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Objective: To determine the prevalence of retinal defect in children with infantile spasms (IS) unrelated to treatment with vigabatrin and clarify if specific primary etiologies for IS are associated with retinal defect more than others., Methods: This was an observational cohort study including 312 patients (176 male, 136 female) with IS who were vigabatrin-naive. Participants ranged from 1.7 to 34.7 months of age (mean 8.8 months). Electroretinograms (ERGs) were performed according to the International Society for Clinical Electrophysiology of Vision. Retinal defect was identified as abnormal if the 30-Hz flicker ERG amplitude was lower than the age-corrected normal 95% prediction interval. The primary etiology for IS, as determined by the treating pediatric neurologist(s), was obtained from patient health records and classified into 1 of 9 etiologic subgroups: (1) genetic disorders alone, (2) genetic-structural disorders, (3) structural-congenital, (4) structural-acquired (perinatal), (5) structural-acquired (postnatal), (6) metabolic disorders, (7) immunologic disorders, (8) infectious, and (9) unknown causes., Results: Fifty-nine of the 312 vigabatrin-naive children (18.9%) showed retinal defect and the prevalence of retinal defect was highest (24.4%) in the structural-acquired (perinatal) subgroup, which included hypoxic-ischemic defect. Retinal function compared across subgroups showed no significant difference., Conclusions: Care is required in diagnosing retinal toxicity, which would be enhanced by baseline flicker ERG in children with IS prior to starting vigabatrin., (© 2019 American Academy of Neurology.)

Objectives: To determine time to vigabatrin (VGB, Sabril; Lundbeck, Deerfield, IL) induced retinal damage in children with infantile spasms (IS) and to identify risk factors for VGB-induced retinal damage (VGB-RD)., Methods: Observational cohort study including 146 participants (68 female, 81 male) with IS, an age-specific epilepsy syndrome of early infancy, treated with VGB. Participants ranged from 3 to 34.9 months of age (median 7.6 months). The median duration of VGB treatment was 16 months (range 4.6-78.5 months). Electroretinograms (ERGs) were performed according to the Standards of the International Society for Clinical Electrophysiology of Vision. Inclusion required baseline (pre-VGB or within 4 weeks of starting VGB treatment) and at least 2 follow-up ERGs. Significant reduction from baseline of the 30-Hz ERG flicker amplitude on 2 consecutive visits identified VGB-RD. Kaplan-Meier survival analyses depicted the effect of duration of VGB on VGB-RD., Results: These data represent the largest survival analysis of children treated with VGB who did not succumb to retinal toxicity during the study. Thirty of the 146 participants (21%) showed VGB-RD. The ERG amplitude reduced with duration of VGB treatment (p = 0.0004) with no recovery after VGB cessation. With 6 and 12 months of VGB treatment, 5.3% and 13.3%, respectively, developed VGB-RD. There was neither effect of age of initiation of VGB treatment nor sex of the child on survival statistics and no significant effect of cumulative dosage on the occurrence of VGB-RD., Conclusions: Minimizing VGB treatment to 6 months will reduce the prevalence of VGB-RD in patients with IS., (© 2014 American Academy of Neurology.)

Vigabatrin, an irreversible inhibitor of γ-aminobutyric acid transaminase, is an antiepileptic drug indicated in the United States as adjunctive therapy for adult patients with refractory complex partial seizures who have responded inadequately to several alternative treatments and for monotherapy treatment of infantile spasms in patients 1 month to 2 years of age. Approval of vigabatrin in the United States was contingent on the implementation of a Risk Evaluation and Mitigation Strategy (REMS) to manage the threat of a progressive, permanent bilateral concentric peripheral visual field defects (pVFDs) that may occur in patients treated with vigabatrin. The REMS is designed to promote compliance with evidence-based recommendations for baseline (within 4 weeks of the start of treatment) ophthalmologic evaluations and ongoing vision monitoring in all patients treated with vigabatrin. In view of the challenges associated with visual field testing in patients with epilepsy and in infants, clinicians must understand the qualitative (pattern of damage), quantitative (degree of damage), electrophysiologic, and adjunctive techniques recommended for monitoring vigabatrin-treated patients. The objectives of ongoing research are to characterize the onset, progression, and risk of developing vision loss during the first year of vigabatrin treatment and to evaluate the potential of noninvasive imaging as a method for monitoring retinal changes corresponding to the pVFD. This article provides an overview of visual field testing procedures and electroretinography, summarizes the clinical characteristics of vigabatrin-associated pVFDs, and provides recommendations for visual field and visual electrophysiology testing relevant to both adult and infant patients treated with vigabatrin., (© 2011 John Wiley & Sons A/S.)

