EDITOR-IN-CHIEF The hong Kong epilepsy guideline … Cheuk Wing, MBBS, FHKAM (Paediatrics), Specialist in Paediatrics HUI Che Fai, Andrew, MBBS, FRCP (Edin), FHKAM (Medicine), Specialist

HongKongMedJVol15No5# Supplement5# October2009 1

EDITOR-IN-CHIEF

Richard Kay 祁理治

SENIOR EDITORS

PT Cheung 張璧濤

Albert KK Chui 徐家強

Michael G IrwinIgnatius TS Yu 余德新

EDITORS

KL Chan 陳廣亮

KS Chan 陳健生

Henry LY Chan 陳力元

Annie OO Chan 陳安安

CB Chow 周鎮邦

William B Goggins WK Hung 熊維嘉

Alvin KH Kwok 郭坤豪

Paul BS Lai 賴寶山

Eddy KF Lam 林國輝

Stephen TS Lam 林德深

WY Lam 林永賢

Nelson LS Lee 李禮舜

Danny WH Lee 李偉雄

Danny TN Leung 梁子昂

WK Leung 梁惠強

Janice YC Lo 羅懿之

Herbert HF Loong 龍浩鋒

James KH Luk 陸嘉熙

Jacobus KF Ng 吳國夫

Hextan YS Ngan 顏婉嫦

Martin W Pak 白威

PC Tam 談寶雛

SW Tang 鄧兆華

William YM Tang 鄧旭明

Clement CY Tham 譚智勇

Peter CY Tong 唐俊業

TW Wong 黃大偉

Patrick CY Woo 胡釗逸

TK Yau 游子覺

SH Yeung 楊世雄

Volume 15 # Number 5 # October 2009

S U P P L E M E N T 5

The hong Kong epilepsy guideline 2009

The Hong Kong Epilepsy Society (HKES) 3

Editorial 4

The Guideline

1. Preamble 6

2. Diagnosis,review,andreferral 6

3. Patienteducation 6

4. Followingafirstseizure 6

5. Investigations 8

6. Classification 9

7. Principlesofmanagement 9

8. PharmacologicalorAEDmanagement 9

9. Managementofdrug-resistantepilepsy 10

10.Side-effectsofAEDs 11

11.Presurgicalevaluationofdrug-resistantepilepsy 11

12.Otherformsoftreatment 12

13.Prolongedseizuresinthecommunity 13

14.Treatmentofstatusepilepticus 13

15.Perioperativemanagementofseizure 14

16.Womenwithepilepsy 14

17.Olderpeoplewithepilepsy 15

18.Childrenandyoungpeoplewithepilepsy 15

19.Lifestyleandsocialissues 17

References 18

Appendices

AppendixA:Gradingschemeofevidence 21

AppendixB:Differentialdiagnosisofepilepticseizuresandepileptiformdischarges

AppendixB1:Differentialdiagnosisofepilepsyinadults 22AppendixB2:Differentialdiagnosisofepileptiformdischarges 22AppendixB3:Differentialdiagnosisofepilepsyinchildren 23

AppendixC:Classificationofseizuretypeandepilepsysyndrome

AppendixC1:TheILAEclassificationofepilepticseizures 24

2 HongKongMedJVol15No5# Supplement5# October2009

INTERNATIONAL EDITORIAL ADVISORY BOARD

Sabaratnam Arulkumaran United Kingdom

Robert AtkinsAustralia

Peter CameronAustralia

James DickinsonCanada

Adrian DixonUnited Kingdom

Willard Fee, JrUnited States

Robert HoffmanUnited States

Serena HuUnited States

Sean HughesUnited Kingdom

Arthur KleinmanUnited States

Xiaoping LuoChina

Jonathan SametUnited States

Rainer SchmelzeisenGermany

David WeatherallUnited Kingdom

Homer YangCanada

EXECUTIVE EDITORS

Margaret H ChengCyrus R Kumana

MANAGING EDITOR

Yvonne Kwok 郭佩賢

ASSISTANT MANAGING EDITORS

Warren Chan 陳俊華

Betty Lau 劉薇薇

AppendixC2:TheILAEclassificationofepilepsiesandepilepsysyndromes 25

AppendixD:Pharmacologicaltreatment

AppendixD1:SuggestedchoiceofAEDsbyseizuretypesinadolescentsand 26adults(modifiedfromNICE)

AppendixD2:SuggestedchoiceofAEDsbyepilepsysyndromes 26AppendixD3:PositionstatementofHKESongenericAEDsubstitution 27AppendixD4:Side-effectsofAEDs 27

AppendixE:ExamplesoffactorstoconsiderinselectinganAED 28innewlydiagnosedepilepsy

DeclarationThe authors received an educational grant from the Hong Kong Epilepsy Society in supportof theirresearchforandpreparationof thisguideline.Theydidnotreceivepaymentsorotherbenefits,oracommitmentoragreementtoprovidesuchbenefitsfromacommercialentity.

List of abbreviations

AED antiepilepticdrugCNS centralnervoussystemCT computedtomographyECG electrocardiogramEEG electroencephalogram/electroencephalographyHKES HongKongEpilepsySocietyICU IntensiveCareUnitILAE InternationalLeagueAgainstEpilepsyIM intramuscularIV intravenousMEG magnetencephalogramMRI magneticresonanceimagingPET positronemissiontomographySPECT singlephotonemissioncomputedtomography

# Percentage body fat in Chinese children #

Hong Kong Med J Vol 15 No 5 # Supplement 5 # October 2009 �

The Hong Kong Epilepsy SocietyThe Guideline Development Group

Chairman FONG Ka Yeung, Jason, MBBS, FRCP (Lond, Edin), FHKAM (Medicine), Specialist in Neurology

Vice Chairman KWAN Kwok Leung, Patrick, MBBChir (Camb), PhD, FRCP (Lond), FHKAM (Medicine), Specialist in Neurology

Members CHAK Wai Kwong, MBBS, FHKAM (Paediatrics), Specialist in Paediatrics

FONG Chung Yan, Gardian, MBBS, MD, PhD, FRCP (Glasg), FHKAM (Medicine), Specialist in Neurology

FONG Dawson, MBBS, FRCS (Edin), FHKAM (Surgery), Specialist in Neurosurgery

FUNG Cheuk Wing, MBBS, FHKAM (Paediatrics), Specialist in Paediatrics

HUI Che Fai, Andrew, MBBS, FRCP (Edin), FHKAM (Medicine), Specialist in Neurology

LEUNG Howan, MBBS, FHKAM (Medicine), Specialist in Neurology

LUI Hui Tung, MBBS, FHKAM (Medicine), Specialist in Neurology

WONG Virginia, MBBS, FRCP (Lond, Edin), FRCPCH, DCH, FHKAM (Paediatrics), Specialist in Paediatrics

YAM Kwong Yui, MBBS, FRCS (Edin), FHKAM (Surgery), Specialist in Neurosurgery

YEUNG Hon Ming, Jonas, MBBS, FRCP (Lond, Edin, Glasg), FHKAM (Medicine), Specialist in Neurology

YUNG Wing Yan, Ada, MBBS, FHKAM (Paediatrics), Specialist in Paediatrics

ZHU Xia Lun, LMCHK, FRCS (Edin), FHKAM (Surgery), Specialist in Neurosurgery

External Reviewer Prof Josemir W SANDER, MD, PhD, FRCP

UCL Institute of Neurology, University Department of Clinical and Experimental Epilepsy, Queen Square, London, United Kingdom

� HongKongMedJVol15No5# Supplement5# October2009

The Hong Kong Epilepsy Guideline 2009E D I T O R I A L

Introduction to Hong Kong Epilepsy Society (HKES)The HKES is a non–profit-making organisation established in November 2002. It aims at maintaining effective cooperation of all persons active in the field of medical sciences, public health, and social care, who are concerned with problems related to epilepsy. Every year various congresses, symposia, workshops or meetings are held to promote dissemination of scientific knowledge on epilepsy. The executive council mainly consists of medical professionals with adult and child neurologists, neurosurgeons, neuroradiologists, and neuopsychologists. The Society has published a booklet “Your Guide of Epilepsy” which covers essential information regarding epilepsy and enjoys popularity among people with epilepsy.

Modern management of epilepsyIn the past two decades we have witnessed a huge explosion in literature on epilepsy, followed by introduction of many more AEDs and innovative surgical techniques in controlling intractable seizures. Modern management of epilepsy requires sound knowledge on seizure differential diagnosis and neuropharmacology, proper classification of epilepsy, prompt referral for epilepsy surgery in drug-resistant epilepsy, as well as providing counselling and information at appropriate times.1 Special population groups comprising children, elderly, and women require careful considerations on certain issues, eg learning and behaviour in children, pregnancy and AED teratogenicity in reproductive women, drug interactions with polypharmacy and co-morbidities in the elderly. An appraisal of the medical literature and translating evidence into practice guideline appears timely.

Epilepsy care in Hong KongThe standard of epilepsy care in Hong Kong is heterogeneous and people with epilepsy are often managed by general practitioners, physicians, paediatricians, geriatricians, psychiatrists, neurosurgeons, neurologists, developmental paediatricians, child neurologists, or child psychiatrists. While quality care is often deficient in the primary sector, the specialist clinics are overloaded with people with stable epilepsy. People with drug-resistant epilepsy also lack referral channels. These problems may be attributed to the absence of a tertiary epilepsy centre, which accounts for underdevelopment of epilepsy surgery and paucity in structured

teaching programmes. It is envisaged that the future establishment of the Neurosicence Institute in Hong Kong would resolve these issues. During this interim period, an evidence-based and up-to-date epilepsy guideline would be useful in setting the standard of medical care.

Epilepsy guidelinesGuidelines can be defined as systematically developed statements to assist practitioner decisions about appropriate health care for specific clinical circumstances. Professional societies and scientific bodies have published various guidelines and topical reviews on epilepsy, such as the NICE (www.nice.org.uk) and SIGN (www.sign.ac.uk) guidelines from the UK and Scotland respectively, practice parameters by American Academy of Neurology (www.aan.com), and topical reviews by ILAE (www.ilea-epilepsy.org). Other regional guidelines are available from Malaysia, China, and Italy. As always, people are skeptical about guidelines. Criticisms include non–evidence-based, potential for misuse during legal litigations, bias towards health economics with restriction of physician’s autonomy, and irrelevant to clinical practice. On the other hand, formulation of a guideline does provide an essential link between clinical practice and advances in basic and clinical sciences. It helps us to identify gaps in evidence and areas of uncertainty, which in turn would generate further research. Modification of clinical practice would ensue following clinical auditing and medical education and after all the benefit will be translated into patient’s interest.

