Vol 55, No 5 (2021)
Review Article
Published online: 2021-09-20

open access

Page views 7942
Article views/downloads 2196
Get Citation

Connect on Social Media

Connect on Social Media

Vigabatrin — new data on indications and safety in paediatric epilepsy

Weronika Golec1, Elżbieta Sołowiej1, Jolanta Strzelecka1, Elżbieta Jurkiewicz2, Sergiusz Jóźwiak1
Pubmed: 34541635
Neurol Neurochir Pol 2021;55(5):429-439.


Introduction: Vigabatrin (VGB), a second-generation antiepileptic drug, is effective for the treatment of infantile spasms and focal seizures, primarily in tuberous sclerosis complex (TSC) patients. However, reports of adverse events of VGB, including VGB-associated visual field loss and brain abnormalities in neuroimaging, have raised concerns about the broader use of VGB and thus significantly limited its application.

Aim of the study: The goal of this review was to summarise the recent therapeutic guidelines, the use of VGB in focal seizures and new VGB applications as a disease-modifying treatment in TSC patients. Moreover, we discuss the current opinions on potential VGB-associated toxicity and the safety of VGB.

Article available in PDF format

View PDF Download PDF file


  1. Ben-Menachem E. Mechanism of action of vigabatrin: correcting misperceptions. Acta Neurol Scand Suppl. 2011(192): 5–15.
  2. Yang J, Shen J. Elevated endogenous GABA concentration attenuates glutamate-glutamine cycling between neurons and astroglia. J Neural Transm (Vienna). 2009; 116(3): 291–300.
  3. Iannetti P, Spalice A, Perla FM, et al. Visual field constriction in children with epilepsy on vigabatrin treatment. Pediatrics. 2000; 106(4): 838–842.
  4. Wohlrab G, Boltshauser E, Schmitt B, et al. Visual field constriction is not limited to children treated with vigabatrin. Neuropediatrics. 1999; 30(3): 130–132.
  5. Elterman RD, Shields WD, Bittman RM, et al. Vigabatrin for the treatment of infantile spasms: final report of a randomized trial. J Child Neurol. 2010; 25(11): 1340–1347.
  6. European Medicines Agency. Opinion of the committee for proprietary medicinal products pursuant to article 12 of council directive 75/319/EEC as amended, for vigabatrin. 1999.
  7. Specchio N, Pietrafusa N, Ferretti A, et al. Treatment of infantile spasms: why do we know so little? Expert Rev Neurother. 2020; 20(6): 551–566.
  8. van der Poest Clement E, Jansen FE, Braun KPJ, et al. Update on Drug Management of Refractory Epilepsy in Tuberous Sclerosis Complex. Paediatr Drugs. 2020; 22(1): 73–84.
  9. Sabril [package insert]. Deerfield, IL: Lundbeck LLC; 2013. n.d.
  10. Hancock E, Osborne JP. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review. J Child Neurol. 1999; 14(2): 71–74.
  11. Klein P, Friedman A, Hameed MQ, et al. Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy? Epilepsia. 2020; 61(3): 359–386.
  12. Zhang Bo, McDaniel SS, Rensing NR, et al. Vigabatrin inhibits seizures and mTOR pathway activation in a mouse model of tuberous sclerosis complex. PLoS One. 2013; 8(2): e57445.
  13. Wilmshurst JoM, Gaillard WD, Vinayan KP, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia. 2015; 56(8): 1185–1197.
  14. Thodeson D, Sogawa Y. Practice experience in the treatment of infantile spasms at a tertiary care center. Pediatr Neurol. 2014; 51(5): 696–700.
  15. Friedman D, Bogner M, Parker-Menzer K, et al. Vigabatrin for partial-onset seizure treatment in patients with tuberous sclerosis complex. Epilepsy Behav. 2013; 27(1): 118–120.
