THE BETTER HALF OF EPILEPSY

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THE BETTER HALF OF EPILEPSY
BIRMINGHAM UNIVERSITY SEIZURE CLINIC

• Lyn Greenhill
• Epilepsy Specialist Nurse

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Women and Epilepsy

• Lyn Greenhill
• MSc student group 2006

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Epilepsy Womens Issues

• Menarche
• Catamenial epilepsy
• Fertility
• Sexuality
• Contraception
• Preconception counselling
• Pregnancy
• Labour and puerperium

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Epilepsy An Overview
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Epilepsy

• Epilepsy is the commonest serious chronic disease
  of the nervous system affecting approx 380,000
  people in England
• It has a prevalence rate of 0.5-1
• Every year in England about 800 people die
  during, or shortly after, an epileptic seizure

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Epilepsy

• Up to 20 of patients may be misdiagnosed and
  receive inappropriate and unnecessary treatment
• Approx 30 of patients are not receiving
  treatment from a specialist
• It takes on average 6-12 months from onset of
  first seizure to definitive diagnosis
• Epilepsy in pregnancy is managed to a variable
  standard
• Standards of care are described as fragmented and
  patchy

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Epilepsy

• Societies attitudes mean people with epilepsy are
  at triple jeopardy suffering social stigma
• Understanding of the illness among professionals
  is not high,and their problems are not addressed
  by health services (unlike other chronic long
  term conditions such as diabetes mellitus)
• Despite recent advances in medication the
  majority of people with epilepsy still receive
  medication that is archaic and has a high side
  effect profile

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WOMEN AND EPILEPSY

• Some epilepsy syndromes are found exclusively, or
  significantly more commonly in women
• Rett Syndrome
• Aicardi Syndrome
• Periventricular nodular heterotopia
• Childhood absence epilepsy
• Photosensitive epilepsy
• exclusively so

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Menarche
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MENARCHE

• Some epilepsies start at menarche
• Rarely some stop at menarche
• If they start at menarche, they may remain
  cyclical during the reproductive years

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MENARCHE

• A proportion of girls with epilepsy reach
  menarche with smaller stature than their peers
  and with significant obesity
• Epilepsy can delay (rarely prevent) menarche the
  role of medication in this is uncertain. Our
  experience is that valproate may be implicated

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Catamenial Epilepsy
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CATAMENIAL SEIZURES

• 12 of women do have true catamenial epilepsy
• more likely if non-ovulatory cycles
• ?oestrogen proconvulsant action?
• ?negated anti convulsant action of progesterone?
• ?changes in AED pharmacokinetics?
• ?premenstrual tension?
• ?fluid retention?
• Remember possible biased reporting

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Fertility
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EPILEPSY AND FERTILITY

• Women with epilepsy are slightly, but
  significantly less fertile than their peer group
  this remains true even when adjustments are
  made for differing marriage rates, etc

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EPILEPSY AND FERTILITY

• REASONS FOR LOWER FERTILITY IN WOMEN WITH
  EPILEPSY
• anovulatory cycles common
• polycystic ovary syndrome commoner
• altered Luteinising Hormone Release
• ? medication effect

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EPILEPSY AND FERTILITYPOLYCYSTIC OVARY SYNDROME

• Women with epilepsy are significantly more likely
  to have polyfollicular ovaries and probably the
  Polycystic Ovary Syndrome
• Prevalence of polyfollicular ovaries (40-60)
  independent of medication (normal is 6-10) but
  polycystic ovary syndrome significantly more
  likely in women with epilepsy taking valproate
  (Epilim) in monotherapy

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POLYCYSTIC OVARIES

• Polyfollicular ovaries probably an epilepsy
  effect, but clear relationship between exclusive
  valproate use and the polycystic ovary syndrome
  (partly masked by the use of the oral
  contraceptive)
• Syndrome usually regresses if valproate
  withdrawn, or if lamotrigine added before
  valproate withdrawn

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Sexuality
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EPILEPSY AND SEXUALITY

• Majority of women have normal sexual desire and
  arousal
• A few do not
• Rarely, sexual feelings occur as part of the
  seizure

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Contraception
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EPILEPSY AND CONTRACEPTION

• Women with epilepsy can use most forms of
  contraception, but they and their advisors need
  to know a few simple rules
• The first rule is that if the woman has frequent
  seizures with lapses of memory and concentration
  she may need a partner who can remind her when to
  use her chosen method, particularly if she uses a
  barrier device

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CONTRACEPTION

• Non enzyme inducing AEDs can use standard O/Cs
• Enzyme inducing AEDs reduce the efficiency of
  combined O/Cs and make progesterone only O/Cs
  totally unreliable
• This reduced efficiency is still true even if the
  oestrogen dose in the O/C is increased and good
  cycle control is maintained

