title: Vigabatrin: 2008 update.
abstract: Vigabatrin (VGB) is a structural analogue of gamma-aminobutyric acid (GABA) that irreversibly inhibits GABA-transaminase (GABA-T), increasing brain levels of GABA. VGB is under assessment for treatment of infantile spasms (IS) and refractory complex partial seizures (CPS). Response can be rapid with spasm cessation following approximately 2 weeks of therapy. Patients with symptomatic tuberous sclerosis (TS) and other patients have achieved spasm cessation. Comparison with ACTH has been performed. Patients with refractory CPS have responded as well. Adverse effects and structural findings on imaging occur with VGB treatment. T2 hyperintensities within brain have been observed. Psychotic disorders or hallucinations have occurred rarely. A specific adverse effects is associated VGB, with a peripheral visual field defect (VFD) detected in some patients. Prevalence and incidence of the VGB-induced peripheral VFD varied depending on the age of the patient and the extent of exposure to VGB, with 25% to 50% prevalence in adults; the prevalence in children was 15% and retinal defect in infants ranged from 15% to 31%. A bilateral nasal defect may be the first clinical indication and may progress to a concentric, bilateral field defect observed in many affected patients; central visual acuity is almost always preserved. The earliest finding of the first abnormal field examination in adults was after 9 months of treatment; with a mean duration of VGB exposure of 4.8 years. In children, the earliest onset of a first abnormal field examination was after 11 months, with a mean time to onset of 5.5 years. The earliest sustained onset of the VGB-induced retinal defect in infants was 3.1 months.
  
  
  CONCLUSIONS
  Cognitive, age-appropriate visual field testing is required at baseline and then repeated at intervals in patients who continue therapy. Infants are tested at baseline and at 3-month intervals for the first 18 months of treatment, and then every 6 months thereafter. Adults with CPS are tested at baseline and at 6-month intervals. To select patients who are appropriate for VGB therapy, physicians must consider the benefits of fewer seizures and improved quality of life versus the potential risk of developing a VGBinduced peripheral VFD. Effectiveness of VGB can be detected within 12 weeks of initiating therapy. There appears to be minimal risk associated with a 2- to 3-month trial of VGB to evaluate effectiveness before there is a demonstrable risk of developing the VGB-induced peripheral VFD. If patients do not have a clinical benefit from VGB within 12 weeks of treatment initiation, VGB should be discontinued. If patients have a meaningful reduction in seizures or achieve seizure freedom, then the physician and patient or caregiver must determine if the benefits outweigh the potential risk of developing a peripheral VFD. When VGB is prescribed, the patient must be closely monitored for visual field changes. In cases where spasm or seizure improvement is not achieved within 12 weeks of initiation, VGB should be discontinued. In cases where complete spasm cessation, seizure control, or meaningful improvement is achieved within 12 weeks, continued treatment with VGB is warranted; subsequent periodic monitoring for the peripheral VFD is necessary and should be used to mitigate the risk of the defect. The risk of developing the peripheral VFD with short-term exposure seems to be low, therefore, VGB is an appropriate option for patients with IS or refractory CPS who receive a clinical benefit from its effectiveness, given the clinical consequences of uncontrolled seizures and spasms.
authors.affiliation: Department of Neurology and Psychiatry, Saint Louis University School of Medicine, Saint Louis, Missouri 63104, USA.
authors.forename: L James
authors.initials: LJ
authors.lastname: Willmore
authors.forename: Mark B
authors.initials: MB
authors.lastname: Abelson
authors.forename: Elinor
authors.initials: E
authors.lastname: Ben-Menachem
authors.forename: John M
authors.initials: JM
authors.lastname: Pellock
authors.forename: W Donald
authors.initials: WD
authors.lastname: Shields
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003071:Cognition / Q000187:drug effects; D018849:Controlled Clinical Trials as Topic; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017029:Epilepsy, Complex Partial / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D013036:Spasms, Infantile / Q000188:drug therapy*; D020888:Vigabatrin / Q000009:adverse effects / Q000627:therapeutic use*; D014794:Visual Fields / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin