A randomized trial on the treatment of the first epileptic seizure scientific background, rationale, study design and protocol

  • Beghi E. 
  • Musicco M. 
  • Viani F. 
  • Bordo B. 
  • Hauser W. A. 
  • Nicolosi A. 
Original Articles

Abstract

Observational studies suggest that the sooner treatment is started after the onset of seizures the better is the outcome of the disease. However, when to start antiepileptic treatment is still debated and this may explain the different behaviour of practising physicians. For these reasons, a multicenter randomized controlled trial comparing the treatment of the first seizure and the treatment of the recurrences (the two most common strategies in clinical practice) has been started in Italy. The scientific background, the study rationale and design, and the general characteristics of the study population (498 patients) are presented here.

Key Words

Seizures Epilepsy Anticonvulsants Clinical trials Prognosis 

Sommario

I risultati di studi osservazionali indicano che quanto più precoce è il trattamento delle crisi epilettiche tanto migliore è la prognosi della malattia. Comunque, è tuttora discusso quando iniziare il trattamento. Ciò tende a giustificare la variabilità degli approcci terapeutici attuati nella pratica clinica corrente. Per tali motivi, è stato intrapreso in Italia uno studio clinico controllato multicentrico volto a comparare le due modalità terapeutiche più comuni, cioè l'inizio del trattamento dopo la prima crisi epilettica ed il trattamento solo dopo una ricorrenza delle crisi. Nel presente articolo sono illustrati i principali dati bibliografici di riferimento, il razionale ed il disegno dello studio, e le caratteristiche principali della popolazione in esame (498 casi).