  16. Greiner HM, Lynch ER, Fordyce S, et al. Vigabatrin for childhood partial-onset epilepsies. Pediatr Neurol. 2012; 46(2): 83–88.
  17. Nabbout RC, Chiron C, Mumford J, et al. Vigabatrin in partial seizures in children. J Child Neurol. 1997; 12(3): 172–177.
  18. Jackson MC, Jafarpour S, Klehm J, et al. Effect of vigabatrin on seizure control and safety profile in different subgroups of children with epilepsy. Epilepsia. 2017; 58(9): 1575–1585.
  19. Jia JL, Chen S, Sivarajah V, et al. Latitudinal differences on the global epidemiology of infantile spasms: systematic review and meta-analysis. Orphanet J Rare Dis. 2018; 13(1): 216.
  20. Talwar D, Baldwin MA, Hutzler R, et al. Epileptic spasms in older children: persistence beyond infancy. Epilepsia. 1995; 36(2): 151–155.
  21. Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58(4): 512–521.
  22. Messer R, Knupp KG. Infantile Spasms: Opportunities to Improve Care. Semin Neurol. 2020; 40(2): 236–245.
  23. Elterman RD, Shields WD, Bittman RM, et al. US Infantile Spasms Vigabatrin Study Group. Randomized trial of vigabatrin in patients with infantile spasms. Neurology. 2001; 57(8): 1416–1421.
  24. Primec ZR, Stare J, Neubauer D. The risk of lower mental outcome in infantile spasms increases after three weeks of hypsarrhythmia duration. Epilepsia. 2006; 47(12): 2202–2205.
  25. Widjaja E, Go C, McCoy B, et al. Neurodevelopmental outcome of infantile spasms: A systematic review and meta-analysis. Epilepsy Res. 2015; 109: 155–162.
  26. O'Callaghan FJK, Lux AL, Darke K, et al. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia. 2011; 52(7): 1359–1364.
  27. Darke K, Edwards SW, Hancock E, et al. trial steering committee on behalf of participating investigators, United Kingdom Infantile Spasms Study. The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial. Lancet. 2004; 364(9447): 1773–1778.
  28. Lux AL, Edwards SW, Hancock E, et al. United Kingdom Infantile Spasms Study. The United Kingdom Infantile Spasms Study (UKISS) comparing hormone treatment with vigabatrin on developmental and epilepsy outcomes to age 14 months: a multicentre randomised trial. Lancet Neurol. 2005; 4(11): 712–717.
  29. Djuric M, Kravljanac R, Tadic B, et al. Long-term outcome in children with infantile spasms treated with vigabatrin: a cohort of 180 patients. Epilepsia. 2014; 55(12): 1918–1925.
  30. Darke K, Edwards SW, Hancock E, et al. trial steering committee on behalf of participating investigators. Developmental and epilepsy outcomes at age 4 years in the UKISS trial comparing hormonal treatments to vigabatrin for infantile spasms: a multi-centre randomised trial. Arch Dis Child. 2010; 95(5): 382–386.
  31. Knupp KG, Coryell J, Nickels KC, et al. Pediatric Epilepsy Research Consortium. Response to treatment in a prospective national infantile spasms cohort. Ann Neurol. 2016; 79(3): 475–484.
  32. O'Callaghan FJK, Edwards SW, Alber FD, et al. participating investigators. Safety and effectiveness of hormonal treatment versus hormonal treatment with vigabatrin for infantile spasms (ICISS): a randomised, multicentre, open-label trial. Lancet Neurol. 2017; 16(1): 33–42.
  33. O'Callaghan FJK, Edwards SW, Alber FD, et al. International Collaborative Infantile Spasms Study (ICISS) investigators. Vigabatrin with hormonal treatment versus hormonal treatment alone (ICISS) for infantile spasms: 18-month outcomes of an open-label, randomised controlled trial. Lancet Child Adolesc Health. 2018; 2(10): 715–725.
