guideline for epilepsy

7/23/2019 Guideline for Epilepsy

1/25

1

Evidence Based Guidelines

Management of Epilepsy

in Adults

Evidence Based Guidelines recommended for use inThe Royal Melbourne Hospital

July 2002

Review Date: July 2004

Department of Neurology & Clinical Epidemiology and Health ServiceEvaluation Unit

Supported by funding from the Department of Human Services


2/25

2

Table of ContentsIntroduction......................................................................................................................................................3

Multi-disciplinary Review Group ................................................................................................................3

Other Contributors .......................................................................................................................................3

Document Preparation..................................................................................................................................3

Intent of the guidelines.................................................................................................................................3

Process of Guidelines Development ............................................................................................................4Levels of Evidence for Evaluating the Clinical Research data....................................................................4

Emergency Department management of First Seizure in adults 1 Page Flow-Chart..................................5

Emergency Department management of Status Epilepticus in adults 1 Page Flow-Chart..........................6

1. FIRST SEIZURE click for evidence review.........................................................................................7

1.a Emergency department management of first seizure in adults ............................................................7

Table 1. Recommendations: Emergency Department management of first seizure..............................7

1.b Decision to start an Antiepileptic Drug................................................................................................8

Table 2: Information to discuss with patient prior to commencing AED...............................................8

Table 3. Recommendations. Decision to start AED following first seizure..........................................8

Table 4. Choice of antiepileptic drug for seizure type ............................................................................9

2. ESTABLISHED EPILEPSY....................................................................................................................9

2.a Ongoing management of patients with Epilepsy .................................................................................9

Table 5: Recommendations: Ongoing management of patients with epilepsy......................................9

2.b Therapeutic dose & haematological monitoring for adverse effects - click for evidence review .......9

Table 6: Recommendations: Therapeutic dose & haematological monitoring for adverse effects ......10

2.c Treatment of refractory epilepsy........................................................................................................10

Table 7: Recommendations: Treatment of refractory epilepsy.............................................................10

3. STATUS EPILEPTICUS - click for evidence review ...........................................................................11

Table 8: Recommendations: Management of Convulsive Status Epilepticus .....................................11

4. VIDEO EEG MONITORING - click for evidence review....................................................................12

Table 9: Recommendation: Indications for Video EEG monitoring ...................................................12

5. SURGERY - click for evidence review .................................................................................................12

Table 10: Recommendations: Surgery for epilepsy.............................................................................12

6. WOMEN WITH EPILEPSY- click for evidence review.......................................................................13

Table 11: Recommendations. Management of women with epilepsy .................................................13

7. DRIVING GUIDELINES......................................................................................................................14Table 12. Recommendations: Driving guidelines................................................................................14

Appendix 1: International Classification of Epileptic Seizures (abbreviated)..............................................15

Appendix 2: Guidelines for fitness to drive following an epileptic seizure...................................................16

For non-commercial drivers.......................................................................................................................16

For Commercial licences ...........................................................................................................................16

Appendix 3: Emergency Department Discharge Pack - First Seizure ..........................................................17

Appendix 4: Letter to General Practitioner following a presumed seizure First Seizure ..........................18

Appendix 5: Emergency Department Discharge Pack Established Epilepsy ............................................19

Appendix 6: Letter to General Practitioner following a presumed seizure Established Epilepsy .............20

References ......................................................................................................................................................21


3/25

3

Introduction

Multi-disciplinary Review Group

The guidelines were developed by Christine Kilpatrick, Donald Campbell, and Adrian Lowe. The

following multi-disciplinary group reviewed and contributed to the guidelines.

A/Prof Christine Kilpatrick Deputy Director Department of NeurologyDr Alastair Meyer Acting Director, Emergency

Medicine

Emergency Department

A/Prof David Russell Director Department of General Medicine

A/Prof Donald Campbell Unit Head Clinical Epidemiology

Mr Andrew Van Slobbe Nurse Unit Manager Ward 4 South

A/Prof David Taylor Director of Emergency

Medicine Research

Emergency Department

Dr Cassandra Szoeke Epilepsy Registrar Department of Neurology

Dr Kasha Singh Stroke Registrar Department of Neurology

Dr Isabella Taylor Neurology Registrar Department of NeurologyDr Anita Vinton Neurology Registrar Department of Neurology

Dr Mark Parsons Neurologist Department of Neurology

Dr Mark Hew Senior Medical Registrar Department of General Medicine

Dr Helmut Butzkueven Neurologist Department of Neurology

Dr Peter Greenberg Director of Evidence Based

Medicine

Department of General Medicine

Dr Karen Honson Neuroscience Pharmacist Department of Pharmacy

Dr Ian Fraser Director of Physician Training Department of Nephrology

Dr Heather Smith Medical Education Officer Medical Administration

Mr Adrian Lowe Epilepsy Project Officer Department of Neurology

Other Contributors

Internal review of the guidelines was performed by A/Prof Terry OBrien and Dr Zelko Matkovic, who are

both epileptologists and work at The Royal Melbourne Hospital. Dr Raymond Martyres reviewed the

guidelines from the perspective of a General Practitioner.

Document Preparation

This document was prepared by Adrian Lowe, and reviewed by all members of the multi-disciplinary

reference group.

Intent of the guidelines

This document provides current evidence-based guidance about critical decisions in the management of

adult patients with epilepsy and a first seizure attending Royal Melbourne Hospital.

These guidelines are not a prescriptivestandard of medical care. Standards of medical care aredetermined on the basis of all clinical data available for an individual patient.

This is a guide to evidence-based practice. Adherence to these guidelines will not ensurea successfuloutcome in every case. The guidelines may not include all proper methods of care or exclude other

acceptable methods of care aimed at achieving the same results.

The ultimate choice about clinical procedures and/or treatments are made by the patient (and/or carer)following recommendations from the treating medical practitioner based on the range of options

available.


4/25

4

Process of Guidelines Development

The development of these guidelines has been based on existing international and national guidelines for

the overall management of epilepsy1 2

and specific aspects of epilepsy3-13

. Further systematic searching of

the literature has been undertaken to supplement the information presented in existing guidelines. Key

articles referenced by existing guidelines were retrieved, and search strategies were devised around the

Medical Subject Headings (MeSH) and key words that described these core papers. The reference list of

each article retrieved was reviewed for articles relevant to the topic under review. These articles were

obtained, checked, and summarised if appropriate. If the article was appropriate, but did not appear in theresults from the original search strategy, the articles MESH headings were examined to determine why it

was not identified previously, and the search strategy modified accordingly to determine if other articles

had also been missed for the same reason. As such, a cascade approach was adopted.

Individual searches were conducted on various topics (see

http://www.mh.org.au/clinicalepidemiology/epreview.pdf)for full details of each search strategys results).The search strategy aimed to find the highest level of evidence possible for a particular question. If a high

level of evidence was located, then the search ceased. If not, the search continued for lower levels of

evidence. To view the evidence review on a particular topic, click on the heading of the topic in this

document. This will open the evidence review document used to from this document.

Two general search limits were applied to all strategies. Due to time and budget limitations, only articles

in English were retrieved. As these guidelines are directed only at treatment of adult patients at Royal

Melbourne Hospital, articles that only studied children were excluded, unless no other studies existed.

The guidelines were developed through weekly focus group meetings conducted at The Royal Melbourne

Hospital between Christine Kilpatrick, Donald Campbell, and Adrian Lowe. Please send any comments or

recommendations concerning these guidelines please [email protected]

.

Levels of Evidence for Evaluating the Clin ical Research dataThe National Health and Medical Research Councils (NH&MRCs) levels of evidence when evaluating

clinic research data have been used.77el Type of Evidence

Level Type of Evidence.

