Clinical Practice Guidelines
for Epilepsy 2018

Published on: March 15, 2018

first edition first printing

Editorial supervisor: Japanese Society of Neurology
Editor: “Clinical Practice Guidelines for Epilepsy” Development Committee
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ii

Clinical Practice Guidelines for Epilepsy 2018

List of Authors
Editorial supervisor
Japanese Society of Neurology
(Collaborating Societies: Japan Epilepsy Society, Japan Neurosurgical Society, Japanese Society of Child Neurology,
Japanese Society of Neurological Therapeutics)

EditorClinical Practice Guidelines for Epilepsy Development Committee

Chairman:
Yoshikazu Ugawa, Professor, Department of Neurology, Fukushima Medical University

Vice-chairman:
Naoki Akamatsu, Professor, Department of Neurology, International University of Health and Welfare

Committee Members:
Akio Ikeda, Professor, Department of Epilepsy, Movement Disorders & Physiology, Kyoto University School of Medicine
Hiroto Iwasa, Director, Kisarazu Hospital, Kisarazu Epilepsy Center
Hirokazu Oguni, Professor, Department of Pediatrics, Tokyo Women’s Medical University
Kensuke Kawai, Professor, Department of Neurosurgery, Jichi Medical University
Kazutaka Jin, Associate Professor, Department of Epileptology, Tohoku University
Kenji Sugai, Director, Epilepsy Center, National Center of Neurology and Psychiatry
Kiyohito Terada, Chief, Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders
Shozo Tobimatsu, Professor, Department of Clinical Neurophysiology, Graduate School of Medical Sciences, Kyushu
University
Masato Matsuura, Vice-Director, Tazaki Hospital
Masahiro Mizobuchi, Director, Epilepsy Center, Department of Neurology, Nakamura Memorial Hospital
Eishu Nango, Chief Physician, Department of General Medicine, Tokyo Kita Social Insurance Hospital

Research collaborators and administrative staff:
Yoshihiro Sugiura, Associate Professor, Department of Neurology, Fukushima Medical University
Masahiro Iguchi, Assistant Professor, Department of Neurology, Fukushima Medical University
Madoka Yamazaki, Project Lecturer, Faculty of Health Science, Daito Bunka University

Evaluation & coordination members:
Sadatoshi Tsuji, Dean and Professor, School of Health Sciences at Fukuoka, International University of Health and Welfare
Shinichi Niwa, Adjunct Professor, Department of Psychiatry, Aizu Medical Center, Fukushima Medical University
Genjiro Hirose, Director of Neurological Center and Director of Epilepsy Center, Asanogawa General Hospital
Tateki Fujiwara, Honorary Director, Shizuoka Institute of Epilepsy and Neurological. Disorders

