Absence Epilepsy: Older vs Newer AEDs

EPILEPSY (E WATERHOUSE, SECTION EDITOR)
Part of the following topical collections:
  1. Topical Collection on Epilepsy

Opinion statement

Over the last one to two decades, several new antiepileptic drugs (AEDs) have become available. These medications have different mechanisms of action, metabolism, efficacy, and side effect profiles. Hence, it has become possible to customize medications for a particular patient. It has also become possible to use various combinations of treatments for refractory epilepsies. As medication options have increased, our goal has shifted to not only to maximize seizure control but also to minimize side effects. However, the older AEDs are still widely used. So the question arises—are newer medications better than older AEDs for the treatment of absence epilepsy? Based on a large multicenter class I study, older AEDs—ethosuximide and valproic acid—are more efficacious than newer AEDs. Due to reduced side effects, ethosuximide remains the first line treatment for childhood absence epilepsy.

Keywords

Epilepsy Antiepileptic drugs Treatment AED Childhood absence epilepsy Juvenile absence epilepsy Jeavons syndrome 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Jeffrey R. Tenney has received grant support from Citizens United for Research in Epilepsy (CURE). Sejal Jain declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

  1. 1.
    Penry JK, Dreifuss FE. Automatisms associated with the absence of petit mal epilepsy. Arch Neurol. 1969;21(2):142–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B, et al. Two-year remission and subsequent relapse in children with newly diagnosed epilepsy. Epilepsia. 2001;42(12):1553–62.PubMedCrossRefGoogle Scholar
  3. 3.
    Fois A, Malandrini F, Mostardini R. Clinical experiences of petit mal. Brain Dev. 1987;9(1):54–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Loiseau P, Pestre M, Dartigues JF, Commenges D, Barberger-Gateau C, Cohadon S. Long-term prognosis in two forms of childhood epilepsy: typical absence seizures and epilepsy with rolandic (centrotemporal) EEG foci. Ann Neurol. 1983;13(6):642–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Sato S, Dreifuss FE, Penry JK, Kirby DD, Palesch Y. Long-term follow-up of absence seizures. Neurology. 1983;33(12):1590–5.PubMedCrossRefGoogle Scholar
  6. 6.
    Sillanpaa M, Jalava M, Kaleva O, Shinnar S. Long-term prognosis of seizures with onset in childhood. N Engl J Med. 1998;338(24):1715–22.PubMedCrossRefGoogle Scholar
  7. 7.
    Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, et al. Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol. 2004;251(10):1235–41.PubMedCrossRefGoogle Scholar
  8. 8.••
    Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: initial monotherapy outcomes at 12 months. Epilepsia. 2013;54(1):141–55. This article reports longer-term results from a large multi-center, randomized controlled study in children with CAE.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.••
    Glauser TA, Cnaan A, Shinnar S, Hirtz DG, Dlugos D, Masur D, et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med. 2010;362(9):790–9. This article reports initial results from a large multi-center, randomized controlled study in children with CAE.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Henkin Y, Sadeh M, Kivity S, Shabtai E, Kishon-Rabin L, Gadoth N. Cognitive function in idiopathic generalized epilepsy of childhood. Dev Med Child Neurol. 2005;47(2):126–32.PubMedCrossRefGoogle Scholar
  11. 11.
    Levav M, Mirsky AF, Herault J, Xiong L, Amir N, Andermann E. Familial association of neuropsychological traits in patients with generalized and partial seizure disorders. J Clin Exp Neuropsychol. 2002;24(3):311–26.PubMedCrossRefGoogle Scholar
