Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-22T05:50:52.904Z Has data issue: false hasContentIssue false
  • English
  • Français

Lennox-Gastaut Syndrome: An Update on Treatment

Published online by Cambridge University Press:  02 December 2014

Lionel Carmant  and
Sharon Whiting
Lionel Carmant*
Affiliation:
Université de Montréal, Hôpital Sainte-Justine, Montreal, Quebec
Sharon Whiting
Affiliation:
Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
*
Lionel Carmant, Université de Montréal, Hôpital Sainte-Justine, Room 5421, 3175 Côte Ste-Catherine, Montréal (Québec) H3T 1C5, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy. Few current treatment options are effective in improving seizure control. This paper reviews the available treatments of LGS and discusses a new option in Canada, rufinamide. It is a wide spectrum anticonvulsant, approved in a number of countries for the treatment of LGS. In a randomized controlled trial in the LGS population, adjunctive rufinamide therapy has been shown to offer significantly greater reduction in total seizure frequency and tonic-atonic seizure frequency in comparison to placebo. Efficacy has been assessed over three years and appears to be sustained. Most adverse events were cognitive (e.g. somnolence) or gastrointestinal in nature and in many cases transient or mild. Based on the efficacy and safety data on rufinamide obtained to date, this medication will provide additional benefits to patients with LGS in Canada and is an important consideration for our patients in the adjunctive treatment setting.

Résumé

RÉSUMÉ

Le syndrome de Lennox-Gastaut (SLG) est une encéphalopathie épileptique sévère. Peu des options thérapeutiques actuelles sont efficaces pour améliorer le contrôle des crises. Dans cet article, nous revoyons les traitements du SLG qui sont disponibles et nous discutons d'une nouvelle option thérapeutique disponible au Canada, le rufmamide. Il s'agit d'un anticonvulsivant à large spectre qui a été approuvé dans certains pays pour traiter le SLG. Un essai clinique randomisé chez des patients atteints du SLG a démontré qu'un traitement d'appoint par le rufmamide entraînait une diminution significativement supérieure de la fréquence totale des crises et de la fréquence des crises toniques-atoniques comparé au placebo. Son efficacité a été évaluée pendant 3 ans et semble persister. La plupart des incidents thérapeutiques étaient de nature cognitive (e.g. la somnolence) ou gastrointestinaux et ils étaient transitoires ou légers chez plusieurs patients. Les données actuelles sur l'efficacité et la sécurité du rufmamide indiquent que cette médication apportera des bénéfices additionnels aux patients atteints de SLG au Canada et constitue un traitement d'appoint intéressant à considérer chez nos patients.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 39 , Issue 6 , November 2012 , pp. 702 - 711
Copyright
Copyright © The Canadian Journal of Neurological 2012

