Frauen mit Epilepsie: 7 wichtige Aspekte

Zusammenfassung

Weibliche Geschlechtshormone scheinen eine Rolle in der Epileptogenese zu spielen. Ein Teil der Frauen mit Epilepsie leidet unter zyklusabhängigen Anfällen. Die Fertilität von Frauen mit Epilepsie ist geringer als jene der Allgemeinbevölkerung. Antiepileptika haben einen Einfluss auf weibliche Geschlechtshormone. Für einige Antiepileptika wurden Wechselwirkungen mit hormonellen Kontrazeptiva beschrieben. So schwanken z. B. die Plasmaspiegel von Lamotrigin während des normalen Zyklus bzw. unter Einnahme von oralen Kontrazeptiva. Umgekehrt können Enzym-induzierende Antikonvulsiva (Carbamazepin, Eslicarbazepin, Oxcarbazepin, Phenytoin, Primidon) die Wirksamkeit von oralen Kontrazeptiva deutlich abschwächen. Ein polyzystisches Ovar-Syndrom wird häufiger bei Frauen, die Valproinsäure einnehmen, diagnostiziert. 50% der Patientinnen unter einer antiepileptischen Dauermedikation leidet unter einer Osteopathie. Das Risiko einer Malformation ist bei Kindern von Müttern mit Epilepsie, die Antiepileptika einnehmen, etwa doppelt so hoch wie bei Kindern von gesunden Müttern. Die häufigsten Malformationen nach Antiepileptika-Exposition des Kindes während der Schwangerschaft betreffen das Herz. Das Risiko einer Malformation dürfte besonders hoch bei Valproinsäure-Tagesdosen von über 1 000 mg sein. Im Gegensatz dazu legen die Ergebnisse einer rezenten Populations-basierten Studie nahe, dass unter folgenden neueren Antikonvulsiva kein erhöhtes Risiko für schwere kindliche Malformationen bestehen dürfte: Lamotrigin, Oxcarbazepin, Topiramat, Gabapentin und Levetiracetam. Kinder, deren Mütter während der Schwangerschaft mit Valproinsäure behandelt wurden, wiesen geringere IQ Werte auf als Kinder, deren Mütter ein anderes Antiepileptikum einnahmen. Zur Verhinderung von Neuralrohrdefekten sollte bei allen gebärfähigen Frauen mit Epilepsie unbedingt eine Folsäure-Prophylaxe erfolgen.

Abstract

Sex steroid hormones are thought to play a role in epileptogenesis. Thus, seizure patterns may fluctuate with the menstrual cycle. In women with epilepsy, fertility is lower compared with the general population. Antiepileptic drugs influence fertility and some of them interact with oral contraceptives. Plasma levels of lamotrigine, for example, vary during the regular menstrual cycle as well as in women who take hormonal contraceptives. Conversely, enzyme-inducing antiepileptic drugs (carbamazepine, eslicarbazepine, oxcarbazepine, phenytoin, primidon) influence the effectivity of oral contraceptives. A polycystic ovary syndrome is frequent in women with epilepsy under treatment with valproic acid. 50% of women with epilepsy receiving antiepileptic drugs suffer from osteopathy. Children exposed to antiepileptic drugs during pregnancy have a higher risk for malformations than unexposed children. In this population, cardiac defects are the most common form of malformations. Treatment with valproic acid, especially in daily doses exceeding 1 000 mg, carries a particularly high risk for congenital malformations. In contrast, according to a population based trial, the risk for malformations may not be increased with the new antiepileptic drugs gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate. Children exposed to valproic acid during pregnancy had lower IQ levels than children exposed to other antiepileptic drugs. Folic acid supplementation is recommended in all women with epilepsy in child-bearing age to prevent neural-tube defects.

