How to Treat EPILEPSY - Suzanne Davis and Elizabeth Walker - New Zealand Doctor
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Online reading and accredited assessment Free Access Code: available at www.howtotreat.co.nz/epilepsy epilepsy How to Treat EPILEPSY Suzanne Davis and Elizabeth Walker
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1. A seizure is classified as
1 CR 1.5 HRS focal based on the signs
and symptoms present at
the onset of the seizure.
True/False
EARN CPD CREDITS WITH ELEARNING 2. The drug of first choice
for any epilepsy type is
This continuing medical education activity has carbamazepine.
been endorsed by the RNZCGP and has been True/False
1 CR 3. Rectal diazepam has
approved for up to 1 CME credit for the General
a better safety profile
Practice Educational Programme and continuing compared with buccal
professional development purposes. This activity midazolam when used
will take up to 1 hour to complete (1 credit/hour). as rescue medication for
prolonged seizures.
True/False
The College of Nurses Aotearoa (NZ) has 4. The risk of
neurodevelopmental
endorsed this education/training for 1.5 hours
1.5 HRS deficits in a child exposed
professional development (CNA070). to an anti-seizure
medication in utero
is greatest with sodium
valproate.
True/False
Simply complete the online quiz-based assessment 5. Topiramate does
at www.howtotreat.co.nz/epilepsy not interfere with the
effectiveness of oral
contraceptives.
True/False
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+HOW TO TREAT
Epilepsy
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Epilepsy is a common neurological condition encountered inquote
pull general practice. This article, by
Suzanne Davis and Elizabeth Walker, discusses recommendations regarding diagnosis and indications for
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starting anti-seizure medication. It also reviews self-management and lifestyle issues for people with epilepsy
Learning objectives (ILAE; www.ilae.org) defines epilepsy as: Suzanne Davis In many individuals, it has an underlying
• Discuss the diagnosis and •at least two unprovoked (or reflex) ep- is a retired genetic cause. This can be due to an ab-
classification of epilepsy syndromes ileptic seizures occurring more than 24 paediatric normality in a single gene or due to the
• Identify appropriate anti- hours apart neurologist and interaction of multiple genes, but it is of-
seizure medications for • one unprovoked (or reflex) epileptic sei- president of the ten not inherited. Epilepsy can also be
different types of epilepsy zure and a probability of further epileptic New Zealand acquired due to an insult to the brain, such
• Recognise adverse effects of seizures, similar to the general recur- League Against as head injury, hypoxic ischaemic injury
anti-seizure medications rence risk after two unprovoked seizures Epilepsy (including stroke), infection or immuno-
• Explain the risks related to epilepsy (at least 60 per cent), occurring over the logically mediated disorders.1,2
Elizabeth
for women of childbearing age next 10 years Walker is a A 2017 systematic review and meta-
• Discuss the role of primary care in •diagnosis of an epilepsy syndrome. neurologist and analysis of international studies reporting
managing patients with epilepsy clinical neuro the prevalence and incidence of epilepsy
For example, a person with tuber- physiologist found the pooled point prevalence of ac-
E
pilepsy is a group of disorders ous sclerosis who has a single seizure at Auckland tive epilepsy in high-income countries
defined by the occurrence of ep- would have a probability of experienc- City Hospital, to be 5.49 per 1000 people. The pooled
ileptic seizures, which are events ing a second seizure of greater than 60 and honorary estimate for the incidence of epilepsy
that arise due to abnormal electrical ac- per cent. A young adult who had a sin- senior clinical in high-income countries was 48.86 per
tivity in the brain. Epileptic disorders can gle generalised tonic-clonic seizure, has lecturer at the 100,000 people.3
University of
present at any age but have peaks of on- myoclonic jerks in the mornings, and Applying these international esti-
Auckland School
set in infancy/childhood and in older age. generalised polyspike discharges with of Medicine mates to our New Zealand population
Epileptic seizures can range from photosensitivity on electroencepha- suggests that approximately 2400 peo-
brief behavioural arrests to stiffening logram (EEG) would have an epilepsy ple are diagnosed with epilepsy each year
and/or jerking of the whole body. The syndrome – juvenile myoclonic epilepsy. and approximately 27,000 people in New
International League Against Epilepsy There are multiple causes of epilepsy. Continued on page 4
www.howtotreat.co.nz/epilepsy HOW TO TREAT 3
→EPILEPSY
Diagnosis involves identifying the
type of seizure and type of epilepsy
T
he first step in the management
of epilepsy is to establish the Table 1. Classification of epileptic seizure types1
correct diagnosis. Current guide-
lines require that the diagnosis of an Focal onset Generalised onset Unknown onset
epileptic seizure be made by a specialist
– either a paediatrician or neurologist. Aware/impaired awareness
(optionally included)
Identify the type of epileptic
seizure Motor onset Motor Motor
A new terminology for describing and • Automatisms • Tonic-clonic • Tonic-clonic
classifying epileptic seizures was in- • Atonic • Clonic • Epileptic spasms
troduced by the ILAE in 2017.1 It is • Clonic • Tonic
summarised in Table 1. • Epileptic spasms • Myoclonic Non-motor
An accurate history of events is • Hyperkinetic • Myoclonic-tonic-clonic • Behaviour arrest
most important in determining a pa- • Myoclonic • Myoclonic atonic
tient’s seizure type. Focal seizures • Tonic • Atonic Unclassified
are first defined by the earliest symp- • Epileptic spasms
tom or sign as motor (eg, clonic or Non-motor onset
atonic) or non-motor (eg , sen- • Autonomic Non-motor (absence)
sor y or cognitive). The second • Behaviour arrest • Typical
step in the definition is determination • Cognitive • Atypical
of altered awareness at any stage in the • Emotional • Myoclonic
progression of the seizure event. • Sensory • Eyelid myoclonia
For example, in a focal aware motor
seizure, the patient is aware and fully Focal to bilateral tonic-clonic
oriented to the environment through-
out the seizure. In a focal sensory
seizure with impaired awareness, the Identify the type of epilepsy driving, education and employment.