References

1. Niedermeyer, E. The Lennox-Gastaut syndrome: a severe type of childhood epilepsy. Dtsch Z Nervenheilkd. 1969;195(4):263–82.CrossRefGoogle ScholarPubMed
2. 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.CrossRefGoogle Scholar
3. Berg, AT, Berkovic, SF, Brodie, MJ, 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.CrossRefGoogle ScholarPubMed
4. Glauser, T, Kluger, G, Sachdeo, R, Krauss, G, Perdomo, C, Arroyo, S. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology. 2008;70(21):1950–8.CrossRefGoogle ScholarPubMed
5. Michoulas, A, Farrell, K. Medical management of Lennox-Gastaut syndrome. CNS Drugs. 2010;24(5):363–74.CrossRefGoogle ScholarPubMed
6. Rantala, H, Putkonen, T. Occurrence, outcome, and prognostic factors of infantile spasms and Lennox-Gastaut syndrome. Epilepsia. 1999;40(3):286–9.CrossRefGoogle ScholarPubMed
7. Markand, ON. Lennox-Gastaut syndrome (childhood epileptic encephalopathy). J Clin Neurophysiol. 2003;20(6):426–41.CrossRefGoogle ScholarPubMed
8. Camfield, P. Definition and natural history of Lennox-Gastaut syndrome. Epilepsia. 2011;52(Suppl. 5):3–9.Google Scholar
9. Camfield, CS, Camfield, PR, Gordon, K, Wirrell, E, Dooley, JM. Incidence of epilepsy in childhood and adolescence: a population based study in Nova Scotia from 1977 to 1985. Epilepsia. 1996;37:19–23.CrossRefGoogle ScholarPubMed
10. Trevathan, E, Murphy, CC, Yeargin-Allsopp, M. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. Epilepsia. 1997;38(12):1283–8.CrossRefGoogle ScholarPubMed
11. Dulac, O, Nguyen, T. The Lennox-Gastaut syndrome. Epilepsia. 1993;34:S7–S17.CrossRefGoogle ScholarPubMed
12. Arzimanoglou, A, French, J, Blume, WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol. 2009;8(1):82–93.CrossRefGoogle ScholarPubMed
13. Deekollu, D, Besag, FMC, Aylett, SE. Seizure-related injuries in a group of young people with epilepsy wearing protective helmets: incidence, types and circumstances. Seizure. 2005;14(5):347–53.CrossRefGoogle Scholar
14. Gallop, K, Wild, D, Nixon, A, Verdian, L, Cramer, JA. Impact of Lennox-Gastaut syndrome (LGS) on health-related quality of life (HRQL) of patients and caregivers: literature review. Seizure. 2009;18(8):554–8.CrossRefGoogle ScholarPubMed
15. Ferlazzo, E, Nikaronova, M, Italiano, D, et al. Lennox-Gastaut syndrome in adulthood: clinical and EEG features. Epilepsy Res. 2010;89(2–3):271–7.CrossRefGoogle ScholarPubMed
16. Beaumanoir, A. The Lennox-Gastaut syndrome: a personal study. Electroencephalogr Clin Neurophysiol Suppl. 1982;(35):85–99.Google ScholarPubMed
17. Chevrie, JJ, Aicardi, J. Childhood epileptic encephalopathy with slow spike-wave. A statistical study of 80 cases. Epilepsia. 1972;13(2)259–71.Google ScholarPubMed
18. Berg, AT, Scheffer, IE. New concepts in classification of the epilepsies: entering the 21st century. Epilepsia. 2011;52(6):1058–62.CrossRefGoogle Scholar
19. Harkin, LA, McMahon, JM, Iona, X, et al. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain. 2007;130:843–52.CrossRefGoogle ScholarPubMed
20. Selmer, KK, Lund, C, Brandal, K, Undlien, DE, Brodtkorb, E. SCN1A mutation screening in adult patients with Lennox-Gastaut syndrome features. Epilepsia. 2009;50:555–7.Google Scholar
21. Miller, IO, Sotero de Menezes, MA. SCN1A-related seizure disorders. In: Pagon, RA, Bird, TD, Dolan, CR, Stephens, K, editors. GeneReviews. Seattle (WA): University of Washington; 1993.Google Scholar
22. You, SJ, Kim, HD, Kang, H. Factors influencing the evolution of West syndrome to Lennox-Gastaut syndrome. Pediatr Neurol. 2009;41(2):111–3.CrossRefGoogle ScholarPubMed
23. French, J, Kanner, AM, Bautista, J, et al. Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy. Report of the TTA and QSS subcommittees of the American Academy of Neurology and the American Epilepsy Society. Epilepsia. 2004;45(5):410–23.Google ScholarPubMed