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PRESCRIBING O/Cs TO WOMEN TAKING ENZYME INDUCING
AEDs

• Start with 50mcg oestrogen O/C observe for 3
  cycles (use other precautions)
• If breakthrough bleeding occurs increase the
  oestrogen dose to 75 / 80mcg or even 100mcg until
  cycle control
• Warn women not 100 effective even if good cycle
  control - use additional method if complete
  protection needed

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PROGESTERONE ONLY O/Cs, IMPLANTS AND DEVICES

• If enzyme inducing AED is being taken,
  progesterone only O/Cs are much less reliable
  than usual
• Depot progesterones (e.g. Depo-provera) are
  recommended (inject every 10 weeks if enzyme
  inducing AED in use)
• Progesterone implants not recommended for women
  with epilepsy
• Mirena coil no problems
• not all agree

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OTHER METHODS

• IUD no problems (occasional seizures during
  insertion)
• Barrier methods no problem
• Persona / rhythm methods, not currently
  recommended because of effect of epilepsy on LHRH
  release making these methods potentially
  unreliable

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ENZYME INDUCING AEDS ARE

• Phenobarbitone
• Phenytoin
• Carbamazepine
• Oxcarbazepine
• Topiramate
• O/C only

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NON ENZYME INDUCING AEDs ARE

• Vigabatrin
• Lamotrigine
• Gabapentin
• Tiagabine
• Levetiracetam
• Ethosuximide
• Only 4 of US Neurologists could correctly
  identify which were which

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Preconception Counselling
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PRECONCEPTION COUNSELLINGDRUG ASSESSMENT

• Is withdrawal possible before conception ?
• Should we rationalise to monotherapy ?
• Should we substitute a lower risk drug ?

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PRECONCEPTION COUNSELLINGDO AED DRUGS DAMAGE THE
FOETUS ?

• EVIDENCE IS STILL BEING GATHERED
• Animal work important
• Human registers starting to yield results
• Need to look at development of foetus, not just
  its condition at birth
• Clear evidence that monotherapy is advantageous
• Increasing evidence that some AEDs are high risk
• Role of high dose folic acid needs better
  evidence base

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Epilepsy Teratogenesis

• The risk depends on
• Number of AEDs taken (up to 50 with three)
• Type of drug taken
• Whether taking prophylactic high dose folic acid
  (probably reduces risk)
• But not seizure frequency
• Animal data probably fairly accurate in
  predicting human teratogenesis

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PRECONCEPTION COUNSELLING
? human except at high dose
animal
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Teratogenic risk of AEDs.
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Newer evidence. Is dosage a cosideration?

• Recent result of registers suggest links between
  dosage and risk factors.
• Can we predict outcomes comparing low dose VPA v
  high dose Lamotrogine?
• Or low versus high dose Carbamazepine?
• Preconceptual counselling suddenly more difficult!

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PRECONCEPTION COUNSELLINGWHAT ARE THE
ABNORMALITIES?

• MAJOR
• Severe spina bifida (valproate, carbamazepine)
• Cardiac (valproate, carbamazepine)
• Cleft palate, etc (valproate, phenytoin)
• Bladder / penis (valproate)
• Syndactaly, etc (valproate, phentytoin)

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PRECONCEPTION COUNSELLINGWHAT ARE THE
ABNORMALITIES?

• MINOR
• Dysmorphic features
• Facial abnormalities (e.g. abnormal philtrum,
  hypertelorism) - valproate? carbamazepine?
• Distal limb abnormalities (e.g. rudimentary
  nails) - valproate, phenytoin, carbamazepine
• Dysmorphic features may well be an indication of
  more widespread abnormalities and future
  intellectual challenge (remember Downs Syndrome)

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British Epilepsy Pregnancy Register

• 0800 389 1248
• www.epilepsyandpregnancy.co.uk

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British Epilepsy Pregnancy Register

• Aims
• To register the outcome of pregnancies of all
  women with epilepsy
• Looking at the condition of the child at birth
• Shortfalls
• Limited registration, usually only specialist
  centres therefore biased group of women
• Picking up only major abnormalities
• Not looking at long term effects of medication

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PRECONCEPTION COUNSELLING

• Evidence from the British Epilepsy Pregnancy
  Register that sodium valproate poses highest risk
  (up to 18 in monotherapy)
• possibly dose dependant
• folic acid, even in high dose, may not protect
  with valproate
• Evidence from Liverpool, Manchester and Aberdeen
  that sodium valproate and high doses of
  carbamazepine both significantly impair the
  psychological development of the child exposed to
  them in the womb