patient experiences a sensory phenom- The next step, after diagnosis of the It is imperative to be confident in the
enon, such as an unusual smell, then type of seizure, is diagnosis of the type diagnosis of an epileptic disorder be-
loses awareness and may have no mem- of epilepsy. Epilepsy syndromes were fore recommending and commencing
ory of the event. Note that focal seizures also reclassified by the ILAE in 2017, treatment with an anti-seizure med-
with altered awareness were previously into four types: focal, generalised, ication (ASM). The features of some
termed “partial complex seizures”. combined generalised and focal, and un- epileptic and non-epileptic events are
Another important feature of the known.2 These epilepsy syndromes are summarised in Table 2.
new classification is the term “focal to defined according to seizure type, age of
bilateral seizure”. This term replaces the onset and comorbidities, such as cogni- Acute symptomatic seizures
previous “secondarily generalised sei- tive and behavioural disorders. The EEG An accurate Acute symptomatic seizures have a
zure”. and brain imaging findings (discussed history of direct reversible cause and do not in-
Often, the onset of an epileptic sei- later) may also play a role in identifica- events is most dicate that seizures will recur when the
zure is not witnessed. In this case, a tion of an epilepsy syndrome. important in immediate cause is removed. Examples
seizure with bilateral motor signs, such determining include drug exposure (eg, tramadol or
as tonic or tonic-clonic movements, is Confirm the diagnosis a patient’s alcohol), hypoglycaemia, electrolyte
classified as an “unknown” seizure type The diagnosis of epilepsy carries seizure type disorders, acute head injury, stroke, ce-
as the description of the onset of the s ignificant implications for the pa- rebral hypoxia, central nervous system
event is not available. tient, particularly with respect to infections and autoimmune enceph-
alitis. The seizures may be managed
acutely with an ASM, but medication
Continued from page 3 is not necessarily continued after the
patient has recovered from the under-
Zealand live with epilepsy. Thus, it is like- tion per year. lying condition.
ly that most practices have patients in The age-adjusted incidence of lon-
their care who have epilepsy. ger seizures was higher in Māori Febrile seizures
A recent report of prolonged seizures (29.31/100,000/year) and Pacific pa- The ILAE defines a febrile seizure as a
in patients presenting to Auckland hos- tients (26.55/100,000/year) than in seizure occurring in childhood after one
pitals from 2015 to 2016 found the those with European (19.13/100,000/ month of age and associated with a fe-
age-adjusted incidence of patients with year) or A si an/o ther descent brile illness not caused by any infection
seizures lasting 10 minutes or longer to (17.76/100,000/year).4 of the central nervous system. It occurs
be 22.22 per 100,000 head of popula- Continued on page 6
4 HOW TO TREAT www.howtotreat.co.nz/epilepsy
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Table 2. Differential diagnosis of epileptic seizures
Clinical event Provoking factors Discriminating clinical features
Generalised tonic-clonic Sleep deprivation, alcohol, drugs Cry followed by tonic posturing of limbs, then rhythmic jerking of limbs and face
epileptic seizure Eyes open
Duration of 2–3 minutes
Postictal drowsiness and confusion for 10–20 minutes
Focal seizure with Stress, sleep deprivation Stereotyped automatism with unresponsiveness
altered awareness May be tonic posturing of one arm and/or leg
Duration of 30–90 seconds
Postictal confusion for up to 20 minutes and amnesia for the event
Absence seizure None, more frequent when tired Abrupt onset and offset
Duration of 10–20 seconds
Unresponsive to external stimulation
Eyes remain open, face may relax
May be fidgeting movements of hands, clonic movements of face
Induced by hyperventilation
Non-epileptic blank spell Often in a school situation in Can be stopped by touch or distraction
children with learning difficulty Occur in specific contexts (eg, in school)
Syncope Prolonged standing, heat, painful Light-headedness, dimming of vision, sweating, pallor
procedure, dehydration May be tonic stiffening and small jerking movements of one or more limbs
Duration of 20–30 seconds
Rapid recovery of cognition followed by lethargy
Cardiac arrhythmia Stress, fright, exercise May be a prolonged prodrome of dizziness
Patient pale and limp
May be tonic stiffening and limb jerking with prolonged cerebral hypoxia
May be a family history of sudden death at a young age (under age 30)
Sleep attack Sleep deprivation, history of Often unobserved brief blackout
snoring and daytime sleepiness Eyes closed
Rapid recovery with no confusion
Breath-holding attack Fright, minor injury, frustration Provoking event always present