I Evidence obtained from a systematic review of all relevant randomised controlled trials

II Evidence obtained from at least one properly designed randomised controlled trial

III 1 Evidence obtained from well-designed controlled studies without randomisation

III 2 Evidence obtained from well-designed cohort or case-control analytic studies preferably

from more than one centre or research group

III 3 Evidence obtained from multiple time series with or without the intervention. Dramatic

results in uncontrolled experiments (such as the results of the introduction of penicillin

treatment in the 1940s) are examples of this type of evidence

IV Opinions of respected authorities, based on clinical experience, descriptive studies

and/or reports of expert committees
http://www.mh.org.au/clinicalepidemiology/epreview.pdfmailto:[email protected]:[email protected]:[email protected]:[email protected]://www.mh.org.au/clinicalepidemiology/epreview.pdf


5/25

5

Emergency Department management of First Seizure in adults 1 Page Flow-Chart

Evaluate potential causes of SeizureConsider: Infection, provoked seizure (medication, alcohol, drug use or sleep

deprivation), metabolic disturbance & non-epileptic seizure

CT brain & contrast, ECG, FBE, U&E, LFTin Emergency Department

Order outpatient EEG

Initial treatment to stop seizure activity if patientin Status or has multiple seizures. See Emergency

Department Status Protocol

Abnormal test resul ts If appropriate treat underlying cause.

(eg CT lesion/tumour)

Normal test results

AED usually not commenced if sing le seizure and investigat ions normal

Consider commencement of AED medication

If definite Seizure &CT reveals an epileptogenic lesion

or history of recent previous seizure

Admit or Discharge?Admit if:

Multiple Seizures or Status

Prolonged post ictal confusion, or focal neurological deficit

Investigations reveal underlying condition that requires treatment

Discharge if:

Patient has normal test results, and has fully recovered.

Actions on Discharge

Confirm EEG ordered

Make appointment for First Seizure ClinicGive safety advice (no driving or operating heavy machinery, swimming alone,

heights, or baths)

Give patient discharge pack (see appendix 3 & 4)

Confirm diagnosisand type of seizure

Discuss with Neurology registrar

If epileptic seizure not suspected refer ifappropriate to General Medical Registrar


6/25

6

Emergency Department management of Status Epilepticus in adults 1 Page Flow-Chart

IMMEDIATE ACTIONS

FOLLOWED BY

IF STATUS / SEIZURESCONTINUE

1. Secure airway2. Commence oxygen

3. Assessment of cardiac and respiratory function4. IV access5. Draw blood for FBC, U&E, LFTs, Ca, Glucose,

clotting, AED levels and storage for later analysis

IV Diazepam (0.15mg/kg at 5mg/min). Repeat if

status epilepticus continues

Establish aetiology.50ml 50% glucose IV if suggestion of hypoglycaemia;

250mg thiamine IV if suggestion of alcohol abuse or

impaired nutritional status

IV Phenytoin (18mg/kg at 50mg/min)

Resume or commence oral AED when patient is able

Call Neurology registrar for all cases of status

epilepticus

Transfer to ICU


7/25

7

1. FIRST SEIZURE click for evidence review

1.a Emergency department management of first seizure in adults

Seizures and seizure like events may be induced by a myriad of conditions. The role of the Emergency

Department assessment of patients presenting with a seizure is to confirm that the patient is in no

immediate danger, establish a probable cause for the seizure, and to refer the patient to appropriate follow-

up services.

Table 1. Recommendations: Emergency Department management of first seizure Evidencegrade

Perform physical and neurologic examination, and take medical history that includes:1 3 14-19

- Provoking factors (sleep deprivation, medication, alcohol or drugs)- Type of seizure- Details of previous seizures

IV

Brain CT scan with contrast. This will help determine if there is an underlying cause for the

seizure and assist makinga differential diagnosis20-2223-33.

III-2

Perform EEG within 48 hours of seizure if possible. If not, as soon as available20-22 34-39

III-2

MRI brain scan will be ordered through First Seizure clinic, if indicated IV

Consider differential diagnosis. Common conditions that should be considered are1 14 16 18

1. Syncope 2. Migraine3. TIA 4. Psychogenic seizures

5. Metabolic disturbances (eg. Na, Mg)

IV

An attempt to determine the seizure type, as per the International Classification of Seizures

(See appendix 1), should be made1 14 18 40

IV

Discuss with Neurology registrar, including need for Anti-epileptic drug (AED) treatment if:

- Multiple seizures- History of recent previous seizures- CT brain scan reveals an epileptogenic lesion

See table 4 choice of AED drug

IV

The decision to admit or discharge the patient should be made on the following grounds14

Discharge if Admit if

-patient fully recovered - Prolonged postictal state

- brain CT satisfactory and - Multiple seizures or status epilepticus

- laboratory tests satisfactory - Focal signs on examination

- Investigations reveal underlying

condition that requires treatment

IV

If a patient is deemed appropriate for discharge, and an epileptic seizure is suspected, the

following actions should be taken:14

1. Make appointment for First Seizure Clinic, and an outpatient EEG, or organise

follow up as a private patient

2. Give advice that due to the risk of further seizures, patients should

a. Not drive any form of motor vehicle (see appendix 2 for guidelines)b. Not swim alonec. Have a shower instead of a bath. Turn on the cold tap first. Lower the

temperature on the hot water service.

d. Avoid heightse. Avoid dangerous machinery

3. Give patient a copy of the First Seizure Discharge Pack (see appendix 3 & 4). Fill

in details of the patients follow up appointments

IV

If the patient has an established diagnosis of epilepsy, give them the Established EpilepsyDischarge Pack (see appendix 5 & 6). Refer the patient to their GP, or to their specialist or

the Epilepsy Clinic at the Royal Melbourne Hospital.

IV
http://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdf


8/25

8

1.b Decision to start an Antiepileptic Drug

There are a number of antiepileptic medications available. The possibility of commencing medication

should be raised with the patient following a seizure. It is ultimately the patients decision as to whether or

not to start this medication. The following information should be discussed with patients prior to deciding

to take AED medication.

Table 2: Information to discuss with patient prior to commencing AED Evidence

grade

The overall risk of a second seizure over a 3-year period is 40 - 50%20-22 34-39 41-53

III-2

The risk of further seizures is highest in the first months following a seizure, and drops

quickly following this period20-22 34-39 41-53

III-2

An epileptic discharge on an EEG test increases the risk of recurrence, to approximately

80%20 21 34-39

III-2

An epileptogenic lesion on CT scan increases the risk of recurrence to approximately 80%20-

22

III-2

AED medication lowers risk of a further seizure to 20 - 25%

39 51-53

IIAll AED medication can cause adverse reactions (such as somnolence and rash). If these do

occur, most effects are reversible simply by discontinuing the medication54-69

I

Very rarely, a patient may have severe or even fatal adverse reaction to AED. This will

normally occur in the first 6 months of treatment70

III-3

AEDs can cause reproductive difficulties and possibly have some teratogenic effects in some

women, and reduce the effectiveness of oral contraception6 11 72-74

III-3

Staff should consider discussing the risk of Sudden Unexplained Death in Epilepsy (SUDEP)

with the patient. SUDEP is a rare event (0.5 to 2 per 1,000 patient years) where a patient

with epilepsy dies for no known reason. The causes of SUDEP are uncertain75-78

IV

Patients should consider the benefit of this reduced risk of seizures, but also the lifestyle and

safety issues of taking AED67

IV

Table 3. Recommendations. Decision to start AED following first seizure Evidence

grade

Use of an AED following a single seizure is generally not recommended, if tests are normal1

67

IV

If epileptic discharge is detected on EEG, or neuroimaging reveals an epileptogenic lesion,

or the patient has had one or more seizures in the recent past, then commencing an AED is

recommended1 67

IV

If the patient elects to begin AED therapy, they should be warned that the AED may haveadverse effects, and to seek medical attention for symptoms including rash, bruising or

somnolence with vomiting especially if they occur in the first weeks of treatment. If a rash

develops the drug should be ceased1 67

IV


9/25

9

Table 4. Choice of antiepileptic drug for seizure type

Recommendations made by Therapeutic Guidelines2

Seizure Type Anti-epileptic drug

Partial Seizures (simple or complex) Carbamazepine

Tonic-clonic seizures

- generalised

- secondarily generalised- undetermined if generalised or partial

Sodium valproate

CarbamazepineCarbamazepine, Sodium valproate

Absence seizures Ethosuximide (absence only)

Sodium valproate (absence and tonic-clonic)

Myoclonic seizures Sodium valproate

For additional information on the use of AEDs, please refer to the Clinicians Health Channel and

(http://www.clinicians.vic.gov.au/eleclib.htm) and click on the Neurology section of the Therapeutic

Guidelines.

