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Biomedical subjects

J Overweg

Publications and source records attributed to J Overweg.

At least 37 records · Page 2Linked to original sources

Clinical and EEG prediction of seizure recurrence following antiepileptic drug withdrawal.

A prospective study is reported of antiepileptic drug withdrawal in 62 neurologically intact adult patients who had become seizure-free at least 3 years previously. No single clinical or laboratory finding was reliably predictive of outcome and in particular the presence of epileptiform EEG activity prior to AED withdrawal or appearance of such activity during withdrawal was not associated with relapse. A multivariate model was however developed which suggested that patients capable of remaining seizure-free without medication could be reliably identified at a much reduced cost of relapses in the remainder.

Adolescent↗

Electroencephalographic findings in antiepileptic drug trials: a review and report of 6 studies.

A recent survey has shown that the EEG is of doubtful value as an outcome variable in clinical antiepileptic drug (AED) trials. Analysis of findings in 6 trials shows that in only two no consistent effect was seen; that in two power spectral analysis provided additional information to confirm changes in background activity; that in one a close relationship could be established between reduction in frequency of epileptiform discharges and administration of the trial drug (lamotrigine), and that in one, even though no correlation was apparent during use of the AED, there was an increase in frequency of both discharges and seizures on withdrawal (CGP 11952). In general the EEG would appear to be unsuitable as an outcome variable for assessing drug efficacy in AED trials. On the other hand it may give insight into the mode of drug action. Conceivably more efficient use could be made of the EEG if the methodology--including patient selection, consideration of circadian rhythms and of combination AED therapy, and standardized long-term recording--were to be improved and automation and quantification techniques used.

Adolescent↗

Add-on therapy in epilepsy with calcium entry blockers.

In view of the known role of Ca2+ in the paroxysmal depolarization shifts of epileptic neurones, the possibility arises that certain Ca2+ entry blockers possess antiepileptic activity. The only drug of the class which readily passes the blood-brain barrier is flunarizine. This is effective in experimental models of epilepsy and produced significant seizure reduction in two therapeutic trials in therapy-resistant patients. It has few and mild side effects at therapeutic blood levels.

Adolescent↗

Temporal characteristics of seizures and epileptiform discharges.

The time relations of epileptic events have been studied in 3 sets of data: (I) counts of individual epileptiform discharges in twelve 48 h EEG recordings, (IIa) seizure calendars of 30 therapy-resistant outpatients participating in a drug trial, (IIb) seizure calendars of 10 mentally subnormal epileptic patients resident in a long-stay unit. The EEG data I were characterized most often by a Poisson distribution of intervals between discharges and the occurrence of marked periodicities, particularly at night. The periods of rhythmic nocturnal events ranged from 13 to 142 min and did not appear to correspond to the REM/non-REM cycle. In the seizure data IIa and b a Poisson distribution of intervals between events was found in half the patients. Periodicities occurred only in group IIa and did not correspond to weekly or monthly cycles. A stochastic process is considered to be the model which best fits these data.

Adolescent↗

Epileptic nystagmus.

"Epileptic nystagmus" unaccompanied by other ictal phenomena is rare. We report four new cases confirmed by ictal EEG and video or cine recording in which nystagmus was a prominent and sometimes the only clinical manifestation of the seizures. The ictal EEG showed a parietal focus in three instances and generalized spike-wave activity in one.

Adolescent↗

Double-blind placebo-controlled trial of flunarizine as add-on therapy in epilepsy.

In a therapy-resistant epileptic population with partial complex seizures with or without secondary generalization, addition of flunarizine to existing therapy was accompanied by a significant reduction in complex partial and tonic-clonic seizures. This result did not appear to be due to serial effects or changes in the plasma levels of the co-medication. Side effects were rare. The serum flunarizine levels (13.8 ng/ml; range, 3-32.5 ng/ml) were lower than previously reported on a daily dose of 10 mg. This may reflect increased metabolism due to induction of liver enzymes by the co-medication. Given this finding, together with the low incidence of side effects, a further study is required to determine whether higher blood levels would give an improved degree and incidence of seizure reduction.

Adolescent↗

Telemetric EEG and video monitoring in epilepsy.

We report a clinical evaluation of EEG and video monitoring. In 181 consecutive records, the most common clinical indications were differentiation of epileptic and nonepileptic events (99), seizure recordings for locating a possible focus (23), seizure frequency determination (32), and investigation of possible trigger factors (19). Overall, useful information was obtained in 72% and the clinical question was answered in 67% of records. Prolonged EEG and video monitoring is therefore an important diagnostic aid in patients with proven or suspected epilepsy.

