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PubMed1993

Plasma vigabatrin enantiomer ratios in adults and children.

The new anticonvulsant vigabatrin (gamma-vinyl-gamma-aminobutyric acid) is normally supplied as a racemate, but its anticonvulsant effect is thought to reside in its [S]-enantiomer only. The plasma concentration ratio of the [R] to [S] enantiomers appears to remain constant across the vigabatrin dosage interval in adult volunteers, and in the present study this has also proved to be the case in 12 chronically treated adult epileptic patients. However, in 8 epileptic children chronically treated with other anticonvulsants and given add-on vigabatrin therapy because of failure to control seizures, plasma [R]:[S]-vigabatrin ratios changed across the drug dosage interval, the [R]-vigabatrin levels tending to be relatively higher soon after intake, and to fall more rapidly than the [S]-vigabatrin concentrations over the next few hours (mean half-lives 2.52 +/- SD 0.49 and 6.53 +/- SD 6.62 hours). The reason for the shorter half-life of [R]-vigabatrin in children remains to be elucidated, but it appears that measurement of racemic vigabatrin plasma concentrations in children, though not in adults, may lead to somewhat misleading conclusions as regards the amount of the circulating anticonvulsant [S]-vigabatrin.

Aged↗
PubMed1996

In vitro effects of the novel anti-epileptic agent vigabatrin on alanine aminotransferase and aspartate aminotransferase activities in rat serum.

The in vitro effects of vigabatrin (CAS 60643-86-9, MDL 71,754) on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were examined in rat serum. Initially, vigabatrin (30-100 micrograms/ml) produced a concentration-dependent decrease in ALT activity at 100 micrograms/ml or more after 15 min incubation with the rat serum. AST activity, in contrast, was unaffected by concentrations up to 1,000 micrograms/ml. Next, treating the rat serum with vigabatrin (30-300 micrograms/ml) for up to 5 h produced a concentration- and time-dependent decrease in ALT activity. On the other hand, a decrease in AST activity was observed only after incubation with the highest concentration of vigabatrin for 3 h or more. Finally, an investigation was made on the antagonistic effect of L-alanine, a natural substrate for ALT, on the vigabatrin-induced decrease in ALT activity to elucidate possible mechanisms underlying the inhibitory effect of vigabatrin on ALT activity. L-alanine, depending on its concentration, countered the effects of vigabatrin (100 micrograms/ml) at a 10- or 100-fold higher molar ratio than vigabatrin. These findings suggest that vigabatrin favorably decreases ALT activity by blocking the L-alanine binding site of enzymes.

Alanine↗
PubMed1993

Pharmacokinetics of vigabatrin following single and multiple oral doses in normal volunteers.

The pharmacokinetics of vigabatrin were investigated after single and multiple oral doses in two groups of 24 healthy male volunteers. Vigabatrin was well tolerated by the volunteers; headache was the most frequently reported adverse event. There were no clinically remarkable changes in serum chemistry, urinalysis, or hematology attributable to vigabatrin. For the single-dose study, a stepwise linear contrast method was used to assess dose proportionality. The results showed that vigabatrin exhibited dose linear pharmacokinetics after single oral doses ranging from 0.5 to 4.0 g. Slight changes in the terminal phase half-life and renal clearance were evident in the higher dosage groups. These changes with increasing dose of vigabatrin were relatively minor and not considered to be clinically important. Evaluation of the multiple-dose pharmacokinetics indicated that vigabatrin exhibited dose linearity over the range of 0.5 to 2.0 g administered every 12 hours. The terminal phase half-life and renal clearance of vigabatrin during multiple dosing were consistent with that after single doses. During multiple dosing, steady-state concentrations of vigabatrin were reached on the second day of dosing, and drug accumulation was minimal.

Administration, Oral↗
PubMedDate not supplied

The United Kingdom Infantile Spasms Study comparing vigabatrin with prednisolone or tetracosactide at 14 days: a multicentre, randomised controlled trial.