Preface  

iii

Publication of Clinical Practice Guidelines for Neurological Diseases
In 2001, the Executive Board of the Japanese Society of Neurology decided to develop clinical practice guidelines for the
major neurological diseases, based on a proposal by the then President Nobuo Yanagisawa. In 2002, “Treatment Guidelines
2002” for six diseases comprising “chronic headache”, “Parkinson disease, “epilepsy”, “amyotrophic lateral sclerosis”,“dementia”, and “cerebrovascular disease” were published.
Following the publication of “Treatment Guidelines 2002”, new knowledge was accumulated at an accelerated rate. In
2008, the Executive Board of the Japanese Society of Neurology (Past President, Shigeki Kuzuhara) decided to revise theguidelines. Six guideline development committees were organized to develop “Treatment Guidelines 2010” for “chronicheadache” (published in 2013), “dementia” (published in 2010), “epilepsy” (published in 2010), “multiple sclerosis” (publishedin 2010), “Parkinson disease” (published in 2011), and cerebrovascular disease (published in 2009), as well as a guideline
development committee for “genetic diagnosis of neurological disorders” (published in 2009).
On the occasion of the development of “Treatment Guidelines 2010”, the Japanese Society of Neurology established aconsistent structure, the guideline development committee, and procedures for all the guidelines to be developed by theSociety. Regarding conflicts of interest, the committee members involved in the development of these guidelines submitted
to the President a “Japan Neurological Society Declaration of Conflict of Interest” and obtained an “Approval Regarding
Conflict of Interest” from the Japanese Society of Neurology. With the exception of Parkinson’s disease, the revised guidelines
for all other diseases were developed by joint committees with corroboration from other academic societies.
The guidelines published between 2009 and 2011 were those for representative neurological diseases. However, due to anincrease in demand of guidelines for other neurological diseases, a decision was made at the Executive Board in 2011 to
publish new clinical practice guidelines for six additional neurological disorders (Guillain-Barré syndrome/Fisher syndrome,chronic inflammatory demyelinating polyneuropathy/multifocal motor neuropathy, amyotrophic lateral sclerosis, bacterial
meningitis, Duchenne muscular dystrophy, and myasthenia gravis). These guidelines were published in 2013‒2014, and havebeen widely used clinically as “Guidelines 2013”.
For the present series of guideline revision/development, revision of the guidelines for “genetic diagnosis” (published in2009), “epilepsy” (published in 2010), “dementia” (published in 2010), “multiple sclerosis” (published in 2010), and“Parkinson disease” (published in 2011) as well as development of guidelines for “herpes simplex encephalitis” and “dystonia”
were approved at the Executive Board in 2013, while the development of “Clinical practice guideline for spinocerebelladegeneration and multiple system atrophy” was approved at the Executive Board in 2014.
As with previous guidelines, revision or development of the above guidelines was based on the concept of evidence-based
medicine (EBM) and guided by Minds Manual for Guideline Development 2007 edition, or 2014 edition for those guidelinesthat were able to utilize the 2014 edition (guidelines for multiple sclerosis/neuromyelitis optica, Parkinson’s disease, andepilepsy were developed according to the 2014 edition). The 2014 edition recommends introduction of the GRADE system,with the participation of both patients and medical staff in formulating the clinical questions. The GRADE system approachis also adopted as a part of the new guidelines.
Clinical practice guidelines are developed based on current medical knowledge with the purpose to assist clinicians inmaking clinical decisions to provide appropriate medical care. Clinical care provided for each patient should be decided
individually by the attending doctor based on all the clinical data, and the clinical practice guidelines by no means restrict
the clinical discretion of doctors. Clinical practice guidelines are not supposed to be applicable to all the patients; they are
created as a reference for each treatment setting after the doctor has accurately grasped the patient’s condition.
Treatments for neurological diseases are advancing rapidly, and the clinical practice guidelines will need to be revised
regularly in the future. We sincerely hope that the new clinical practice guidelines will help members of our Society in theirroutine medical practice, and we look forward to your evaluations and opinions to improve the clinical practice guidelines
for the next revision.
May 2017
Hidehiro Mizusawa, Past President
Ryosuke Takahashi, Executive President
Gen Sobue, Past Chairman, Guideline Executive Committee
Satoshi Kamei, Chairman, Guideline Executive Committee
Japanese Society of Neurology