Schlüsselwörter

Schwangerschaft - Frauen mit Epilepsie - Anfälle - weiblich

Key words

pregnancy - women with epilepsy - seizure - female

• Literatur

• 1 Herzog AG, Seibel MM, Schomer DL et al. Reproductive endocrine disorders in women with partial seizures of temporal lobe origin. Arch Neurol 1986; 43 (04) 341-346
• 2 Verrotti A, D’Egidio C, Coppola G et al. Epilepsy, sex hormones and antiepileptic drugs in female patients. Expert Rev Neurother 2009; 9 (12) 1803-1814
• 3 Herzog AG. Disorders of reproduction in patients with epilepsy: primary neurological mechanisms. Seizure 2008; 17: 101-110
• 4 Hu X, Wang J, Dong W et al. A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy. Epilepsy Res 2011; 97 (1-2) 73-82
• 5 Sukumaran SC, Sarma PS, Thomas SV. Polytherapy increases the risk of infertility in women with epilepsy. Neurology 2010; 75 (15) 1351-1355
• 6 Schwenkhagen AM, Stodieck SR. Which contraception for women with epilepsy?. Seizure 2008; 17 (02) 145-150
• 7 Pennell PB. Hormonal aspects of epilepsy. Neurol Clin 2009; 27 (04) 941-965
• 8 Weil S, Deppe C, Noachtar S. The treatment of women with epilepsy. Dtsch Arztebl Int 2010; 107 (45) 787-793
• 9 Ohman I, Luef G, Tomson T. Effects of pregnancy and contraception on lamotrigine disposition: new insights through analysis of lamotrigine metabolites. Seizure 2008; 17 (02) 199-202
• 10 Christensen J, Petrenaite V, Atterman J et al. Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia 2007; 48 (03) 484-489
• 11 Tomson T, Battino D, Bonizzoni E et al. EURAP study group . Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry. Lancet Neurol 2011; 10: 609-617
• 12 Harden CL, Meador KJ, Pennell PB et al. Practice parameter update: management issues for women with epilepsy – focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009; 73 (02) 133-141
• 13 The EURAP Study Group . Seizure control and treatment in pregnancy: observations from the EURAP epilepsy pregnancy registry. Neurology 2006; 66 (03) 354-360
• 14 Pennell PB, Peng L, Newport DJ et al. Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology 2008; 70: 2130-2136
• 15 Fotopoulou C, Kretz R, Bauer S et al. Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res 2009; 85: 60-64
• 16 Harden CL, Herzog AG, Nikolov BG et al. Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study. Epilepsia 2006; 47 (09) 1447-1451
• 17 Harden CL, Hopp J, Ting TY et al. Practice parameter update: management issues for women with epilepsy – focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009; 73 (02) 126-132
• 18 Westin AA, Nakken KO, Johannessen SI et al. Serum concentration/dose ratio of topiramate during pregnancy. Epilepsia 2009; 50 (03) 480-485
• 19 Longo B, Forinash AB, Murphy JA. Levetiracetam use in pregnancy. Ann Pharmacother 2009; 43 (10) 1692-1695
• 20 Pennell PB. Pregnancy in the woman with epilepsy: maternal and fetal outcomes. Semin Neurol 2002; 22 (03) 299-308
• 21 Chen YH, Chiou HY, Lin HC et al. Affect of seizures during gestation on pregnancy outcomes in women with epilepsy. Arch Neurol 2009; 66 (08) 979-984
• 22 Adab N, Kini U, Vinten J et al. The longer term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 2004; 75 (11) 1575-1583
• 23 Harden CL, Pennell PB, Koppel BS et al. Practice parameter update: management issues for women with epilepsy – focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology 2009; 73 (02) 142-149
• 24 Bagshaw J, Crawford P, Chappell B. Problems that mothers' with epilepsy experience when caring for their children. Seizure 2008; 17 (01) 42-48