BACKGROUND: Infantile spasms, which comprise a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms. METHODS: The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre, randomised controlled trial in 150 hospitals in the UK. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin 100 mg/kg per day, oral prednisolone 40 mg per day, or intramuscular tetracosactide depot 0.5 mg (40 IU) on alternate days. Analysis was by intention to treat. FINDINGS: Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin (n=52) or hormonal treatments (prednisolone n=30, tetracosactide n=25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were: 40 (73%) of 55 infants assigned hormonal treatments (prednisolone 21/30 [70%], tetracosactide 19/25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference 19%, 95% CI 1%-36%, p=0.043). Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants on hormonal treatments and 28 (54%) of 52 infants on vigabatrin. No deaths were recorded. INTERPRETATION: Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments.

Anticonvulsants↗
PubMed2002

Effects of vigabatrin on epileptiform abnormal discharges in hippocampal CA3 neurons of spontaneously epileptic rats (SER).

Vigabatrin, a gamma-amino butyric acid (GABA) transaminase inhibitor, is known to inhibit partial epilepsy in humans. The spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsion and absence-like seizures from the age of 8 weeks. Hippocampal CA3 pyramidal neurons in SER show a long-lasting depolarization shift with accompanying repetitive firing when a single stimulus is delivered to the mossy fibers in slice preparations. The effects of vigabatrin on the abnormal excitability of hippocampal CA3 pyramidal neurons in SER were examined to elucidate the mechanism underlying the antiepileptic action of the drug. Intracellular recordings were performed in 24 hippocampal slice preparations of 20 SER aged 8-17 weeks old. Bath application of vigabatrin (1 mM) inhibited the depolarizing shifts with repetitive firing induced by mossy fiber stimulation in 15 min without affecting the first spike and resting membrane potentials in hippocampal CA3 neurons of SER. A higher dose of vigabatrin (10 mM) sometimes inhibited the first spike. However, vigabatrin at doses up to 10 mM did not significantly affect the single action potential elicited by stimulation of the mossy fibers in the hippocampal CA3 neurons of age-matched Wistar rats. In addition, application of vigabatrin (10 mM) did not significantly affect the firing induced by depolarizing pulse applied in the CA3 neurons of the SER, nor the miniature excitatory postsynaptic potential (mEPSP) recorded in the CA3 neurons of SER. The inhibitory effect of vigabatrin (1 mM) on the mossy fiber stimulation-induced depolarization shift with repetitive firing was blocked by concomitant application of bicuculline (10 microM), a GABA(A) receptor antagonist. These findings strongly suggested that GABA increased by inhibition of GABA transaminase with vigabatrin inhibits abnormal excitation of hippocampal CA3 neurons of SER via GABA(A) receptors, although the possibility that the drug acted directly on the GABA(A) receptors of CA3 neurons could not be completely excluded.

Action Potentials↗
PubMed1999

Changes in plasma GABA concentration during vigabatrin treatment of epilepsy: a prospective study.

The aim of the present prospective study was to evaluate changes in plasma GABA concentration in relation to clinical response during vigabatrin treatment of epilepsy. We studied 29 patients with uncontrolled partial-onset seizures during open add-on vigabatrin treatment and measured plasma GABA and vigabatrin concentrations by a sensitive HPLC method. Following short-term treatment 17 out of 28 patients had a seizure reduction of > 50% (responders). After long-term treatment 16 out of 22 patients were responders. There was no difference between responders and nonresponders regarding pretreatment seizure frequency, treatment duration, vigabatrin dose, or plasma vigabatrin concentration. Responders had a significant (p < 0.001) increase in mean plasma GABA both after short-term (from 0.380 to 0.530 nmol/ml; mean increase: 48%) and after long-term (from 0.392 to 0.618 nmol/ml; mean increase: 71%) vigabatrin treatment, whilst nonresponders had no significant changes in GABA levels. However, since plasma GABA increased in a subgroup of nonresponders, mean plasma GABA levels did not differ between responders and nonresponders. Although plasma GABA increased significantly in the responder but not in the nonresponder group during vigabatrin treatment of patients with epilepsy, it does not seem to be a reliable marker of individual clinical response to vigabatrin treatment.

