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Management of Seizures in Lennox-Gastaut Syndrome

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Abstract

Lennox-Gastaut syndrome is an epilepsy syndrome that begins in childhood (between 1 and 8 years of age), worsens during latency and persists frequently into adulthood, is refractory to antiepileptic medications, and results in cognitive decline and behavioral problems in affected individuals. Seizure types consist primarily of axial tonic, atonic, and atypical absence; nocturnal tonic seizures are the most common seizure pattern in this population, but often are not one of the initial seizure patterns. Some patients also have myoclonic seizures; this seizure pattern is less frequent than the three preceding types. Although there are some cases that are cryptogenic, most are symptomatic, arising during prenatal and perinatal periods from intrauterine infections, and vascular insults to the brain. Examples of causes of Lennox-Gastaut syndrome include migrational abnormalities of the brain, late effects of CNS infections, certain genetic disorders such as tuberous sclerosis, and inherited metabolic disorders. The difficulty early in the course of Lennox-Gastaut syndrome is distinguishing this diagnosis from severe myoclonic epilepsy of infancy (Dravet syndrome) or from myoclonic-astatic epilepsy (Doose syndrome), as the seizure patterns in these three syndromes may overlap at the onset. EEG is a helpful diagnostic tool in the diagnosis of Lennox-Gastaut syndrome, usually demonstrating high voltage, bifrontal 1.5–2.5 Hz spike and wave complexes interictally, and attenuation with paroxysmal fast activity (10–13 Hz) during the ictal phase.

Treatment options for Lennox-Gastaut syndrome have been less than optimal. In recent years, several drugs have been tested and approved for the treatment of this syndrome; these include felbamate, lamotrigine, topiramate, and rufinamide. The long-term outcome does not appear to be any better with the newer antiepileptic drugs than when using earlier prescribed antiepileptic drugs or polytherapy. Treatment options other than antiepileptic drugs include a ketogenic diet, vagus nerve stimulation, and corpus callosotomy. Long-term outcome of these patients relative to seizure control and cognition is poor. Most develop moderate intellectual disability within a few years of onset of the syndrome. Many develop behavioral problems with inattention, hyperactivity, and aggression.

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References

  1. Arzimanoglou A, French J, Blume WT, et al. Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol 2009 Jan; 8(1): 82–93

    Article  PubMed  Google Scholar 

  2. Gastaut H. The Lennox-Gastaut syndrome: comments on the syndrome’s terminology and nosological position amongst the secondary generalized epilepsies of childhood. Electroencephalogr Clin Neurophysiol Suppl 1982; 35: 71–84

    PubMed  Google Scholar 

  3. Gibbs FA, Davis H, Lennox WG. The electroencephalogram in epilepsy and in conditions of impaired consciousness. Arch Neural Psychiatry 1935; 34: 1133–48

    Article  Google Scholar 

  4. Markand ON. Lennox-Gastaut syndrome (childhood epileptic encepthalopathy). J Clin Neurophysiol 2003; 20(6): 426–41

    Article  PubMed  Google Scholar 

  5. Morita DA, Glauser T. Lennox-Gastaut syndrome. In: Pellock JM, Bourgeois B, Dodson WE, editors. Pediatric epilepsy: diagnosis and therapy. 3rd ed. New York: Demos Medical Publishing, 2008; 307–22

    Google Scholar 

  6. Dravet C. Encephalopathie epileptique de l’Enfant avec Pointe-Onde lente diffuse [PhD thesis]. University of Marseille: Marseille, 1965

    Google Scholar 

  7. Gastaut H, Roger J, Soulayrol R, et al. Childhood epileptic encephalopathy of children with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia 1966; 7: 139–79

    Article  Google Scholar 

  8. Engel J. Introduction. In: Engel J, Pedley T, Aicardi J, editors. Epilepsy: a comprehensive textbook. Philadelphia (PA): Wolters Kluwer Health, 2008: 32

    Google Scholar 

  9. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia 1989; 30(4): 389–99

    Article  Google Scholar 

  10. Markand ON. Slow spike-wave activity in EEG and associated clinical features: often called “Lennox” or “Lennox-Gastaut” syndrome. Neurology 1977; 27: 746–57

    Article  PubMed  CAS  Google Scholar 

  11. Beaumanoir A, Dravet C. The Lennox-Gastaut syndrome. In: Roger J, Bureau M, Dravet C, et al, editors. Epileptic syndromes in infancy, childhood and adolescence. 2nd ed. London: John Libbey, 1992; 115–32

    Google Scholar 

  12. Chevrie JJ, Aicardi J. Childhood epileptic encephalopathy with slow spike-wave: a statistical study of 80 cases. Epilepsia 1972; 13: 259–71