  12. 12.
    Pavone P, Bianchini R, Trifiletti RR, Incorpora G, Pavone A, Parano E. Neuropsychological assessment in children with absence epilepsy. Neurology. 2001;56(8):1047–51.PubMedCrossRefGoogle Scholar
  13. 13.
    Vega C, Guo J, Killory B, Danielson N, Vestal M, Berman R, et al. Symptoms of anxiety and depression in childhood absence epilepsy. Epilepsia. 2011;52(8):e70–4.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Wirrell EC, Camfield CS, Camfield PR, Dooley JM, Gordon KE, Smith B. Long-term psychosocial outcome in typical absence epilepsy. Sometimes a wolf in sheeps’ clothing. Arch Pediatr Adolesc Med. 1997;151(2):152–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Berg AT, Shinnar S, Levy SR, Testa FM, Smith-Rapaport S, Beckerman B. How well can epilepsy syndromes be identified at diagnosis? A reassessment 2 years after initial diagnosis. Epilepsia. 2000;41(10):1269–75.PubMedCrossRefGoogle Scholar
  16. 16.
    Jallon P, Loiseau P, Loiseau J. Newly diagnosed unprovoked epileptic seizures: presentation at diagnosis in CAROLE study. Coordination Active du Reseau Observatoire Longitudinal de l’ Epilepsie. Epilepsia. 2001;42(4):464–75.PubMedCrossRefGoogle Scholar
  17. 17.
    Panayiotopoulos CP. Typical absence seizures and their treatment. Arch Dis Child. 1999;81(4):351–5.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1989;30(4):389‒99.Google Scholar
  19. 19.
    Fisher RS, van Emde BW, Blume W, Elger C, Genton P, Lee P, et al. Epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia. 2005;46(4):470–2.PubMedCrossRefGoogle Scholar
  20. 20.
    Mullen SA, Suls A, De Jonghe P, Berkovic SF, Scheffer IE. Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency. Neurology. 2010;75(5):432–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Bouma PA, Westendorp RG, van Dijk JG, Peters AC, Brouwer OF. The outcome of absence epilepsy: a meta-analysis. Neurology. 1996;47(3):802–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Bartolomei F, Roger J, Bureau M, Genton P, Dravet C, Viallat D, et al. Prognostic factors for childhood and juvenile absence epilepsies. Eur Neurol. 1997;37(3):169–75.PubMedCrossRefGoogle Scholar
  23. 23.
    Chaix Y, Daquin G, Monteiro F, Villeneuve N, Laguitton V, Genton P. Absence epilepsy with onset before age three years: a heterogeneous and often severe condition. Epilepsia. 2003;44(7):944–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Grosso S, Galimberti D, Vezzosi P, Farnetani M, Di Bartolo RM, Bazzotti S, et al. Childhood absence epilepsy: evolution and prognostic factors. Epilepsia. 2005;46(11):1796–801.PubMedCrossRefGoogle Scholar
  25. 25.
    Sillanpaa M, Jalava M, Shinnar S. Epilepsy syndromes in patients with childhood-onset seizures in Finland. Pediatr Neurol. 1999;21(2):533–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Sinclair DB, Unwala H. Absence epilepsy in childhood: electroencephalography (EEG) does not predict outcome. J Child Neurol. 2007;22(7):799–802.PubMedCrossRefGoogle Scholar
  27. 27.
    Wirrell E, Camfield C, Camfield P, Dooley J. Prognostic significance of failure of the initial antiepileptic drug in children with absence epilepsy. Epilepsia. 2001;42(6):760–3.PubMedCrossRefGoogle Scholar
  28. 28.
    Wirrell EC, Camfield CS, Camfield PR, Gordon KE, Dooley JM. Long-term prognosis of typical childhood absence epilepsy: remission or progression to juvenile myoclonic epilepsy [see comments]. Neurology. 1996;47(4):912–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Wirrell EC, Camfield PR, Camfield CS, Dooley JM, Gordon KE. Accidental injury is a serious risk in children with typical absence epilepsy [see comments]. Arch Neurol. 1996;53(9):929–32.PubMedCrossRefGoogle Scholar
