Therapeutic approach to Lennox–Gastaut syndrome: a systematic review

  • Serena BorrelliEmail author
  • Riem El Tahry
Review article


Lennox–Gastaut syndrome (LGS) is a rare, age-related syndrome, characterized by multiple seizure types, mental regression, and specific EEG abnormalities. It is one of the most challenging epilepsy: treatment is rarely effective and the final prognosis remains poor, despite the availability of several antiepileptic drugs, validated through well-designed, randomized, controlled trials. However, it is reasonable to consider non-medical treatments, such as surgery, after failure of two-to-three drugs. This review has as goal to describe systematically the different therapeutic options for LGS, including, not only recognized antiepileptic drugs, but also new oral drugs, immune therapy, diet, surgery, and neurostimulation techniques.


Lennox–Gastaut syndrome LGS Treatment Epilepsy surgery Epileptic encephalopathies 


Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

This article does not include any studies on human or animal participants performed by the authors.

Informed consent



  1. 1.
    van Rijckevorsel K (2008) Treatment of Lennox–Gastaut syndrome: overview and recent findings. Neuropsychiatr Dis Treat 4(6):1001–1019Google Scholar
  2. 2.
    Arzimanoglou A et al (2009) Lennox–Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology. Lancet Neurol 8(1):82–93Google Scholar
  3. 3.
    Crumrine PK (2002) Lennox–Gastaut syndrome. J Child Neurol 17(Suppl 1):S70–S75Google Scholar
  4. 4.
    Vassella F et al (1978) Double-blind study on the anti-convulsive effect of phenobarbital and valproate in the Lennox syndrome. Schweiz Med Wochenschr 108(19):713–716Google Scholar
  5. 5.
    Covanis A, Gupta AK, Jeavons PM (1982) Sodium valproate: monotherapy and polytherapy. Epilepsia 23(6):693–720Google Scholar
  6. 6.
    Motte J et al (1997) Lamotrigine for generalized seizures associated with the Lennox–Gastaut syndrome. Lamictal Lennox–Gastaut Study Group. N Engl J Med 337(25): 1807-1812Google Scholar
  7. 7.
    Sachdeo RC et al (1999) A double-blind, randomized trial of topiramate in Lennox–Gastaut syndrome. Topiramate YL Study Group. Neurology 52(9):1882–1887Google Scholar
  8. 8.
    Kim HJ et al (2014) Adjunctive levetiracetam treatment in pediatric Lennox–Gastaut syndrome. Pediatr Neurol 51(4):527–531Google Scholar
  9. 9.
    Conry JA et al (2014) Stable dosages of clobazam for Lennox–Gastaut syndrome are associated with sustained drop-seizure and total-seizure improvements over 3 years. Epilepsia 55(4):558–567Google Scholar
  10. 10.
    Isojarvi J et al (2016) Clobazam-treated patients with Lennox–Gastaut syndrome experienced fewer seizure-related injuries than placebo patients during trial OV-1012. Epilepsia 57(6):e113–e116Google Scholar
  11. 11.
    Isojarvi J et al (2018) Optimizing clobazam treatment in patients with Lennox–Gastaut syndrome. Epilepsy Behav 78:149–154Google Scholar
  12. 12.
    Sankar R et al (2014) Clinical considerations in transitioning patients with epilepsy from clonazepam to clobazam: a case series. J Med Case Rep 8:429Google Scholar
  13. 13.
    Vassella F et al (1973) Treatment of infantile spasms and Lennox–Gastaut syndrome with clonazepam (Rivotril). Epilepsia 14(2):165–175Google Scholar
  14. 14.
    Glauser T et al (2008) Rufinamide for generalized seizures associated with Lennox–Gastaut syndrome. Neurology 70(21):1950–1958Google Scholar
  15. 15.
    You SJ et al (2008) Clinical efficacy of zonisamide in Lennox–Gastaut syndrome: Korean multicentric experience. Brain Dev 30(4):287–290Google Scholar
  16. 16.
    Felbamate Study Group in Lennox–Gastaut, S (1993) Efficacy of felbamate in childhood epileptic encephalopathy (Lennox–Gastaut syndrome). N Engl J Med 328(1): 29–33Google Scholar
