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In this study, we assessed the toxicity and toxicokinetics of racemic vigabatrin and its S- and R-enantiomers (vigabatrin consists of 50:50% of the two enantiomers) by administering doses of the three test articles to male Long Evans rats via oral gavage. The animals were housed under high-intensity light conditions and the study consisted of an escalating dose phase and a 21-day fixed-dose phase. Systemic toxicity of vigabatrin appears to be due to the Vig-S-enantiomer only, as increasing doses of Vig-S or Vig-RS caused body weight loss, decreased food consumption, and affected activity. Administration of the Vig-R-enantiomer did not cause any such effects. Systemic exposure to R- and S-enantiomers was approximately linear with dose. Compared to administration of the racemate, there appeared to be a tendency for animals to take up higher amounts of Vig-R and lower amounts of Vig-S when administered as enantiomer. Bilateral retinal atrophy was observed in the fixed-dose phase in rats receiving Vig-S (either alone or as part of Vig-RS) and was characterized by irregular thinning and disorganization of the outer nuclear layer and thinning of the photoreceptor layer. The administration of the R-enantiomer alone did not cause any microscopic retinal change. [ABSTRACT FROM AUTHOR]

Background: West syndrome (WS) is a frequent epileptic encephalopathy associated with Down syndrome (DS). This study evaluated an outpatient protocol for WS in patients with DS who received vigabatrin (VGB) or VGB plus adrenocorticotrophic hormone. Methods: We analyzed infants treated in two neuropediatric centers from 2001–2021. We reviewed perinatal and familial history of epilepsy, spasm onset, treatment lag, electroencephalogram, neuroimaging, progression to epilepsy, and other neurological conditions. The outcomes were electroclinical resolution (ECR), relapses, and epilepsy progression. Results: Nineteen infants were included; 57.8% were male. The average spasm onset, follow-up, and treatment lag were 6.4 months, 8.15 years, and 2.33 months, respectively. Almost 74% had ECR after protocol intervention and minor epilepsy progression. Relapses occurred during combined therapy. Conclusions: The treatment protocol, especially combined therapy, was effective for WS in DS, impacting epilepsy progression and indicating the effectiveness of combined therapy to treat WS in patients with trisomy 21. [ABSTRACT FROM AUTHOR]

We evaluated the efficacy and safety of vigabatrin in focal epilepsy associated with tuberous sclerosis complex by retrospectively reviewing patients with focal epilepsy and tuberous sclerosis complex treated with vigabatrin at a pediatric epilepsy center over an 8-year period. Of 85 patients, 20 (23.5%) were seizure-free for >12 months, 45 (52.9%) were responders (≥50% seizure reduction), and 20 (23.5%) were nonresponders. The median age (in months) at seizure onset in the seizure-free group (median, 15; interquartile range [IQR], 6-23.3) was higher than that of responders (median, 5; IQR, 3-14) and nonresponders (median, 6; IQR, 2-12). Fewer patients in the seizure-free group had calcification in their largest tubers, but the presence of tuber calcification did not differ among groups. Vigabatrin is more likely to result in seizure freedom in children with tuberous sclerosis complex who have later infantile onset of focal seizures and no calcification in their largest tuber. [ABSTRACT FROM AUTHOR]

EEG fulfils the role of a candidate biomarker by being able to detect changes early, predict the development of epilepsy, and follow it over time.[4] However, EEG may only be done practically at intervals of a few weeks, so may miss an earlier onset of EA. In the meantime, EEG surveillance for EA and seizures, and caregiver and parent education to recognise early or subtle seizures should facilitate early referral and treatment for TSC-associated epilepsy. Subtle seizures such as focal tonic or clonic seizures, often missed by parents, can occur in the neonatal period, and these can evolve into drug-refractory epilepsy in the first few months of life.[6] A window may exist to act before the development of drug-refractory epilepsy or infantile spasms, where we could prevent or limit the epilepsy, and perhaps improve neurodevelopmental outcomes. Keywords: tuberous sclerosis; epilepsy; antiepileptic; vigabatrin; electroencephalography; prevention EN tuberous sclerosis epilepsy antiepileptic vigabatrin electroencephalography prevention 346 348 3 12/14/21 20211001 NES 211001 B Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial b Kotulska K, Kwiatkowski DJ, Curatolo P, et al. I Ann Neurol i . 2021;89:304-314. doi:10.1002/ana.25956 ObjectiveEpilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. [Extracted from the article]