  30. 30.
    Yoshinaga H, Ohtsuka Y, Tamai K, Tamura I, Ito M, Ohmori I, et al. EEG in childhood absence epilepsy. Seizure. 2004;13(5):296–302.PubMedCrossRefGoogle Scholar
  31. 31.
    Caplan R, Siddarth P, Stahl L, Lanphier E, Vona P, Gurbani S, et al. Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities. Epilepsia. 2008;49(11):1838–46.PubMedCrossRefGoogle Scholar
  32. 32.
    Masur D, Shinnar S, Cnaan A, Shinnar RC, Clark P, Wang J, et al. Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy. Neurology. 2013;81(18):1572–80.PubMedCrossRefGoogle Scholar
  33. 33.
    Shinnar S, Berg AT, Moshe SL, Kang H, O'Dell C, Alemany M, et al. Discontinuing antiepileptic drugs in children with epilepsy: a prospective study. Ann Neurol. 1994;35(5):534–45.PubMedCrossRefGoogle Scholar
  34. 34.
    Loiseau P, Duche B, Pedespan JM. Absence epilepsies. Epilepsia. 1995;36(12):1182–6.PubMedCrossRefGoogle Scholar
  35. 35.
    Dreifuss FEND. Classification of epilepsies in childhood. In: Pellock JMDW, Bourgeois BF, editors. Pediatric epilepsy: diagnosis and therapy. 2nd ed. New York: Demos Medical Publishing; 2001. p. 74–5.Google Scholar
  36. 36.
    Wolf P, Inoue Y. Therapeutic response of absence seizures in patients of an epilepsy clinic for adolescents and adults. J Neurol. 1984;231(4):225–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Tovia E, Goldberg-Stern H, Shahar E, Kramer U. Outcome of children with juvenile absence epilepsy. J Child Neurol. 2006;21(9):766–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde BW, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005‒2009. Epilepsia. 2010;51(4):676–85.PubMedCrossRefGoogle Scholar
  39. 39.
    Senbil N, Soyer O, Turanly G, Gurer YK. Fixation-off sensitivity and generalized epileptic EEG induced by eyes closed. Pediatr Neurol. 2006;35(5):363–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Striano S, Capovilla G, Sofia V, Romeo A, Rubboli G, Striano P, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia. 2009;50 Suppl 5:15–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Panayiotopoulos CP. Typical absence seizures and related epileptic syndromes: assessment of current state and directions for future research. Epilepsia. 2008;49(12):2131–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Chadwick D, Guerreiro C, et al. ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2006;47(7):1094–120.PubMedCrossRefGoogle Scholar
  43. 43.•
    Fattore C, Boniver C, Capovilla G, Cerminara C, Citterio A, Coppola G, et al. A multicenter, randomized, placebo-controlled trial of levetiracetam in children and adolescents with newly diagnosed absence epilepsy. Epilepsia. 2011;52(4):802–9. This article reports results from a recent Class III study evaluating the efficacy of levetiracetam in patients with absence epilepsy.PubMedCrossRefGoogle Scholar
  44. 44.
    Genton P. When antiepileptic drugs aggravate epilepsy. Brain Dev. 2000;22(2):75–80.PubMedCrossRefGoogle Scholar
  45. 45.
    Guerrini R, Belmonte A, Genton P. Antiepileptic drug-induced worsening of seizures in children. Epilepsia. 1998;39 Suppl 3:S2–S10.PubMedCrossRefGoogle Scholar
  46. 46.
    Somerville ER. Some treatments cause seizure aggravation in idiopathic epilepsies (especially absence epilepsy). Epilepsia. 2009;50 Suppl 8:31–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Trudeau V, Myers S, LaMoreaux L, Anhut H, Garofalo E, Ebersole J. Gabapentin in naive childhood absence epilepsy: results from two double-blind, placebo-controlled, multicenter studies. J Child Neurol. 1996;11(6):470–5.PubMedCrossRefGoogle Scholar