iv

Clinical Practice Guidelines for Epilepsy 2018

Revision of the Clinical Practice Guidelines for Epilepsy
Introduction
Epilepsy affects a large number of people, and many doctors other than epilepsy specialists are involved in providing
treatment for these patients. For this reason, the Epilepsy Treatment Guideline Development Committee developed the
Epilepsy Treatment Guideline 2010 as a guide for general practitioners who treat patients with epilepsy. Following publicationof the guideline, new antiepileptic drugs were launched, and the British epilepsy guideline (NICE) was revised, so was
epilepsy classification by the International League Against Epilepsy (ILAE). In this revision, descriptions of new antiepileptic
drugs have been added. As the first attempt of the Society, systematic review was performed using the GRADE (Grading ofRecommendations Assessment, Development and Evaluation) system for three clinical questions (CQ) to be described later.
Anti-NMDA receptor antibody encephalitis, the treatment method of which has drawn attention in recent years, is also
described in the revised guideline, together with a brief summary of the latest diagnosis, tests, treatments and prognosis ofadult and childhood epilepsies.
Adopting the same approach as the previous edition, this revised guideline uses the format consisting of CQ (purpose) and
its answer. The CQs that have been systematically reviewed are colored in green to distinguish them from other CQs, andthe strength of recommendation and quality of evidence are described, followed by comment on the evidence. For the other
CQs, “Summary” is used to describe the overall opinions of experts (colored in red), followed by comment.
This guideline was prepared by the Clinical Practice Guidelines for Epilepsy Development Committee (abbreviated as
Guideline Development Committee hereinafter) of the Japanese Society of Neurology, and was developed in collaboration
with the Japan Epilepsy Society, the Japan Neurosurgical Society, the Japan Society of Child Neurology, and the JapaneseSociety of Neurological Therapeutics. The Guideline Development Committee consists of neurologists, pediatricians,
psychiatrists, and neurosurgeons who are members of the above-mentioned academic societies.

1. F
 unding Sources for the development of Clinical Practice Guidelines for Epilepsy and conflictsof Interest (COI) of committee members
Preparation of this guideline was funded by the Japanese Society of Neurology. The proceeds from sales of this guideline
will be appropriated to cover the cost of preparation.
The chairman, vice-chairman, committee members, external members, collaborators, and evaluation/coordinationcommittee members who are involved in the preparation of this guideline have submitted the “Declaration Form of Conflictof Interest for Preparation of the Japanese Society of Neurology Clinical Practice Guidelines” to the Executive President of
the Japanese Society of Neurology, and obtained approval from the Japanese Society of Neurology for the disclosure ofconflicts of interest.
The companies that have declared COI are shown below.
• ASKA Pharmaceutical Co. Ltd.
• Eisai Co., Ltd.
• Otsuka Pharmaceutical Co. Ltd.
• GlacoSmithKline K.K.
• Southern TOHOKU Hospital Group• Daiichi Sankyo Co., Ltd.
• Sumitomo Dainippon Pharma Co., Ltd.
• Association of Radio Industries and Businesses• MSD K.K.
• Nihon Kohden Corp.
• Novartis Pharma K.K.
• Medical Review Co., Ltd• UCB Japan Co. Ltd.

Preface  v

2. On the use of this guideline
This clinical practice guideline provides recommendations to support the clinical decisions of healthcare professionals,
and the recommendations have no enforcing power. The actual clinical decision should be made upon comprehensively
considering not only this clinical practice guideline, but also the latest evidence, patient values, and environmental factors.
This clinical practice guideline does not promise to improve clinical outcomes. The Guideline Development Committee
is not responsible for the results of medical treatments conducted using this clinical practice guideline.
This clinical practice guideline is not supposed to be used as evidence in a medical lawsuit. Since decision-making in
actual clinical practice is based on comprehensive assessments including patients’ values ​​and environmental factors whilereferring to the recommendations in the clinical practice guidelines, providing medical treatment that deviates from therecommendations of the clinical practice guideline does not necessarily imply negligence. This Guideline Development
Committee does not approve the use of this clinical practice guideline as evidence in a legal trial.