Adult↗
PubMed1999

Prospective study of first-line vigabatrin monotherapy in childhood partial epilepsies.

This was a prospective open comparative pilot study to assess the efficacy and tolerability of first-line vigabatrin monotherapy in childhood partial epilepsies. Two groups of patients were recruited over the same period. The vigabatrin monotherapy group comprised 40 patients (18 male, 22 female; mean age at last visit 7.5 years); the comparative carbamazepine monotherapy group comprised 40 consecutive clinic patients (22 male, 18 female; mean age at last visit 7.8 years). Seizures disappeared in 82% of vigabatrin patients and in all carbamazepine patients with idiopathic partial epilepsy, and in 50% of vigabatrin patients and 55% of carbamazepine patients with symptomatic partial epilepsy. Interictal EEG abnormalities decreased in vigabatrin patients more than in carbamazepine patients (P < 0.05). Tolerability was good in vigabatrin patients, but four out of 37 showed mild irritability by the end of the trial. Persistent sedation was observed in eight of the 40 patients receiving carbamazepine. No patient had drug therapy discontinued because of side-effects. During vigabatrin long-term monotherapy, efficacy and good clinical tolerability were maintained. These results suggest that vigabatrin may be an alternative first-line treatment for childhood partial epilepsies. Further blinded comparative randomized trials are needed.

Adolescent↗
PubMed1998

Long-term follow-up study of vigabatrin in pretreated children with West syndrome.

A multicentre, long-term, open-label, add-on study of vigabatrin was undertaken in 23 pretreated children with infantile spasms. After 3 months of vigabatrin therapy 11 of the 23 patients had become seizure-free. At this time two-thirds of these 11 children still received other antiepileptic drugs (AEDs) in addition to vigabatrin (mostly valproic acid and/or dexamethasone). After a mean follow-up time of 5 1/4 years (range: 4 1/4-6 1/2) 72% of 18 evaluable patients (two children died, three were lost to follow-up) revealed seizure freedom for at least 1 year. The mean duration of vigabatrin therapy had been 2 1/2 years (range: 2 weeks to 4 3/4 years). Two-thirds of the 18 children continued to take AEDs, three of them undergoing vigabatrin monotherapy. Relapses of infantile spasms had occurred in 14% of the children. The rate of vigabatrin side effects (10%) was low. At follow-up, the EEG of 13 and the 18 patients demonstrated focal or multifocal epileptic discharges. Fifty-five percent had developed another epilepsy (focal epilepsy, secondary generalized epilepsy or myoclonic-astatic epilepsy). With respect to mental functions, three children were normal or slightly retarded, four showed moderate retardation and 11 revealed severe or very severe retardation. This long-term result is comparable to that in ACTH studies with unselected patients. The conclusions are: (1) vigabatrin is an effective drug for the short-term and long-term treatment of refractory infantile spasms; (2) the relapse rate is low; (3) vigabatrin is well tolerated; (4) with respect to secondary epilepsies and mental functions the long-term outcome in these pretreated children is similar to that in earlier studies with ACTH or corticosteroids.

Adrenocorticotropic Hormone↗
PubMed2002

Vigabatrin and retinal changes.

