SWEDISH EPILEPSY SOCIETY ABSTRACTS

The treatment of pregnant epileptic women from the southeast region of Stockholm is centralised to a specialist clinic aiming at seizure control with as few drugs and drug levels as low as possible. We select a matched control to each baby at birth. All examinations are done blindly. Neo- natally the children are examined for minor malformations and basic body measurements are made. A child psychol- ogist performs a Griffith test at 9 months and 4 years of age. An eye examination is done at 7 years of age. To date, 90 pairs are included.

The preliminary results show a slight but statistically sig- nificant reduction in body length (11 mm) at birth, but no difference in head circumference. The total number of minor malformations is increased in the study group. There is no difference in the results of the Griffith test at 9 months nor in the eye examination. These preliminary results indi- cate that closely monitored treatment during pregnancy with low drug doses can limit the increased risk of abnor- malities in the children of epileptic women.

VASCULAR DISRUPTION AND FETAL HYPOXIA AS A MECHANISM FOR PHENYTOIN TERATOGENICITY: MORPHOLOGIC, HEMODYNAMIC, AND PHARMA- COKINETIC EVIDENCE IN AN ANIMAL MODEL. B.R. Danielsson, IC Danieisson, and T. Tomson (Department of Toxicology, Uppsala University, and Department of Neurology, Si~der Hospital, Stockholm).

Phenytoin (PHT) is an established human teratogen. Hypoplasia of nails and distal phalanges are the most con- sistent morphological findings. Less frequently, orofacial, central nervous system (CNS), and other major abnormal- ities have been reported. All these defects have been in- duced by PHT in nonepileptic animals (mice, rats, rabbits) as well. The same early pathological changes, resulting in the above-mentioned fetal defects at term, were observed after a single teratogenic dose of PHT as after temporary mechanical clamping of uterine vessels for 45 min during early postorganogenesis (day 16 of gestation). Histologi- cally, the digital areas of the limb plates showed extensive edema (within 3 h) followed by vascular disruption, hemor- rhages, and necrosis (within 24 h) of the distal parts of the digits. In the craniofacial region, superficial hemorrhage was seen in the frontal region, and some fetuses also showed hemorrhage in CNS. Hemodynamic results showed a de- crease in maternal heart rate and blood pressure (~15%) after a teratogenic dose of PHT, resulting in a decrease in Po 2 (~15%), an increase in Pco 2 (~ 15%), and a decrease in fetal heart rate (~ 15%). The maternal and fetal free plasma concentrations of PHT causing defects were in the range 6.0-12.7 lamol/L A nonteratogenic dose resulted in con- centrations between 0.6 and 5.0 lamol/L. Altogether, the results indicate that PHT causes malformations by dis- rupting previously established structures, secondary to pharmacologically induced fetal hypoxia during the sensi- tive period.

and Clinical Pharmacology, Karolinska Hospital, and Children's Hospital, University of HelsinkL Helsinki, Finland).

We studied the pharmacokinetics of lamotrigine in 31 epileptic children and young adults (mean age, 9.9 years; range, 2.5-22.0 years). The study was performed in the be- ginning of an open-dose-finding phase preceding a double- blind crossover study to evaluate the efficacy of lamotrigine in children with generalized intractable epilepsy. The chil- dren were treated with one to three concomitant antiepi- leptic drugs (AEDs). A single mean lamotrigine dose of 0.8 mg/kg was administered orally. Blood samples were drawn at 0, 0.5, 1, 3, 6, 9, 12, 24, 48, 60, and 72 h after the dose. Plasma lamotrigine concentrations were assayed with a novel high-performance liquid chromatography method. The patients simultaneously treated with valproate had a sig- nificantly longer tz/2 (mean, 52.5 h), and those on carbama- zepine (CBZ) a shorter tl/2 (17.2 h) than those on both val- proate and CBZ (32.7 h) or those on other AEDs (30.9 h).

Clearance was significantly higher in the CBZ group (mean, 1.41 ml/kg/h) than in all other groups (valproate, 0.47; valproate + CBZ, 0.59; other AEDs, 0.52). There was no statistically significant difference between the groups in Crn,x (mean, 0.72 ~g/ml), Tma x (mean, 2.5 H), or Varea/F/kg (mean, 1.63 L/kg).

Concomitant treatment with CBZ increases lamotrigine elimination in children and young adults. Combination treatment requires increased dose of lamotrigine. Combin- ation with valproate, on the other hand, should be started with a lower dose of lamotrigine.

LOW-DOSE TREATMENT WITH VIGABATRIN IN CHIL- DREN WITH TUBEROUS SCLEROSIS. A.-S. Eriksson and A. Nerg~rdh (Departments of Pediatrics and Clinical Pharmacol- ogy, Karolinska Hospital, Stockholm).

Eight children (4-20 years) with MRT-diagnosed tuber- ous sclerosis and epilepsy of generalized type were not sei- zure-free with available AEDs. They all had severe behav- ioral problems and seven were mentally retarded. Each patient was initially observed in steady state of antiepileptic treatment by the patients and the hospital staff and the level of aggressiveness and hyperactivity were recorded.

Add-on treatment of vigabatrin was then started in the first four patients in a dose of 40-50 mg/kg/day. Two pa- tients showed a good response in seizure reduction, but they all got increasing behavioral problems. To minimize the side effects and maintain the reduction in seizure fre- quency, we gradually reduced the vigabatrin dose to ap- proximately 20 mg/kg/day. We started the remaining four patients in a low dose of 12-27 mg/kg/day. Five of eight patients responded with >50% seizure reduction. Three patients became seizure-free. Fiveof eight patients are now treated with vigabatrin in monotherapy.

Our patients with tuberous sclerosis and epilepsy have had an excellent antiepileptic effect when treated with low doses of vigabatrin and without obvious side effects.

PHARMACOKINETICS OF LAMOTRIGINE IN CHIL- DREN WITH INTRACTABLE EPILEPSY. A.-S. Eriksson, IC Hoppu, A. Nerg~rdh, and L Boreus (Departments of Pediatrics

GROUP EDUCATION OF PATIENTS WITH EPILEPSY. A VALUABLE REHABILITATION METHOD.A. Nordeson, V.-A. Wikstr6m, G. Janz~n, B. Engstr6m, and J. Ekstedt

326 J EPILEPSY, VOL. 7, NO. 4, 1994