1. health and fitness
2. disease
3. epilepsy

Scottish Intercollegiate Guidelines Network
70
Diagnosis and Management of
Epilepsy in Adults
A national clinical guideline
1
Introduction
1
2
Diagnosis
3
3
Treatment
8
4
Contraception, pregnancy and HRT
21
5
Models of care
28
6
Information for discussion with
patients and carers
31
7
Implementation and audit
34
8
Outcome measures
36
9
Development of the guideline
38
Abbreviations
44
References
45
April 2003
KEY TO EVIDENCE STATEMENTS AND GRADES OF RECOMMENDATIONS
LEVELS OF EVIDENCE
1++
High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs),
or RCTs with a very low risk of bias
1+
Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low
risk of bias
1-
Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2
High quality systematic reviews of case control or cohort studies
High quality case control or cohort studies with a very low risk of confounding or bias
and a high probability that the relationship is causal
++
2+
Well conducted case control or cohort studies with a low risk of confounding or bias
and a moderate probability that the relationship is causal
2-
Case control or cohort studies with a high risk of confounding or bias
and a significant risk that the relationship is not causal
3
Non-analytic studies, e.g. case reports, case series
4
Expert opinion
GRADES OF RECOMMENDATION
Note: The grade of recommendation relates to the strength of the evidence on which the
recommendation is based. It does not reflect the clinical importance of the recommendation.
A
At least one meta-analysis, systematic review of RCTs, or RCT rated as 1++
and directly applicable to the target population; or
A body of evidence consisting principally of studies rated as 1+, directly applicable to
the target population, and demonstrating overall consistency of results
B
A body of evidence including studies rated as 2++, directly applicable to the target
population, and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 1++ or 1+
C
A body of evidence including studies rated as 2+, directly applicable to the target
population and demonstrating overall consistency of results; or
Extrapolated evidence from studies rated as 2++
D
Evidence level 3 or 4; or
Extrapolated evidence from studies rated as 2+
GOOD PRACTICE POINTS
þ
Recommended best practice based on the clinical experience of the guideline
development group
© Scottish Intercollegiate Guidelines Network
ISBN 1 899893 58 X
First published 2003
SIGN consents to the photocopying of this guideline for the
purpose of implementation in NHSScotland
Scottish Intercollegiate Guidelines Network
Royal College of Physicians
9 Queen Street
Edinburgh EH2 1JQ
www.sign.ac.uk
1 INTRODUCTION
1
Introduction
1.1
THE NEED FOR A GUIDELINE
In Scotland there are 20,000 - 40,000 people with active epilepsy and there will be between
2,000 and 3,500 new diagnoses each year.1 As it is a common condition, and the number of
epilepsy specialists is very small, many people with epilepsy have been diagnosed and treated by
non-specialists in both primary and secondary care. There is evidence that management can
sometimes be sub-optimal.2,3 Areas of specific concern include initial diagnosis, drug treatment,
management of pregnant women with epilepsy and the provision of patient information. Up to
a quarter of patients referred for specialist management of apparent drug-resistant epilepsy do not
have epilepsy at all. Antiepileptic drugs (AEDs) are not always chosen and used appropriately by
clinicians. It is likely that the incidence of sudden unexpected death in epilepsy could be reduced
if antiepileptic treatment was always optimised. There is room for improvement in the management
of status epilepticus and in the care and advice provided for women with epilepsy before and
during pregnancy. People with epilepsy often report inadequate provision of information and
advice. There remains considerable scope for the development of better epilepsy services in both
primary and secondary care.
Since publication of the previous SIGN guideline on epilepsy in 1997 there have been significant
developments in the diagnosis and management of the condition. Three new AEDs have been
licensed. The number of epilepsy specialist nurses has greatly increased. This guideline review
will include new sections on the management of status epilepticus, non-pharmacological
treatments and issues relating to contraception and pregnancy.
It is hoped that this guideline will contribute to continued improvement in the diagnosis and
management of epilepsy in Scotland.
1.2
REMIT OF THE GUIDELINE
This guideline provides evidence based recommendations on the diagnosis and treatment of
epilepsy. The section on treatment gives broad recommendations on initial AED treatment,
management of drug-resistant epilepsy, management of status epilepticus, management of provoked
seizures and the management of people with learning disability and epilepsy.
The remaining sections deal with issues relating to contraception, pregnancy and the menopause,
models of care for epilepsy, audit of epilepsy care and provision of information for patients and
carers. It is beyond the remit of the guideline to provide a full detailed discussion of differential
diagnosis.
Epilepsy in the elderly is addressed only indirectly. Other text exists detailing the management of
epilepsy in the elderly and after stroke.4
The guideline will be of interest to all health professionals in primary and secondary care involved
in the management of people with epilepsy, including general practitioners, practice nurses,
epilepsy specialist nurses, general physicians, A&E specialists, neurologists and obstetricians. It
will also be of interest to those commissioning epilepsy services, public health physicians,
pharmacists, social work staff, carers and relatives of people with epilepsy and to people with
epilepsy themselves.
1.3
STATEMENT OF INTENT
This guideline is not intended to be construed or to serve as a standard of medical care. Standards
of care are determined on the basis of all clinical data available for an individual case and are
subject to change as scientific knowledge and technology advance and patterns of care evolve.
These parameters of practice should be considered guidelines only. Adherence to them will not
ensure a successful outcome in every case, nor should they be construed as including all proper
methods of care or excluding other acceptable methods of care aimed at the same results. The
ultimate judgement regarding a particular clinical procedure or treatment plan must be made by
1
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
the doctor, following discussion of the options with the patient, in light of the diagnostic and
treatment choices available. However, it is advised that significant departures from the national
guideline or any local guidelines derived from it should be fully documented in the patient’s
case notes at the time the relevant decision is taken.
1.4
REVIEW AND UPDATING
This guideline was issued in 2003 and will be considered for review as new evidence becomes
available. Any updates to the guideline in the interim period will be noted on the SIGN website:
www.sign.ac.uk
2
2 DIAGNOSIS
2
Diagnosis
2.1
WHO SHOULD MAKE THE DIAGNOSIS OF EPILEPSY?
The diagnosis of epilepsy has important physical, psychosocial and economic implications for
the patient. It is therefore important that the diagnosis is correct. It has been shown that a
significant proportion of epilepsy diagnoses made by non specialists is incorrect. 2,3 Epilepsy may
be difficult to diagnose in the early stages5 especially in the absence of a witnessed account.
Differentiation of epileptic seizures and stereotyped behavioural phenomena can be difficult in
people with a learning disability.
C
The diagnosis of epilepsy should be made by a neurologist or other epilepsy specialist.
þ
The diagnosis of epilepsy is most appropriately delivered in the setting of a dedicated first
seizure clinic. Appropriate patient information should be given (see Section 6).
An epilepsy specialist has been defined as a consultant with expertise in epilepsy as demonstrated
by training and continuing education in epilepsy, peer review of practice and regular audit of
diagnosis. Epilepsy must be a significant part of their clinical workload (equivalent to at least
one session a week).6
2.2
2+
4
CLASSIFICATION
Classification of seizure types and epilepsy syndromes should always be attempted, as both may
have implications for management and prognosis.
2.2.1
CLASSIFICATION OF EPILEPTIC SEIZURES
International classification of epileptic seizures:7
I. Partial seizures
A. simple partial seizures (no loss of consciousness)
B. complex partial seizures
1. with impairment of consciousness at onset
2. simple partial onset followed by impairment of consciousness
C. partial seizures evolving to generalised tonic-clonic (GTC) convulsions.
II. Generalised seizures
(convulsive or nonconvulsive with bilateral discharges involving subcortical structures)
A. absence
B. myoclonic
C. clonic
D. tonic
E. tonic-clonic
F. atonic.
III. Unclassified epileptic seizures
(usually used when an adequate description is not available).
2.2.2
CLASSIFICATION OF EPILEPSY SYNDROMES
It is important to make the distinction between idiopathic generalised epilepsies (IGEs) and focal
(localisation-related) epilepsies, as this affects treatment choices, investigation, prognosis and
counselling. Identifying the aetiology is important in focal epilepsies.
The onset of IGEs is unusual over the age of 25.8 The most common IGEs in adolescence are
juvenile myoclonic epilepsy (generalised tonic-clonic seizures with myoclonic seizures on waking,
sometimes with absence seizures, with photoparoxysmal response in 30% of cases), early morning
tonic-clonic seizures in adolescence, and juvenile-absence epilepsy. These phenotypes may
overlap.9-13
2+
4
3
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
Features suggesting idiopathic generalised epilepsies:
childhood or teenage onset
triggered by sleep deprivation & alcohol
early morning tonic-clonic seizures or myoclonic jerks
short absence seizures
photoparoxysmal response on electroencephalography (EEG)
generalised 3 per second spike and wave or polyspike and wave on EEG.
n
n
n
n
n
n
Features suggesting focal epilepsies:
history of potential cause
aura
focal motor activity during seizure
automatisms.
n
n
n
n
C
The seizure type(s) and epilepsy syndrome should be identified.
C
The distinction should be made between a focal epilepsy and an idiopathic generalised
epilepsy.
Tonic-clonic seizures without any focal features or any positive features of an idiopathic generalised
epilepsy cannot be confidently classified.
2.3
CLINICAL FACTORS AND DIAGNOSIS
Attack disorders such as faint and epilepsy produce their effects because some element of physiology
becomes disordered, temporarily disturbing the function of the brain. For a test to positively
identify the nature of an attack disorder, an attack must be recorded, and the disturbed physiology
detected. As this is usually impractical, the routine diagnosis of attack disorders is largely clinical,
based on history. The history should make clear what occurred before, during and after the
attack, from both patient and eyewitness points of view. A number of clinical features are
common to different types of attack, so diagnosis should be based on the ensemble of the
clinical features, not on single features. A generalised tonic-clonic seizure may be the presenting
symptom in people with previously unrecognised epilepsy and a detailed history should be taken
to uncover previous myoclonic, absence or partial seizures.10,14-25
C
A clear history from the patient and an eyewitness to the attack give the most important
diagnostic information, and should be the mainstay of diagnosis.
Table 1 is a guide to how history may assist in diagnosis. Syncope is the most common attack
disorder presenting to hospital emergency departments.26 Non-epileptic attack disorder may be
defined as attacks which clinically resemble or may be mistaken for epileptic seizures, but which
are not accompanied by any pathological disturbance of brain function, and which have a presumed
or known psychological cause. Other disorders may also have to be considered (see Annex 1).
4
2+
3
4
3
2 DIAGNOSIS
Table 1: Useful clinical features in differential diagnosis of epilepsy
Epileptic seizure
Syncope
Non-epileptic
attack disorder
Cardiac
arrhythmia
Hyperventilation
or panic attacks
Female sex (3:1)
Congenital heart
disease
Anxiety disorders
Stress
Social distress
Exercise
Social situations
Sometimes have a
variable
prodrome
Palpitations
Fear
Feeling of unreality
Breathlessness
Parasthesiae
Pallor
May have few
brief jerks or
stiffening
Agitation
Rapid breathing
Stiffening of hands
(carpopedal
spasm)
The background of the patient
Previous:
Head injury
Alcohol abuse
Drug abuse
Prolonged febrile
convulsion
Meningitis
Encephalitis
Stroke
Family history of epilepsy
Antihypertensive
drugs
Antidepressant
drugs
(especially
tricyclics)
Sexual or physical
abuse
Provoking factors for attacks
Sleep deprivation
Alcohol withdrawal
Flashing lights
Postural change
Medical procedures
Micturition Heat
Prolonged standing
Neck movement
(carotid
baroreceptor
hypersensitivity)
Clinical characteristics of attack - prodrome or aura
Stereotyped, brief
(seconds) in localisation
related epilepsy only
Déjà vu
Taste/smell
Rising abdominal
sensation
Lightheadedness
Visual symptoms
Darkening
Blurring
Buzzing, echoing
Clinical characteristics of attack - features of the attack itself
Movements:
Tonic (stiffening)
followed by
rhythmic jerking
Complex automatic
movements
Cyanosis
Timing:
Relationship to waking
and sleep, clustering
with menses
Pallor
May have few brief
jerks or stiffening
May look similar to
seizure but
thrashing, side to
side head or
alternating limb
movements,
prolonged
motionless
collapse or
pelvic thrusting
suggest
non-epileptic
attack disorder
Residual symptoms after attack
Drowsiness
Bitten tongue
Limb aching
Focal neurological deficit
(Todd’s paresis)
Lassitude
Lassitude
Note: injury, incontinence and pallor can occur in syncope, epilepsy and pseudoseizures and are poor
discriminators for this differential diagnosis.
5
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
2.4
USE OF EEG IN THE DIAGNOSIS AND CLASSIFICATION OF EPILEPSY
2.4.1
ELECTROENCEPHALOGRAPHY
Electroencephalography (EEG) is often helpful in the diagnosis and classification of epilepsy.10,27
However, it is essential to understand the scope and limitations of the technique when requesting
an EEG examination and subsequently evaluating an expert report on the recording.2 Non-specific
EEG abnormalities are relatively common, especially in the elderly, patients with migraine,
psychotic illness and psychotropic medication. Non-specific abnormalities should not be
interpreted as supporting a diagnosis of epilepsy.
A normal EEG does not exclude a diagnosis of epilepsy. A single routine EEG recording will
show definite epileptiform abnormalities in 29-38% of adults who have epilepsy. With repeat
recordings this rises to 69-77%.10,28-31 The sensitivity is improved by performing an EEG soon after
a seizure, and by recordings with sleep or following sleep deprivation.10,32,33
Incidental epileptiform abnormalities are found in 0.5% of healthy young adults, but are more
likely in people with learning disability and psychiatric disorders, patients with previous
neurological insult (e.g. head injury, meningitis, stroke, cerebral palsy) and patients who have
undergone neurosurgery.34-36
2+
In a patient in whom the clinical history suggests an epileptic seizure but is not conclusive, the
prevalence of epilepsy will be high. The finding of epileptiform abnormalities is specific, and
the diagnostic value of the test is good. In a patient in whom the history is typical of some other
disorder, such as syncope, the prevalence of epilepsy will be low, and any epileptiform
abnormalities are more likely to be incidental. The test should not be performed in this
circumstance.
EEG can aid classification of epileptic seizures and epilepsy syndromes. The finding or not of a
photoparoxysmal response can allow appropriate advice to be given.37 If performed within the
first few weeks after a first seizure, EEG has prognostic value; patients with epileptiform
abnormalities are more likely to have a second attack.38
2.4.2
LONG TERM EEG MONITORING
When clinical information and standard investigations do not allow a confident diagnosis, referral
for the recording of attacks should be considered. The attacks should usually be occurring at least
once a week. If non-epileptic attack disorder is a possibility, then monitoring in patients with
less frequent attacks may be worthwhile, as they are often easily provoked.39-46 The best method
is inpatient video EEG recording.47 Twenty four hour ambulatory EEG recording has the advantage
of recording attacks in the patient’s usual setting, but does not usually allow correlation of EEG
and video data. Home video recordings can be useful, but rarely capture the onset of attacks.47,48
These investigations should include single channel electrocardiography recording.49
2.4.3
OTHER INVESTIGATIONS
Electrocardiography (ECG) should be performed in the assessment of all patients with altered
consciousness, particularly those in older age-groups, when disorders of cardiac rhythm may
simulate epilepsy. Twenty four hour ambulatory ECG and other cardiovascular tests may also be
helpful.49
6
2+
3
4
C
Electroencephalography (EEG) is not routinely indicated and should not be performed to
“exclude” a diagnosis of epilepsy.
C
EEG can be used to support the diagnosis in patients in whom the clinical history indicates
a significant probability of an epileptic seizure or epilepsy.
C
EEG should be used to support the classification of epileptic seizures and epilepsy syndromes
when there is clinical doubt.
C
EEG should be performed in young people with generalised seizures to aid classification
and to detect a photoparoxysmal response.
3
2 DIAGNOSIS
2.5
C
Video EEG and other specialist investigations should be available for patients who present
diagnostic difficulties.
þ
Patients who have blackouts, strange feelings or “funny turns” should have a 12-lead
electrocardiogram.
BRAIN IMAGING
Brain imaging detects lesions in 21-37% of patients presenting with epilepsy. Such lesions require
treatment in only a small minority, but their detection may have implications for future
management should the epilepsy become intractable. Idiopathic generalised epilepsies are not
associated with an increased prevalence of brain lesions.10,50-53
2.5.1
MAGNETIC RESONANCE IMAGING
Magnetic resonance imaging (MRI) scanning is the current standard of reference in the investigation
of patients with epilepsy. Routine MRI brain scanning using simple standard sequences will
detect lesions (eg small tumours, vascular malformations and cortical dysplasia) that are not
detected by computed tomography (CT) scanning. MRI carried out for the assessment of drugresistant epilepsy requires specialised protocols and expertise (eg to detect hippocampal
sclerosis).53-61
2.5.2
2+
2++
2+
4
COMPUTED TOMOGRAPHY SCANNING
CT scanning has a role in the urgent assessment of seizures, or when MRI is contraindicated (eg
when patients have pacemakers or metallic implants). A non-contrast CT scan will fail to identify
some vascular lesions and tumours. CT has only a limited role in the assessment of intractable
epilepsy.54,61,62
C
MRI is the modality of choice for brain imaging in patients with epilepsy.
C
Brain imaging is not routinely required when there is a confident diagnosis of an idiopathic
generalised epilepsy and if there is rapid and complete response to the first line
antiepileptic drug.
D
CT has a role in the urgent assessment of seizures, or when MRI is contraindicated.
2++
2+
7
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
3
Treatment
3.1
WHEN AND BY WHOM SHOULD ANTIEPILEPTIC DRUG TREATMENT BE
COMMENCED?
The crucial decision whether or not to start antiepileptic drug (AED) treatment must take into
account the relative risks of recurrent seizures (including the small but important risk of sudden
unexplained death in epilepsy) and the commitment to long term medication with potential side
effects.
3.1.1
EPILEPSY
Antiepileptic drugs should not be given until the diagnosis of epilepsy has been confirmed (see
Section 2). If there is uncertainty, a period of observation will usually clarify the epilepsy syndrome
and confirm the need for treatment.5,6
3.1.2
SINGLE SEIZURES
A detailed history should be taken to exclude previous myoclonic, absence or partial seizures as
patients with undiagnosed epilepsy may present with a single generalised tonic-clonic seizure.10
Whether to treat a single seizure or not is largely decided by the risk of further seizures (see
Annex 2). Estimates of recurrence risk vary. Highest recurrence rates (up to 90%) are seen in
patients with epileptic discharges on EEG or congenital neurological deficits. Lowest rates (1340%) are associated with acute symptomatic seizures (provoked) or patients with a normal EEG
and no identifiable cause for seizures.38,63-65 Overall the risk is 30-40%;66 this is greatest in the
first twelve months and falls to <10% after two years.67
1+
2++
2+
4
Treatment with AEDs reduces the risk of recurrence by half.68,69 Early treatment with AEDs does
not appear to alter the prognosis of epilepsy which is best predicted by the number of seizures in
the first six months after diagnosis and response to first AED.70-72
The patient’s view on medication should be considered. Women planning a pregnancy may
choose to avoid AEDs in the short term, though they must be warned of the attendant risks (see
Section 4.3). Individuals wishing to avoid recurrent seizures, eg for driving, should be offered
immediate treatment.