Methodology Both the NICE (CG 20, 2004) and SIGN (no. 70, 2003, revised 2005) guidelines were well-written, comprehensive, and evidence-based. They were employed as templates in preparing the Hong Kong Epilepsy Guideline. Literature search was conducted via Medline retrieving original and review articles using key words—eg epilepsy, epileptic seizures, convulsions, neuroimaging, EEG, meta-analysis—from 2003 to mid-2007. The new evidence is classified and translated into recommendations as shown in Appendix A. The first draft was prepared in 2007 and revised after a number of consensus meetings. The second version was scrutinised by our external reviewer in 2008. Review of the latest medical literature from mid-2008 to mid-2009 was finally conducted and new recommendations were added.

#TheHongKongEpilepsyGuideline2009#


Appraisal of evidenceThe choice of AED in newly diagnosed epilepsy has been a controversial topic for many years, and this is taken as an example to illustrate the gap between existing evidence and translated recommendation. Many studies have shown that the newer AEDs are similar to standard AEDs in terms of efficacy. The SANAD trial (UK)2,3 was a pragmatic study designed to answer the question of the best monotherapy for new-onset epilepsy. It comprised two populations with partial (arm A, n=1721) and generalised/unclassified epilepsy (arm B, n=716) respectively. Arm A was randomised to carbamazepine (standard), or gabapentin, lamotrigine, topiramate or oxcarbazepine and arm B was randomised to valproate, lamotrigine or topiramate. The endpoints were time to treatment failure and time to 12 months’ remission.

In conclusion, valproate was more effective than lamotrigine and better tolerated than topiramate in arm A. Hence valproate is the drug of choice except in reproductive women because of concern of teratogenicity. This recommendation was consistent with our daily clinical practice. In arm B, lamotrigine was comparable to carbamazepine or oxcarbazepine in terms of efficacy but tolerability is better. Gabapentin and topiramate were relatively less potent. Shall we recom-mend lamotrigine as the standard AED in partial epilepsy based on SANAD study? The simple answer is “no”.

The recommendation based on a composite measure of efficacy and general side-effects is not far from the truth. However, a number of points have to be borne in mind. First, the impact of rare but serious side-effects of lamotrigine has not been considered (eg toxic epidermal necrolysis and Stevens-Johnson syndrome). Second, different titration schedule of lamotrigine vs carbamazepine may account for the observed difference in tolerability. Third, other new AEDs such as levetiracetam and pregabalin are not included in this randomised drug trial. Our consensus is that such a simple approach may limit physician’s choice of AED in matching AED profile with patient’s characteristics. Instead of making specific recommendations about AED therapy, we feel that the best treatment strategy should be individualised according to the seizure type and severity, epilepsy syndrome, co-medication and co-morbidity, the individual’s lifestyle and preference (see Guideline Section 8).

Dissemination of the guidelineIt is a common conception that passive methods of dissemination (eg professional journals) rarely lead to changes in practice. This impression is reinforced by the UK TIGER trial, which aimed at determining the effectiveness of dissemination strategies regarding the use of the 1997 SIGN guideline.4 Altogether 68 practices were randomised as follows:

(1) Control group were sent copies of guideline in post;

(2) Intermediate group received guideline plus invitation to workshops and two protocol documents; and

(3) Intensive group was also offered services of Epilepsy Specialist Nurse.

It turned out that the number of planned reviews per patient did not change after the intervention and the number of sessions at which counselling given only increased marginally. Essentially there was no change in practice among the three groups.

ConclusionPhysicians are busy but they may find a guideline useful if this is brief, simple, evidence-based, and comes from reputable source and quality. Alternatively, the guideline is also invaluable if the problem is complex or it adapts to particular patient needs. The Hong Kong Epilepsy Guideline is prepared to fulfil these criteria and we are looking forward to a change in clinical practice in the next decade.

AcknowledgementWe are indebted to Prof JW Sander, Professor of Neurology, UCL Institute of Neurology, UK, for his critical comments and proofreading of our drafts.

Jason KY Fong, MBBS, FRCP (Lond, Edin), FHKAM

(Medicine)

E-mail: [email protected] Specialist in NeurologyOn behalf of the Guideline Development GroupHong Kong Epilepsy Society

References1. Elger CE, Schmidt D. Modern management of epilepsy: a practical approach. Epilepsy Behav 2008;12:501-39. Erratum in:

EpilepsyBehav2008;13:575.2. MarsonAG,Al-KharusiAM,Alwaidh M, et al, SANAD Study group.The SANAD study of effectiveness of carbamazepine,

gabapentin, lamotrigine,oxcarbazepine,or topiramatefor treatmentofpartialepilepsy:anunblindedrandomisedcontrolledtrial.Lancet2007;369:1000-15.

3. MarsonAG,Al-KharusiAM,AlwaidhM,etal,SANADStudygroup.TheSANADstudyofeffectivenessofvalproate,lamotrigine,ortopiramateforgeneralisedandunclassifiableepilepsy:anunblindedrandomisedcontrolledtrial.Lancet2007;369:1016-26.

4. DavisJ,RobertsR,DavidsonDL,etal.ImplementationstrategiesforaScottishnationalepilepsyguidelineinprimarycare:resultsoftheTaysideimplementationofGuidelinesinEpilepsyRandomized(TIGER)trial.Epilepsia2004;45:28-34.


The Hong Kong Epilepsy Guideline 2009T H E G U I D E L I N E

1 Preamble1.1 This guideline addresses the diagnosis and

medical management of epilepsy in children,adults, and older people. It does not coverneonatalseizuresorthemanagementoffebrileconvulsions.Theguidelinemayalsoberelevantto professionals working in the occupationalhealth services, social services, educationalservices,orthevoluntarysectors.

1.2 Thisguidelineisevidence-basedandthegradingschemeusedfortherecommendations(A,B,C,D, good practice point [GPP]) is described inAppendixA.

1.3 Thisguidelinerepresentsconsensusviewsofthe Guideline Development Group and hasbeen approved by the council of HKES. It isbased on an appraisal of current scientificevidence and clinical information. It is notintended to cover all treatment modalitiesrelevant to epilepsy, or to replace clinicaljudgement.Thefinaltreatmentdecisionpathshould be reached by a formal discussionbetween individual patient and the treatingphysician.

2 Diagnosis, review, and referral 2.1 Diagnosis

• All individuals with a recent-onset seizureshould be seen urgently (ie being seenwithin2weeks)byaspecialist(aspecialistis defined as a medical practitioner withtraining and expertise in epilepsy) toensure correct diagnosis and initiation ofappropriatetherapy.

• Theseizuretype(s)andepilepsysyndrome,aetiology, and co-morbidity should bedetermined.

2.2 Reviewandreferral• A comprehensive care plan should be

agreedamonghealthcareprofessional,theindividual with epilepsy, and their familyor carers. All parties should participate indecisionsabouttheirhealthcare,andtakeintoaccountanyspecificneeds.

• All individuals with epilepsy should havea regular structured review. This reviewshould be carried out at least yearlydepending on how well the epilepsy iscontrolled and the presence of specificlifestyleissues.

3 Patient education3.1 Individuals with epilepsy and their families or

carersshouldbegiveninformationabout:C• epilepsyingeneral• diagnosisandtreatmentoptions• medicationandside-effects• seizure type(s), triggers and seizure

control• riskmanagementandself-care• first aid, safety and injury prevention at

home/school/work• psychologicalissues• socialservices• educationandhealthcareatschool• employment and independent living for

adults• importanceofdisclosingepilepsyatwork• homesafetyanddriving• prognosis• suddendeathinepilepsy• statusepilepticus• lifestyle,leisure,andsocialissues(including

recreational drugs, alcohol, sexual activity,andsleepdeprivation)

• familyplanningandpregnancy• voluntary organisations, eg support

groupsMost of the above information is included inthebooklet,Your Guide to Epilepsy,publishedbytheHKES(4thedition,2008).

3.2 Thetimeatwhichthisinformationisgivenwilldependon thecertaintyof thediagnosis, andtheneedforconfirmatoryinvestigations.GPP

3.3 Adequate time should be given to provideinformation.Checklistsmaybeusedtoremindboth individualsandhealthcareprofessionalsabout information that should be discussedduringconsultations.GPP

4 Following a first seizure4.1 Urgencyofevaluation

Hospital admission is recommended after theoccurrenceofafirstconvulsiveseizureorinthepresenceofthefollowingconditions:D• Feverorsignssuggestiveofinfection• Prolonged seizure lasting more than 5

minutes• Clusterofseizuresegtwoormoreseizures

within24hours• Incomplete recovery after a seizure, eg

drowsinessformorethan2hours


HongKongMedJVol15No5# Supplement5# October2009 �

• Persistent post-ictal focal neurologicaldeficit

Advantagesofhospitaladmissioninclude:• Prompt diagnostic evaluation looking for

animportantortreatablecause• Close monitoring for possible emergence

intostatusepilepticus• Gatheringimportantprognosticinformation

forcounsellingIfhospitaladmissionisconsideredunnecessary,aspecialistappointmentshouldbemadewithin2weeks.GPP

4.2 Theinitialevaluation• A detailed history including a witness

accountandthecircumstancesatthetimeofseizureisnecessary.B

• The differential diagnosis is wide (AppendixB1)andmisdiagnosisiscommon.