(common from age 6 months Initial cry
to 3 years) Loss of responsiveness
Tonic posturing followed by small jerking movements of limbs
Rapid recovery
Panic attack, Stressful social situation, anxiety Anxiety
hyperventilation Dizziness, breathlessness, paraesthesia
Psychogenic Stressful social situation May be prolonged motionless collapse with eyes closed
non-epileptic event Side-to-side thrashing, alternating limb movements
Rapid recovery of cognition
Focal dystonia Voluntary movement, pain Focal dystonic posturing of one or more limbs of limited duration
Often occurs with movement after a period of rest
No altered awareness
Transient global amnesia Physical exertion Amnesia lasting several hours, during which the patient is alert and can
perform tasks but cannot form new memories
Migraine Sleep deprivation Visual hallucinations are monochromatic or dichromatic and begin centrally
Duration typically longer than 3 minutes
Rarely move to the opposite field
No tonic eye deviation
Headache and vomiting are common
Focal unimpaired Visual hallucinations are multicoloured and often begin peripherally
awareness sensory May move to the opposite visual field
seizure with visual There is commonly eye deviation
symptoms Headache is common, vomiting is rare
www.howtotreat.co.nz/epilepsy HOW TO TREAT 5
→EPILEPSY
without previous neonatal seizures or
MRI is the
previous unprovoked seizures and does
investigation of
not meet the criteria for other symp-
choice for identifying
tomatic seizures.
structural changes
A simple febrile seizure is a gener-
in the brain that may
alised tonic-clonic seizure under 10
cause seizures
minutes in duration with no recurrence
within 24 hours or within the same fe-
brile illness. A complex febrile seizure
may have some focal features, be longer
than 10 minutes in duration, and two
or more may occur within 24 hours or
within the same febrile illness.
Hospital admission should be consid-
ered after the first febrile seizure if the
child is under 18 months of age, has a
complex febrile seizure, has no identi- i ncreased incidence of epileptic seizures
fied focus of infection, or where there is in other family members. CASE STUDY 1
high parental or carer anxiety.
The risk of recurrence after a febrile Electroencephalogram A timely second opinion
seizure is 30–40 per cent and is high- The EEG is often helpful in determin- Presentation and history
er in infants under 12 months (50 per ing whether an epileptic disorder is Susan is a 52-year-old woman who consults her GP
cent) than in children over three years focal or generalised; some EEG findings about a recent probable seizure and her disallowed
(20 per cent). There is a low but in- will point to a specific epilepsy syndrome. driving. She has no past history of seizures. Susan re-
creased risk of epilepsy after a febrile In New Zealand, an EEG is recom- cently had herpes ophthalmicus complicated by acute
seizure (3 per cent overall). The risk mended after the first epileptic seizure glaucoma, for which she received aggressive therapy,
is higher (up to 10 per cent) if there is and is ordered by the specialist who including timolol maleate ophthalmic solution. She has
abnormal neurological examination, carries out the initial diagnostic eval- hypertension treated with a diuretic.
a family history of epilepsy in a first- uation.
degree relative, and after a complex The EEG cannot be used to identify Recent seizure event
febrile seizure. a seizure event as epileptic because ab- On the day of the event, Susan went with her husband
Regular or intermittent ASM is not normalities defined as epileptiform can to a movie. She had been feeling a little unwell before
recommended for febrile seizures. be present in people who do not have leaving home. When she was watching the movie, she
Infants and children should be referred epilepsy, especially in children. On the began to feel nauseated and sweaty. Her husband de-
to a paediatrician if they have more than other hand, many people with epilepsy scribes her as moaning, then becoming rigid with her
three discrete febrile seizure events, if will have a normal EEG. right arm elevated for about one minute. She then
they are younger than six months or In New Zealand, a routine EEG is of- slumped and her head dropped onto his shoulder.
older than six years, if the seizures last ten performed after sleep deprivation She was incontinent of urine.
longer than 30 minutes or they have fo- to increase the likelihood of finding di- The ambulance was called. Susan recalls walking in
cal features. agnostic abnormalities. The inclusion the aisle to the ambulance, and her husband says she
of a period of natural sleep in the EEG did not appear confused. Her blood pressure, recorded
Investigate the cause recording also increases the diagnos- at the scene, was 60/80mmHg.