3. Outline of the method of systematic review (Part II)
In the present guideline, systematic review was conducted in three CQs described below, and the digest is summarized inPart II. Details are published on the website of Japanese Society of Neurology.
CQ9-2 	Should temporal lobe resection be added to drug therapy in drug-resistant temporal lobe epilepsy?
CQ10-1	Should vagus nerve stimulation therapy be added to drug therapies for drug-resistant temporal lobe epilepsy?
CQ10-2	When conducting vagus nerve stimulation for drug resistant epilepsy, which intensity of stimulation (high orlow) should we use?
The recommendations were made according to the GRADE system, which is an international standard approach for
guideline development. In the GRADE system, a systematic review is conducted for each outcome; then based on the results,a panel meeting is convened to formulate the recommendations.
Formulating clinical question (CQ)
The CQ was decided by the Guideline Development Committee, as the clinical issue for which a recommendations canbe expected to improve the quality of diagnosis and treatment for drug-resistant epilepsy.
CQ was formulated by the PICO format. PICO is the acronym for patient (P), intervention (I), comparison (C) andoutcome (C). For each CQ, outcome was decided at the Guideline Development Committee meeting. The outcome wasgraded on a scale of 9 to 1 in descending order of importance. Eventually, outcomes graded as critical (scores 9 to 7) or
important (scores 6 to 4) were selected for systematic review.
Literature search
We requested a librarian who had a contract with Japanese Society of Neurology to construct literature search formulaeand conduct literature search. MEDLINE and Cochrane CENTRAL were used in the search. From the articles yielded fromthe search, duplicates were excluded, the remaining papers were screened by title and abstract, then the full texts were
evaluated, and sorted by outcome. Only literature of randomized controlled trials (RCTs) was adopted for systematic review.
The outline of literature search is shown in the flow diagram.
Integrating evidence data
For each CQ, meta-analysis was conducted for each outcome, where possible. Meta-analysis was performed using the
Cochrane standard application, Review Manager (RevMan) [Computer program] version 5.3 (Copenhagen: The Nordic
Cochrane Centre, The Cochrane Collaboration, 2014).
Fixed-effect models were used for integration of outcomes: Mantel-Haenszel method was used when the outcomes werebinary variables, and inverse variance method was used when the outcomes were continuous variables.
Risk ratio and 95% confidence interval were calculated for outcomes that were binary variables, and mean difference andstandard deviation were calculated for outcomes that were continuous variables, and presented as forest plots.
When the data was not adequate for performing meta-analysis, requests were made to the researchers to obtain more data.
Evaluating quality of evidence
The quality of evidence was evaluated by the method proposed by the GRADE working group, and was graded as “high”,“moderate”, “low”, and “very low”. Since only RCTs were evaluated in this clinical practice guideline, the quality of evidence
started from a score of “high”. From there, the score might be downgraded depending on the result of evaluation of theviClinical Practice Guidelines for Epilepsy 2018