• Preceding auras (eg epigastric risingsensation,auditoryorvisualhallucination,déjà vu) or Todd’s paralysis are suggestiveofpartialseizure.C

• Limb stiffening, myoclonic jerks, jawclenching, cyanosis, hypersalivation, headandneckversion,andpost-ictalconfusionarefeaturessuggestiveofgeneralisedtonic-clonicseizure.C

• Physical examination during the post-ictalperiodisusuallynon-rewardingbutcertainclinicalsigns(eglateraltonguebiting,scaldinjury, posterior shoulder dislocation)would lend support to the diagnosis ofepilepticseizure. C

4.3 ClassificationofsingleseizuresSingleseizurescanbeclassifiedintotwogroups(AandB):GroupA:reactiveorsystemiccauses• Reactive seizures due to sleep

deprivation, fever, drug withdrawal ortoxicity

• Systemic diseases, eg infection,hypoglycaemia, hypoxia, hypocal-caemia

Group B: central nervous system insult orepilepsy• Direct central nervous system insult, eg

head injury, stroke, encephalitis, brainneoplasm

• First-seizure manifestation ofsymptomaticoridiopathicepilepsy

4.4 Theclinicalimportanceofclassification• In Group A, seizures are usually self-

limiting and recurrence may be reducedby correction of the provoking factor. Incontrast,seizuresinGroupBareassociatedwithsubsequentrecurrenceandlong-termAEDsmaybenecessary.

• AlthoughAEDmayreducetheriskofseizuresinreactiontohead injury,craniotomyandcerebral malaria, such treatment does notaffect the future development of epilepsyand hence routine prophylaxis is notindicated.C

4.5 BiochemicalandhaematologicaltestsThefollowingtestsshouldbeperformed:B• Completebloodcellcount• Urea, creatinine, electrolytes, calcium,

glucose• Liverfunctiontest,creatinekinase• Urinalysis and toxicology screening (if

indicated)

4.6 Otherinvestigations• EEGperformedwithin24hoursof seizure

has a higher probability of detectingepileptiformdischarges thananEEGdoneonsubsequentdays. B

• CT/MRI of the brain is indicated to lookfor a structural brain lesion—CT brainis more appropriate in the emergencysettinginassociationwithbonefractureorhaematoma, otherwise MRI brain is moresensitive.C

• Cerebrospinalfluidexaminationisindicatedin the presence of fever and meningealsignstoestablishthediagnosisofcerebralinfection. D

4.7 Emergencymanagementafterthefirstseizure• In general, a single seizure usually self-

terminateswithin2 to3minutesanddrugtreatmentmaynotbenecessary.D

• Short-acting benzodiazepine (eg IVdiazepam, diazemuls or midazolam)is indicated under the followingcircumstancestoaborttheonsetofstatusepilepticus: C(a) aconvulsiveattacklastingmorethan

2minutes(b) remaining drowsy in between

attacks(c) in the presence of a serious

underlying cause, eg encephalitis,stroke

• See also the management of statusepilepticus(Section14)

• Theunderlyingcauseshouldbedeterminedand specific treatment should commenceas soon as possible (eg correction ofbiochemical abnormality, acyclovir forherpesencephalitis).GPP

4.8 AEDtreatmentafterfirstseizure• The initiation of AED treatment is

determined by the risk of recurrence.GPP

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• AED is not recommended in those with anormal workup as the cumulative risk ofrelapsein2yearsislessthan20%.GPP

• The highest risk of recurrence occurs inthose with both epileptiform EEG and astructural brain lesion (80-100%). An EEGwith epileptiform discharges will increasethechanceofrecurrencefrom20%to80%(AppendixB2).

• AED may be commenced if the benefitsof reducing the risk of a second seizureoutweightheriskofpharmacologicalside-effects.GPP

• The initial choice of AED should beindividualised(seeSection8).A

• Early AED treatment does not affect thelong-termremissionofepilepsy.B

• Multiple seizures within 24 hours areregardedasasingleevent.B

4.9 Generaladvicetopatientsafterafirstseizure• The overall probability of developing a

secondseizureisabout42%.• The tendency of recurrence can be

determined after a period of observation,eg6monthsto2years

• To minimise the risk and impact ofrecurrence,advisethefollowing: GPP(a) Stopdrivingandinformthetransport

department(b) Avoidoperatingdangerousmachinery

orworkatheight(c) Restriction for at-risk hobbies, eg

hiking,diving,androckclimbing(d) Avoid sleep deprivation, recreational

drugs,andalcohol(e) Learn about the first-aid measures

duringaseizure

5 Investigations5.1 EEG

• EEGisausefultesttoconfirmthediagnosisof epilepsy but it must be appropriatelyinterpretedtoavoidmisdiagnosis.Itshouldbe performed within 4 weeks after it hasbeenrequested.GPP

• An EEG may be used to help determineseizuretypeandepilepsysyndromewhichcarry prognostic information. C Followinga first unprovoked seizure, epileptiformdischarges shown on EEG can be used toassess the risk of seizure recurrence (seeSection4.8).B

• A normal EEG should not be used toexcludeepilepsyeventhoughtheclinicalpresentation supports the diagnosis ofnon-epileptic event. On the other hand,an abnormal EEG should not be used

alonetomakeadiagnosisofepilepsyasfalse-positiveresultmayoccur(AppendixB2).C

• Repeated standard EEGs may be helpfulwhen the diagnosis of the epilepsy orthe syndrome is unclear. However, if thediagnosis has been established, repeatEEGs are unlikely to be helpful in guidingresponsetotreatment.C

• When a standard EEG is non-rewarding,a sleep or sleep-deprived EEG should beperformed.C

• Long-term video/ambulatory EEG mayestablish diagnosis in difficult cases.Provocationbysuggestionmaybeusedinthe evaluation of non-epileptic seizures.However, false-positive results may occurinsomeindividuals.C

• Photic stimulation and hyperventilationshould remain part of standard EEGassessment unless contra-indicated (egcarotidstenosis).Theindividualandfamilyand/or carer should be made aware thatsuch activation procedures may induceaseizureandtheyhavearight torefuse.GPP

5.2 Neuroimaging• Neuroimaging should be used to identify

structural abnormalities that cause certainepilepsies and MRI is the preferred modeofimaging.C

• MRIbrainisparticularlyindicatedinthose:C(a) with partial seizure onset based on

history,examination,orEEG(b) with seizures continuing in spite of

first-linemedication• Neuroimaging should not be routinely

requested when a diagnosis of idiopathicgeneralised epilepsy is firmly established.C

• CT brain should be used to identifyunderlying gross pathology if MRI is notavailableor iscontra-indicatedor inacutesetting.C

5.3 Othertests• Serumprolactinlevelisnotrecommended

fordiagnosisofepilepsy.C• Other investigations, includingbloodand

urinebiochemistry,shouldbeundertakenat the discretion of the specialist toexcludeotherdiagnoses,todeterminetheunderlying cause of the epilepsy and co-morbidity.GPP

• A 12-lead ECG should be performedwith suspected epilepsy or diagnosticuncertainty.Referraltoacardiologistshouldbeconsidered.GPP



• Genetic or metabolic causes of epilepsyshould be considered and investigatedin selected cases, eg muscle biopsyfor mitochondrial disease, urine foruroporphyrinogeninsuspectedporphyria.GPP

5.4 Neuropsychologicalassessment• Neuropsychological assessment should

beconsideredin individuals inwhomit isimportant to evaluate learning disabilitiesand cognitive dysfunction, particularly inregardtolanguageandmemory.D

• Referral for a neuropsychologicalassessmentshouldbeconsidered: D(a) ifthereareeducationaloroccupational

difficulties(b) when MRI shows abnormalities in

certain brain regions (eg temporallobe)

(c) when an individual complains ofmemoryorothercognitivedeficits

(d) aspartofpresurgicalevaluation

6 Classification6.1 Epileptic seizures and epilepsy syndromes in

individuals should be classified using a multi-axial diagnostic scheme. The axes that shouldbeconsideredare:descriptionofseizure(ictalphenomenology); seizure type; syndromeand aetiology. Failure to classify the epilepsysyndrome correctly can lead to inappropriatetreatmentandpersistenceofseizures.C

6.2 Individuals with epilepsy should be giveninformation about their seizure type(s) andepilepsy syndrome, and the likely prognosis.GPP

6.3 The ILAE diagnostic scheme (1981) dividedthe various seizures into partial-onset andgeneralised-onset. The former seizure type isfurther subdivided into simple and complexpartial seizures and seizures evolving tosecondarilygeneralisedseizures.ClassificationofseizuretypeprovidesaguidetoAEDtherapy(AppendixC1).

6.4 TheILAErevisedclassificationoftheepilepsiesand epileptic syndrome in 1989 has gainedwidespread acceptance among worldwideepileptologists (Appendix C2). It takes intoaccountaetiologicfactors,ageofonset,regionof onset, and carries prognostic information.ThechoiceofAEDcanbefurtherrefinedbasedonthesyndromicdiagnosis(AppendixD2).

7 Principles of management7.1 A comprehensive care plan and counselling

on important issues (eg driving, schooling,employment, and pregnancy) should bediscussed.GPP

7.2 In newly diagnosed epilepsy, the aim of AEDtreatment is to achieve seizure freedom withminimal or no side-effect. In drug-resistantepilepsy, the treatment target would beachieving the best quality of life by strikinga balance between AED efficacy and theirassociatedside-effects.GPP

8 Pharmacological or AED management8.1 The AED treatment strategy should be

individualised according to the seizure typeandseverity,epilepsysyndrome,co-medicationand co-morbidity, the individual’s lifestyle,characteristics,andpreference(Table1).A

8.2 TheinitialchoiceofAEDisguidedbytheseizuretypeorepilepsysyndrome(AppendicesDandE).Becauseoflackofhigh-qualitycomparativestudiesamongAED,onlysuggestionsaremadeforeachcategory.Otherpublishedguidelines(eg ILAE, American Academy of Neurology)maybeconsulted.D

8.3 In general, patient factors should be matchedwith AED characteristics in terms of efficacyagainst seizure type/epilepsy syndrome,potential side-effects, teratogenicity, meta-bolism, and possible AED interactions. Forinstance,theside-effectsofAEDmaybemoreapparent in certain patient groups and thesemayaffectthechoiceofAED(Table2).GPP

8.4 Switching AED between different manufacturersis not recommended because of differentbioavailability and pharmacokinetic profiles.Substitution may increase the potential forbreakthroughseizuresorexcessiveside-effects(AppendixD3).GPP

TABLE 1. Factors affecting the choice of AEDs

AED-specific variable Patient-specific variable Nation-specific variable

Seizure or epilepsy syndrome

Genetic background AED availability

Specific efficacy/effectiveness

Gender AED cost

Dose-dependent adverse effects

Age

Idiosyncratic reactions Co-medications

Chronic toxicities Co-morbidities

Teratogenicity Insurance coverage

Carcinogenicity Relative wealth

Pharmacokinetics Ability to swallow pills/tablets

Interaction potential

Formulations

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8.5 Single AED (monotherapy) treatment ispreferred to polytherapy wherever possible.A If the first AED is unsuccessful, anothermonotherapymaybestartedandbuiltuptoanadequate dose before the first AED is taperedoffslowly.GPP

8.6 Iftheseconddrugisunhelpful,eitherthefirstorseconddrugmaybetapered,dependingontheirrelativeefficacyandside-effects.GPP

8.7 Combination (adjunctive or ‘add-on’) therapyshouldbeconsideredifmonotherapytrialsfailtocontroltheepilepsy.A

8.8 Bewareofdrug-druginteractionsamongAEDsandbetweenAEDsandnon-AEDs,egwarfarin,oral contraceptive pills via effects of AED onhepatic cytochrome P450 enzyme system.Carbamazepine, phenobarbital, phenytoinare broad enzyme inducers with manyinteractions including oral contraceptive pills.Oxcarbazepine and topiramate (>200 mg perday) induce metabolism of oral contraceptivepills.Gabapentinandpregabalin(bothexcretedrenally unchanged), and levetiracetam (non-hepatic hydrolysis) have lowest potential ofdrug-druginteractions. A

8.9 Valproatesignificantly inhibits themetabolismof lamotrigine. When lamotrigine is addedto a drug regimen containing valproate, itshouldbetitratedmoreslowlytoreachalowermaintenancedose.A Thispracticemayreducethe incidence of dose-dependent adverseeffectsoflamotrigine,particularlyskinrash.B

8.10 Regularbloodtestsfor‘routine’haematologicalandrenalandliverfunctionsarenotnecessaryandshouldbedoneonlyifclinicallyindicated.Asymptomatic minor laboratory abnormalitiesdo not necessarily require changes inmedication.C

8.11 Routine monitoring of serum AED level is not

indicated. Specific indications for monitoringofserumAEDlevelsinclude: D• suspectedAEDtoxicity• detection of non-compliance to the

prescribedAED• adjustmentofphenytoindose• management of pharmacokinetic inter-

actions• specific conditions, eg status epilepticus,

organfailure,andpregnancy

Withdrawal of pharmacological treatment

8.12 Foradultswhohavebeenseizure-freefor2yearsormore,thedecisiontocontinueorwithdrawAEDshouldbetakenbytheindividualandthespecialistafterafulldiscussionoftherisksandbenefitsofwithdrawal.A (seeSections18.1 to18.13).

8.13 AED treatment should be discontinued slowlywithonedrugbeingwithdrawnata time.DAmoreprolongedtimecourse(upto6months)isrequiredforwithdrawingbenzodiazepinesandbarbituratetoavoidwithdrawalsymptomsandseizure recurrence. If seizure recurs, the lastdosereductionisreversedandmedicaladviceissought.GPP

9 Management of drug-resistant epilepsy

9.1 About 70% of people with newly diagnosedepilepsy respond well to AED. Drug-resistantepilepsy may be operationally defined aspersistence of seizures despite optimal andadequatetreatmenttrialswithtwoAEDs(eithermonotherapy or polytherapy) appropriatelychosenfortheseizuretype/epilepsysyndrome.D

9.2 In people with drug-resistant epilepsy,

TABLE 2. Special considerations in different patient groups

Patient group Considerations

Elderly Impaired drug clearance and increased susceptibility to side-effect, eg hyponatremia due to carbamazepine; risk of polypharmacy and potential drug interactions

Children Avoid phenobarbitone (behavioural disturbance) and phenytoin (cosmetic side-effect and erratic absorption)

Reproductive women Avoid high-dose valproate (teratogenicity [see Section 16.5]), and avoid enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital) if oral contraceptives are required

Cognitive dysfunction Avoid phenobarbitone, benzodiazepines and topiramate if risk of cognitive slowing is unacceptable

Mitochondrial diseases Avoid valproate

Advanced renal failure Reduce dose of AEDs that are primarily excreted by renal route, eg gabapentin, pregabalin

Active liver disease Avoid valproate (risk of hepatic encephalopathy)

Eating disorders Avoid topiramate

Morbid obesity Avoid valproate, pregabalin



considerationshouldbegiventothepossibilityof ‘pseudo-resistance’, referring to treatmentfailuredueto:C• incorrectdiagnosisofepilepsy• inappropriatechoiceofAEDfortheseizure

type/epilepsysyndrome• inadequatedosageofAED• poorcompliancetotreatment• unsatisfactory lifestyle such as drug or

alcoholabuse

9.3 People fulfilling a diagnosis of drug-resistantepilepsy should undergo, preferably at aspecialist centre, comprehensive evaluationof the diagnosis and management, which mayincludeworkupforepilepsysurgery.C

10 Side-effects of AEDs (Appendix D4)Dose-related adverse reactions

10.1 Neurotoxic side-effects (eg dizziness,somnolence, diplopia, ataxia) are mostlydose-related and predictable. These can bereducedbygradualescalationofdoseanddosereductionifsymptomspersist.A

Idiosyncratic drug reactions

10.2 Idiosyncraticdrugreactionsusuallyoccurinthefirstfewweeksoftreatmentandarepotentiallyserious.Skinrashisthemostcommon,occurringin up to 10% of patients on carbamazepine,lamotrigine, oxcarbazepine, phenobarbital,and phenytoin. Cross hypersensitivity iscommon. Most rashes are mild and resolvepromptly on discontinuation of the AED, butsevere cutaneous reactions (Stevens-Johnsonsyndrome and toxic epidermal necrolysis) areseeninupto1:1000patients.

10.3 HLA-B*1502 allele (present in 10-20% ChineseinHongKong)isassociatedwithadramaticallyincreasedriskofcarbamazepine-inducedseverecutaneousreactionsinpeoplewithsusceptibleethnic backgrounds, eg Han Chinese. Priorto starting carbamazepine, people who areethnically Chinese should be tested for HLA-B*1502. Carbamazepine should be avoidedif the test is positive unless the benefits fromtreatment outweigh the risk of developingsevere cutaneous reactions (see FDA Alert:Information for healthcare professionals:carbamazepine <www.ifap.de/pdf/FDA_carba-mazepin-warning_2007-12-12.pdf>).

10.4 AED hypersensitivity syndrome of fever, rash,lympadenopathy, and multi-organ failureoccurs in up to 4:10 000 patients, mostly witharomatic AEDs (carbamazepine, phenytoin,phenobarbital)orlamotrigine.Cross-sensitivity

mayoccurbetweenaromaticAEDsinupto50%ofpatients.B

10.5 Minor blood dyscrasias are associated withmanyAEDs,egleukopeniawithcarbamazepine,thrombocytopeniawithvalproate. GPP

10.6 Hyponatremia(sodium125-135mmol/L)isseeninabout20%ofpatientstakingcarbamazepineoroxcarbazepine,whichisusuallyasymptomatic.Mild elevation of liver enzymes (gamma GTPor alkaline phosphatase) is commonly seen inpeopletakingenzyme-inducingAEDs.GPP

Chronic side-effects

10.7 Vigabatrin should be used as drug of lastchoice (except infantile spasm) because of itsassociation with high incidence of visual fielddefects.B

10.8 Weight gain is seen with many AEDs (egvalproate, gabapentin, pregabalin) and maybesignificant(>10%bodyweight).Incontrast,topiramatecancauseweightloss.B

10.9 Peoplewithepilepsytakinglong-termAEDarepronetohaveosteoporosis,osteomalacia,andfractures. Cytochrome P450 enzyme-inducingAEDs are most commonly associated with anegative impact on bone, but studies alsosuggestaneffectofvalproate.TherearelimiteddataregardingthenewerAED.Theyareadvisedtohaveadequateintakeofdietarycalciumandvitamin D together with regular bone densitymonitoring.D

10.10TeratogenicityofAEDisdiscussedinSection16.

10.11CertainAEDmayexacerbatesomeseizuretypesandepilepsysyndromesandshouldbeavoidedaccordingly(AppendixD1andD2).

11 Presurgical evaluation of drug-resistant epilepsy

11.1 A comprehensive presurgical evaluationentails a multidisciplinary team of experts(neurologists, paediatricians specialising inneurology/epilepsy, neurosurgeons, neuro-radiologists, psychiatrists, and clinicalpsychologists).Multi-modalinvestigationsmaybeundertaken includingvideo-EEGrecording,CT, MRI, functional MRI, PET, SPECT, MEG,angiogram and intracarotid amobarbital test,intracranial EEG monitoring, and functionalmappingtoevaluatebrainfunction.

Referrals for presurgical evaluation

11.2 If there is diagnostic uncertainty or treatmentfailure,individualsshouldbereferredtotertiary

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servicesforfurtherassessment.Indicationsforreferralincludethefollowing:D• drug-resistantepilepsy• theindividualisagedunder2years• unacceptable side-effects from

medication• thereisaunilateralstructurallesion• there is psychological and/or psychiatric

co-morbidity• thereisdiagnosticdoubtastothenatureof

theseizures• thereisatestablehypothesisforlocalising

theepileptogeniczone

11.3 Different scenarios determine complexity ofinvestigations:

Scenario 1: a focal lesion on MRI withconcordantscalpEEGandcongruentresultsoffunctional evaluation. The classical prototypeis a right-handed individual with right mesialtemporal sclerosis, ictal right temporal EEGonset,interictalrighttemporalEEGdischarges,clinicalpsychologicaltestingshowingimpairedfigurativememoryandnormalverbalmemory.A

Scenario 2: focal or multiple lesions on MRIwith our without discordant scalp EEG orincongruent results of functional evaluation.This entails a heterogeneous group ofpatients with discordant results. Multi-modalinvestigationsandmultidisciplinarydiscussionsareusuallyundertakenandtheremaybeaneedfor intracranial implantation to localise theepileptogenic zones. Individualised approachisusuallyadopted.C

Scenario 3: resection close to eloquent areas.Consideration should be given to functionalmapping, which may be undertaken intra-operatively or extra-operatively with gridimplantation. Extra-operative functionalmapping may provide more sophisticatedtestingofbrainfunctions.C

Scenario 4: non-lesional or ‘cryptogenic’cases. Investigations are necessary to rule outidiopathic generalised epilepsy. Multi-modalinvestigationsandintracranialimplantationwillberequiredinthemajorityofcases.C

Scenario 5: resective surgery not applicable.Palliativeneurosurgery,egcorpuscallosotomyorvagusnervestimulation,maybeconsidered.C

Special considerations in paediatric epilepsy surgery

11.4 The spectrum of localisation-related epilepsyis often heterogeneous in childhood andmay present with generalised seizures or EEG

patterns, as well as progressive neurologicaldysfunction.C

11.5 Unclassifiable childhood epilepsy should bereferred for presurgical evaluation, eg non-idiopathicpartialseizuresor lesionalepilepsy.D

11.6. Age-appropriate neuropsychological anddevelopmental assessments are mandatoryin those with developmental delay but suchimpairment should not exclude them fromepilepsysurgery.D

11.7 Epilepsysurgeryconsistsofcorticalresectionordisconnectionprocedures.Surgicalremediablesyndromes were more diverse in children,including mesial temporal sclerosis, corticaldysplasia, developmental brain anomaliesand tumour, tuberous sclerosis, Rasmussen’sencephalitis, hypothalamic hamartoma, andvascularmalformations.D

11.8 Functional plasticity in the child’s brain couldenhancetherecoveryoflinguisticcompetenceand facilitate neurological re-organisationafter surgical treatment. Early intervention istherefore critical in infants with catastrophicepilepsy to prevent developmental arrest orregression. C

11.9 Corpus callosotomy is a palliative epilepsysurgery to block interhemispheric spreadof secondarily generalised seizures. Corpuscallosotomyisespeciallyeffectivefortonicandatonic seizures causing falls and consequentinjuries,egLennox-Gastautsyndrome.C

12 Other forms of treatmentPsychological interventions

12.1 Psychological interventions (relaxation, cogni-tive behaviour therapy, biofeedback) may beused in conjunction with AED in adults. Thisapproachmaybeassociatedwithanimprovedqualityoflifeinsomeindividuals.A

12.2 Psychological therapy has not been proven toaffectseizurefrequencyandisnotanalternativetoAEDtreatment.A

Ketogenic diet

12.3 The ketogenic may be considered anadjunctive treatment in children with drug-resistant epilepsy. The responder rate (morethan 50% seizure reduction) is close to 40%.A Side-effects include constipation, vomiting,lethargy, hunger, acidosis, easy bruising, andnephrolithiasis. Contra-indications includethose with fat metabolic disorders andporphyria.



12.4 The modified Atkins diet (restrictingcarbohydrateintaketo10ginchildrenand15ginadults)hasa45%responderrate.C

Vagus nerve stimulation

12.5 Vagus nerve stimulation is indicated as anadjunctive therapy in reducing the frequencyof seizures in drug-resistant epilepsy notamenabletosurgery.TheefficacyofvagusnervestimulationissimilartothatobtainedwithnewAEDs.A Side-effectsareusuallymild,egcoughandtransienthoarsenessofvoice.

Gamma knife radiosurgery

12.6 Gamma knife radio surgery may be effectivein patients with mesial temporal sclerosis butadelayedresponseby10months isobserved.The long-term side-effects are unknown. Itis also effective in treating focal epilepsy dueto cavernous angiomas in central region andgelasticseizures inhypothalamichamartomas.C

13 Prolonged seizures in the community13.1 An individual who has prolonged convulsive

seizures (lasting 5 minutes or more) or serialseizures(threeormoreseizuresinanhour)inthecommunityshouldreceiveurgentcareandtreatment. A

13.2 Rectal diazepam is a safe and effective first-linetreatmentofprolongedseizures.A Buccalmidazolamisanalternativewhichiseasiertobeadministeredandconsideredmoreacceptableforpatientsandadministers.C

14 Treatment of status epilepticus 14.1 Convulsive status epilepticus is a medical

emergency.• General measures include airway

management,settingupIVaccess,oxygensupplement, cardiorespiratory functionmonitoring. GPP

• IV lorazepam is a first-line treatment instatus epilepticus and alternatives includeIVdiazemuls,diazepam,andmidazolam.DThese can be repeated if necessary. Closemonitoringofcardiorespiratoryfunctionismandatory.

• Full blood count, urea, and electrolytes,liver function tests, blood gases, calcium,glucose, clotting profile andAED level(s)

General measures Pharmacological treatment

Premonitory status (prehospital)• Out-of-hospital management for acute seizure• Common sense to prevent injuries, eg cushion the person’s head,

loosen any tight neckwear, turn the person on his or her side• Do not hold the person down or restrain the person• Do not place anything in the mouth • Do not try to pry the teeth apart• Observe seizure characteristics—length, type of movements, direction

of head or eye turning

1. Rectal diazepam 10-20 mg, repeated once 15 minutes later if seizure continues, OR

2. Buccal midazolam 10 mg

If seizures continue, call emergency ambulance service and continue anticonvulsant as below.

Early status I (0-10 minutes) • Resuscitation, secure airway (consider intubation), administer

oxygen, assess cardiorespiratory function and establish IV access, haemoglucostix

1. Lorazepam IV 0.1 mg/kg (usually 2-4 mg bolus, repeated once after 10-20 minutes) OR

2. Diazepam IV 0.1 mg/kg (usually IV 5-10 mg bolus, repeated once after 5-10 minutes) OR

3. If already on AED, resume usual medication

For sustained control or if seizures continue, treat as below.

Early status II (0-30 minutes) • Institute regular monitoring, emergency investigations• Administer glucose (50 mL of 50% solution) and/or IV thiamine (250

mg) • Treat acidosis if severe • Consider the possibility of non-epileptic status

Established status (0-60 minutes) • To establish aetiology • Arrange ICU bed• Identify and treat complications, including use of vasopressor, if

appropriate

1. Phenytoin infusion at a dose of 15-18 mg/kg at a rate of 50 mg/minute OR

2. Fosphenytoin infusion at a dose of 15-20 mg phenytoin equivalents (PE) per kg at a rate of 50-150 mg PE/minute AND/OR

3. phenobarbitone bolus of 10-15 mg/kg at a rate of 100 mg/minute

Refractory status (30-90 minutes) • Transfer to ICU, and EEG monitoring• Consider the possibility of non-epileptic status• Intracranial pressure monitoring, if appropriate • Initiate long-term, maintenance AED therapy

General anaesthesia, with one of the following:a. propofol (1-2 mg/kg bolus, then 2-10 mg/kg/hour) b. midazolam (0.1-0.2 mg/kg bolus, then 0.05-0.5 mg/kg/hour) c. thiopentone (3-5 mg/kg bolus, then 3-5 mg/kg/hour) [after 2-3

days infusion rate needs reduction as fat stores are saturated]

Anaesthetic continued for 12-24 hours after the last clinical or electrographic seizure, then dose tapered.

TABLE 3. Guideline for treating convulsive status epilepticus

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areindicated. C• Give 50 mL of 50% glucose IV for

hypoglycaemia and IV thiamine if alcoholabuseorpoornutritionalstatusissuspected.C

• For patients with epilepsy, the usual AEDshall be resumed with dosage adjustmentif necessary. Otherwise a loading dose ofAED should be given (Table 3). B The rateof AED infusion may need to be adjustedif hypotension or arrhythmia occurs. Inselectedcases,IVvalproateorlevetiracetammaybeused. D

• If seizure continues, ICU admission isindicatedforadministrationofanaestheticagent (Table 3), EEG monitoring andcritical life support.The cause of statusepilepticus shall be investigated andtreated.C

14.2 Non-convulsive status epilepticus is lesscommon. Continuation of usual AED and IVbenzodiazepines with EEG monitoring areuseful.GPP

15 Perioperative management of seizure15.1 LossofseizurecontrolduetomissedoralAED

can occur during surgery, labour and whenthere is difficulty in swallowing. Table 4 listssomealternativeroutesofAEDadministration.Sometimes changes in drug doses will benecessary due to pharmacokinetic differencesbetweenformulations.C

15.2 AEDs should be administered by alternativeroutes or by giving additional doses asappropriate. When patients have beendesignatednilbymouthpriortosurgery, theyshouldstillbegiventheirusualoralAEDunlessabsorptionisimpaired.GPP

15.3 Whenaprolongedproblemwithadministered

drugs not available parenterally is anticipated,and oral or enteral administration is notpossible, consideration should be given toseizureprophylaxiswithparenterally availableagents.GPP

16 Women with epilepsy16.1 Women with epilepsy and their spouses

shouldreceiveinformationandcounsellingoncontraception, conception, pregnancy, child-care,breastfeeding,andmenopause.C

16.2 Preconceptioncounsellingshouldbegiven towomenofchildbearingagewithepilepsy.Theyshould be reassured that most can have anuneventfulpregnancyanddelivery.GPP

16.3 In women of childbearing potential, the riskof AEDs causing harm to foetus should beadequately discussed. The treatment strategyshouldbetargetedatthelowesteffectivedoseof the most appropriate AED. Monotherapy ispreferredtopolytherapy.C

Teratogenicity of AEDs

16.4 Common associated major congenitalanomaliesconsistofhypospadias,heartdefects,clubfoot,cleftliporpalate.Theseoccurinthegeneralpopulationatarateof2to5%.Theriskofsuchmajorcongenitalanomaliesisincreasedto4to10%ininfantsexposedtotheoldAEDsespecially for those who are receiving AEDpolytherapy.C

16.5 Neural tube defects occur in 1 to 2.2% withcarbamazepine but a dose-escalating riskhas been observed with both valproate andlamotrigine: 4.1% with valproate at <600 mg/day;1.3% with lamotrigine <100 mg/day, 6% withvalproate600-1000mg/day,1.9%withlamotrigineat100-200mg/day,9.1%withvalproateat>1000mg/day, 5.4% with lamotrigine >200 mg/day. CScreeningofneuraltubedefectsbyultrasoundandalpha-fetoproteinshouldbecarriedoutat18to22weeks’gestation.GPP

16.6 In-utero exposure to high-dose valproate isassociated with an increased risk of impairedcognitive function at 3 years of age. Thisfindingsupportsarecommendationthatotheralternativesshouldbeconsideredasfirst-choicetherapyinwomenofchildbearingpotential.C

16.7 There are insufficient data to evaluate theteratogenicity potential among other newerAEDs, eg topiramate, levetiracetam, andgabapentin.

16.8 Dailyfolate(5mg)supplementshouldbegivenbeforepregnancy.D

AED Alternative administration

Carbamazepine Liquid or suppositories (dose amendment required)

Phenytoin IV or liquid phenytoin; IV or IM fosphenytoin

Gabapentin Capsule contents via feeding tube (unlicensed)

Levetiracetam Liquid or IV

Lamotrigine Dispersible tablets can be given via feeding tube

Valproate IV, liquid, or suppositories (unlicensed)

Topiramate Sprinkle capsules

Vigabatrin Powder

Phenobarbital Liquid; IV or IM injection

TABLE 4. Alternative methods of AED administration



Contraception

16.9 AED interaction with oral contraceptive pillsshouldbediscussed.GPP

16.10If a woman taking enzyme-inducing AEDs(carbamazepine,oxcarbazepine,phenobarbital,phenytoin, primidone, topiramate) requireshormonal contraception, the followingregimensarerecommended:• For combined oral contraceptive pills, a

minimuminitialdoseof50µgofoestrogenshouldbecommenced.D

• Ifbreakthroughbleedingoccurs,thedoseof oestrogen should be increased to 75or 100µg per day, and ‘tricycling’ (takingthree packs without a break) should beconsidered.D

• A shorter repeat injection interval isrecommended (10 weeks rather than12 weeks) for depot injections ofprogesterone (eg Depo-Provera 150 mg)D

• Foremergencycontraception, thedoseoflevonorgestrel should be increased to 1.5mgand750µgwith12hoursapart.D

Pregnancy

16.11Women should be reassured that there is noevidence that simple partial, complex partial,absence and myoclonic seizures affect thepregnancy or developing foetus adverselyunlesstheyfallandsustainaninjury.D

16.12Sixtypercentofwomenexperiencenochangeinfrequencyduringpregnancy,30%increasedfrequency and 10% decreased frequency. Theincrease in seizure frequency may be due topregnancy-related fall in AED concentration,sleepdeprivation,orpoorcompliance.B

16.13Routine monitoring of most AED levels inpregnancyisnotnecessary.However,thismaybe used to guide dosage adjustment shouldseizurefrequencyincrease.D

16.14Both total and free clearance of lamotriginemay increase substantially during pregnancywith peak at the third trimester (up to 90-230%). A drop of lamotrigine level to 65% ofthepreconceptionallevelisassociatedwithanincreaseinseizurefrequency.A Monitoringoflamotriginelevel,ifavailable,isusefultoadjustdosageoflamotrigineduringpregnancy.

Labour

16.15About1to2%ofwomenwithepilepsydevelopa generalised tonic-clonic seizure duringlabour.AEDsshouldbecontinuedorallyorviaIV route if necessary. Epidural anaesthesia is

recommended to reduce pain and emotionaldistress. Elective caesarean section may benecessaryifseizuresarefrequent.D

16.16To prevent haemorrhagic disease of newborn,mothers taking enzyme-inducing AEDs maybe given 20 mg/day of oral vitamin K1 in thelast month of pregnancy. Alternatively, theirnewborns should be given 1mg of vitamin K1parenterallyatdelivery.C

Breastfeeding and the puerperium

16.17Allwomenwithepilepsyshouldbeencouragedto breastfeed, which is safe in the majorityof cases. GPP As most AEDs are secreted inbreast milk in small quantities, the infant maybecomesedated(inabout5-10%).Underthesecircumstances, bottle-feeding can be used tosupplementbreastfeeding.

16.18Mothers should breastfeed their babies whilesittingonfloorcushionstoavoiddroppingtheirbabyshouldaseizureoccur.Bathingthebabiesinthebathtubisnotrecommended.GPP

Menopause

16.19Clinician must remind patients that hormonalreplacementtherapyissignificantlyassociatedwith increase in seizure frequency duringmenopause,particularlyinwomenwithhistoryofcatamenialepilepsy.C

17 Older people with epilepsy17.1 Generalised convulsions and complex partial

seizures (mainly extra-temporal) are the mainclinicalmanifestationsofepilepsyintheelderly.The lattermaypresentwithstaring,blackouts,ordizzinesswhichmaybemistakenastransientischaemicattackorsyncope.

17.2 In view of the altered pharmacokinetics andpharmacodynamics in the elderly, side-effects ofmost AEDs are more apparent and a lower start-ing dosage is recommended. Drug interactionsmay constitute a significant problem because ofpolytherapy associated with co-morbidities. ThenewerAED,eggabapentin,lamotrigineareshownto be better tolerated in the elderly with similarefficacycomparedwiththeoldAEDs.B

18 Children and young people with epilepsy

After first seizure

18.1 ‘Airway, breathing and circulation’ should bepreserved according to established paediatriclife support guideline. If the child shows full

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1� HongKongMedJVol15No5# Supplement5# October2009

recoveryafterthefirstseizure,itisnotnecessarytocheckfullbloodcountorelectrolytesunlessthere are specific features on history andexaminationtosuggestthismightbehelpful.

Differential diagnosis

18.2 Misdiagnosis of epilepsy appears to be asignificantproblemandmayhavemajorlonger-termimplications(AppendixB3).Thediagnosisof epilepsy should be made by a paediatricneurologist or paediatrician with expertise inchildhood epilepsy. D Home video camerarecordingsshouldbeusedinordertocapturerecurrent events where the diagnosis is indoubt. GPP

Investigations

18.3 Investigations• All children presenting with convulsive

seizures should have an ECG with acalculation of the QTc interval, in orderto rule out epileptic or epileptic eventsassociatedwithcardiogenicsyncope.GPP

• All children with recurrent epilepticseizures other than recurrent or complexfebrileseizuresshouldhaveanEEG.C AEDsshouldnotusuallybestartedbeforeanEEGrecording since it may mask a syndromicdiagnosis.GPP

• Most children with epilepsy should havean elective MRI brain scan. Children withthe following epilepsy syndromes (whichfollow a typical course) do not needbrain imaging—eg idiopathic generalisedepilepsies (childhood absence epilepsy,juvenile myoclonic epilepsy, juvenileabsence epilepsy etc); benign childhoodepilepsywithcentrotemporalspikes.D

Genetic testing

18.4 Where one person in a family has idiopathicepilepsy, the recurrence risk for siblings is2.5to6.7%andforchildrenis1.6to6.3%.Therecurrence risk for symptomatic epilepsiesrelates to the underlying aetiology. In allpatients with newly diagnosed epilepsy, athree-generation family history should betaken (ie siblings, parents and grandparents,uncles,aunts,cousins).Familieswithahistoryof epilepsy should be referred to the ClinicalGenetic Service particularly if three or moremembersofthefamilyareaffected.GPP

Pyridoxine dependency

18.5 Pyridoxine-dependent seizures form a rare,

but easily treatable epilepsy syndrome whereseizuresarelargelyresistanttoAED.Whilethereare typical neonatal presentations, childrenmaypresentupuntilthethirdyearoflife.Atrialof pyridoxine and its withdrawal is needed todiagnosepyridoxinedependencyandshouldbeconsideredinchildrenwithintractableepilepsywithonsetundertheageof3years.GPP

Febrile seizures

18.6 Childrenwithfebrileseizures,evenifrecurrent,should not be treated prophylactically withAED. B Fordetails,pleaserefertothefollowingwebsite: <http://www.fmshk.org/hkcpaed/member/guideline/fc.pdf>

Choice of AEDs (Appendices D and E)

18.7 WhenWest’ssyndrome iscausedby tuberoussclerosis, vigabatrin is superior. For otheraetiologies and cryptogenic forms of West’ssyndrome, corticotrophin or corticosteroidsshouldbeusedasfirst-linetreatment.B

18.8 In drug-resistant idiopathic generalised epilepsy,topiramate, lamotrigine, levetiracetam andclobazam are effective as add-on treatments.Lamotrigine, topiramate and nitrazepam areeffective add-on treatments in Lennox-Gastautsyndrome. Stiripentol has antiepileptic activityinDravet’ssyndromewhenusedwithclobazamand sodium valproate. High-dose valproate,nitrazepam and topiramate are efficacious inresistantWest’ssyndrome.B

18.9 Prolongedorserialseizuresshouldbetreatedwith either nasal or buccal midazolam orrectaldiazepam.B Allunitsadmittingchildrenshouldhaveaprotocolforthemanagementofconvulsivestatusepilepticus.GPP

18.10Clearadviceonthemanagementofthepotentialadverse effects of AED should be discussedwithchildrenandparentsorcarers.Adolescentgirls taking AED and their parents should beadvisedoftherisksoffoetalmalformationsanddevelopmentaldelay(seeSection16).GPP

Withdrawal of AED treatment

18.11AED withdrawal should be considered inchildren who have been seizure-free for 2 ormoreyears.Reasonsforwithdrawalinclude:• concernaboutside-effectsofAED• avoid teratogenic side-effects on the

foetus• psychological gratification, eg feeling

cured,removalofstigmata

18.12Risk factors for seizure relapse include


HongKongMedJVol15No5# Supplement5# October2009 1�

symptomatic epilepsy, more than 12 years ofageatseizureonset,shortdurationofseizurefreedom (less than 6 months), an abnormalEEG at discontinuation and certain syndromaldiagnosis,suchasjuvenilemyoclonicepilepsy.A

18.13Ifseizurerecurs,itusuallyoccursshortlyafterAED withdrawal. The risk of relapse is about30% in children and 40% in adults. Seizurecontrolmaynotberegainedinupto20%afterrelapse. These risks have to be balanced withthepotentialgainandthefinaldecisionshouldbeindividualised.GPP

Behaviour and learning

18.14Learningandbehaviouralproblemsaremoreprevalentinchildrenwithepilepsythaninthegeneral childhood population. All childrenwith epilepsy should have their behaviouraland academic progress reviewed on aregular basis by the epilepsy team. Childrenwith academic or behavioural difficultiesshould have appropriate educational and/orpsychological assessment and intervention. GPP

