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Effects of Levetiracetam on EEG Activity and Regularity of the Menstrual Cycle in Women Suffering from Epilepsy

  • L. ZhizhiashviliEmail author
  • G. Japaridze
  • G. Lomidze
  • L. Maisuradze
  • S. Kasradze
Article
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Epilepsy itself and its treatment with anticonvulsants noticeably affect the reproductive function in women suffering from this disease. Levetiracetam (LEV) was shown to be highly effective for the reduction of clinical seizures and EEG epileptic activity. At the same time, its impact on the reproductive/endocrine functions is still unclear. The aim of our study was to evaluate the influence of LEV on the frequency of seizures and epilepsy-related EEG discharges, and also on the regularity of menstrual cycles (MCs) among women with epilepsy (WE) in Georgia. Seizures entirely disappeared in all examined WE with focal and bilateral tonico-clonic seizures (BTCSs), as well as in all cases with juvenile myoclonic epilepsy (JME) (P = 0.008). Six months after starting LEV monotherapy, a reduction in single and burst EEG epileptic discharges was observed in all eight women with JME (P = 0.031); weakening of burst discharges was also revealed in all patients with focal epilepsy (P = 0.046). Among examined WE with regular MCs, oligomenorrhea was observed in two cases from eight patients with focal epilepsy and in one case from seven women with JME treated with LEV. In general, LEV effectively suppresses paroxysmal EEG discharges and also improves clinical seizure control. There was no significant influence of LEV on the MC disturbances, while oligomenorrhea was found in some cases; thus, the respective effects on the MC were at least relatively moderate. More data are needed to establish the level of association between LEV therapy and reproductive endocrine disorders in WE.

