Vigabatrin Use Research Articles

What is the optimal duration for vigabatrin monotherapy in patients with infantile spasms: 6 months or longer?

Vigabatrin (VGB) is approved as monotherapy for pediatric patients with Infantile Spasms (IS). Duration of VGB use should be limited because of the risk of retinal and neurotoxicity, but the optimal length of treatment is unknown. Our study aimed to determine the risk of spasms relapse after 6 months of VGB as first-line therapy in IS patients deemed VGB good responders.The participants were 44 infants with IS who demonstrated both absence of clinical spasms and hypsarrhythmia four weeks after starting VGB, obtained from two cohorts: 29 patients from a multicenter prospective cohort and 15 patients from a retrospective single-center cohort. We divided them post hoc into two groups according to the duration of VGB treatment: 6-month group (n=34) and >6-month group (n=10) and compared outcome between the two groups.No patient in either group had a relapse of spasms. For patients with non-identified etiology (NIE) in the 6 months treatment group, no other seizure types were observed. Late epilepsy, in the form of focal seizures, emerged in only 5/37 patients (3/30 in the 6-month treatment group; 2/7 in the extended treatment group); all within the first 6-9 months after VGB initiation.Our study provides substantial evidence that a shortened VGB course of 6 months could be sufficient to treat and prevent relapse of spasms in children with IS, particularly those with NIE.

Prescription patterns of antiseizure drugs in tuberous sclerosis complex (TSC)-associated epilepsy: a multicenter cohort study from Germany and review of the literature

ABSTRACT Objective Seizures are a primary and early disease manifestation of Tuberous Sclerosis Complex (TSC). We aimed to describe the age-stratified patterns of antiseizure drug (ASD) treatments among children, adolescents, and adults with TSC in Germany. Additionally, we reviewed real-world and clinical study evidence regarding ASD utilization in patients with TSC. Methods We evaluated the pattern of routine ASD use and everolimus prescriptions based on a 2019 multicenter survey of 268 individuals with TSC-associated epilepsy. We contextualized the results with a structured review of real-world and clinical study evidence. Results TSC-associated epilepsy treatment comprises a wide variety of ASDs. In this German sample, the majority of patients were treated with polytherapy, and lamotrigine (34.7%), valproate (32.8%), oxcarbazepine (28.7%), vigabatrin (19.0%), and levetiracetam (17.9%) were identified as the most-commonly used ASDs. In addition, everolimus was used by 32.5% of patients. In adherence to current TSC guidelines, the disease-modifying ASD vigabatrin was widely used in children (58% below the age of 5 years), whereas treatment in adults did not necessarily reflect guideline preference for (partial) GABAergic ASDs. Conclusions The selection of ASDs for patients with TSC-associated epilepsy follows well-evaluated recommendations, including the guidelines regarding vigabatrin use in children. Several characteristics, such as the comparatively high frequency of valproate use and polytherapy, reflect the severity of TSC-associated epilepsy.

Clinical Utility of Electroretinograms for Evaluating Vigabatrin Toxicity in Children.

To determine changes in the clinical treatment of pediatric patients taking vigabatrin for seizure control in response to results of electroretinogram (ERG) performed for retinal toxicity screening. The authors retrospectively reviewed the medical records of patients who received ERGs at Children's Hospital of Colorado from 2009 to 2012. Age, indication for ERG, ERG data, and clinical management of vigabatrin were extracted from the records. ERGs were interpreted according to LKC Technologies normative values. A physician trained in ERG analysis interpreted each ERG. One hundred seventy ERGs were performed during the study period, and 147 ERGs were available for analysis. Every patient received general anesthesia for the procedure. Thirty-three ERGs were performed in 29 patients specifically as screening for retinal toxicity due to vigabatrin use, and 30 were available for analysis. Within this cohort, only 2 ERGs were normal (6.6%), and 28 were abnormal (93.3%). In patients who received abnormal results, 1 patient discontinued vigabatrin in response to the screening. In this study cohort, clinical management generally did not change in response to an abnormal screening result. Given the need for general anesthesia in the pediatric population receiving ERG testing, and minimal change in clinical decision-making in the face of abnormal results, ERG screening for retinal toxicity due to vigabatrin in the pediatric cohort should be reconsidered. [J Pediatr Ophthalmol Strabismus. 2021;58(3):174-179.].