• 25 Meador KJ, Baker GA, Browning N et al. NEAD Study Group . Foetal antiepileptic drug exposure and verbal versus non-verbal abilities at three years of age. Brain 2011; 134 (02) 396-404
• 26 Hovinga CA, Pennell PB. Antiepileptic drug therapy in pregnancy II: fetal and neonatal exposure. Int Rev Neurobiol 2008; 83: 241-258
• 27 Chen L, Liu F, Yoshida S et al. Is breast-feeding of infants advisable for epileptic mothers taking antiepileptic drugs?. Psychiatry Clin Neurosci 2010; 64: 460-468
• 28 Fried S, Kozer E, Nulman I et al. Malformation rates in children of women with untreated epilepsy: a meta-analysis. Drug Saf 2004; 27 (03) 197-202
• 29 Meador K, Reynolds MW, Crean S et al. Pregnancy outcomes in women with epilepsy: a systematic review and meta-analysis of published pregnancy registries and cohorts. Epilepsy Res 2008; 81 (01) 1-13
• 30 Mølgaard-Nielsen D, Hviid A. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA 2011; 305 (19) 1996-2002
• 31 Linnebank M, Moskau S, Semmler A et al. Antiepileptic drugs interact with folate and vitamin B12 serum levels. Ann Neurol 2011; 69: 352-359
• 32 Meador KJ, Baker GA, Browning N et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs. N Engl J Med 2009; 360 (16) 1597-1605
• 33 Shallcross R, Bromley RL, Irwin B et al. Liverpool Manchester Neurodevelopment Group; UK Epilepsy and Pregnancy Register . Child development following in utero exposure: levetiracetam vs sodium valproate. Neurology 2011; 76 (04) 383-389
• 34 Cohen MJ, Meador KJ, Browning N et al. Fetal antiepileptic drug exposure: motor, adaptive, and emotional/behavioral functioning at age 3 years. Epilepsy Behav 2011; 22 (02) 240-246
• 35 Forsberg L, Wide K, Källén B. School performance at age 16 in children exposed to antiepileptic drugs in utero – a population-based study. Epilepsia 2011; 52 (02) 364-369
• 36 Winawer MR, Shinnar S. Genetic epidemiology of epilepsy or what do we tell families?. Epilepsia 2005; 46 (Suppl. 10) 24-30
• 37 Bauer J, Cooper-Mahkorn D. Reproductive dysfunction in women with epilepsy: menstrual cycle abnormalities, fertility, and polycystic ovary syndrome. Int Rev Neurobiol 2008; 83: 135-155
• 38 Bauer J. Interactions between hormones and epilepsy in female patients. Epilepsia 2001; 42 (Suppl. 03) 20-22
• 39 Herzog AG. Catamenial epilepsy: definition, prevalence pathophysiology and treatment. Seizure 2008; 17 (02) 151-159
• 40 Feely M, Gibson J. Intermittent clobazam for catamenial epilepsy: tolerance avoided. J Neurol Neurosurg Psychiatry 1984; 47 (12) 1279-1282
• 41 Morrell MJ, Hayes FJ, Sluss PM et al. Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine. Ann Neurol Aug 2008; 64 (02) 200-211
• 42 Vainionpää LK, Rättyä J, Knip M et al. Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. Ann Neurol 1999; 45 (05) 444-450
• 43 Isojärvi JI, Rattya J, Myllyla VV et al. Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. Ann Neurol 1998; 43 (04) 446-451
• 44 Rauchenzauner M, Haberlandt E, Scholl-Bürgi S et al. Effect of valproic acid treatment on body composition, leptin and the soluble leptin receptor in epileptic children. Epilepsy Res 2008; 80 (2–3) 142-149
• 45 Bartl R. Antiepileptic drug-induced osteopathy. Subtypes, pathogenesis, prevention, early diagnosis and treatment. Dtsch Med Wochenschr 2007; 132 (27) 1475-1479
• 46 Pack A. Bone health in people with epilepsy: is it impaired and what are the risk factors?. Seizure Mar 2008; 17 (02) 181-186
• 47 Harden CL. Issues for mature women with epilepsy. Int Rev Neurobiol 2008; 83: 385-395
• 48 Erel T, Guralp O. Epilepsy and menopause. Arch Gynecol Obstet 2011; 284 (03) 749-755