B
B
B
B
D
3.2
The decision to start antiepileptic drugs (AEDs) should be made by the patient and an
epilepsy specialist.
AEDs should be offered after a first tonic-clonic seizure if:
n
the patient has had previous myoclonic, absence or partial seizures
n
the EEG shows unequivocal epileptic discharges
n
the patient has a congenital neurological deficit
n
the patient considers the risk of recurrence unacceptable.
ANTIEPILEPTIC DRUG MONOTHERAPY
Comparative, randomised, double-blind trials in patients with newly-diagnosed partial and
generalised tonic-clonic seizures suggest similar efficacy for phenytoin, carbamazepine, sodium
valproate, lamotrigine and oxcarbazepine.73-81 The newer AEDs, lamotrigine and oxcarbazepine
seem to be better tolerated and may produce fewer long term side effects and adverse interactions.7678,80,82
Sodium valproate and lamotrigine also have efficacy for absence and myoclonic seizures
but lamotrigine can worsen myoclonus in some cases.83,84 Ethosuximide has been used for absence
seizures in children for many decades.83 Lamotrigine may have advantages for adolescents, young
women and the elderly because it is well tolerated,76,80,85 has a favourable cognitive and behavioural
profile,86 does not induce the metabolism of lipid-soluble drugs (such as the hormonal components
of the oral contraceptive agent)82,87,88 and does not lead to weight gain.89
8
1++
1+
1-
3 TREATMENT
Formulations of AEDs are not interchangeable and generic substitution should not be employed.90,91
A
Carbamazepine, sodium valproate, lamotrigine and oxcarbazepine can all be regarded as
first-line treatments for partial and secondary generalised seizures.
A
Sodium valproate and lamotrigine are drugs of choice for primary generalised seizures
and should also be prescribed if there is any doubt about the seizure types and/or syndrome
classification.
All antiepileptic drugs licensed for monotherapy have similar efficacy in newly-diagnosed
epilepsy.82,92,93
A
3.3
1++
1+
The side effect and interaction profiles should direct the choice of drug for the individual
patient.
MANAGEMENT OF DRUG-RESISTANT EPILEPSY
Drug-resistant epilepsy is defined as continuation of seizures despite optimal monotherapy with
two successive first-line AEDs or with one monotherapy and one combination regimen.
The majority of patients with newly-diagnosed epilepsy respond well to AEDs. Failure to do so
may be due to:
n
n
n
n
n
an incorrect diagnosis of epilepsy2,93
an inappropriate choice of AED for the epilepsy syndrome93,94
failure to take the prescribed AED
an underlying cerebral neoplasm
covert drug or alcohol abuse.
Given a correct diagnosis of epilepsy, failure to control seizures completely with the first welltolerated AED is a powerful predictor of drug-resistant epilepsy.72,95 When two AEDs have failed
as monotherapy the chance of seizure-freedom with further monotherapy is very low.72
Improvement in seizure control may be obtained by combining AEDs.96,97 Choice of AED
combinations should be guided by side effect profile and drug interactions. There is some evidence
that combining AEDs which have different mechanisms of action may enhance effectiveness eg
lamotrigine with sodium valproate98,99 but not with carbamazepine or phenytoin.98
3.3.1
DRUG-RESISTANT FOCAL EPILEPSY
Seven AEDs have been licensed in the UK in the last decade. These are, in chronological order,
vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine and levetiracetam.
Systematic reviews have confirmed the efficacy and tolerability of all these new agents as adjunctive
therapy for patients with drug-resistant, focal epilepsy.100-108 The development of concentric visual
field defects with vigabatrin has substantially limited its clinical use.109
3.3.2
1++
1+
12++
2+
1++
1+
12++
DRUG-RESISTANT IDIOPATHIC GENERALISED EPILEPSY
Lamotrigine,110-112 topiramate,113,114 levetiracetam115 and sodium valproate83 have a wide spectrum
of activity that includes most types of generalised seizures. Clonazepam may be used for refractory
myoclonic seizures. The older agents clobazam116 and acetazolamide117 can be effective for both
idiopathic generalised and focal epilepsy when other AEDs have failed.
Once the decision has been made to use combination therapy, the patient should be established
on the best monotherapy option at the optimal dose, ie one that does not produce side effects.84
A range of different AEDs appropriate to the epilepsy syndrome should be added as necessary in
sequence, increasing the dose of each slowly to obtain the maximal response with minimal
toxicity. The aim should be seizure-freedom. If an encouraging but sub-optimal effect is obtained
with a particular combination, it may be worthwhile trying the addition of a small dose of a
third AED.
1++
1+
12++
9
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
The law of diminishing returns may require patient and doctor to accept the persistence of some
seizures once a range of treatment options has been tried. Adequacy of seizure control must be
balanced with optimal quality of life. Little can be lost by carefully reducing the drug burden in
a patient with continuing seizure activity aiming for the most effective combination of two or at
most three AEDs. Producing less intrusive episodes, abolishing tonic-clonic seizures, preventing
falls and decreasing automatisms can be acceptable end points for some patients.
3.4
C
Failure to respond to appropriate AEDs should prompt a review of the diagnosis of
epilepsy and adherence to medication.
A
Combination therapy should be considered when treatment with two first line AEDs has
failed or when the first well-tolerated drug substantially improves seizure control but
fails to produce seizure-freedom at maximal dosage.
B
The choice of drugs in combination should be matched to the patient’s seizure type(s)
and should be limited to two or at most three AEDs.
þ
Vigabatrin can be regarded as the drug of last choice because of its association with
irreversible visual field defects.
ANTIEPILEPTIC DRUG BLOOD LEVELS
There is no indication for routine monitoring of AED concentrations.118-120 Evidence supports
clinically useful dose-response and dose-toxicity relationships for carbamazepine and phenytoin.
These relationships do not occur with sodium valproate or any of the newer AEDs. Phenytoin
also undergoes saturation kinetics which can make accurate dosage adjustment without
concentration monitoring problematical. Even with these two drugs, however, the upper and
lower borders of the “target ranges” are imprecise and are not applicable to all patients.118
1+
4
Blood level monitoring should be undertaken to answer a specific clinical question; does imperfect
adherence to the treatment schedule explain the poor seizure control? Specialist knowledge is
required to interpret assay results as the pharmacokinetics of some AEDs are non-linear and
because of the pharmacokinetic interactions that may take place. This is particularly important
given the lack of a useful “target range” for the majority of AEDs.
3.5
D
Routine monitoring of AED concentrations is not indicated. Measurement can sometimes
be useful in the following circumstances:
n
adjustment of phenytoin dose
n
assessment of adherence and toxicity.
D
Assay of lamotrigine, vigabatrin, gabapentin, topiramate, tiagabine, oxcarbazepine and
levetiracetam concentrations should not be undertaken routinely.
þ
AED blood level measurement is best supervised by an epilepsy specialist.
MANAGEMENT OF PROVOKED SEIZURES
Seizures can be provoked by acute metabolic disturbances, treatment with certain drugs (see
Section 3.13) and drug withdrawal (eg alcohol, benzodiazepines, barbiturates). Provoked seizures
may occur in the context of drug abuse (heroin, cocaine, methadone, amphetamine, ecstasy).
The risk of recurrence of such provoked seizures can be reduced by correction or withdrawal of
the provocative factor. The risk of seizures related to acute alcohol withdrawal can be reduced by
short term treatment with lorazepam.121 Commencement of longer term AED treatment is only
indicated if unprovoked seizures occur.
Provoked seizures can also occur with acute conditions such as encephalitis, head injury, cerebral
infarction and cerebral haemorrhage, when they are defined as seizures occurring within seven
days of an acute brain insult. There is evidence that treatment can reduce the risk of such provoked
seizures in the context of traumatic brain injury (by phenytoin and carbamazepine), craniotomy
10
1+
3 TREATMENT
(by phenytoin) and cerebral malaria (by phenobarbital).121,122 There is no evidence however, that
prophylactic treatment and prevention of provoked seizures influences the subsequent development
of epilepsy with unprovoked seizures. For acute traumatic brain injury, there is no evidence that
the prevention of early provoked seizures by AED treatment influences other outcomes such as
death and neurological disability.122 There is no justification for the routine prophylactic use of
AED treatment to prevent provoked seizures in the context of acute brain insults. If AED treatment
is commenced following the occurrence of provoked seizures, it should be used only in the short
term, unless unprovoked seizures occur later.
Attacks occurring immediately after a concussive closed-head injury have been described as
concussive convulsions. There is no evidence that these will recur and AED treatment is not
indicated.123
3.6
þ
When seizures are provoked by metabolic disturbances or drugs, attention should be
directed to correction or withdrawal of the provocative factor.
B
Short term benzodiazepine treatment may be given to reduce the risk of seizures in the
context of acute alcohol withdrawal and delirium tremens.
B
Following an acute brain insult or neurosurgery, prophylactic AED treatment is not
indicated.
C
Following an acute brain insult, AEDs used to treat the provoked seizures should be
withdrawn (unless unprovoked seizures occur later).
D
AED treatment is not indicated for concussive convulsions.
ANTIEPILEPTIC DRUG SIDE EFFECTS
Antiepileptic drug side effects are common and a major cause of drug withdrawal. Most are mild
but a minority can be life threatening.73,102,124 Accurate data on the prevalence of adverse drug
reactions (ADRs) with long term AED treatment is scarce; almost all reports refer to short term
clinical trials and, as experience with vigabatrin and visual field defects has shown, long term
surveillance is needed to identify all ADRs.125 The elderly are more sensitive to AED side effects
due to altered pharmacokinetics.
3.6.1
3
1++
1+
3
DOSE-RELATED ADVERSE REACTIONS
Many AED side effects are dose-related and predictable. These can be minimised by gradual
escalation of dose, with dose reduction if symptoms persist. Use of slow release carbamazepine
can reduce peak dose-related side effects of dizziness and blurred vision.126
3.6.2
IDIOSYNCRATIC ADVERSE DRUG REACTIONS
Idiosyncratic drug reactions usually occur in the first weeks of treatment and are potentially
serious. Rash is the most common, occurring in up to 10% of patients on carbamazepine,
phenytoin or lamotrigine. Most rashes are mild and resolve promptly on discontinuation of the
AED, but severe cutaneous reactions are seen in up to 1:1,000 patients. 127-129 This incidence is
increased if the initial dose is increased rapidly.130
2+
4
The life-threatening AED hypersensitivity syndrome of fever, rash, lymphadenopathy and multiorgan
failure occurs in up to 4.5:10,000 patients, mostly with carbamazepine, lamotrigine or
phenytoin.127 It is important to note that cross sensitivity occurs between these AEDs in up to
70% of patients.
2+
Minor blood dyscrasias are associated with many AEDs; the majority (mild leucopaenia with
carbamazepine, thrombocytopaenia with valproate) require no action. Severe blood dyscrasia
occurs in 6:10,000 patients but there is no evidence to suggest that routine monitoring can
reduce this risk.131,132
2+
4
11
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
Hyponatraemia (sodium <135 but usually >125mmol/L) is seen in about 20% of patients taking
carbamazepine or oxcarbazepine; it is usually well tolerated and of no significance.133 Elevation
of liver enzymes (δ-glutamyl transferase 90%, alkaline phosphatase 30%) is seen in people taking
enzyme-inducing AEDs and is usually of no clinical significance.134 Clinical symptoms have
been shown to be more useful than routine monitoring of liver function in identifying the onset
of serious ADRs.132,135
4
Acute psychotic reactions are seen occasionally with newer AEDs, particularly in those patients
with a previous history of psychiatric disease; withdrawal from the drug usually results in recovery.136
3.6.3
3.7
CHRONIC SIDE EFFECTS
Weight gain is seen with many AEDs75 but significant (>10% body weight) weight gain is associated
particularly with valproate.89 Topiramate can cause weight loss.137
1+
Sedation and dizziness are common complaints of patients starting AED therapy but usually
resolve with time.102 Sedation may be less with the newer AEDs.86 Many patients on long term
AED therapy report cognitive side effects but studies to confirm this have been contradictory and
confounded by the effects of chronic epilepsy.138,139 Polytherapy is probably associated with more
cognitive side effects than monotherapy.140
1++
2+
4
Osteopenia, osteomalacia and increased risk of hip fracture have been associated with AED use
but their aetiology is likely to be multifactorial.141-144
2+
þ
Antiepileptic drugs should be commenced in a dose no higher than recommended by the
manufacturer.
C
Patients should be warned of potential side effects and given clear instructions to seek
medical attention urgently for symptoms including rash, bruising or somnolence with
vomiting especially in the first weeks of treatment.
D
Patients taking AEDs should receive dietary and other lifestyle advice to minimise the
risk of osteoporosis.
C
Liver function and full blood count should not be monitored routinely.
ANTIEPILEPTIC DRUG WITHDRAWAL
Estimates of the risks of seizure recurrence after discontinuation of AEDs were provided by a
large, multicentre, randomised, prospective trial of continued antiepileptic treatment versus slow
withdrawal in adults and children with epilepsy, who had been seizure free for at least two
years.145 AED withdrawal was associated with an increased risk of seizure recurrence, which was
influenced by the duration of seizure freedom, the history of seizure types, the occurrence of one
or more seizures after the start of treatment and whether one, or more than one, AED was being
taken. The data from the study were used to develop a prognostic index for seizure recurrence. 146
This has been used to calculate the risks of seizure recurrence with continued treatment or with
slow AED withdrawal (see Tables 2 and 3). An abnormal EEG at the time of entry into the study
was associated with only a small increased risk of seizure recurrence. Since this is unlikely to
influence a decision about whether to withdraw AED treatment or not in adults, EEG recording
is not necessary for an informed decision to be made. The higher risks of seizure recurrence with
a history of myoclonus reflect the high risk of seizure recurrence following AED withdrawal in
juvenile myoclonic epilepsy. The prognostic index has not been validated on an external population,
and should be used with caution.
No information is available on the risks of seizure recurrence following drug withdrawal in
adults who have been less than two years seizure free, although for children the risks are higher
after less than two years seizure freedom than for more than two years. 147
The effect of different rates of AED withdrawal on the risk of seizure recurrence has not been
adequately studied.
12
1++
3 TREATMENT
Important factors influencing a decision about AED withdrawal in adults include driving,
employment, fear of further seizures, risks of injury or death with further seizures and concerns
about prolonged AED treatment. The Driver and Vehicle Licensing Agency recommends that
driving should cease during the period of AED withdrawal and for six months afterwards, and for
many this factor alone may lead to a decision to continue treatment.
A
Prognostic index indicators can be used to give an estimate of the risks of seizure recurrence
following AED withdrawal (see Tables 2 and 3).
þ
The question of continued treatment or AED withdrawal should be discussed with people
with epilepsy, who are at least two years seizure free, so that they can make an informed
choice. Factors to be discussed should include driving, employment, fear and risks of
further seizures and concerns about prolonged AED treatment.
þ
n
n
The rate of withdrawal of AEDs should be slow, usually over a few months, and longer
with barbiturates and benzodiazepines.
One drug should be withdrawn at a time.
13
Table 2: Prognostic index for recurrence of seizures after remission of epilepsy for patients taking only one antiepileptic drug (AED)
Risk of seizure recurrence by two years (%)
Period free from seizures
Seizure history*
TC
2 years
My Oth
TC
4 years
My Oth
TC
6 years
My Oth
TC
8 years
My Oth
TC
10 years
My Oth
TC
15 years
My Oth
Current EEG unavailable
35
60
50
75
25
45
20
40
35
60
15
30
20
35
30
55
15
25
20
35
25
50
15
25
15
35
25
50
10
25
15
30
25
45
10
25
Current EEG abnormal
35
60
50
80
25
50
25
45
35
60
15
35
20
40
30
55
15
30
20
35
30
50
15
25
20
35
25
50
15
25
15
30
25
45
10
25
Current EEG normal
30
55
45
70
20
40
20
35
30
55
15
30
15
30
25
45
10
25
15
30
25
45
10
20
15
30
25
45
10
20
15
25
20
40
10
20
top figure=patient
continues with AED
bottom figure=slow
withdrawal of AED
No seizures after start of AED therapy
Current EEG unavailable
25
45
40
65
20
35
15
30
25
45
10
25
15
25
20
40
10
20
15
25
20
40
10
20
10
25
20
35
10
20
10
20
20
35
10
15
Current EEG abnormal
25
50
40
65
20
35
15
35
25
50
10
25
15
30
25
40
10
20
15
25
20
40
10
20
15
25
20
40
10
20
10
25
20
35
10
20
Current EEG normal
20
40
35
60
15
30
15
30
20
40
10
20
10
25
20
35
10
20
10
20
20
35
10
15
10
20
15
35
10
15
10
20
15
30
10
20
*TC: history of idiopathic or secondary generalised tonic-clonic seizures
My: history of myoclonic seizures with tonic-clonic seizures (myoclonic seizures rarely occur alone)
Oth: history of seizures other than tonic-clonic or myoclonic
14
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
Seizures after start of AED therapy
15
3 TREATMENT
Table 3: Prognostic index for recurrence of seizures after remission of epilepsy for patients taking more than one antiepileptic drug (AED)
Risk of seizure recurrence by two years (%)
Period free from seizures
Seizure history*
2 years
TC
My Oth
4 years
TC
My Oth
6 years
TC
My Oth
8 years
TC
My Oth
10 years
TC
My Oth
15 years
TC
My Oth
Seizures after start of AED therapy
Current EEG unavailable
50
75
65
75
40
65
35
60
50
75
25
45
30
55
45
70
20
40
25
50
40
70
20
40
25
50
40
65
20
35
25
45
35
65
20
35
Current EEG abnormal
50
80
70
90
40
65
35
60
50
80
25
50
30
55
45
75
25
40
30
50
40
70
20
40
25
50
40
70
20
40
25
45
40
65
20
35
Current EEG normal
45
70
60
85
35
60
30
55
45
70
20
40
25
45
40
65
20
35
25
45
35
60
20
35
25
45
35
60
15
35
20
40
35
60
15
30
No seizures after start of AED therapy
Current EEG unavailable
40
65
55
80
30
50
25
45
40
65
20
35
20
40
35
60
15
30
20
40
30
55
15
30
20
35
30
55
15
30
20
35
30
50
15
25
Current EEG abnormal
40
65
55
85
30
55
25
50
40
65
20
35
25
40
35
60
15
30
20
40
30
55
10
30
20
40
30
55
15
30
20
35
30
55
15
25
Current EEG normal
35
60
50
75
25
45
20
40
35
60
15
30
25
35
30
55
15
25
20
35
25
50
15
25
15
35
25
50
10
25
15
30
25
45
10
25
*TC: history of idiopathic or secondary generalised tonic-clonic seizures
My: history of myoclonic seizures with tonic-clonic seizures (myoclonic seizures rarely occur alone)
Oth: history of seizures other than tonic-clonic or myoclonic
top figure=patient
continues with AED
bottom figure=slow
withdrawal of AED
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
3.8
PSYCHOLOGICAL TREATMENT OF EPILEPSY
A variety of treatment types has been used in the psychological management of epilepsy.148
There is evidence that seizures may respond to operant and/or classical conditioning and that
seizure spread may be inhibited by the patient’s own intervention, either by interruption strategies
or EEG biofeedback.
