Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations

Dufour, Franck; Nałęcz, Katarzyna A.; Nałȩcz, Maciej J.; Nehlig, Astrid

doi:10.1016/s0168-0102(01)00232-2

Cited by 22 publications

(23 citation statements)

References 44 publications

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“…16 Thus, branched chain amino acids, by decreasing the effects of glutamatergic neurotransmission could facilitate those of GABAergic neurotransmission. 17 In addition, the ketogenic diet appears to favor the synthesis of glutamine, an essential precursor to GABA. This occurs because ketone body carbon is metabolized to glutamine and also because there is increased consumption of acetate in ketosis, which is quickly converted into glutamine in the brain by astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Branched Chain Amino Acids as Adjunctive Therapy to Ketogenic Diet in Epilepsy: Pilot Study and Hypothesis

et al. 2009

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A pilot prospective follow-up study of the role of the branched chain amino acids as additional therapy to the ketogenic diet was carried out in 17 children, aged between 2 and 7 years, with refractory epilepsy. All of these patients were on the ketogenic diet; none of them was seizure free, while only 13 had more or less benefited from the diet. The addition of branched chain amino acids induced a 100% seizure reduction in 3 patients, while a 50% to 90% reduction was noticed in 5. Moreover, in all of the patients, no reduction in ketosis was recorded despite the change in the fat-to-protein ratio from 4:1 to 2.5:1. Although our data are preliminary, we suggest that branched chain amino acids may increase the effectiveness of the ketogenic diet and the diet could be more easily tolerated by the patients because of the change in the ratio of fat to protein.

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Section: Discussionmentioning

confidence: 99%

Branched Chain Amino Acids as Adjunctive Therapy to Ketogenic Diet in Epilepsy: Pilot Study and Hypothesis

et al. 2009

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“…In the chronic VNS experiment, cumulative SWD duration was significantly reduced in the VNS group, but the effect was very similar in the control group, where it just did not reach significance. A previously reported spontaneous reduction of seizures in GAERS may be an interfering factor (17,18). This phenomenon is correlated with the decrease of vigilance resulting in more sleep episodes and less and shorter seizures (17,18).…”

Section: Discussionmentioning

confidence: 99%

The Acute and Chronic Effect of Vagus Nerve Stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS)

et al. 2005

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Summary:Purpose: The aim of this study was to evaluate the efficacy of acute and chronic vagus nerve stimulation (VNS) in genetic absence epilepsy rats from Strasbourg (GAERS). This is a validated model for absence epilepsy, characterized by frequent spontaneous absences concomitant with spike and wave discharges (SWD) on the EEG. Although absences are a benign form of seizures, it is conceptually important to investigate the efficacy of VNS in a controlled study by using this chronic epilepsy model.Methods: Both control and stimulated GAERS were implanted with five epidural EEG electrodes and a stimulation electrode around the left vagus nerve.In the first experiment, VNS was given when SWD occurred in the EEG; this was repeated the next day. A randomized crossover design (n = 8) was used.In the chronic experiment, GAERS underwent EEG monitoring during a first baseline week. During the second week, the treated group (n = 18) received VNS; controls (n = 13), on the other hand, only underwent EEG recordings.Results: On day 1 of the acute VNS experiment, the mean duration of the SWD when VNS was applied was higher than in baseline conditions (p < 0.05). However, on day 2, there was no difference in mean duration of the SWD. In the chronic VNS experiment, no statistically significant differences were found between control and stimulated GAERS.Conclusions: Acute VNS applied shortly after the onset of SWD prolonged the mean duration of SWD in GAERS at least during the first day of VNS. Chronic stimulation hardly affected SWD in GAERS. Key Words: Vagus nerve stimulation (VNS)-GAERS-Absence epilepsy.Vagus nerve stimulation (VNS) is an adjunctive treatment for refractory epilepsy. It is used in generalized and partial epilepsy (1), although responder groups have not been clearly identified. Knowledge about the efficacy profile of VNS in nonconvulsive generalized epilepsy, i.e., absence epilepsy, is limited because patients with this type of epilepsy generally have a good pharmacological response. Extensive therapeutical use of VNS in absence epilepsy is therefore unlikely, but information about the potential efficacy of VNS in this type of epilepsy could help to clarify the general principles that underlie VNS.GAERS are a validated genetic model for absence epilepsy characterized by typical spike and wave discharges (SWD) on the EEG during absence seizures (2). This work evaluates the efficacy of acute and chronic VNS in this model of primary generalized epilepsy. We investigated if acute VNS can abort SWD and if chronic stimulation suppresses absence seizures.

