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Women and Epilepsy

Women and Epilepsy. Lyn Greenhill MSc student group 2006. Epilepsy & Womens’ Issues. Menarche Catamenial epilepsy Fertility Sexuality Contraception Preconception counselling Pregnancy Labour and puerperium. WOMEN AND EPILEPSY.

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Women and Epilepsy

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  1. Women and Epilepsy Lyn Greenhill MSc student group 2006

  2. Epilepsy & Womens’ Issues • Menarche • Catamenial epilepsy • Fertility • Sexuality • Contraception • Preconception counselling • Pregnancy • Labour and puerperium Lyn Greenhill

  3. 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 Lyn Greenhill

  4. Menarche

  5. MENARCHE • Some epilepsies start at menarche • Rarely some stop at menarche • If they start at menarche, they may remain cyclical during the reproductive years Lyn Greenhill

  6. 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 Lyn Greenhill

  7. Catamenial Epilepsy

  8. 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 Lyn Greenhill

  9. Fertility

  10. 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 Lyn Greenhill

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

  12. 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 Lyn Greenhill

  13. 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 Lyn Greenhill

  14. Sexuality

  15. 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 Lyn Greenhill

  16. Contraception

  17. 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 Lyn Greenhill

  18. 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 Lyn Greenhill

  19. 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 Lyn Greenhill

  20. PROGESTERONE ONLY O/Cs, IMPLANTS AND DEVICES • If enzyme inducing AED is being taken, progesterone only O/C’s 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 Lyn Greenhill

  21. 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 Lyn Greenhill

  22. ENZYME INDUCING AED’S ARE : • Phenobarbitone • Phenytoin • Carbamazepine • *Oxcarbazepine • Topiramate * O/C only Lyn Greenhill

  23. NON ENZYME INDUCING AEDs ARE: • Vigabatrin • Lamotrigine • Gabapentin • Tiagabine • Levetiracetam • Ethosuximide Only 4% of US Neurologists could correctly identify which were which Lyn Greenhill

  24. Preconception Counselling

  25. PRECONCEPTION COUNSELLINGDRUG ASSESSMENT • Is withdrawal possible before conception ? • Should we rationalise to monotherapy ? • Should we substitute a lower risk drug ? Lyn Greenhill

  26. 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 Lyn Greenhill

  27. 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 Lyn Greenhill

  28. Teratogenic risk of AEDs. Lyn Greenhill

  29. 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! Lyn Greenhill

  30. 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) Lyn Greenhill

  31. 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) Lyn Greenhill

  32. British Epilepsy Pregnancy Register 0800 389 1248 www.epilepsyandpregnancy.co.uk

  33. 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 Lyn Greenhill

  34. 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 Lyn Greenhill

  35. 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 Lyn Greenhill

  36. Pregnancy

  37. 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 Lyn Greenhill

  38. Committee on Safety of Medicines (CSM)

  39. 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: Lyn Greenhill

  40. 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) Lyn Greenhill

  41. 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 Lyn Greenhill

  42. 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? Lyn Greenhill

  43. 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 Lyn Greenhill

  44. 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

  45. 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 Lyn Greenhill

  46. 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 Lyn Greenhill

  47. 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 Lyn Greenhill

  48. 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 Lyn Greenhill

  49. 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. Lyn Greenhill

  50. 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. Lyn Greenhill

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