following: “risk of bias”, “inconsistency: variation of treatment estimates between studies”, “indirectness: dissociation
between PICO of primary study and PICO of CQ”, “imprecision: low precision of the effect estimate due to small numberof samples or events”, and “publication bias: influence by studies that are not published due to negative results”, according to
the method defined by the GARDE working group.
After determining the final quality of evidence, the results of systematic review were tabulated in the Summary of Findings(SoF) table and GRADE Evidence Profile. GRADEproGDT (https://gradepro.org/) was used for tabulation.
Determination of overall quality of evidence for all outcomes
For each CQ, we adopted the highest quality of evidence if the effects of all the important outcomes were in the same
direction of either benefit or harm to the patient. On the other hand, we adopted the lowest quality of evidence if the effects
of some outcomes were in the direction of benefit while others were in the direction of harm . This quality of evidence issynonymous with the “certainty of evidence” in the recommendation statement.
In the alphabetical notation of GRADE, “high” certainty of evidence is represented by “A”, “moderate” by “B”, “low” by“C”, and “very low” by “D”.
Formulating recommendation from evidence
Recommendation was formulated using the SoF table and GRADE Evidence Profile.
Four factors determine recommendation: “overall quality of evidence for all outcomes”, “balance of benefit and harm”,“variation in values and preferences” and “resources (cost)”.
To determine recommendation at the panel meeting, the following were discussed: “priority of the issue”, “desirable
effects”, “undesirable effects”, “certainty of evidence”, “uncertainty and diversity of values towards major outcomes”, “balance
between desirable and undesired effects”, “costs and resources required”, “acceptability to stakeholders”, and “feasibility”.
The results are described in in the former half of the Evidence-to-Decision (EtD) table; “Evaluation table of recommendation
judgment criteria”.
Then, based on the “Evaluation table of criteria for determining recommendation”, consensus was formed regarding thestrength and direction of recommendation. The grade of recommendation was presented by a combination of the strength
determined as “strong or weak” and the direction determined as “recommended or not recommended”. In GRADE numericalnotation, strong recommendation is represented by “1” and weak recommendation by “2”. The rationale for therecommendation is shown in the latter part of the EtD table; “Recommendation decision table”.
Panel meeting
Panelists participated in the panel meeting include epilepsy specialists (neurologists, pediatricians, psychiatrists andneurosurgeons) who are members of the Clinical Practice Guideline Developing Committee, as well as primary care
physicians, representatives of patients’ families, lawyers, and all other stakeholders.
A panel meeting was held on October 23, 2016, in which CQ9-2, CQ10-1 and CQ10-2 were discussed from noon toevening. The panel meeting was moderated by Eishu Nango, an expert in clinical practice guideline development methods.
After commenting on the GRADE system, participants discussed based on the SoF table, GRADE Evidence Profile, anddraft recommendation statements.
For CQ10-1 and CQ10-2, the recommendations were unanimously agreed. Regarding CQ9-2, almost all the panelists
expressed the opinion that the strength of recommendation was “strong”, but the certainty of evidence was “very low”.
Therefore, “weak recommendation” was decided according to the GRADE rules.
Writing the clinical practice guidelines
Based on the recommendations decided at the panel meeting, the draft of the guidelines was written, was externallyevaluated, and then finalized.

Preface  vii

4. About the notation of antiepileptic drug
For all the drugs that are approved in Japan, the names are written in katakana in the text (Table 1). On the other hand,† is added to denote drugs that are not covered by insurance in Japan.
February 2018
“Clinical Practice Guidelines for Epilepsy” Development Committee
Chairman Yoshikazu Ugawa
Secretariat Yoshihiro Sugiura

Table 1. Antiepileptic drugs approved in Japan.
Generic nameacetazolamide
ethosuximide
oxcarbazepine1)
gabapentin2)
carbamazepine
clonazepam3)
clobazamdiazepam
potassium bromide
stiripentol4)
sultiame
zonisamide
topiramate5)
nitrazepam
valproate
vigabatrin6)
phenytoin
phenobarbital
primidone
perampanel7)
lacosamide8)
lamotrigine9)
ruﬁnamide10)
levetiracetam11)

Abbreviation
AZM
ESM
OXC
GBP
CBZ
CZP
CLB
DZP
KBr
STP
ST
ZNS
TPM
NZP
VPA
VGB
PHT
PB
PRM
PER
LCM
LTG
RFN
LEV

Major brand name
DiamoxEpileo pepti mal, Zarontin
OcnobelGabapenTegretolLandsen, Rivotril,
MystanCercine, Horizon, Diapp
Potassium bromide
Diacomit
Ospolot
ExcegranTopinaBenzalin
Depakene, Selenica
SabrilAleviatin, Hydantol
PhenobalPrimidone
Fycompa
VimpatLamictal
Inovelon
E Keppra1) Oxcarbazepine is approved as combination therapy for partial seizures in children aged 4 years or older, who do not respondadequately to other antiepileptic drugs.
2) Gabapentin is approved as combination therapy for partial seizures in patients aged 3 years or older, who do not respond adequately
to other antiepileptic drugs.
3) Clobazam is approved as combination therapy for partial or generalized seizures not responding adequately to other antiepileptic
drugs.
4) Stiripentol is approved as adjunctive therapy to valproic acid and clobazam for Dravet syndrome.
5) Topiramate is approved as combination therapy for partial seizures in patients aged 2 years or older, who do not respond adequately
to other antiepileptic drugs.
6) Vigabatrin is approved for West syndrome.
7) Perampanel is approved as combination therapy for partial seizures and tonic-clonic seizures in patients aged 12 years or older, who
do not respond adequately to other antiepileptic drugs.
8) Lacosamide is approved as combination therapy for partial seizures not responding adequately to other antiepileptic drugs.
9) Lamotrigine is approved as monotherapy for partial seizures, tonic-clonic seizures and typical absence seizures (aged 15 or older), andas combination therapy for partial seizures, tonic-clonic seizures and generalized seizures in Lennox-Gastaut syndrome notresponding adequately to other antiepileptic drugs.
10) Rufinamide is approved as combination therapy for tonic seizures and atonic seizures in Lennox-Gastaut syndrome in patients aged
4 years or older, who do not respond adequately to other antiepileptic drugs.
11) Levetiracetam is approved as monotherapy for partial seizures in patients aged 4 years or older, and as combination therapy for tonicclonic seizures.