Electroencephalography↗

Seizure prognosis in long-stay mentally subnormal epileptic patients: interrater EEG and clinical studies.

Two groups of long-stay mentally subnormal epileptic patients, those with a chronically high seizure frequency and those who had become seizure-free, were studied for clinical and EEG factors relating to the prognosis of seizures. The mean period of observation was 20 and 22 years, respectively. All patients had a detailed clinical examination including psychometric testing, and for each, two EEG records were selected for blind semi-quantitative interrater analysis: an admission EEG and an EEG obtained within 6 months of the start of the study. Early onset of seizures, a high initial seizure frequency, multiple seizure types, upper motor neuron signs, and severe mental retardation characterized the seizure group. Significant admission EEG findings in this group included an absence of posterior dominant rhythmic activity, generalized delta activity, and frequent generalized paroxysmal discharges. Results of a linear discriminant analysis confirm that the admission EEG and clinical findings provide a basis for predicting outcome with a reliability on the order of 80%.

Adult↗

Double-blind crossover trial of lamotrigine (Lamictal) as add-on therapy in intractable epilepsy.

A double-blind, placebo-controlled trial is reported of lamotrigine as add-on treatment in therapy-resistant epilepsy. A within-patients serial design was used, with two 3-month treatment periods and an intervening 6-week washout/crossover period. An unblinded investigator adjusted lamotrigine dosage to achieve a plasma concentration within a previously predicted therapeutic range. All patients had therapy-resistant partial seizures, some in combination with other seizure types and were without serious neurological or intellectual deficit. Of 34 patients recruited only one was withdrawn because of an adverse experience (maculo-papular rash) probably related to the experimental drug and 30 completed the trial. The other 3 withdrawals were due to default during baseline, dispensing error and cholecystectomy. There was a modest statistically significant reduction in total and partial seizures on lamotrigine compared to placebo treatment. There was no difference in adverse experiences or abnormal biochemical or haematological findings between the lamotrigine and placebo periods. The plasma concentrations of concomitantly administered antiepileptic drugs were not affected by lamotrigine treatment. It is concluded that lamotrigine shows promise as an antiepileptic drug with low toxicity.

Adolescent↗

A double-blind, placebo-controlled evaluation of the efficacy and safety of loreclezole as add-on therapy in patients with uncontrolled partial seizures.

Sixty-two patients with uncontrolled partial seizures participated in a 12-week, double-blind, placebo-controlled add-on-trial. Thirty-two patients received loreclezole and 30 a placebo as add-on therapy. Loreclezole was targeted at a plasma level of 1-2 mg/l. In spite of an antiepileptic therapy, usually with 2 or 3 antiepileptic drugs, these patients had at least 4 seizures a month during the baseline period. At the end of the treatment phase with loreclezole and placebo, individual responses varied widely. The median change in the daily seizure frequency was not significantly different in the 2 groups. However, when individual responses are considered, 6 patients in the verum group (19%) experienced a seizure reduction of 50% or more, compared with no patients in the placebo group. During the trial, only mild adverse events were reported in both the loreclezole and the placebo group, nor were any clinically relevant abnormalities seen in the haematological and biochemical analysis. The efficacy and safety of higher loreclezole plasma concentrations were studied in a long-term follow-up trial, the results of which are presented in the following article.

Adult↗

Long-term evaluation of the efficacy and safety of loreclezole as add-on therapy in patients with uncontrolled partial seizures: a 1-year open follow-up.

The effect and safety of loreclezole were evaluated during a long-term follow-up trial targeting higher plasma concentrations than those of the preceding controlled trial. The result is better than in the double-blind trial, in which loreclezole doses were administered to reach plasma concentrations of 1-2 mg/l and 6/32 patients (19%) of the verum group experienced a seizure reduction of 50% or more. None of the 30 placebo-treated patients experienced a similar decrease. At the end of the double-blind trial, 56 patients (29 from the original loreclezole and 27 from the original placebo group) elected to participate in the open follow-up trial. After 12 months' add-on treatment with loreclezole, mean plasma concentrations of 5.53 and 5.97 mg/l for the original placebo and loreclezole group were measured and the median decreases in seizure frequency were -44% and -40. At these concentrations, 22/56 patients (39%) showed a seizure reduction of at least 50%.

Adult↗