Reproductive endocrine health in pubertal females with epilepsy on antiepileptic drugs: time to screen?

OBJECTIVES: Although previous studies suggest that valproate (VPA) may induce reproductive endocrine disorders, the effects of newer antiepileptic drugs (AEDs) on reproductive endocrine health have not been widely investigated and compared with those of older AEDs. Therefore, this multicenter cross-sectional study aimed to evaluate the prevalence of reproductive endocrine dysfunctions in pubertal females with epilepsy receiving VPA, lamotrigine (LTG), or levetiracetam (LEV) monotherapy. PATIENTS AND METHODS: Pubertal girls on VPA (n = 11), LTG (n = 8), or LEV (n = 13) monotherapy for at least 6 months were recruited. Healthy sex-matched and age-matched subjects were enrolled as controls (n = 32). Each participant underwent a comprehensive physical examination concerning signs of hyperandrogenism. The Ferriman-Gallwey score of hirsutism was assessed. In addition, all patients completed a standardized questionnaire regarding epilepsy, menstrual cycle, and hirsutism features. Adiposity indices were measured and weight gain was documented for each subject. RESULTS: Hirsutism score, occurrence of hyperandrogenism features, and adiposity indices were significantly higher in the VPA group when compared with LEV and control groups. VPA therapy was more frequently associated with weight gain when compared with LTG and controls, whereas no significant differences with regard to signs of hyperandrogenism were found between VPA and LTG groups. Furthermore, no differences in menstrual disorders were observed between groups. CONCLUSIONS: Pubertal girls with epilepsy receiving VPA monotherapy were more likely to develop signs of hyperandrogenism, that is, hirsutism and acanthosis, than those on LEV or controls. However, no differences in occurrence of menstrual disorders and other reproductive dysfunctions were found between VPA, LTG, LEV, and control groups. These findings do not allow us to clearly determine whether or not VPA, LEV, and LTG monotherapies considerably affect reproductive endocrine health in pubertal girls with epilepsy. Therefore, further prospective studies of larger sample sizes are needed to establish if screening tests should be recommended.

Complete removal of vagus nerve stimulator generator and electrodes.

Vagus nerve stimulation has become widely used in the palliative treatment of refractory epilepsy. Removal of a vagus nerve stimulator may be desirable or even necessary due to lack of efficacy, intolerable side effects, signs of infection, or failure of the device. Unless the lead or the helical electrodes are defective, only the generator is explanted and the electrodes are usually left behind for fear of damaging nerve or surrounding structures. The authors review their experience with complete removal of the stimulating electrodes and pacemaker-like generator device in 9 consecutive patients, 3 of whom were children. Using microsurgical techniques, the authors were able to completely remove the stimulator, including electrodes in all patients. All nerves remained morphologically intact. One case of temporary and one of permanent clinically silent ipsilateral vocal cord paresis were observed.

Brain-type natriuretic peptide release and seizure activity during vagal nerve stimulation.

Vagus nerve stimulation (VNS) has emerged as an effective adjunctive therapy for medically refractory epilepsy when surgery is inadvisable. N-terminal brain-type natriuretic peptide (NT-proBNP) is a potent natriuretic, diuretic, and vasodilatative compound first discovered in the human brain but mainly synthesized in the myocardium. The monitoring of VNS effectiveness in reducing seizure frequency or the detection of possible cardiac adverse effects would be helped by a reliable biochemical marker, which has not been available thus far. We report a four-year-old boy with drug-resistant idiopathic generalized epilepsy whose NT-proBNP levels increased during VNS and seizures.