viii

Clinical Practice Guidelines for Epilepsy 2018

CONTENTS
Publication of Clinical Practice Guidelines for Neurological Diseases
Revision of the Clinical Practice Guidelines for Epilepsy

Part I Clinical Practice Guidelines for Epilepsy 2018
Chapter 1 Diagnosis, Classification and Differential Diagnosis of Epilepsies (Including REM Sleep
Behavior Disorder)
CQ1-1
CQ1-2
CQ1-3
CQ1-4
CQ1-5
CQ1-6

What is epilepsy?...........................................................................................................................................2
What are the key clinical features to be included in history taking for epilepsy diagnosis?............................4
How are epileptic seizure types, epilepsies, epilepsy syndromes, and related seizure disorders
classified?.......................................................................................................................................................6
Which diseases should be differentiated from epilepsy in adults?.................................................................10
Which diseases should be differentiated from epilepsy in children?.............................................................11
What are the practical procedures for the diagnosis of epilepsy?..................................................................13

Chapter 2 Examinations for Clinical Practice of Epilepsy
CQ2-1
CQ2-2
CQ2-3
CQ2-4
CQ2-5

How useful is EEG for the diagnosis of epilepsy?.........................................................................................14
What is the significance of EEG examination in the treatment of epilepsy?................................................16
What is the significance of long-term video-EEG monitoring in clinical practice of epilepsy?.....................17
What are the essential neuroimaging studies for clinical practice of epilepsy?.............................................18
What are the useful functional neuroimaging studies for presurgical evaluation of epilepsy?......................19

Chapter 3 Drug Therapy for Adult Epilepsy
CQ3-1
CQ3-2
CQ3-3
CQ3-4
CQ3-5
CQ3-6
CQ3-7
CQ3-8
CQ3-9

Should drug therapy be started after the first epileptic seizure?....................................................................21
What are the recommended drugs for new-onset partial epilepsy?...............................................................22
What are the recommended drugs for new-onset generalized epilepsy?.......................................................24
Which antiepileptic drugs should be avoided for generalized epilepsies?......................................................25
What are the recommended drugs for patients with a risk of psychiatric symptoms?...................................26
What are the recommended drugs when complicated with medical diseases?..............................................28
What are the recommended drugs for elderly-onset epilepsy? .....................................................................29
What are the combined drugs that require special caution for epilepsy patients?.........................................30
What are the precautions when switching from the original antiepileptic drugs to generic drugs?..............32

Chapter 4 Epilepsies in Children and Adolescents and Their Treatment
CQ4-1
CQ4-2
CQ4-3
CQ4-4
CQ4-5
CQ4-6

Which epilepsy syndromes with childhood or adolescent onset have high prevalence?................................33
What examinations are recommended for the first unprovoked seizure in children and adolescents?..........35
For unprovoked seizures in children and adolescents, is the long-term prognosis worse if treatment
would start after the second seizure.............................................................................................................37
How to make a diagnosis of juvenile myoclonic epilepsy?............................................................................38
What are the first-line drugs for childhood- or adolescence-onset epilepsy with undetermined
seizure type (partial or generalized)?............................................................................................................39
If seizures recur in those treated with valproate for childhood/adolescent generalized seizure or
carbamazepine for childhood/adolescent partial seizures, even when their drug concentrations arein the therapeutic ranges, which drugs should be the next candidates?....................................................... 40