The first step in the identification tic yield. In the emergency department, Susan’s head CT scan
of the cause of an epileptic disorder was normal. Routine blood tests, including electrolytes,
is the accurate definition of the type Brain imaging were also normal. A diagnosis of seizure was made, and
of seizure(s) based on a detailed his- MRI is the technique of choice in in- she was instructed not to drive for 12 months.
tory. This includes review of video vestigation of an epileptic disorder. It
recordings of typical events if these are is recommended for any patient un- Referral
available. der the age of two presenting with an The driving restriction is significant as Susan is a sales
As so many people carry smart epileptic seizure, following a focal ep- representative. Her GP decides to refer her to a neurolo-
phones, video recording of seizure ileptic seizure, in the presence of focal gist for an opinion.
events is now commonplace. People neurological signs, and in patients with
who witness recurrent seizures should specific comorbidities, such as cognitive Diagnosis
be encouraged to record the events and behavioural disorders. The neurologist makes a confident diagnosis of a con
on their phones. It is important to CT imaging is not sufficient to inves- vulsive syncope based on the preceding symptoms of
remember that in most videos, only tigate the cause of an epileptic disorder. nausea and sweating, the low blood pressure on initial
the second half or end of an event is A CT scan is indicated when acute focal assessment and relatively rapid recovery without confu-
recorded. pathology (eg, trauma, haemorrhage sion. The event was more severe than a typical syncope
or stroke) is suspected in the setting as Susan was wedged upright in her seat. Urine incon-
Family history of an acute presentation of an epileptic tinence can occur in the context of prolonged cerebral
Genetic causes of epilepsy may or may seizure and an MRI is not immediate- hypoxia.
not be associated with inheritability, ly available. Predisposing factors were the beta-blocker used for
and the family history may be non- Brain imaging is not necessary when glaucoma and the diuretic for hypertension. Syncope is
contributary. On the other hand, a definite diagnosis of a generalised confirmed by a cardiologist and the diuretic is stopped.
many genetic epilepsies (eg, childhood genetic epilepsy, such as childhood ab- Susan is able to return to driving after two months.
absence epilepsy and juvenile myo- sence epilepsy or juvenile myoclonic
clonic epilepsy) are associated with an epilepsy, is made.
6 HOW TO TREAT www.howtotreat.co.nz/epilepsy
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Type of epileptic seizure and epileptic
syndrome guides treatment
I
n general, treatment is considered and the ASM can be commenced as Focal epilepsies
when there is evidence of recurrent recommended by the specialist. Carbamazepine, lamotrigine and leveti-
seizures and is usually initiated af- Patients are encouraged to practice racetam have been shown to be equally
ter a second epileptic seizure. In some self-management, including good com- effective as first-line therapy for focal
epileptic disorders, depending on the pliance with the medication regimen, if seizures, with lamotrigine having a bet-
identification of the cause of the epilep- education regarding the justification for ter adverse effects profile. Levetiracetam
sy, treatment is indicated after the first treatment and expectations about pos- has the advantage of a more rapid
seizure when the probability of subse- sible adverse effects is available from the titration than carbamazepine or la-
quent recurrent seizures is greater than onset of treatment. There is excellent motrigine, but it has the disadvantage
60 per cent. information regarding epilepsy and its of causing unacceptable psychiatric side
Recurrence risk after the first epilep- treatment available online that should effects of behavioural agitation, depres-
tic seizure varies, with the highest risk be provided to the patient and family as sion and anxiety in approximately 10
(up to 90 per cent) in people with epi- appropriate (see the patient informa- per cent of patients.
leptic discharges in the EEG and focal tion resources listed at the end of this
neurological deficits. In people with a article). People who Generalised epilepsies
normal EEG and no identifiable cause In most circumstances, this pro- witness Sodium valproate has been shown to
for the epilepsy, the recurrence risk is tocol of delaying treatment until recurrent be the most effective medication for
lower (13–40 per cent). Overall, the risk a diagnostic assessment has been seizures first-line therapy in genetic generalised
of a second seizure is 30–40 per cent and completed is safe and effective. should be epilepsies, such as juvenile myoclonic
is greatest in the first 12 months, falling There is evidence that the timing of encouraged epilepsy. However, as sodium valpro-
to less than 10 per cent after two years. onset of treatment does not alter the to record the ate is associated with the highest risk
In New Zealand, it is recommend- long-term prognosis for seizure con- events on of foetal malformations and neuro-
ed that an evaluation be made by a trol. Factors that predict outcome their phones developmental disorders in children
specialist after the first suspected include the response to the appropriate- exposed in utero, it is not indicated as
epileptic seizure. Current recommen- ly selected first-line medication and the first-line therapy for generalised epi-
dations state that this should occur number of seizures occurring in the first lepsies in women of childbearing age.
within three weeks of the initial pre- six months from presentation. Levetiracetam or lamotrigine are the
sentation. Many DHBs have established most appropriate first-line therapies
first-seizure clinics or have made other Which medication to choose? for these patients.