Anxiety or stress may precipitate seizures, possibly through hyperventilation.149 Treatments aimed
at reducing anxiety may reduce seizure frequency150-154 and are free of significant side effects.
Psychological symptoms associated with epilepsy may merit treatment in their own right.155
B
3.9
1+
2++
2+
3
Psychological treatments are not an alternative to pharmacological treatments, but their
use can be considered in patients with poorly controlled seizures.
COMPLEMENTARY THERAPY FOR EPILEPSY
Complementary therapy is increasingly popular with patients, who may use this in addition to
conventional medication.156,157 The term covers a wide variety of treatments such as acupuncture,
chiropractic, herbal medicine, homeopathy, osteopathy and yoga. There is no evidence that
these improve seizure control.158,159
Patients should be asked if they are using any complementary medicines and warned about the
possibility of adverse effects. Problems may arise with the use of some herbal medicines because
of interaction with prescribed medication. The potential reduction of the plasma concentrations
of carbamazepine, phenobarbital and phenytoin should be noted if St John’s Wort is used
concomitantly.160 The British National Formulary advises against this. Caution is also advised in
the use of evening primrose oil but the evidence for this is less robust.
4
Some aromatherapy preparations (eg hyssop, rosemary, sweet fennel, sage and wormwood) may
have an alerting effect on the brain and so may exacerbate seizures.161,162
3.10
SURGICAL REFERRAL
Neurosurgical procedures are an effective treatment for some patients with epilepsy resistant to
drug treatment.163,164 Patients can be classified as probably having drug resistant epilepsy once
they have failed to obtain seizure control with two appropriate AEDs given in adequate dosage
(see Section 3.3).72 It is important that surgery be considered as soon as it is established that the
epilepsy is drug resistant, as the benefits will be greater in younger patients. Some neurosurgical
procedures involve resection of part of the brain, and the aim is to obtain complete seizure
freedom. For the most commonly performed procedures, involving anterior and medial temporal
lobe resection, about 70% of patients will become seizure free.165 Other procedures are palliative
and include corpus callosotomy, subpial transection and vagus nerve stimulation.166 Assessment
for suitability for surgery should be performed in a specialist unit. For each individual the potential
benefits of improved seizure control, quality of life and possible reduction in antiepileptic
medication need to balanced against the risks of the surgical procedure.
3.11
B
Referral for assessment for neurosurgical treatment should be considered if the epilepsy
is drug resistant.
D
Assessment as to suitability for a potentially curative resective procedure should be made
before consideration of palliative procedures such as vagus nerve stimulation.
1+
MANAGEMENT OF STATUS EPILEPTICUS
Status epilepticus has been defined as a condition in which “epileptic activity persists for 30
minutes or more, causing a wide spectrum of clinical symptoms, ...”.167
Emergency treatment should be sought or given by carers of people with epilepsy once a seizure
has persisted, or there are serial seizures, for more than five minutes. Generalised tonic-clonic
status epilepticus is a medical emergency with significant morbidity and mortality, which can
16
3
3 TREATMENT
often be attributed to inadequate or delayed treatment.168-170 Other types of status epilepticus
(including simple partial, complex partial and absence status epilepticus) are often associated
with delayed diagnosis and treatment, but have a much lower risk of morbidity. Prompt and
accurate differentiation of status epilepticus from pseudo-status epilepticus and other non-epileptic
disorders is crucial if inappropriate treatment and iatrogenic morbidity are to be avoided.168,171
EEG recording may be necessary to confirm the diagnosis and to assess control, when seizures are
clinically subtle (eg in partial status, or following treatment of tonic-clonic status epilepticus).172
3.11.1
GENERALISED TONIC-CLONIC STATUS EPILEPTICUS
Recommendations for treatment are based on two large prospective, randomised trials of the
management of status epilepticus173,174 and on small or uncontrolled studies, physiological principles
and pharmacokinetic considerations.167,175-180 Intravenous lorazepam and diazepam are both effective
and safe in controlling tonic-clonic status epilepticus, when administered by paramedics, prior
to transport to hospital, with a trend in favour of lorazepam. 173 Intravenous lorazepam,
phenobarbital and diazepam plus phenytoin are all effective initial treatments on hospital
admission, with a trend again in favour of lorazepam, which is significantly more effective than
phenytoin alone.174 Lorazepam has the advantage over diazepam of a much longer duration of
action, but its use in the community is limited by the need for refrigerated storage. There should
be a high level of awareness of the risk of respiratory depression. Additional maintenance treatment
is required following initial use of either benzodiazepine. Fosphenytoin is less irritant to veins
than phenytoin and can be administered more rapidly (but still needs to be given slowly).
1++
3
4
IMMEDIATE MEASURES
D
In the community or in hospital, patients with generalised tonic-clonic status epilepticus
should be managed immediately as follows (with local protocols being in place):
n
secure airway
n
give oxygen
n
assess cardiac and respiratory function
n
secure IV access in large veins.
A
Give lorazepam 4mg IV or diazepam 10 mg IV if lorazepam is unavailable. This can be
repeated in hospital after 10 minutes if there is no response. If there is a delay in gaining
IV access in the community: give diazepam 10-20mg rectally (rectal solution or IV
solution).
D
In hospital:
n
collect blood for full blood count, urea and electrolyte, liver function tests, calcium,
glucose, clotting, AED levels and storage for later analyses
n
measure blood gases to assess extent of acidosis
n
establish aetiology. Give 50ml 50% glucose IV if there is any suggestion of
hypoglycaemia and IV thiamine (given as Pabrinex two pairs of ampoules) if there is
any suggestion of alcohol abuse or impaired nutritional status.
WITHIN 30 MINUTES
D
For sustained control in patients with established epilepsy, within 30 minutes:
give usual AED treatment orally or by nasogastric tube (or IV if necessary for phenytoin,
sodium valproate and phenobarbital).
n
B
For sustained control in other patients or if seizures continue, within 30 minutes:
n
give fosphenytoin in a dose of 18mg/kg phenytoin equivalent (PE) IV, up to 150mg/
min with ECG monitoring; or phenytoin 18mg/kg IV, 50mg/min with ECG monitoring
or phenobarbital 15mg/kg IV, 100mg/min. Rates of infusion may need to be reduced
if hypotension or arrythmia occur or in elderley or renal/ hepatic impairment.
þ
Clear policies should be in place to avoid confusion between doses, formulations, routes
and rates of administration of fosphenytoin and phenytoin.
17
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
LONGER THAN 30 MINUTES
If status epilepticus persists the patient needs to be admitted to an intensive treatment unit (ITU)
and anaesthetised with EEG monitoring. Midazolam, pentobarbital (unlicensed), propofol or
thiopentone are most commonly used in these circumstances.180
D
3.11.2
If status persists, then within 60 minutes:
n
admit to ITU and administer general anaesthesia
n
monitor using EEG to assess seizure control
n
refer for specialist advice.
NON-CONVULSIVE STATUS EPILEPTICUS
D
3.11.3
Patients with non-convulsive status epilepticus should be managed as follows:
n
maintain or reinstate usual oral AED treatment
n
consider lorazepam 4mg IV or diazepam 10 mg IV
n
refer for specialist advice.
PATIENTS WITH RECURRENT PROLONGED OR SERIAL SEIZURES IN THE COMMUNITY
Carers of patients with recurrent episodes of serial seizures, or prolonged seizures may be able to
terminate the episodes and perhaps prevent the development of status epilepticus by the
administration of rectal diazepam 10-20mg.181,182 An administration protocol should be followed
(see Section 3.13).183,184 Buccal or intranasal midazolam has also been used as a more convenient
(but unlicensed) alternative, mainly in children, and needs further assessment.185,186
A
3.12
1+
13
Patients with recurrent prolonged or serial seizures in the community should be initially
managed by carers who should give diazepam 10-20mg rectally according to an agreed
protocol (protocols must include advice on when to transfer to hospital).
MANAGEMENT OF PEOPLE WITH LEARNING DISABILITY AND EPILEPSY
People with learning disability and epilepsy should have access to the same range of investigations
and treatment as the rest of the population.187,188 The high prevalence of epilepsy associated with
learning disability is at its greatest (about 50%) in people with severe disability and cerebral
palsy.189 Quality of life may be affected because of injuries sustained during seizures and because
of the side effects of medication.190 An excess mortality has also been reported.191 In some adults
who have learning disability it may be difficult to distinguish epilepsy from psychiatric illness,
emotional and behavioural outbursts.188,192 Where doubts exist, video recording of the episode
may help to secure diagnosis, with appropriate consent. Clinical guidelines exist for the management
of epilepsy in adults with an intellectual disability.193 Treatment may need to be given under the
provisions of the Adults with Incapacity (Scotland) Act 2000 if the person cannot give informed
consent. Seizure freedom is an appropriate endpoint for many patients with learning disability
and epilepsy.
D
18
4
In the management of people with learning disability and epilepsy:
n
adequate time should be allowed for the consultation
n
the carer should know the patient and bring relevant information on seizure type,
frequency, possible side effects of medication, general health and behaviour to the
consultation
n
information in an accessible form should be available to clients and carers
n
there should be a multidisciplinary approach to treatment, delivered by professionals
with an expertise in epilepsy, to improve quality of life. Community learning disability
nurses have an important role in liaising between the specialist services and clients
and carers.
4
3 TREATMENT
3.13
ADVICE ON RECTAL DIAZEPAM OR EQUIVALENT EMERGENCY MEDICATION
Rectal diazepam is a relatively safe and effective medication for the control of serial and/or
prolonged seizures in patients in the community. Parents and carers who have been trained in the
procedure can administer the medication as a first aid measure by following clear written guidelines
set by the prescribing doctor.
4
Recognised training should be given to carers and updated at regular intervals; a care plan should
be used to ensure consistency of treatment.183,184,194
3.14
D
All carers of patients with learning disability and epilepsy who may require rectal diazepam,
should receive recognised training in its administration. Retraining should take place
every two years.
D
A care plan should be drawn up in consultation with the GP and/or specialist service,
used by everyone working with the individual client, and reviewed at regular intervals.
D
Adequate support and instruction should be given to families.
DRUGS WHICH EXACERBATE EPILEPTIC SEIZURES
Drugs may occasionally precipitate seizures particularly in patients with epilepsy or other risk
factors.195 Commonly used drugs are listed in Table 4 (causality is not always certain and may be
multifactorial).196-205
4
Table 4: Drugs which may precipitate epileptic seizures
Aminophylline/theophylline
Amphetamines
Analgesics eg tramadol
Antibiotics eg penicillins,
cephalosporins, quinolones
Antidepressants
Anticholinergics eg benzatropine
Anti-emetics eg prochlorperazine
Antipsychotics eg chlorpromazine
Baclofen
Bupropion [Zyban ®]
Cholinesterase inhibitors eg donepezil
Ciclosporin
Cocaine
Isoniazid
Ketamine
Lidocaine (lignocaine)
Lithium
Mefloquine
Methylene dioxymethamfetamine (ecstasy)
Non-steroidal anti-inflammatory
drugs (especially in combination
with quinolone antibiotics)
Opioids eg diamorphine, pethidine
Oral contraceptives
Vincristine
Mechanisms for triggering seizures may include:
n
n
n
n
n
lowering of seizure threshold - this is usually dose/plasma concentration dependent and
factors such as renal impairment (eg pethidine) or coadministration of interacting drugs (eg
ciprofloxacin/theophylline) may contribute
decrease in AED levels via pharmacokinetic drug interactions (eg hepatic microsomal enzyme
induction with rifampicin)
effects secondary to other medical causes precipitated by drugs eg drug-induced hyponatraemia
or serotonin syndrome
individual AEDs which themselves may cause worsening of some types of seizures94
drug withdrawal eg from AEDs, alcohol, benzodiazepines, barbiturates and baclofen.206,207
þ
3
4
All healthcare professionals should be vigilant for prescription of drugs that may cause or
exacerbate seizures in patients with epilepsy.
19
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
þ
3.15
A wide variety of drugs has been reported to precipitate or potentiate seizures in patients
with or without a history of epilepsy. This does not preclude their use when indicated in
patients with epilepsy and supported by a risk-benefit assessment. Common examples
include:
n
antidepressants, when a selective serotonin re-uptake inhibitor (SSRI, eg sertraline,
citalopram) may be a reasonable choice
n
antipsychotics, when drugs with lower seizure risk such as haloperidol, risperidone,
sulpiride should be used in preference to drugs thought to have higher risk such as
clozapine and chlorpromazine
n
antimalarials, when chloroquine and mefloquine are unsuitable for malaria
prophylaxis.The current guidelines from the Malaria Reference Laboratory (included in
the British National Formulary) should be consulted to choose an appropriate
alternative.208
MANAGEMENT OF PATIENTS WITH EPILEPSY IN THE PERIOPERATIVE PERIOD
Loss of seizure control due to missed oral medication can occur in the context of surgery, labour,
and when there is difficulty in swallowing. Table 5 lists some alternative routes of AED
administration. Sometimes changes in drug doses or frequency will be necessary due to
pharmacokinetic differences between formulations.
Table 5: Alternative methods of AED administration
AED
Carbamazepine
Phenytoin
Gabapentin
Lamotrigine
Valproate
Topiramate
Vigabatrin
Phenobarbital
Primidone
Tiagabine
Alternative administration
Liquid or suppositories (dose/frequency amendment required)
Intravenous or liquid phenytoin; intravenous or intramuscular
fosphenytoin*
Capsule contents can be administered via enteral feeding tube
(unlicensed)
Dispersible tablets can be administered via enteral feeding tube
Intravenous, liquid, or suppositories (unlicensed)
Sprinkle capsules ®
Powder
Liquid; intravenous or intra-muscular injection
Liquid
Crush tablets can be administered via enteral feeding tube (unlicensed)
*safety advantage over intravenous route
20
þ
Healthcare professionals should consider the possible consequences of missed AED doses
when planning hospital admission.
þ
AEDs should be administered by alternative routes or by giving additional doses as
appropriate. When patients have been designated nil by mouth prior to surgery, they
should still be given their usual oral AED unless absorption is impaired.
þ
When a prolonged problem with administration of drugs not available parenterally is
anticipated, and oral or enteral administration is not possible, consideration should be
given to seizure prophylaxis with parenterally available agents.
4 CONTRACEPTION, PREGNANCY AND HRT
4
Contraception, pregnancy and HRT
Women with epilepsy, who are of childbearing age, need additional advice about issues such as
contraception and pregnancy. The choice of epilepsy medication for women may be influenced
by factors that include potential teratogenicity of the AED, interactions with the oral contraceptive
and cosmetic side effects.
4.1
CONTRACEPTION
Many pregnancies in women with epilepsy are unplanned.209
þ
4.1.1
Advice on contraception should be given before young women are sexually active. Women
with epilepsy should be advised to plan their pregnancies.
COMBINED ORAL CONTRACEPTIVE (COC)
Women taking AEDs which induce hepatic enzymes (see Table 6) are at increased risk of
breakthrough bleeding and COC failure, estimated at up to 7 per 100 woman years, due to
accelerated oestrogen metabolism.210-212 Current guidelines recommend a COC containing a
minimum of 50micrograms oestrogen to reduce this risk, increasing to 80 or 100micrograms if
breakthrough bleeding occurs.213,214 Even with these measures the risk of pregnancy remains high
and expert opinion advises “tricycling” ie taking three packs of the high dose COC consecutively
and reducing pill-free days to four.215 Enzyme induction persists up to four weeks after the AED is
withdrawn.216 AEDs which do not induce hepatic enzymes do not alter the efficacy of the COC.
þ
If a patient is using oral contraception, an AED that does not induce hepatic enzymes is
preferable.
D
When the combined oral contraceptive is given with an enzyme-inducing AED, one
containing a minimum of 50micrograms of oestrogen should be used; women should be
warned that its efficacy is reduced and barrier methods of contraception should also be
used if maximal contraceptive effect is required.
D
If breakthrough bleeding occurs with 50micrograms of oestrogen the dose should be
increased and “tricycling” of the combined oral contraceptive should be considered.
24
Table 6: Action of AEDs on hepatic enzymes
AEDs which induce hepatic enzymes
carbamazepine217
oxcarbazepine218
phenobarbital219
phenytoin217
primidone
topiramate220
4.1.2
Non-enzyme inducing AEDs
acetazolamide
benzodiazepines
ethosuximide
gabapentin221
lamotrigine222
levetiracetam
tiagabine223
valproate224
vigabatrin223
PROGESTERONE-ONLY CONTRACEPTION
Progesterone metabolism is increased by enzyme-inducing AEDs and the efficacy of the
progesterone-only oral contraceptive cannot be guaranteed with these. Medroxyprogesterone (DepoProvera) can be used with enzyme-inducing AEDs but the efficacy may be reduced after ten
weeks. Implants of progesterone are not effective if given with enzyme-inducing AEDs.225
4
21
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
4.1.3
D
The progesterone-only oral contraceptive is not recommended for women taking enzymeinducing AEDs.
D
Depot injections of progesterone may be used with enzyme-inducing AEDs but should be
given every 10 weeks.
D
Progesterone implants are not suitable for women taking enzyme-inducing AEDs.
EMERGENCY CONTRACEPTION
Levonorgestrel 750micrograms two tablets taken not more than 12 hours apart is probably
inadequate emergency contraception for women taking enzyme-inducing AEDs.226,296
D
4.2
4
The dose of levonorgestrel for emergency contraception should be increased to 1.5mg
and 750micrograms 12 hours apart in women taking enzyme-inducing AEDs.
PRECONCEPTUAL COUNSELLING
Epilepsy is common in women of child-bearing age and exposure to AEDs occurs in approximately
1 in 250 pregnancies.227 Complications of pregnancy, mean birth weight and perinatal mortality
are similar to those in the general population.209,228
Many women with epilepsy are not given preconceptual counselling and those that are, often
forget it.209
4.2.1
þ
Women with epilepsy should be reassured that most will have a normal pregnancy and
delivery.
þ
Information about the risk of epilepsy and AEDs in pregnancy and the need for folate and
vitamin K should be given to all women of childbearing age and repeated at review
appointments.
RISKS TO THE FETUS FROM MATERNAL EPILEPSY
Seizure frequency increases during pregnancy in between a quarter and a third of women247 due
to a number of factors including changes in pharmacokinetics of AEDs and poor adherence to
treatment because of concerns about adverse effects on the fetus.209
The long term effect of tonic-clonic seizures on the fetus is not well established although the
associated hypoxia and acidosis may adversely affect the obstetric outcome, particularly if the
seizures are prolonged. Risks to the woman of injury and, rarely, death in a seizure remain in
pregnancy.229
D
4.2.2
Women should be made aware of the risks of uncontrolled seizures both to themselves
and to the fetus.
RISKS TO THE FETUS FROM ANTIEPILEPTIC DRUGS
Major and minor fetal malformations occur more commonly in infants exposed to AEDs during
pregnancy.209,230-232 The overall risk of major fetal malformation in any pregnancy is approximately
2%. This increases two to three fold in women taking a single AED. Current data suggest that the
risk with valproate may be higher than with carbamazepine or lamotrigine.233 Polytherapy,
particularly with certain combinations of drugs, carries a much higher risk (up to 24% in women
taking four AEDs).
