Comparison of twice- and three times daily tiagabine for the adjunctive treatment of partial seizures in refractory patients with epilepsy: an open label, randomised, parallel-group study.

UNLABELLED: A multicentre, open label, randomised, parallel group study compared the efficacy, tolerability and safety of two dosing regimens, t.i.d. and b.i.d., of tiagabine as an adjunctive therapy for the treatment of refractory patients with partial seizures. A total of 347 patients were randomised and treated (175 t.i.d. and 172 b.i.d.). Each group was administered the same daily dose of tiagabine incremented stepwise during a 12-week fixed-schedule titration period to a target dose of 40 mg/day. The patients were followed for a further 12-week flexible continuation phase. A significantly greater number of patients in the t.i.d. group completed the fixed schedule titration period (81.4% versus 73.1%; 95% CI of odds ratio = 0.331, 0.970; p = 0.038). The proportion of responders (patients showing at least a 50% decrease in all-seizure frequency from baseline) was similar for both groups (42.3% for b.i.d. and 47.1% for t.i.d.) during the last 8 weeks of the flexible phase and seven (4.0%) patients in the b.i.d. group were seizure-free compared to 14 (8.1%) patients in the t.i.d. group. Adverse events were of similar incidence in both groups, and mainly occurred during the fixed schedule titration period; they were mainly mild and CNS-related with somnolence being the most frequently reported. CONCLUSION: Tiagabine was effective as add-on treatment of refractory partial seizures. Although both regimens appear to offer a similar efficacy and safety profile, significantly more patients completed the study in the t.i.d. group compared to b.i.d., probably as a consequence of a lesser tolerability when high doses are given undivided. These results confirm that a slow titration and appropriate adjustment of dosing are essential conditions to ensure optimal use of tiagabine.

Symptomatology and prognosis in adolescent epilepsies (a study of 1033 cases).

A follow-up study was carried out on a group of 1033 epilepsy patients seen consecutively between 1955 and 1979. They were all aged between 11 and 19 years at the time of first seizure. Nine hundred and twelve patients were followed up for periods of 5-30 years. The aims of the study were (1) to test the practical applicability of the International Classification of Epilepsy and Epileptic Syndromes, and (2) to examine its prognostic value. The International Classification fitted this group of epileptic patients rather well. The prognosis of adolescent epilepsy varies with the particular syndrome, the probability of being in remission after 10 years ranging from 30 to 67%.

[Discontinuation of treatment in epileptic seizures in adolescence]. / Arrêt du traitement dans les crises épileptiques de l'adolescence.

A retrospective survey on the frequency of seizure-recurrence after drug withdrawal in all forms of adolescent seizures has been undertaken to detect possible prognostic criteria. Patients were selected according to 3 criteria: first seizure between 11 and 19 years of age; out-patients seen by one of us between 1955 and 1979 within the year of onset of epilepsy; all patients followed for at least 5 years after the first seizure. Two-hundred and seventy two patients entered the study. One-hundred and four patients (49 per cent) relapsed, most of them (83 per cent) within the first year after drug withdrawal. In univariate analysis, partial seizures, a normal initial EEG, an isolated seizure, a short length of illness, a long seizure-free period, one seizure only during the first year were significantly linked to a low relapse rate. The probability of being seizure-free after drug withdrawal was about 73 per cent in partial epilepsy, 20 per cent in idiopathic generalized epilepsy, and 36 per cent in undetermined generalized epilepsy. In patients having had a single seizure a dramatic difference was noted according to the seizure type: 12 per cent of relapses after a partial seizure, 69 per cent after a generalized seizure. Neither the age of onset of epilepsy nor the presence of an etiological factor were significant variables in predicting the outcome. When all factors were analysed simultaneously with Cox's hazard function, the type of seizure and the initial EEG appeared to be the only two independent factors significant for a risk of relapse.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

Prognosis of partial epileptic seizures in the adolescent.

Actuarial analysis was applied to the notes of 235 patients having a partial seizure for the first time between the ages of 12 and 18 years to establish the best predictive indicators of outcome. Among the factors considered to affect significantly the outcome were the seizure type (elementary or complex symptomatology), the initial EEG, the seizure frequency, the etiological factors, and an association with generalized seizures. Sex, age of onset, and topography of EEG paroxysmal abnormalities had no significance. An algorithm allows the prediction of the prognosis of these seizures at two different times immediately after a first seizure in some cases and after a 1-year survey in others.

Long-term prognosis in two forms of childhood epilepsy: typical absence seizures and epilepsy with rolandic (centrotemporal) EEG foci.

Findings in children seen between 1955 and 1965 during the year of onset of typical absence seizures (90 patients) or rolandic epilepsy (79 patients) were analyzed by actuarial methods. One hundred and eighteen patients were followed for more than 15 years. Rolandic epilepsy is a true benign epilepsy ending with puberty. Although school and family problems are common during the acute stage of the disease, the social adaptability of such patients is excellent. We considered only typical absences occurring as a first epileptic sign in normal children. Myoclonic or atonic absences have a poor prognosis. Many patients with simple and automatic absences experience remission 15 years after withdrawal of medication. The overall cessation rate in those experiencing absences was only 57.5%, however, and 36% of patients developed tonic-clonic seizures. Social adaptability was often inadequate. Simple and automatic absences (constituting a homogeneous group) are not truly a benign form of epilepsy, even though prognosis for those afflicted is better than that for those with other forms of primary generalized epilepsy.

Effects of estrogens on the responses of caudate neurons to microiontophoretically applied dopamine.

The electrical activity of caudate neurons and their response to iontophoretically applied dopamine (DA) were tested at different time intervals before and after i.m. injection of estradiol benzoate in rats ovariectomized one week previously. One hundred and three neurons were recorded before estradiol injection and, of these, 25% were spontaneously active and 75% were driven by glutamate. The firing activity of the majority (86%) of the neurons was inhibited on application of DA. At 2--6 after the estradiol injections, the proportion of spontaneously active neurons was elevated to 87% and their firing rate was dramatically increased. Concomitantly, the proportion of cells affected by DA decreased to 39%; moreover, the majority of cells responsive to DA was now excited following it. We conclude that estrogens are able to influence the global activity of caudate neurons and to reverse their sensitivity to DA. This action may be partly mediated by the pituitary since it was not observed in ovariectomized rats which were also hypophysectomized.