how are women different from men? barbara c. jobst, md professor of neurology geisel school of...
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How are women different from men?
Barbara C. Jobst, MD
Professor of Neurology
Geisel School of Medicine
Director, Dartmouth-Hitchcock
Epilepsy Center
Women with Epilepsy:
Maintaining Health
Are women stronger?
Are women smarter?
Are women more beautiful?
Are women less aggressive?
Are women more likely to have epilepsy? Women get
pregnant and have babies
Risk of Malformation
Antiepileptic medication which
epilepsy Seizures during pregnancy
30 % cleft lipNeural tube defects/
open spineheart disease“look funny”
2-3%
4-8%
Intelligence? Behavior?
IQ in offspring of epileptic mothers
Gaily et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology 2004:62:28-32
Group n V-IQ P-IQ Full scale IQ
all epileptics 182 92.8 100.3 96.0no drugs 45 94.3 98.6 95.6monotherapy 107 94.4 101.9 98.0CBZ monotherapy 86 96.2 103.1 99.7VPA monotherapy 13 83.5 96.3 89.7polytherapy 30 84.9 97.1 89.5VPA polytherapy 17 81.5 96.1 86.6control 141 94.9 102.4 97.6
Neural tube defects/ open spine
6:10,000=0.0006%
Valproic acid 1%-2%1
Carbamazepine 0.5%2
Others
? Dose dependent3
Folate 600mcg – 4mg
1 Lindhout et al. In-utero exposure to valproate and neural tube defects. Lancet 1986;1:1392-13932 Rosa FW. Spina bifida in infants of women treated with with Carbamazepine during pregnancy, N Engl J med 1991;324:674-677.3 Kaneko S et al. Congenital malformations due to
antiepileptic drugs . Epilepsy Research 199;3:145-158.
Medications in pregnancy Phenobarbital D Diazepam / Valium® D Phenytoin/ Dilantin® D Carbamazepine/ Carbatrol ® D Valproic acid/Depakote ® D Felbatol/ Felbamate ® C Lamotrigine/ Lamitctal ® C Gabapentin/ Neurontin ® C Topiramate/ Topamax ® C
Zonisamide/ Zonegran ® C Tiagabin/ Gabatril ®
C Levetiracetam/ Keppra ® C Oxcarbazepine/ Trileptal ®
C
D= evidence of risk for humansC= evidence of risks for animals, not proven in humans
Pregnancy Registries
North American Registry
Australian Registry
UK registry
Indian Registry
EURAP
N=5750
N=485
N=3609
N=1071
N=3749
North American Registry
Valproic Acid (Depakote®) has increased malformation , possibly dose dependent > 1000mg
Phenobarbital increases malformation rate more than others
Carbamazepine (Tegretol® and Carbatrol ®) fares well; overrepresentation of cleft lip and palate
Topiramate (Topamax®) associated with cleft lip
Malformation rates
Valproate (Depakote®) 9.3% Phenobarbital 4.2% Topiramate(Topamax®) 3% Phenytoin (Dilantin®) 2.9 % Levetiracetam (Keppra®) 2.4% Lamotrigine (Lamictal®) 2.0%
Lamotrigine (Lamictal® in pregnancy Association of cleft lip with lamotrigine as reported by North American
Registry is still discussed. Cleft lip is overrepresented in still low percentage of malformations (2.6% in 1053 monotherapy pregnancies).
UDP glucoronosyltransferase
LTG
Glucuronidation
Steroids
Induction
Postpartum median increase in plasma concentration 170% per dose
Pennell PB, Newport DJ, Stowe ZN, et al. The impact of pregnancy and childbirth on the metabolism oflamotrigine. Neurology 2004; 62(2): 292-5
Recommendations
Plan your pregnancy! Talk to your doctor Don’t have epilepsy run your life! Switch to one drug if possible Have levels checked before pregnancy Take folic acid at a higher dose (1-4 mg)
Seizures during Pregnancy
1/3 less, 1/3 more seizures, 1/3 same 1st trimester seizures: 12.3 % risk of
malformation, 4% at other times higher risk of malformation Grand Mal seizures are assumed to be more
harmful No increased seizures during delivery No Cesarean section necessary, normal birth
Other considerations
•Vitamin K needs to be taken throughout the last month of pregnancy to prevent bleeding in mother and baby
•Medications levels change during pregnancy and levels should be checked every month or every other month.
•Breastfeeding is generally okay, as the baby is exposed to most medication in the womb
What we do Provide clinical services to women
with epilepsy and women’s health related issues
Provide counseling in pregnancy Follow the patient during pregnancy and
develop a delivery plan Provide hormonal treatment, research
regarding hormonal therapy Encourage registration into pregnancy
registries
Delivery and breast feeding
No special precautions for delivery
Breast feeding is in generally encouraged
Birth control
Birth control pills: Estrogen generally increases seizure frequency Progesterone seems to be anticonvulsive
Can worsen seizures
Methylprogesterone (Depot-Provera®) Concerns about osteoporosis
Barrier methods IUDs
Birth control
Seizure medications can make birth control pills ineffective
Inducers
Carbamazepine Tegretol®, Carbatrol ®
Oxcarbazepine Trileptal ®Phenytoin Dilantin ®
Topiramate Topamax ® >200mg Phenobarbital
No effectLamotrigine Lamictal ®Gabapentin Neurotin ®
Ethosuximide Zarontin ®Levetiracetam Keppra ®
Tiagabine Gabatril ®Zonisamide Zonegran ®
Valproic acid Depakote ®
Stronger birth control pill recommended
Preferred mode of birth control
IUD: intrauterine device (mirena) Can be easily placed and removed No hormones to the blood or brain Low failure rate
Epilepsy and Hormones
10%-78% of patients have worse seizures around their period, or only at the time of their period.
Estrogen makes seizures worse and progesterone make seizures better
Treatment with hormones
Depot- Provera (three month shot) Prosterone logenzes work when seizures
cluster around the period (need special compounding)
Bone healthAll female patients (>12 years old) taking seizure medications for 2-5 years
Bone density scan
NormalT score>-1
OsteopeniaT score -1 to 2.5
OsteoporosisT-score >-2.5
Calcium 1200mgVitamin 400 U
Repeat scan in 2-4 years
Calcium 1800mgVit D 800U or >
lifestyle
Repeat scan in 18 months
Take calcium and Vit D and Bone build up medications
American Epilepsy Society Task Force on Concerns for women with Epilepsy: Neurology 2003;61:S16-22
Weight
•Valproic Acid (Depakote) •Pregabalin (Lyrica)•Gabapentin (Neurontin)
•Topiramate (Topamax)•Ethosuximide (Zarontin)•Zonisamide (Zonegran)•Levetiracetam (Keppra)
•Lamotrigine (Lamictal)•Carbamazepine (Tegretol)•Oxcarbazepin (Trileptal)•Phenytoin (Dilantin)
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