This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    Annegers J.F., Hauser W.A., Elveback L.R.:Remission of seizures and relapse in patients with epilepsy. Epilepsia 20:729–737, 1979.PubMedGoogle Scholar
  2. [2]
    Annegers J.F., Shirts S.B., Hauser W.A., Kurland L.T.:Risk of recurrence after an initial unprovoked seizure. Epilepsia 27:43–50, 1986.PubMedGoogle Scholar
  3. [3]
    Beghi E., Viani F., Avanzini G., Canger R.:Current practice and opinions on pharmacological treatment of epilepsies: a mail interview of a sample of italian physicians. Boll. Lega It. Epil. 57:27–32, 1987.Google Scholar
  4. [4]
    Berg A.T., Shinnar S.:The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 41:965–972, 1991.PubMedGoogle Scholar
  5. [5]
    Camfield P.R., Camfield C.S., Smith E.C., Tibbles J.A.R.:Newly treated childhood epilepsy: a prospective study of recurrences and side effects. Neurology 35:722–725, 1985.PubMedGoogle Scholar
  6. [6]
    Camfield P.R., Camfield C.S., Dooley J.M., et al.:Epilepsy after a first unprovoked seizure in childhood. Neurology 35:1657–1660, 1985.PubMedGoogle Scholar
  7. [7]
    Collaborative Group for the study of epilepsy:Prognosis of epilepsy in newly referred patients: a multicenter prospective study of the effects of monotherapy on the long-term course of epilepsy. Epilepsia 33:45–51, 1992.Google Scholar
  8. [8]
    Commission on classification and terminology of the international league against epilepsy:Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 22:489–501, 1981.Google Scholar
  9. [9]
    Commission on classification and terminology of the international league against epilepsy.Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 30:389–399, 1989.Google Scholar
  10. [10]
    Cox D.R.:Regression models and life tables. J. R. Statist. Soc. B. 34:187–220, 1972.Google Scholar
  11. [11]
    De Silva M., McArdle B., McGowan M., Reynolds E.H., Neville B., Johnson A.L.:Monotherapy for newly diagnosed childhood epilepsy: a comparative trial and prognostic evaluation. Epilepsia 30:662, 1989.Google Scholar
  12. [12]
    Elwes R.D.C., Johnson A.L., Shorvon S.D., Reynolds E.H.:The prognosis for seizure control in newly diagnosed epilepsy. N. Engl. J. Med. 311:944–947, 1984.PubMedGoogle Scholar
  13. [13]
    Elwes R.D.C., Chesterman P., Reynolds E.H.:Prognosis after a first untreated tonic-clonic seizure. Lancet ii:752–753, 1985.Google Scholar
  14. [14]
    Emerson R., D'Souza B.J., Vining E., et al.:Stopping medication in children with epilepsy. Predictors of outcome. N. Engl. J. Med. 304:1125–1129, 1981.PubMedGoogle Scholar
  15. [15]
    Goodridge D.M.G., Shorvon S.D.:Epileptic seizures in a population of 6000. II: treatment and prognosis. Br. Med. J. 287:645–647, 1983.Google Scholar
  16. [16]
    Hart R.G., Eaton J.D.:Seizure recurrence after a first, unprovoked seizure. Arch. Neurol. 43:1289–1290, 1986.PubMedGoogle Scholar
  17. [17]
    Hart Y.M., Sander J.W.A.S., Johnson A.L., Shorvon S.D. for the NGPSE:National General Practice Study of Epilepsy: recurrence after a first seizure. Lancet 336:1271–1274, 1990.CrossRefPubMedGoogle Scholar
  18. [18]
    Hauser W.A., Anderson V.E., Lowenson R.B., McRoberts S.M.:Seizure recurrence after a first unprovoked seizure. N. Engl. J. Med. 307:522–528, 1982.PubMedGoogle Scholar
  19. [19]
    Hauser W.A.:Should people be treated after a first seizure. Arch. Neurol. 43:1287–1288, 1986.PubMedGoogle Scholar
  20. [20]
    Hauser W.A., Rich S.S., Annegers J.F., Anderson V.E.:Seizure recurrence after a 1st unprovoked seizure: An extended follow-up. Neurology 40:1163–1170, 1990.PubMedGoogle Scholar
  21. [21]
    Heller A.J., Chesterman P., Elwes R.D.C., Reynolds E.H., Crawford P., Chadwick D., Johnson A.L.:Monotherapy for newly diagnosed adult epilepsy: a comparative trial and prognostic evaluation. Epilepsia 30:648, 1989.Google Scholar
  22. [22]
    Hirtz D.G., Ellenberg J.H., Nelson K.B.:The risk of recurrence of nonfibrile seizures in children. Neurology 34:637–641, 1984.PubMedGoogle Scholar
  23. [23]
    Holowach J., Thurston D.L. O'Leary J.:Prognosis in childhood epilepsy. N. Engl. J. Med. 286:169–174, 1972.PubMedGoogle Scholar
  24. [24]
    Hopkins A., Garman A., Clarke C.:The first seizure in adult life. Lancet i:721–726, 1988.Google Scholar
  25. [25]
    Kaplan E.L., Meier P.:Nonparametric estimation from incomplete observations. J. Am. Statist. Ass. 53:457–481, 1958.Google Scholar
  26. [26]
    Mattson R.H., Cramer J.A., Collins J.F., et al.:Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. N. Engl. J. Med. 313:145–151, 1985.PubMedGoogle Scholar
  27. [27]
    Okuma T., Kumashiro H.:Natural history and prognosis of epilepsy: report of a multi-institutional study in Japan. Epilepsia 22:35–53, 1981.PubMedGoogle Scholar
  28. [28]
    Reidenberg M.M., Lowenthal D.T.:Adverse non drug reactions. N. Engl. J. Med. 279:678–679, 1968.PubMedGoogle Scholar
  29. [29]
    Reynolds E.H.:The process of epilepsy: Is kindling relevant? In: Boldwing T., Trimble M.R., (Eds.), The Clinical Relevance of Kindling. Chichester, J. Wiley & Sons, 149–160, 1989.Google Scholar
  30. [30]
    Shinnar S., Berg A.T., Moshé S.L. et al.:Risk of seizure recurrence following a first unprovoked seizure in childhood: A prospective study. Pediatrics 85:1076–1085, 1990.PubMedGoogle Scholar
  31. [31]
    Shorvon S.D., Reynolds E.H.:Early prognosis of epilepsy. Br. Med. J. 285:1699–1701, 1982.Google Scholar
  32. [32]
    Søfijanov N.G.:Clinical evolution and prognosis of childhood epilepsies. Epilepsia 23:61–69, 1982.PubMedGoogle Scholar
  33. [33]
    Viani F., Musicco M., Romeo A., et al.:Prognosis of epilepsy in children: remission rates in newly diagnosed and newly treated patients. Boll. Lega It. Epil. 54/55:331–332, 1986.Google Scholar

Copyright information

© Masson Italia Editori 1993

Authors and Affiliations

  • Beghi E. 
    • 1
    • 2
    • 3
    • 4
  • Musicco M. 
    • 1
    • 2
    • 3
    • 4
  • Viani F. 
    • 1
    • 2
    • 3
    • 4
  • Bordo B. 
    • 1
    • 2
    • 3
    • 4
  • Hauser W. A. 
    • 1
    • 2
    • 3
    • 4
  • Nicolosi A. 
    • 1
    • 2
    • 3
    • 4
  1. 1.Istituto di Ricerche Biomediche AvanzateCNRMilano
  2. 2.Istituto di Ricerche Farmacologiche “Mario Negri”Milano
  3. 3.Sezione di Neuroepidemiologia della SIN
  4. 4.Clinica NeurologicaOspedale S. GerardoMonza

Personalised recommendations