  34. Hahn J, Park G, Kang HC, et al. Optimized treatment for infantile spasms: Vigabatrin versus Prednisolone versus combination therapy. J Clin Med. 2019; 8(10).
  35. Camposano SE, Major P, Halpern E, et al. Vigabatrin in the treatment of childhood epilepsy: a retrospective chart review of efficacy and safety profile. Epilepsia. 2008; 49(7): 1186–1191.
  36. Bresnahan R, Gianatsi M, Maguire MJ, et al. Vigabatrin add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2020; 7: CD007302.
  37. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. The Lancet. 2008; 372(9639): 657–668.
  38. Stafstrom CE, Staedtke V, Comi AM. Epilepsy mechanisms in neurocutaneous disorders: tuberous sclerosis complex, neurofibromatosis type 1, and Sturge-Weber syndrome. Front Neurol. 2017; 8: 87.
  39. Curatolo P, Nabbout R, Lagae L, et al. Management of epilepsy associated with tuberous sclerosis complex: Updated clinical recommendations. Eur J Paediatr Neurol. 2018; 22(5): 738–748.
  40. Overwater IE, Bindels-de Heus K, Rietman AB, et al. Epilepsy in children with tuberous sclerosis complex: Chance of remission and response to antiepileptic drugs. Epilepsia. 2015; 56(8): 1239–1245.
  41. Chu-Shore CJ, Major P, Camposano S, et al. The natural history of epilepsy in tuberous sclerosis complex. Epilepsia. 2010; 51(7): 1236–1241.
  42. Kingswood JC, Belousova E, Benedik MP, et al. TOSCA Consortium and TOSCA Investigators. Epilepsy in tuberous sclerosis complex: Findings from the TOSCA study. Epilepsia Open. 2019; 4(1): 73–84.
  43. Krueger DA, Northrup H, Northrup H, et al. International Tuberous Sclerosis Complex Consensus Group, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49(4): 243–254.
  44. Yum MS, Lee EH, Ko TS. Vigabatrin and mental retardation in tuberous sclerosis: infantile spasms versus focal seizures. J Child Neurol. 2013; 28(3): 308–313.
  45. Jóźwiak S, Kotulska K, Domańska-Pakieła D, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol. 2011; 15(5): 424–431.
  46. Bombardieri R, Pinci M, Moavero R, et al. Early control of seizures improves long-term outcome in children with tuberous sclerosis complex. Eur J Paediatr Neurol. 2010; 14(2): 146–149.
  47. Cusmai R, Moavero R, Bombardieri R, et al. Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis. Epilepsy Behav. 2011; 22(4): 735–739.
  48. Riikonen RS. Favourable prognostic factors with infantile spasms. Eur J Paediatr Neurol. 2010; 14(1): 13–18.
  49. Hussain SA, Schmid E, Peters JM, et al. Tuberous Sclerosis Complex Autism Center of Excellence Network. High vigabatrin dosage is associated with lower risk of infantile spasms relapse among children with tuberous sclerosis complex. Epilepsy Res. 2018; 148: 1–7.
  50. Galanopoulou AS, Gorter JA, Cepeda C. Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target. Epilepsia. 2012; 53(7): 1119–1130.
  51. Słowińska M, Jóźwiak S, Peron A, et al. Early diagnosis of tuberous sclerosis complex: a race against time. How to make the diagnosis before seizures? Orphanet J Rare Dis. 2018; 13(1): 25.
  52. Słowińska M, Golec W, Jóźwiak S. Prevention of epilepsy in humans - truth or myth? The experience from Sturge-Weber syndrome and Tuberous Sclerosis Complex. Neurol Neurochir Pol. 2019; 53(3): 190–193.