Vigabatrin is recommended as first-line treatment for infantile spasms in tuberous sclerosis complex (TSC), but other indications in children with tuberous sclerosis complex are less known. We retrospectively reviewed 201 children with tuberous sclerosis complex, and identified 21 children older than 1 year started on vigabatrin for any indication and with sufficient follow-up data. The indication for vigabatrin was epileptic spasms (n = 13), tonic seizures (n = 5), both (n = 2), and status epilepticus (n = 1). Mean age of treatment onset was 4.0 years (range 1.1-18.3). All but 1 patient had a reduction in seizures. Ten patients became seizure free and 4 had an improvement of >90%. In 9 patients, vigabatrin was tapered successfully after 8 to 33 months. Side effects reported included rash (n = 1) and behavioral decline (n = 1). No retinal toxicity was detected in 14 of 21 patients with adequate ophthalmologic surveillance data. In conclusion, vigabatrin may be an effective treatment for epileptic spasms and tonic seizures beyond the infantile age. [ABSTRACT FROM AUTHOR]

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group. [ABSTRACT FROM AUTHOR]

Neurohistopathological changes in the brain were assessed in juvenile beagle dogs given vigabatrin at 30 or 100 mg/kg/day by oral gavage from postnatal day 22 (PND22) until 16 weeks of age (PND112), when brain myelination is considered to reach the adult stage in dogs. Separate subgroups were treated from PND22 to PND35 or PND36 to PND49 to assess early effects. In addition to extensive brain histopathology, there were assessments of toxicokinetics, clinical condition, body weight, organ weights, and macroscopic pathology. In animals treated for 14 days from PND22, minimal or slight vacuolation was seen in the neuropil of the septal nuclei, hippocampus, hypothalamus, thalamus, cerebellum, and globus pallidus at 100 mg/kg/day and minimal vacuolation in the thalamus, globus pallidus, and cerebellum at 30 mg/kg/day. In animals given 100 mg/kg/day for 91 days from PND22, minimal or slight vacuolation was observed only in the hippocampus, hypothalamus, and thalamus. No vigabatrin-related brain vacuolation was observed in animals given 30 or 100 mg/kg/day for 14 days from PND36. Clear evidence of recovery was observed after 14-day and 6-week off-dose periods that followed treatment from PND22 to PND35 or PND22 to PND112, respectively. [ABSTRACT FROM AUTHOR]

Vigabatrin is an antiepileptic drug used for treatment of infantile spasms. We present a female patient with infantile spasms in treatment with vigabatrin who developed ataxic movements. MRI demonstrated a symmetrical pattern of thalamic and globi pallidi diffusion restriction. While these image features have been widely described to be related to the use of vigabatrin, this case highlights the development of movement disorders in association with MRI signal changes. Awareness of the reversible nature of this condition is reassuring for the treating team and avoids unjustified studies. [ABSTRACT FROM AUTHOR]

The Child Neurology Society/American Academy of Neurology practice parameter has recommended adrenocorticotropic hormone or vigabatrin in the short-term treatment of infantile spasms. When vigabatrin is unavailable or ineffective and adrenocorticotropic hormone is not a treatment option because of the prohibitive cost, other forms of corticosteroids have been considered in the treatment of infantile spasms. This retrospective study reviewed the Hospital for Sick Children’s experience with the short-term effectiveness of prednisolone versus adrenocorticotropic hormone in patients with infantile spasms who have failed vigabatrin. The results showed that while adrenocorticotropic hormone was more likely to lead to short-term spasm freedom, there was no difference in the likelihood of longer-term spasm resolution without relapse. These findings can guide clinicians in the treatment of infantile spasms post vigabatrin failure. [ABSTRACT FROM PUBLISHER]

