- •Pathogenic Mechanisms
- •Treatment
- •4.3.8.1 Epidemiology
- •4.3.8.3 Anti-seizure Medication Selection
- •4.4.1.1 Historical Evolution
- •4.4.1.2 Epidemiology
- •4.4.1.5 Treatment
- •4.4.1.6 Prognosis
- •4.4.2.1 Historical Evolution
- •4.4.2.2 Epidemiological Investigation
- •Other Manifestations
- •4.4.2.6 Treatment
- •References

Pharmacological
Treatment
ofEpileptic Seizures
XuefengWang
LieminZhou
Editors

Pharmacological Treatment of Epileptic Seizures

Xuefeng Wang • Liemin Zhou
Editors
Pharmacological Treatment
of Epileptic Seizures

Editors
Xuefeng Wang
Neurology
The First Afliated Hospital of Chongqing
Medical University
Chongqing, China
Liemin Zhou
Neurology
The Seventh Afliated Hospital of Sun
Yat-Sen University
Shenzhen, China
ISBN 978-981-96-8519-6 ISBN 978-981-96-8520-2 (eBook)
https://doi.org/10.1007/978-981-96-8520-2
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore
Pte Ltd. 2025
This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether
the whole or part of the material is concerned, specically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microlms or in any other physical way, and
transmission or information storage and retrieval, electronic adaptation, computer software, or by similar
or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication
does not imply, even in the absence of a specic statement, that such names are exempt from the relevant
protective laws and regulations and therefore free for general use.
The publisher, the authors and the editors are safe to assume that the advice and information in this book
are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the
editors give a warranty, expressed or implied, with respect to the material contained herein or for any
errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional
claims in published maps and institutional afliations.
This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd.
The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721,
Singapore
If disposing of this product, please recycle the paper.

Preface
Epilepsy is a neurological disorder that has impacted humanity for thousands of
years, transcending borders, cultures, and social strata. While advances in medicine
have dramatically improved the understanding and management of epilepsy, the
social consequences of this condition remain profound. People with epilepsy often
face signicant stigma, discrimination, and psychological challenges that can be as
debilitating as the seizures themselves. In this context, effective treatment is not
only a medical imperative but also a social one, crucial for improving the quality of
life for millions worldwide.
This book, Pharmacological Treatment of Epileptic Seizures, is a comprehensive
resource compiled by the leading epileptologists in China, whose work has signicantly advanced the eld of epilepsy treatment, with the contribution of worldfamous experts in epilepsy. It aims to equip healthcare professionals with the
knowledge and tools necessary to address both the clinical and social dimensions of
epilepsy.
This book begins by dening epilepsy and providing a thorough exploration of
the Denition and the Classication and diagnosis of epileptic seizures.
Understanding the various forms of epilepsy is essential for developing targeted
treatment plans that address the specic needs of each patient. Accurate diagnosis is
the rst step toward effective management, which can signicantly reduce the social
burden of the disease.
Section 1.3 offers a broader context for understanding how epilepsy treatment
has evolved over time. This historical perspective is crucial for appreciating the
advances that have brought us to the present day and for anticipating future developments that may further alleviate the social impact of epilepsy.
Section 1.4, addressing “Research on Animal Models of Epilepsy,” provides
insight into the scientic foundations of epilepsy treatment. This research is vital for
developing new therapies that are more effective and have fewer side effects, thus
improving the overall well-being of patients and their ability to participate fully in
society.
The book also delves into the Antiseizure medication mechanisms of action and
reviews currently available medications and those in pipeline. This part of the book
v

vi
Preface
is focused on the pharmacological interventions that are the cornerstone of epilepsy
management. By controlling seizures, these medications play a key role in reducing
the social stigma and limitations associated with epilepsy, enabling patients to lead
more stable and fullling lives.
In Chap. 3 the authors review the fundamentals of selection of antiseizure medications and emphasize the importance of individualized treatment plans in individuals across the life span; the treatment options should be based on not only the
medical aspects of epilepsy but also the social and psychological needs of patients.
Effective treatment can greatly enhance a patient’s ability to engage in everyday
activities, pursue education, maintain employment, and build relationships—all of
which are crucial for social inclusion.
Chapter 4 offers practical guidance for clinicians, helping them to optimize treatment strategies that improve patient outcomes in different clinical conditions,
including epilepsy after stroke, brain trauma, tumor-associated epilepsy, and others.
Special attention is given to Chaps. 5 and 6, both of which are critical for managing more severe forms of epilepsy. These chapters highlight the importance of
timely and effective treatment in preventing the long-term clinical, social, and psychological consequences of uncontrolled seizures.
An important part of the book, Chap. 7, addresses the “Diagnosis and Treatment
of Epilepsy Comorbidities,” recognizing that epilepsy often coexists with other conditions such as depression, anxiety, and cognitive impairments. These comorbidities
can exacerbate the challenges faced by individuals with epilepsy, making their management an essential component of comprehensive care. Following the same line,
Chap. 8 provides highly relevant information for the successful management on the
complex issues surrounding epilepsy treatment in individuals with epilepsy.
Throughout this book, the editors, who are the most distinguished epileptologists
in China, and eminent authors bring their extensive clinical experience and research
expertise to the readers. Their work reects a deep commitment to improving both
the medical and social outcomes for people with epilepsy.
This book will serve as a vital resource for those dedicated to improving the lives
of people with epilepsy, helping to create a future where effective treatment leads
not only to better health outcomes but also to greater social acceptance and
integration.
Director, Moscow Research
AllaGuekht
and Clinical Center for Neuropsychiatry,
Professor of Neurology
Pirogov Russian Medical Research
University, Treasurer and President-Elect,
International League Against Epilepsy (ILAE)
Moscow, Russia

