P. Loiseau

Multicenter Double‐Blind, Randomized, Placebo‐Controlled Trial of Levetiracetam as Add‐On Therapy in Patients with Refractory Partial Seizures

Summary: Purpose: To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add‐on therapy in patients with refractory partial seizures.

The seizures of benign childhood epilepsy with rolandic paroxysmal discharges

We analyzed the “signs”, i.e. the components, of 275 seizures of 190 children with benign epilepsy associated with Rolandic spikes; 36 signs were listed. Primarily generalized convulsions were rare, occurring in 18% of our series. The other seizures were partial and remained so or became secondarily generalized; the usual signs were motor though some were sensory.

Prognosis of Benign Childhood Epilepsy with Centrotemporal Spikes: A Foliow‐Up Study of 168 Patients

Summary: A spontaneous and complete recovery of benign childhood epilepsy with centrotemporal or rolandic spikes (BECT) is taken for granted. However, some authors have reported the occurrence of generalized tonic‐clonic seizures in a few adult patients and in some children who have seizures after a long period without problems. The aims of this study were (a).to search for early predictors of outcome and (b) to ascertain the long‐term prognosis of BECT in a large group of patients. An attempt to relocate 268 patients born between 1941 and 1967 and consecutively seen as outpatients was undertaken. The outcome after age 20 is known for only 168. Being adults and cured, the others are no longer in touch with their clinics or have moved. Only one indicator of short‐term prognosis was found: The earlier the onset of BECT, the longer the period with seizures. Of the 168 patients, 165 are seizure‐free with follow‐up ranging from 7 to 30 years. Three patients experienced generalized tonic‐clonic seizures at age 18, 22–24, and 35. Two apparently had an isolated seizure. The occurrence of such seizures after recovery from BECT is a rare event (∼2% of cases) and a relapse with partial seizures is quite uncommon. These patients do not differ from patients remaining seizure‐free.

Concentration of Dipropylacetate in Plasma

Dipropylacetate is absorbed rapidly and attains a maximum concentrati n in serum 1 to 3 hr after ingestion. Since its half‐life is on the order of 8 to 10 hr, it must be prescribed three times a day, every 8 hr. It reaches a stable concentration in blood within 48 hr after treatment is begun (by contrast with diphenyl‐hydantoin and phenobarbital) and might therefore be useful when seizures must be controlled quickly. The serum concentration can be altered by some other anticonvulsant drugs, butThèse interactions should be studied in more detail. The serum concentration varies considerably in the course of a day and from one day to the next in the same subject, which makes it difficult to adjust the blood level. Depamide is rapidly transformed in vivo to dipropylacetate.

Sodium Valproate, Platelet Dysfunction, and Bleeding

Summary: The antiepileptic drug sodium valproate (VPA) can provoke a thrombocytopenia or platelet dysfunction, with or without hemorrhages. These unwanted side effects are probably infrequent or, at least, have little clinical importance except in patients undergoing surgery. Thromboelastography appears to be a reliable screening test. As hematological abnormalities are often dose related, VPA dosages greater than 40 mg/kg/day are not advised.

Gelastic Epilepsy A Review and Report of Five Cases

Gelastic epilepsy does not exist–or, rather, the concept of gelastic epilepsy has no basis, another example of the futility of classifications based on a single symptom. What does exist is ictal laughter. How often it occurs is not known. Pre‐ictal or post‐ictal laughter seems to be rather common in the West syndrome and in the tonic seizures of encephalopathy, as shown by the relatively substantial series of cases collected by Druckman and Chao (1957). Aside from such cases, epileptic laughter would seem to be rare.

