Review article| Volume 23, ISSUE 7, P649-653, November 2001

Vigabatrin for tuberous sclerosis complex


      Vigabatrin (VGB) was found to be an effective anti-epileptic drug to reduce infantile spasms in about 50% of patients and it has been found most effective in infantile spasms due to tuberous sclerosis (TSC) in which up to 95% of infants had complete cessation of their spasms. VGB was synthesized to enhance inhibitory gamma-aminobutyric acidergic (GABAergic) transmission by elevating GABA levels via irreversible inhibition of GABA transaminase. The mechanism underlying the particular efficacy of VGB in TSC is still unknown. However, its efficacy suggests that epileptogenesis in TSC may be related to an impairment of GABAergic transmission. VGB should be considered as the first line monotheraphy for the treatment of infantile spasms in infants with confirmed diagnosis of TSC. The efficacy of VGB treatment can be assessed in less than 10 days, but usually a few days treatment with a dose of about 100 mg/kg/day stops infantile spasms. The cessation of the spasms is associated with a marked improvement of behaviour and mental development. Unfortunately, it has become clear that the use of VGB is associated with a late appearance of visual-field defects in up to 50% of patients. Currently the minimum duration and doses of VGB treatment that can produce side effects are unknown. The feasibility of using short treatment periods (2–3 months) should be investigated.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Brain and Development
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • French J.A.
        Epilepsia. 1999; 40: S11-S16
        • Tong X.
        • O'Connell M.T.
        • Ratnaraj N.
        • Patsalos P.N.
        Vigabatrin and GABA concentration inter-relationship in rat extracellular fluid (EDF) from frontal cortex and hippocampus.
        Epilepsia. 2000; 41: 95
        • Curatolo P.
        Vigabatrin for refractory partial seizures in children with tuberous sclerosis.
        Neuropediatrics. 1994; 25: 55-56
        • Curatolo P.
        • Cusmai R.
        MRI in Bourneville disease: relationship with EEG findings.
        Neurophysiol Clin. 1988; 18: 149-157
        • Wolf H.K.
        • Birkholz T.
        • Wellmer J.
        • Blumcke I.
        • Pietsch T.
        • Wiestler O.D.
        Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies.
        J Neuropathol Exp Neurol. 1995; 54: 689-697
        • Crino P.B.
        • Henske E.P.
        New developments in the neurobiology of the tuberous sclerosis complex.
        Neurology. 1999; 53: 1384-1390
        • Olsen R.W.
        • Avoli M.
        GABA and epileptogenesis.
        Epilepsia. 1997; 38: 399-407
        • Concas A.
        • Follesa P.
        • Barbaccia M.L.
        • Purdy R.H.
        • Biggio G.
        Physiological modulation of GABA(A) receptor plasticity by progesterone metabolites.
        Eur J Pharmacol. 1999; 375: 225-235
        • Maitra R.
        • Reynolds J.N.
        Modulation of GABA(A) receptor function by neuroactive steroids: evidence for heterogeneity of steroid sensitivity of recombinant GABA(A) receptor isoforms.
        Can J Physiol Pharmacol. 1998; 76: 909-920
        • White R.
        • Hua Y.
        • Scheithauer B.
        • Lynch D.R.
        • Henske E.P.
        • Crino P.B.
        Selective alterations in glutamate and GABA receptor subunit mRNA expression in dysplastic neurons and giant cells of cortical tubers.
        Ann Neurol. 2001; 49: 67-78
        • Smith S.S.
        • Gong Q.H.
        • Hsu F.
        • Markowitz R.S.
        • French-Mullen J.M.H.
        • Li X.
        GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.
        Nature. 1998; 392: 926-929
        • Verdecchia M.
        • Temin P.
        • Dorofeeva M.
        • Di Michele F.
        • Porfirio M.C.
        • Furnari C.
        • et al.
        Relationship between neurosteroid gamma-aminobutyric-acid A modulators and seizure frequency in epileptic children.
        Ann Neurol. 1998; 44: 565
        • Chiron C.
        • Dulac O.
        • Beaumont D.
        • Palacios L.
        • Pajot N.
        • Mumford J.
        Therapeutic trial of Vigabatrin in refractory infantile spasms.