Vigabatrin is an antiepileptic drug that results in higher gamma-aminobutyrate levels in the brain and retina. Vigabatrin-induced visual field defects are usually asymptomatic and only detectable by perimetry. Further, perimetry requires good cooperation, and children aged under 10 years cannot do it. Electroretinogram response amplitude to full-field 30-Hz flicker shine has been offered to be more specific in predicting visual field defects. This study is scheduled to investigate the vigabatrin-associated visual complications in 67 epileptic children taking vigabatrin using full-field electroretinogram. Electroretinographic surveys showed normal range parameters despite 3 months of vigabatrin treatment, and just 3 (4.47%) children had been visually impaired at the end of 6-month treatment. Among these 3 cases, 1 patient had persistent electroretinogram abnormality despite vigabatrin discontinuation. Our study suggests that vigabatrin is secure for short-term pediatric antiepileptic treatment, with few cases of visual impairments and that are often reversible. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex is a genetic disorder resulting in epilepsy and mental retardation. Vigabatrin has shown efficacy in the treatment of infantile spasms caused by tuberous sclerosis complex, but its effects on focal seizures caused by tuberous sclerosis complex have not been determined. We compared the efficacy of vigabatrin in patients with tuberous sclerosis complex–induced focal seizures and infantile spasms and assessed the mental outcomes in both groups. We retrospectively evaluated 31 children with tuberous sclerosis complex and epilepsy, who were treated with vigabatrin in a single tertiary center in Seoul, Korea. Vigabatrin treatment resulted in spasms cessation in 16 of 18 (88.9%) patients with infantile spasms, whereas 6 of 13 (46.2%) patients with focal seizures became seizure free. Initial response to vigabatrin had no effect on intellectual disability. Vigabatrin was highly effective in eliminating infantile spasms caused by tuberous sclerosis complex but was less effective in patients with focal seizures. [ABSTRACT FROM AUTHOR]

The optimal evaluation and treatment of children with infantile spasms is unknown. To aid in the development of a standardized approach to infantile spasms, members of the Child Neurology Society were surveyed to determine common practice. The survey had 222 responders with a responder rate of 18.5%. We found that the diagnostic evaluation and the use of first-line treatments varied among responders. For example, although adrenocorticotropic hormone continues to be the most commonly used first-line treatment for infantile spasms not due to tuberous sclerosis, some clinicians use corticosteroids, vigabatrin, and topiramate as first-line treatments for this group. Seventy percent of our responders reported seeing fewer than 10 new-onset cases of infantile spasms per year. Thus, future clinical trials will require multicenter collaboration. An important first step in such collaboration is to standardize the evaluation and treatment of infantile spasms within and between participating centers. [ABSTRACT FROM PUBLISHER]

Infantile spasms is an epileptic encephalopathy of early infancy with specific clinical and electroencephalographic (EEG) features, limited treatment options, and a poor prognosis. Efforts to develop improved treatment options have been hindered by the lack of experimental models in which to test prospective therapies. The neuropeptide adrenocorticotropic hormone (ACTH) is effective in many cases of infantile spasms, although its mechanism(s) of action is unknown. This review describes the emerging candidate mechanisms that can underlie the therapeutic effects of ACTH in infantile spasms. These mechanisms can ultimately help to improve understanding and treatment of the disease. An overview of current treatments of infantile spasms, novel conceptual and experimental approaches to infantile spasms treatment, and a perspective on remaining clinical challenges and current research questions are presented here. This summary derives from a meeting of specialists in infantile spasms clinical care and research held in New York City on June 14, 2010. [ABSTRACT FROM PUBLISHER]

The authors present 2 girls with progressive encephalopathy, hypsarrhythmia, and optic atrophy syndrome. They describe a novel finding, precocious puberty, a feature not previously reported in this syndrome. The authors also present their clinical features and the results of investigations, including radiological findings, and compare the patients of this report to previously reported cases. [ABSTRACT FROM AUTHOR]

Vigabatrin, a structural analogue of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is widely used as initial monotherapy in infantile spasms and add on therapy in partial onset seizures. Vigabatrin is associated with retinal toxicity causing constriction of the visual field. Our aim was to assess what effect add-on antiepileptic drug therapy has on the incidence of retinal toxicity in patients being treated with vigabatrin. Medication dosages, duration of treatment, and electroretinogram results were examined in a single center retrospective study. Retinal toxicity was detected in 18 of 160 patients (11.25%) over a 10-year period. A total of 14 (77%) were in the group treated with additional antiepileptic drugs, the other 4 received vigabatrin as monotherapy. We detected a significantly higher percentage of toxicity in the group of patients treated with vigabatrin and additional antiepileptic drugs. Our numbers were not sufficient to detect which drug or combination of drugs might be associated with higher risk. [ABSTRACT FROM AUTHOR]