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PRECONCEPTION COUNSELLING

• OUR POLICY
• Folic acid 5mg daily indefinitely
• Get to monotherapy if at all possible
• Withdraw valproate, phenytoin, phenobarbitone if
  possible
• Substitute, if needed, lamotrigine (gabaoentin)
• Always withdraw valproate if history of spina
  bifida
• Withdrawal / switching takes significant time
  (especially in the seizure free) so use effective
  contraception during this period

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Pregnancy
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Epilepsy Pregnancy

• Epilepsy is now the second commonest cause of
  maternal death
• Woman suddenly stops medication on discovering
  she is pregnant
• Anticonvulsant dose not increased during the
  pregnancy resulting in an increase in seizure
  frequency
• Seizures during labour and in the immediate
  puerperium
• Deaths due to either status epilepticus or Sudden
  Death in Epilepsy

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Committee on Safety of Medicines (CSM)
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Committee on Safety of Medicines

• Acknowledges that the risk of congenital
  malformations in infants born to mothers
  receiving AEDs is approx 2-3 times higher than in
  the general population. Valproate constitutes one
  of the highest risks.
• The CSM has advised the following in the light of
  data from the UK Pregnancy and Epilepsy Register

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CSM Advises

• Women of child-bearing potential should not be
  started on valproate (VPA) without specialist
  neurological advice
• Women using VPA who are likely to become pregnant
  should receive specialist advice because of the
  potential teratogenic risk to the foetus
• If used in pregnancy, VPA should be as
  monotherapy at lowest effective dose, in divided
  doses and as controlled-release
• Women should use high dose Folic Acid supplements
  (5mg daily)

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Epilepsy Pregnancy

• We have evidence that women in our city blunder
  into pregnancy, uninformed, uncontrolled and
  unsupported many do not have epilepsy and are
  taking anticonvulsants unnecessarily and throw
  away their pills as soon as they find out they
  are pregnant

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• MONITOR SEIZURE FREQUENCY
• In about 1/3 seizures stay the same
• In about 1/3 seizures reduce in frequency (or
  disappear)
• In about 1/3 there may may a seizure increase, or
  the return of seizures
• WHY?

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• FACTORS INVOLVED IN SEIZURE INCREASE
• Deliberate non-compliance
• Change in AED kinetics and binding
• Sleep deprivation
• Vomiting
• Metabolic / haemodynamic changes
• Deliberate non-compliance is much less likely in
  women who have been fully counselled and already
  made decisions about drug withdrawal

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• CHANGE OF AED KINETICS DURING PREGNANCY
• Reduction of gastric mobility / absorption
• Vomiting
• Increased plasma volume (50)
• Increased cardiac output (30)
• Increased body water
• Change in liver enzyme function
• Reduction in protein binding
• To be accurate unbound AED levels should be
  measured during pregnancy few clinics have the
  facility ordinary blood level monitoring is
  potentially very misleading

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• MORNING SICKNESS
• Not commoner in women with epilepsy
• If there is a pattern take drugs when least
  likely to be sick
• If sick within 1 hour of taking AED repeat dose
  (or if tablets recognisable in vomitus)
• Standard remedies (i.e. ginger, acupuncture /
  acupressure) safe
• Hyperemesis gravidarum serious in women with
  epilepsy - treat vigourously

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• Monitoring Seizures
• In women still having seizures
• Monitor seizure frequency often, and increase
  dose (monitoring neurotoxicity)as often as needed
  to keep seizure frequency relatively unchanged
• Be cautious about dropping dose straight after
  delivery
• Teach women to recognise neurotoxic side effects

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• SEIZURES THAT START IN PREGNANCY
• May be coincidence
• May only have seizures when pregnant (rare)
• May have been there all the time, but
  unrecognised
• May have been simple partial, which now
  generalise
• May be symptomatic of a cerebral lesion provoked
  by pregnancy (e.g. AVM, meningioma)
• In later pregnancy may be eclamptic
• If there is any doubt that they are lesional they
  need full investigation

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CARE OF WOMEN WITH EPILEPSY DURING PREGNANCY

• Ensure first class obstetric care
• Hospital delivery for most
• Ensure full foetal screening for abnormalities
• Ensure effective liaison between GP / epilepsy /
  obstetric services
• Women taking enzyme-inducing AEDs should have
  10mg vitamin K orally dose from 36 weeks
• Women whose epilepsy has not been previously
  assessed need careful monitoring
• Provide support, information and TLC, especially
  in the primip

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• In July 2001, we set up an epilepsy service with
  an adjacent Womens hospital with a nurse run
  liaison clinic with the foetal medicine team plus
  a direct referral service of all women presenting
  already pregnant to the hospital with a history
  of epilepsy
• We are seeing many more patients than predicted
  (39 in 5 months)
• 28 of these were new to our service (the other 11
  from our preconception service)

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• Of these 28 patients presenting already pregnant
  with epilepsy
• 28 - NOT epilepsy
• 24 - stopped medication on discovering pregnancy
• 4 only were taking adequate folic acid (5mg
  daily)
• 70 were pregnant by accident
• 4 only had had formal preconception review
• 50 were taking sodium valproate (none knew of
  its potential teratogenicity)

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In July 2001,we set up a joint pregnancy/epilepsy
service at BWH in conjunction with the foetal
medicine team.We see far more women than ever
expected.
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Recent audit.