  53. Jozwiak S, Słowińska M, Borkowska J, et al. Preventive antiepileptic treatment in tuberous sclerosis complex: A long-term, prospective trial. Pediatr Neurol. 2019; 101: 18–25.
  54. Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex - Full Text View - ClinicalTrials.gov n.d. https://clinicaltrials.gov/ct2/show/NCT02849457 (February 21, 2021).
  55. Long-term, Prospective Study Evaluating Clinical and Molecular Biomarkers of Epileptogenesis in a Genetic Model of Epilepsy - Tuberous Sclerosis Complex - Full Text View - ClinicalTrials.gov n.d. https://clinicaltrials.gov/ct2/show/NCT02098759 (February 21, 2021).
  56. Kotulska K, Kwiatkowski DJ, Curatolo P, et al. EPISTOP Investigators. Prevention of epilepsy in infants with tuberous sclerosis complex in the EPISTOP trial. Ann Neurol. 2021; 89(2): 304–314.
  57. Carmant L. Vigabatrin therapy for infantile spasms: review of major trials in Europe, Canada, and the United States; and recommendations for dosing. Acta Neurol Scand Suppl. 2011(192): 36–47.
  58. Moavero R, Pisani LR, Pisani F, et al. Safety and tolerability profile of new antiepileptic drug treatment in children with epilepsy. Expert Opin Drug Saf. 2018; 17(10): 1015–1028.
  59. Eke T, Talbot JF, Lawden MC. Severe persistent visual field constriction associated with vigabatrin. BMJ. 1997; 314(7075): 180–181.
  60. Krauss GL, Johnson MA, Miller NR. Vigabatrin-associated retinal cone system dysfunction: electroretinogram and ophthalmologic findings. Neurology. 1998; 50(3): 614–618.
  61. Vanhatalo S, Pääkkönen L, Nousiainen I. Visual field constriction in children treated with vigabatrin. Neurology. 1999; 52(8): 1713–1714.
  62. Vanhatalo S, Nousiainen I, Eriksson K, et al. Visual field constriction in 91 Finnish children treated with vigabatrin. Epilepsia. 2002; 43(7): 748–756.
  63. Maguire MJ, Hemming K, Wild JM, et al. Prevalence of visual field loss following exposure to vigabatrin therapy: a systematic review. Epilepsia. 2010; 51(12): 2423–2431.
  64. Gaily E, Jonsson H, Lappi M. Visual fields at school-age in children treated with vigabatrin in infancy. Epilepsia. 2009; 50(2): 206–216.
  65. Wohlrab G, Leiba H, Kästle R, et al. Vigabatrin therapy in infantile spasms: solving one problem and inducing another? Epilepsia. 2009; 50(8): 2006–2008.
  66. Westall CA, Wright T, Cortese F, et al. Vigabatrin retinal toxicity in children with infantile spasms: An observational cohort study. Neurology. 2014; 83(24): 2262–2268.
  67. Moskowitz A, Hansen RM, Eklund SE, et al. Electroretinographic (ERG) responses in pediatric patients using vigabatrin. Doc Ophthalmol. 2012; 124(3): 197–209.
  68. Moseng L, Sæter M, Mørch-Johnsen GH, et al. Retinal nerve fibre layer attenuation: clinical indicator for vigabatrin toxicity. Acta Ophthalmol. 2011; 89(5): 452–458.
  69. Nousiainen I, Mäntyjärvi M, Kälviäinen R. No reversion in vigabatrin-associated visual field defects. Neurology. 2001; 57(10): 1916–1917.
  70. Chiron C, Dulac O. Epilepsy: Vigabatrin treatment and visual field loss. Nat Rev Neurol. 2011; 7(4): 189–190.
  71. Hardus P, Verduin WM, Engelsman M, et al. Visual field loss associated with vigabatrin: quantification and relation to dosage. Epilepsia. 2001; 42(2): 262–267.
  72. Wild JM, Chiron C, Ahn H, et al. Visual field loss in patients with refractory partial epilepsy treated with vigabatrin: final results from an open-label, observational, multicentre study. CNS Drugs. 2009; 23(11): 965–982.