arrangements for patients to be seen in Treatment should include the most
a timely fashion after the first seizure. effective medication for achieving Rescue medications
It is expected that the specialist complete seizure control with the least Buccal midazolam
completes a diagnostic evaluation and adverse effects. An inappropriately Patients who have experienced pro-
orders an EEG if a probable epileptic chosen medication may be ineffective longed seizures of greater than five
seizure is identified. A decision re- and produce adverse effects that are minutes should be prescribed midazol-
garding brain imaging and a choice of more disabling than the seizures them- am, taken by the buccal or nasal route.
first-line ASM is then made. In many selves. The choice of treatment should Midazolam is available in New Zealand
circumstances, the patient will present be guided by seizure and epilepsy type in plastic ampoules (15mg/5ml).
to their GP with a subsequent seizure, (Table 3). Continued on page 8
Table 3. Anti-seizure medications for epilepsy type
Seizure type First-line ASM Alternative ASMs
Generalised epilepsy with tonic-clonic seizures Sodium valproate, except for women Lamotrigine, levetiracetam
of childbearing age
Childhood absence epilepsy Ethosuximide Sodium valproate, lamotrigine, levetiracetam
Focal epilepsy, including focal to bilateral seizures Lamotrigine Carbamazepine, levetiracetam, sodium valproate
Myoclonic epilepsy Sodium valproate Clobazam
Epilepsy with seizures of undetermined type Sodium valproate, except for women Lamotrigine, levetiracetam
of childbearing age
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Consider potential adverse effects,
especially in women of childbearing age
I
t should be assumed that every pa-
Older people have greater
tient taking ASMs may experience
sensitivity to the adverse
some side effects, mostly by causing
effects of ASMs due to
sedation or mood changes. This should
altered pharmacokinetics
be taken into consideration when a de-
and comorbidities requiring
cision is made to treat the disorder, and
multiple medications
good patient self-management requires
an understanding of how side effects
can be managed.
Many side effects are dose relat-
ed, predictable and can be minimised
by a gradual escalation in the dose.
Carbamazepine is a typical example
of a medication that should be com-
menced at a low dose (100–200mg/day
in an adult) and increased in increments
of 100–200mg over the course of two
weeks as it increases its own metabo-
lism over this time period. Older people
are more susceptible to medication side
effects due to altered pharmacokinetics. discontinue the medication immediate- count is not recommended as there is
ly. Most rashes will resolve over days no evidence that this reduces the risk.
Adverse effects and monitoring when the medication is discontinued. Hyponatraemia is common in peo-
Rare idiosyncratic medication reactions Life-threatening ASM hypersensitivity ple taking carbamazepine, especially
mostly occur in the first few weeks of with multi-organ failure occurs rarely – in children, older people and those
treatment, and they can be severe. in up to 4.5 per 10,000 people exposed. with restricted dietary salt intake.
Rash is the most common and occurs Mild blood dyscrasias (eg, leucopenia Monitoring of electrolytes and liv-
most often with carbamazepine and with carbamazepine and thrombocy- er function should depend on clinical
lamotrigine. The incidence of rash is topenia with sodium valproate) are symptoms and is not recommended as
reduced by slow introduction of the common and no intervention is need- routine in asymptomatic people taking
medication. A rash occurring between ed. Severe blood dyscrasias are rare, ASMs. Enzyme induction is common
two weeks and two months of medi- occurring in up to six per 10,000 people with carbamazepine and phenytoin,
cation introduction is an indication to exposed. Routine monitoring of blood resulting inelevation of enzymes, such
It is important
to advise
Continued from page 7 all girls and
women of
Training is necessary for caregivers c luster (eg, perimenstrually in women brain imaging with MRI. the issues
and family who will administer the who experience catamenial seizures). A second-line medication is indi- related to
midazolam. cated when first-line medication has epilepsy and
Medication-resistant epilepsy clearly failed. However, up to 30 per pregnancy
Rectal diazepam Approximately 60 per cent of people cent of patients will have medication- when ASMs
Diazepam administered rectally has with newly diagnosed epilepsy become resistant epilepsy, which is defined as are first
been used in the past as a rescue med- seizure free on first-line medication. If a failure of two tolerated and appropri- prescribed
ication. It has been shown to be less seizures recur, it may be because the ately chosen and used ASM schedules
effective than buccal midazolam in diagnosis of epilepsy was incorrect, an (whether as monotherapies or in com-
stopping prolonged seizures and has inappropriate medication was chosen bination) to achieve sustained seizure
a higher incidence of respiratory de- for the epilepsy syndrome or the person freedom.
pression. is not compliant with the medication Some people with medication-re-
regimen. sistant epilepsy have a developmental
Oral clobazam In some cases, other medications, and epileptic encephalopathy, with
Clobazam can be administered orally drugs or alcohol may cause further cognitive and behavioural disorders in
after a seizure when the person habit- seizures or there may be an undetect- addition to epilepsy. Any person who
ually experiences seizures in clusters ed epileptogenic cerebral lesion, such has failed two appropriately chosen and
over several hours, especially if there as a tumour. tolerated ASMs should be referred to a
has been a provocation, such as sleep Failure of a first-line medication to specialist – paediatrician or neurologist
deprivation. Clobazam can also be control seizures may be an indication – for diagnostic re-evaluation and con-
taken as a single daily dose on sever- to repeat the EEG to confirm the epi- sideration of non-medical treatment,
al consecutive days during a seizure lepsy syndrome, and to review or repeat such as diet or epilepsy surgery.
