Dr Atul Prasad MBBS,DM ( Neurology )

Transcription

1 Photograph Dr Atul Prasad MBBS,DM ( Neurology ) Director and Senior Consultant BLK Superspeciality Hospital - New Delhi He did his Neurology training from National Institute of Mental Health and Neuro Sciences (NIMHANS) Bangalore in 1992 He was Associate Professor and Head of Neurology at Institute of Human Behavior and Allied Sciences (IHBAS) Delhi till 2002 Jan He subsequently joined University Science Malaysia Malaysia as Associate professor in Neurology from 2002 till July 2006 He has authored / coauthored 17 chapters in Books He has 37 Publications in various International journals He has been involved in teaching Medical students, Post Graduates in Medicine and Post Doctoral students in Neurology for more than 15 years. He has been guide for Thesis for Medicine and Neurology Post Graduates for the last 8 years

2 Managing Epilepsy in Women of Childbearing Age

3 Umbrella term defined by: Two or more seizures more than 24 hours apart Development of recurrent unprovoked seizures

4 Please always remember Misdiagnosis is common (25% of cases) Just because somebody shakes and wets does not mean they are having a seizure Heath M. The Spectator cartoon book 2000: St Edmundsbury Press Ltd, London

5 Women of child bearing age provide epilepsy professionals with unique treatment dilemmas Epilepsy drugs and appearance.pcod Female hormones and seizure control..catamenial Ep Contraception Fertility Pregnancy and Labor effects of drugs effects of seizures Puerperium

6 Women of child bearing age provide epilepsy professionals with unique treatment dilemmas Epilepsy drugs and appearance.pcod

7 Polycystic Ovary Syndrome (PCOS) Prevalence General Population 4-11% Prevalence Women with Epilepsy 10-26%

8 Polycystic Ovary Syndrome (PCOS) Hyperandrogenergic state (relative increase in testosterone Vs estrogen) Increase facial hair/acne Alopecia (hair loss) Chronic anovulation infertility

9 Epilepsy and PCOS Brain activity related to epilepsy (especially temporal lobe epilepsy) can affect hypothalamus and pituitary gland This could effect hormone secretion in brain

10 AEDs and PCOS Studies suggest that Valproate has high association with PCOS in epilepsy patients (60%), vs 33% in carbamazepine, 14% other drugs VPA more likely to be associated with PCOS if patient started drug in childhood or adolescence PCOS can reverse or improve when VPA switched to another AED

11 Contraception..

12 Carbamazepine Sodium Valproate Lacosamide Levetiracetam Zonisamide Commonly used AED s Clobazam Lamotrigine Pregabalin Phenytoin Topiramate

13 Carbamazepine / Oxcarbazepine / Eslicarbazepine / Topiramate / Phenytoin / Phenobarbitone / Primadone all induce hepatic P-450 These effect the metabolism of oestrogens and progestogens Leading to ineffective Oral Combined Contraceptive Pill (OCP) at normal doses These will also effect emergency contraception Lamotrigine levels are significantly reduced by the OCP

14 Recommendations.. For women taking enzyme inducing medications: Works Well Caution Not recommended Coil / Mirena Barrier OCP (increased dose required) Depo (time) Emergency contraception Implant Patch Progestogen

15 For women NOT taking enzyme inducing medications: Works Well Caution Coil / Mirena Barrier OCP Implant Patch Emergency Contraception Depo (time) Progestogen

16 For women taking Lamotrigine Works Well Caution Coil / Mirena Barrier Implant Patch Emergency Contraception OCP (recommend slight increase in Lamotrigine dose) Depo (time) Progestogen

17 Infertility

18 Fertility Rate in Women with Epilepsy (WWE) Fertility rate: Population: WWE* 47.1 livebirths per 1,000 women Women in the general population* 62.6 livebirths per 1,000 women *Women aged years in England and Wales, Wallace H, Shorvon S, Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates in women with epilepsy. Lancet 1998; 352:

