Clinical and EEG findings in complex partial status epilepticus with tiagabine.
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A case of complex partial status epilepticus (CPSE) with high dose treatment of tiagabine (TGB) is reported. Seizure aggravation and CPSE developed after stepwise increase of TGB to a dose of 60 mg per day as add-on treatment to carbamazepine (CBZ) 1200 mg/day and vigabatrine (VGB) 1000 mg/day. The EEG during CPSE showed bilateral rhythmic slow activity. Clinical symptoms of CPSE and the EEG normalized after i.v. treatment with clonazepam. The literature and the possible mechanism of this paradoxical phenomenon are discussed. (+info)
The management of epilepsy in a hospital for people with a learning disability.
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The study examined changes in the use of antiepileptic drugs (AEDs) in a large hospital for people with a learning disability over a 2 year period, the use of investigations, and the presence of medication side-effects. The surveys were carried out in 1993 and 1995/6. In 1993, 27% of patients were being treated for epilepsy and in 1995/6, 30.1%. Ninety percent and 82.4% of patients, respectively, were receiving one or two AEDs. In the second survey there were fewer prescriptions for phenobarbitone (5.8% vs. 12.5%) and an increase in the use of lamotrigine (21.6% vs. 5%), gabapentin (5.8% vs. 0) and vigabatrin (3.9% vs. 2.5% in 1993). Side-effects were recorded in 6 (11.8%) patients. Seven (21.2%) patients receiving carbamazepine were found to have hyponatraemia. Of the 54 electroencephalograms (EEGs) requested, 41 (76%) were reported as abnormal. Six CT brain scans had been conducted, of which five were abnormal. People receiving antipsychotic drugs had fewer seizures than average. (+info)
Long-term treatment with vigabatrin - 10 years of clinical experience.
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This report describes the long-term follow-up of 56 patients with refractory partial epilepsy who, within 3 months of vigabatrin add-on therapy (3 g/day), showed a reduction in monthly seizure frequency of more than 50%. The short-term (6 months) and long-term (5 years) effects of vigabatrin on seizure frequency in this patient cohort have been published separately. The reduction in seizure frequency appeared to be long-lasting in the patients followed-up (n = 36) and, importantly, a significant number of the patients (n = 7) became seizure-free, especially during long-term treatment. Thus, the efficacy of vigabatrin appears to be progressive, at least in patients who show an early response to treatment. These results are consistent with experimental findings that suggest that vigabatrin may have anti-epileptogenic and neuroprotective effects. (+info)
A case of fever following antiepileptic treatment.
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A 23-year-old female patient treated with 900 mg oxcarbazepine for complex partial seizures is presented. Good seizure control and slight fever were noted a few weeks after drug administration. Reduction of oxcarbazepine and replacement with valproate resulted in a transient normothermia. Because of fever reappearance, vigabatrin was added and valproate was gradually reduced. Seizures reappeared, but the body temperature fell below 37 degrees C. Substitution of valproate for lamotrigine resulted in seizure control but abnormal body temperature (37- 37.6 degrees C) was noted again. Repeated hospital admission for clinical and laboratory investigation before any change of treatment revealed no other abnormal findings. The patient's abnormal temperature possibly reflects a derangement of high-level temperature control. (+info)
The irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor gamma-vinyl-GABA blocks cocaine self-administration in rats.
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gamma-Vinyl gamma-aminobutyric acid (GABA) (GVG) is an irreversible inhibitor of GABA transaminase, the primary enzyme involved in GABA metabolism. Acute administration of GVG increases brain GABA levels and blocks cocaine-induced locomotor activity, cocaine-induced lowering of brain stimulation reward thresholds, and cocaine-induced conditioned place preference. To further evaluate the effects of GVG on cocaine-induced reward, we examined its effects on cocaine self-administration in male Wistar rats on fixed ratio 5 and progressive ratio schedules of reinforcement. Additionally, the effects of GVG on operant responding for a food reward were examined on the same two schedules to determine whether the effects of GVG were specific to cocaine reward or generalized to other types of reward. GVG dose dependently decreased responding for cocaine on both schedules of reinforcement, suggesting that GVG attenuated the reward value of the cocaine. Responding for food was also decreased by GVG, suggesting that the effects of increased GABA levels induced by GVG may have a general effect on central reward systems. Data from this and other studies indicate that GVG does not induce motor impairment, decrease spontaneous locomotor activity, or induce catalepsy. Taken together, these data suggest that increases in GABAergic activity induced by GVG have an attenuating effect on centrally mediated reward systems and that the GABA system may be a useful target in the development of new therapeutic strategies for cocaine addiction. (+info)
Effects of blocking GABA degradation on corticotropin-releasing hormone gene expression in selected brain regions.