Vigabatrin add-on therapy for drug-resistant focal epilepsy.

This is an updated version of the original Cochrane Review published in 2008 and updated in 2013. Epilepsy is a common neurological condition which affects up to 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs. The majority of these people have focal epilepsy. Vigabatrin is an antiepileptic drug licensed for use in drug-resistant epilepsy. To assess the efficacy and tolerability of vigabatrin as an add-on therapy for people with drug-resistant focal epilepsy. For the latest update of this review, we searched the following databases on 1 November 2018: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid 1946 to 31 October 2018), ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. The Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL) are both included in the Cochrane Register of Studies (CRS Web). We checked reference lists of retrieved studies for additional reports of relevant studies and contacted Hoechst Marion Roussel (manufacturers of vigabatrin) in 2000. We included randomised, double-blind, placebo-controlled, fully published trials of vigabatrin in people of any age with drug-resistant focal epilepsy. Two review authors assessed trials for inclusion and extracted data using the standard methodological procedures expected by Cochrane. Primary analysis was by intention-to-treat (ITT). We evaluated: 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, dose-response analysis, cognitive outcomes and quality of life. We presented results as risk ratios (RR) with 95% or 99% confidence intervals (CI). We identified 11 trials that included 756 participants (age range: 10 to 64 years). The trials tested vigabatrin doses between 1 g/day and 6 g/day. All 11 trials displayed a risk of bias across at least three risk of bias domains. Predominantly, the risk of bias was associated with: allocation concealment (selection bias), blinding of outcome assessment (detection bias) and incomplete outcome data (attrition bias). Participants treated with vigabatrin may be two to three times more likely to obtain a 50% or greater reduction in seizure frequency compared with those treated with placebo (RR 2.60, 95% CI 1.87 to 3.63; 4 studies; low-certainty evidence). Those treated with vigabatrin may also be three times more likely to have treatment withdrawn although we are uncertain (RR 2.86, 95% CI 1.25 to 6.55; 4 studies; very low-certainty evidence). Compared to placebo, participants given vigabatrin were more likely to experience adverse effects: dizziness/light-headedness (RR 1.74, 95% CI 1.05 to 2.87; 9 studies; low-certainty evidence), fatigue (RR 1.65, 95% CI 1.08 to 2.51; 9 studies; low-certainty evidence), drowsiness (RR 1.70, 95% CI 1.18 to 2.44; 8 studies) and depression (RR 3.28, 95% CI 1.30 to 8.27; 6 studies). Although the incidence rates were higher among participants receiving vigabatrin compared to those receiving placebo, the effect was not significant for the following adverse effects: ataxia (RR 2.76, 95% CI 0.96 to 7.94; 7 studies; very low-certainty evidence), nausea (RR 3.57, 95% CI 0.63 to 20.30; 4 studies), abnormal vision (RR 1.64, 95% CI 0.67 to 4.02; 5 studies; very low-certainty evidence), headache (RR 1.23, 95% CI 0.79 to 1.92; 9 studies), diplopia (RR 1.76, 99% CI 0.94 to 3.30) and nystagmus (RR 1.53, 99% CI 0.62 to 3.76; 2 studies; low-certainty evidence). Vigabatrin had little to no effect on cognitive outcomes or quality of life. Vigabatrin may significantly reduce seizure frequency in people with drug-resistant focal epilepsy. The results largely apply to adults and should not be extrapolated to children under 10 years old. Short-term follow-up of participants showed that some adverse effects were associated with its use. Analysis of longer-term observational studies elsewhere, however, has demonstrated that vigabatrin use can lead to the development of visual field defects.

Plasma taurine levels are not affected by vigabatrin in pediatric patients.

Vigabatrin is a highly effective antiseizure medication, but its use is limited due to concerns about retinal toxicity. One proposed mechanism for this toxicity is vigabatrin-mediated reduction of taurine. Herein we assess plasma taurine levels in a retrospective cohort of children with epilepsy, including a subset receiving vigabatrin. All children who underwent a plasma amino acid analysis as part of their clinical evaluation between 2006 and 2015 at Stanford Children's Health were included in the analysis. There were no significant differences in plasma taurine levels between children taking vigabatrin (n = 16), children taking other anti-seizure medications, and children not taking any anti-seizure medication (n = 556) (analysis of variance [ANOVA] p = 0.841). There were, however, age-dependent decreases in plasma taurine levels. Multiple linear regression revealed no significant association between vigabatrin use and plasma taurine level (p = 0.87) when controlling for age. These results suggest that children taking vigabatrin maintain normal plasma taurine levels, although they leave unanswered whether taurine supplementation is necessary or sufficient to prevent vigabatrin-associated visual field loss. They also indicate that age should be taken into consideration when evaluating taurine levels in young children.

Trends in Antiepileptic Drug Prescriptions for Childhood Epilepsy at a Tertiary Children's Hospital in Korea, 2001-2012.

Longitudinal prescription patterns of antiepileptic drugs (AEDs) have not been described to date in Korea. Here we aimed to describe AED prescribing trends over a 12-year period and assess age differences in AED prescribing patterns in a pediatric epilepsy population. We retrieved and analyzed all AED prescribing and dispensing data in 2001-2012 in patients aged 0-18 years with an established diagnosis of epilepsy at the largest tertiary children's hospital in Korea. AEDs included for analysis were classified as older (i.e., carbamazepine, ethosuximide, phenobarbital, phenytoin, and valproic acid) and newer (i.e., gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, topiramate, vigabatrin, zonisamide, lacosamide, and rufinamide) on the basis of market availability before versus after 1991. A total of 5593 patients with epilepsy were prescribed an AED during the 12-year period. The proportion of newer AED prescriptions was 52.6 % in 2001 and continuously increased to 74.3 % in 2012. Oxcarbazepine was most widely used, followed by valproic acid. While carbamazepine and vigabatrin use progressively decreased over the 12-year period, those of lamotrigine and topiramate rapidly increased. Age differences in prescribing patterns were observed. Polytherapy was observed in 49.7 % of the total population, while 83.9 % of new users were prescribed monotherapy. This study provided updated information on AED prescription trends for childhood epilepsy. We found a progressive increase in the use of newer AEDs. However, valproic acid, the only prevalent older AED, continued to be widely prescribed. A high rate of polytherapy among the prescriptions overall raises some safety concerns.

Changes in the ERG d-wave with vigabatrin treatment in a pediatric cohort.

Vigabatrin (VGB), a treatment for the childhood epilepsy, infantile spasms (IS), is implicated in visual field constriction. Electroretinograms (ERGs) are used as a substitute for visual field testing in infants. We use the VGB-associated ERG reduction (VAER), defined as reduction in age-corrected light adapted 30 Hz flicker amplitude from a pre-treatment measurement in the absence of other retinal defects, as an indicator of retinal toxicity resulting from VGB use. The d-wave ERG response is predominantly the result of OFF-bipolar cell depolarization response to light offset. The purpose of this study is to evaluate the ERG d-wave response as a marker for VAER toxicity in an infant population. One hundred children with IS treated with VGB (median age at baseline: 7.6 months; range 1.7-38.4) were tested for the cone-OFF response elicited to a 250 cd s m(2) flash with 200 ms duration (long flash ERG). Diagnosis of VAER requires baseline testing of the flicker ERG and at least one follow up ERG; Fifty-one patients fulfilled this criteria. Fifty-eight children received the long flash ERG at baseline. Thirteen retinally normal controls with a median age of 32 months (5.7-65) were also tested. Amplitude and implicit time of the d-wave response were measured manually. Longer duration of treatment was associated with reduced d-wave amplitude (ANOVA p < 0.05) in patients taking VGB. Nine patients demonstrated VAER during the course of the study. D-wave amplitude was reduced in the IS group with VAER compared to those without VAER (p < 0.05). Vigabatrin associated retinal defects may be reflected in reduction of the cone d-wave amplitude.