In 2009, vigabatrin became the first FDA approved medication for the treatment of infantile spasms in the United States. There are few well-designed prospective studies comparing the drug to placebo or other modalities used in the treatment of infantile spasms. The available data have demonstrated that vigabatrin is efficacious in the treatment of infantile spasms regardless of underlying etiology, but that it is particularly beneficial in patients with a diagnosis of tuberous sclerosis. Adrenocorticotropic hormone (ACTH), the only other medication with robust efficacy data, has been used as first line therapy for infantile spasms associated with other etiologies, and in general controls spasms sooner than vigabatrin, though relapse is common with both therapies. Vigabatrin is generally well tolerated. However, use has been associated with permanent loss of peripheral vision in some patients. In children with tuberous sclerosis, vigabatrin should be considered as initial therapy for infantile spasms. It is a viable alternative for patients with suboptimal response, contraindications or intolerance to ACTH. [ABSTRACT FROM AUTHOR]

A large randomized study was conducted in patients with newly diagnosed infantile spasms to compare 2 doses of vigabatrin in achieving spasm cessation. High (100-148 mg/kg/d) and low (18-36 mg/kg/d) oral doses of vigabatrin were evaluated in a randomized, single-blind study of 14 to 21 days with subsequent open-label treatment up to 3 years. Spasm cessation was defined as 7 consecutive days of spasm freedom beginning within the first 14 days, confirmed by video-electroencephalogram. A total of 221 subjects comprised the modified intent-to-treat cohort. More subjects in the high-dose group achieved spasm cessation compared with the low-dose vigabatrin group (15.9% [17/107] vs 7.0% [8/114]; P = .0375). During follow-up, 39 of 171 (23%) subjects relapsed; 28 of 39 (72%) regained spasm freedom. Adverse events were primarily mild to moderate in severity. Vigabatrin had a dose-dependent effect in spasm reduction. Spasm cessation occurred rapidly and was maintained in the majority of infants. [ABSTRACT FROM PUBLISHER]

Vigabatrin (Sabril®) has recently been granted approval in the Unites States for the adjunctive treatment of complex-partial seizures in adults. The drug was first evaluated as a potential therapy for this population decades ago, and it has been available in other parts of the world for some time. Well controlled studies demonstrate that at doses up to 3 g/day, the drug is efficacious as add-on therapy for treatment resistant seizures. However, vigabatrin has been associated with significant side-effects limiting its use, and relegating it to a late therapeutic alternative. Specifically, vigabatrin has been implicated in the development of irreversible peripheral vision loss in a significant number of patients. For this reason, the approval of the drug in the United States was contingent upon the introduction of a rigorous monitoring protocol that must accompany its use. Additionally, the drug has been associated with a relatively high incidence of psychiatric disturbances, although there is disagreement about a direct correlation of these symptoms to the drug. Still, the drug remains a viable alternative for patients who have failed therapy with traditional anti-seizure medications. [ABSTRACT FROM AUTHOR]

Vigabatrin, a γ-aminobutyric acid (GABA) aminotransferase- inhibiting drug used for seizure control, has been associated with white matter vacuolation and intramyelinic edema in animal studies. Similar pathological lesions have never been described in the central nervous system of human participants treated with the drug. Described here is a child with quadriparetic cerebral palsy secondary to hypoxic-ischemic brain injury following premature birth, who received vigabatrin for the treatment of infantile spasms at 9 months of age. A severe deterioration of neurologic function immediately followed the initiation of vigabatrin, and the child died 3 weeks later. Neuropathological examination revealed white matter vacuolation and intramyelinic edema. This represents the first reported case of vigabatrin-induced intramyelinic edema in humans. It validates the concerns regarding vigabatrin safety in infants and individuals with preexisting abnormalities of myelin. [ABSTRACT FROM AUTHOR]