Chapter 5 Drug-Resistant Epilepsy
CQ5-1
CQ5-2
CQ5-3

What is the definition of drug-resistant epilepsy?........................................................................................ 44
What are the true drug-resistant epilepsies in adults?.................................................................................. 46
What are the drug-resistant epilepsies in children?......................................................................................47

Preface  ix

CQ5-4
CQ5-5
CQ5-6

What is pseudo-resistant epilepsy?...............................................................................................................49
How to manage drug-resistant epilepsies?....................................................................................................50
What are the intellectual prognosis and social prognosis of drug-resistant epilepsy?....................................52

Chapter 6 Treatment Guide by Epilepsy Syndrome
CQ6-1
CQ6-2
CQ6-3
CQ6-4
CQ6-5

What are the drug options for idiopathic partial epilepsy?...........................................................................55
What are the drug options for childhood absence epilepsy?.........................................................................56
What are the drug options for Lennox-Gastaut syndrome?..........................................................................57
What are the drug options for juvenile myoclonic epilepsy?.........................................................................59
What are the drug options for epilepsy with generalized tonic-clonic seizures alone (epilepsy with
grand mal on awakening)?...........................................................................................................................61

Chapter 7 Adverse Effects of Antiepileptic Drugs
CQ7-1

What are the adverse effects of antiepileptic drugs?.....................................................................................63

Chapter 8 Status Epilepticus
CQ8-1
CQ8-2
CQ8-2-(1)CQ8-2-(2)CQ8-2-(3)CQ8-2-(4)CQ8-2-(5)CQ8-2-(6)
CQ8-3
CQ8-4

What is the definition of status epilepticus?.................................................................................................65
Which drugs are used for convulsive status epilepticus?.............................................................................. 66
What treatment should be given when intravenous line has not yet been established?.................................68
What are the drugs for stage 1 status epilepticus?........................................................................................69
How effective is intravenous fosphenytoin for status epilepticus?.................................................................70
How effective is intravenous phenobarbital for status epilepticus?...............................................................71
How effective is midazolam for status epilepticus?.......................................................................................72
How effective is intravenous levetiracetam for status epilepticus?................................................................73
How effective is general anesthesia for refractory status epilepticus?............................................................74
Does EEG monitoring during status epilepticus have clinical significance?.................................................75

Chapter 9 Surgical Treatment for Epilepsy
CQ9-1
CQ9-2
CQ9-3
CQ9-4
CQ9-5
CQ9-6
CQ9-2

Which kinds of epilepsies (syndromes) are indications for surgical treatment?............................................76
Is temporal lobe resection effective for drug-resistant temporal lobe epilepsy?............................................ 77
What are the indications for chronic intracranial EEG (long-term intracranial EEG) in presurgicalevaluation?...................................................................................................................................................79
How to determine the timing of considering surgical treatment?................................................................ 80
Is surgical treatment effective even for drug-resistant epilepsies in children?................................................81
What is the risk of psychiatric symptoms after epilepsy surgery?.................................................................82
Should temporal lobe resection be added to drug therapy in drug-resistant temporal lobe epilepsy?............83

Chapter 10 Stimulation Therapy for Epilepsy
CQ10-1
CQ10-3
CQ10-1
CQ10-2Is vagus nerve stimulation therapy effective for drug resistant epilepsy?.......................................................86
Is intracranial electrical stimulation therapy with implanted electrodes effective for epilepsy?.....................88
Should vagus nerve stimulation therapy be added to drug therapies for drug-resistant temporal lobe
epilepsy?.......................................................................................................................................................89
When conducting vagus nerve stimulation for drug-resistant epilepsy, which intensity of stimulation(high or low) should we use?........................................................................................................................92