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PURPOSE: The gamma-aminobutyric acid (GABA) degradation blocker gamma-vinyl-GABA (VGB) is used clinically to treat seizures in both adult and immature individuals. The mechanism by which VGB controls developmental seizures is not fully understood. Specifically, whether the anticonvulsant properties of VGB arise only from its elevation of brain GABA levels and the resulting activation of GABA receptors, or also from associated mechanisms, remains unresolved. Corticotropin-releasing hormone (CRH), a neuropeptide present in many brain regions involved in developmental seizures, is a known convulsant in the immature brain and has been implicated in some developmental seizures. In certain brain regions, it has been suggested that CRH synthesis and release may be regulated by GABA. Therefore we tested the hypothesis that VGB decreases CRH gene expression in the immature rat brain, consistent with the notion that VGB may decrease seizures also by reducing the levels of the convulsant molecule, CRH. METHODS: VGB was administered to immature, 9-day-old rats in clinically relevant doses, whereas littermate controls received vehicle. RESULTS: In situ hybridization histochemistry demonstrated a downregulation of CRH mRNA levels in the hypothalamic paraventricular nucleus but not in other limbic regions of VGB-treated pups compared with controls. In addition, VGB-treated pups had increased CRH peptide levels in the anterior hypothalamus, as shown by radioimmunoassay. CONCLUSIONS: These findings are consistent with a reduction of both CRH gene expression and secretion in the hypothalamus, but do not support an indirect anticonvulsant mechanism of VGB via downregulation of CRH levels in limbic structures. However, the data support a region-specific regulation of CRH gene expression by GABA. (+info)
Inhibition of uptake, steady-state currents, and transient charge movements generated by the neuronal GABA transporter by various anticonvulsant drugs.
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1. We have expressed the GABA transporter (GAT1) of mouse brain in Xenopus oocytes and have investigated the effects of four antiepileptic drugs, tiagabine (TGB), vigabatrin (VGB), gabapentin (GBP) and valproate (VAL), on GAT1 transporter function by measurements of 3H-labelled GABA uptake and GAT1-mediated currents. 2. Not only TGB, a well-known inhibitor of GAT1-mediated transport, but also the other drugs efficiently inhibit the uptake of [3H]-GABA by GAT1. Inhibition at 50% is obtained for VGB, TGB, GBP, and VAL at concentrations of about 1 nM, 1 microM, 50 microM and 100 microM, respectively. 3. However, GAT1-mediated steady-state and transient currents are nearly unaffected by VGB, GBP, and VAL at even five times higher concentrations. Only TGB blocks the uptake and steady-state and transient currents at micromolar concentrations. 4. VGB exhibits a complex interaction with GAT1; at concentrations about 1 nM, the inhibition of uptake is released, but at millimolar concentrations the uptake is inhibited again, and also the GAT1-mediated current is finally inhibited at these concentrations with a KI value of 0.5 mM. The concentration dependency of inhibition of uptake can be explained by two interaction sites with different affinities, a blocking site and a transport site. 5. The differences in effects of VAL, GBP, and VGB on uptake and currents can be attributed to the fact that GAT1 has the capability to operate in an electrogenic mode without uptake of GABA. We suggest that inhibition occurs only when GAT1 operates in the GABA-uptake mode. 6. The inhibition of GABA uptake by these four drugs will result in an elevation of the GABA concentration in the synaptic cleft, which will enhance synaptic inhibition and thereby contribute to their antiepileptic effects. (+info)
Visual field defects associated with vigabatrin therapy.
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OBJECTIVE: To estimate the prevalence of visual field defects in patients taking the anticonvulsant drug vigabatrin and to characterise the features of visual dysfunction found. METHODS: Thirty three unselected patients attending neurology and epilepsy clinics were identified as taking vigabatrin and asked to attend for neuro-ophthalmic evaluation. A control group of 16 patients with epilepsy unexposed to vigabatrin was also evaluated. Visual fields were examined by static perimetry using a Humphrey field analyser. Patients underwent detailed ophthalmic examination, various blood tests, and brain MRI where necessary. Visual evoked responses (VERs), electro-oculograms (EOGs), and electroretinograms (ERGs) were recorded. RESULTS: Of 31 assessable patients treated with vigabatrin, 16 (52%) had definitely abnormal visual fields, nine (29%) had fields that were inconclusive, four (13%) had normal fields, and two (6%) proved unable to cooperate with testing. In four patients some plausible cause was found for the field abnormality leaving 12 patients (39%) in whom a definite bilateral field defect was found, possibly caused by vigabatrin treatment. Of 16 control patients none had definitely abnormal fields, 12 (75%) had normal fields, and four (25%) had fields that were inconclusive. The field defects associated with vigabatrin treatment showed a characteristic pattern of concentric peripheral field loss with temporal and macular sparing. The VERs and ERGs were normal. The EOG Arden Index was reduced in patients taking vigabatrin, although this returned towards normal when vigabatrin was stopped, even in the presence of persistent field defects. Multifocal ERGs recorded in two patients were abnormal, showing marked reduction in amplitude of the peripheral focal ERG. CONCLUSIONS: Treatment with vigabatrin was associated with a high prevalence of peripheral visual field defects. This seemed to be the result of a toxic effect of vigabatrin on the retina and seemed to persist if the drug was withdrawn. (+info)