8 HOW TO TREAT www.howtotreat.co.nz/epilepsy+HOW TO TREAT
as gamma-glutamyl transferase. This contraception, such as intrauterine de-
is not an indication to change or cease vices, is recommended. CASE STUDY 2
therapy. It is also important to be aware that
Long-term treatment with ASMs lamotrigine levels are reduced by oral Day and night seizures
may reduce bone density, especially in contraceptives. Women taking la-
people with limited mobility. There are motrigine for epilepsy need to have Presentation and assessment
no current guidelines regarding rou- levels monitored when oral contra- Jen is a 20-year-old woman who visits her GP for
tine monitoring of bone density, but ceptives are commenced, and signs of advice. For the last two to three years, she has had
prophylactic vitamin D should be con- toxicity should be monitored when oral spells when she blanks out and loses track of conversa-
sidered for people at highest risk. contraceptives are discontinued. tions. She also has muscle twitches in her hands in the
mornings. She awoke on the morning before this visit
Psychiatric comorbidity Anti-seizure medication during with a sore mouth and found she had bitten her tongue
Depression is the most common psy- pregnancy during her sleep. Her muscles also felt sore.
chiatric comorbidity in people with Uncontrolled generalised tonic-clon- Jen appears normal except for bruising on one side
epilepsy – it occurs in up to 45 per cent ic seizures expose both the pregnant of her tongue. Her bitten tongue and sore muscles sug-
of patients at some stage. All ASMs mother and foetus to significant risk for gest she had a convulsion during her sleep. As she
are associated with behavioural side morbidity and mortality. For some wom- lives alone, there is no witness to the event. Her GP as-
effects, and some (particularly leveti- en, pregnancy exposes them to a higher sumes that the history indicates both focal seizures and
racetam and topiramate) have a higher risk for seizures. Lamotrigine levels are a generalised seizure. Jen is prescribed carbamazepine
incidence of significant psychiatric ad- significantly reduced during the second 200mg twice daily.
verse effects, including depression. trimester of pregnancy, requiring close
monitoring of the dose and blood levels. Referral and diagnosis
Women of childbearing age Another frequent cause of breakthrough Jen returns four weeks later as she is concerned that
Women of childbearing age should be seizures during pregnancy is self-manip- her hand twitching has increased. Her GP refers her for
fully informed of the risks to the foetus ulation of the medication dose. a neurological assessment.
with any of the medications prescribed, ASM exposure to the foetus is known The neurologist orders an EEG, which shows a gen-
as well as the risks to both herself and to increase the risk of major foetal mal- eralised spike wave discharge when Jen is asleep. She
her foetus from uncontrolled seizures formations and, in some cases, also also has a photoconvulsive response to flashing lights.
during pregnancy. As about half of preg- increase the risk of later developing The neurologist makes a diagnosis of a genetic gener-
nancies are unplanned, it is important to neurodevelopmental disorders, in- alised epilepsy (juvenile myoclonic epilepsy) based on
advise all girls and women of the issues cluding autistic spectrum disorder. For the history of daytime myoclonic and absence seizures,
related to epilepsy and pregnancy when some ASMs, such as sodium valproate, the nocturnal generalised seizure and the EEG findings.
ASMs are first prescribed. the risk to the foetus is dose related: Brain imaging is not recommended.
Women are advised to use two forms • Sodium valproate at doses greater
of contraception when taking ASMs than 1500mg/day exposes the foetus Management
and should be assessed and managed to the highest risk for foetal malforma- In juvenile myoclonic epilepsy, carbamazepine is likely
by a neurologist before planning a preg- tions, such as spina bifida, cleft palate to exacerbate the myoclonic seizures. Although sodium
nancy. Daily folic acid at a dose of 5mg and heart defects – 24 per cent risk of valproate is the medication of choice, it has the potential
per day is recommended in all women of babies are affected, compared with 2–3 for teratogenic and neurodevelopmental effects on an
childbearing age with epilepsy. per cent of babies unexposed to ASMs exposed foetus. The neurologist recommends that Jen
Educational resources about the use and 4–7 per cent of babies exposed to starts on levetiracetam. Jen is advised to stop driving
of ASMs in pregnancy are available for any ASM. because of her daytime absence seizures.
both prescribers and patients (see the • Sodium valproate at doses greater
lists at the end of this article), including than 800mg/day are associated with
two booklets prepared by ACC (go to: acc. an increased risk for childhood devel- Stopping anti-seizure medication
co.nz/treatmentsafety). opmental delays, and autistic spectrum The timing of a decision to discontinue
disorder occurs in 4–15 per cent of chil- ASMs will depend on the specific epi-
Hormonal contraception dren exposed in utero compared with lepsy syndrome as this will determine
Enzyme-inducing ASMs (eg, carbam- 2–7 per cent of children unexposed to the prognosis for seizure freedom when
azepine and topiramate) reduce the ASMs. Children exposed to sodium off medication. Some epilepsies may re-
contraceptive effect of oral contracep- valproate in utero are eight times more quire long-term ASM therapy. When a
tives. There is evidence that lamotrigine likely to need extra help in school than person with epilepsy has been seizure
induces the metabolism of the progestin other children. free on medication for two or more years,
levonorgestrel. If an oral contracep- Carbamazepine, lamotrigine and it is customary to begin a discussion re-
tive is used with an enzyme-inducing levetiracetam are associated with a garding discontinuation of medication.