19 Does polytherapy worsen infertility? A prospective cohort of WWE enrolled in the Kerala (India) Registry of Epilepsy and Pregnancy ( ) in the preconception stage Out of 375 women followed up for 1 10 years, 231 had pregnancy and 144 remained infertile (38.4%) Infertility was least (7.1%) for those with no antiepileptic drug (AED) exposure and higher (p = 0.001) with AED exposure (31.8% with 1 AED, 40.7% with 2 AED, and 60.3% with 3 or more AED exposure) Sukumaran SC, Sarma PS, Thomas SV. Polytherapy increases the risk of infertility in women with epilepsy. Neurology Oct 12;75(15):1351-5

20 Sexual Dysfunction and Hormones in Women With Epilepsy Women ages 18 to 40, cycling, at least 4 years post-menarche and taking a single AED Sexual dysfunction more prevalent in women receiving enzyme- inducing AEDs than in controls (P<.05) Deficits in sexual desire correlated with reductions in androgens Deficits in sexual arousal correlated with reductions in estrogen Sexual dysfunction also associated with comorbid depression Morrell M, et al. Epilepsy Behav 2005;6(3):360-5.

21 Catamenial Epilepsy From the Greek katamenios meaning monthly

22 Seizures and Hormone Fluctuations Estrogens LOWER seizure threshold more likely to have seizure Progestins RAISE seizure threshold less likely to have a seizure

23 The Menstrual Cycle

24 Catamenial Epilepsy Patients report seizures related to menses 24-78% or the time Usually around ovulation just prior to menses (-3-+3d) Anovulatory cycles quite common in epilepsy patients (up to 35% cycles vs 8% controls) Seizure 1.5x more frequent during anovulatory cycles

25 Treatment of Catamenial Epilepsy Difficult to control with AEDs Increasing doses of AEDs premenstrually may be beneficial Important to monitor serum levels to avoid under- or overdosing Acetozolamide of limited benefit Natural progesterone for women with regular menses Clobazam 20mg /day for 10 days (starting 2-4 days prior to menses or ovulation) Overall, therapies not well studied and more research needs to be done

26 Pregnancy

27 Issues for women with Epilepsy planning pregnancy Fertility Can I get pregnant? AED selection Should I be on an AED? If so, am I on the best AED? Seizure control Will my seizure control change during pregnancy?

28 Pre-conceptual treatment choices Remain on current medication Change to alternative medication Withdraw medication (medication should NEVER be stopped suddenly) Reduce medication for 1st trimester 5mgs Folic Acid

29 Discontinuing AEDs before pregnancy Seizure-free 2-5 years Single seizure type Normal neuro exam and normal IQ Normal EEG on medication This process should be complete 9 months prior to conception

30 Changing AED before pregnancy If patient is on drug with high teratogenic risk CHANGE SHOULD BE MADE 9 months PRIOR to pregnancy Do not start changing drugs once patient is pregnant because of High risk of breakthrough seizures and Time-window of embryo development is past

31 Neural Tube Development

32 Seizure Control During Pregnancy

33 Care During Pregnancy Most women have no change in seizure frequency during pregnancy. Only 15-33% had increased seizures Increased seizures could relate to Hormonal changes Decreased drug levels due to increased blood volume, decreased absorption, Decreased compliance Sleep deprivation Increased stress/anxiety

34 Primary Goal: Optimal Seizure Control Risk to fetus of generalized tonic-clonic seizure is of hypoxia and acidosis Increase risk of abruptio placenta, miscarriage, stillbirth, blunt trauma, intracranial hemorrhage Unclear whether complex partial seizures or absence seizures pose risk to fetus

35 Care During Pregnancy: AED management If possible Monotherapy Lowest effective dose

36 Single Drug vs Multidrug It is better to be on one drug at the lowest dose that controls seizures The risk of major malformations is 2 to 7% for those on a single drug as compared to 6 to 18% for those on a multi-drug regimen, particularly if it includes VPA1,2 BUT Having a tonic-clonic seizure during pregnancy could potentially cause harm to the fetus Therefore, if one AED does not control seizures, it is better to be on two drugs than to have seizures 1. Holmes et al., N Engl J Med Artma et al., Neurology 2005