Vigabatrin for partial-onset seizure treatment in patients with tuberous sclerosis complex

Vigabatrin (VGB) has been shown to be particularly effective in the treatment of infantile spasms for those with tuberous sclerosis complex (TSC). However, many patients with TSC continue to have treatment-resistant seizures. For many patients with TSC, partial-onset seizures are prominent. Therefore, we examined the efficacy and tolerability of VGB for treatment of refractory partial-onset seizures. We performed a retrospective cohort study on 49 TSC patients with treatment-resistant seen at our center from 1997 to 2010, examined seizure outcomes, and reported adverse effects. We found that 13 (24.5%) patients became seizure-free or experienced a >90% decrease in seizure episode frequency with the addition of VGB to their regimens. Only one patient stopped VGB use because of excess sedation. The remaining 21 patients discontinued VGB use because of lack of efficacy. We conclude that VGB may be a safe and effective treatment in TSC patients with refractory partial-onset seizures.

Electroretinographic (ERG) responses in pediatric patients using vigabatrin

The antiepileptic drug vigabatrin is known to cause retinal and visual dysfunction, particularly visual field defects, in some patients. Electroretinography (ERG) is used in an attempt to identify adverse effects of vigabatrin (VGB) in patients who are not candidates for conventional perimetry. We report data from 114 pediatric patients taking VGB referred for clinical evaluation; median age at test was 22.9 (2.4 to 266.1) months, and median duration of VGB use was 9.7 (0.3 to 140.7) months. Twenty-seven of them were tested longitudinally (3 to 12 ERG tests). ERG responses to full-field stimuli were recorded in scotopic and photopic conditions, and results were compared to responses from healthy control subjects. We found that abnormalities of photoreceptor and post-receptor ERG responses are frequent in these young patients. The most frequently abnormal scotopic parameter was post-receptor sensitivity, log σ, derived from the b-wave stimulus-response function; the most frequently abnormal photopic parameter was the implicit time of the OFF response (d-wave) to a long (150 ms) flash. Abnormal 30-Hz flicker response amplitude, previously reported to be a predictor of visual field loss, occurred infrequently. For the group as a whole, none of the ERG parameters changed significantly with increasing duration of VGB use. Four of the 27 patients tested longitudinally showed systematic worsening of log σ with duration of VGB use. In a subset of patients who underwent perimetry (N = 39), there was no significant association of any ERG parameter with visual field defects. We cannot determine whether the ERG abnormalities we found were due solely to the effects of VGB. We caution against over-reliance on the ERG to monitor pediatric patients for VGB toxicity and recommend further development of a reliable test of peripheral vision to supplant ERG testing.

Development of Acute Encephalopathy Due to Vigabatrin Use in A Case of Nonketotic Hyperglycinemia

Development of Acute Encephalopathy Due to Vigabatrin Use in A Case of Nonketotic Hyperglycinemia

Expanding Treatment Options for Cocaine Dependence

Expanding Treatment Options for Cocaine Dependence

Visual Fields in Young Children Treated with Vigabatrin

To evaluate white sphere kinetic perimetry (WSKP) as a test of the peripheral visual field in young children with a history of epilepsy and treatment with Vigabatrin (VGB). VGB is an antiepileptic medication that is associated with visual field constriction. Thirty-one VGB patients and 10 control subjects, median age 6 years, were recruited. Visual field extent on the major oblique meridia was tested with a 6 degrees white sphere and WSKP, a method used by Quinn et al. to study field extent in children with retinopathy of prematurity. The same meridia were tested using Goldmann kinetic perimetry (GKP; 1.7 degrees target) in those who were capable. Monocular and binocular tests were conducted. Visual field extent for WSKP and GKP were compared in VGB patients and control subjects. Twenty-eight of 31 VGB patients were testable with binocular WSKP and their median visual field extents were smaller than controls. In 8 of 28 (29%) VGB patients, binocular field extents were smaller than the minimum in the control subjects. Monocular WSKP results did not differ between VGB patients and control subjects. Nine VGB patients were testable with both WSKP and GKP; visual field extents did not differ between tests. WSKP is feasible in VGB patients, even in those with developmental delays. WSKP has the potential to detect visual field constriction associated with VGB use.