Approximately 30 to 40 percent of adults with epilepsy treated chronically with vigabatrin develop concentric visual field constrictions. These deficits are generally mild and asymptomatic, but are usually irreversible, so risks and benefits for vigabatrin treatment must be carefully reviewed. Infantile spasms, a particularly severe form of epilepsy, may respond to vigabatrin; however, some infants treated with the drug develop MRI evidence of possible intramyelinic edema in subcortical structures. This article reviews the benefits of vigabatrin treatment, the risks it poses to the retina and the developing brain, as well as possible subgroups of adults and infants with severe epilepsy for whom treatment may, nevertheless, be warranted. [ABSTRACT FROM AUTHOR]

Vigabatrin is an antiepileptic drug that produces intramyelinic edema in several animal models. This study investigates the effect of vigabatrin on the developing human brain. The authors retrospectively blindly review 34 brain magnetic resonance imaging of 22 epileptic infants (age: 9 ± 1 months) that received vigabatrin, focusing on the presence of hyperintensity on T2- and diffusion-weighted images. Patients treated with vigabatrin displayed significant magnetic resonance imaging hyperintensity of basal ganglia and brain stem (P < .001, Wilcoxon test). This hyperintensity was transient and maximal 3 to 6 months after the beginning of vigabatrin. Hyperintensity was independent from duration and type of epilepsy, and from the presence or absence of seizures. The authors conclude that vigabatrin treatment is associated with transient hypersignal of the basal ganglia and brain stem in epileptic infants. Such transient hyperintensity is likely to be age-dependent and time-dependent because it has never been observed in adult patients. [ABSTRACT FROM AUTHOR]

Up-to date information about corticotropin (ACTH) in the treatment of infantile spasms and evaluation of the long-term outcome was provided to answer questions about (1) the efficacy of doses of ACTH in comparison with other drugs, especially with vigabatrin, and the efficacy in patients with tuberous sclerosis; (2) tolerability; and (3) long-term outcome. In two studies, high doses were not more effective than low doses but were more effective in another study. In the follow-up of the studies, there was no difference. In an open, randomized, prospective study, the efficacy and relapse rates of ACTH and vigabatrin treatment did not differ significantly. The high response rates in tuberous sclerosis complex were similar. Both drugs had severe side effects. In the long-term follow-up of 20 to 35 years, one third of the patients died, the intellectual outcome of the remaining patients was normal or slightly subnormal, and one quarter and one third of the patients were seizure free. ACTH should be the first choice for treatment of infantile spasms. The side effects of ACTH, unlike those of vigabatrin, are well known, treatable, and reversible. However, an open, prospective study to compare the efficacy, relapse rate, and long-term outcome of treatment with ACTH and vigabatrin is urgently needed. The frequency of visual field defects after vigabatrin therapy should be evaluated. (J Child Neurol 2004;19:401-404). [ABSTRACT FROM AUTHOR]

Drugs that enhance gamma-aminobutyric acid (GABA) activity by interacting at post-synaptic GABA(A) receptors have long been used as hypnotics, sedatives, tranquillizers and anticonvulsants. In this category, benzodiazepines rapidly gained pride of place, replacing barbiturates and becoming the most commonly prescribed of all drugs in the Western world in the 1970s. However, problems such as dependence and withdrawal reactions became apparent in the 1980s, and it seemed that the usefulness of drugs with this mode of action was limited. Recently, focus has shifted to a new group of drugs with GABA-ergic actions mediated through various mechanisms not directly involving the GABA(A) receptor. These drugs include gabapentin, vigabatrin, tiagabine, lamotrigine, pregabalin and others. Although originally developed as anticonvulsants for epilepsy, they appear to have wider applications for use in affective disorders, especially bipolar depression, anxiety disorders and pain conditions. The current information on the properties and therapeutic potential of this new generation of GABA-ergic drugs is reviewed. It remains to be seen whether long-term use leads to tolerance, dependence and withdrawal or discontinuation reactions. [ABSTRACT FROM AUTHOR]