Use of other medications

18.15Neurostimulantsshouldnotbewithheld,whenindicated, from children with epilepsy andattention deficit and hyperactivity disorders. D

18.16Selective serotonin reuptake inhibitors andatypicalneurolepticssuchasrisperidoneshouldnot be withheld, when indicated, in childrenwith epilepsy and associated behavioural andpsychiatricdisorders.GPP

Transitional care

18.17Duringadolescence,smoothtransitionofcareto adult services and the possible need forcontinuing multi-agency support should beconsidered.GPP

18.18Adolescents may be stressed by restriction ofrecreationalactivities.Theyareconcernedaboutside-effectsofAEDs (egweightgain) andmayfeel inferiortotheirpeergroup.Psychologicalcounsellingisessential.GPP

19 Lifestyle and social issues Advice on minimising hazards at home

19.1 Clinicians should give advice on minimisingpossible hazards at home in case seizureshappen(eguseshowerratherthanbathtub).D

Hazards at work

19.2 Advice should be given on suitability ofparticular job to people with epilepsy takingintoaccountthejobrequirementsandseizurecharacteristics.D

Sports and leisure activities

19.3 People with epilepsy are recommended tohaveappropriatesports forhealthandsocialwell-being.Epilepsyisnotareasontoprohibitthem from sports (even competitive types),providedadequatesafetymeasureshavebeentaken.D

19.4 Seizurerisk ishigherduringrelaxationperiodaftersportascomparedtoduringsport-playing.D

19.5 Eitherswimmingaloneordiving ishazardous.Accompanying person with lifesaving skills isessential.D

Driving and epilepsy

19.6 Since seizures may result in losing control ofthe vehicle leading to road traffic accidents,people with epilepsy are legally prohibited todriveinHongKong.

19.7 People with epilepsy are obliged to notify theTransportDepartment regarding theirmedicaldiagnosis.

19.8 Anindividualwithinactiveepilepsymayapplyforadrivinglicenceunderspecialcircumstancesbut theoutcome issubject toapprovalby theTransportDepartment.

19.9 Driving is considered a privilege, not a right.Use of public transport is recommended forpeoplewithepilepsy.

19.10Certain occupations are restricted for peoplewith epilepsy, eg drivers for public transport,pilots,operatorsofheavymachinery,egcranes,tractors.

# Sung et al #

18 Hong Kong Med J Vol 15 No 5 # Supplement 5 # October 2009

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# Posterior reversible encephalopathy syndrome #


Recommendation grade Evidence

A Directly based on category I evidence

B Directly based on:• category II evidence, or• extrapolated recommendation from category I evidence

C Directly based on:• category III evidence, or• extrapolated recommendation from category I or II evidence

D Directly based on:• category IV evidence, or• extrapolated recommendation from category I,II or III evidence

GPP Good practice point based on the clinical experience of the Guideline Development Group

Evidence category Source

I Evidence from:• meta-analysis of randomised controlled trials, or at least one randomised controlled trial

II Evidence from:• at least one controlled study without randomisation, or• at least one other type of quasi-experimental study

III Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case-control studies

IV Evidence from expert committee reports or opinions and/or clinical experience of respected authorities

AppendicesAppendix A. Grading scheme of evidence

# xxxxx #


Appendix B. Differential diagnosis of epileptic seizures and epileptiform dischargesAppendix B1. Differential diagnosis of epilepsy in adults

PsychologicalAdjustment, stress Affective orders, OCDPanic attacksConversion, PTSDPersonality disorderBehavioural disorderMalingeringSomatoform disorderTrauma, abuse

PhysiologicalCardiac/syncopeDrugsMetabolic/toxic infectionMigraine, TGATIASleep disorderMovement disorderDystonia, drop attack

Provoked (group A)AlcoholLack of sleepDrugsMetabolicFeverInfection

Unprovoked (group B)

Epilepsy

Recurrent

Generalised Focal

Non-epileptic seizures Epileptic seizures

Seizures (paroxysmal events)

TGA denotes transient global amnesia, TIA transient ischaemic attack, OCD obsessive compulsive disorder, and PTSD post-traumatic stress disorder

Interictal epileptiform discharges Benign EEG variants and sleep transients Common EEG artifacts

Spikes Small sharp spikes Eye movement

Spikes and slow waves Occipital spikes of the blind Electrocardiogram

Sharp waves 14 and 6 Hz positive spike Head movement

Sharp and slow waves Rhythmic temporal theta bursts Muscle

Polyspikes±slow waves Wicket spikes Swallowing

(Pseudo) Periodic complexes Occipital 6 Hz spike and wave Tongue movement

Paroxysmal lateralised epileptiform discharges Vertex sharp waves Electrode

Positive sharp transients of sleep Pulse

K-complexes Electrical mains

Appendix B2. Differential diagnosis of epileptiform discharges



Group Age Diagnosis

Infants 2 months-2 years Stiff baby/hyperekplexiaCyanotic and pallid breath-holding spells, reflex anoxic seizure, reflex asystolic syncopeShuddering attacksParoxysmal torticollis, extrapyramidal drug reactions, dystoniaSandifer syndromeStereotypies, constipation, infantile gratification disorderFabricated and induced illnessSpasmus nutans Benign paroxysmal vertigoBenign myoclonus of early infancyAlternating hemiplegia of childhoodSleep disorders: rhythmic movement sleep onset disorder, benign neonatal sleep myoclonus

Childhood 2-12 years Cyanotic and pallid breath-holding spells, reflex anoxic seizure, reflex asystolic syncopeSyncopeMigraine and migraine equivalentsRecurrent abdominal painCyclic vomitingBenign paroxysmal vertigoTicsParoxysmal torticollisParoxysmal kinesigenic choreoathetosisSandifer syndromeDystonic drug reactionConstipationStereotypies, daydreamingGratification disorderFabricated and induced illnessPsychogenic seizuresSleep disorders: rhythmic movement sleep onset disorder, night terrors, sleep walking, talking in sleep, narcolepsy

Adolescent 12 years to adult SyncopeMigraine and migraine equivalentsPsychogenic seizuresMovement disordersParoxysmal kinesigenic choreoathetosisParoxysmal dystonic choreoathetosisParoxysmal hereditary ataxiasTremorTicsTransient global amnesiaSleep disorders: nocturnal myoclonus, hypnic jerks, night terrors, sleep walking, talking in sleep, narcolepsyAdditional non-epiletpic events in children with learning difficultiesSelf stimulationHyperventilationSterotypiesSandifer syndromeSpasticityConusHeadache/painDystonic posturingChoreoathetosis

Appendix B3. Differential diagnosis of epilepsy in children

# xxxxx #


Appendix C. Classification of seizure type and epilepsy syndromeAppendix C1. The ILAE classification of epileptic seizures

(I) Partial (focal, local) seizures(A) Simple partial seizures (consciousness not impaired)

(1) With motor signs(2) With sensory symptoms(3) With autonomic symptoms or signs(4) With psychic symptoms

(B) Complex partial seizures (consciousness impaired)(1) Simple partial onset, followed by impairment of consciousness

(a) With simple partial features (A1-A4), followed by impaired consciousness(b) With automatisms

(2) With impairment of consciousness at onset(a) With impairment of consciousness only(b) With automatisms

(C) Partial seizures evolving to secondarily generalised seizures (tonic-clonic, tonic or clonic)(1) Simple partial seizures (A) evolving to generalised seizures(2) Complex partial seizures (B) evolving to generalised seizures(3) Simple partial seizures evolving to complex partial seizures, evolving to generalised seizures

(II) Generalised seizures (convulsive or nonconvulsive)(A) Absence (petit mal) seizures(B) Myoclonic seizures(C) Tonic seizures(D) Atonic seizures(E) Clonic seizures(F) Tonic-clonic (grand mal) seizures

(III) Unclassified epileptic seizures (caused by incomplete data)



Appendix C2. The ILAE classification of epilepsies and epilepsy syndromes

(1) GeneralisedIdiopathic generalised epilepsies with age-related onset (in order of age)

Benign neonatal familial convulsionsBenign neonatal convulsionsBenign myoclonic epilepsy in infancyChildhood absence epilepsyJuvenile absence epilepsyJuvenile myoclonic epilepsyEpilepsy with generalised tonic-clonic seizures on awakeningOther generalised idiopathic epilepsies not defined aboveEpilepsies with seizures precipitated by specific modes of activation

Cryptogenic or symptomatic generalised epilepsies (in order of age)West syndromeLennox-Gastaut syndromeEpilepsy with myoclonic-astatic seizuresEpilepsy with myoclonic absences

Symptomatic generalised epilepsiesNon-specific aetiologyEarly myoclonic encephalopathiesEarly infantile encephalopathy with burst suppressionOther symptomatic epilepsies not defined aboveSpecific syndromesEpilepsies in other disease states

(2) Localisation-relatedLocalisation-related epilepsies—idiopathic with age-related onset

Benign epilepsy with centrotemporal spikesChildhood epilepsy with occipital paroxysmsPrimary reading epilepsy

Localisation-related epilepsies—symptomaticEpilepsia partialis continuaSyndromes characterised by specific modes of precipitationTemporal lobe epilepsies

Central region epilepsiesFrontal lobe epilepsiesParietal lobe epilepsiesOccipital lobe epilepsies

Localisation-related epilepsies—cryptogenic

(3) Epilepsies undetermined as to whether focal or generalisedWith both generalised and focal seizures

Neonatal seizuresSevere myoclonic epilepsy in infancyElectrical status epilepticus in slow wave sleepAcquired epileptic aphasia

Other undetermined epilepsies (not defined above) with unequivocal generalised or focal features(4) Special syndromes

Febrile convulsionsIsolated seizures or isolated status epilepticusSeizures occurring only when there is an acute metabolic or toxic event caused by factors such as alcohol, drugs, eclampsia, non-ketotic hyperglycaemia

# xxxxx #


Seizure type First-line drugs Second-line drugs Other options Drugs to be avoided