2. ESTABLISHED EPILEPSY

2.a Ongoing management of patients with Epilepsy

Epilepsy is a chronic condition, with potentially complex management issues. Communication between

hospital staff and the patients General Practitioner (GP) is essential to maintain a continuum of care for the

patient. Unfortunately, patients with epilepsy often report feeling that care for their condition is not being

shared properly between hospital staff and their GP.

Table 5: Recommendations: Ongoing management of patients with epilepsy Evidence

grade

Staff from the First Seizure Clinic and Epilepsy Clinic should correspond with the patientsGP concerning the diagnosis and management of the patients epilepsy IV

Patients with epilepsy should be encouraged to visit their GP every 3 months, to review their

conditionIV

GPs should be encouraged to refer patients with refractory epilepsy, or who require

medication regime alterations, to the Epilepsy ClinicIV

Staff should encourage patients to gain a greater understanding of their epilepsy. Patient

information on various topics concerning epilepsy has been produced by the Epilepsy

Foundation of Victoria, which can be contacted with the following details:

Epilepsy Foundation of Victorias: http://www.epinet.org.au/, or by calling 1300 852 853

IV

2.b Therapeutic dose & haematological monitor ing for adverse effects - click forevidence review

All AEDs may cause adverse effects, with the majority being dose related. The effectiveness of AED

medication is determined by the free plasma concentration of the active anti-epileptic drug. Routine

plasma AED concentration measures total not free drug. This needs to be taken into consideration when

interpreting levels. Each AED has a recommended dosage regime, and plasma concentration of the active

drug (see http://www.amh.hcn.net.au/).

There is no evidence that routine AED level monitoring increases seizure control, when compared to

clinical management of dosage level based on seizure frequency and signs of toxicity. However, there areinstances where AED level monitoring is appropriate (see table 6).
http://www.clinicians.vic.gov.au/eleclib.htmhttp://www.clinicians.vic.gov.au/eleclib.htmhttp://www.epinet.org.au/http://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.amh.hcn.net.au/http://www.amh.hcn.net.au/http://www.amh.hcn.net.au/http://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.epinet.org.au/http://etg.hcn.net.au/http://www.clinicians.vic.gov.au/eleclib.htm


10/25

10

Due to the potential for serious adverse effects, haematological monitoring for liver function and blood cell

count has been proposed. There is however, no evidence that such monitoring reduces the risk of such

events, due to the enormous sample sizes required to form a definitive answer to this question.

Table 6: Recommendations: Therapeutic dose & haematological monitoring for

adverse effects

Evidence

grade

Routine AED plasma level monitoring should not be undertaken79-87

III-2

Measurement of plasma AED levels should be taken only for one of the following purposes

84

88 89

1. Establishing compliance2. Establishing baseline effective concentrations3. Evaluating potential cause for lack of efficacy4. Evaluation potential cause for toxicity5. Evaluating potential cause for loss of efficacy6. Judging room to move or when to change AEDs7. Patients who are pregnant

IV

There is no conclusive evidence to support or refute the use of haematological monitoring

for serious adverse effects90 91

III-2

Many however, recommend FBE, U&E and LFT be performed on initiation of AED therapy

and every 6 months thereafter92-95

IV

2.c Treatment of refractory epilepsy

In approximately 30% of patients, the initial AED will not prevent all seizures. The patient has a number

of options in this situation.

Table 7: Recommendations: Treatment of refractory epilepsy Evidence

grade

Patients with refractory epilepsy should be referred to the epilepsy clinic IVIf seizures continue following initiation of AED medication at an appropriate dose, the

patient should be presented with the following options

1. If reasonable response to initial AED, add another AED54 56-59 64 96

2. If limited response to initial AED, replace with another AED2 97

I

IV


11/25

11

3. STATUS EPILEPTICUS - click for evidence review

Status epilepticus is defined as epileptic activity lasting longer than 30 minutes. Generalised convulsive

status epilepticus is a medical emergency, and is associated with high levels of morbidity and mortality.

Frequent recurrence seizures should also be treated in this manner.

Table 8: Recommendations: Management of Convulsive Status Epilepticus Evidence

grade

Immediate measures: Secure airway; commence oxygen; assessment of cardiac and

respiratory function; IV access; draw blood for FBC, U&E, LFTs, Ca, Glucose, clotting,

AED levels and storage for later analysis1 15 98

IV

IV Diazepam (0.15mg/kg at 5mg/min). Repeat if status epilepticus/seizures continue99 100

II

Establish aetiology. Give 50ml 50% glucose IV if any suggestion of hypoglycaemia; IV

thiamine 250mg if any suggestion of alcohol abuse or impaired nutritional status15 98

IV

Followed by: IV Phenytoin (18mg/kg at 50mg/min).100

II

When the patient is able, long term oral AED medication should be initiated as indicated byseizure type

2

IV

If status continues or seizures recur: Transfer the patient to ICU101

III - 3

The Neurology registrar should be informed of all cases of status epilepticus IV
http://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdf


12/25

12

4. VIDEO EEG MONITORING - click for evidence review

Video EEG monitoring involves the simultaneous recording of a patients EEG pattern and a video

recording of the patients behaviour. Epileptic seizures are defined by abnormal electrical patterns in the

brain. An interictal EEG is conducted between seizures, and aims to detect epileptiform activity not

associated with a seizure. However, not all patients with epilepsy will have epileptiform EEG activity

between seizures. The aim of video-EEG is to record a patients EEG activity whilst having a seizure, and

correlate this with their behaviour. To do this, patients are recorded for extended periods of time. Due to

the time and the intensive nature of Video EEG, indications for its use are limited.

Table 9: Recommendation: Indications for Video EEG monitoring Evidence

grade

Indications for Video-EEG monitoring4 7 102-106

1. Diagnosis of non-epileptic attacks

2. Classification of seizure types (eg complex partial and atypical absence seizure),

particularly where seizures are refractory to AED therapy

3. Localisation of epileptogenic region in preparation for epilepsy surgery

IV

5. SURGERY-click for evidence review

Surgery can be performed in some patients to remove the region of the brain responsible for the epileptic

activity. However, only a small group of patients are suitable for this form of therapy. Patients with

Temporal Lobe Epilepsy caused by hippocampal sclerosis are the most common surgical candidates. Such

patients normally undergo a temporal lobectomy. Surgery for epilepsy is invasive, and is associated withsome risk of adverse effects.

Table 10: Recommendations: Surgery for epilepsy Evidence

grade

Patients who have intractable epilepsy, despite appropriate use of AEDs, should be referred

for surgical evaluation1 4

IV

Approximately 63% of patients with temporal lobe epilepsy who undergo surgery will be

seizure free at twelve months following the operation, compared to only 8% of patients

treated medically107

II

70-80% of patients with well lateralised temporal lobe seizure focus due to hippocampalsclerosis, have an excellent outcome. AED medication should be continued following

surgery108

III - 1

Approximately 5% of patients will have a major complication associated with surgery for

epilepsy (such as infarct, infection, and decline in memory), while approximately 10% will

have minor and resolvable complications108

III - 2
http://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdf


13/25

13

6. WOMEN WITH EPILEPSY- click for evidence review

Women with epilepsy face a number of potential problems, particularly concerning child-bearing. These

problems include decreased effectiveness of oral contraception whilst taking AED medications, increased

risk of adverse outcomes associated with pregnancy and other health related issues.