PURPOSE: Vigabatrin is an effective antiepileptic drug but visual field constriction (VFC) is found to be a severe side-effect. The aims have been to investigate whether visual field constriction (VFC) is related to changes in the electroretinography (ERG). METHODS: Twenty patients with localisations related epilepsy of whom one half had received vigabatrin were subjected to examination without informing about the treatment given. The eye examination included Goldmann perimetry and ERG. RESULTS: All the patients had normal visual acuity. A total of three patients (30%) in the vigabatrin group and none in the control group were found to have VFC. In the vigabatrin group ERG examination were normal in one case, in five cases there were changes scotopic, photopic and in the oscillatory potentials (OP), while the remaining four had changes in two of these parameters. OPs were abnormal in eight of 10 patients. Of the three patients with VFC all had changes in ERG. The four patients with the most severe abnormalities in ERG had received high daily doses of vigabatrin (4 - 6 mg) in a period. In the control group no abnormality was observed in five cases, and in the remaining five changes were present in one or two of the potentials. CONCLUSION: It is found that 30% of patients treated with vigabatrin, develop VFC, and none in the control group. Similarly more patients in the vigabatrin group had changes in the ERG as compared to the control group, and the number of abnormal potentials are significantly higher among patients with VFC compared to those without. But the finding of abnormal ERG results is not synonymous with VFC, and this is important to bear in mind when examining patients that cannot cooperate to a VF examination. An individual sensitivity to vigabatrin is supposed, but severe ERG changes occurred in all patients having had high daily doses > or = 4 g.

Adolescent↗
PubMed2004

Alterations in electroretinograms and retinal morphology in rabbits treated with vigabatrin.

PURPOSE: To determine whether long-term treatment with the anti-epileptic drug vigabatrin causes damage to rabbit retina. METHODS: Five rabbits were treated continuously with a daily dose of vigabatrin solution per orally during a period of 1-8 months. Two rabbits receiving water were used as controls. Repeated full-field electroretinograms (every two weeks) were assessed during this period. Vigabatrin serum concentration was repeatedly measured for securing successful drug administration. After termination of treatment the rabbits were sacrificed and the morphology of the sectioned retina was studied. RESULTS: In all rabbits treated with vigabatrin the serum analyses repeatedly demonstrated elevated drug concentration. Full-field electroretinograms demonstrated normal rod function in all treated rabbits, but reduced cone function in two of the five treated rabbits verified by 30Hz flicker stimulation. Morphologic studies of the sectioned retina demonstrated GFAP immunoactivity of the glial cells localized in the retinal periphery in all five treated rabbits, one of which had staining also in the centrally localized glial cells. The treated rabbits also demonstrated a weaker GAD staining in the IPL and less positive amacrine cells, compared to the controls. Only two treated rabbits had normal GABA staining while three had an enhanced GABA immunoreactivity and undistinguishable fibers in the IPL. In three out of five treated rabbits the Müller cells were short, stubby and fragmented, with swollen endfeet. CONCLUSION: This study demonstrates changes in histopathology caused by vigabatrin in an animal model, which has not been reported previously. We have found that vigabatrin orally administrated to rabbits does not affect rod function but may reduce cone function in the full-field electroretinogram, which is similar to the previously reported vigabatrin effect on the human ERG. The results indicate that vigabatrin may damage or influence, at least one cell type in the rabbit retina.

Animals↗
PubMed2001

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

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Adult↗
PubMed1998

Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in vitro model of epilepsy.

1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a change in GABA-metabolism have been suggested as mechanisms of action of gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA-transaminase but it also interferes with GABA-release and GABA-uptake. On the basis of these mechanisms of action, a pharmacodynamic interaction of the two antiepileptic drugs could be supposed which might be of relevance in the sense of a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments were carried out on hippocampal slices (n=107) of guinea-pigs (n=70). Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from the bath solution and recorded in the stratum pyramidale of the CA3 region. Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM, 6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100 microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations up to 600 microM, failed to decrease the repetition rate or duration of e.f.p. (n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h (n=11). With simultaneous administration of vigabatrin (100 microM) and gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased down to 8+/-3%, which is significantly different from the values obtained after administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic effect of vigabatrin alone and the enhancement by gabapentin were blocked by the GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results demonstrate that gabapentin is able to augment the antiepileptic effects of vigabatrin significantly. It is possible that a change in the GABA-release machinery is induced by vigabatrin which then can be augmented by gabapentin.

4-Aminobutyrate Transaminase↗
PubMed1995

Pharmacokinetic interaction studies between felbamate and vigabatrin.