• 50 of patients taking VPA.
• 23 of patients Not epilepsy.
• 25 taking adequate folic acid.
• 24 stopped taking medication on discovering
  pregnancy.
• 70 pregnant by accident.
• 15 only had formal preconcept review.

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Labour puerperium
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CARE OF WOMEN WITH EPILEPSY DURING LABOUR

• Try to have an agreed plan
• Avoid prolonged labour (especially second stage)
• Avoid maternal exhaustion
• Avoid hyperventilation in those sensitive to it
• Make sure that AEDs are taken properly
• Have a plan to deal with seizures in labour
• Ensure adequate pain relief
• Have plan for vomiting
• e.g. elective caesarean
• women taking newer AEDs may need to bring
  them in
• woman can bring her preferred rescue remedy
  with her (e.g. frisium)

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CARE OF WOMEN WITH EPILEPSY DURING LABOUR

• Some anecdotal evidence that pethidine is
  potentially convulsant
• TENS safe
• Epidural safe
• Gas and air OK (avoid hyperventilation)
• Avoid overuse of local anaesthetics

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CARE OF WOMEN WITH EPILEPSY DURING LABOUR

• SEIZURES DURING LABOUR
• Ensure not eclampsia
• I/V benzodiazapines (e.g. lorazepam)
• 2-3 days clobazam in the seizure brittle
• If seizures known to be prolonged interrupt
  quickly
• Baby not likely to be damaged by occasional tonic
  clonic seizures, but status potentially fatal for
  mother and child

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COMPLICATIONS OF PREGNANCYIN WOMEN WITH EPILEPSY

• Probably very little increase nowadays for the
  woman with epilepsy or her offspring, despite the
  earlier gloomy literature.
• Pre-eclampsia, premature birth and excessive
  maternal haemorrhage may still be slightly higher
  in incidence

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CARE OF THE WOMEN WITH EPILEPSY AND HER CHILD IN
THE PUERPERIUM

• Risk of having a seizure that could harm the baby
  is actually very small
• In our experience, women with Juvenile Myoclonic
  Epilepsy need to take particular care because of
  increased risk of having jerks for a while after
  the babys birth

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CARE OF THE WOMEN WITH EPILEPSY AND HER CHILD IN
THE PUERPERIUM

• Ensure vitamin K for the child at birth if mother
  on enzyme inducing AEDs
• Avoid overprotection of the mother
• Encourage breastfeeding
• Ensure mother and partner know safety steps
• Ensure medication continues but be alert to
  neurotoxicity
• Ensure sufficient rest and sleep
• even women long since seizure free may have
  seizures again in the puerperium (especially JME)
  it is such an exhausting time

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CARE OF THE WOMEN WITH EPILEPSY AND HER CHILD IN
THE PUERPERIUM

• BREAST FEEDING
• Encourage and support (but dont proselytise )
• Only avoid if child very premature
• Only withdraw if child obviously adversely
  affected
• Ensure woman has breast pump and partner feeds in
  night
• Breast feeding for a few days may prevent abrupt
  withdrawal effects - the AEDs have been in the
  childs blood stream for the last nine months

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CARE OF THE WOMAN WITH EPILEPSY AND HER CHILD IN
THE PUERPERIUM

• OTHER ISSUES
• Reassess before next pregnancy if needed
• Review medication
• Contraception
• Teaching the child about epilepsy / first aid
• Bonding issues after seizure

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CARE OF THE WOMAN WITH EPILEPSY AND HER CHILD IN
THE PUERPERIUM

• Rarely epilepsy may start in the puerperium
• This may be eclampsia, if near to the birth
• It may be lesional
• It may be amniotic fluid embolism
• It may be coincidence

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A DEDICATED CLINIC

• Specialist review
• Answer questions
• Monitor seizures
• Improve control
• Formulate labour plan
• Counselling
• Reassess before next pregnancy

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Ward Admission

• Monitor seizure activity
• Encourage breastfeeding
• Ensure antiepileptic medication continued
• Advise specialist on discharge, possible
  discharge letter?

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CONCLUSIONS

• 0.5 to 1 of population have epilepsy
• Women of childbearing age make up 40 of this
  group
• Important that we make provisions for this group
  of patients