Table 11: Recommendations. Management of women with epilepsy Evidence

grade

Contraception. Due to their liver enzyme inducing properties, the following AEDs are

associated with decreased effectiveness of oral contraception: carbamazepine, phenytoin,

phenobarbitone, primidone, and possibly topiramate. A high dose contraceptive

formulations may provide some protection, but women should be warned that there is still an

increased risk of conception whilst taking these AEDs109-120

IV

Referral for women considering pregnancy. Any woman with epilepsy who is

considering a pregnancy should be referred to a Neurologist/Epileptologist or a physician

with particular knowledge of this topic

IV

Pre-pregnancy. To reduce risk of neural tube defects in the foetus, all women of child-

bearing age on an AED should take a folate supplement (5mg/day).121-124However, women should also be warned that folate supplementation may be associated with

an increased incidence of multiple births125 126

IV

Risk of seizures during pregnancy. Women should be warned that there maybe an

increased risk of seizures during pregnancy, although the majority of patients remain

stable127-138

III-2

AED treatment practice during pregnancy. Women with epilepsy should be treated with

the lowest effective dose of AED. Where possible, monotherapy should be used. The need

for AED medication should be re-evaluated prior to a woman becoming pregnant, to ensure

the medication is truly needed73 139

IV

AED serum monitoring during pregnancy. The pharmacokinetics of AEDs change duringpregnancy, resulting in reduced serum levels. Serum AED levels may need to be monitored

more closely during pregnancy and post partum. Ideally, the free level of the AED should be

measured, due to decreased protein binding during pregnancy10 72 73 139 140

IV

Risk of foetal malformation. Women on AEDs should be warned that the risk of major

malformations in their foetus is twice to three times that of the general population, and is

probably between 4-9%. This risk increases with the number of AEDs used, and higher

doses of AEDs during the pregnancy11 72 73 139 140

III-2

At birth.Vitamin K supplement should be administered, to reduce the risks of cerebral

haemorrhage in the neonate, due to the inhibitory actions of AEDs on vitamin K

production.141-145

III-2

Following birth. Close attention should be paid to the mother following delivery. AED

levels can rise rapidly, as the pharmacokinetics of the AEDs return to normal state10 72 73 139

140

IV

Breast-feeding. All AEDs are excreted in breast milk. The rates of transfer vary between

AEDs. If it is decided to breast feed, attention should be paid to ensure that the infant is not

sedated by the AEDs. Breast-feeding is contraindicated if the patient is taking

benzodiazepines or barbiturates146 147

IV

Other health issues. AEDs may be associated with dyslipidemia and accelerated

osteoporosis11

III-3
http://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdfhttp://www.mh.org.au/clinicalepidemiology/epreview.pdf


14/25

14

7. DRIVING GUIDELINES

The effect of having an epileptic seizure whilst driving a car, or other vehicle, can be devastating for both

the patient and the public. To balance the needs of the individual and the public, and maintain fairness and

a uniform approach, guidelines have been produced by Austroads and National Road Transport

Commission (NRTC). These should be used to assess a patients fitness to drive. The Medical Advisory

Board of VicRoads may be contacted to clarify recommendations for specific patients.

Table 12. Recommendations: Driving guidelines Evidence

grade

What to tell the patient: Advice must be given to patients concerning their fitness to drive

following a seizure. The guidelines formulated by Austroads (non-commercial licences)12

&

NRTC (commercial licences)13

should be utilised (see appendix 2)

IV

Where to go if the guidelines are unclear: If the Austroads or NRTC guidelines are

unclear on their recommendations for a particular patients circumstances, or there is some

dispute over the recommended seizure free time, the Medical Advisory Board from

VicRoads should be contacted (Medical Review, VicRoads Registration and Licensing, PO

Box 2504, Kew 3101)

IV


15/25

15

Appendix 1: International Classificat ion of Epileptic Seizures (abbreviated)

I Partial (arising from a focal or local cortical lesion, most commonlythe temporal lobe)

ASimple partial

(no loss of consciousness)

BComplex partial(loss of consciousness; may start with loss of awareness or may follow a simple partial seizure; may be with or

without automatisms, e.g. lipsmacking, rubbing hands, walking, running with no recollection)

CPartial evolving to secondarily generalised seizure with tonic, tonic-clonic or clonic features

II Generalised (with bilateral discharges involving subcortical structures -convulsive or non-

convulsive; EEG shows bilateral discharges; consciousness is lost at the onset except in myoclonus;

motor features bilateral)

AAbsence(previously called petit mal; last seconds; +/- minor automatisms)

BMyoclonic(may be simple or multiple jerks, often upper limbs)

C, D, ETonic, Tonic-clonic or Clonic(previously called grand mal)

FAtonic(a form of drop attack; sudden loss of posture of head, limbs or body)

III Unclassified(usually used when an adequate description is not available, e.g. often in seizuresfrom sleep)

Adapted from Commission of Classification and Terminology of the International League against Epilepsy.

Epilepsia 1981; 22:489-501.148

Graphic


16/25

16

Appendix 2: Guidelines for fi tness to drive following an epileptic seizure

For non-commercial drivers

Excerpt from Austroads (2001). Assessing fitness to drive: Guidelines and standards for health

professionals in Australia. Austroads: Sydney. pp 27-2912

. Also located at

http://www.austroads.com.au/austroads/Others/ftd2001(sec).pdf. Please see this document for a discussionof the principles behind these recommendations. The Medical Advisory Board of VicRoads may be

contacted to clarify recommendations for specific patients.

MEDICALSTANDARDSEPILEPSY(recommended seizure-free periods)

Condition Drivers of cars and light trucks, motorcycle riders

Chronic Epilepsy

(history of previously uncontrolled

seizures)

Generally 2 years. A shorter period only on

recommendation of an experienced consultant where

there is clear evidence of seizure control (eg. following

adjustment and stabilisation of anti-epileptic drug

treatment)

Isolated Seizure 3-6 months. Consultant opinion recommendedRecently Diagnosed Epilepsy 3-6 months. Consultant opinion recommended

Recurrent Seizure in a Person Previously

Seizure Free due to Identifiable

Provocation

3 months from last seizure, if fulfilling all other

criteria as set out in these guidelines. Provocation may

include illness, drug interaction, sleep deprivation

Recurrent Seizure on Withdrawal of

Medication on Medical Advice

1 month after resuming previously effective

medication or 2 years if refusing to resume medication

Seizure Causing Accident Minimum of 1 year. Consultant opinion essential

Seizures only in Sleep 12 months from the last seizure whilst awake

Surgery for Epilepsy 12 months

Withdrawal of Anti-Epileptic DrugTherapy where there is significant risk of

recurrent seizure

The full period of withdrawal and at least 3 monthsthereafter. Consultant opinion is recommended to

determine if there is a significant level of risk or

otherwise.

For Commercial licences

Excerpt from National Road Transport Commission (1994). Medical Guidelines for Commercial Vehicle

Drivers13

. NRTC. Located at http://www.nrtc.gov.au/publications/med-e.asp?lo=public. Please see this

document for a discussion of the principles behind these recommendations.

CriteriaThe criteria are NOT met:

!if epilepsy is confirmed.

A conditional licence may be considered:

!if the person has - a past history of febrile convulsions; or

- a past history of epilepsy with seizure free period of 5 years whilst not on any

anticonvulsant medication; or

- had a past single seizure, or cluster of seizures, due to exceptional and non-

repeatable circumstances; or

!if the person has epilepsy which is so well controlled as to reduce the risk of a convulsion to that of

any member of the general population, noting the inherent features of the individuals job.
http://www.austroads.com.au/austroads/Others/ftd2001(sec).pdfhttp://www.austroads.com.au/austroads/Others/ftd2001(sec).pdfhttp://www.nrtc.gov.au/publications/med-e.asp?lo=publichttp://www.nrtc.gov.au/publications/med-e.asp?lo=publichttp://www.nrtc.gov.au/publications/med-e.asp?lo=publichttp://www.austroads.com.au/austroads/Others/ftd2001(sec).pdf


17/25

17

Appendix 3: Emergency Department Discharge Pack -First Seizure

AppointmentsYou have experienced what is suspected to be a seizure. To investigate the cause of this seizure the

following appointments have been made for you.

First Seizure Clinic appointment:Date: ____________________

Location: Royal Melbourne Hospital,

1stFloor Main Block, Ambulatory Care Centre

Contact Number: 9342 7393

EEG appointment

Date: ____________________

Location: Royal Melbourne Hospital,

4thFloor, Ward 4 North, Main Block.

Contact Number: 9342 7583

Safety informationAs you have had one seizure, there is a risk you may have another, particularly in the next few months. To

avoid injuring yourself, and others, please observe these safety precautions.

Do not drive a motor vehicle or operate dangerous machinery until advised otherwise by a doctor.