  17. 17.
    Caraballo RH et al (2018) Sulthiame add-on therapy in children with Lennox–Gastaut syndrome: a study of 44 patients. Seizure 62:55–58Google Scholar
  18. 18.
    Devinsky O et al (2016) Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol 15(3):270–278Google Scholar
  19. 19.
    Geffrey AL et al (2015) Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia 56(8):1246–1251Google Scholar
  20. 20.
    GW Pharmaceutical Announces Positive Phase 3 Pivotal Study Results for Epidiolex®(cannabidiol) in the Treatment of Lennox–Gastaut Syndrome (2016) GW Pharmaceuticals website. Accessed 9 Nov 2016
  21. 21.
    GW Pharmaceuticals Announces Second Positive Phase 3 Pivotal Trial for Epidiolex®(cannabidiol) in the Treatment of Lennox–Gastaut Syndrome (2016) GW Pharmaceuticals website. Accessed 9 Nov 2016
  22. 22.
    Grosso S et al (2014) Efficacy and tolerability of add-on lacosamide in children with Lennox–Gastaut syndrome. Acta Neurol Scand 129(6):420–424Google Scholar
  23. 23.
    Andrade-Machado R et al (2015) Efficacy and tolerability of add-on Lacosamide treatment in adults with Lennox–Gastaut syndrome: an observational study. Seizure 33:81–87Google Scholar
  24. 24.
    Miskin C et al (2016) Efficacy and tolerability of lacosamide in the treatment of children with refractory generalized epilepsy. J Child Neurol 31(7):925–928Google Scholar
  25. 25.
    Auvin S et al (2017) Use of perampanel in children and adolescents with Lennox–Gastaut Syndrome. Epilepsy Behav 74:59–63Google Scholar
  26. 26.
    Steinhoff BJ et al (2014) First clinical experiences with perampanel–the Kork experience in 74 patients. Epilepsia 55(Suppl 1):16–18Google Scholar
  27. 27.
    Huber B, Schmid G (2017) A two-year retrospective evaluation of perampanel in patients with highly drug-resistant epilepsy and cognitive impairment. Epilepsy Behav 66:74–79Google Scholar
  28. 28.
    Lagae L et al (2018) A pilot, open-label study of the effectiveness and tolerability of low-dose ZX008 (fenfluramine HCl) in Lennox–Gastaut syndrome. Epilepsia 59(10):1881–1888Google Scholar
  29. 29.
    Yamatogi Y et al (1979) Treatment of the Lennox syndrome with ACTH: a clinical and electroencephalographic study. Brain Dev 1(4):267–276Google Scholar
  30. 30.
    O'Regan ME, Brown JK (1998) Is ACTH a key to understanding anticonvulsant action? Dev Med Child Neurol 40(2):82–89Google Scholar
  31. 31.
    Sinclair DB (2003) Prednisone therapy in pediatric epilepsy. Pediatr Neurol 28(3):194–198Google Scholar
  32. 32.
    Gross-Tsur V et al (1993) Intravenous high-dose gammaglobulins for intractable childhood epilepsy. Acta Neurol Scand 88(3):204–209Google Scholar
  33. 33.
    Illum N et al (1990) Intravenous immunoglobulin: a single-blind trial in children with Lennox–Gastaut syndrome. Neuropediatrics 21(2):87–90Google Scholar
  34. 34.
    van Rijckevorsel-Harmant K, Delire M, Rucquoy-Ponsar M (1986) Treatment of idiopathic West and Lennox–Gastaut syndromes by intravenous administration of human polyvalent immunoglobulins. Eur Arch Psychiatry Neurol Sci 236(2):119–122Google Scholar
  35. 35.
    Caraballo RH et al (2014) Ketogenic diet in patients with Lennox–Gastaut syndrome. Seizure 23(9):751–755Google Scholar
  36. 36.
    Freeman JM et al (2009) A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia 50(2):322–325Google Scholar
  37. 37.
    Lemmon ME et al (2012) Efficacy of the ketogenic diet in Lennox–Gastaut syndrome: a retrospective review of one institution's experience and summary of the literature. Dev Med Child Neurol 54(5):464–468Google Scholar
  38. 38.
    Zhang Y et al (2016) Therapeutic effects of the ketogenic diet in children with Lennox–Gastaut syndrome. Epilepsy Res 128:176–180Google Scholar
  39. 39.
    Sharma S et al (2015) Use of the modified Atkins diet in Lennox Gastaut syndrome. J Child Neurol 30(5):576–579Google Scholar