    Article  PubMed  CAS  Google Scholar 

  13. Genton P, Gierromo R, Dravet C. The Lennox-Gastaut syndrome. In: Meinardi H, editor. Handbood of clinical neurology. Amsterdam: Elsevier Science, 2000: 211–22

    Google Scholar 

  14. Aicardi J. Lennox-Gastaut Syndrome. In: Aicardi J, editor. Epilepsy in children. 2nd ed. New York: Raven Press, 1994: 44–66

    Google Scholar 

  15. Chatrian GE, Lettich E, Wilkus RJ, et al. Polygraphic and clinical observations on tonic-autonomic seizures. Electroencephalogr Clin Neurophysiol Suppl 1982; 35: 101–24

    PubMed  Google Scholar 

  16. Stephani U. The natural history of myoclonic astatic epilepsy (Doose syndrome) and Lennox-Gastaut syndrome. Epilepsia 2006; 47Suppl. 2: 53–6

    Article  PubMed  Google Scholar 

  17. ILAE Commission on Classification Terminology. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1981; 22: 489–501

    Article  Google Scholar 

  18. Bonanni P, Parmeggiani L, Guerrini R. Different neurophysiologic patterns of myoclonus characterize Lennox-Gastaut syndrome and myoclonic astatic epilepsy. Epilepsia 2002; 43(6): 609–15

    Article  PubMed  Google Scholar 

  19. Guerrini R, Aicardi J. Epileptic encephalopathies with myoclonic seizures in infants and children (severe myoclonic epilepsy and myoclonic-astatic epilepsy. J Clin Neurophysiol 2003; 20(6): 449–61

    Article  PubMed  Google Scholar 

  20. Crumrine PK. Lennox-Gastaut syndrome. J Child Neurol 2002; 71Supp. 1: S70–6

    Article  Google Scholar 

  21. Covanis A, Gupta AK, Jeavons PM. Sodium valproate monotherapy and polytherapy. Epilepsia 1982; 23: 692–720

    Article  Google Scholar 

  22. Vassella F, Pavlincova E, Schneider HJ, et al. Treatment of infantile spasms and Lennox-Gastaut syndrome with clonazepam (Rivotril). Epilepsia 1973; 14: 165–75

    Article  PubMed  CAS  Google Scholar 

  23. The Group for the Evaluation of Cinromide in the Lennox-Gastaut Syndrome. Double-blind, placebo-controlled evaluation of cinromide in patients with the Lennox-Gastaut syndrome. Epilepsia 1989; 30(4): 422–9

    Article  Google Scholar 

  24. Chamberlain MC. Nitrazepam for refractory infantile spasms and the Lennox-Gastaut syndrome. J Child Neurol 1996; 11: 31–4

    Article  PubMed  CAS  Google Scholar 

  25. The Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). N Engl J Med 1993; 328: 29–33

    Article  Google Scholar 

  26. Motte J, Trevathan E, Arvidsson JF, et al. Lamotrigine for generalized seizures associated with the Lennox-Gastaut syndrome. Lamictal Lennox-Gastaut Study Group. N Engl J Med 1997; 337(25): 1807–12

    Article  PubMed  CAS  Google Scholar 

  27. Sacheo RD, Glauser TA, Ritter F, et al. A double-blind, randomized trial of topiramate in Lennox-Gastaut Syndrome. Neurology 1999; 52: 1882–7

    Article  Google Scholar 

  28. Glauser TA, Pellock JM. Zonisamide in pediatric epilepsy: review of the Japanese experience. J Child Neurology 2002; 17: 87–96

    Article  Google Scholar 

  29. You SJ, Kang HC, Kim HD, et al. Clinical efficacy of zonisamide in Lennox-Gastaut syndrome: Korean multicentric experience. Brain Devel 2008; 30: 287–90

    Article  Google Scholar 

  30. Conry JA, Ng YT, Paolicchi JM, et al. Clobazam in the treatment of Lennox-Gastaut Syndrome. Epilepsia 2009; 50(5): 1158–66

    Article  PubMed  CAS  Google Scholar 

  31. Glauser TA, Kluger G, Sachedo R, et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008; 71: 1950–8

    Article  Google Scholar 

  32. Freeman JM, Vining EP. Seizures decrease rapidly after fasting: preliminary studies with the ketogenic diet. Arch Pediatr Adoles Med 1999; 53(946): 949