Keywords

levetiracetam epileptic seizures epilepsy-related EEG phenomena menstrual cycle 

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References

  1. 1.
    A. K. Bassel, “Levetiracetam in the treatment of epilepsy,” Neuropsychiat. Dis. Treat., 4, No. 3, 507-523 (2008).Google Scholar
  2. 2.
    S. C. Sukumaran, P. S. Sarma, and S. V. Thomas, “Polytherapy increases the risk of infertility in women with epilepsy,” Neurology, 75, 1351-1355 (2010).CrossRefGoogle Scholar
  3. 3.
    P. Singh, M. Singh, G. Cugati, and A. K. Singh, “Effect of epilepsy on female fertility and reproductive abnormalities,” J. Human Reprod. Sci., 4, No. 2, 100-101 (2011).CrossRefGoogle Scholar
  4. 4.
    E. Tauboll, L. Sveberg Roste, S. Svalheim, and L. Gjerstad, “Disorders of reproduction in epilepsy-What can we learn from animal studies?” Seizure, 17, 120-126 (2008).CrossRefGoogle Scholar
  5. 5.
    G. H. Beastall, R. A. Cowan, J. M. Gray, and I. Fogelman, “Hormone binding globulins and anticonvulsant therapy,” Scott. Med. J., 30, 101-105 (1985).CrossRefGoogle Scholar
  6. 6.
    G. Murialdo, C. A. Galimberti, M. V. Gianelli, et al., “Effects of valproate, phenobarbital and carbamazepine on sex steroid setup in women with epilepsy,” Clin. Neuropharmacol., 21, 52-58 (1988).Google Scholar
  7. 7.
    J. I. Isojärvi, T. J. Laatikainen, A. J. Pakarinen, et al., “Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy,” New Engl. J. Med., 329, 1383-1388 (1993).CrossRefGoogle Scholar
  8. 8.
    J. I. Isojärvi, T. J, Laatikainen, M. Knip, et al., “Obesity and endocrine disorders in women taking valproate for epilepsy,” Ann Neurol., 39, 579-584 (1996).Google Scholar
  9. 9.
    J. I. Isojärvi, J. Rätty, V. V. Myllylä, et al., “Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy,” Ann. Neurol., 43, 446-451 (1998).CrossRefGoogle Scholar
  10. 10.
    L. K. Vainionpa, J. Rättya, M. Knip, et al., “Valproate induced hyperandrogenism during pubertal maturation in girls with epilepsy,” Ann. Neurol., 45, 444-450 (1999).CrossRefGoogle Scholar
  11. 11.
    J. Rättyä, A. J. Pakarinen, M. Knip, et al., “Early hormonal changes during valproate or carbamezapine treatment: a 3-month study,” Neurology, 57, 440-444 (2001).CrossRefGoogle Scholar
  12. 12.
    T. Betts, H. Yarrow, N. Dutton, et al., “A study of anticonvulsant medication on ovarian function in a group of women with epilepsy who have only ever taken one anticonvulsant compared with a group of women without epilepsy,” Seizure, 12, 323-329 (2003).CrossRefGoogle Scholar
  13. 13.
    V. L. Nelson-DeGrave, J. K. Wickenheisser, J. E. Cockrell, et al. “Valproate potentiates androgen biosynthesis in human ovarian theca cells,” Endocrinology, 1459, 799-808 (2004).CrossRefGoogle Scholar
  14. 14.
    J. Isojärvi, “Disorders of reproduction in patients with epilepsy: Antiepileptic drug related mechanisms,” Seizure, 17, 111-119 (2008).CrossRefGoogle Scholar
  15. 15.
    B. A. Lynch, N. Lambeng, K. Nocka Kensel-Hammes, et al., “The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam,” Proc. Natl. Acad. Sci. USA, 101, 9861-9866 (2004)CrossRefGoogle Scholar
  16. 16.
    I. Niespodziany, H. Klitgaard, and D. G. Margineanu, “Desynchronizing effect of levetiracetam on epileptiform responses in rat hippocampal slices,” NeuroReport, 14, 1273-1276 (2003).CrossRefGoogle Scholar
  17. 17.
    A. J. Gower, E. Hirsch, A. Boehrer, et al., “Effects of levetiracetam, a novel antiepileptic drug, on convulsant activity in two genetic rat models of epilepsy,” Epilepsy Res., 22, 207-213 (1995).CrossRefGoogle Scholar
  18. 18.
    S. D. Shorvon, A. Lowental, D. Janz, et al., “Multicenter double-blind, randomized, placebo-controlled trial of levetiracetam as add-on therapy in patients with refractory partial seizures European Levetiracetam Study Group,” Epilepsia, 41, 1179-1186 (2000).CrossRefGoogle Scholar
  19. 19.
    J. J. Cereghino, V. Biton, A. K. Bassel, et al., “Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial,” Neurology, 55, 236-242 (2000).CrossRefGoogle Scholar
  20. 20.
    E. Ben-Menachem and U. Falter, “Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European levetiracetam study group,” Epilepsia, 41, 1276-1283 (2000).CrossRefGoogle Scholar
  21. 21.
    J. J. Tsai, D. J. Yen, M. S. Hsih, et al., “Efficacy and safety of levetiracetam [up to 2000 mg/day] in Taiwanese patients with refractory partial seizures: a multicenter, randomized, double-blind, placebo-controlled study,” Epilepsia, 47, 72-81 (2006).CrossRefGoogle Scholar
  22. 22.
    T. M. Alsaadi, A. Shatzel, A. V. Marquez, et al., “Clinical experience of levetiracetam monotherapy for adults with epilepsy: 1-year follow-up study,” Seizure, 14, 139-142 (2005).CrossRefGoogle Scholar
  23. 23.
    M. J. Brodie, E. Perucca, P. Ryvilin, et al., “Comparison of levetiracetam and controlled release carbamazepine in newly diagnosed epilepsy,” Neurology, 68, No. 6, 402-408 (2007).CrossRefGoogle Scholar
  24. 24.
    C. Di Bonaventura, J. Fattouch, F. Mari, et al., “Clinical experience with levetiracetam in idiopathic generalized epilepsy according to different syndrome subtypes,” Epileptic Dis., 7, 31-35 (2005).Google Scholar
  25. 25.