24. van Rijckevorsel, K. Treatment of Lennox-Gastaut syndrome: overview and recent findings. Neuropsychiatr Dis Treat. 2008;4(6):1001–19.CrossRefGoogle ScholarPubMed
25. Goldsmith, I, Zupanc, M, Buchhalter, J. Long-term seizure outcome in 74 patients with Lennox-Gastaut syndrome: effects of incorporating MRI head imaging in defining the cryptogenic subgroup. Epilepsia. 2000;41(4):395–9.CrossRefGoogle ScholarPubMed
26. Yagi, K. Evolution of Lennox-Gastaut syndrome: a long-term longitudinal study. Epilepsia. 1996;37:48–51.CrossRefGoogle ScholarPubMed
27. Gallop, K, Wild, D, Verdian, L, et al. Lennox-Gastaut syndrome (LGS): development of conceptual models of health-related quality of life (HRQL) for caregivers and children. Seizure. 2010;19(1):23–30.CrossRefGoogle ScholarPubMed
28. French, JA, Kanner, AM, Bautista, J, et al. Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy – report of the therapeutics and technology assessment subcommittee and quality standards subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2004;62(8):1252–60.CrossRefGoogle Scholar
29. National Institute for Clinical Excellence (NICE) [Internet]. The epilepsies – the diagnosis and management of the epilepsies in adults and children in primary and secondary care. NICE partial update of clinical guidelines. [Updated 2011 January; cited 2011 October]. Available from: http://www.nice.org.uk.libaccess.lib.mcmaster.ca/nicemedia/live/12108/52447/52447.pdf Google Scholar
30. Wheless, J, Clarke, D, Carpenter, D. Treatment of pediatric epilepsy: expert opinion, 2005. J Child Neurol. 2005;20:S1–S56.CrossRefGoogle ScholarPubMed
31. Montouris, G. Rational approach to treatment options for Lennox-Gastaut syndrome. Epilepsia. 2011;52(Suppl. 5):10–20.CrossRefGoogle ScholarPubMed
32. Wheless, JW, Clarke, DF, Arzimanoglou, A, Carpenter, D. Treatment of pediatric epilepsy: European expert opinion, 2007. Epileptic Disord. 2007;9(4):353–412.Google ScholarPubMed
33. Covanis, A, Gupta, A, Jeavons, P. Sodium valproate – monotherapy and polytherapy. Epilepsia. 1982;23(6):693–720.CrossRefGoogle ScholarPubMed
34. Jeavons, P, Clark, J, Maheshwari, M. Treatment of generalized epilepsies of childhood and adolescence with sodium valproate (Epilim). dev Med Child Neurol. 1977;19(1):9–25.CrossRefGoogle ScholarPubMed
35. Yu, PM, Zhu, GX, Wu, X, et al. A 6-month prospective study on efficacy safety and QOL profiles of extended-release formulation of valproate in patients with epilepsy. Seizure. 2011;20(1):23–6.CrossRefGoogle ScholarPubMed
36. Motte, J, Trevathan, E, Arvidsson, J, et al. For generalized seizures associated with the Lennox-Gastaut syndrome. N Engl J Med. 1997;337(25):1807–12.CrossRefGoogle ScholarPubMed
37. Messenheimer, J. Rash in adult and pediatric patients treated with lamotrigine. Can J Neurol Sci. 1998;25(4):S14–8.CrossRefGoogle ScholarPubMed
38. Schmidt, D, Bourgeois, B. A risk-benefit assessment of therapies for Lennox-Gastaut syndrome. Drug Saf. 2000;22(6):467–77.CrossRefGoogle ScholarPubMed
39. Sachdeo, R, Glauser, T, Ritter, F, Reife, R, Lim, P, Pledger, G. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology. 1999;52(9):1882–7.CrossRefGoogle ScholarPubMed
40. The Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). The Felbamate Study Group in Lennox-Gastaut Syndrome. N Engl J Med. 1993;328(1):29–33.CrossRefGoogle Scholar
41. Carmant, L, Holmes, GL, Sawyer, S, Rifai, N, Anderson, J, Mikati, MAl. Efficacy of felbamate in therapy for partial epilepsy in children. J Pediatr. 1994;125(3):481–6.CrossRefGoogle ScholarPubMed
42. de los Reyes, E, Sharp, G, Williams, J, Hale, S. Levetiracetam in the treatment of Lennox-Gastaut syndrome. Pediatr Neurol. 2004;30(4):254–6.CrossRefGoogle ScholarPubMed