  73. Sergott R, Wheless J, Smith M, et al. Evidence-based review of recommendations for visual function testing in patients treated with vigabatrin. Neuro-Ophthalmology. 2010; 34(1): 20–35.
  74. Pellock JM, Faught E, Foroozan R, et al. Which children receive vigabatrin? Characteristics of pediatric patients enrolled in the mandatory FDA registry. Epilepsy Behav. 2016; 60: 174–180.
  75. Krauss G, Faught E, Foroozan R, et al. Sabril® registry 5-year results: Characteristics of adult patients treated with vigabatrin. Epilepsy Behav. 2016; 56: 15–19.
  76. Foroozan R. Vigabatrin: lessons learned from the United States experience. J Neuroophthalmol. 2018; 38(4): 442–450.
  77. Sergott RC, Johnson CA, Laxer KD, et al. Retinal structure and function in vigabatrin-treated adult patients with refractory complex partial seizures. Epilepsia. 2016; 57(10): 1634–1642.
  78. Plant GT, Sergott RC. Understanding and interpreting vision safety issues with vigabatrin therapy. Acta Neurol Scand Suppl. 2011(192): 57–71.
  79. Balestrini S, Clayton LMS, Bartmann AP, et al. Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy. J Neurol Neurosurg Psychiatry. 2016; 87(4): 396–401.
  80. Schwarz MD, Li M, Tsao J, et al. A lack of clinically apparent vision loss among patients treated with vigabatrin with infantile spasms: The UCLA experience. Epilepsy Behav. 2016; 57(Pt A): 29–33.
  81. McFarlane MT, Wright T, McCoy B, et al. Retinal defect in children with infantile spasms of varying etiologies: An observational study. Neurology. 2020; 94(6): e575–e582.
  82. Dracopoulos A, Widjaja E, Raybaud C, et al. Vigabatrin-associated reversible MRI signal changes in patients with infantile spasms. Epilepsia. 2010; 51(7): 1297–1304.
  83. Wheless JW, Carmant L, Bebin M, et al. Magnetic resonance imaging abnormalities associated with vigabatrin in patients with epilepsy. Epilepsia. 2009; 50(2): 195–205.
  84. Simao GN, Zarei Mahmoodabadi S, Snead OC, et al. Abnormal axial diffusivity in the deep gray nuclei and dorsal brain stem in infantile spasm treated with vigabatrin. AJNR Am J Neuroradiol. 2011; 32(1): 199–203.
  85. Hussain SA, Tsao J, Li M, et al. Risk of vigabatrin-associated brain abnormalities on MRI in the treatment of infantile spasms is dose-dependent. Epilepsia. 2017; 58(4): 674–682.
  86. Pearl PL, Vezina LG, Saneto RP, et al. Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia. 2009; 50(2): 184–194.
  87. Dill P, Datta AN, Weber P, et al. Are vigabatrin induced T2 hyperintensities in cranial MRI associated with acute encephalopathy and extrapyramidal symptoms? Eur J Paediatr Neurol. 2013; 17(3): 311–315.
  88. Hernández Vega Y, Kaliakatsos M, U-King-Im JM, et al. Reversible vigabatrin-induced life-threatening encephalopathy. JAMA Neurol. 2014; 71(1): 108–109.
  89. Fong CYi, Osborne JP, Edwards SW, et al. An investigation into the relationship between vigabatrin, movement disorders, and brain magnetic resonance imaging abnormalities in children with infantile spasms. Dev Med Child Neurol. 2013; 55(9): 862–867.
  90. Lotan E, Bluvstein J, Zan E. Vigabatrin toxicity in a patient with infantile spasms treated with concomitant hormonal therapy. Isr Med Assoc J. 2020; 22(7): 461–462.
  91. A Novel Approach to Infantile Spasms - Full Text View - ClinicalTrials.gov n.d. https://clinicaltrials.gov/ct2/show/NCT03347526 (February 21, 2021).