Purpose: To evaluate the magnetic resonance imaging (MRI) of pediatric patients with infantile spasms (IS) treated with vigabatrin (VGB) in order to investigate whether VGB affects the brain., Methods: One hundred seven pediatric patients diagnosed with IS and treated with (n = 95) >or=120 mg/kg/day VGB or without (n = 12) VGB were included. MRI and diffusion-weighted imaging (DWI) were retrospectively analyzed., Results: Of the patients who had MRI scans during, but not before, VGB treatment (n = 81), 25 (30.9%) exhibited abnormal MRI signal intensity and/or restricted DWI in the deep gray nuclei and brainstem. Follow-up scans (performed in 15 of the 25 patients) revealed that these changes were reversible upon withdrawal of the medication. Analysis of patients undergoing scans before, during, and after VGB treatment (n = 14) revealed that four patients had abnormal MRI signal during treatment with VBG, two of whom reversed with cessation of VGB, one reversed without cessation of VGB, and another had persistent abnormal signal while being weaned from the VGB. Patients who had not received VGB treatment (n = 12) displayed normal imaging. Younger infants (

Purpose: To determine whether visual functions are decreased in children with infantile spasms and vigabatrin-attributed retinal toxicity., Methods: Contrast sensitivity and grating acuity were measured by using sweep visual evoked potential (VEP) testing in 42 children with infantile spasms (mean age, 29.23 +/- 18.31 months). All children had been exposed to vigabatrin (VGB) for a minimum of 1 month. These children were divided into retinal toxicity and no toxicity groupings based on 30-Hz flicker amplitude reductions on the full-field electroretinogram. A multivariate analysis of variance (MANOVA) compared visual functions between children with and without retinal toxicity., Results: The MANOVA showed that visual function was significantly affected by VGB retinal toxicity. Further univariate analysis revealed that grating acuity was significantly reduced in children with toxicity. No differences in contrast sensitivity were found between children with toxicity and those without., Conclusions: Reduced visual functions from VGB-attributed retinal toxicity can be detected in children with infantile spasms with the sweep VEP.

Purpose: To investigate whether visual deficits in children with infantile spasm (IS) are the result of seizure activity or of treatment with the anticonvulsant drug vigabatrin (VGB)., Methods: Vision function was determined in three experiments by determining peak contrast sensitivity (CS) and grating acuity (GA) with the sweep visual evoked potential. Cross-sectional study A: 34 children, including 11 patients with childhood epilepsy with exposure to VGB for at least 6 months, 10 with childhood epilepsy exposed to antiepileptic drugs other than VGB, and 13 normally developing children. Cross-sectional study B: 32 children, including 16 with IS naïve to VGB and 16 normally developing children. Longitudinal study: seven children with IS naïve to VGB, with subsequent follow-up 5 to 10 months after starting VGB., Results: In cross-sectional study A, the median CS was reduced by 0.5 log units (P = 0.025) in children with epilepsy exposed to VGB compared with those exposed to other antiepileptic drugs and normally developing children. In cross-sectional study B, the median CS was reduced by 0.25 log units (P = 0.0015) in children with IS (VGB naïve) compared with normally developing children. Longitudinal assessment showed no decrease in CS in children with IS who were followed up 5 to 10 months after starting VGB. There was no difference in GA among groups in any of the experiments., Conclusions: Patients with IS have CS deficits, but a sparing of GA. This deficit is present before VGB treatment and does not worsen with treatment onset. Results suggest that visual dysfunction is largely the result of the seizures themselves.

Purpose: To use visual evoked potential (VEP) testing to determine whether visual deficits are present in children with a history of vigabatrin use., Methods: Contrast sensitivity and visual acuity were assessed by visual evoked potential testing and compared between 28 children (mean age, 4.90 +/- 4.92 years) with seizure disorders who had taken vigabatrin and 14 typically developing children (mean age, 3.14 +/- 1.70 years). Exclusion criteria were heritable eye disease, suspected cortical visual impairment, nystagmus, and prematurity >2 weeks. The effects of the following factors on contrast sensitivity and visual acuity were examined: type of seizure (infantile spasms versus other), ERG result, duration of vigabatrin therapy, cumulative dosage of vigabatrin, and other seizure medications (other versus no other medication)., Results: Contrast sensitivity and visual acuity were reduced in vigabatrin-treated children with infantile spasms compared with vigabatrin-treated children with other seizure disorders and typically developing control subjects. The other factors examined had no significant effect on contrast sensitivity or visual acuity, with adjustment for seizure type., Conclusions: Children with infantile spasms on vigabatrin may have compromised visual function, even in the absence of suspected cortical visual impairment. The children tested in the present study have reduced vision, probably associated with infantile spasms rather than vigabatrin.