Retinal nerve fibre layer characteristics with vigabatrin-associated visual field loss—could scanning laser polarimetry aid diagnosis?

To describe the retinal nerve fibre layer (RNFL) characteristics in patients suffering vigabatrin-associated visual field loss or behaviour consistent with field loss. Eight patients with visual field loss attributed to vigabatrin use had their RNFL evaluated by scanning laser polarimetry. All eight patients managed to perform the test reliably. The mean length of vigabatrin treatment was 81 months with a mean cumulative dose of vigabatrin being 5.4 kg. All patients had significantly reduced RNFL parameters; mean TSNIT=36.5 microm, mean nerve fibre indicator=63.1, mean superior average=42.7 microm, and mean inferior average=39.2 microm. There was no correlation between cumulative dose or time on treatment and RNFL thickness. Scanning laser polarimetry can be performed safely and reliably on patients with vigabatrin-associated field loss. RNFL thickness is reduced in these patients with vigabatrin-associated field loss. RNFL loss concentrates on the long nerve fibres, which explains the nasal pattern of field loss seen in these patients. This investigation shows promise in the screening of vigabatrin patients, especially in those patients that may not tolerate formal field testing well.

Vigabatrin use appears to be associated with visual field defects (VFDs) in paediatric patients with epilepsy,

Vigabatrin use appears to be associated with visual field defects (VFDs) in paediatric patients with epilepsy,

Vigabatrin use appears to be associated with visual field defects (VFDs) in paediatric patients with epilepsy,

Vigabatrin use appears to be associated with visual field defects (VFDs) in paediatric patients with epilepsy,

GABA and the ornithineδ-aminotransferase gene in vigabatrin-associated visual field defects

Vigabatrin use in some epilepsy patients has been associated with persistent visual field constriction and retinal dysfunction. The mechanism is unknown, but could be related to vigabatrin, chronic epilepsy, GABA toxicity, or the effect of a metabolite in combination with a predisposing genotype. The aim of this study was to investigate the latter two hypotheses. Levels of brain gamma-aminobutyric acid (GABA) measured by nuclear magnetic resonance spectroscopy were similar in subjects taking vigabatrin who developed visual field constriction and those who did not. We tested whether allelic heterogeneity of the ornithine aminotransferase gene occurs in the affected patients . No clinically significant mutation was detected, although a common intronic polymorphism was identified.

The value of electrophysiology results in patients with epilepsy and vigabatrin associated visual field loss.

To determine the value of electrophysiological findings in patients with temporal lobe epilepsy and to relate these findings to the amount of concentric contraction of the visual field and the use of vigabatrin. Electro-retinograms and electro-oculograms were done on 30 patients, operated for temporal lobe epilepsy. The patients were divided into three groups: (A) concentric contraction of the visual field associated with a history of vigabatrin medication (15 patients), (B) normal visual field with vigabatrin use (11 patients) and (C) normal visual field without vigabatrin medication (4 patients). Electrophysiological abnormalities were found in 50% of the patients in group A. The Arden ratio of the EOG was lowered in 57%. Abnormalities in the ERG were found: b-wave implicit time photopic F was prolonged (50%), b-wave amplitudes scotopic B (53%), C (73%) and G (50%) and photopic H (50%) were diminished. The amount of visual field loss and the total dose of vigabatrin used, showed only slight correlation with the ERG and EOG. The use of vigabatrin during the ERG and EOG recording in group A, gave a higher b-wave amplitude scotopic G in 64% of cases. The a-wave implicit times scotopic G (73%) and photopic G (59%) and H (73%) were shortened in group B. EOG was abnormal in 57% in group A. ERG abnormalities could only be found in 50% of group A, mainly in the inner retina. Since also the total dose of vigabatrin and the amount of visual field loss did not really show a correlation with the electrophysiological findings and results of literature are not unanimous, electrophysiology does not appear at present to be a good method to detect patients with, or at risk of, vigabatrin associated visual field loss. Regularly performed visual field examination remains the cornerstone in screening.