The most common major malformations associated with established AEDs are: neural tube defects
(valproate 3%, carbamazepine 1%), orofacial defects, congenital heart abnormalities and
hypospadias.230,234 The risk of minor malformations including hypertelorism, epicanthic folds
and digital hypoplasia is increased with AED therapy in pregnancy.231
22
3
2+
2+
4
4 CONTRACEPTION, PREGNANCY AND HRT
“Fetal anticonvulsant syndromes” comprising typical dysmorphic craniofacial appearances and a
variety of musculoskeletal abnormalities have been described in association with AED treatment
in pregnancy.235,236 Although individual drugs have been associated with specific patterns, there
is overlap between them and genetic factors may influence susceptibility.237
3
4
Whether AEDs taken during pregnancy can affect the child’s intellectual development is uncertain
but concern about the effects of valproate on infant development has recently been raised.238,239
3
At present there is insufficient evidence on which to base advice about the risks of most of the
newer AEDs (gabapentin, levetiracetam, tiagabine, topiramate, vigabatrin) in pregnancy. Current
data on lamotrigine show a malformation rate of 3% (95% confidence interval 1.5-5.7).233
4.2.3
þ
Where possible women should have their epilepsy treatment reviewed before becoming
pregnant. They should be advised about the risks of seizures and effects of AEDs on the
fetus.
þ
If the woman’s epilepsy is in remission, the risk of recurrent seizures is low and the
woman is aware of the consequences of recurrent seizures, consideration may be given to
withdrawal of AEDs prior to conception.
C
If AEDs are to be used in pregnancy the relative risks of seizures and fetal malformation
should be discussed with the woman.
C
Whenever possible, a woman should conceive on the lowest effective dose of one AED
appropriate for her epilepsy syndrome. If she has good seizure control and presents
already pregnant, there is probably little to be gained by altering her AEDs.
D
Any woman who has given birth to a child with a malformation while taking AEDs
should be offered review by an epilepsy specialist before becoming pregnant again.
þ
All pregnant women with epilepsy, whether or not they are on medication, should be
notified, with their consent, to the UK Pregnancy Register (Tel: 0800 389 1248).
FOLIC ACID
Many pregnancies in women with epilepsy are unplanned, very few women take folate in the
correct dose at the appropriate time and advice given about malformation risk and folate is often
forgotten.209
Women taking AEDs, particularly valproate, are at greater risk of having a child with neural tube
defects (NTD) and other malformations which may be related to altered folate metabolism.240,241
It is recommended that all women should take daily folic acid from preconception and during
the first trimester of pregnancy to reduce the incidence of NTD.242-244 While there is no evidence
to show that folate can reduce the incidence of AED-associated malformations, current guidelines
recommend that a high dose of folate, 5mg daily, be given from pre-conception to the end of the
first trimester.213
D
4.2.4
2+
4
All women with epilepsy should be prescribed a daily dose of 5mg folic acid from
preconception until the end of the first trimester.
VITAMIN K1
Current guidelines recommend maternal Vitamin K1 supplementation with phytomenadione 10mg
daily from 36 weeks of pregnancy for all mothers taking enzyme-inducing AEDs
(see Table 6).245 However, the small risk of haemorrhagic disease of the newborn is not increased
in infants of mothers taking enzyme-inducing AEDs provided the infant receives 1mg Vitamin K1
intramuscularly at birth.246
2+
3
23
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
4.3
C
All infants born to mothers taking AEDs should be given Vitamin K1 1mg intramuscularly
at birth.
D
If there are additional risk factors for haemorrhagic disease of the newborn (eg maternal
liver disease, anticipated premature delivery) oral vitamin K 1 (phytomenadione 10mg
daily) should also be given in the last month of pregnancy.
PREGNANCY
In a maternity unit with 5,000 births per year, there will be around 20 pregnancies in women
with epilepsy.227 Pregnancy may be associated with changes in seizure frequency requiring alteration
in AEDs.247
Infants exposed to AEDs in utero are at higher risk of major and minor abnormalities. Ultrasound
scanning can detect most major structural abnormalities if performed at 18 weeks gestation by
skilled sonographers.248
3
4
Enzyme-inducing AEDs (see Table 6) accelerate metabolism of steroids, including betamethasone,
given to mothers to reduce the risk of neonatal respiratory distress in preterm infants.249
4.3.1
þ
Pregnancies in women with epilepsy should be supervised in an obstetric clinic with
access to a physician specialising in epilepsy.
þ
Seizure frequency should be monitored carefully during the pregnancy and adjustments
made to AED doses to minimise the number of seizures, particularly generalised tonicclonic seizures.
þ
Detailed ultrasound scanning for detection of fetal abnormality should be done at 18
weeks.
D
If preterm labour is threatened in women taking enzyme-inducing AEDs, 48mg
betamethasone (double the normal dose) should be given over 48 hours.
AED DOSES AND BLOOD LEVEL MONITORING DURING PREGNANCY
Pregnancy is associated with pharmacokinetic changes including: an increase in volume of
distribution, an increase in drug metabolism through hepatic microsomal enzyme induction, a
reduction in serum albumin concentration and an increase in renal clearance.250 There is a tendency
for plasma levels of AEDs to fall during pregnancy251 but there is no evidence to support routine
increase of AED doses. The value of plasma AED monitoring in pregnancy is questionable; AED
levels correlate poorly with seizure control except in the case of phenytoin. Total plasma levels
may be misleading and the relationship between free levels and seizure control is complex.252
Most published reviews and consensus guidelines recommend avoiding routine AED monitoring
in pregnancy.245,253,254 Plasma level monitoring may occasionally be of use when there is concern
about toxicity or adherence to therapy.255
24
D
Dose of AEDs should not be increased routinely in pregnancy but should only be adjusted
on clinical grounds.
þ
Other factors affecting AED levels in pregnancy, eg vomiting, should be considered if
seizure control deteriorates.
þ
Routine monitoring of AED concentrations is not indicated. Measurement can be useful
in the following circumstances: adjustment of phenytoin dose, assessment of adherence
and toxicity.
þ
Interpretation of AED blood levels is best done by a doctor specialising in the management
of epilepsy.
3
4
4 CONTRACEPTION, PREGNANCY AND HRT
4.4
LABOUR
Most women with epilepsy will have a normal labour and vaginal delivery 209,228 but stress, pain,
sleep deprivation, over-breathing and dehydration increase the risk of seizures during labour.
4.4.1
þ
Women with epilepsy should be delivered in a consultant led maternity unit and one to
one midwifery care given during labour.
þ
Factors predisposing to increased risk of seizures in labour should be reduced as much as
possible and there should be a low threshold for epidural anaesthesia.
D
The usual oral AED medication should be continued during labour and postnatally. In
women unable to tolerate oral medication, AEDs can be given by other routes.
þ
An elective Caesarean section should be considered if there have been frequent tonicclonic or prolonged complex partial seizures towards the end of pregnancy.
3
4
SEIZURES IN LABOUR
Up to five percent of women with epilepsy will have a tonic-clonic seizure during labour or the
puerperium.247 In women with no prior history of epilepsy, eclampsia is the most common cause
of seizures in labour. If tonic-clonic seizures occur during labour, maternal hypoxia, fetal hypoxia
and acidosis will result. Status epilepticus (see section 3.11) in labour is associated with maternal
as well as fetal mortality.
3
There are no clinical trials to inform choice of emergency treatment of seizures in labour.
4.5
D
Seizures in labour should be terminated as soon as possible using intravenous lorazepam
or diazepam. If seizures persist, manage as for status epilepticus.
þ
Maternal airway and oxygenation should be maintained at all times.
þ
If there is doubt whether a seizure in labour is due to eclampsia or epilepsy, then, in
addition to intravenous lorazepam or diazepam, a slow intravenous bolus of 4grams
magnesium sulphate over 5-10 minutes followed by 1gram/hour for 24 hours is recommended.
þ
Delivery should be expedited following a seizure during labour, and neonatal expertise
should be available.
ADVICE FOR MOTHERS POSTPARTUM
Following labour, physiological changes associated with pregnancy gradually remit and blood
levels of AEDs may rise; if an increase in AED dose was made in pregnancy this may lead to
toxicity postpartum and AED doses need to be adjusted accordingly.
The postnatal check provides an opportunity to examine the infant for any abnormality and to
discuss contraception and preconception advice for future pregnancies with the mother.
Caring for a young baby is often associated with fatigue and sleep deprivation, both of which can
provoke seizures.
Although injuries to infants from maternal seizures are thought to be uncommon, babies of
women with epilepsy, especially those with myoclonic epilepsies, are at risk. Bathing infants is
potentially hazardous if the mother has seizures associated with loss of awareness.
þ
The pregnant woman who has epilepsy should be encouraged to plan ahead before the
birth of her child, particularly in relation to breastfeeding and safe practice in caring for
the child. The safety of the infant should be paramount.
þ
After the birth a review of the mother’s AED therapy should be undertaken.
25
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
4.6
þ
Advice regarding contraception, the need for planning future pregnancies, folate requirements
and risks associated with AEDs in pregnancy should be offered at the postnatal visit.
þ
Extra support should be available to mothers who have a physical or learning disability.
ADVICE ABOUT BREASTFEEDING
Blood levels of AEDs in infants who are breastfed are probably lower than in utero provided the
infant is healthy and born close to term. Accumulation of AEDs may occur in the neonate as
mechanisms for drug elimination are not fully developed at birth. AEDs will pass into the breast
milk at varying levels but breastfeeding and subsequent weaning usually allow for a gradual
withdrawal.256-258
4.7
þ
All mothers should be encouraged to breastfeed and receive support from their health
visitor, midwife and GP.
þ
The possibility of sedation should be considered in infants of mothers taking phenobarbital.
RISKS OF INHERITING EPILEPSY
Chromosomal and single gene disorders causing epilepsy are rare, and the genetics of most
epilepsies are complex with multiple genes involved and interaction with environmental factors.
The risks of passing on epilepsy are higher for mothers with idiopathic than with symptomatic
epilepsies.
4.7.1
IDIOPATHIC GENERALISED EPILEPSIES (IGE)
Based on retrospective studies the risk of any type of seizure in a child of a mother with IGE is 48%; in a child of a father with IGE, the risk is only slightly higher than that of the general
population.259 When more than one first degree relative is affected the risk of a child being
affected will be higher, and may sometimes approach 30% or more.
Multiple genes influence the phenotypes of idiopathic generalized epilepsy.260 The genetic
susceptibility in IGE increases the risk of epilepsy associated with cerebral palsy as well as of
IGE. The genetic contribution to epilepsy appears limited to epilepsy with onset aged under 35
years.261,262 Photosensitive epilepsy is inherited in an autosomal dominant manner with agedependent penetrance of the photoparoxysmal response. During maximum penetrance between
the ages of 5 and 15, 50% of children of a photosensitive parent, will be photosensitive. 263
4.7.2
FOCAL EPILEPSIES
In relatives of patients with symptomatic focal epilepsy, there is no evidence for a significantly
increased risk of epilepsy.261,262 In idiopathic focal epilepsies the risks are higher. For example in
autosomal dominant nocturnal frontal lobe epilepsy the risk of a child developing this disorder
may be up to 50% depending on penetrance.264
4.7.3
2+
3
4
FEBRILE CONVULSIONS
Susceptibility to febrile convulsions also follows a multifactorial polygenic mode of inheritance
with a maternal preponderance in transmission. There is a 27% risk in a child with an affected
mother and 6% with an affected father.265 Population based studies indicate that 2-7% of children
with febrile seizures will go on to develop epilepsy with afebrile seizures, the risk being higher
with complicated febrile convulsions.266
In general the risk of epilepsy developing in the children of parents with epilepsy is low.
D
26
2+
3
4
A comprehensive family history of epilepsy should be taken and expert advice on the
genetics of epilepsy should be available as required.
3
4
4 CONTRACEPTION, PREGNANCY AND HRT
4.8
HORMONE REPLACEMENT THERAPY (HRT)
Information about the effects of the menopause on epilepsy is limited but there is evidence to
suggest that some women experience an increase in seizure frequency at this time.267 HRT may
improve seizure control in those who previously experienced catamenial epilepsy (seizures with
menstruation) but others may experience an increase in their seizure frequency on HRT.268,269
The benefit of HRT (oestrogen with or without progesterone) in reducing the risk of osteoporosis
and hip fracture is well recognised.270 Women who have taken AEDs are known to be at increased
risk of hip fractures.142
2+
3
4
Enzyme-inducing AEDs (see Table 6) reduce the efficacy of standard doses of HRT.
D
Women should be aware that their seizure pattern may change at the time of the
menopause.
D
HRT should be prescribed for the same indications as in women who do not have epilepsy.
27
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
5
Models of care
5.1
MODELS OF PRIMARY AND SHARED CARE FOR EPILEPSY
There are few models of care for epilepsy in primary care described in the literature. These have
been practice-based descriptions but there has been no general adoption of any particular model.
Several descriptive studies have indicated the shortfalls of epilepsy management in primary care.
Only 37% of epileptic patients have consulted their GP about their illness within the last year,
with “little evidence of any regular review being undertaken” and “counselling about non-clinical
aspects... is ... inadequate”.271
Such shortfalls are reflected in descriptive studies of patients’ views. “Only around a fifth of
patients felt that their care is being (properly) shared between hospital and general practice”, and
“provision of information (about epilepsy) is perceived to be poor at all levels”.272 “In conclusion
general practice care for epilepsy is still reactive”.273
However, “most people with epilepsy (67.6%) would prefer their care to be community based,
especially older patients and patients with mild epilepsy”.272 Also “61% of patients would
prefer their care to be shared between primary and secondary services”.273
The primary care needs of patients with epilepsy have been well stated in a UK epilepsy needs
document.274 These include the suggestion of a structured annual review, as has now become
common with other chronic diseases, such as asthma and diabetes. Suggested tasks for primary
care are listed in the document. Implementation of such management in primary care would be
facilitated by the deployment of specialist epilepsy nurses, who can liaise between primary care
and hospital care, and promote a shared care model.272
28
D
A structured management system for epilepsy should be established in primary care. As
with other chronic diseases, an annual review is desirable.
D
The annual review would be facilitated and enhanced by the deployment of specialist
epilepsy nurses, linking primary care to the hospital system (shared care).
D
The shared care management system adopted should seek to:
n
identify all patients with epilepsy, register/record basic demographic data, validate
the classification of seizures and syndromes
n
make the provisional diagnosis in new patients, provide appropriate information and
refer to a specialist centre
n
monitor seizures, aiming to improve control by adjustment of medication or rereferral to hospital services
n
minimise side effects of medications and their interactions
n
facilitate structured withdrawal from medication where appropriate, and if agreed by
the patient
n
introduce non-clinical interventions, and disseminate information to help improve
quality of life for patients with epilepsy
n
address specific women’s issues and needs of patients with learning disabilities.
þ
Healthcare professionals, at all levels, should be aware of the valuable contribution which
can be made by Voluntary Sector Field Workers.
3
5 MODELS OF CARE
5.2
MODELS OF SECONDARY AND TERTIARY CARE FOR EPILEPSY
5.2.1
ROLE OF EPILEPSY CLINICS
The need for clinical epilepsy services is outlined in Annex 3.
A Cochrane review examined the evidence for the effectiveness of epilepsy clinics in comparison
to medical clinics.275 Only one randomised trial was identified and this was excluded on
methodological grounds. Therefore, relevant clinical studies have not yet been undertaken to
establish the effectiveness of epilepsy clinics.
Current preferred practice is for epilepsy clinics to be developed in hospitals. These clinics
provide the expertise of epilepsy specialists, epilepsy specialist nurses, access to further specialised
investigations and, when necessary, to inpatient facilities. Epilepsy clinics also have important
roles in teaching and research in epilepsy.
There are two broad roles for epilepsy clinics:
n
assessment and management of recent-onset epilepsy
n
care of patients with drug-resistant epilepsy.
Some epilepsy centres have developed further specialisation of the epilepsy clinics such as ‘fasttrack’ clinics for early diagnosis, clinics for epilepsy in children, in young people, in pregnancy,
and in learning disability.
5.3
þ
Services should be provided in acute hospitals (or the new Ambulatory Care and Diagnostic
Centres (ACADs)) to enable patients with probable recent-onset seizures to be seen within
two weeks of onset.
þ
Hospitals should provide services to review people with drug-resistant epilepsy.
þ
Subspecialty epilepsy clinics should also be available to meet the needs of specific
groups of patients (epilepsy in learning disability, in pregnancy, in adolescence and in
potential surgical candidates).
ROLE OF EPILEPSY NURSE SPECIALISTS
The Joint Epilepsy Council276 noted that epilepsy specialist nurses are cost effective, a point also
highlighted by another study.277 Epilepsy nurses can also reduce the length of stay in hospital for
people with epilepsy and increase patient satisfaction.277
A Cochrane review concluded that although the potential benefits of epilepsy nurses varied in all
studies reviewed, there was a perceived higher quality of care, less time spent on travel, reduction
of the waiting times, and better continuity of care noted by the patients who had contact with an
epilepsy nurse specialist.278
High-quality studies have not yet been performed to identify the effectiveness of epilepsy specialist
nurses. In the studies reviewed, no roles performed by epilepsy nurse specialist were shown to be
detrimental. Consensus opinion agrees that they are a fundamental element of a multidisciplinary
epilepsy team, working alongside consultants playing a part in the assessment and diagnostic
process and alongside counsellors establishing the quality of life impact on the patient as well as
giving advice and support.279
2++
2+
4
One study showed that patients seen by an epilepsy nurse specialist were more likely to have
discussed general epilepsy topics and less likely to report missing taking their medication.280
Patients and carers are also reported to benefit from nurse specialists who were readily accessible
and had time to discuss patients’ problems, and who could act as the patients’ advocates.281
Another study showed that 70% of patients with epilepsy attending clinics run by epilepsy nurse
specialists had previously unidentified problems successfully resolved by the nurse including
misdiagnosis, overmedication and lack of awareness of drug side effects.282
The role of epilepsy nurses generally follows the wider role of the specialist nurse and includes:
support and information for the patient, carer and family; provision of up-to-date information
29
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
and advice; support and information for the multidisciplinary team involved in the patients’
care; education for statutory and voluntary organisations and a source of expert knowledge. More
specific roles include adjusting medication, ordering relevant tests, and patient review on return
clinic visits.
Just as it is essential to have a clinician who is a specialist in epilepsy leading the epilepsy unit,
having epilepsy nurse specialists can enhance the quality of life for patients and seems to give
more of a patient-centred approach to their care.
þ
30
Each epilepsy team should include epilepsy nurse specialists.
6 INFORMATION FOR DISCUSSION WITH PATIENTS AND CARERS
6
Information for discussion with patients
and carers
This section of the guideline is intended to highlight the main issues that healthcare professionals
should discuss with patients and carers. It is based on the best available evidence of what is
effective.
6.1
ADVICE AND INFORMATION ON EPILEPSY
People with epilepsy and carers have a need for clear, accurate and appropriate information and
advice. Surveys have reported that up to 90% of patients want more information and felt that
they had received little advice about the cause of epilepsy, effects and interactions of drugs and
the avoidance of potentially dangerous situations.283,284 Conversely, it is known that patients can
forget or fail to take in much of what they are told during clinic visits so written information,
helpline telephone numbers and contact details of voluntary organisations should be given to all
patients.