Have a shower instead of a bath. Run the cold water first, then the hot. Lower the temperature settingon your hot water service.

Do not go swimming alone.

Avoid heights (eg. walking on roofs).

Please consider and avoid any other activities that could cause serious harm to yourself or others in theevent of another seizure. Discuss with your doctor if you are uncertain.

Avoid consuming excess alcohol, sleep deprivation and flashing lights. These may trigger seizures insome people.

In the event of another seizure, an observer should

Clear the area around the person so that they do not injure themselves.

Do notplace anything in the persons mouth, or try to restrain them.

If possible, place a pillow or soft item under their head.

When the seizure finishes, place the person into the recovery position, lying them on their side.

Arrange for the patient to return to hospital as soon as possible. If needed call an ambulance on 000,and say epileptic seizure

If you need further in formation about seizures or epilepsyIf you wish to talk to a doctor at the Royal Melbourne Hospital, please ring the

Royal Melbourne Hospital Switch: 9342-7000 or

Neurology Department: 9342 7722 and ask to speak to the Neurology orEpilepsy registrar

Alternatively, you can contact your local General Practitioner (GP).

Also, if you would like to talk to someone about your experience, you can contact the Epilepsy Foundation

of Victoria. The contact details for the Epilepsy Foundation of Victorias are as follows:

http://www.epinet.org.au/,or by calling 1300 852 853
http://www.epinet.org.au/http://www.epinet.org.au/http://www.epinet.org.au/


18/25

18

Appendix 4: Letter to General Pract it ioner following a presumed seizure First Seizure

Dear Dr _____________________________

Your patient, __________________________(patient name),attended the emergency department at the

Royal Melbourne Hospital following a presumed first seizure. Whilst in the emergency department they

received a CT brain scan. This scan revealed Insert Details

An outpatient EEG appointment has been made for __________________(insert date), and an appointment

has been made for the First Seizure Clinic for __________________(insert date). The doctor at the First

Seizure Clinic will write to you to inform you of the results of these further investigations.

Your patient has been discharged, but due to the risk of further seizures, I have warned him/her of a

number of safety issues. Specifically, the patient should not drive or operate heavy machinery, should

avoid heights, have a shower instead of a bath, and avoid any other situations where a seizure may cause

themselves or others harm.

I have prescribed the following medication

Medication Indication Dose Plan

Royal Melbourne Hospital contact detailsIf you wish to talk to a doctor at the Royal Melbourne Hospital with regards to this patient, please ring the



(Insert any other comments)

Yours sincerely,

Insert ED doctors name.


19/25

19

Appendix 5: Emergency Department Discharge Pack Established Epilepsy

Safety informationYou have experienced what is suspected to be another epileptic seizure. As you will be aware, you have

previously been diagnosed with epilepsy. To avoid injuring yourself, and others, please observe thesesafety precautions.

Do not drive a motor vehicle or operate dangerous machinery until advised otherwise by a doctor.

Have a shower instead of a bath. Run the cold water first, then the hot. Lower the temperature settingon your hot water service.

Do not go swimming alone.

Avoid heights (eg. walking on roofs).

Please consider and avoid any other activities that could cause serious harm to yourself or others in theevent of another seizure. Discuss with your doctor if you are uncertain.

Avoid consuming excess alcohol, sleep deprivation and flashing lights. These may trigger seizures in

some people.

In the event of another seizure, an observer should

Clear the area around the person so that they do not injure themselves.

Do notplace anything in the persons mouth, or try to restrain them.

If possible, place a pillow or soft item under their head.

When the seizure finishes, place the person into the recovery position, lying them on their side.

If needed, take the patient to hospital, or call an ambulance on 000, and say epileptic seizure.

If you need fur ther information about seizures or epilepsyIf you wish to talk to a doctor at the Royal Melbourne Hospital, please ring the



Alternatively, you can contact your local General Practitioner (GP).

Also, if you would like to talk to someone about your experience, you can contact the Epilepsy Foundation

of Victoria. The contact details for the Epilepsy Foundation of Victorias are as follows:

http://www.epinet.org.au/, or by calling 1300 852 853
http://www.epinet.org.au/http://www.epinet.org.au/


20/25

20

Appendix 6: Letter to General Practit ioner following a presumed seizure Establ ished Epi lepsy

Dear Dr _____________________________

Your patient, __________________________(patient name),attended the emergency department at theRoyal Melbourne Hospital following a presumed seizure. As you will be aware, this patient has been

diagnosed with epilepsy.

Your patient has been discharged, but due to the risk of further seizures, I have warned him/her of a

number of safety issues. Specifically, the patient should not drive or operate heavy machinery, should

avoid heights, have a shower instead of a bath, and avoid any other situations where a seizure may cause

themselves or others harm.

This patient is on the following medications.

Medication Indication Dose Plan

Follow up arrangementsI have made the following follow up arrangements for this patient.

Referred to General Practitioner or current specialist.

Referred to Royal Melbourne Hospital Epilepsy Clinic.

Royal Melbourne Hospital contact detailsIf you wish to talk to a doctor at the Royal Melbourne Hospital with regards to this patient, please ring the



Pathology Results: 9342 8000

(Insert any other comments)

Yours sincerely,

Insert ED doctors name.


21/25

21

References

1. SIGN. Diagnosis and management of epilepsy in adults: A national clinical guideline. Edinburgh: Scottish Intercollegiate

Guideline Network, 1997.

2. Anonymous. Epilepsy. Therapeutic Guidelines: Neurology. 2 ed. Melbourne: Therapeutic Guidelines Limited, 2002: .

3. AHRQ. Management of newly diagnosed patients with epilepsy: a systematic review of the literature: AHRQ, 2001.

4. anonymous. Surgery for Epilepsy. NIH Consensus Statement: NIH, 1990.

5. anonymous. Guidelines for therapeutic monitoring on antiepileptic drugs. Commission on Antiepileptic Drugs,

International League Against Epilepsy. Epilepsia 1993; 34(4): 585-7.

6. anonymous. Guidelines for the care of women of childbearing age with epilepsy. Commission on Genetics, Pregnancy,

and the Child, International League Against Epilepsy. Epilepsia 1993; 34(4): 588-9.

7. anonymous. Guideline twelve: guidelines for long-term monitoring for epilepsy. American Electroencephalographic

Society. Journal of Clinical Neurophysiology 1994; 11(1): 88-110.

8. International-League-Against-Epilepsy. Recommendations for neuroimaging of patients with epilepsy. Commission on

Neuroimaging of the International League Against Epilepsy. Epilepsia 1997; 38(11): 1255-6.

9. anonymous. Guidelines for neuroimaging evaluation of patients with uncontrolled epilepsy considered for surgery.

Commission on Neuroimaging of the International League Against Epilepsy. Epilepsia 1998; 39(12): 1375-6.

10. anonymous. Consensus statements: medical management of epilepsy. Neurology 1998; 51(5 Suppl 4): S39-43.

11. Morrell MJ. Guidelines for the care of women with epilepsy. Neurology 1998; 51(5 Suppl 4): S21-7.

12. Austroads. Assessing fitness to drive: Guidelines and standards for health professionals in Australia. Sydney: Austroads,

2001: 27-29.

13. NRTC. Epilepsy.Medical Guidelines for Commercial Vehicle Drivers. Melbourne: NRTC, 2001: .

14. Pellegrino TR. An emergency department approach to first-time seizures. Emergency Medicine Clinics of North America

1994; 12(4): 925-39.

15. Willmore LJ. Epilepsy emergencies: the first seizure and status epilepticus. Neurology 1998; 51(5 Suppl 4): S34-8.16. anonymous. Clinical policy for the initial approach to patients presenting with a chief complaint of seizure who are not in

status epilepticus. American College of Emergency Physicians. Annals of Emergency Medicine 1997; 29(5): 706-24.

17. Bradford JC, Kyriakedes CG. Evaluation of the patient with seizures: an evidence based approach. Emergency Medicine

Clinics of North America 1999; 17(1): 203-20.