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“…GABA A ‐receptor agonists, GABA transaminase inhibitors, and GABA reuptake inhibitors dose‐dependently increase the duration of SWDs (37,38), whereas glutamatergic N ‐methyl‐ d ‐aspartate (NMDA)‐receptor agonists, competitive and noncompetitive antagonists and antagonists of the glycine site suppress absence seizures in that strain (25,38). Recent data from our group led to the hypothesis that the occurrence of SWDs in GAERS would reflect a subtle imbalance between glutamate and GABA transmission (39) that occurs in the absence of any change in the basal levels of the amino acids (28). Any change in this subtle imbalance would thus prevent the expression of absence seizures.…”

Section: Discussionmentioning

confidence: 99%

Effects of Topiramate in Two Models of Genetically Determined Generalized Epilepsy, the GAERS and the Audiogenic Wistar AS

2003

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Summary:Purpose: The antiepileptic effects of topiramate (TPM) were assessed in two models of genetically determined generalized epilepsy. The model of nonconvulsive epilepsy used was a model of absence seizures, the GAERS (Genetic Absence Epilepsy Rat from Strasbourg); and the model of convulsive seizures was an audiogenic rat model, the Wistar Audiogenic Sensitive (AS) rat.Methods: GAERS were equipped with four cortical electrodes over the frontoparietal cortex, and the duration of spikeand-wave discharges (SWDs) on the EEG was recorded for periods of 20 to 120 or 300 min. In Wistar AS, the occurrence of, latency to, and duration of one or two wild running episodes and tonic seizures were recorded.Results: In the 16 GAERS studied, TPM (10, 30, and 60 mg/kg) dose-dependently reduced the expression of SWD that almost totally disappeared at the two highest doses between 40 and 120 min. SWD duration returned to control levels by 180 and 280 min after the injection of 30 and 60 mg/kg TPM, respectively. In Wistar AS, 10 mg/kg TPM induced the occurrence of a second running episode not present in control rats, indicative of a decrease in sensitivity of the rats to the stimulus and increased by 330% the latency to the tonic seizure that still occurred in the eight rats studied. At 30 and 60 mg/kg, the latency to wild running increased by 140%; the second running episode was suppressed in six and seven rats, respectively, whereas the tonic seizure occurred only in one of the eight rats studied at these two doses.Conclusions: These results support the broad spectrum of antiepileptic activity of TPM, confirming its efficacy in primary generalized seizures of both tonic-clonic and of the absence type.

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Modulation of absence seizures by branched-chain amino acids: correlation with brain amino acid concentrations

Cited by 22 publications

References 44 publications

Branched Chain Amino Acids as Adjunctive Therapy to Ketogenic Diet in Epilepsy: Pilot Study and Hypothesis

Branched Chain Amino Acids as Adjunctive Therapy to Ketogenic Diet in Epilepsy: Pilot Study and Hypothesis

The Acute and Chronic Effect of Vagus Nerve Stimulation in Genetic Absence Epilepsy Rats from Strasbourg (GAERS)

Effects of Topiramate in Two Models of Genetically Determined Generalized Epilepsy, the GAERS and the Audiogenic Wistar AS

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