Clinical studies indicate anti-migraneous efficacy of the probably GABAergic anti-convulsants valproate and gabapentin. For the GABAergic anticonvulsants vigabatrin and tiagabine, studies about antimigraneous efficacy are missing. The aim of this study was to test the GABAergic potency of these drugs in vitro before further clinical studies. Intracellular recordings were obtained from hippocampal pyramidal cells. Spontaneous GABAergic hyperpolarizations (SGH) elicited by 75 µm 4-aminopyridine were used to test the effect of these drugs on GABA-dependent potentials. Tiagabine (0.1 mm) prolonged the duration of SGH. Furthermore, monophasic SGH turned over into triphasic typical GABAergic membrane potential fluctuations within 20 min. In contrast, valproate, gabapentin, and vigabatrin failed to affect SGH up to 60 min of application. The reason for the fast action of tiagabine on SGH may be caused by a faster increase of synaptic GABA levels compared with other drugs. As migraine therapy benefits from an augmentation of GABA activity, we recommend clinical studies of tiagabine as a fast-acting agent in migraine attacks. [ABSTRACT FROM AUTHOR]

SUMMARY. A simple and rapid high-performance liquid chromatographic method has been developed for the determination of vigabatrin concentrations in plasma or serum. The assay uses only 100 µL of specimen and has been found to be linear over a concentration range of 1 to 50 mg/L. The limit of detection has been determined as 1 mg/L, and the between-batch coefficient of variation for the two internal quality controls routinely analysed (n=33) has been found to be less than 5%. There was no evidence of interferences in the assay from other commonly prescribed anti-epileptic drugs. This method has been applied to routine clinical specimens to determine the concentration of vigabatrin in 47 patient specimens over a 12-month period. It was found that only 63% of the male group and 53% of the female group were within the proposed target concentration of 5 to 35 mg/L. In addition, it was found that 26% of the male group and 36% of the female group were found to have concentrations below 5 mg/L, which may indicate lack of compliance and/or lack of therapeutic efficacy of treatment. [ABSTRACT FROM AUTHOR]

The primary aim of this quality improvement initiative was to increase the number of patients receiving first-line therapy (adrenocorticotropic hormone, corticosteroids, vigabatrin) as the initial treatment for infantile spasms. We implemented a standardized management protocol for infantile spasms based on the best available data and expert consensus. To assess the impact of this intervention, we compared the 3-month remission rates between prestandardization (January 2009 to August 2012) and poststandardization (September 2012 to May 2014) cohorts. We found that the percentage of patients receiving first-line therapy as the initial treatment was 57% (31/54) in the prestandardization cohort and 100% (35/35) in the poststandardization cohort (P < .001). The rate of infantile spasms remission was higher poststandardization compared to prestandardization (78.8% vs 30.6%, P < .001). Management standardization led to all patients receiving first-line therapy as the initial treatment and was associated with a significantly improved rate of infantile spasms remission 3 months after diagnosis. [ABSTRACT FROM AUTHOR]

PURPOSE: The use of vigabatrin (VGB) as an antiepileptic drug (AED) has been limited by evidence showing that it causes vigabatrin-attributed visual field loss (VAVFL) in at least 20–40% of patients exposed at school age or later. VGB is an effective drug for infantile spasms, but there are no reports on later visual field testing after such treatment. Our aim was to investigate the risk of VAVFL in school-age children who had received VGB in infancy. METHODS: Visual fields of 16 children treated with VGB for infantile spasms were examined by Goldmann kinetic perimetry at age 6–12 years. Normal fields were defined as the temporal meridian extending to more than 70°, and mild VAVFL between 50 and 70°. Abnormal findings were always confirmed by repeating the test. Exposure data were collected from hospital charts. RESULTS: Vigabatrin was started at a mean age of 7.6 (range, 3.2–20.3) months. The mean duration of therapy was 21.0 (9.3–29.8) months and cumulative dose 655 g (209–1,109 g). Eight children were never treated with other AEDs, five received only adrenocorticotropic hormone (ACTH) in addition to VGB, and three children had been treated with other AEDs. Fifteen children had normal visual fields. Mild VAVFL was observed in one child (6%) who had been treated with VGB for 19 months and who received a cumulative dose of 572 g. CONCLUSIONS: The risk of VAVFL may be lower in children who are treated with VGB in infancy compared to patients who receive VGB at a later age. PURPOSE: Vigabatrin used to treat infantile spasms (IS) has been associated with transient magnetic resonance imaging (MRI) abnormalities. We carried out a retrospective review to better characterize the frequency of those abnormalities in IS and in children and adults treated with vigabatrin for refractory complex partial seizures (CPS). METHODS: Medical records and 332 cranial MRIs from 205 infants (aged ≤24 months) with IS treated at 10 sites in the United States and Canada were collected. Similarly, 2,074 images from 668 children (aged 2–16 years) and adults (aged >16 years) with CPS were re-reviewed. Prespecified MRI abnormalities were defined as any hyperintensity on T2-weighted or fluid-attenuated inversion-recovery (FLAIR) sequences with or without diffusion restriction not readily explained by a radiographically well-characterized pathology. MRIs were read by two neuroradiologists blinded to treatment group. The incidence and prevalence of MRI abnormalities associated with vigabatrin were estimated. RESULTS: Among infants with IS, the prevalence of prespecified MRI abnormalities was significantly higher among vigabatrin-treated versus vigabatrin-naive subjects (22% vs. 4%; p < 0.001). Of nine subjects in the prevalence population with at least one subsequent determinate MRI, resolution of MRI abnormalities occurred in six (66.7%)—vigabatrin was discontinued in four. Among adults and children treated with vigabatrin for CPS, there was no statistically significant difference in the incidence or prevalence of prespecified MRI abnormalities between vigabatrin-exposed and vigabatrin-naive subjects. DISCUSSION: Vigabatrin is associated with transient, asymptomatic MRI abnormalities in infants treated for IS. The majority of these MRI abnormalities resolved, even in subjects who remained on vigabatrin therapy. [ABSTRACT FROM AUTHOR]