43. Conry, JA, Ng, Y, Paolicchi, JM, et al. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009;50(5):1158–66.CrossRefGoogle ScholarPubMed
44. Tassinari, CA, Dravet, C, Roger, J, Cano, JP, Gastaut, H. Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox-Gastaut syndrome. Epilepsia. 1972;13(3):421–35.CrossRefGoogle ScholarPubMed
45. Gelisse, P, Genton, T, Kuate, C, Pesenti, A, Baldy-Moulinier, M, Crespel, A. Worsening of seizures by oxcarbazepine in juvenile idiopathic generalized epilepsies. Epilepsia. 2004;45(10):1282–6.CrossRefGoogle ScholarPubMed
46. Genton, P, Gelisse, P, Thomas, P, Dravet, C. Do carbamazepine and phenytoin aggravate juvenile myoclonic epilepsy? Neurology. 2000;55(8):1106–9.CrossRefGoogle ScholarPubMed
47. Asconape, J, Diedrich, A, Dellabadia, J. Myoclonus associated with the use of gabapentin. Epilepsia. 2000;41(4):479–81.CrossRefGoogle ScholarPubMed
48. Schapel, G, Chadwick, D. Tiagabine and non-convulsive status epilepticus. Seizure. 1996;5(2):153–6.CrossRefGoogle ScholarPubMed
49. Lortie, A, Chiron, C, Mumford, J, Dulac, O. The potential for increasing seizure frequency, relapse, and appearance of new seizure types with vigabatrin. Neurology. 1993;43(11):S24–7.Google ScholarPubMed
50. Freeman, J, Vining, E. Seizures decrease rapidly after fasting-preliminary studies of the ketogenic diet. Arch Pediatr Adolesc Med. 1999;153(9):946–9.CrossRefGoogle ScholarPubMed
51. Frost, M, Gates, J, Helmers, S, et al. Vagus nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia. 2001;42(9):1148–52.CrossRefGoogle ScholarPubMed
52. Kostov, K, Kostov, H, Tauboll, E. Long-term vagus nerve stimulation in the treatment of Lennox-Gastaut syndrome. Epilepsy behav. 2009;16(2):321–4.CrossRefGoogle ScholarPubMed
53. You, SJ, Kang, H, Ko, T, et al. Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox-Gastaut syndrome. Brain Dev. 2008;30(3):195–9.CrossRefGoogle ScholarPubMed
54. Rossignol, E, Lortie, A, Thomas, T, et al. Vagus nerve stimulation in pediatric epileptic syndromes. Seizure. 2009;18(1):34–7.CrossRefGoogle ScholarPubMed
55. Zamponi, N, Passamonti, C, Cesaroni, E, Trignani, R, Rychlicki, F. Effectiveness of vagal nerve stimulation (VNS) in patients with drop-attacks and different epileptic syndromes. Seizure. 2011;20(6):468–74.CrossRefGoogle ScholarPubMed
56. Bialer, M, Johannessen, S, Kupferberg, H, Levy, R, Loiseau, P, Perucca, E. Progress report on new antiepileptic drugs: a summary of the fifth EILAT conference (EILAT V). Epilepsy Res. 2001;43(1):11–58.CrossRefGoogle ScholarPubMed
57. Banzel® (rufinamide) [product monograph]. Mississauga, ON: Eisai Limited; June 20, 2011.Google Scholar
58. Kluger, G, Glauser, T, Krauss, G, Seeruthun, R, Perdomo, C, Arroyo, S. Adjunctive rufinamide in Lennox-Gastaut syndrome: a long-term, open-label extension study. Acta Neurol Scand. 2010;122(3):202–8 CrossRefGoogle ScholarPubMed
59. Wisniewski, CS. Rufinamide: a new antiepileptic medication for the treatment of seizures associated with Lennox-Gastaut syndrome. Ann Pharmacother. 2010;44(4):658–67.CrossRefGoogle ScholarPubMed
60. Kluger, G, Haberlandt, E, Kurlemann, G, et al. First European long-term experience with the orphan drug rufinamide in childhood-onset refractory epilepsy. Epilepsy Behav. 2010;17(4):546–8.CrossRefGoogle ScholarPubMed
61. Vendrame, M, Loddenkemper, T, Gooty, VD, et al. Experience with rufinamide in a pediatric population: A single center’s experience. Pediatr Neurol. 2010;43(3):155–8.CrossRefGoogle Scholar
62. Coppola, G, Grosso, S, Franzoni, E, et al. Rufinamide in children and adults with Lennox-Gastaut syndrome: first Italian multicenter experience. Seizure. 2010;19(9):587–91.CrossRefGoogle ScholarPubMed
63. Chieffo, D, Battaglia, D, Lettori, D, et al. Neuropsychological development in children with dravet syndrome. Epilepsy Res. 2011;95(1–2):86–93.CrossRefGoogle ScholarPubMed