  40. 40.
    Kossoff EH et al (2018) Optimal clinical management of children receiving dietary therapies for epilepsy: updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open 3(2):175–192Google Scholar
  41. 41.
    Lee YJ et al (2010) Resective pediatric epilepsy surgery in Lennox–Gastaut syndrome. Pediatrics 125(1):e58–66Google Scholar
  42. 42.
    Liu SY et al (2012) Surgical treatment of patients with Lennox-Gastaut syndrome phenotype. Sci World J 2012:614263. Google Scholar
  43. 43.
    Rolston JD et al (2018) Multiple subpial transections for medically refractory epilepsy: a disaggregated review of patient-level data. Neurosurgery 82(5):613–620Google Scholar
  44. 44.
    Spencer SS et al (2002) Multiple subpial transection for intractable partial epilepsy: an international meta-analysis. Epilepsia 43(2):141–145Google Scholar
  45. 45.
    Cukiert A et al (2006) Extended, one-stage callosal section for treatment of refractory secondarily generalized epilepsy in patients with Lennox–Gastaut and Lennox-like syndromes. Epilepsia 47(2):371–374Google Scholar
  46. 46.
    Liang S et al (2014) Anterior corpus callosotomy in school-aged children with Lennox–Gastaut syndrome: a prospective study. Eur J Paediatr Neurol 18(6):670–676Google Scholar
  47. 47.
    Kwan SY et al (2000) Seizure outcome after corpus callosotomy: the Taiwan experience. Childs Nerv Syst 16(2):87–92Google Scholar
  48. 48.
    You SJ et al (2008) Comparison of corpus callosotomy and vagus nerve stimulation in children with Lennox–Gastaut syndrome. Brain Dev 30(3):195–199Google Scholar
  49. 49.
    Morris GL 3rd et al (2013) Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 81(16):1453–1459Google Scholar
  50. 50.
    Cersosimo RO et al (2011) Vagus nerve stimulation: effectiveness and tolerability in 64 paediatric patients with refractory epilepsies. Epileptic Disord 13(4):382–388Google Scholar
  51. 51.
    Cukiert A et al (2013) A prospective long-term study on the outcome after vagus nerve stimulation at maximally tolerated current intensity in a cohort of children with refractory secondary generalized epilepsy. Neuromodulation 16(6):551–556 (discussion 556)Google Scholar
  52. 52.
    Cukiert A et al (2013) Long-term outcome after callosotomy or vagus nerve stimulation in consecutive prospective cohorts of children with Lennox–Gastaut or Lennox-like syndrome and non-specific MRI findings. Seizure 22(5):396–400Google Scholar
  53. 53.
    Li MCH, Cook MJ (2018) Deep brain stimulation for drug-resistant epilepsy. Epilepsia 59(2):273–290Google Scholar
  54. 54.
    Fisher RS et al (1992) Placebo-controlled pilot study of centromedian thalamic stimulation in treatment of intractable seizures. Epilepsia 33(5):841–851Google Scholar
  55. 55.
    Velasco F et al (2000) Predictors in the treatment of difficult-to-control seizures by electrical stimulation of the centromedian thalamic nucleus. Neurosurgery 47(2):295–304 (discussion 304-5)Google Scholar
  56. 56.
    Son BC et al (2016) Clinical outcome of patients with deep brain stimulation of the centromedian thalamic nucleus for refractory epilepsy and location of the active contacts. Stereotact Funct Neurosurg 94(3):187–197Google Scholar
  57. 57.
    Auvichayapat N et al (2016) Transcranial direct current stimulation for treatment of childhood pharmacoresistant lennox–Gastaut syndrome: a pilot study. Front Neurol 7:66Google Scholar

Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  1. 1.Department of NeurologyCliniques Universitaires Saint-Luc, Université Catholique de LouvainBrusselsBelgium
  2. 2.Department of Neurology, Center for Refractory EpilepsyCliniques Universitaires Saint-Luc, Université Catholique de LouvainBrusselsBelgium

Personalised recommendations