    Google Scholar 

  33. Ferrie C, Patel A. Treatment of Lennox-Gastaut syndrome (LGS). Eur J Paediatr Neurol 2009; 13: 493–34

    Article  PubMed  Google Scholar 

  34. You SJ, Kang HC, Ko TS, et al. Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox-Gastaut syndrome. Brain Dev 2008 Mar; 30(3): 195–9

    Article  PubMed  Google Scholar 

  35. Frost M, Gates J, Helmers SL, et al. Vagal nerve stimulation in children with refractory seizures associated with Lennox-Gastaut syndrome. Epilepsia 2001; 42(9): 1148–52

    Article  PubMed  CAS  Google Scholar 

  36. Fromm GH, Terrence CF, Chattha AS. Effect of cinromide on inhibitory and excitatory mechanisms. Epilepsia 1983; 24(4): 394–400

    Article  PubMed  CAS  Google Scholar 

  37. Dimario FJ, Clancy RR. Paradoxical precipitation of tonic seizures by lorazepam in a child with atypical absence seizures. Pediatr Neurol 1982; 4: 249–51

    Article  Google Scholar 

  38. Knudsen JF, Thambi LR, Kapcala LP MD, et al. Oligohydrosis and fever in pediatric patients treated with zonisamide. Pediatr Neurol 2003; 28(3): 184–9

    Article  PubMed  Google Scholar 

  39. de los Reyes EC, Sharp GB, Williams JP, et al. Levetiracetam in the treatment of Lennox-Gastaut syndrome. Pediatr Neurol 2004; 30: 254–6

    Article  Google Scholar 

  40. Van Engelen BG, Renier W, Weemaed CM, et al. High-dose intravenous immunoglobulin treatment in cryptogenic west and Lennox-Gastaut syndrome. Eur J Paediatr 2009; 153: 762–9

    Article  Google Scholar 

  41. Velasco AL, Velasco F, Jimenez F, et al. Neuromodulation of the centromedian thalamic nuclei in the treatment of generalized seizures and the improvement of the quality of life in patients with Lennox-Gastaut syndrome. Epilepsia 2006; 47(7): 1203–12

    Article  PubMed  Google Scholar 

  42. Wilder RM. The effect of ketonemia on the course of epilepsy. Mayo Clinic Bull 1921; 2: 307–8

    Google Scholar 

  43. Freeman JM, Vining EPG, Kossoff EH, et al. A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia 2009; 50(2): 322–5

    Article  PubMed  Google Scholar 

  44. Groves DA, Brown VJ. Vagus nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neurosci Biobehav Rev 2005; 29: 493–500

    Article  PubMed  Google Scholar 

  45. Maehara T, Shimizu H. Surgical outcome of corpus callosotomy in patients with drop attacks. Epilepsia 2001; 42(1): 67–71

    Article  PubMed  CAS  Google Scholar 

  46. Schmidt D, Bourgeois B. A risk-benefit assessment of therapies for Lennox-Gastaut syndrome. Drug Saf 2000; 22(6): 467–77

    Article  PubMed  CAS  Google Scholar 

  47. Arzimanoglou A, Guerrini R, Aicardi J. Lennox-Gastaut syndrome. In: Aicardi J, editor. Aicardi’s epilepsy in children. Philadelphia (PA): Lippincott, Williams & Wilkins; 2004: 38–50

    Google Scholar 

  48. French JA, Kanner AM, Bautista J, et al. Efficacy and tolerability of the new antiepileptic drugs: II. Treatment of refractory epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommitee of the American Academy of Neurology and the American Epilepsy Society. Neurology 2004; 62: 1261–73

    Article  PubMed  CAS  Google Scholar 

  49. Glauser T, Kluger G, Sachedeo R, et al. Rufinamide for generalized seizures associated with Lennox-Gastaut syndrome. Neurology 2008; 70: 1950–8

    Article  PubMed  CAS  Google Scholar 

  50. Livingston JH. The Lennox-Gastaut syndrome. Dev Med Child Neurol 1988; 30: 536–40

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Dr Crumrine acknowledges that she received no funding for the preparation of this review. No funding organization or sponsor played any role in the collection of information for this article, and the preparation, review, or approval of the manuscript. Dr Crumrine has a grant pending from Ovation Pharmaceuticals for a clinical study of clobazam in Lennox-Gastaut syndrome. No monies have been received to date and the grant is pending institutional review board approval in the Clinical Trials Office at the University of Pittsburgh.

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    Patricia K. Crumrine MD

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Correspondence to Patricia K. Crumrine MD.

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Crumrine, P.K. Management of Seizures in Lennox-Gastaut Syndrome. Pediatr-Drugs 13, 107–118 (2011). https://doi.org/10.2165/11536940-000000000-00000

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