Is Ethosuximide a Risk Factor for Generalised Tonic-clonic Seizures in Absence Epilepsy?

Abstract

The occurrence of generalised tonic-clonic seizures (GTCS) was investigated in patients with absence epilepsy (AE), evaluating the opinion that ethosuximide does not protect against GTCS. Our retrospective study included 238 patients with absences and generalised 3-Hz spike waves (SW). We analysed the efficacy of antiepileptic drugs (AED) and the occurrence of GTCS before, during and after treatment. We surveyed family history, treatment delay and EEG findings. Family history of epilepsy was positive in 28%. Children with 3-Hz SW lasting >10 s suffered less frequently from GTCS (p=0.002). Photosensitivity (3-Hz SW during photic stimulation) recorded in 47 children was more frequent in juvenile AE (p=0.0001), but not associated with higher rates of GTCS. GTCS occurred in 27 children (11%) before treatment, in 14 (5.8%) during treatment and in 8 (4.8%) after tapering AED. Valproate and ethosuximide monotherapy were equally effective on absences, carrying the same low risk of GTCS during treatment (2 valproate, 1 ethosuximide). Most GTCS occurred on drug combinations considered effective against GTCS. Risk factors for relapses after tapering AED were photosensitivity (p=0.002) and GTCS during treatment (p=0.02). GTCS are rare in patients with typical AE. Our data do not support the current opinion that ethosuximide is inefficacious on GTCS in AE.

Key words

Absence epilepsy - tonic clonic epilepsy - ethosuximide - children

References

• 1 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;  37 169-175
• 2 Baykan B, Matur Z, Gurses C, Aykutlu E, Gokyigit A. Typical absence seizures triggered by photosensitivity.  Epilepsia. 2005;  46 159-163
• 3 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 1553-1562
• 4 Berkovic SF. Childhood absence epilepsy and juvenile absence epilepsy. In: Wyllie E (Eds), The treatment of epilepsy Principles and practice. Philadelphia London: Lea & Febiger 1993: 547-551
• 5 Browne TR, Dreifuss FE, Dyken PR, Goode DJ, Penry JK, Porter RJ. et al . Ethosuximide in the treatment of absence (peptit mal) seizures.  Neurology. 1975;  25 515-524
• 6 Buoni S, Grosso S, Fois A. Lamotrigine in typical absence epilepsy.  Brain Dev. 1999;  21 303-306
• 7 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 1049-1053
• 8 Covanis A, Skiadas K, Loli N, Lada C, Theodorou V. Absence epilepsy: early prognostic signs.  Seizure. 1992;  1 281-289
• 9 Dieterich E, Baier WK, Doose H, Tuxhorn I, Fichsel H. Longterm follow-up of childhood epilepsy with absences. I. Epilepsy with absences at onset.  Neuropediatrics. 1985;  16 149-154
• 10 Dieterich E, Doose H, Baier WK, Fichsel H. Longterm follow-up of childhood epilepsy with absences. II. Absence-epilepsy with initial grand mal.  Neuropediatrics. 1985;  16 155-158
• 11 Doose H. Epilepsien im Kindes- und Jugendalter [Epilepsies in childhood and adolescence]. Hamburg: Desitin Arzneimittel GmbH 1998
• 12 Eeg-Olofsson O, Petersen I, Sellden U. The development of the electroencephalogram in normal children from the age of 1 through 15 years. Paroxysmal activity.  Neuropaediatrie. 1971;  2 375-404
• 13 Fisher RS, Harding G, Erba G, Barkley GL, Wilkins A. Photic- and pattern-induced seizures: a review for the Epilepsy Foundation of America Working Group.  Epilepsia. 2005;  46 1426-1441
• 14 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;  40 973-979
• 15 Friedel B, Lempp R. Grand-mal-Provokation bei der Behandlung kindlicher petit-mal mit Oxazolidinen oder Succinimiden und ihre therapeutischen Konsequenzen [Grand mal provocation in the treatment of petit mal in children with oxazolidines or succinimides and its therapeutic consequences].  Z Kinderheilkd. 1962;  87 42-51
• 16 Glauser TA. Succinimides Adverse effects. In: Levy RH, Mattson RH, Meldrum BS, Perucca E (Eds), Antiepileptic Drugs 5th edn. Philadelphia Baltimore, New York, London, Buenos Aires, Hong Kong, Sydney, Tokyo: Lippincott Williams & Wilkins 2002: 658-664
• 17 Gordon N. Treatment of epilepsy with alpha-ethyl-alpha-methyl-succinimide (P.M. 671).  Neurology. 1961;  11 266-268
• 18 Grosso S, Galimberti D, Vezzosi P, Farnetani M, Bartolo RM Di, Bazzotti S. et al . Childhood absence epilepsy: evolution and prognostic factors.  Epilepsia. 2005;  46 1796-1801
• 19 Guiwer J, Valenti MP, Bourazza A, Hirsch E. Loiseau P Prognosis of idiopathic absence epilepsies. In: Jallon P (Ed), Prognosis of epilepsies. Paris: John Libbey Eurotext 2003: 249-257
• 20 Hedstrom A, Olsson I. Epidemiology of absence epilepsy: EEG findings and their predictive value.  Pediatr Neurol. 1991;  7 100-104
• 21 ILAE CoCaTot . Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy.  Epilepsia. 1989;  30 389-399
• 22 Jeavons PM. Harding GFA Photosensitive epilepsy. London Philadelphia: Spastics International Medical Publications 1975
• 23 Loiseau P, Duche B, Pedespan JM. Absence epilepsies.  Epilepsia. 1995;  36 1182-1186
• 24 Lorentzdehaas AM, Kuilman M. Ethosuximide (alpha-ethyl-alpha-methylsuccinimide) and grand mal.  Epilepsia. 1964;  23 90-96
• 25 Olsson I. Epidemiology of absence epilepsy. I. Concept and incidence.  Acta Paediatr Scand. 1988;  77 860-866
• 26 Panayiotopoulos CP. Typical absence seizures and their treatment.  Arch Dis Child. 1999;  81 351-355
• 27 Pearl PL, Holmes GL. Absence seizures. In: Pellock JM, Dodson WE, Bourgeois BFD (Eds), Pediatric epilepsy. New York: Demos 2004: 219-231
• 28 Posner EB, Mohamed K, Marson AG. Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents.  Cochrane Database Syst Rev. 2003;  CD003032
• 29 Todorov AB, Lenn NJ, Gabor AJ. Exacerbation of generalized nonconvulsive seizures with ethosuximide therapy.  Arch Neurol. 1978;  35 389-391
• 30 Waltz S, Christen HJ, Doose H. The different patterns of the photoparoxysmal response - a genetic study.  Electroencephalogr Clin Neurophysiol. 1992;  83 138-145
• 31 Wirrell E, Camfield C, Camfield P, Dooley J. Prognostic significance of failure of the initial antiepileptic drug in children with absence epilepsy.  Epilepsia. 2001;  42 760-763
• 32 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.  Neurology. 1996;  47 912-918
• 33 Wolf P, Goosses R. Relation of photosensitivity to epileptic syndromes.  J Neurol Neurosurg Psychiatry. 1986;  49 1386-1391
• 34 Wolf P, Inoue Y. Therapeutic response of absence seizures in patients of an epilepsy clinic for adolescents and adults.  J Neurol. 1984;  231 225-229

Correspondence