18. Holmes GL. How to evaluate the patient after a first seizure. Postgraduate Medicine 1988; 83(2): 199-209.

19. McLachlan RS. Managing the first seizure. Canadian Family Physician 1993; 39: 885-8.20. Hopkins A, Garman A, Clarke C. The first seizure in adult life. Value of clinical features, electroencephalography, and

computerised tomographic scanning in prediction of seizure recurrence. Lancet 1988; 1(8588): 721-6.

21. Annegers JF, Shirts SB, Hauser WA, Kurland LT. Risk of recurrence after an initial unprovoked seizure. Epilepsia 1986;27(1): 43-50.

22. Hui AC, Tang A, Wong KS, Mok V, Kay R. Recurrence after a first untreated seizure in the Hong Kong Chinese

population. Epilepsia 2001; 42(1): 94-7.23. Schoenenberger RA, Heim SM. Indication for computed tomography of the brain in patients with first uncomplicated

generalised seizure. BMJ 1994; 309(6960): 986-9.

24. Reinus WR, Wippold FJ, 2nd, Erickson KK. Seizure patient selection for emergency computed tomography. Annals of

Emergency Medicine 1993; 22(8): 1298-303.

25. Forsgren L, Fagerlund M, Zetterlund B. Electroencephalographic and neuroradiological findings in adults with newlydiagnosed unprovoked seizures. European Neurology 1991; 31(2): 61-7.

26. Eisner RF, Turnbull TL, Howes DS, Gold IW. Efficacy of a "standard" seizure workup in the emergency department.

Annals of Emergency Medicine 1986; 15(1): 33-9.

27. Henneman PL, DeRoos F, Lewis RJ. Determining the need for admission in patients with new-onset seizures. Annals of

Emergency Medicine 1994; 24(6): 1108-14.28. Sempere AP, Villaverde FJ, Martinez-Menendez B, Cabeza C, Pena P, Tejerina JA. First seizure in adults: a prospectivestudy from the emergency department. Acta Neurologica Scandinavica 1992; 86(2): 134-8.

29. Russo LS, Goldstein KH. The diagnostic assessment of single seizures. Is cranial computed tomography necessary?

Archives of Neurology 1983; 40(12): 744-6.

30. Ramirez-Lassepas M, Cipolle RJ, Morillo LR, Gumnit RJ. Value of computed tomographic scan in the evaluation of

adult patients after their first seizure. Annals of Neurology 1984; 15(6): 536-43.

31. Scollo-Lavizzari G, Eichhorn K, Wuthrich R. Computerized transverse axial tomography (CTAT) in the diagnosis ofepilepsy. European Neurology 1977; 15(1): 5-8.

32. McGahan JP, Dublin AB, Hill RP. The evaluation of seizure disorders by computerized tomography. Journal of

Neurosurgery 1979; 50(3): 328-32.

33. Young AC, Costanzi JB, Mohr PD, Forbes WS. Is routine computerised axial tomography in epilepsy worth while?

Lancet 1982; 2(8313): 1446-7.

34. Hauser WA, Rich SS, Annegers JF, Anderson VE. Seizure recurrence after a 1st unprovoked seizure: an extended follow-up. Neurology 1990; 40(8): 1163-70.

35. Lindsten H, Stenlund H, Forsgren L. Seizure recurrence in adults after a newly diagnosed unprovoked epileptic seizure.

Acta Neurologica Scandinavica 2001; 104(4): 202-7.


22/25

22

36. Cleland PG, Mosquera I, Steward WP, Foster JB. Prognosis of isolated seizures in adult life. British Medical Journal

Clinical Research Ed. 1981; 283(6303): 1364.

37. Thomas M. The single seizure - its study and management. JAMA 1959; 169: 457-733.

38. van Donselaar CA, Geerts AT, Schimsheimer RJ. Idiopathic first seizure in adult life: who should be treated? BMJ 1991;

302(6777): 620-3.39. Das CP, Sawhney IM, Lal V, Prabhakar S. Risk of recurrence of seizures following single unprovoked idiopathic seizure.

Neurology India 2000; 48(4): 357-60.

40. anonymous. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. From the

Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1981; 22(4):

489-501.41. Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review.Neurology 1991; 41(7): 965-72.

42. Elwes RD, Chesterman P, Reynolds EH. Prognosis after a first untreated tonic-clonic seizure. Lancet 1985; 2(8458): 752-

3.

43. Hyllested K. Prognosis in epilepsy of late onset. Neurology 1963; 13: 641-644.

44. Saunders M, Marshall C. Isolated seizures: an EEG and clinical assessment. Epilepsia 1975; 16(5): 731-3.

45. Johnson LC, DeBolt WL, Long MT, Ross JJ, Sassin JF, Arthur RJ, et al. Diagnostic factors in adult males followinginitial seizures. A three-year follow-up. Archives of Neurology 1972; 27(3): 193-7.

46. Luhdorf K, Jensen LK, Plesner AM. Epilepsy in the elderly: prognosis. Acta Neurologica Scandinavica 1986; 74(5): 409-

15.

47. Hart YM, Sander JW, Johnson AL, Shorvon SD. National General Practice Study of Epilepsy: recurrence after a first

seizure. Lancet 1990; 336(8726): 1271-4.

48. Gupta SK, Satishchandra P, Venkatesh A, Subbakrishna DK. Prognosis of single unprovoked seizure. Journal of theAssociation of Physicians of India 1993; 41(11): 709-10.

49. Bora I, Seckin B, Zarifoglu M, Turan F, Sadikoglu S, Ogul E. Risk of recurrence after first unprovoked tonic-clonic

seizure in adults. Journal of Neurology 1995; 242(3): 157-63.

50. Hauser WA, Rich SS, Lee JR, Annegers JF, Anderson VE. Risk of recurrent seizures after two unprovoked seizures. New

England Journal of Medicine 1998; 338(7): 429-34.

51. Musicco M, Beghi E, Solari A, Viani F. Treatment of first tonic-clonic seizure does not improve the prognosis of

epilepsy. First Seizure Trial Group (FIRST Group). Neurology 1997; 49(4): 991-8.

52. Gilad R, Lampl Y, Gabbay U, Eshel Y, Sarova-Pinhas I. Early treatment of a single generalized tonic-clonic seizure to

prevent recurrence. Archives of Neurology 1996; 53(11): 1149-52.

53. Chandra B. First seizure in adults: to treat or not to treat. Clinical Neurology & Neurosurgery 1992; 94 Suppl: S61-3.

54. Chaisewikul R, Privitera MD, Hutton JL, Marson AG. Levetiracetam add-on for drug-resistant localization related

(partial) epilepsy. Cochrane Database Syst Rev 2001; 1: .

55. Chaisewikul R, Baillie N, Marson AG. Calcium antagonists as an add-on therapy for drug-resistant epilepsy (CochraneReview). Cochrane Database Syst Rev 2001; 4: .

56. Chadwick DW, Marson AG. Zonisamide for drug-resistant partial epilepsy. Cochrane Database Syst Rev 2000; 2: .

57. Jette NJ, Marson AG, Kadir ZA, Hutton JL. Topiramate for drug-resistant partial epilepsy. Cochrane Database Syst Rev

2000; 2: .

58. Marson AG, Kadir ZA, Hutton JL, Chadwick DW. Gabapentin add-on for drug-resistant partial epilepsy. Cochrane

Database Syst Rev 2000; 3: .

59. Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant partial epilepsy. Cochrane Database Syst

Rev 2000; 3: .

60. Harden CL. Therapeutic safety monitoring: what to look for and when to look for it. Epilepsia 2000; 41 Suppl 8: S37-44.61. Perucca E, Gram L, Avanzini G, Dulac O. Antiepileptic drugs as a cause of worsening seizures. Epilepsia 1998; 39(1): 5-

17.

62. Greenwood RS. Adverse effects of antiepileptic drugs. Epilepsia 2000; 41 Suppl 2: S42-52.

63. French JA, Gidal BE. Antiepileptic drug interactions. Epilepsia 2000; 41 Suppl 8: S30-6.64. Marson AG, Kadir ZA, Hutton JL, Chadwick DW. The new antiepileptic drugs: a systematic review of their efficacy and

tolerability. Epilepsia 1997; 38(8): 859-80.65. Wong IC, Lhatoo SD. Adverse reactions to new anticonvulsant drugs. Drug Safety 2000; 23(1): 35-56.