Primary Generalised Tonic-clonic

Sodium valproateCarbamazepinePhenytoinLamotrigineTopiramate

Clobazam LevetiracetamOxcarbazepine

PrimidoneClonazepam Phenobarbital

Absence EthosuximideSodium valproate Lamotrigine

ClobazamClonazepamTopiramate

CarbamazepineGabapentinPregabalinOxcarbazepine

Myoclonic Sodium valproateLevetiracetam

ClobazamClonazepam PiracetamTopiramate

Lamotrigine CarbamazepineGabapentinPregabalinOxcarbazepine

Tonic Sodium valproate Lamotrigine

ClobazamClonazepam TopiramateLevetiracetam

PrimidonePhenobarbitalPhenytoin

CarbamazepineOxcarbazepine

Atonic Sodium valproate Lamotrigine

ClobazamClonazepamLevetiracetamTopiramate

PhenobarbitalPrimidone

CarbamazepineOxcarbazepinePhenytoin

Focal with/without secondary generalisation

CarbamazepinePhenytoinSodium valproateLamotrigineOxcarbazepineTopiramateLevetiracetam

ClobazamGabapentinPregabalin

ClonazepamPhenobarbitalPrimidone

Appendix D. Pharmacological treatmentAppendix D1. Suggested choice of AEDs by seizure types in adolescents and adults (modified from NICE)

Epilepsy syndrome First-line drugs Second-line drugs Other drugs Drugs to be avoided

Childhood or juvenile absence epilepsy

EthosuximideSodium valproateLamotrigine

LevetiracetamTopiramate

CarbamazepineGabapentinPregabalinOxcarbazepinePhenytoin

Juvenile myoclonic epilepsy

Sodium valproate Levetiracetam LamotrigineClobazamClonazepam Topiramate

CarbamazepineGabapentinPregabalinOxcarbazepinePhenytoin

Infantile spasms (IS) ACTH/SteroidsVigabatrin** (first line for IS with tuberous sclerosis)

ClobazamClonazepam Sodium valproateTopiramate

Nitrazepam CarbamazepineOxcarbazepine

Benign epilepsy with centrotemporal spikes or occipital paroxysms

CarbamazepineLamotrigineOxcarbazepineSodium valproate


Severe myoclonic epilepsy of infancy

ClobazamClonazepamSodium valproateTopiramate

Levetiracetam Phenobarbital CarbamazepineLamotrigineOxcarbazepine

Lennox-Gastaut syndrome LamotrigineSodium valproateTopiramate

ClobazamClonazepamEthosuximideLevetiracetam


Landau-Kleffner syndrome LamotrigineSodium valproateSteroids



Myoclonic astatic epilepsy ClobazamClonazepamSodium valproateTopiramate

LamotrigineLevetiracetam


Appendix D2. Suggested choice of AEDs by epilepsy syndromes



Appendix D3. Position statement of HKES on generic AED substitution

• A narrow therapeutic range is well known for many AEDs, eg phenytoin, carbamazepine, valproate. Although a wider therapeutic range probably exists for new AEDs, serum drug concentration monitoring is not routinely available to measure the difference in AED absorption and guide the proper dosage.

• There are many case reports of adverse events or breakthrough seizures following generic substitution but systematic studies are lacking to determine the impact of generic substitution.

• According to the US Food and Drug Administration (FDA) requirement, bioequivalent generic AEDs have serum drug concentrations between 80 and 125% of the brand AED. Mathematical deduction implies that the variation in rate and extent of absorption among multiple generic AEDs (with different manufacturers) may result in up to 50% difference in serum drug concentrations.

• Switching of AEDs (brand to generic or generic to generic) may result in breakthrough seizures with serious physical and psychosocial consequences, including unemployment, injury and even death.

The HKES recommends the following regarding generic AED substitution

• The treating physician is allowed to choose between brand and generic AEDs at initiation of treatment and subsequent switching should be avoided whenever possible.

• Switching from brand to generic or between generics should be avoided if possible.• We oppose automatic substitution of generic AEDs at pharmacy level.• Before switching from brand to generic AEDs, or between different generic AEDs, verbal consent should be obtained

from patient by the treating physician.• When generic AEDs are prescribed, counselling should be given to patient to improve compliance and reduce anxiety.

Adequate follow-up and monitoring logistics should be implemented wherever possible.• Switching from brand to generic AEDs or between generic AEDs is not recommended in patients whose epilepsy is in

remission.

AED Side-effects

Carbamazepine Allergic skin reactions may be severe. Blurred vision, diplopia, ataxia and nausea common

Clobazam Drowsiness but tolerance may develop after prolonged use

Clonazepam Somnolence and fatigue are usually transitory

Ethosuximide Headache, nausea, and drowsiness are usually mild and transient

Gabapentin Somnolence, dizziness, and fatigue; emotional lability in children

Lamotrigine Skin rash or fever usually within 8 weeks of starting treatment. Adverse effects include drowsiness, diplopia, dizziness, headache, insomnia, confusion, and hallucinations

Levetiracetam Common undesirable effects include dizziness and somnolence. Irritability, insomnia, ataxia, tremor, headache, nausea, and affective symptoms are rare

Oxcarbazepine Diplopia, headache, nausea, skin rash, ataxia, and confusion

Phenobarbital Drowsiness, lethargy, mental depression, and allergic skin reactions

Phenytoin Hypersensitivity reactions including skin rash. Dose-related side-effects include drowsiness, ataxia, and slurred speech. Coarsening of facial features, gingival hyperplasia, and hirsutism may occur rarely. Anaemias are usually responsive to folic acid. Dyskinesias, tremor, and mental confusion are rare

Piracetam Weight gain, somnolence, nervousness, depression, and rash

Primidone Drowsiness and listlessness are common

Sodium valproate Sedation, tremor, weight gain, and transient hair loss has often been reported. Severe liver damage, encephalopathy, pancreatitis, transient hyperammonaemia and blood dyscrasias are rare. Amenorrhoea, irregular periods and foetal neural tube defect may occur

Topiramate Headache, somnolence, dizziness, paraesthesia, weight loss, difficulty with memory and concentration has been reported. Increased risk of nephrolithiasis and glaucoma; rarely reduced sweating in children

Vigabatrin Somnolence, nausea, agitation, aggression, irritability, and depression are common. Psychosis is rare. Visual field defects common and may occur after months to years of vigabatrin treatment. Visual field should be tested every 6 months

Appendix D4. Side-effects of AEDs

# xxxxx #


Example 1

F/17, College student

Seizure types: Generalised tonic-clonic seizure and early morning myoclonus

Syndromic diagnosis:Juvenile myoclonic epilepsy

• Valproate is the standard AED to be used but in view of its teratogenicity, other broad-spectrum AEDs may be selected.

• Topiramate has more cognitive side-effect but it may be preferred if there is co-existing migraine or morbid obesity. • Lamotrigine is a reasonable alternative but it may worsen myoclonus; its serious allegic reaction should be made

known to the patient. • Clonazepam or clobazam may cause daytime sleepiness with issues of tolerance in the long term. • Levetiracetam is a suitable alternative as it has a good side-effect profile.

Example 2

M/70, retired businessman

Seizure type:Secondary generalised tonic-clonic seizure

Aetiological diagnosis:Post-stroke epilepsy, atrial fibrillation on warfarin

• Carbamazepine and oxcarbazepine are more likely to give rise to hyponatremia with its consequent side-effects; testing for HLA B1502 should be done before commencement of carbamazepine; oxcarbazepine is better than carbamazepine as it does not interact with warfarin.

• Phenytoin is favoured by some physicians as response to treatment is usually satisfactory, but dosage adjustment should be cautious in view of its non-linear pharmacokinetics. It may increase or decrease efficacy of warfarin.

• For sodium valproate, some side-effects (eg hand tremor) may be more common in the elderly and valproate may enhance effect of warfarin.

• Lamotrigine and levetiracetam are better tolerated in the elderly without problem of drug interaction but their use is limited by their cost. Gabapentin and pregabalin are useful if there is co-existing neuropathic pain (eg thalamic stroke) and polypharmacy (virtual absence of drug interactions).

• Topiramate may have a negative impact on cognition which may already be compromised after stroke; side-effects, eg paresthesia, may generate worries about recurrent stroke.

• Clonazepam and clobazam are sometimes useful if there is co-existing tremor, myoclonus, anxiety, sleep-related behavioural disorder, insomnia, or restless leg syndrome.

• Phenobarbitone may adversely affect cognition but advantages include low cost and availability of parenteral formulation. It is an enzyme inducer, which may reduce efficacy of warfarin.

Example 3

F/9, schoolgirl Seizure type:Partial motor seizure of left face with secondary generalised tonic-clonic seizure

Epilepsy syndrome:Benign epilepsy with centraltemporal spikes (BECT)

Co-morbidityMigraine

• Carbamazepine and oxcarbazepine are the standard drugs of treatment but HLA B1502 status should be checked before commencement of carbamazepine.

• Sodium valproate is useful for preventing co-existing migraine; side-effects including weight gain, transient hair loss and menstrual disturbances are undesirable.

• Lamotrigine may induce serious drug rash particularly in children and very slow escalation of dose is necessary; it has not been licensed for monotherapy in children younger than 12 years old.

• Topiramate is non–enzyme inducing and also effective against migraine but it may cause anhydrosis in children. • Levetiracetam may rarely induce behavioural disturbance especially for those with a history of psychiatric disorder; it

has not been licensed for monotherapy in children younger than 16 years old.• Gabapentin is less efficacious compared with other standard AEDs.• Pregabalin is only licensed for treatment of adult epilepsy.• Phenytoin is not favoured in view of its cosmetic side-effects, erratic absorption and non-linear pharmacokinetics.• Phenobarbitone is not preferred as it may cause irritability, behavioural disturbance and cognitive impairment in

children.• Clobazam and clonazepam may cause excess daytime drowsiness; they are mainly used as adjunctive therapy instead

of monotherapy.

Appendix E. Examples of factors to consider in selecting an AED in newly diagnosed epilepsy

Documents

EDITOR-IN-CHIEF The hong Kong epilepsy guideline … Cheuk Wing, MBBS, FHKAM (Paediatrics), Specialist in Paediatrics HUI Che Fai, Andrew, MBBS, FRCP (Edin), FHKAM (Medicine), Specialist