Chapter 11 Termination of Epilepsy Treatment
CQ11-1
CQ11-2
CQ11-3
CQ11-4
CQ11-5x

How many years after seizure remission should treatment termination be considered?................................95
Does the risk of seizure recurrence differ depending on seizure type, epilepsy type, or epilepsy
syndrome?....................................................................................................................................................97
Is there an optimal dose reduction speed of antiepileptic drugs?..................................................................98
What are the poor prognostic factors in treatment termination?..................................................................99
Should driving be avoided during dose reduction of antiepileptic drug?....................................................100

Clinical Practice Guidelines for Epilepsy 2018

Chapter 12 Drug Concentration Monitoring
CQ12-1
CQ12-2
CQ12-3
CQ12-4

When should serum concentrations of antiepileptic drugs be monitored?..................................................101
Serum concentration monitoring is useful for which drugs?......................................................................103
Is serum concentration monitoring a requisite in the treatment of patients with hepatic or renal
dysfunction?...............................................................................................................................................106
What are the drugs that interact with antiepileptic drugs?.........................................................................108

Chapter 13 Epilepsy and Women
CQ13-1
CQ13-2
CQ13-3
CQ13-4
CQ13-5
CQ13-6
CQ13-7

What kind of advice and information should be provided regarding pregnancy and childbirth
for women with epilepsy?...........................................................................................................................113
What is to be noted for antiepileptic medication in women at childbearing age?....................................... 116
Is folic acid supplementation needed?......................................................................................................... 118
Is it useful to monitor serum concentrations of antiepileptic drugs during pregnancy?.............................. 119
Are women with epilepsy more likely to have complications during pregnancy?........................................120
Can women with epilepsy have a natural delivery? How are seizures treated during delivery?...................121
Can women taking antiepileptic drugs breastfeed a baby?.........................................................................122

Chapter 14 Diagnosis of psychogenic nonepileptic seizures
CQ14-1
CQ14-2

How are psychogenic nonepileptic seizures differentiated from epileptic seizures?.....................................123
How are psychogenic nonepileptic seizures treated?...................................................................................125

Chapter 15 Psychotic Symptoms of Epilepsy
CQ15-1
CQ15-2

What kinds of psychoses accompany epilepsy and what are their treatments?...........................................127
How to manage depression and suicide-related behaviors associated with epilepsy?...................................129

Chapter 16 Acute Symptomatic Seizures
CQ16-1
CQ16-2
CQ16-3
CQ16-4
CQ16-5
CQ16-6

What is the definition of acute symptomatic seizure?.................................................................................131
What are the causes of acute symptomatic seizures?...................................................................................132
How to manage patients with acute symptomatic seizures?........................................................................133
What kinds of examination are needed for acute symptomatic seizures?....................................................135
How to treat acute symptomatic seizures?..................................................................................................136
How to diagnose and treat anti-NMDA receptor encephalitis?..................................................................137

Chapter 17 Epilepsy and Genetics
CQ17-1
CQ17-2

Relation between epilepsy and genetics......................................................................................................138
Current situation of genetic research and genetic testing for epilepsy........................................................139

Chapter 18 Advice and Information for Patients
CQ18-1
CQ18-2

What kinds of advice should be given to patients?.....................................................................................142
How to give advice on driver’s license?.......................................................................................................143

Part II Systematic Review Digest
CQ9-2
CQ10-1
CQ10-2

Should temporal lobe resection be added to drug therapy in drug-resistant temporal lobe epilepsy?..........148
Should vagus nerve stimulation therapy be added to drug therapies for drug-resistant temporal lobe
epilepsy?.....................................................................................................................................................162
When conducting vagus nerve stimulation for drug resistant epilepsy, which intensity of stimulation(high or low) should we use?......................................................................................................................178

Preface  xi