Vigabatrin, a structural analogue of γ-aminobutyric acid (GABA), is used for the treatment of generalized and partial seizures in infants. The drug inhibits the GABA transaminase and elevates the GABA concentration in the brain. Here we present the vigabatrin experience in two patients with early myoclonic encephalopathy owing to nonketotic hyperglycinemia (glycine encephalopathy). Both patients had early infantile seizures characterized by fragmentary myoclonic jerks associated with burst-suppression pattern on electroencephalography. Nonketotic hyperglycinemia was diagnosed with elevated cerebrospinal fluid and plasma glycine levels. The seizures were initially thought to be infantile spasms, and vigabatrin (50 mg /kg/day) was started for the treatment of seizures. Rapidly progressive deterioration was noticed after a few days. Acute encephalopathy associated with sleepiness and respiratory failure developed. Vigabatrin produced acute encephalopathy, which regressed in a few days after vigabatrin was stopped in the first patient. However, in the second case, despite the discontinuation of vigabatrin, there was no recovery of general conditions. Our observations in two cases indicate the risk of using vigabatrin in patients with nonketotic hyperglycinemia. The elevated GABA concentration in the brain can enhance the encephalopathy, together with the elevated levels of glycine. [ABSTRACT FROM AUTHOR]

In addition to the typical infantile spasm symptoms, several other symptoms, such as eye movements, have been reported to be associated with infantile spasms, although the relationship between the typical spasms and these other events is not fully understood. Here we present a case with West syndrome. We observed the appearance of periodic eye movements followed by the onset of typical spasms and the appearance/disappearance of periodic eye movements during withdrawal/increases of vigabatrin. We believe that the case strongly supports the notion that periodic eye movements and typical spasms represent a spectrum of symptoms related to the same phenomenon of West syndrome. [ABSTRACT FROM AUTHOR]

The clinical and electroencephalographic (EEG) response to combined therapy with vigabatrin and topirarnate was evaluated in five patients ages 7 to 15 months affected by West, syndrome in an open-label trial. Four patients had cryptogenic and one patient had symptomatic (tuberous sclerosis) West syndrome. In cryptogenic patients who failed to respond to pyridoxine, vigabatrin was titrated to 80 to 100 mg/kg. Because control of infantile spasms or an EEG improvement was not obtained with vigabatrin treatment, topiramate was added (3-3.8 mg/kg/day). In all patients, the combined therapy with topiratnate and vigabatrin achieved a rapid and complete normalization of infantile spasms, and in three patients with cryptogenic West syndrome, the EKG also became normal. In only one patient, transient anorexia was observed. This drug combination led to rapid neurodevelopmental normalization in cryptogenic patients. The results are promising and justify more trials in larger numbers of children with West syndrome. (J Child Neurol 2004; 19:385-386). [ABSTRACT FROM AUTHOR]