Carbamazepine/Valproic Acid Interaction in Man and Rhesus Monkey

Summary: Sodium valproate (VPA) was administered for 1 week (1 g b.i.d.) to seven epileptic patients receiving chronic carbamazepine (CBZ) therapy. Steady‐state CBZ levels determined before and after VPA therapy were reduced by 3–59% in six patients and were unchanged in one patient. The plasma concentration ratio of carbam‐azepine‐10, 11‐epoxide (CBZE) to CBZ increased in all patients by 11–500%. The plasma binding of CBZ was determined in six healthy volunteers given a single 400 mg CBZ dose with and without the coadministration of 1 g VPA in a cross‐over design. The mean CBZ free‐fraction was increased in three of the subjects (p = 0.008‐0.031), decreased in one subject (p < 0.002), and remained unchanged in two subjects when VPA was administered. Four male rhesus monkeys were infused intravenously with CBZ (15 mg h‐1) for 5 days and then three consecutive 24‐h infusions were given: I, CBZ alone; II, CBZ with 75 mg h‐1 VPA; III, CBZ with 150 mg h‐1 VPA. The mean free‐fraction of CBZ and CBZE increased during infusions II and III from 31.5 ± 2.7% to 33.2 ± 6.6% (p < 0.05) and 37.7 ± 1.3% (p < 0.01) for CBZ and from 46.9 ± 9.2% to 53.6 ± 5.7% (p ± 0.05) and 60.1 ± 4.0% (p < 0.01) for CBZE. The clearance of free CBZ declined from 7.96 ± 1.75 to 4.84 ± 1.26 (p < 0.01) and 4.12 ± 1.75 (p < 0.01) 1 kg‐1 hr‐1 during infusions II and III, respectively. The mean free CBZE/CBZ ratio increased from 0.12 ± 0.03 to 0.24 ± 0.03 and 0.36 ± 0.04 during infusions II and III, respectively (p < 0.001). These findings indicate a decrease in the elimination clearance of CBZE possibly coupled with a decrease in its formation clearance. VPA also appears to decrease the binding of CBZ in man and CBZ and CBZE in the monkey.

Meal‐Dependent Absorption of Enteric‐Coated Sodium Valproate

Summary: The effect of meals on valproic acid (VPA) absorption from an enteric coated (EC) formulation was investigated. In study I, six adult normal volunteers received a single 500 mg dose of sodium valproate in randomized treatments: fasting (A), with a meal (B) or 3 hours after a meal (C). There were significant differences between treatments in the latency period (Lp) defined as the time during which measured concentrations of VPA were less than 1 μg/ml. Lp values for treatments A, B and C were: 1.67 ± 1.25 hr, 6.75± 3.98 hr and 7.63 ± 3.15 hr respectively. In study II, six subjects (five from study I) received in a randomized fashion a 400 mg intravenous bolus dose of VPA and a 500 mg EC VPA tablet, 3 hours after a meal. The mean Lp value was 8.1 ± 1.6 hr and the mean bioavailability was 100%. Clearance, volume of distribution and half‐life values obtained after intravenous dosing were comparable to literature values. These results indicate that food intake delays but does not decrease the extent of absorption of VPA from an enteric coated formulation.

Encéphalopathies myocloniques iatrogènes aux sels de bismuth

Abstract Since the beginning of 1974, we have studied 17 cases of iatrogenic encephalopathy due to the ingestion of bismuth taken for the treatment of chronic digestive disorders. More than 100 similar cases have been reported in France within the same period. The clinical picture is remarkably consistent: there is a relatively long prodromal phase with difficulties in gait and writing, followed by a phase characterised by four signs, namely a severe confusional syndrome, myoclonus, astasia-abasia and disorders of language. In our cases, after withdrawal of bismuth, recovery invariably began within 2 to 3 weeks but fatal cases have been described. All our patients had taken, for periods of between 3 weeks and 20 years, bismuth subnitrate. The levels of bismuth in the blood and urine in these patients were between 10 and 100 times as great as those in patients who had taken the same treatment without ill effect. The exact mechanism by which bismuth causes this complication, described only recently, is totally unknown.

Review of Controlled Trials of Gabitril (Tiagabine): A Clinician's Viewpoint

Summary: A recent problem for doctors has been the choice of which new antiepileptic drug (AED) to select for treatment of pharmacoresistant epilepsy. This article summarizes the clinical experience to date regarding the efficacy and safety of tiagabine (TGB; Gabitril) as adjunctive therapy in patients with partial‐onset seizures. In its early Phase II development, TGB was evaluated in two multicenter pilot studies. Each had an open‐label enrichment phase followed by a treatment phase with randomized, double‐blind, two‐period, cross‐over phases. Between 24 and 50% of patients experienced reductions in seizure rates of ≥50%, depending on the type of partial seizure. In Phase III, three double‐blind, parallel group, placebo‐controlled adjunctive studies determined the efficacy of TGB in patients with refractory partial seizures. The first was a dose‐response study employing doses of TGB‐HCl of 16, 32 or 56 mg/day. Significant reductions in seizure rates were found with 32 and 56 mg/day. The second and third studies evaluated the efficacy of dosing TGB twice, three times, and four times daily, all of which showed similar efficacy. TGB efficacy in partial seizures was supported in several open trials, and no tolerance to efficacy was noted in long‐term continuation studies. Tolerability was documented in all trials. Most adverse events were mild or moderate and transient, occurring during dose titration. They were clearly dose‐related. No relevant changes in hematologic and biochemical tests, vital signs, or body weight were attributable to TGB. TGB appears to be an effective new drug for partial seizures with an acceptable safety profile.