Almost as important as the quality of information is the manner in which it is given. Many
patients prefer talking to an epilepsy nurse or someone from a voluntary organisation with whom
they feel more at ease.285 Some information may have to be repeated on different occasions to
ensure understanding. A general information leaflet should be given to all patients at the time of
diagnosis. Checklists and tests of epilepsy knowledge are available from support organisations. A
recent study concluded that information for patients should be suited to their understanding,
making adjustments for different socio-cultural contexts.286 It should be noted that children are
frequently carers of a parent with epilepsy, and need to be given proper support. Patients with
epilepsy place great importance on having a doctor who is approachable, communicative and
knowledgeable and on receiving adequate information on their condition.287
3
4
Guidelines for teachers have been produced by Epilepsy Scotland. A recent survey found that
there had been little improvement in information provision despite the problem having been
highlighted previously.288 It was concluded that reducing the information deficit would significantly
reduce the morbidity associated with epilepsy.
þ
Information should be given in an appropriate manner with sufficient time to answer
questions. The type of information given should be recorded in the patient notes.
þ
Information should be repeated over time and reinforced to ensure understanding.
þ
Patients should be given information to take home in the most suitable format eg leaflets,
factsheets, video or specialised material for people with learning disability, making
adjustments for different socio-cultural contexts.
D
A checklist should be used to help healthcare professionals to give patients and carers the
information they need in an appropriate format.
31
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
6.1.1
EXAMPLE INFORMATION CHECKLIST
Example checklist that can be used by healthcare professionals to identify what information to
give patients and carers:
q
q
q
General epilepsy information
explanation of what epilepsy is*
probable cause
explanation of investigative procedures
classification of seizures*
syndrome
epidemiology
prognosis*
genetics
Sudden Unexpected Death in Epilepsy
(SUDEP)*
Antiepileptic drugs
choice of drug*
efficacy*
side effects*
adherence*
drug interactions*
free prescriptions*
Seizure triggers
lack of sleep*
alcohol and recreational drugs*
stress*
photosensitivity
q
First Aid
general guidelines*
status epilepticus
q
Format
appropriate language
appropriate size
appropriate level of comprehension
appropriate format
q
Issues for women
contraception*
pre-conception*
pregnancy and breastfeeding*
menopause
q
Lifestyle
driving regulations*
employment
education (eg ES guidelines for teachers)
leisure
relationships
safety in the home*
q
Possible psychosocial consequences
perceived stigma*
memory loss*
depression
anxiety
maintaining mental well being
self esteem*
sexual difficulties
q
Support organisations
addresses and telephone numbers of
national and local epilepsy
organisations* (see Section 6.2)
* Items marked with an asterisk are considered essential information. The other material
should be given when it is relevant. Patient information is readily available from the websites
listed in Section 6.2.
32
6 INFORMATION FOR DISCUSSION WITH PATIENTS AND CARERS
6.2
LIST OF USEFUL CONTACT DETAILS INCLUDING WEB-BASED INFORMATION
Epilepsy Scotland
48 Govan Road, Glasgow G51 1JL
Helpline: 0808 800 2200 Fax: 0141 419 1709
E-mail: [email protected] Website: www.epilepsyscotland.org.uk
The National Society for Epilepsy
Chesham Lane, Chalfont St Peter, Bucks SL9 0RJ
Helpline: 01494 601400 Tel: 01494 601300 Fax: 01494 871927
Website: www.epilepsynse.org.uk
Epilepsy Bereaved (for the relatives of people who have died from epilepsy)
PO Box 112, Wantage, Oxon OX12 8XT
Bereavement Support Contact Line -24 hour answering service: 01235 772852
Tel: 01235 772850
Email: [email protected] Website: www.sudep.org
Quarriers (residential epilepsy assessment centre and information on Quarriers Epilepsy
Fieldwork Services)
Hunter House, Quarriers Village, Bridge of Weir, Renfrewshire PA11 3SX
Tel: 01505 616006
Email: [email protected] Website: www.quarriers.org.uk
Epilepsy Action
New Anstey House, Gate Way Drive,Yeadon, Leeds LS19 7XY
Helpline: 0808 800 5050 Free Fax: 0808 800 5555
Email: [email protected] Website: www.epilepsy.org.uk
Enlighten - Action for Epilepsy
5 Coates Place, Edinburgh EH3 7AA
Tel: 0131 226 5458 Fax: 0131 220 2855
Email: [email protected]
Epilepsy Connections
100 Wellington Street, Glasgow G2 6DH
Tel: 0141 248 4125 Fax: 0141 248 5887
Website: www.epilepsyconnections.org.uk
Joint Epilepsy Council of the UK and Ireland
Tel: 01943 871 852
Website: www.jointepilepsycouncil.org.uk
Epilepsy Pregnancy Register
Tel: 0800 3891248
NHS 24
Nurse-led helpline: 08454 24 24 24
33
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
7
Implementation and audit
7.1
LOCAL IMPLEMENTATION
Implementation of national clinical guidelines is the responsibility of local NHS organisations
and is an essential part of clinical governance. It is acknowledged that not every guideline can be
implemented immediately on publication, but mechanisms should be in place to ensure that the
care provided is reviewed against the guideline recommendations and the reasons for any differences
assessed and, where appropriate, addressed. These discussions should involve both clinical staff
and management. Local arrangements may then be made to implement the national guideline in
individual hospitals, units and practices, and to monitor adherence. This may be done by a
variety of means including patient-specific reminders, continuing education and training, and
clinical audit. Managed Clinical Networks for epilepsy are being developed.
7.2
KEY POINTS FOR AUDIT
Diagnosis
n
n
n
n
n
n
n
n
n
time to specialist assessment following first seizure
proportion of first seizure patients seeing an epilepsy specialist
time to EEG
time to brain imaging
proportion of patients having MRI and CT
proportion of patients seeing an epilepsy nurse specialist when diagnosis discussed
proportion of patients and carers receiving written information when diagnosis discussed
accuracy of diagnosis of epilepsy, seizure classification and epilepsy syndrome classification
appropriateness of EEG requests.
Treatment
n
n
n
n
n
n
n
n
n
proportion in which treatment recommended by a specialist with an interest in epilepsy
proportion of patients seizure free
number on monotherapy, two, three and four drugs
drug appropriate for seizure type(s)
information on adverse AED effects given and documented
drugs levels only done for appropriate indications
discussion of AED withdrawal or continuation in those seizure free more than 2 years
surgery considered in those established to be drug resistant
existence and use of local protocol for management of status epilepticus.
Contraception, pregnancy and HRT
n
n
n
n
34
documentation of:
- contraceptive advice
- preconceptual counselling
- risks of epilepsy and antiepileptic drugs in pregnancy
- advice about care of baby and breastfeeding
proportion of pregnant women taking folic acid appropriately
proportion of infants given vitamin K1 at birth
proportion of pregnant women receiving appropriate ultrasound scanning.
7 IMPLEMENTATION AND AUDIT
Models of care
n
n
n
n
extent to which data on measures above routinely shared between primary and secondary care
proportion of patients in primary care
- receiving structured annual review
- with documentation within past year of:
- seizure frequency
- last seizure
- drug adverse effects
- review of medication
access to epilepsy nurse specialist
secondary care
- availability and speed of access to specialist first seizure clinics
- availability and speed of access to specialist epilepsy clinic
- availability and speed of access to subspecialty joint clinics (teenage, pregnancy)
- availability and speed of access to specialist investigations.
35
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
8
Outcome measures
A recent systematic review of methodology and reporting standards for quality of life and
behavioural outcome measures in epilepsy found that from 46 RCTs of AEDs, a total of 52
different measures were used. There was a failure to apply such measures in a consistent manner
and due to the wide variety of measures used, it is not possible to make valid comparisons
between studies and consequently to draw any meaningful conclusions about the effect of AEDs
on behaviour or quality of life.289
3
4
The Commission on the Outcome Measurement in Epilepsy (COME report) highlighted that
behavioural outcome measures have been used selectively for assessment of therapeutic approaches,
assessment of impairments, disabilities and handicaps and assessment of ongoing treatment.290,291
8.1
SEIZURE FREQUENCY
The COME report stated that “When measured as a continuous variable, seizure frequency is by
far the most sensitive measure of efficacy and should be used whenever possible”. This information
is most commonly gathered through patient diaries, which have been found to vary considerably
in quality. Alternatives to the reporting of seizure frequency have included percentage reduction
in seizures, the categorisation of seizure frequency into percentage groups or time to first seizure
recurrence.290
D
8.2
Assessments should always include seizure frequency and date of last seizure.
SEIZURE SEVERITY SCALES
With regards to seizure severity, three frequently-used measurement scales were highlighted by
COME: The Veterans Administration Seizure Frequency and Rating Scale, The Liverpool Seizure
Severity Scale and the National Hospital Seizure Severity Scale. There was little evidence of
sensitivity to change and until more data is available no seizure severity scale can be recommended
as a standard outcome measure in clinical trials.290
8.3
ASSESSMENT OF THE INTERICTAL STATE- ADVERSE EVENTS
A number of Adverse Events scales have been developed. COME highlighted the Veterans
Administration Systemic and Neurotoxicity Scale to evaluate common problems caused by AEDs
and the Veterans Administration Composite Rating Scale which provides a composite score that
represents the patient’s overall status. The Liverpool Adverse Events Profile covers similar areas
and has some evidence of sensitivity to change. COME recommended that further work is required
in order to improve and expand the assessment of adverse events.
8.4
NEUROPSYCHOLOGICAL ASSESSMENT
COME recognised the importance of determining the effects of AEDs on cognition, although
clinical investigations to date have been limited due to failures to adhere to basic standards of
method, design, analysis and neuropsychological evaluation. A systematic review of RCTs which
evaluated neuropsychological outcome of AEDs found that 98 different tests had been used and
only five were used in more than one study. Of these, only two test batteries were developed and
standardised specifically for epilepsy (Dodrill’s Neuropsychological Battery and the FePsy system).138
36
4
8 OUTCOME MEASURES
8.5
QUALITY OF LIFE
There are three main reasons for difficulty in drawing consistent conclusions from existing quality
of life (QoL) research. Firstly, there is a lack of consistency regarding the implementation of QoL
measures. A systematic review of methodology of quality of life and behavioural outcome measures
in epilepsy, reported that often no reason was provided for test selection and when generic
measures were used, there was little evidence of their reliability, validity or sensitivity in this
population.289 Secondly, many domains in epilepsy-specific measures are important to people
with epilepsy but are not amenable to change during a clinical trial eg driving. Finally, most of
the available evidence on QoL measures relates to instrument validation rather than concerning
their practical use. Consequently it is difficult to assess the level of change that would be
clinically meaningful.289-291
8.6
CONCLUSIONS
The COME report concluded that the International League Against Epilepsy should establish
clear recommendations for minimum standards for the use of outcome measures in clinical trials
and practice. There should be uniformity in the selection of measures with evidence of reliability,
validity and sensitivity to change. Reporting of the outcomes should also be standardised. The
aims of the measurements, the rationale for selecting a particular measure, the psychometric
properties of the scale and its previous application to epilepsy should be considered. Caution
should also be taken with regard to the use of outcome measures in routine clinical practice.
Indeed, COME states that “the assessment of seizure response in routine clinical practice, for the
most part, still relies on clinical judgement, a nebulous but pragmatic reality of treating an
individual patient”.290
In conclusion, there is no single outcome scale that can be recommended for use in clinical
practice.
þ
The assessment of seizure severity, adverse effects and the impact of epilepsy on the
quality of life should be considered in assessing individuals in clinical practice. Care
should be taken to use appropriate outcome measures.
37
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
9
Development of the guideline
9.1
INTRODUCTION
SIGN is a collaborative network of clinicians, other healthcare professionals, and patient
organisations, funded by NHS Quality Improvement Scotland. SIGN guidelines are developed by
multidisciplinary groups of practising clinicians using a standard methodology based on a
systematic review of the evidence. Further details about SIGN and the guideline development
methodology are contained in “SIGN 50: A Guideline Developer’s Handbook”, available at
www.sign.ac.uk
9.2
THE GUIDELINE DEVELOPMENT GROUP
Dr Richard Roberts
Chairman
Dr Maria Elena Farrugia
Secretary
Ms Sheena Bevan
Professor Martin Brodie
Ms Eleanor Caldwell
Ms Francesca Chappell
Dr Roger Cull
Dr Duncan Davidson
Dr Rod Duncan
Dr Ali El-Ghorr
Dr Janet Fitton
Dr Linda Gerrie
Dr Rod Gibson
Dr Ruth Gillham
Dr Margaret Jackson
Dr Stewart Jarvie
Ms Hilary Mounfield
Ms Fiona Needleman
Ms Angela Norman
Dr Anne O’Hare
Dr Mary O’Regan
Dr Andrew Orr
Dr Pauline Robertson
Dr Norman Smith
Dr Linda Stephen
Consultant Neurologist, Ninewells Hospital, Dundee
Specialist Registrar, Ninewells Hospital, Dundee
Quarriers Epilepsy Fieldworker, Aberdeen
Director, Epilepsy Unit, Western Infirmary, Glasgow
Patient Representative, Stirling
Information Officer, SIGN
Consultant Clinical Neurophysiologist,
Western General Hospital, Edinburgh
Consultant Neurologist, Ninewells Hospital, Dundee
Lead Clinician, West of Scotland Regional Epilepsy Service
Programme Manager, SIGN
General Practitioner, Strathdon Medical Centre, Aberdeenshire
Consultant Neurologist, Aberdeen Royal Infirmary
Consultant Neuroradiologist,
Western General Hospital, Edinburgh
Neuropsychologist, Southern General Hospital, Glasgow
Consultant Neurologist, Royal Victoria Infirmary, Newcastle
Clinical Psychologist, Leverndale Hospital, Glasgow
Chief Executive, Epilepsy Scotland
Senior Pharmacist, Southern General Hospital, Glasgow
Epilepsy Nurse Specialist, Ryehill Health Centre, Dundee
Consultant Paediatrician, Community Child Health, Edinburgh
Consultant Paediatric Neurologist, Glasgow
General Practitioner, Montrose
Consultant Psychiatrist, Eastern General Hospital, Edinburgh
Consultant Obstetrician, Aberdeen Maternity Hospital
Deputy Director, Epilepsy Unit, Western Infirmary, Glasgow
The membership of the guideline development group was confirmed following consultation
with the member organisations of SIGN. Declarations of interests were made by all members of
the guideline development group. Further details are available from the SIGN Executive. Guideline
development and literature review expertise, support, and facilitation were provided by the SIGN
Executive.
38
9 DEVELOPMENT OF THE GUIDELINE
9.3
SYSTEMATIC LITERATURE REVIEW
The evidence base for this guideline was synthesised in accordance with SIGN methodology. A
systematic review of the literature was carried out using an explicit search strategy devised by a
SIGN Information Officer. Databases searched include Medline, Embase, Healthstar, Cinahl,
PsychINFO, and the Cochrane Library. The year range covered was 1996-2001. Internet searches
were carried out on various websites including the New Zealand Guidelines Programme, the UK
Health Technology Assessment programme, and the US National Guidelines Clearinghouse. The
Medline version of the main search strategies can be found on the SIGN Website, in the section
covering supplementary guideline material. The main searches were supplemented by material
identified by individual members of the development group. All selected papers were evaluated
by two members of the group using standard SIGN methodological checklists before conclusions
were considered as evidence.
9.4
CONSULTATION AND PEER REVIEW
9.4.1
NATIONAL OPEN MEETING
A national open meeting is the main consultative phase of SIGN guideline development, at
which the guideline development group present their draft recommendations for the first time.
The national open meeting for this guideline was held on 23 November 2001 and was attended
by around 150 representatives of all the key specialties relevant to the guideline. The draft
guideline was also available on the SIGN Website for a limited period at this stage to allow
those unable to attend the meeting to contribute to the development of the guideline.
9.4.2
SPECIALIST REVIEW
The guideline was reviewed in draft form by a panel of independent expert referees, who were
asked to comment primarily on the comprehensiveness and accuracy of interpretation of the
evidence base supporting the recommendations in the guideline. SIGN is very grateful to all of
these experts for their contribution to this guideline.
Dr Alan Begg
Professor David Chadwick
Professor John Duncan
Dr Morgan Feely
Dr Bill Hall
Ms Sharon Hems
Dr Frank Johnstone
Dr Mike Kerr
Ms Jan Maxwell
Ms Shirley Maxwell
Dr Allan Merry
Dr Grahame Mitchell
Dr Jim Morrow
Ms Alessia Radice
Dr John Reid
Dr Tim Shallcross
Professor Simon Shorvon
Dr Matthew Walker
General Practitioner, Montrose
Consultant in Neurology,
Walton Centre for Neurology and Neurosugery, Liverpool
Consultant in Neurology,
National Hospital for Neurology and Neurosurgery, London
Physician/Clinical Pharmacologist, Leeds General Infirmary
General Practitioner, Settle
Pharmacy Department, St Johns’s Hospital at
Howden, Livingston
Consultant in Obstetrics and Gynaecology, Department of
Obstetrics and Gynaecology, University of Edinburgh
Consultant Neuropsychiatrist, Clinical Studies Unit, Cardiff
Nurse Specialist, Yorkhill NHS Trust
Project Coordinator, Epilepsy Connections, Glasgow
General Practitioner, Ardrossan
General Practitioner, Aultbea
Consultant in Neurology, Belfast City Hospital
Enlighten - Action for Epilepsy, Edinburgh
General Practitioner, Alford
Consultant in General Medicine,
Caithness General Hospital, Wick
Professor of Neurology, National Hospital for
Neurology and Neurosurgery, London
Lecturer in Neurology, Department of Clinical and
Experimental Epilepsy, London
39
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
9.4.3
SIGN EDITORIAL GROUP
As a final quality control check, the guideline is reviewed by an Editorial Group comprising the
relevant specialty representatives on SIGN Council to ensure that the peer reviewers’ comments
have been addressed adequately and that any risk of bias in the guideline development process as
a whole has been minimised. The Editorial Group for this guideline was as follows:
Dr David Alexander
Professor Gordon Lowe
Dr Lesley Macdonald
Mrs Fiona McMillan
Dr Safia Qureshi
Dr Sara Twaddle
Professor Joanna Wardlaw
Dr Peter Wimpenny
British Medical Association Scottish General
Practice Committee
Chairman of SIGN; Co-Editor
Faculty of Public Health Medicine
Royal Pharmaceutical Society
Programme Director, SIGN; Co-Editor
Director of SIGN; Co-Editor
Royal College of Radiologists
School of Nursing and Midwifery,
The Robert Gordon University
Each member of the guideline development group then approved the final guideline for publication.