Acknowledgments
We would like to thank the following authors for their participation in the preparation of this book:
Guanzhong Ni, Hui Zhang, Junhong Wu, Shenglin Wang, Shuda Chen, Xiaowei Xu,
Xianyue Liu, Yingfang She, Yuping Zhao, Juan Li.
vii

Contents
1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Qun Wang, Xuefeng Wang, Emilio Perucca, Zhuo Huang,
and Xiaofeng Yang
2 Antiseizure Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Wei Jing, Meizhen Sun, and Chao Yan
3 The Basic Principles and Precautions of Drug Therapy . . . . . . . . . . . . 329
Qun Wang, Xuefeng Wang, Li Jiang, and Hong Zhang
4 Clinical Application of Anti-seizure Medication
as Drug Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 391
Liemin Zhou and Ziyi Chen
5 Diagnosis and Treatment of Epilepsy Syndromes . . . . . . . . . . . . . . . . . 503
Yin Yan, Yi Wang, Fei Xiao, Xuefeng Wang, Haiqing Zhang,
Yue Hu, Rong Luo, Li Jiang, Ye Wu, Xuewu Liu, Xin Tian,
Xiangqing Wang, and Tingsong Li
6 Pharmacological Treatment of Status Epilepticus . . . . . . . . . . . . . . . . . 757
Xuefeng Wang, Feng Li, Yin Yan, Wei Wang, and Fei Xiao
7 Diagnosis and Treatment of Epilepsy Comorbidities . . . . . . . . . . . . . . 799
Yanbing Han, Yixue Gu, Yin Yan, Guohui Jiang, and Xin Tian
8 Side Effects of Anti-seizure Medication . . . . . . . . . . . . . . . . . . . . . . . . . 861
Liming Zhang, Wen-Hung Chung, Xin Xu, Zucai Xu, Songyan Liu,
Ling Li, Fei Xiao, Zan Wang, Zhen Hong, Ying Wang, and
Huapin Huang
9 Role of Artificial Intelligence Technology in Drug
Therapy of Epilepsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 999
Richard Shek-kwan Chang, Zhibin Chen, Emma Foster,
Terence J. O’Brien, and Patrick Kwan
ix

Contributors
Richard Shek-kwan Chang Department of Neuroscience, Central Clinical
School, Monash University, Melbourne, VIC, Australia
Wen-HungChung Department of Dermatology, Xiamen Chang Gung Hospital,
Xiamen, China
ZhibinChen Department of Neuroscience, Central Clinical School, Monash Uni-
versity, Melbourne, VIC, Australia
ZiyiChen Department of Neurology, The Seven Afliated Hospital of Sun Yat-sen
University, Shenzhen, China
EmmaFoster Department of Neuroscience, Central Clinical School, Monash Uni-
versity, Melbourne, VIC, Australia
YixueGu Department of Neurology, The First Afliated Hospital of Chongqing
Medical University, Chongqing, China
Yanbing Han
Medical University, Kunming, China
ZhenHong Department of Neurology, West China Hospital, Sichuan University,
Chengdu, China
Yue Hu Department of Neurology, Children’s Hospital of Chongqing Medical
University, Chongqing, China
HuapinHuang Department of Neurology, Fujian Medical University Union Hos-
pital, Fuzhou, China
ZhuoHuang State Key Laboratory of Natural and Biomimetic Drugs, Department
of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences,
Peking University, Beijing, China
Guohui Jiang Department of Neurology, Afliated Hospital of North Sichuan
Medical College, Nanchong, Sichuan, China
Department of Neurology, First Afliated Hospital of Kunming
xi

xii
Contributors
Li Jiang Department of Neurology, Children’s Hospital of Chongqing Medical
University, National Clinical Research Center for Child Health and Disorders,
Chongqing, China
WeiJing Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third
Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan,
Shanxi, China
Patrick Kwan Department of Neuroscience, Central Clinical School, Monash
University, Melbourne, VIC, Australia
FengLi
Department of Neurology, The First Afliated Hospital of Chongqing
Medical University, Chongqing, China
LingLi Department of Neurology, Qilu Hospital (Qingdao), Cheeloo College of
Medicine, Shandong University, Qingdao, China
Tingsong Li Department of Rehabilitation, Children’s Hospital of Chongqing
Medical University, National Clinical Research Center for Child Health and Disorders, Chongqing, China
SongyanLiu Department of Neurology, China-Japan Union Hospital, Jilin Uni-
versity, Changchun, Jilin, China
XuewuLiu Department of Neurology, Shandong Provincial Hospital Afliated to
Shandong First Medical University, Jinan, Shandong, China
Rong Luo Department of Pediatrics, West China Second University Hospital,
Sichuan University, Chengdu, China
TerenceJ.O’Brien Department of Neuroscience, Central Clinical School, Monash
University, Melbourne, VIC, Australia
EmilioPerucca Department of Medicine (Austin Health), The University of Mel-
bourne, Melbourne, VIC, Australia
Department of Neuroscience, Central Clinical School, Monash University, Mel-
bourne, VIC, Australia
Meizhen Sun Department of Neurology, The First Hospital of Shanxi Medical
University, Taiyuan, Shanxi, China
XinTian Department of Neurology, The First Afliated Hospital of Chongqing
Medical University, Chongqing, China
QunWang Department of Neurology, Beijing Tiantan Hospital, Capital Medical
University, Beijing, China
WeiWang Department of Neurology, The First Afliated Hospital of Chongqing
Medical University, Chongqing, China
XiangqingWang Department of Neurology, The First Medical Center of Chinese
PLA General Hospital, Beijing, China
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