Visual function loss from vigabatrin: effect of stopping the drug.

To determine if visual function loss from vigabatrin use recovers after the drug is discontinued. Vigabatrin is an effective antiepileptic drug, but it is known to cause a variety of changes in visual function, including reductions in the visual field, visual acuity, color vision, and in electroretinogram (ERG) and electro-oculogram amplitudes. It is not known whether these changes are reversible. Measurements of static and kinetic visual fields, visual acuity, color vision, and the ERG were recorded while patients were taking vigabatrin and again in 13 patients who had discontinued the drug because of lack of efficacy or reductions in visual field. Most of the patients had been off the drug for 3 to 6 months, although two patients had been drug-free for almost 1 year. Although ERG cone implicit time improved, most of the patients did not show improvement in either clinical measures of visual function (i.e., visual acuity, color vision, visual fields) or in ERG amplitudes. However, several patients who showed minimal visual field loss while on the drug had substantial recovery of ERG amplitudes. There was no statistical association between recovery of function and either duration of treatment or cumulative dosage. The multifocal ERG showed a diffuse loss of function that was not isolated to the periphery. Although the visual deficits in patients taking vigabatrin tend to be mild, most patients do not show improvement after they stop taking the drug. Visual field loss resulting from vigabatrin was not reversible. Visual acuity, color vision, and ERG amplitude loss may be reversible in patients with minimal or no field loss.

Interim report on the incidence of visual field defects in patients on long term vigabatrin therapy.

The incidence was determined of visual field defects in patients in the Prescription-Event Monitoring (PEM) study, treated for > or =6 months with the antiepileptic drug vigabatrin. Questionnaires were sent to the general practitioners of the 7228 patients in the PEM study, treated with vigabatrin for > or =6 months, to ascertain whether any serious adverse events, including changes in vision, had occurred. Ophthalmologists were asked to give the results of the perimetry tests and their opinion of the cause of the visual field defect for those patients referred to them. 6793 (94%) of the 7228 questionnaires were returned. 5090 (75%) contained clinical data. 328 patients were deceased. Seventy seven cases identified from the 4762 surviving patients, are being followed up with ophthalmologists. To date, 2 weeks after posting, 12 cases of visual field defect have been confirmed by formal perimetry tests. Ten of these 12 were considered to be probably or possibly related to vigabatrin use, giving an incidence of 2.0 per 1000 patients compared with 0.4 per 1000 patients in the original PEM cohort. These interim results show a substantial increase in the incidence of visual field defects associated with long term use of vigabatrin and demonstrate that PEM can be used to assess long latency adverse events.

The economic effects of introducing vigabatrin, a new antiepileptic medication.

Epilepsy is a common disorder, the prevalence of which is estimated at between 0.1 and 1% of the population. Although there are a number of medications available for treating the disorder, 20 to 35% of affected individuals are resistant to standard treatments. Many of these patients could benefit from a new anti-epileptic, vigabatrin. Because the current indication for vigabatrin is as an adjunct in a specific subgroup of epileptic patients, which implies an increased cost of drug therapy, an ex ante economic appraisal of the expected consequences of its introduction in the treatment of epilepsy is valuable. This would provide decision makers with information to complement standard clinical data. Using administrative records of healthcare services utilisation by epileptic patients, we performed a simulation of the expected economic repercussions of vigabatrin use on direct costs related to disease management. The results show that whether or not the introduction of vigabatrin results in an increase or a reduction in costs to the healthcare system depends largely on 3 factors: (i) the administered dosage of vigabatrin; (ii) the effect that vigabatrin has on hospital admissions; and (iii) the proportion of epileptic patients who take the drug. Moreover, this study underlines the usefulness of administrative data in forecasting the economic impact of new health technologies.