        J Child Neurol. 1991; 6: 2552-2559
        • Aicardi J.
        • Mumford J.P.
        • Dumas C.
        • Wood S.
        • Peer Review Groups
        Vigabatrin as initial therapy for infantile spasms; a European retrospective survey.
        Epilepsia. 1996; 37: 638-642
        • Jambaqué I.
        • Chiron C.
        • Dumas C.
        • Mumford J.
        • Dulac O.
        Mental and behavioural outcome of infantile epilepsy treated by vigabatrin in tuberous sclerosis patients.
        Epilepsy Res. 2000; 38: 151-160
        • Hancock E.
        • Osborne J.P.
        Vigabatrin in the treatment of infantile spasm in tuberous sclerosis: literature review.
        J Child Neurol. 1999; 14: 71-74
        • Chiron C.
        • Dulac O.
        • Luna L.
        Vigabatrin in infantile spasms.
        Lancet. 1990; 10: 363-364
        • Appleton R.E.
        Vigabatrin in the management of generalized seizures in children.
        Seizure. 1995; 4: 45-48
        • Vles J.S.H.
        • van der Heyden A.M.H.G.
        • Ghijs A.
        • Troost J.
        Vigabatrin in the treatment of infantile spasms.
        Neuropediatrics. 1993; 24: 230-231
        • Schmitt B.
        • Wohlrab G.
        • Boltshauser E.
        Vigabatrin in newly diagnosed infantile spasms.
        Neuropediatrics. 1994; 25: 54
        • Vigevano F.
        • Cilio M.R.
        • Faberi A.
        • Giscondi A.
        • Cusmai R.
        Vigabatrin versus ACTH in the treatment of infantile spasms.
        Epilepsia. 1995; 36: s265
        • Chiron C.
        • Dumas C.
        • Jambaqué I.
        • Mumford J.
        • Dulac O.
        Randomized trial comparing vigabatrin and hydrocortisone in infantile spasms due to tuberous sclerosis.
        Epilepsy Res. 1997; 26: 389-395
        • Mitchell W.G.
        • Shah N.S.
        Vigabatrin (VGB) for infantile spasms: non-dose dependent response.
        Epilepsia. 2000; 41: 187
        • Xavier M.
        • Bento M.S.
        • Pereira D.P.
        • De Almeida J.M.
        Acute psychotic disorder associated with Vigabatrin.
        Acta Med Port. 2000; 13: 111-114
        • Gidal B.E.
        • Privitera M.D.
        • Sheth R.D.
        • Gilman J.T.
        Vigabatrin: a novel therapy for seizure disorders.
        Ann Pharmacother. 1999; 33: 1277-1286
        • Eke T.
        • Talbot J.F.
        • Lawden M.C.
        Severe persistent visual field constriction associated with vigabatrin.
        BMJ. 1997; 314: 180-181
        • Van Veelen C.W.M.
        • Hardus P.
        • Verduin W.M.
        • Berendschot T.J.M.
        • Van Rijen P.C.
        • Postma G.
        • et al.
        Concentric contraction of the visual field in patients with temporal lobe epilepsy using vigabatrin, long term results.
        Epilepsia. 2000; 41: 136
        • Mauri-Llerda J.A.
        • Iniguez C.
        • Tejero-Juste C.
        • Santos-Lasaosa S.
        • Escalza-Cortina I.
        • Ascaso-Puyuelo J.
        • et al.
        Visual field changes secondary to Vigabatrin treatment.
        Rev Neurol. 2000; 31: 1104-1108
        • Arndt C.F.
        • Derambure P.
        • Defoort S.
        • Hache J.C.
        Is visual impairment related to vigabatrin reversible?.
        Epilepsia. 1999; 40: 256
        • Versino M.
        • Veggiotti P.
        Reversibility of vigabatrin-induced visual-field defect.
        Lancet. 1999; 354: 486
        • Giordano L.
        • Valseriati D.
        • Vignoli A.
        • Morescalchi F.
        • Gandolfo E.
        Another case of reversibility of visual-field defect induced by vigabatrin monotherapy: is young age a favorable factor?.
        Neurol Sci. 2000; 21: 185-186