66. Vermeulen J, Aldenkamp AP. Cognitive side-effects of chronic antiepileptic drug treatment: a review of 25 years of

research. Epilepsy Research 1995; 22(2): 65-95.

67. Perucca E, Beghi E, Dulac O, Shorvon S, Tomson T. Assessing risk to benefit ratio in antiepileptic drug therapy.

Epilepsy Research 2000; 41(2): 107-39.

68. Schmidt D, Kramer G. The new anticonvulsant drugs. Implications for avoidance of adverse effects. Drug Safety 1994;11(6): 422-31.

69. Wallace SJ. Newer antiepileptic drugs: advantages and disadvantages. Brain & Development 2001; 23(5): 277-83.

70. Arroyo S, de la Morena A. Life-threatening adverse events of antiepileptic drugs. Epilepsy Research 2001; 47(1-2): 155-

74.

71. Schlienger RG, Shear NH. Antiepileptic drug hypersensitivity syndrome. Epilepsia 1998; 39(Suppl 7): S3-7.72. Yerby MS. The use of anticonvulsants during pregnancy. Seminars in Perinatology 2001; 25(3): 153-8.

73. Pschirrer ER, Monga M. Seizure disorders in pregnancy. Obstetrics & Gynecology Clinics of North America 2001;

28(3): 601-11.


23/25

23

74. Delgado-Escueta AV, Janz D. Consensus guidelines: preconception counseling, management, and care of the pregnant

woman with epilepsy. Neurology 1992; 42(4 Suppl 5): 149-60.

75. Walczak TS, Leppik IE, D'Amelio M, Rarick J, So E, Ahman P, et al. Incidence and risk factors in sudden unexpected

death in epilepsy: a prospective cohort study. Neurology 2001; 56(4): 519-25.

76. Nilsson L, Bergman U, Diwan V, Farahmand BY, Persson PG, Tomson T. Antiepileptic drug therapy and itsmanagement in sudden unexpected death in epilepsy: a case-control study. Epilepsia 2001; 42(5): 667-73.

77. Opeskin K, Harvey AS, Cordner SM, Berkovic SF. Sudden unexpected death in epilepsy in Victoria. J Clin Neurosci

2000; 7(1): 34-7.

78. Nilsson L, Farahmand BY, Persson PG, Thiblin I, Tomson T. Risk factors for sudden unexpected death in epilepsy: a

case-control study. Lancet 1999; 353(9156): 888-93.79. Jannuzzi G, Cian P, Fattore C, Gatti G, Bartoli A, Monaco F, et al. A multicenter randomized controlled trial on theclinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study

Group in Epilepsy. [see comments]. Epilepsia 2000; 41(2): 222-30.

80. Woo E, Chan YM, Yu YL, Chan YW, Huang CY. If a well-stabilized epileptic patient has a subtherapeutic antiepileptic

drug level, should the dose be increased? A randomized prospective study. Epilepsia 1988; 29(2): 129-39.

81. Froscher W, Eichelbaum M, Gugler R, Hildenbrand G, Penin H. A prospective randomised trial on the effect of

monitoring plasma anticonvulsant levels in epilepsy. Journal of Neurology 1981; 224(3): 193-201.82. Wing DS, Duff HJ. The impact of a therapeutic drug monitoring program for phenytoin. Therapeutic Drug Monitoring

1989; 11(1): 32-7.

83. Sherwin AL, Robb JP, Lechter M. Improved control of epilepsy by monitoring plasma ethosuximide. Archives of

Neurology 1973; 28(3): 178-81.

84. Eadie MJ. Plasma antiepileptic drug monitoring in a neurological practice: a 25-year experience. Therapeutic Drug

Monitoring 1994; 16(5): 458-68.85. Jackson M, Dawson P, McCrea W. The hazards of prescribing from serum levels. Seizure 1994; 3(3): 225-33.

86. McKee PJ, Percy-Robb I, Brodie MJ. Therapeutic drug monitoring improves seizure control and reduces anticonvulsant

side-effects in patients with refractory epilepsy. Seizure 1992; 1(4): 275-9.

87. Beardsley RS, Freeman JM, Appel FA. Anticonvulsant serum levels are useful only if the physician appropriately uses

them: an assessment of the impact of providing serum level data to physicians. Epilepsia 1983; 24(3): 330-5.

88. Glauser TA, Pippenger CE. Controversies in blood-level monitoring: reexamining its role in the treatment of epilepsy.

Epilepsia 2000; 41 Suppl 8: S6-15.

89. Tomson T, Johannessen SI. Therapeutic monitoring of the new antiepileptic drugs. European Journal of Clinical

Pharmacology 2000; 55(10): 697-705.

90. Mattson r, Cramer j, Collins j, al. e. Connective tissue changes, hypersensitivity rash and blood laboratory test changes

associated with antiepileptic drug therapy (absract). Annals of Neurology 1986; 20: 119-120.

91. Camfield C, Camfield P, Smith E, Tibbles JA. Asymptomatic children with epilepsy: little benefit from screening for

anticonvulsant-induced liver, blood, or renal damage. Neurology 1986; 36(6): 838-41.92. Pellock JM, Willmore LJ. A rational guide to routine blood monitoring in patients receiving antiepileptic drugs.

Neurology 1991; 41(7): 961-4.

93. Camfield P, Camfield C, Dooley J, Farrell K, Humphreys P, Langevin P. Routine screening of blood and urine for severe

reactions to anticonvulsant drugs in asymptomatic patients is of doubtful value. CMAJ 1989; 140(11): 1303-5.

94. Green SH. Sodium valproate and routine liver function tests. Archives of Disease in Childhood 1984; 59(9): 813-4.

95. De Vries S. Haematological aspects during treatment with anticonvulsant drugs. Epilepsia 1965; 6: 1-15.

96. Castillo S, Schmidt DB, White S. Oxcarbazepine add-on for drug-resistant partial epilepsy. Cochrane Database Syst Rev

2000; 3: .

97. Brodie MJ. Management strategies for refractory localization-related seizures. Epilepsia 2001; 42 Suppl 3: 27-30.98. Treatment of convulsive status epilepticus. Recommendations of the Epilepsy Foundation of America's Working Group

on Status Epilepticus. Jama 1993; 270(7): 854-9.

99. Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, et al. A comparison of lorazepam, diazepam, and

placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001; 345(9): 631-7.100. Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al. A comparison of four treatments for

generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med1998; 339(12): 792-8.

101. Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol,

or midazolam: a systematic review. Epilepsia 2002; 43(2): 146-53.

102. Lagerlund TD, Cascino GD, Cicora KM, Sharbrough FW. Long-term electroencephalographic monitoring for diagnosis

and management of seizures. Mayo Clinic Proceedings 1996; 71(10): 1000-6.

103. Thompson JL, Ebersole JS. Long-term inpatient audiovisual scalp EEG monitoring. Journal of ClinicalNeurophysiology 1999; 16(2): 91-9.

104. Erlichman M. Electroencephalographic (EEG) video monitoring. Health Technology Assessment Reports 1990; (4): 1-

14.

105. anonymous. Assessment: intensive EEG/video monitoring for epilepsy. Report of the American Academy of Neurology,

Therapeutics and Technology Assessment Subcommittee. [erratum appears in Neurology 1989 Nov;39(11):1437.].Neurology 1989; 39(8): 1101-2.

106. Quesney LF, Gloor P. Localization of epileptic foci. Electroencephalogr Clin Neurophysiol Suppl 1985; 37: 165-200.

107. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N

Engl J Med 2001; 345(5): 311-8.


24/25

24

108. McIntosh AM, Wilson SJ, Berkovic SF. Seizure outcome after temporal lobectomy: current research practice and

findings. Epilepsia 2001; 42(10): 1288-307.

109. Fattore C, Cipolla G, Gatti G, Limido GL, Sturm Y, Bernasconi C, et al. Induction of ethinylestradiol and levonorgestrel

metabolism by oxcarbazepine in healthy women. Epilepsia 1999; 40(6): 783-7.

110. Eldon MA, Underwood BA, Randinitis EJ, Sedman AJ. Gabapentin does not interact with a contraceptive regimen ofnorethindrone acetate and ethinyl estradiol. Neurology 1998; 50(4): 1146-8.

