Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed an open, double-blind, and long-term study of vigabatrin (gamma-vinyl-GABA, GVG) in patients with treatment-resistant epilepsy who were receiving only one or at most two standard antiepileptic drugs (AEDs). The novel design included a parallel, double-blind, placebo-controlled phase that minimized the number of patients receiving placebo and allowed determination of the optimum dose of GVG for each patient before initiation of the double-blind phase. The study was divided into four phases. The first phase was a 6-week period of baseline observation. In the second phase, GVG was added openly to previous AEDs for 8 weeks. During the first 2 weeks of this phase, the dose of GVG was increased weekly and then, in the absence of adverse effects, was held constant for the next 6 weeks. At the end of this open phase, seizure frequency during the 6 weeks of constant treatment was compared with the baseline seizure frequency for each patient. Patients who experienced reduction greater than 50% in the frequency of any seizure type during the open phase were defined as responders. These responders were then entered into the third and double-blind phase, in which they were randomly allocated wither to continue active GVG treatment or placebo for 8 weeks. Thirty-three patients entered the study; 31 of 33 patients completed the initial open phase. Twenty patients achieved a reduction greater than or equal to 50% in the frequency of one or more seizure types and were eligible for the double-blind phase; 10 were randomized to continue GVG and 10 were randomized to placebo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Open, double-blind and long-term study of vigabatrin in chronic epilepsy. 186 11

1. A meta-analysis has been performed on nine placebo controlled trials of vigabatrin (GVG) administered as add-on therapy to patients suffering from drug resistant epilepsy. 2. There were two pilot placebo-controlled dose ranging studies, six double-blind crossover studies and a multicentre response controlled study. 3. There were a total of 398 patients entered and 390 have been evaluated for safety and 337 for efficacy. 4. In spite of the difficulties in the clinical evaluation of new antiepileptic drug, a reduction in seizure frequency was reported following the addition of vigabatrin to the concomitant medication in all studies. This was statistically significant in the larger of the two pilot studies, the multicentre study and three of the six double-blind studies. 5. There was a statistically significant reduction in seizures of in all six double-blind studies when the 98 patients suffering from complex partial seizures with or without generalisation were considered. Seventy two percent of these patients showed a greater than 25% reduction in seizure frequency. 6. Vigabatrin was well tolerated. The frequency of adverse events was similar to that reported elsewhere.
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PMID:Meta-analysis of European placebo controlled studies of vigabatrin in drug resistant epilepsy. 266 2

1. Vigabatrin (GVG) was given in a single-blind fashion to 89 patients with complex partial seizures (CPS) refractory to conventional drugs. 2. The median number of CPS per month decreased from 11.0 to 5.0 after addition of GVG, and 51% of patients had a 50% or greater decrease in CPS frequency (P less than 0.001). 3. Side effects (principally drowsiness, ataxia, headache) occurred mainly during the initiation of therapy and decreased during therapy. After 12 weeks on GVG side effects significantly interfered with functioning in only 13% of patients, and the efficacy: toxicity ratio warranted continued administration in 74% of patients. 4. Co-administration of GVG resulted in a mean decrease of 20% in phenytoin serum concentration (P less than 0.001). 5. Sixty-six patients having a favourable response to GVG during the single-blind study have been followed for 6-54 (median 33) months on GVG. Only 17 patients have dropped out of long-term follow-up due to break through seizures and/or side effects. No serious systemic or neurological toxicity has been detected.
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PMID:A multicentre study of vigabatrin for drug-resistant epilepsy. 266 6

1. The anticonvulsant potency of vigabatrin (gamma-vinyl GABA, GVG) was studied in an open trial in a group of 21 mentally handicapped patients with drug-resistant epilepsy. 2. With this treatment one third of these patients had more than 50% reduction in seizure frequency. The anticonvulsant effect appeared during the first month of therapy and was maintained during a 7-month study. The side effects were mild: mainly tiredness, aggressiveness, and ataxia. Other anticonvulsant drugs remained at baseline levels during GVG therapy. GVG was not found to modulate EEG recordings. 3. According to our results, GVG is effective for treating intractable epilepsy in mentally handicapped patients.
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PMID:Vigabatrin in epilepsy in mentally retarded patients. 275 2

1. To evaluate the relationship between the clinical response and enhancement of GABAergic neurotransmission, for 6 months we administered vigabatrin (gamma-vinyl-GABA, GVG) to 75 patients with complex partial epilepsy. Total GABA (TGABA), free GABA (FGABA), homocarnosine (HC), and GVG concentrations were measured in CSF of these patients before and during GVG treatment. 2. Over 50% reduction in seizures was found in 55% of the patients. Dose-reduction resulted in a relapse, i.e. the return of seizures. 3. At baseline TGABA, FGABA, and HC did not differ in responders and nonresponders. After GVG treatment, the TGABA and HC levels were lower in nonresponders (P less than 0.001), but the GVG and FGABA levels did not differ. The GVG dose reduction resulted in a concomitant decrease in TGABA, FGABA, HC and GVG (P less than 0.001). 4. According to our results GVG is an effective anticonvulsant drug in complex partial seizures. In nonresponders the poor anticonvulsant response may be related to the lower elevation of the CSF markers of GABAergic neuronal activity in this group compared with the responders.
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PMID:Cerebrospinal fluid GABA and seizure control with vigabatrin. 275 14