To assess the possible occurrence of pharmacokinetic interactions between the antiepileptic agents felbamate and vigabatrin, two randomized, double-blind, placebo-controlled, crossover studies were conducted in healthy male volunteers. In Study I, 18 subjects received oral vigabatrin 1000 mg every 12 h for two 8 days periods with felbamate 1200 mg every 12 h or placebo. In Study II, 18 other volunteers were administered oral felbamate 1200 mg every 12 h for two 8 days periods with vigabatrin 1000 mg every 12 h or placebo. On the eighth day of each treatment period, blood and urine samples were collected over 12 h for determination of the active S(+)- and inactive R(-)-vigabatrin enantiomer concentrations (Study I) or felbamate concentrations (Study II). In Study I, the pharmacokinetic parameters of R(-)-vigabatrin were similar during co-administration with felbamate or placebo. Felbamate produced a 13% increase in AUC(0.12 h) and an 8% increase in urinary excretion of S(+)-vigabatrin. Although these changes were statistically significant, their magnitude was small. In Study II, the pharmacokinetic parameters of felbamate were similar during concurrent administration with vigabatrin or placebo. These data indicate that there are no clinically relevant pharmacokinetic interactions between felbamate and vigabatrin in man.

Administration, Oral↗
PubMed1990

Administration of vigabatrin (gamma-vinyl-gamma-aminobutyric acid) affects the levels of both inhibitory and excitatory amino acids in rat cerebrospinal fluid.

The effect of vigabatrin (gamma-vinyl-gamma-aminobutyric acid), a new anticonvulsant drug, on the transmitter amino acids in rat cisternal CSF was studied. CSF was collected through a permanently implanted polyethylene cannula from freely moving rats at 5, 24, 48, and 96 h after administration of 1,000 mg/kg of vigabatrin. The free gamma-aminobutyric acid (GABA) level was elevated maximally (13.5-fold; p less than 0.01) at 24 h after injection. The homocarnosine (GABA-histidine) level also was increased (123%; p less than 0.01) at 24 h after injection, and its concentration remained at the same level for the next 3 days. Glycine and taurine concentrations had increased [31% (p less than 0.05) and 63% (p less than 0.01), respectively] at 5 h after injection. It is interesting that the levels of glutamate and aspartate increased [330% (p less than 0.05) and 421% (p less than 0.01), respectively] at 96 h after injection, the time when the free GABA level had returned to the baseline concentration and the vigabatrin level was 3% of the maximal concentration. The present study indicates that a single dose of vigabatrin in rats elevates levels of both the inhibitory and excitatory amino acids in CSF. However, the temporal profile of observed changes in relation to vigabatrin injection shows that neither the long-lasting elevation of GABA content nor the increase in glutamate and aspartate levels correlates with the level of vigabatrin in CSF. These findings suggest that the excitatory mechanisms are also augmented following acute administration of vigabatrin, especially when the content of GABA had decreased to the baseline level and the level of vigabatrin was low.

Amino Acids↗
PubMed1995

Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy.

Vigabatrin is undoubtedly one of the most exciting anti-epilepsy drugs in use today. Many open and controlled clinical trials have confirmed that it is particularly effective in controlling partial epileptic seizures with or without secondary generalization. Vigabatrin acts to increase GABA levels in the presynaptic nerve terminal by inhibiting the activity of GABA-transaminase. There is no direct correlation between the blood or brain concentration of vigabatrin and its clinical effect, so monitoring vigabatrin levels is not predictive of patient response. However, it is possible to relate the activity of vigabatrin to levels of GABA in the brain, measured by nuclear magnetic resonance spectroscopy (NMRS). NMRS studies show that following administration of vigabatrin, brain concentrations of GABA rise to about 2-3 times their baseline values. This 'extra' GABA is held within the nerve terminal, and is only released during synaptic transmission. Although there appears to be a clear dose-response relationship up to 3 g/day, it is not well documented if higher doses result in proportionately higher brain GABA levels. This finding seems to support the results of clinical studies suggesting that the optimal dose of vigabatrin may be 3 g/day. There is also some evidence for a correlation between the concentration of GABA in the brain and the clinical outcome. Continuing investigations using NMRS aim to confirm these preliminary findings, and to determine the time course and extent of changes in brain GABA levels after vigabatrin administration.