40
ANNEX 1
Annex 1
Differential diagnosis of epileptic seizures
This includes:
Awake episodes
Normal phenomena
Behavioural phenomena
Paralytic syncope
Cardiac arrhythmias
Other cardiac disorders
Panic attacks
Concussive seizures
Hypoglycaemia
Transient ischaemic
attack (TIA)
Paroxysmal movement
disorders
Tonic spasm of multiple
sclerosis (MS)
Tics
Idiopathic drop attacks
Migrainous aura
Transient global amnesia
déjà vu may be normal
particularly in people with a learning disability
due to impaired autonomic function eg drug effects,
autonomic neuropathy
especially in middle and older age but can occur in the young,
may have prodromal palpitations, pallor is common
can sometimes produce focal neurological features
from low output
fear anxiety, light-headedness, peripheral paraesthesiae,
often in anxiety inducing situations
occurring immediately after a concussive closed head injury,
no risk of recurrence
almost always in diabetes or alcoholics after a binge, causing
stupor, confusion, bizarre behaviour, tremulousness,
occasionally seizures
usually older patients, needs to be differentiated from simple
partial seizures
very rare, presents with sudden choreoathetosis or dystonia,
may be triggered by movement, could be mistaken for partial
motor seizures
with intense focal spasm for less than a minute
or longer, in patients with established MS
multiple tics could be confused with myoclonic jerks, but in
the most important disorder, Gilles de la Tourette Syndrome,
there is also an obsessive compulsive behaviour with
accompanying vocalisations
occurs in middle-aged females, with sudden devastating falls
without loss of consciousness, and therefore differs from the
presentation of atonic seizures in children and young adults
a march of less than a minute suggests partial seizures; over
several minutes suggests migraine
usually >40 years of age, with amnesia lasting from 30
minutes to a few hours
Sleep related episodes
Hypnic jerks
Sleep paralysis
on falling asleep
frightening episodes of paralysis of voluntary movement on
awakening or falling asleep
Exploding head syndrome
sensation of exploding on falling asleep
Periodic movements of sleep older patient, flexion of leg for a few seconds, at intervals of 1060 seconds occurring in clusters for several minutes
Non REM parasomnias
sleep walking, sleep talking
REM parasomnias
often violent behaviours, may be related to dream content
Sleep apnoea
snoring, apnoeic episodes, daytime drowsiness
41
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
Annex 2
Algorithm for treatment
after first tonic-clonic seizure
Secure diagnosis of
first unprovoked
tonic-clonic seizure
Previous myoclonic / absence / partial/
complex partial seizures?
NO
YES
Does patient consider risk of
recurrence (and consequences),
unacceptable and will s/he take
AED therapy? *
YES
NO
Defer
treatment
* Risk of recurrence 66
§ overall risk 30-40%
§ risk highest soon after first seizure: up to 80% after one week
§ >80% risk if EEG shows epileptic discharges
§ >90% risk if patient has tumour/neurological deficit from birth
§ <40% risk if seizures are acute symptomatic
Risk of recurrent epileptic seizures
§ sudden unexplained death
§ accidents
§ extended driving licence withdrawal
Risk of AED therapy
§ side effects - minor 20-30%, life-threatening very rare
§ drug interactions eg oral contraceptive, with enzyme-inducing AEDs
§ teratogenesis (4-6% major malformation with one AED)
42
Treat after
first tonic-clonic
seizure
ANNEX 3
Annex 3
Planning services for epilepsy
Numbers requiring health services
Incidence1
40-70 per 100,000 per annum
400-800 per 100,000
Prevalence of active epilepsy1
Referrals with possible seizures
52% of referred patients definitely have epilepsy
21% possible/probably epilepsy
Mortality293-295
increased two to three-fold about 1,000 deaths in
UK/year during or soon after a seizure, many due to
sudden unexpected death in epilepsy (SUDEP) in
young adults
292
Clinical Standards Advisory Group (CSAG) report (2000)295
Services for Patients with Epilepsy: recommendations
General practice
n
Hospital services
n
n
n
n
n
n
Nurses
Services roles
identify lead GPs for epilepsy services
establish more epilepsy centres, appoint extra
neurologists and epilepsy specialist nurses, make
epilepsy centres a focus for local care, training and
support
improve awareness of, and equity of access to
epilepsy surgery
improve standards of care for epilepsy in A&E
Departments
commission specialty services at supra-regional
level (specialised investigations, surgery,
neuropsychiatry, inpatient care)
establish paediatric epilepsy clinics
improve access to epilepsy services for people
with learning disability
n
develop the role of the epilepsy nurse
n
appoint nurses with learning disability experience
n
clarify the roles of primary and secondary care
n
improve communications between primary,
secondary and tertiary care
43
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
Abbreviations
A&E
ACAD
Ambulatory Care and Diagnostic Centre
ADR
Adverse drug reaction
AED
Antiepileptic drugs
COC
Combined oral contraceptive
COME
Commission on the Outcome Measurement in Epilepsy
CSAG
Clinical Standards Advisory Group
CT
Computed tomography
ECG
Electrocardiography
EEG
Electroencephalography
GP
General Practitioner
GTC
Generalised tonic-clonic
HRT
Hormone replacement therapy
IGE
Idiopathic generalised epilepsy
ITU
Intensive treatment unit
IV
Intravenous
MRI
Magnetic resonance imaging
NTD
Neural tube defects
PE
Phenytoin equivalent
QoL
Quality of life
RCT
Randomised controlled trial
SIGN
SSRI
SUDEP
44
Accident and Emergency
Scottish Intercollegiate Guidelines Network
Selective serotonin re-uptake inhibitor
Sudden unexpected death in epilepsy
REFERENCES
References
1
2
3
4.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
Sander JW, Shorvon SD. Epidemiology of the epilepsies. J Neurol Neuosurg
Psychiatry 1996;61:433-43.
Smith D, Defalla BA, Chadwick DW. The misdiagnosis of epilepsy and the
management of refractory epilepsy in a specialist clinic. QJM 1999;92:15-23.
Scheepers B, Clough P, Pickles C. The misdiagnosis of epilepsy: findings of a
population study. Seizure 1998;7:403-6.
Warlow CP, Sandercock PAG, Hankey GJ, Van Gijn J, Dennis MS, Bamford
J, et al. Stroke: A practical guide to management. 2nd ed. Malden (MA): Blackwell
Science; 2000.
Sander JW, Hart YM, Johnson AL, Shorvon SD. National General Practice
Study of Epilepsy: newly diagnosed epileptic seizures in a general population.
Lancet 1990;336:1267-71.
Royal College of Physicians of Edinburgh. Consensus conference on better
care for children and adults with epilepsy. Final consensus statement.
Edinburgh: The College; 2002. [cited 4 Apr 2003]. Available from url: http:/
/www.rcpe.ac.uk/esd/consensus/better_care_02.html
Proposal for revised clinical and electrencephalographic classification of
epileptic seizres. From the Commission of Classification and Terminology of
the International League against Epilepsy. Epilepsia 1981;22:489-501.
Cutting S, Lauchheimer A, Barr W, Devinsky O. Adult-onset idiopathic
generalized epilepsy: clinical and behavioral features. Epilepsia
2001;42:1395-8.
Reutens DC, Berkovic SF. Idiopathic generalized epilepsy of adolescence: are
the syndromes clinically distinct. Neurology 1995;45:1469-76.
King MA, Newton MR, Jackson GD, Fitt GJ, Mitchell LA, Silvapulle MJ, et al.
Epileptology of the first seizure presentation: a clinical, electroencephalographic,
and magnetic resonance imaging study of 300 consecutive patients. Lancet
1998;352:1007-11.
Johnsen SD, TarbyTJ, Sidell AD. Carbamazepine induced seizures. Neurology
1984;16:392-3.
Delgado-Escueta AV, Enrile-Bacsal F. Juvenile myoclonic epilepsy of Janz.
Neurology 1984;34:285-94.
Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures
and with epilepsy: report of the ILAE Task Force on Classification and
Terminology. Epilepsia 2001;42:796-803.
Quirk JA, Fish DR, Smith SJ, Sander JW, Shorvon SD, Allen PJ. Incidence of
photosensitive epilepsy: a prospective national study. Electroencephalogr Clin
Neurophysiol 1995;95:260-7.
Jennett B. Epilepsy after non-missile head injuries. 2nd ed. London: Heinemann
Medical; 1975.
Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes
of transient cerebral hypoxia. Ann Neurol 1994;36:233-7.
Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and
presyncope in 641 patients. Lancet 2001;357:348-53.
Betts T, Boden S. Diagnosis, management and prognosis of a group of 128
patients with non-epileptic attack disorder. Part 1. Seizure 1992;1:19-26.
Meierkord H, Will B, Fish D, Shorvon S. The clinical features and prognosis
of pseudoseizures diagnosed using video-EEG telemetry. Neurology
1991;41:1643-6.
Thacker K, Devinsky O, Oerrine K, Alper K, Luciano D. Nonepileptic seizures
during apparent sleep. Ann Neurol 1993;33:414-8.
Devinsky O, Sanchez Villasenor F, Vasquez B, Kothari M, Alper K, Luciano D.
Clinical profile of patients with epileptic and non epileptic seizures. Neurology
1996:46;1530-3.
Peguero E, Abou-Khalil B, Fakhoury T, Matthews G. Self injury and
incontinence in psychogenic seizures. Epilepsia 1995;36:586-91.
Leis AA, Ross MA, Summers AK. Psychogenic seizures: ictal characteristics
and diagnostic pitfalls. Neurology 1992;42:95-9.
Doose H, Neubauer BA. Preponderance of female sex in the transmission of
seizure liability in idiopathic generalized epilepsy. Epilepsy Res
2001;43:103-14.
Geyer JD, Payne TA, Drury I. The value of pelvic thrusting in the diagnosis of
seizures and pseudoseizures. Neurology 2000;54:227-9.
Day SC, Cook EF, Funkenstein H, Goldman L. Evaluation and outcome of
emergency room patients with transient loss of consciousness. Am J Med
1982:73;15-23.
Fowle AJ, Binnie CD. Uses and abuses of the EEG in epilepsy. Epilepsia 2000;41
Suppl 3:S10-8.
Marson CA, Zivin LS. Factors related to the occurrence of typical paroxysmal
abnormalities in the EEG records of epileptic patients. Epilepsia
1970 11 361-81.
Salinsky M, Kanter R, Dasheiff RM. Effectiveness of multiple EEGs in supporting
the diagnosis of epilepsy: an operational curve. Epilepsia 1987;28:331-4.
Doppelbauer A, Zeitlhofer J, Zifko U, Baumgartner C, Mayr N, Deecke L.
Occurrence of epileptiform activity in the routine EEG of epileptic patients.
Acta Neurol Scand 1993;87:345-52.
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
Goodin DS, Aminoff MJ. Does the interictal EEG have a role in the diagnosis
of epilepsy? Lancet 1984; 837-9.
Roupakiotis SC, Gatzonis SD, Triantafyllou N, Mantouvalos V, Chioni A,
Zournas C, et al. The usefulness of sleep and sleep deprivation as activating
methods in electroencephalographic recording: contribution to a longstanding discussion. Seizure 2000;9:580-4.
Fountain NB, Kim JS, Lee SI. Sleep deprivation activates epileptiform discharges
independent of the activating effects of sleep. J Clin Neurophysiol
1998;15:69-75.
Gregory RP, Oates T, Merry RT. Electroencephalogram epileptiform
abnormalities in candidates for aircrew training. Electroencephalogr Clin
Neurophysiol 1993;86:75-7.
Zivin L, Marsan CA. Incidence and prognostic significance of “epileptiform”
activity in the EEG of non-epileptic subjects. Brain 1968;91:751-78.
Bridgers SL. Epileptiform abnormalities discovered on electroencephalographic
screening of psychiatric inpatients. Arch Neurol 1987;44:312-6.
Harding GF, Edson A, Jeavons PM. Persistence of photosensitivity. Epilepsia
1997;38:663-9.
van Donselaar CA, Schimsheimer RJ, Geerts AT, Declerck AC. Value of the
electroencephalogram in adult patients with untreated idiopathic first seizures.
Arch Neurol 1992;49:231-7.
Gilliam F, Kuzniecky R, Faught E. Ambulatory EEG Monitoring. J Clin
Neurophysiol 1999;16:111-5.
Krumholz A. Nonepileptic seizures: diagnosis and management. Neurology
1999;53:S76-83.
Kuyk J, Leijten F, Meinardi H, Spinhoven PH, van Dyck R. The diagnosis of
psychogenic non-epileptic seizures: a review. Seizure 1997;6:243-53.
Benbadis SR, Johnson K, Anthony K, Caines G, Hess G, Jackson C, et al.
Induction of psychogenic nonepileptic seizures without placebo. Neurology
2000;55:1904-5.
Jedrzejczak J, Owczarek K, Majkowski J. Psychogenic pseudoepileptic seizures:
clinical and electroencephalogram (EEG) video-tape recordings. Eur J Neurol
1999;6:473-9.
Parra J, Kanner AM, Iriarte J, Gil-Nagel A. When should induction protocols
be used in the diagnostic evaluation of patients with paroxysmal events?
Epilepsia 1998;39:863-7.
Bhatia M, Sinha PK, Jain S, Padma MV, Maheshwari MC. Usefulness of shortterm video EEG recording with saline induction in pseudoseizures. Acta
Neurol Scand 1997;95:363-6.
Stagno SJ, Smith ML. Use of induction procedures in diagnosing psychogenic
seizures. J Epilepsy 1996;9:153-8.
Thompson JL, Ebersole JS. Long-term inpatient audiovisual scalp EEG
monitoring. J Clin Neurophysiol 1999;16:91-9.
Shihabuddin B, Abou-Khalil B, Fakhoury T. The value of combined
ambulatory cassette-EEG and video monitoring in the differential diagnosis of
intractable seizures. Clin Neurophysiol 1999;110:1452-7.
Zaidi A, Clough P, Cooper P, Scheepers B, Fitzpatrick AP. Misdiagnosis of
epilepsy: many seizure-like attacks have a cardiovascular cause. J Am Coll
Cardiol 2000;36:181-4.
Schoenenberger RA, Heim SM. Indication for computed tomography of the
brain in patients with first uncomplicated generalised seizure. BMJ
1994;309:986-9.
Roberts RC, Shorvon SD, Cox TC, Gilliatt RW. Clinically unsuspected cerebral
infarction revealed by computed tomography scanning in late onset epilepsy.
Epilepsia 1988;29:190-4.
Ramirez-Lassepas M, Cipolle RJ, Morillo LR, Gumnit RJ. Value of computed
tomographic scan in the evaluation of adult patients after their first seizure.
Ann Neurol 1984;15:536-43.
Recommendations for neuroimaging evaluation of patients with epilepsy.
Commission on Neuroimaging of the International League Against Epilepsy.
Epilepsia 1997;38:1255-6.
Clinical policy for the initial approach to patients with a chief complaint of
seizure who are not in status epilepticus. American College of Emergency
Physicians. Ann Emerg Med 1997;29:706-24.
Bradford JC, Kyriakedes CG. Evaluation of the patient with seizures: an evidence
based approach. Emerg Med Clin North Am 1997;17:203-20.
Duncan JS. Imaging and epilepsy. Brain 1997;120:339-77.
Andermann F. Brain structure and epilepsy: the impact of modern imaging.
Am J Neuroradiol 1997;8:302-6.
Sitoh YY, Tien RD. Neuroimaging in epilepsy. J Magn Reson Imaging
1998;8:277-88.
Elster AD, Mirza W. MR imaging in chronic partial epilepsy: role of contrast
enhancement. Am J Neuroradiol 1991;12:165-70.
Sanders WP, Silbergleit R, Spickler EM, Barkley GL, Mehta BA. Efficacy of
gadolinium administration in magnetic resonance imaging screening of patients
with complex partial seizures and results of a normal neurologic examination.
Invest Radiol 1995;30:634-7.
Guidelines for neuroimaging evaluation of patients with uncontrolled epilepsy
considered for surgery. Commission on Neuroimaging of the International
League Against Epilepsy. Epilepsia 1998;39:1375-6.
Bronen RA, Fulbright RK, Spencer DD, Spencer SS, Kim JH, Lange RL, et al.
Refractory epilepsy: comparison of MR imaging, CT, and histopathological
findings in 117 patients. Radiology 1996;201:97-105.
45
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
46
Hart YM, Sander JW, Johnson AL, Shorvon SD. National General Practice
Study of Epilepsy: recurrence after a first seizure. Lancet 1990;336:1271-4.
Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA. Risk of
unprovoked seizure after acute symptomatic seizure: effect of status epilepticus.
Ann Neurol 1998;44:908-12.
van Donselaar CA, Geerts AT, Schimsheimer RJ. Idiopathic first seizure in
adult life: who should be treated? BMJ 1991;302:620-3.
Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked
seizure: a quantative review. Neurology 1991;41:965-72.
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; 721-6.
Randomised clinical trial on the efficacy of antiepileptic drugs in reducing the
risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial
Group (FIR.S.T. Group). Neurology 1993;43:478-83.
Gilad R, Lampl Y, Gabbay U, Eshel Y, Sarova-Pinhas I. Early treatment of a
single generalized tonic-clonic seizure to prevent recurrence. Arch Neurol
1996;53:49-52.
Musicco M, Beghi E, Solari A, Viani F. Treatment of first tonic clonic seizure
does not improve the prognosis of epilepsy. (FIRST Group). Neurology
1997;49:991-8.
MacDonald BK, Johnson AL, Goodridge DM, Cockerell OC, Sander J, Shorvon
S. Factors predicting prognosis of epilepsy after presentation with seizures.
Ann Neurol 2000;48:833-41.
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med
2000;342:314-9.
Mattson RH, Cramer JA, Collins JF, Smith DB, Delgado-Escueta AV, Browne
TR, et al. Comparison of carbamazepine, phenobarbital, phenytoin and
primidone in partial and secondary generalised tonic-clonic seizures. New
Engl J Med 1985;313:145-51.
Dam M, Ekberg R, Loyning Y, Waltimo O, Jakobsen K. A double-blind study
comparing oxcarbazepine and carbamazepine in patients with newly
diagnosed previously untreated epilepsy. Epilepsy Res 1989;3:70-6.
Mattson RH, Cramer JA, Collins JF. A comparison of valproate with
carbamazepine for the treatment of complex partial seizures and secondarily
generalized tonic-clonic seizures in adults. N Engl J Med 1992;327:765-71.
Brodie MJ, Richens A, Yuen AW. Double-blind comparison of lamotrigine
and carbamazepine in newly diagnosed epilepsy. UK Lamotrigine/
Carbamazepine Monotherapy Trial Group. Lancet 1995;345:476-9.
Bill PA, Vigonius U, Pohlmann H, Guerreiro CA, Kochen S, Saffer D, et al. A
double-blind controlled trial of oxcarbazepine versus phenytoin in adults
with previously untreated epilepsy. Epilepsy Res 1997;27:195-204.
Guerreiro M, Vigonius U, Pohlmann H, de Manreza ML, Fejerman N,
Antoniuk SA, et al. A double-blind controlled clinical trial of oxcarbazepine
versus phenytoin in children and adolescents with epilepsy. Epilepsy Res 1997;
27:205-13.
Christe W, Kramer G, Vigonius U, Pohlmann H, Steinhoff BJ, Brodie MJ, et al.
A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate
in adults with newly diagnosed epilepsy. Epilepsy Res 1997;26:451-60.
Brodie MJ, Overstall PW, Giorgi L. Mutlicentre, double-blind randomised
comparison between lamotrigine and carbamazepine in elderly patients with
newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group. Epilepsy
Res 1999;37:81-7.
Marson AG, Williamson PR, Hutton JL, Clough HE, Chadwick DW; on behalf
of the epilepsy monotherapy trialists. Carbamazepine versus valproate
monotherapy for epilepsy (Cochrane Review). In: The Cochrane Library, Issue
1, 2003. Oxford: Update Software.