In studies spanning more than 5 years, more than 1,100 patients with epilepsy have been treated with vigabatrin (gamma vinyl GABA, GVG). Sixty-two patients with partial seizures with secondary generalization took part in this trial: 41 patients continued in the trial after 19 months of treatment. After 36 months, the median percentage of baseline seizures was less than 20%. GVG is a very potent antiepileptic drug. It is well tolerated in humans. The side effects are few. Skin rash and other allergic reactions have rarely been seen. Tolerance to the sedative effect is in contrast to the lack of tolerance to the anti-epileptic effect.
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PMID:Long-term evaluation of vigabatrin (gamma vinyl GABA) in epilepsy. 276 17

The goal of management in epilepsy is to make patients completely seizure-free without side effects. Currently, this goal can be achieved fully in only about one-half of the 50,000,000 people in the world with epilepsy. Epilepsy is not a benign condition. Uncontrolled epilepsy produces significant morbidity and mortality. Even infrequent seizures put a patient at risk of sudden death and compromise employability and other social functions. The potential risk of a new antiepileptic drug has to be weighted against the potential risk of continuing seizures and the potential for the new drug to control those seizures. Vigabatrin (gamma vinyl GABA, GVG) is one of the promising new antiepileptic drugs now under development. In four large clinical trials half of the patients in each trial had a greater than or equal to 50% reduction in seizure frequency when GVG was added to existing antiepileptic drug. This represents a significant response rate in add-on trials, which are a severe test of a new antiepileptic drug. Although microvacuoles have been seen in the white matter of the brains of rats and dogs treated with GVG, such pathological changes have not yet been observed in humans. Evoked potential studies have failed to reveal any evidence of microvacuolization in humans. Because of the potential efficacy of GVG in controlling previously therapeutic-resistant seizures and of the absence of evidence of significant toxicity in humans, carefully monitored clinical trials of GVG in therapy-resistant patients with epilepsy should continue.
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PMID:gamma Vinyl GABA: current role in the management of drug-resistant epilepsy. 276 18

The effect of chronic administration of gamma-vinyl GABA (GVG; vigabatrin) on levels of neurotransmission-related amino compounds was studied in lumbar cerebrospinal fluid of 65 patients with complex partial epilepsy. The first sample of cerebrospinal fluid was taken before a 3-month period of treatment with 3 g gamma-vinyl GABA/day, and the second was taken afterwards. From patients who showed a greater than 50% reduction in seizures (responders) or marked improvement in global performance, a third sample was taken at the end of the next 3-month phase, during which 3 g or 1.5 g gamma-vinyl GABA had been administered daily. During treatment with 3 g gamma-vinyl GABA/day, 55% of the patients showed more than 50% reduction in complex partial seizures; and at the same time free GABA, total GABA, homocarnosine, and glycine concentrations in the cerebrospinal fluid increased by 104%, 151%, 194% and 16%, respectively. After reduction of the daily dose to 1.5 g, the levels of free GABA, total GABA and homocarnosine were still increased by 65%, 115% and 102%, respectively. gamma-Vinyl GABA correlated with the levels of free GABA (P less than 0.002) and glycine (P less than 0.001). Concentrations of homocarnosine at baseline and homocarnosine and total GABA during gamma-vinyl GABA treatment were lower (P less than 0.005) in the group of non-responders than in the responder group. Glutamic acid, glutamine, aspartic acid, asparagine, and taurine levels did not change during gamma-vinyl GABA treatment. In conclusion, administration of gamma-vinyl GABA reduces epileptic seizures and produces dosage-dependent increases in levels of free GABA, GABA-containing peptides and of glycine in cerebrospinal fluid, without concomitant change in levels of excitatory amino acids.
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PMID:Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with gamma-vinyl GABA (vigabatrin). 314 62

Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administration of a sub-convulsant dose of bicuculline methiodide (100 ng). Significant increases in locomotion occurred when GABA (300 micrograms) was injected along with the inhibitor of GABA-transaminase, d,l-gamma-vinyl-GABA (GVG; 5 micrograms) and the inhibitor of the uptake of GABA, 1-2,4-diaminobutyric acid (DABA; 5 micrograms). No other behavioral effects were observed following injection of GABA into the nigra, either alone or in combination with GVG and DABA. Bilateral injection of bicuculline (100-600 ng) into the nigra had strong convulsant actions. When injected simultaneously with bicuculline, GABA reduced bicuculline-induced seizures. These results are discussed in terms of their relevance to understanding the mechanisms that underlie the behavioral effects produced by injection of muscimol into the nigra.
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PMID:Effects of bilateral injection of GABA into the substantia nigra on spontaneous behavior and measures of analgesia. 321 60

We studied the antiepileptic potency of vigabatrin (gamma-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear.
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PMID:Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study. 336 72


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