Anticonvulsants↗
PubMed2003

A controlled study comparing visual function in patients treated with vigabatrin and tiagabine.

OBJECTIVE: Vigabatrin treatment is frequently associated with irreversible retinal injury and produces retinal electrophysiological changes in nearly all patients. Concern has been raised that tiagabine and other antiepilepsy drugs (AEDs) that increase brain gamma-aminobutyric acid (GABA) might produce similar electrophysiological and clinical changes in visual function. The study compared visual function between groups of patients with epilepsy treated long term with tiagabine, vigabatrin, and patients treated with other AEDs. METHODS: A cross sectional study comparing visual acuity, colour vision, static and kinetic perimetry, and electroretinograms between groups of patients treated with tiagabine, vigabatrin, and other AEDs (control patients). Patients were adults receiving stable AED treatment for >6 months. RESULTS: Vigabatrin treated patients had marked visual field constrictions in kinetic perimetry (mean radius 39.6 degrees OD, 40.5 degrees OS), while tiagabine patients had normal findings (mean 61 degrees OD, 62 degrees OS) (differences OD and OS, p=0.001), which were similar to epilepsy control patients (mean 60 degrees OD, 61 degrees OS). Vigabatrin patients had abnormal electroretinographic photopic B wave, oscillatory, and flicker responses, which correlated with visual field constrictions. These electroretinographic responses were normal for tiagabine patients and control patients. Patients were treated with vigabatrin for a median of 46 months compared with 29 months for tiagabine. Patients taking other AEDs that may change brain GABA had normal visual function. CONCLUSION: Unlike vigabatrin, tiagabine treatment is associated with normal electroretinography and visual fields and ophthalmological function similar to epilepsy control patients. Differences between vigabatrin and other GABA modulating AEDs in retinal drug concentrations and other effects might explain why tiagabine increases in GABA reuptake do not cause retinal injury.

Adult↗
PubMed2005

Reduced visual function associated with infantile spasms in children on vigabatrin therapy.

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.

Adolescent↗
PubMed1998

Vigabatrin-associated retinal cone system dysfunction: electroretinogram and ophthalmologic findings.

OBJECTIVE: To determine the sources of vigabatrin-associated visual disturbances in patients treated for epilepsy. BACKGROUND: Vigabatrin is an extremely effective antiepileptic drug that selectively increases brain gamma-aminobutyric acid (GABA). Several patients recently developed constricted visual fields during vigabatrin treatment in the United Kingdom, indicating the possibility of GABA-associated retinal dysfunction. METHODS: Patients with visual symptoms treated chronically with vigabatrin at our center underwent visual evoked potentials (VEP), electroretinograms (ERG), and visual field and ophthalmologic examinations. RESULTS: Four of 38 patients treated with vigabatrin developed visual symptoms 2 to 40 months after starting the drug. Two patients complained of constricted visual fields and two had blurred vision. ERG demonstrated evidence of bilateral retinal dysfunction consistent with reduced inner retinal cone response in all four patients. Oscillatory potential responses were lost, suggesting impairment of the highly GABAergic amacrine cells. Two of the patients had normal VEPs and minimal findings on clinical ophthalmology examinations despite abnormal ERGs. Abnormal examination findings were narrowed retinal arteries, surface wrinkling retinopathy, and abnormal macular reflexes. One patient also had reduced rod photoreceptor function in the more symptomatic left eye. CONCLUSIONS: Visual field constriction and blurring during vigabatrin therapy is associated with retinal cone system dysfunction. Visual symptoms may represent selective vulnerability of retinas of affected patients to GABAergic effects of vigabatrin. The prevalence and course of retinal changes associated with vigabatrin therapy are important to determine in a larger group of patients.

Adult↗