  48. 48.•
    Arya R, Greiner HM, Lewis A, Mangano FT, Gonsalves C, Holland KD, et al. Vagus nerve stimulation for medically refractory absence epilepsy. Seizure. 2013;22(4):267–70. This article reports results from a small retrospective study, evaluating seizure outcomes in patients with absence epilepsy being treated with VNS.PubMedCrossRefGoogle Scholar
  49. 49.
    Groomes LB, Pyzik PL, Turner Z, Dorward JL, Goode VH, Kossoff EH. Do patients with absence epilepsy respond to ketogenic diets? J Child Neurol. 2011;26(2):160–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Coppola G, Auricchio G, Federico R, Carotenuto M, Pascotto A. Lamotrigine versus valproic acid as first-line monotherapy in newly diagnosed typical absence seizures: an open-label, randomized, parallel-group study. Epilepsia. 2004;45(9):1049–53.PubMedCrossRefGoogle Scholar
  51. 51.
    Coppola G, Licciardi F, Sciscio N, Russo F, Carotenuto M, Pascotto A. Lamotrigine as first-line drug in childhood absence epilepsy: a clinical and neurophysiological study. Brain Dev. 2004;26(1):26–9.PubMedCrossRefGoogle Scholar
  52. 52.
    Frank LM, Enlow T, Holmes GL, Manasco P, Concannon S, Chen C, et al. Lamictal (lamotrigine) monotherapy for typical absence seizures in children. Epilepsia. 1999;40(7):973–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Verrotti A, Cerminara C, Domizio S, Mohn A, Franzoni E, Coppola G, et al. Levetiracetam in absence epilepsy. Dev Med Child Neurol. 2008;50(11):850–3.PubMedCrossRefGoogle Scholar
  54. 54.
    Pina-Garza JE, Schwarzman L, Wiegand F, Hulihan J. A pilot study of topiramate in childhood absence epilepsy. Acta Neurol Scand. 2011;123(1):54–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Wheless JW, Clarke DF, Carpenter D. Treatment of pediatric epilepsy: expert opinion. J Child Neurol. 2005;20 Suppl 1:S1–S56. quiz S9‒60.PubMedGoogle Scholar
  56. 56.
    Wheless JW, Clarke DF, Arzimanoglou A, Carpenter D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007;9(4):353–412.PubMedGoogle Scholar
  57. 57.
    Appleton RE, Panayiotopoulos CP, Acomb BA, Beirne M. Eyelid myoclonia with typical absences: an epilepsy syndrome. J Neurol Neurosurg Psychiatry. 1993;56(12):1312–6.PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Striano P, Sofia V, Capovilla G, Rubboli G, Di Bonaventura C, Coppola A, et al. A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome). Epilepsia. 2008;49(3):425–30.PubMedCrossRefGoogle Scholar
  59. 59.
    Sato S, White BG, Penry JK, Dreifuss FE, Sackellares JC, Kupferberg HJ. Valproic acid versus ethosuximide in the treatment of absence seizures. Neurology. 1982;32(2):157–63.PubMedCrossRefGoogle Scholar
  60. 60.
    Callaghan N, O'Hare J, O'Driscoll D, O'Neill B, Daly M. Comparative study of ethosuximide and sodium valproate in the treatment of typical absence seizures (petit mal). Dev Med Child Neurol. 1982;24(6):830–6.PubMedGoogle Scholar
  61. 61.
    Martinovic Z. Comparison of ethosuximide with sodium valproate as monotherapies of absence seizures. Advances in Epileptology: XIVth Epilepsy International Symposium, New York: Raven Press; 1983.Google Scholar
  62. 62.
    Buoni S, Grosso S, Fois A. Lamotrigine in typical absence epilepsy. Brain Dev. 1999;21(5):303–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Holmes GL, Frank LM, Sheth RD, Philbrook B, Wooten JD, Vuong A, et al. Lamotrigine monotherapy for newly diagnosed typical absence seizures in children. Epilepsy Res. 2008;82(2–3):124–32.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Comprehensive Epilepsy Center, Division of NeurologyCincinnati Children’s Hospital Medical CenterCincinnatiUSA

Personalised recommendations