111. Rosenfeld WE, Doose DR, Walker SA, Nayak RK. Effect of topiramate on the pharmacokinetics of an oral

contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997; 38(3): 317-23.

112. Bartoli A, Nocentini G, Ronchetti S, Moraca R, Riccardi C. A double-blind, placebo-controlled study on the effect of

vigabatrin on in vivo parameters of hepatic microsomal enzyme induction and on the kinetics of steroid oralcontraceptives in healthy female volunteers. Molecular & Cellular Biochemistry 1997; 167(1-2): 135-44.113. Saano V, Glue P, Banfield CR, Reidenberg P, Colucci RD, Meehan JW, et al. Effects of felbamate on the

pharmacokinetics of a low-dose combination oral contraceptive. Clin Pharmacol Ther 1995; 58(5): 523-31.

114. Klosterskov Jensen P, Saano V, Haring P, Svenstrup B, Menge GP. Possible interaction between oxcarbazepine and an

oral contraceptive. Epilepsia 1992; 33 Suppl 1(6): S13-22.

115. Holdich T, Whiteman P, Orme M, Back D, Ward S. Effect of Lamotrigine on the pharmocology of the combined oral

contraceptive pill. Epilepsia 1991; 32(suppl 1): 96.116. Crawford P, Chadwick DJ, Martin C, Tjia J, Back DJ, Orme M. The interaction of phenytoin and carbamazepine with

combined oral contraceptive steroids. British Journal of Clinical Pharmacology 1990; 30(6): 892-6.

117. Haukkamaa M. Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant

treatment. Contraception 1986; 33(6): 559-65.

118. Crawford P, Chadwick D, Cleland P, Tjia J, Cowie A, Back DJ, et al. The lack of effect of sodium valproate on the

pharmacokinetics of oral contraceptive steroids. Contraception 1986; 33(1): 23-9.119. Back DJ, Bates M, Bowden A, Breckenridge AM, Hall MJ, Jones H, et al. The interaction of phenobarbital and other

anticonvulsants with oral contraceptive steroid therapy. Contraception 1980; 22(5): 495-503.

120. Coulam CB, Annegers JF. Do anticonvulsants reduce the efficacy of oral contraceptives? Epilepsia 1979; 20(5): 519-25.

121. Lumley J, Watson L, Watson M, Bower C. Periconceptional supplementation with folate and/or multivitamins for

preventing neural tube defects. Cochrane Database Syst Rev 2002; 2: .

122. Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors associated with adverse pregnancy

outcomes. Part II: Improvement with folic acid. Ann Pharmacother 1998; 32(9): 947-61.

123. Hernandez-Diaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth

defects. N Engl J Med 2000; 343(22): 1608-14.

124. Dansky LV, Andermann E, Rosenblatt D, Sherwin AL, Andermann F. Anticonvulsants, folate levels, and pregnancy

outcome: a prospective study. Annals of Neurology 1987; 21(2): 176-82.

125. Lumley J, Watson L, Watson M, Bower C. Modelling the potential impact of population-wide periconceptional

folate/multivitamin supplementation on multiple births. Bjog 2001; 108(9): 937-42.126. Parazzini F, Chatenoud L, Bettoni G, Tozzi L, Turco S, Surace M, et al. Selected food intake and risk of multiple

pregnancies. Human Reproduction 2001; 16(2): 370-3.

127. Tomson T, Lindbom U, Ekqvist B, Sundqvist A. Epilepsy and pregnancy: a prospective study of seizure control in

relation to free and total plasma concentrations of carbamazepine and phenytoin. Epilepsia 1994; 35(1): 122-30.

128. Tanganelli P, Regesta G. Epilepsy, pregnancy, and major birth anomalies: an Italian prospective, controlled study.

Neurology 1992; 42(4 Suppl 5): 89-93.

129. Lander CM, Eadie MJ. Plasma antiepileptic drug concentrations during pregnancy. Epilepsia 1991; 32(2): 257-66.

130. Wilhelm J, Morris D, Hotham N. Epilepsy and pregnancy--a review of 98 pregnancies. Australian & New Zealand

Journal of Obstetrics & Gynaecology 1990; 30(4): 290-5.131. Bag S, Behari M, Ahuja GK, Karmarkar MG. Pregnancy and epilepsy. Journal of Neurology 1989; 236(5): 311-3.

132. Gjerde IO, Strandjord RE, Ulstein M. The course of epilepsy during pregnancy: a study of 78 cases. Acta Neurologica

Scandinavica 1988; 78(3): 198-205.

133. Schmidt D, Canger R, Avanzini G, Battino D, Cusi C, Beck-Mannagetta G, et al. Change of seizure frequency inpregnant epileptic women. Journal of Neurology, Neurosurgery & Psychiatry 1983; 46(8): 751-5.

134. Canger R, Avanzinin G, Battino D, Bossi L, Franceschetti S, Spina S. Modifications of seizure frequency in pregnantpatients with epilepsy: a prospective study. In: Janz Dea, editor.Epilepsy, pregnancy, and the child. New York: Raven

Press, 1982: 33-38.

135. Schmidt D, Beck-Mannagetta G, Janz D, Koch S. The effect of pregnancy on the course of epilepsy: A prospective

study. In: Janz Dea, editor.Epilepsy, pregnancy, and the child. New York: Raven Press, 1982: 39-49.

136. Bardy AH. Seizure frequency in epileptic women during pregnancy and puerperium: results of the prospective Helsinki

Study. In: Janz Dea, editor.Epilepsy, pregnancy, and the child. New York: Raven Press, 1982: 27-31.137. Remillard G, Dansky L, Andermann E, Andermann F. Seizure frequency during pregnancy and the puerperium. In: Janz

Dea, editor.Epilepsy, pregnancy, and the child. New York: Raven Press, 1982: 15-26.

138. Schmidt D. The effect of pregnancy on the natural history of epilepsy: Review of the literature. In: Janz Dea, editor.

Epilepsy, pregnancy, and the child. New York: Raven Press, 1982: 3-14.

139. O'Brien TJ, Vajda FJ. Contemporary management of epilepsy in pregnancy. Australian & New Zealand Journal ofObstetrics & Gynaecology 2000; 40(4): 413-5.

140. Eller DP, Patterson CA, Webb GW. Maternal and fetal implications of anticonvulsive therapy during pregnancy.

Obstetrics & Gynecology Clinics of North America 1997; 24(3): 523-34.


25/25

141. Hey E. Effect of maternal anticonvulsant treatment on neonatal blood coagulation. Archives of Disease in Childhood:

Fetal & Neonatal Edition 1999; 81(3): F208-10.

142. Cornelissen M, Steegers-Theunissen R, Kollee L, Eskes T, Motohara K, Monnens L. Supplementation of vitamin K in

pregnant women receiving anticonvulsant therapy prevents neonatal vitamin K deficiency. American Journal of

Obstetrics & Gynecology 1993; 168(3 Pt 1): 884-8.143. Cornelissen M, Steegers-Theunissen R, Kollee L, Eskes T, Vogels-Mentink G, Motohara K, et al. Increased incidence

of neonatal vitamin K deficiency resulting from maternal anticonvulsant therapy. American Journal of Obstetrics &

Gynecology 1993; 168(3 Pt 1): 923-8.

144. Deblay MF, Vert P, Andre M, Marchal F. Transplacental vitamin K prevents haemorrhagic disease of infant of epileptic

mother. Lancet 1982; 1247: 1247.145. Mountain KR, Hirsh J, Gallus AS. Neonatal coagulation defect due to anticonvulsant drug treatment in pregnancy.Lancet 1970; 1(7641): 265-8.

146. Chaudron LH, Jefferson JW. Mood stabilizers during breastfeeding: a review. Journal of Clinical Psychiatry 2000;

61(2): 79-90.

147. Hagg S, Spigset O. Anticonvulsant use during lactation. Drug Safety 2000; 22(6): 425-40.

148. Commission of Classification and Terminology of the International League against Epilepsy. Epilepsia 1981; 22: 489-

501.

guideline for epilepsy

Documents