ASM, a higher oestrogen formulation significantly lower risk to the foetus. The balance between adverse effects
is recommended (eg, 50µg). Even at the Monotherapy is recommended during of continued medication and the risk of
higher dose, contraception cannot be pregnancy, and there is substantial ev- further seizures should be discussed. It
guaranteed, and additional protection idence that polytherapy with sodium is reasonable to refer the patient to a spe-
is needed. valproate is associated with higher risks. cialist for this discussion.
Progesterone-only oral contracep- It is recommended that women with Most ASMs can be tapered over two
tives are likely to be ineffective when epilepsy who plan a pregnancy are re- months. However, several ASMs, such
enzyme-inducing ASMs are taken. On ferred for specialist evaluation one year, as phenobarbital and clonazepam, will
the other hand, depot medroxypro- but no less than six months, before dis- require a longer period of dose reduc-
gesterone acetate injections appear to continuing contraception so gradual tion (up to six months). The patient
be effective but need to be given more transition to a more appropriate medi- must cease driving during the taper and
frequently. Use of additional forms of cation regimen can occur. for three months afterwards.
www.howtotreat.co.nz/epilepsy HOW TO TREAT 9→EPILEPSY
Enhancing the roles of primary care
and patient self-management
Climbing to places
about one metre or
more off the ground
should be avoided
T
he GP and practice nurses play A person with epilepsy who contin- When a person with epilepsy is treat-
an important role in support- ues to have seizures, even as infrequently ed with an ASM, they are required to be
ing self-management in people as once per year, and is compliant with free of a seizure for 12 months before
with epilepsy. This includes actions that the recommended medication regimen they are permitted to drive. There is
enhance adherence to a medication reg- should be referred to a paediatrician or also a stand-down period from driving
imen and liaising between patients and neurologist. if the medication is changed or discon-
community, educational or other health tinued.
services, particularly for patients with Minimising risk of injury There is an exception for people who
cognitive, psychiatric and multiple co- People with epilepsy should be aware of have only nocturnal seizures – they
morbidities. the risks they might be exposed to dur- may drive if they have a stable pat-
A person taking medication for ep- ing a seizure. Preventable injuries and tern of seizures at night and are free of
ilepsy should have a review of their deaths during seizures are not uncom- awake seizures for 12 months.
management at least annually, even mon. Drowning is the most common For other classes of licence and en-
if seizure free, but especially if sei- cause of death caused by a seizure. Risk of dorsements, a person with a seizure or
zures are recurring. Even as few as drowning can be minimised by advising A person seizure disorder is considered perma-
one seizure per year can cause major the patient to shower rather than take a taking nently unfit to drive.
disruption to social, educational and bath, and to swim with one-on-one su- medication
employment opportunities, and will pervision from a responsible adult who for epilepsy Sudden unexpected death
prevent the person from legally driv- is aware of their epilepsy. Bicycle riding, should have in epilepsy
ing a vehicle. especially around traffic, and climbing to a review People with epilepsy have a small but
of their
The annual review will determine places about one metre or more off the real risk of death. It is important that
management
medication compliance and assess any ground should be avoided. at least patients and their caregivers are edu-
barriers to full compliance, confirm ap- annually cated regarding this risk at the time of
propriate contraception by two methods Driving after a seizure diagnosis.
and discuss any plans for pregnancy in Seizures are a rare cause of traffic ac- Sudden unexpected death in epilepsy
women of childbearing age, assess any cidents, but the regulations regarding is defined as sudden, unexpected, wit-
adverse effects of medications and driving are clearly laid out by the NZ nessed or unwitnessed, non-traumatic
determine if there are any important Transport Agency. The regulations and non-drowning death in patients
medication interactions. should be brought to the attention of with epilepsy, with or without evidence
At the review, the patient’s man- any patient who is driving, or intends for a seizure and excluding documented
agement of risks in their everyday life to drive, after the first seizure. status epilepticus, in which post-mor-
should be discussed. In addition, the For Class 1 licences, a single seizure tem examination does not reveal a
review should note any barriers to par- means a person will need to stop driving structural or toxicological cause of
ticipation in education or employment for 12 months. In exceptional circum- death.
and reinforce knowledge of the regu- stances, the 12-month stand-down SUDEP is reported to be the cause
lations regarding driving. The patient period may be reduced if there is a clear- of 2–18 per cent of all deaths in people
should be given information about the ly identified, non-recurring cause. This with epilepsy. The overall incidence is
services of Epilepsy New Zealand if they can be reviewed in consultation with a one in 4500 patient-years in children
are not already participating. neurologist. and one in 1000 patient-years in adults.