Brodie MJ, Kwan P. The star systems: overview and use in determining
antiepileptic drug choice. CNS Drugs 2001;15:1-12.
Brodie MJ, Dichter MA. Antiepileptic drugs. N Engl J Med 1996;334:168-74.
Brodie MJ, French JA. Management of epilepsy in adolescents and adults.
Lancet 2000;356:323-9.
Kwan P, Brodie MJ. Effectiveness of first antiepileptic drug. Epilepsia
2001;42:1255-60.
Kwan P, Brodie MJ. Neuropsychological effects of epilepsy and antiepileptic
drugs. Lancet 2001;357:216-22.
Wilbur K, Ensom MH. Pharmacokinetic drug interactions between oral
contraceptives and second-generation anticonvulsants. Clin Pharmacokinet
2000;38:355-65.
Stephen LJ, Brodie MJ. Epilepsy in elderly people. Lancet 2000;355:1441-6.
Biton V, Mirza W, Montouris G, Vuong A, Hammer AE, Barrett PS. Weight
change associated with valproate and lamotrigine monotherapy in patients
with epilepsy. Neurology 2001;56:172-7.
Besag FM. Is generic prescribing acceptable in epilepsy.? Drug Saf
2000;23:173-82.
Guberman A, Corman C. Generic substitution for brand name antiepileptic
drugs: a survey. Can J Neurol Sci 2000;27:37-43.
Perucca E, Beghi E, Dulac O, Shorvon S, Tomson T. Assessing risk to benefit
ratio in antiepileptic drug therapy. Epilepsy Res 2000;41:107-39.
Browne TR, Holmes GL. Epilepsy. N Engl J Med 2001;344:1145-51.
Perucca E, Gram L, Avanzini G, Dulac O. Antiepileptic drugs as a cause of
worsening seizures. Epilepsia 1998;39:5-17.
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
Dlugos DJ, Sammel MD, Strom BL, Farrar JT. Response to first drug trial predicts
outcome in childhood temporal lobe epilepsy. Neurology
2001;57:2259-64.
Deckers CLP, Czuczwar SJ, Hekster YA, Keyser A, Kubova H, Meinardi H, et
al. Selection of antiepileptic drug poltherapy based on mechanisms of action:
the evidence reviewed. Epilepsia 2000;41:1364-74.
Kwan P, Sills GJ, Brodie MJ. The mechanisms of action of commonly used
antiepileptic drugs. Pharmacol Ther 2001;90:21-34.
Brodie MJ, Yuen AW. Lamotrigine substitution study: evidence for synergism
with sodium valproate? 105 Study Group. Epilepsy Res 1997;26:423-32.
Pisani F, Oteri G, Russo MF, Di Perri R, Perucca E, Richens A. The efficacy of
valproate-lamotrigine comedication in refractory complex partial seizures:
evidence for a pharmacodynamic interaction. Epilepsia 1999;40:1141-6.
Ferrie CD, Panayiotopoulos CP. The clinical efficacy of vigabatrin in adults.
Rev Contemp Pharmacother 1995;6:457-68.
Marson AG, Kadir ZA, Chadwick DW. New antiepileptic drugs: a systematic
review of their efficacy and tolerability. BMJ 1996;313:1169-74.
Marson AG, Kadir ZA, Hutton JL, Chadwick DW. The new antiepileptic
drugs: a systematic review of their efficacy and tolerability.
Epilepsia 1997;38:859-80.
Leach JP, Brodie MJ. Tiagabine. Lancet 1998;351:203-7.
Marson AG, Kadir ZA, Hutton JL, Chadwick DW. Gabapentin add-on for
drug-resistant partial epilepsy (Cochrane Review). In: The Cochrane Library,
Issue 1, 2003. Oxford: Update Software.
Ramaratnam S, Marson AG, Baker GA. Lamotrigine add-on for drug-resistant
partial epilepsy (Cochrane review). In: The Cochrane Library, Issue 1, 2003.
Oxford: Update Software.
Chaisewikul R, Privitera MD, Hutton JL, Marson AG. Levetiracetam add-on
for drug-resistant localization related (partial) epilepsy (Cochrane Review). In:
The Cochrane Library, Issue 1, 2003. Oxford: Update Software.
Castillo S, Schmidt DB, White S. Oxcarbazepine add-on for drug-resistant
partial epilepsy (Cochrane review). In: The Cochrane Library, Issue 1, 2003.
Oxford: Update Software.
Jette NJ, Marson AG, Hutton JL. Topiramate add-on for drug-resistant partial
epilepsy (Cochrane Review). In: The Cochrane Library, Issue 1, 2003. Oxford:
Update Software.
Kalviainen R, Nousianen I, Mantyjarvi M, Nikoskelainen E, Partanen J, Partanen
K. Vigabatrin, a gabaergic antiepileptic drug, causes concentric visual field
defects. Neurology 1999;53:922-6.
Motte J, Trevathan E, Arvidsson JF, Barrera MN, Mullens EL, Manasco P.
Lamotrigine for generalised seizures associated with the Lennox-Gastaut
syndrome. Lamictal Lennox-Gastaut Study Group. N Engl J Med
1997;337:1807-12.
Beran RG, Berkovic SF, Dunagan FM, Vajda FA, Danta G, Black AB, et al.
Double-blind, placebo-controlled cross-over study of lamotrigine in treatmentresistant generalised epilepsy. Epilepsia 1998;39:1329-33.
Frank LM, Enlow T, Holmes GL, Manasco P, Concannon S, Chen C, et al.
Lamictal (lamotrigine) monotherapy for typical absence seizures in children.
Epilepsia 1999;40:973-9.
Biton V, Montouris GD, Ritter F, Riviello JJ, Reife R, Lim P, et al. A randomised
placebo-controlled study of topiramate in primary generalised tonic-clonic
seizures. Topiramate YTC Study Group. Neurology 1999;52:1330-7.
Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G. A double-blind
randomized trial of topiramate in Lennox-Gastaut syndrome. Topiramate YL
Study Group. Neurology 1999;52:182-7.
Shorvon SD. The handbook of epilepsy treatment. Oxford: Blackwell Science;
2000.
Schmidt D. Clobazam for treatment of intractable epilepsy: a critical assessment.
Epilepsia 1994;35(Suppl.5):S92-5.
Ramsay RE, Detoledo J. Acetazolamide. In: Engle J, Pedley TA, editors. Epilepsy:
A comprehensive textbook. Philadelphia: Lippincott-Raven;
1997. p. 1445-61
McKee PJW, Brodie MJ. Therapeutic drug monitoring. In: Engle J, Pedley TA,
editors. Epilepsy: A comprehensive textbook. Philadelphia: Lippincott-Raven;
1997. p. 1181-94
Jannuzzi G, Cian P, Fattore C, Gatti G, Bartoli A, Monaco F, et al. A multicenter
randomized controlled trial on the clinical impact of therapeutic drug
monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study
Group in Epilepsy. Epilepsia 2000;41:222-30.
Tomson T, Johannessen SI. Therapeutic monitoring of the new antiepileptic
drugs. Eur J Clin Pharmacol 2000;55:697-705.
Temkin NR. Antiepileptogenesis and seizure prevention trials with antiepileptic
drugs: meta-analysis of controlled trials. Epilepsia, 2001;42:515-24.
Schierhout G, Roberts I. Anti-epileptic drugs for preventing seizures following
acute traumatic brain injury (Cochrane Review). In: The Cochrane Library,
Issue 1, 2003. Oxford: Update Software.
McCrory PR, Bladin PF, Berkovic SF. Retrospective study of concussive
convulsions in elite Australian rules and rugby league footballers:
phenomenology, aetiology, and outcome. BMJ, 1997;314:171-4.
Adverse reactions to antiepileptic drugs: a multicenter survey of clinical practice.
Collaborative Group for the Epidemiology of Epilepsy. Epilepsia
1986;27:323-30.
REFERENCES
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
Lawden MC, Eke T, Degg C, Harding GF, Wild JM. Visual field defects associated
with vigabatrin therapy. J Neurol Neurosurg Psychiatry 1999;67:716-22.
Persson LI, Ben-Menachem E, Bengtsson E, Heinonen E. Differences in side
effects between a conventional carbamazepine preparation and a slow-release
preparation of carbamazepine. Epilepsy Res 1990;6:134-40.
Tennis P, Stern RS. Risk of serious cutaneous disorders after initiation of use
of phenytoin, carbamazepine, or sodium valproate: a record linkage study.
Neurology 1997;49:542-6.
Rzany B, Correia O, Kelly JP, Naldi L, Auquier A, Stern R. Risk of StevensJohnson syndrome and toxic necrolysis during first weeks of antiepileptic
therapy: a case control study. Study Group of the International Case Control
Study on Severe Cutaneous Adverse Reactions. Lancet 1999;353:2190-4.
Schlienger RG, Shapiro LE, Shear NH. Lamotrigine-induced severe cutaneous
adverse reactions. Epilepsia 1998;39(Suppl 7):S22-6.
Guberman A, Besag F, Brodie MJ, Dooley J, Duchowny M, Pellock J, et al.
Lamotrigine-associated rash: risk/benefit considerations for adults and children.
Epilepsia 1999;40:985-91.
Blackburn SC, Oliart AD, Garcia Rodriguez LA, Perez Gutthann S.
Antiepileptics and blood dycrasias: a cohort study. Pharmacotherapy
1998;18:1277-83.
Pellock JM, Willmore LJ. A rational guide to routine blood monitoring in
patients receiving anti-epileptic drugs. Neurology 1991;41:961-4.
Van Amelsvoort T, Bakshi R, Devaux CB, Schwabe S. Hyponatremia associated
with carbamazepine and oxcarbazepine therapy: a review. Epilepsia
1994;35;181-8.
Schmidt W. Adverse effects of antiepileptic drugs. New York:
Raven Press; 1982.
König SA, Elger CE, Vassella F, Schmidt D, Bergmann A, Boenigk HE, et al.
Empfehlungen zu blutuntersuchungen und klinischer überwachung zur
früherkennung des valproat-assoziierten . Nervenarzt Schweiz Ärztezeitung
1998;79:580-5.
Schmitz B. Psychiatric syndromes related to antiepileptic drugs. Epilepsia
1999;40(Suppl 10):S65-70.
Reife R, Pledger G, Wu SC. Topiramate as add-on therapy: pooled analysis of
randomized controlled trials in adults. Epilepsia 2000;41(Suppl 1):S66-71.
Cochrane HC, Marson AG, Baker GA, Chadwick DW. Neuropsychological
outcomes in radomized controlled trials of antiepileptic drugs: a systematic
review of methodology and reporting standards. Epilepsia
1998;39:1088-97.
Vermeulen J, Aldenkamp AP. Cognitive side-effects of chronic antiepileptic
drug treatment: a review of 25 years of research. Epilepsy Res 1995;22:65-95.
Lammers MW, Hekster YA, Keyser AA, Meinardi HH, Renier WO, van Lier H.
Monotherapy or polytherapy for epilepsy revisited: a quantitative assessment.
Epilepsia 1995;36:440-6.
Richens A, Rowe DJ. Disturbance of calcium metabolism by anticonvulsant
drugs. BM J 1970;4:73-6.
Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, et al.
Risk factors for hip fracture in white women. Study of Osteoporotic Fractures
Research Group. N Engl J Med 1995;332:767-73.
Andress DL, Ozuna J, Tirschwell D, Grande L, Johnson M, Jacobson AF, et al.
Antiepileptic drug-induced bone loss in young male patients who have seizures.
Arch Neurol 2002;59:781-6.
Stephen LJ, McLellan AR, Harrison JH, Shapiro D, Dominiczak MH, Sills GJ,
et al. Bone density and antiepileptic drugs: a case-controlled study. Seizure
1999;8:339-42.
Randomised study of antiepleptic drug withdrawal in patients in remission.
Medical Research Council Anitepileptic Drug Withdrawal Study Group.
Lancet 1991;337:1175-80.
Prognositic index for recurrence of seizures after remission of epilepsy. Medical
Research Council Anitepileptic Drug Withdrawal Study Group. BMJ
1993;306:1374-8.
Sirven JI, Sperling M, Wingerchuk DM. Early versus late antiepileptic drug
withdrawal for people with epilepsy in remission (Cochrane Review). In: The
Cochrane Library, Issue 1, 2003. Oxford: Update Software.
Goldstein LH Effectiveness of psychological interventions for people with
poorly controlled epilepsy. J Neurol Neurosurg Psychiatry 1997;63:137-42.
Fenwick P. The behavioral treatment of epilepsy generation and inhibition of
seizures. Neurol Clin 1994;12:175-202.
Dahl J, Melin L, Lund L. Effects of a contingent relaxation treatment program
on adults with refractory epileptic seizures. Epilepsia 1987;28:125-32.
Gillham RA. Refractory epilepsy: an evaluation of psychological methods in
outpatient management. Epilepsia 1990;31:427-32.
Schmid-Schonbein C. Improvement of seizure control by psychological
methods in patients with intractable epilepsies. Seizure 1998;7:261-70.
Spector S, Tranah A, Cull C, Goldstein LH. Reduction in seizure frequency
following a short-term group intervention for adults with epilepsy. Seizure
1999; 8:297-303.
Martinovic Z. Adjunctive behavioural treatment in adolescents and young
adults with juvenile myoclonic epilepsy. Seizure 2001;10:42-7.
Jacoby A, Baker GA, Steen N, Potts P, Chadwick DW. The clinical course of
epilepsy and its psychosocial correlates: findings from a U.K. Community study.
Epilepsia 1996;37:148-61.
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
Owen DK, Lewith G, Stephens CR. Can doctors respond to patients’ increasing
interest in complementary and alternative medicine? BMJ 2001;322:154-8.
Scottish Office Department of Health. Complementary medicine and the
National Health Service: an examination of acupuncture, homoeopathy,
chiropractic and osteopathy. Edinburgh: The Stationery Office; 1997.
Kloster R, Larsson PG, Lossius R, Nakken KO, Dahl R, Xiu-Ling X, et al. The
effect of acupuncture in chronic intractable epilepsy. Seizure 1999;8:170-4.
Stavem K, Kloster R, Rossberg E, Larsson PG, Dahl R, Kinge E, et al. Acupuncture
in intractable epilepsy: lack of effect on health-related quality of life. Seizure
2000;9:422-6.
Cott JM. Herb-drug interactions: focus on pharmacokinetics. CNS Spectrums
2001;6:827-32.
Epilepsy Action. Epilepsy information. Living with epilepsy. Complementary
treatments. Leeds: Epilepsy Action; 2003. [cited 7 Apr 2003]. Available from
url: http://www.epilepsy.org.uk/info/compfrm.html
The National Society for Epilepsy. Epilepsy information: Complementary
therapies. Chalfont St Peter: The Society; 2002. [cited 7 Apr 2003]. Available
from url: http://www.epilepsynse.org.uk/pages/info/leaflets/complime.cfm
Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized controlled trial of
surgery for temporal lobe epilepsy. New Engl J Med 2001;345:311-8.
Chilcott J, Howell S, Kemeney A, Rittey CD, Richards C. The effectiveness of
surgery in the management of epilepsy. Sheffield: Trent Institute for Health
Services Research; 1999. Guidance note for purchasers: 99/06.
McIntosh AM, Wilson SJ, Berkovic SF. Seizure outcome after temporal
lobectomy: current research practice and findings. Epilepsia 2001;42:
1288-307.
A randomized controlled trial of chronic vagus nerve stimulation for treatment
of medically intractable seizures. Vagus Nerve Stimulation Study Group.
Neurology 1995;45:224-30.
Shorvon SD. Status epilepticus: its clinical features and treatment in children
and adults. Cambridge: Cambridge University Press; 1994.
Walker MC, Howard RS, Smith SJ, Miller DH, Shorvon SD, Hirsch NP.
Diagnosis and treatment of status epilepticus on a neurological intensive care
unit. QJM 1996;89:913-20.
Walker MC, Smith SJ, Shorvon SD. The intensive care treatment of convulsive
status epilepticus in the UK. Results of national survey and recommendations.
Anaesthesia 1995;50:130-5.
Scholtes FB, Reiner WO, Meinardi H. Generalized convulsive status epilepticus:
causes, therapy and outcome in 346 patients. Epilepsia 1994;35:1104-12.
Howell SJ, Owen L, Chadwick DW. Pseudostatus epilepticus. QJM
1989;71:507-19.
Krishnamurthy KB, Drislane FW. Depth of EEG suppresson and outcome in
barbiturate anesthetic treatment for refractory status epilepticus. Epilepsia
1999;40:759-62.
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-ofhospital status epilepticus. N Engl J Med 2001;345:631-7.
Treiman DM, Meyers PD, Walton NY, Collins JF, Colling C, Rowan AJ, et al.
A comparison of four treatments for generalized convulsive status epilepticus.
N Engl J Med 1998;339:792-8.
Treiman DM. Convulsive Status Epilepticus. Curr Treat Options Neurol
1999;1:359-69.
Bleck TP. Management approaches to prolonged seizures and status
epilepticus. Epilepsia 1999;40(Suppl 1):S59-63.
Prasad A, Worrall BB, Bertram EH, Bleck TP. Propofol and midazolam in the
treatment of refractory status epilepticus. Epilepsia 2001;42:380-6.
Brown LA, Levin GM. Role of propofol in refractory status epilepticus. Ann
Pharmacother 1998;32:1053-9.
Stecker MM, Kramer TH, Raps EC, O’Meeghan R, Dulaney E, Skaar DJ.
Treatment of refractory status epilepticus with propofol: clinical and
pharmacokinetic findings. Epilepsia 1998;39:18-26.
Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status
epilepticus with pentobarbital, propofol, or midazolam: a systematic review.
Epilepsia 2002;43:146-53.
Cereghino JJ, Mitchell WG, Murphy J, Kriel RL, Rosenfeld WE, Trevathan E.
Treating repetitive seizures with a rectal diazepam formulation: a randomised
study. The North American Diastat Study Group. Neurology 1998;51:127482.
Dreifuss FE, Rosman NP, Cloyd JC, Pellock JM, Kuzniecky RI, Lo WD, et al. A
comparison of rectal diazepam gel and placebo for acute repetitive seizures.
N Eng J Med 1998;338:1869-75.
Joint Epilepsy Council. A guideline on training standards for the administration
of rectal diazepam. Leeds: The Council; 2000.
Sterrick M, Foley J. Educating lay carers of people with learning disability in
epilepsy awareness and in the use of rectal diazepam: a suggested teaching
protocol for use by healthcare personnel. Health Bulletin 1999;57: 198-204
Scott RC, Besag FM, Neville BG. Buccal midazolam and rectal diazepam for
treatment of prolonged seizures in childhood and adolescence: a randomised
trial. Lancet 1999;353:623-6.
Scheepers M, Scheepers B, Clarke M, Comish S, Ibitoye M. Is intranasal
midazolam an effective rescue medication in adolescents and adults with severe
epilepsy? Seizure 2000;9:417-22.
47
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
48
Hannah JA, Brodie MJ. Epilepsy and learning disabilities—a challenge for the
next millennium? Seizure 1998;7:3-13.
Coulter DL. Comprehensive management of epilepsy in persons with mental
retardation. Epilepsia 1997;38(Suppl.4):S24-31.