37 So what about Vitamins(Folic Acid)? No evidence that folic acid specifically reduces the risk of teratogenicity due to AEDs New evidence may indicate that folic acid improves cognitive functional outcomes All women of childbearing potential, with or without Epilepsy should be supplemented with at least 0.4 mg of folic acid daily before conception and during pregnancy, particularly during the first trimester

38 In Brief

39 Epilepsy is not a contraindication to pregnancy 90% of pregnant women with epilepsy deliver healthy newborns There is an increased rate of complications in women with epilepsy Multidisciplinary approach is important and close follow-up is needed Family doctor Obstetrician trained for high-risk pregnancy Neurologist

40 According to the American Academy of Neurology Wo e with epilepsy taki g AED s show o su sta tially i reased risk (greater than two times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (greater than 1.5 times expected) of premature contractions or premature labor and delivery There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke Seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84% 92%) of remaining seizure-free during pregnancy Neurology 2009;73:

41 According to the American Academy of Neurology Women with epilepsy (WWE) should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high rate (84% 92%) of remaining seizure-free during pregnancy. However, WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery during pregnancy Neurology 2009;73:

42 NEW ONSET SEIZURES IN PREGNANCY 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) CVT, Pheochromocytomas, SAH, Amniotic fluid Embolism,TTP In later pregnancy may be eclampsia

43 The Baby

44 All epilepsy medications will increase the risk of having a child with a major congenital malformation Background 2-3% Sodium Valproate 5-9% ** Lamotrigine 3-5% Carbamazepine 3-4% For those on polytherapy the risks increase

45 AAN/AES GUIDELINES It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCM compared to monotherapy. CONCLUSION: If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs

46 CSM advice, Sept 2003 Women of childbearing age should not be started on sodium valproate without specialist neurological advice

47 Care During Pregnancy: Screening for fetal malformations weeks: maternal serum alpha-fetoprotein Ultrasound weeks Together these tests have 95% sensitivity to detect open neural tube defects, 85% to detect cardiac defects Amniocentesis if equivocal results: increases sensitivity to 99%

48 Care During Pregnancy: Vitamin K supplementation May be increase risk of hemorrhagic disease of the newborn in babies of mothers on enzyme-inducing AEDs: mortality of 30% for baby if affected Women taking enzyme-inducing AEDs should have 10mg vitamin K I.M,two doses,at 34 and 36 weeks Vit K 1mg IM to the baby at birth

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50 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

51 CARE OF WOMEN WITH EPILEPSY DURING LABOUR Some anecdotal evidence that pethidine is potentially convulsant Epidural safe Gas and air OK (avoid hyperventilation) Avoid overuse of local anaesthetics

52 CARE OF WOMEN WITH EPILEPSY DURING LABOUR SEIZURES DURING LABOUR Ensure not eclampsia I/V benzodiazapines (e.g. Lorazepam 4mg iv,diazepam)..if not controlled..treat as Status Epilepticus 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

53 Post-Partum Care

54 CARE OF THE WOMEN WITH EPILEPSY AND HER CHILD IN THE PUERPERIUM BREAST FEEDING Encourage and support 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 child s blood stream for the last nine months Safest AED...STILL DEBATABLE

55 Breast Feeding Some AEDs more than others are secreted to some extent in breast milk Most experts believe that benefits of breast feeding outweigh risks of AED Leviteracetam, Primidone have highest concentration in breast milk LTG, gabapentin and topiramate next highest VPA/CBZ/phenytoin/phenobarbitol amounts in breast milk felt not to be clinically significant Not many studies done on this do determine if there are any long-term negative effects

56 * even women long since seizure free may have seizures again in the pue

57 Risk of passing epilepsy on Broad and imprecise 1% if neither parent 4% if father 8% if mother 25% if both parents