10 HOW TO TREAT www.howtotreat.co.nz/epilepsy+HOW TO TREAT
The cause of SUDEP is unknown but is
theorised to be due to respiratory sup-
pression followed by cardiac arrest in the
Patient information
postictal period of a tonic-clonic seizure.
The main risk factor for SUDEP is Health Navigator
the presence of tonic-clonic seizures Search for “epilepsy” at healthnavigator.org.nz
– one or two tonic-clonic seizures per
year increases the risk fivefold, while Epilepsy New Zealand
more than three per year results in a epilepsy.org.nz
15-fold increased risk compared with
those who are seizure free. Other risk My Medicines
factors include age (highest risk in the mymedicines.nz
18–25 age group), uncontrolled epilep-
sy, nocturnal seizures and intellectual Valproate risk in pregnancy
disability. sanofi.com.au/valproate
Community services for people ACC
with epilepsy Medicines for epilepsy, mental health, and pain can harm your unborn baby:
Epilepsy New Zealand is an organ- Talk to your doctor about the risks to you and your baby, and how to balance them.
isation that has a nationwide focus May 2020 – available at acc.co.nz/treatmentsafety
and employs support workers (also
known as field staff and educators)
across 12 field offices. These field of-
fices deliver services through paid staff
and volunteers. Programmes provid-
Useful resources
ed by Epilepsy New Zealand include
advocacy, awareness, research, infor- New Zealand Formulary
mation and education, and support nzf.org.nz
services.
People with epilepsy can engage New Zealand Formulary for Children
with Epilepsy New Zealand casually by nzfchildren.org.nz
attending a seminar or contacting an ep-
ilepsy educator. People may also be more Regional HealthPathways
actively involved by joining as a mem- https://bit.ly/2YRBtTA
ber. It is recommended that all patients
are provided with information regarding International League Against Epilepsy
community support services at the time ilae.org
of diagnosis of their epilepsy. n
EpilepsyDiagnosis.org
References epilepsydiagnosis.org
1. Fisher RS, Cross JH, French JA, et al.
Operational classification of seizure Paediatric Neurology Clinical Network
types by the International League Epilepsy Guidelines and Pathways for Children and Young People. June 2017.
Against Epilepsy: Position paper https://bit.ly/2ZA5TsD
of the ILAE Commission for Clas-
sification and Terminology. Epilepsia National Institute for Health and Care Excellence
2017;58(4):522–30. Epilepsies: diagnosis and management. February 2020. nice.org.uk/guidance/cg137
2. Scheffer IE, Berkovic S, Capovilla G, et
al. ILAE classification of the epilepsies: ACC
Position paper of the ILAE Commis- Benefits and risks of taking anti-seizure medicines for epilepsy, mental health, or pain: Informa-
sion for Classification and Terminology. tion for healthcare professionals to discuss with anyone who could get pregnant. May 2020
Epilepsia. 2017;58(4):512–21. – available at acc.co.nz/treatmentsafety
3. Fiest KM, Sauro KM, Wiebe S, et al.
Prevalence and incidence of epilepsy:
A systematic review and meta-analysis
of international studies. Neurology
2017;88(3):296–303. This article has been reprinted from New Zealand Doctor newspaper, 20 July 2020,
4. Bergin PS, Brockington A, Jayabal J, with support from ACC. The views expressed are not necessarily those of the
et al. Status epilepticus in Auckland, publisher or sponsor.
New Zealand: Incidence, etiology, and
Produced by The Health Media, publisher of New Zealand Doctor,
outcomes. Epilepsia 2019;60(8):1552–
PO Box 31905, Milford, Auckland 0741. Ph (09) 488 4286, Fax (09) 912 9257.
64.
© The Health Media (NZ) Ltd, 2021.
For full details of our Terms of Use, visit
Quiz answers www.thehealthmedia.co.nz/terms-of-trade
1. True 2. False 3. False 4. True 4. False
www.howtotreat.co.nz/epilepsy HOW TO TREAT 11Benefits and risks of anti-seizure medicines in pregnancy In some cases, anti-seizure/mood stabilising medicines may result in Fetal Anti-Convulsant Syndrome (FACS) in babies exposed in utero. Sodium valproate is the medicine known to have the highest risk. Information resources about the benefits and risks of these medicines can be ordered for free at www.acc.co.nz/treatmentsafety. Two booklets are available, one for health professionals and one for people taking the medicines, as well as a flyer suitable for waiting rooms. Please make sure anyone taking these medicines who could get pregnant has a copy of the patient information booklet, and understands the benefits and risks. The resources were developed by medical experts and consumers, and endorsed by ACC, the Health Quality and Safety Commission, the Ministry of Health, and Foetal Anti-Convulsant Syndrome New Zealand.
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