Sillanpaa, M. Epilepsy in the mentally retarded. In: Wallace S, editor. Epilepsy
in children. London: Chapman and Hall Medical; 1996. p. 417-27.
Fischbacher E. Effect of reduction of anticonvulsants on wellbeing. Br Med J
(Clin Res Ed). 1982;285:423-4.
Forsgren L, Edvinsson SO, Nystrom L, Blomquist HK. Influence of epilepsy on
mortality in mental retardation: an epidemiologic study. Epilepsia
1996;37:956-63.
Bird J. Epilepsy and learning disabilities. In: Russell O, editor. The psychiatry of
learning disabilities. London: Royal College of Psychiatrists; 1997. p. 233-44.
Clinical guidelines for the management of epilepsy in adults with an intellectual
disability. Working Group of the International Association of the Scientific
Study of Intellectual Disability. Seizure 2001;10:401-9.
Scottish Executive Education Department. The administration of medicines in
schools. Edinburgh: The Department; 2001. [cited 7 Apr 2003]. Available
from url: http://www.scotland.gov.uk/library3/education/amis-00.asp
Wong ICK, Lhatoo SD. Adverse reactions to new anticonvulsant drugs. Drug
Saf 2000;23:35-56.
Mason PL, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2
cases and review of the literature. Medicine (Baltimore) 2000;79:201-9.
Blain PG, Lane JM. Neurological disorders. In: Davies DM, Ferner RE, De
Glanville H, editors. Davie’s textbook of adverse drug reactions. 5th ed. Oxford:
Chapman and Hall; 1998.
Ball P, Tillotson G. Tolerability of flouroquinolone antibiotics. Past, present
and future. Drug Saf 1995;13:343-58.
Babic T, Zurak N. Convulsions induced by donepezil. J Neurol Neurosurg
Psychiatry 1996;66:410.
In focus: Donepezil (Aricept). Curr Probl Pharmacovigilance 1999;25:7. [cited
7 Apr 2003]. Available from url: http://www.mca.gov.uk/ourwork/
monitorsafequalmed/currentproblems/cpvol25bsec3.htm
In focus: Tramadol (Zydol, Tramake and Zamadol). Curr Probl
Pharmacovigilance 1996;22:11. [cited 7 Apr 2003]. Available from url: http:/
/www.mca.gov.uk/ourwork/monitorsafequalmed/currentproblems/
cp11.htm
Hyponatraemic convulsions in patients with enuresis treated with vasopressin.
Curr Prob in Pharmacovigilance 1996:22;4.
Convulsions due to quinolone antimicrobial agents. Curr Prob in
Pharmacovigilance 1991;32:2.
Curran S, de Pauw K. Selecting an antidepressant for use in a patient with
epilepsy. Safety considerations. Drug Saf 1998;18:125-33.
Schwab M, Ruder H. Hyponatraemia and cerebral convulsions due to DDVAP
administration in patients with enuresis nocturna or urine concentration testing.
Eur J Paediatr 1997;156:668.
Hyser CL, Drake ME Jr. Status epilepticus after baclofen withdrawal. J Natl
Med Assoc 1984;76:533-8.
Barker I, Grant IS. Convulsions after abrupt withdrawal of baclofen. Lancet
1983;2:556-7.
British Medical Association, Royal Pharmaceutical Society of Great Britain.
British National Formulary 44. London: The Association, The Society; 2002.
[cited 11 Feb 2003]. Available from url: http://www.bnf.org
Fairgrieve SD, Jackson M, Jonas P, Walshaw D, White K, Montgomery TL, et
al. Population based, prospective study of the care of women with epilepsy
in pregnancy. BMJ 2000;321:674-5.
Coulam CB, Annegers JF. Do anticonvulsants reduce the efficacy of the oral
contraceptive? Epilepsia 1979;20:519-25.
Trussell J, Hatcher RA, Cates W Jr, Stewart FH, Kost K. A guide to interpreting
contraceptive efficacy studies. Obstet Gynecol 1990;76:558-67.
Orme M, Crawford P, Back D. Contraception, epilepsy and pharmacokinetics.
In: Trimble MR, editor. Women and epilepsy. Chichester: John Wiley and
Sons; 1991.
Crawford P, Appleton R, Betts T, Duncan J, Guthrie E, Morrow J. Best practice
guidelines for the management of women with epilepsy. The Women with
Epilepsy Guidelines Development Group. Seizure 1999;8:201-17.
Shorvon SD, Tallis RC, Wallace HK. Antiepileptic drugs: coprescription of
proconvulsant drugs and oral contraceptives: a national study of antiepileptic
drug prescribing practice. J Neurol Neurosurg Psychiatry 2002;72:114-5.
Guillebaud J. The pill: and other forms of hormonal contraception. 5th ed.
Oxford: Oxford University Press; 1997.
Patsalos PN, Duncan JS, Shorvon SD. Effect of the removal of individual
antiepileptic drugs on antipyrine kinetics, in patients taking polytherapy. Br J
Clin Pharmacol 1988;26:253-9.
Crawford P, Chadwick D, Martin C, Tjia J, Back D, Orme M. The interaction
of phenytoin and carbamazepine with combined oral contraceptive steroids.
Br J Clin Pharm 1990;30:892-6.
Klosterskov Jensen P, Saano V, Haring P, Svenstrup B, Menge GP. Possible
interaction between oxcarbazepine and an oral contraceptive. Epilepsia
1992;33:1149-52.
Back D, Orme M. Pharmacokinetic drug interactions with oral contraceptives.
Clin Pharmcokinet 1990;18:472-84.
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;38:317-23.
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
Eldon MA, Underwood BA, Randinitis EJ, Sedman AJ. Gabapentin does not
interact with a contraceptive regimen of norethindrone acetate and ethinyl
estradiol. Neurology 1998;50:1146-8.
Holdich T, Whiteman P, Orme M, Back D, Ward D. Effect of Lamotrigine on
the pharmacology of the combined oral contraceptive pill [abstract]. Epilepsia
1991;32:96.
Wilbur K, Ensom MH. Pharmacokinetic drug interactions between oral
contraceptives and second-generation anticonvulsants. Clin Pharmcokinet
2000;38:355-65.
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;33:23-9.
Haukkamaa M. Contraception by Norplant subdermal capsules is not reliable
in epileptic patients on anticonvulsant treatment. Contraceptive
1986;33:559-65.
Levonelle-2 for emergency contraception. Drug Ther Bull 2000;38:75-7.
Wallace H, Shorvon S, Tallis R. Age-specific incidence and prevalence of treated
epilepsy in an unselected population of 2,052,922 and age-specific fertilitly
rates of women with epilepsy. Lancet 1998;352:1970-3.
Olafsson E, Hallgrimsson JT, Hauser WA, Ludvigsson P, Gudmundsson G.
Pregnancies of women with epilepsy: a population-based study in Iceland.
Epilepsia 1998;39:887-92.
Department of Health. Why mothers die. Report on confidential enquiries
into maternal deaths 1994-1996. London: The Stationery Office; 1998. [cited
7 Apr 2003]. Available from url: http://www.archive.official-documents.co.uk/
document/doh/wmd/wmd-hm.htm
Samren EB, van Duijn CM, Koch S, Hiilesmaa VK, Klepel H, Bardy AH, et al.
Maternal use of antiepileptic drugs and the risk of major congenital
malformations: a joint european prospective study of human teratogenesis
associated with maternal epilepsy. Epilepsia 1997;38:981-90.
Holmes LB, Harvey EA, Coull BA, Huntington KB, Khoshbin S, Hayes AM, et
al. The teratogenicity of anticonvulsant drugs. N Engl J Med 2001;
344:1132-8.
Kaneko S, Battino D, Andermann E, Wada K, Kan R, Takeda A, et al. Congenital
malformations due to antiepileptic drugs. Epilepsy Res 1999;33:145-58.
Craig J, et al. The UK pregnancy register: update of results 1996-2002 [abstract].
Epilepsia 2002;43(Suppl 8):Abstract 079.
Rosa FW. Spina bifida in infants of women treated with carbamazepine during
pregnancy. N Engl J Med 1991;324:674-7.
Clayton-Smith J, Donnai D. Fetal valproate syndrome. J Med Genet
1995;32:724-7.
Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T, et al.
A clinical study of 57 children with fetal anticonvulsant syndrome. J Med
Genet 2000;37:489-97.
Dean JC, Moore SJ, Osborne A, Howe J,Turnpenny PD Fetal anticonvulsant
syndrome and mutation in the maternal MTHFR gene. Clin Genet
1999;56:216-20.
Adab N, Jacoby A, Smith D, Chadwick D. Additional educational needs in
children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry
2001;70:15-21.
James FH, Fairgrieve S, Lynch SA, Jackson MJ. Prospective study of development
of infants born to mothers with epilepsy [abstract]. J Neurol Neurosurg Psychiatr
2002;72:135. [cited 8 Apr 2003]. Available from url: http://
jnnp.bmjjournals.com/cgi/content/full/72/1/133
Dansky LV, Andermann E, Rosenblatt D, Sherwin AL, Andermann F.
Anticonvulsants, folate levels, and pregnancy outcome: a prospective study.
Ann Neurol 1987;21:177-82.
Ogawa Y, Kaneko S, Otani K, FukushimaY. Serum folic acid levels in epileptic
mothers and their relationship to congenital malformations. Epilepsy Res
1991;8:75-8.
Prevention of neural tube defects: results of the MRC Vitamin Study. MRC
Vitamin Study Research Group. Lancet 1991;338:131-7.
Lewis DP, Van Dyke DC, Stumbo PJ, Berg MJ. Drug and environmental factors
associated with adverse pregnancy outcomes Part ll: Improvement with folic
acid. Annals Pharmacother 1998;32:947-61.
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;343:1608-14.
Scottish Obstetric Guidelines and Audit Project. The management of pregnancy
in women with epilepsy. Aberdeen: Scottish Programme for Clinical
Effectiveness in Reproductive Health; 1997. [cited 8 Apr 2003]. Available
from url: http://www.sign.ac.uk/guidelines/sogap/sogap1.html
Kaaja E, Kaaja R, Matila R, Hiilesmaa V. Enzyme-inducing antiepileptic drugs
in pregnancy and the risk of bleeding in the neonate. Neurology
2002;58:549-53.
Tomson T. Seizure control during pregnancy and delivery. In: Tomson T,
Gram L, Sillanpää M, Johannessen S, editors. Epilepsy and pregnancy.
Petersfield: Wrightson Biomedical; 1997. p. 113-23.
Neilson JP. Ultrasound for fetal assessment in early pregnancy (Cochrane
Review). In: The Cochrane Library, Issue 3, 2001. Oxford: Update Software.
Patsalos PN, Duncan JS. Antiepileptic drugs. A review of clinically significant
drug interactions. Drug Saf 1993;9:156-84.
REFERENCES
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
Johannessen SV. Pharmacokinetics of antiepileptic drugs in pregnant women.
In: Tomson T, Gram L, Sillanpää M, Johannessen S, editors. Epilepsy and
pregnancy. Petersfield: Wrightson Biomedical; 1997. p. 71-80.
Yerby MS, Friel PN, McCormick K. Antiepileptic drug disposition during
pregnancy. Neurology 1992;42:12-6.
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;35:122-30.
Epilepsy and pregnancy. Drug Ther Bull 1994;32:49-51.
Eadie MJ. Plasma antiepileptic drug monitoring in a neurological practice: a
25-year experience. Ther Drug Monit 1994;16:458-68.
Lander CM, Eadie MJ. Plasma antiepileptic drug concentrations during
pregnancy. Epilepsia 1991;32:257-66.
Ohman I, Tomson T, Vitols S. Lamotrigine levels in plasma and breast milk in
nursing women and their infants [abstract]. Epilepsia 1998; 39(Suppl 2):21.
Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference
guide to fetal and neonatal risk. 4th ed. Baltimore: Williams and Wilkins; 1994.
Nau H, Rating D, Koch S, Hauser I, Helge H. Valproic acid and its metabolites:
placental transfer, neonatal pharmacokinetics, transfer via mother’s milk and
clinical status in neonates of epileptic mothers. J Pharmacol Exp Ther
1981;219:768-77.
Doose H, Neubauer BA. Preponderance of female sex in the transmission of
seizure liability in idiopathic generalized epilepsy. Epilepsy Res
2001;43:103-14.
Durner M, Keddache MA, Tomasini L, Shinnar S, Resor SR, Cohen J, et al.
Genome scan of idiopathic generalised epilepsy: evidence for major
susceptibility gene and modifying genes influencing the seizure type. Ann
Neurol 2001;49:328-35.
Ottman R, Lee JH, Hauser WA, Risch N. Are generalized and localizationrelated epilepsies genetically distinct? Arch Neurol 1998;55:339-44.
Ottman R, Annegers JF, Risch N, Hauser WA, Susser M. Relations of genetic
and environmental factors in the etiology of epilepsy. Ann Neurol
1996;39:442-9.
Waltz S, Stephani U. Inheritance of photosensitivity. Neuropaeditrics
2000;31:82-5.
Scheffer IE, Berkovic SF. Genetics of the epilepsies. Curr Opin Pediatr
2000;12:536-42.
Doose H, Maurer A. Seizure risk in offspring of individuals with a history of
febrile convulsions. Eur J Paeditr 1997;156:476-81.
MacDonald BK, Johnson AL, Sander JW, Shorvon SD. Febrile convulsions in
220 children—neurological sequelae at 12 years follow-up. Eur Neurol
1999;41:179-86.
Abbasi F, Krumholz A, Kittner SJ, Langenberg P. Effects of the menopause on
seizures in women with epilepsy. Epilepsia 1999;40:205-10.
Crawford P, Lee P. Gender difference in the management of epilepsy-what
women are hearing. Seizure 1999;8:135-9.
Harden CL, Pulver MC, Ravdin L, Jacobs AR. The effects of the menopause
and perimenopause on the course of epilepsy. Epilepsia 1999;40:1402-7.
Scottish Intercollegiate Guidelines Network (SIGN). Management of
osteoporosis. Edinburgh: SIGN; In press 2003.
Jacoby A, Graham-Jones S, Baker G, Ratoff L, Heyes J, Dewey M, et al. A
general practice records audit of the process of care for people with epilepsy.
Br J Gen Pract 1996;46:595-9.
Poole K, Moran N, Bell G, Solomon J, Kendall S, McCarthy, et al. Patients’
perspectives on services for epilepsy: a survey of patient satisfaction preferences
and information provision in 2394 people with epilepsy. Seizure
2000;9:551-8.
Chappell B, Smithson WH. Patient views on primary care services for epilepsy
and areas where additional professional knowledge would be welcome.
Seizure 1998;7:447-57.
Brown S, Betts T, Crawford P, Hall B, Shorvon S, Wallace S. Epilepsy needs
revisited: a revised epilepsy needs document for the UK. Seizure
1998;7:435-46.
Bradley P, Lindsay B. Epilepsy clinics versus general neurology or medical
clinics (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Oxford:
Update Software.
Frost S, Crawford P, Mera S, Chappell B. National statement of good practice
for the treatment and care of people who have epilepsy. Leeds: Joint Epilepsy
Council; 2002. [cited 8 Apr 2003]. Available from url: http://
www.jointepilepsycouncil.org.uk/textpages.pdf
Sarkissian S, Wennberg R. Effects of the acute care practitioner role on epilepsy
monitoring outcomes. Outcomes Manag Nurs Pract 1999;3:161-6.
Bradley P, Lindsay B. Specialist epilepsy nurses for treating epilepsy (Cochrane
Review). In: The Cochrane Library, Issue 3, 2001. Oxford: Update Software.
Crawford P, Nicholson C. Epilepsy management. Prof Nurse
1999;14:565-9.
Mills N, Bachmann MO, Harvey I, Hine I, McGowan M. Effect of a primarycare-based epilepsy specialist nurse service on quality of care from the patients’
perspective: quasi-experimental evaluation. Seizure 1999;8:1-7.
Graydon M. Do learning disability services need epilepsy specialist nurses?
Seizure 2000;9:294-6.
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
MacDonald D, Torrance N, Wood S, Womerstey J. General-practice-based
nurse specialists-taking a lead in improving care for people with epilepsy.
Seizure 2000;9:31-5.
Hart YM, Shorvon SD. The nature of epilepsy in the general population. II.
Medical care. Epilepsy Res 1995;21:51-8.
Jain P, Patterson VH, Morrow JI. What people with epilepsy want from a
hospital clinic. Seizure 1993;2:75-8.
Goldstein LH, Minchin L, Stubbs P, Fenwick PB. Are what people know
about their epilepsy and what they want from a service related? Seizure
1997;6:435-42.
Choi-Kwon S, Yoon SM, Choi MR, Kang DW, Lee SK. The difference in
perceptions of educational need between epilepsy patients and medical
personnel. Epilepsia 2001;42:785-9.
Buck D, Jacoby A, Baker GA, Graham-Jones S, Chadwick DW. Patients’
experiences of and satisfaction with care for their epilepsy. Epilepsia
1996;37:841-9.
Poole K, Moran N, Bell G, Solomon J, Kendall S, McCarthy M, et al. Patients’
perspectives of services for epilepsy: a survey of patient satisfaction, preferences
and information provision in 2394 people with epilepsy. Seizure
2000;9:551-8.
Baker GA, Hesdon B, Marson AG. Quality-of-life and behavioural outcome
measures in randomized controlled trials of antiepileptic drugs: a systematic
review of methodology and reporting standards. Epilepsia
2000;41:1357-63.
Baker GA, Camfield C, Camfield P, Cramer JA, Elger CE, Johnson AL, et al.
Commission on Outcome Measurement in Epilepsy,1994-1997: final report.
Epilepsia 1998;39:213-31.
Cramer JA. Principles of health-related quality of life assessment in clinical
trails. Epilepsia 2002;43:1084-95.
MacDonald BK, Cockerell OC, Sander JW, Shorvon SD. The incidence and
lifetime prevalence of neurological disorders in a prospective communitybased study in the UK. Brain 2000;123:663-4.
Hanna NJ, Black M, Sander JWS, Smithson WH, Appleton R, Brown S, et al.
The National Sentinel Clinical Audit of Epilepsy-Related Death: Epilepsy­death
in the shadows. London: The Stationery Office; 2002. [cited 8 Apr 2003].
Available from url: http://www.official-documents.co.uk/document/reps/
nscaerd/nscaerd.pdf
Cockerall O, Johnson AL, Sander JW, Shorvon SD. The prognosis of epilepsy:
a review and further analysis of the first nine years of the British National
General Practice Study of Epilepsy, a prospective population-based study.
Epilepsia 1997;38:31-46.
Clinical Standards Advisory Group. Services for patients with epilepsy: report
of a CSAG Committee chaired by Professor Alison Kitson. London: Department
of Health; 1999. [cited 8 Apr2003]. Available from url: http://
www.info.doh.gov.uk/doh/point.nsf/page/
3743BAEF069C54A8002568AF005729C8?OpenDocument
Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness
Unit. FFPRHC Guidance: emergency contraception (April 2003). J Fam Plann
Reprod Health Care 2003;29:9-16. [cited 10 Jul 2003]. Available from url
http://www.ffprhc.org.uk/clinical_effect/
EC%20revised%20PDF%2019.06.03.pdf
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70
DIAGNOSIS AND MANAGEMENT OF EPILEPSY IN ADULTS