Abstracts

RATIONALE: Seizure frequency and severity may be influenced by changes of ovarian steroids over the menstrual cycle (catamenial seizures)and throughout life. Very little is published about the effects of perimenopause on seizures: a decrease, no change or an increase in seizures has been reported. Patients who had a catamenial seizure pattern seem to be be more likely to suffer from an increase in seizure severity or frequency during perimenopause.
METHODS: Case report:
47 year old female, idiopathic generalized epilepsy with generalized tonic-clonic seizures after awakening since age 13. Since than under treatment with primidone monotherapy 1-2 GTCS/year, most seizurers occurring between days -2 and +2 of menstruation; 2 years completely seizure-free in her twenties while on depot progestins for contraception. Within the last 2 years seizure frequency increased to 2-3 GTCS/month despite dose increase of primidone to 750mg (PB 12,8 mg/l) with intolerable sedation. The patient suffered from mild climacteric symptoms and increasing irregularity of the menstrual cycle. Repeated laboratory testing revealed the perimenstrual status of the patient with increased FSH, elevated estradiol levels and inadequate synthesis of progesteron. After switch to lamotrigine monotherapy (400mg; 8,7 mg/l) no more sedation and better seizure control (0-1 GTCS/month), but not seizure-free.
RESULTS: Since add-on therapy with 4 mg chlormadinonacetat and 1 mg estradiolvalerate with no adverse effects and resolution of climacteric symptoms the patient is completely free of seizures for more than 18 month.
CONCLUSIONS: During premenopause follicular maturation is disturbed prior to exhaustion of follicles. Endocrinologically this process is associated with fluctuating ovarian hormon production and altered feedback regulation of the pituitary: Inhibine declines, FSH increases and estrogen levels vary. Progesterone production is impaired, but peak estrogen levels are no different or even higher than in younger women. Since progesterone has anticonvulsive and estrogene proconvulsive properties, it is not surprising that these perimenopausal hormonal changes may lead to poorer seizure control.
Various strategies to suppress hormonal fluctuations have been proposed: gonadotropine-releasing-hormone-analoga are effective in suppressing ovarian function but have many unfavourable side effects. A continous-combined progestin/estrogen therapy is also effective in suppressing the ovarian function with much less side-effects. This therapy is well tolerated and may be a treatment option in patiens with decreased seizure control due to hormonal fluctuations during perimenopause, as described in our case for the first time.
Disclosure: Honoraria - GlaxoSmithKline, Janssen-Cilag, Sanofi-Synthelabo, UCB, Novartis, Pfizer, Schering, Jenapharm