    S. P. Kumar and P. E. Smith, “Levetiracetam as add-on therapy in generalized epilepsies,” Seizure, 13, 475-477 (2004).CrossRefGoogle Scholar
  26. 26.
    G. L. Krauss, T. Betts, A. K. Bassel, et al., “Levetiracetam treatment of idiopathic generalised epilepsy,” Seizure, 12, 617-620 (2003).CrossRefGoogle Scholar
  27. 27.
    L. M. Specchio, A. Gambardella, A. T. Giallonardo, et al., “Open label, long-term, pragmatic study on levetiracetam in the treatment of juvenile myoclonic epilepsy,” Epilepsy Res., 71, 32-39 (2006).CrossRefGoogle Scholar
  28. 28.
    D. V. Sharpe, A. D. Patel, A. K. Bassel, et al., “Levetir-acetam monotherapy in juvenile myoclonic epilepsy,” Seizure, 17, 64-68 (2008).CrossRefGoogle Scholar
  29. 29.
    S. Stodieck, B. J. Steinhoff, S. Kolmsee, and K. van Rijckevorsel, “Effect of levetiracetam in patients with epilepsy and interictal epileptiform discharges,” Seizure, 10, 583-587 (2001).CrossRefGoogle Scholar
  30. 30.
    N. Specchio, G. Boero, R. Michelucci, et al., “Effects of levetiracetam on EEG abnormalities in juvenile myoclonic epilepsy,” Epilepsia, 49, 663-669 (2008).CrossRefGoogle Scholar
  31. 31.
    M. J. Gallagher, L. N. Eisenman, K. M. Brown, et al., “Levetiracetam reduces spike-wave density and duration during long-term EEG monitoring in patients with idiopathic generalized epilepsy,” Epilepsia, 45, 90-91 (2004).CrossRefGoogle Scholar
  32. 32.
    J. Cavitt and M. Privitera, “Levetiracetam induces a rapid and sustained reduction of generalized spike-wave and clinical absence,” Arch. Neurol., 61, 1604-1607 (2004).CrossRefGoogle Scholar
  33. 33.
    A. Covanis and M. Katsalouli, “Levetiracetam monotherapy in generalized epilepsy and photosensitivity,” Epilepsia, 44, Suppl. 8, 80 (2003).Google Scholar
  34. 34.
    E. Tauboll, E. L. Gregoraszczuk, A. Tworzydo, et al., “Comparison of reproductive effects of levetiracetam and valproate studied in prepubertal porcine ovarian follicular cells,” Epilepsia, 47, 1580-1583 (2006).CrossRefGoogle Scholar
  35. 35.
    S. Svalheim, E. Tauboll, K, Surdova, et al., “Long-term levetiracetam treatment affects reproductive endocrine function in female Wistar rats,” Seizure, 17, 203-209 (2008).Google Scholar
  36. 36.
    E. Tauboll, L. E. Gregoraszczuk, A. K. Wojtowicz, and T. Milewicz, “Effects of levetiracetam and valproate on reproductive endocrine function studied in human ovarian follicular cells,” Epilepsia, 50, No. 8, 1868-1874 (2009).CrossRefGoogle Scholar
  37. 37.
    A. T. Berg, S. F. Berkovic, M. J. Brodie, et al., “Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology 2005-2009,” Epilepsia, 51, 676-685 (2010).CrossRefGoogle Scholar
  38. 38.
    D. G. Kasteleijn-Nolst Trenité, C. D. Binnie, G. F. Harding, et al., “Photic stimulation: Standardization of screening methods,” Epilepsia, 40, 75-79 (1999).CrossRefGoogle Scholar
  39. 39.
    H. O. Luders and S. S. Noachter, Atlas and Classification of Electroencephalography, WB Saunders, Philadelphia (2000).Google Scholar
  40. 40.
    S. Noachtar, C. Binnie, J. Ebersole, et al., “A glossary of terms most commonly used by clinical electroencephalographers and proposal for the report for the EEG findings,” Electroencephalogr. Clin. Neurophysiol., 52, Suppl, 21-41 (1999).Google Scholar
  41. 41.
    S. Beniczky, H. Aurlien, J. C. Brøgger, et al., “Standardized computer-based organized reporting of EEG: SCORE,” Epilepsia, 54, No. 6, 1112-1124 (2013).CrossRefGoogle Scholar
  42. 42.
    D. G. Kasteleijn-Nolst Trenité, , R. Guerrini, C. D. Binnie, and P. Genton, “Visual sensitivity and epilepsy: a proposed terminology and classification for clinical and EEG phenomenology,” Epilepsia, 42, No. 5, 692-701 (2001).Google Scholar
  43. 43.
    O. F. Vollman, “The menstrual cycle,” in: Major Problems in Obstetrics and Gynecology, Friedman E. (ed.), WB Saunders, Philadelphia (1977), pp. 1-193.Google Scholar
  44. 44.
    A. E. Treloar, R. E. Boynton, G. B. Borghild, et al., “Variation of the human menstrual cycle through reproductive life,” Int. J. Fertil., 12, 77-126 (1967).Google Scholar
  45. 45.
    A. G. Herzog and M. N. Friedman, “Menstrual cycle interval and ovulation in women with localization-related epilepsy,” Neurology, 57, 2133-2135 (2001).CrossRefGoogle Scholar
  46. 46.
    D. S. Kiddy, P. S. Sharp, D. M. White, et al., “Differences in clinical and endocrine features between obese and non-obese subjects with polycystic ovary syndrome, an analysis of 263 consecutive cases,” Clin. Endocrinol., 32, 213-230 (1990).CrossRefGoogle Scholar
  47. 47.
    J. M. Tanner and R. H. Whitehouse, “Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty,” Arch. Dis. Childhood, 51, 170-179 (1976).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • L. Zhizhiashvili
    • 1
    • 2
    Email author
  • G. Japaridze
    • 1
  • G. Lomidze
    • 1
    • 2
  • L. Maisuradze
    • 1
    • 4
  • S. Kasradze
    • 1
    • 3
  1. 1.Institute of Neurology and NeuropsychologyTbilisiGeorgia
  2. 2.Javakhishvili Tbilisi State UniversityTbilisiGeorgia
  3. 3.Caucasus International UniversityTbilisiGeorgia
  4. 4.Ilia State UniversityTbilisiGeorgia

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