W. van Emde Boas

Acute Effects of Lamotrigine (BW430C) in Persons With Epilepsy

Summary: Sixteen epileptic patients took single doses of lamotrigine, 120 mg or 240 mg. Six photosensitive patients showed reduction (with abolition in two) in photo‐sensitivity after lamotrigine administration. Five subjects with frequent interjetai spikes showed reduction in spike frequency over 24 h after lamotrigine administration. The half‐life (t1/2) of lamotrigine in subjects taking sodium val‐proate was prolonged, whereas the t1/2 in subjects taking carbamazepine and/or phenytoin was reduced. The area under the curve of co‐medication plasma levels was not affected by a single dose of lamotrigine. Five patients reported mild and generally transitory side effects; some of which represented exacerbation of preexisting complaints.

Combined use of subdural and intracerebral electrodes in preoperative evaluation of epilepsy.

For intracranial recording of partial seizures considered to originate from one of the temporal or frontal lobes, the team in the Utrecht Academic Hospital has used subdural, multicontact, flexible electrodes since 1972. These are introduced through bilateral, frontocentral trephine holes and are manipulated under fluoroscopy to cover most of the cerebral convexity. It became evident that in many patients, additional placements to record from intracerebral structures were indispensable. Therefore, using the same trephine holes, an additional 2 to 4 depth electrodes were stereotactically implanted in the mesial temporal and/or frontal structures, as appropriate. An extensive intra- and extracerebral spatial representation of the epileptogenic zone was thus obtained. We report here the methods for manufacturing and applying these electrodes and our clinical experience with 28 patients. The results obtained so far stress the value of combining subdural and depth electroencephalographic monitoring in the presurgical selection of patients suffering from medically refractory complex partial seizures. By miniaturizing the electrodes, extensive areas of the brain can be investigated without craniotomy or multiple burr holes.

Regional brain glucose metabolism in patients with complex partial seizures investigated by intracranial EEG

We performed interictal 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) studies in 57 patients with complex partial epilepsy (CPE), not controlled by medical treatment and considered for surgical resection of their epileptic focus. A precise localization of the epileptic focus was obtained in 37 of these patients with a combination of subdural and depth electrodes. We visually inspected the metabolic images; we also measured glucose consumption in a number of brain regions and compared the values with those obtained in 17 normal controls. Eighty-two percent of the 57 patients had an area of glucose hypometabolism on the 18FDG-PET images. Six patients had a frontal epileptic focus, 3 of them had a frontal lobe hypometabolism. Twenty-six patients had a unilateral temporal lobe focus and all of them displayed a temporal lobe hypometabolism. The asymmetry was more pronounced in the lateral temporal cortex (-20%) than in the mesial part of the temporal lobe (-9.6%). In each cortical brain region on the side of the epileptic focus (except the sensorimotor cortex), glucose consumption rate was lower than in the contralateral region or than in controls. No differences could be found between patients with a seizure onset restricted to the hippocampus and patients with a seizure onset involving the hippocampus and the adjacent neocortex. Divergent metabolic patterns were obtained in 5 patients with bilateral temporal seizure foci. Combined with other non invasive techniques (EEG, neuroradiology), PET contributes increasingly to the selection of patients with CPE who could benefit from surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

On‐Line Detection of Transient Neuropsychological Disturbances During Eeg Discharges in Children with Epilepsy

Short‐term memory tasks (visual‐spatial and verbal) were devised to identify the influence of transient EEG discharges, without clinically manifest disturbances, on neuropsychological performance. 53 children with subclinical focal and generalized EEG discharges were tested 72 times and 16‐channel telemetered EEG and video‐recordings were made. 36 per cent of test sessions showed a significant preponderance of errors when discharges were recorded. Children with right‐sided discharges had impaired performance in 50 per cent of their test sessions, with performance on the visual‐spatial task most affected: left‐sided discharges appeared to exert greater influence on the verbal task. These tests can easily be used to monitor six‐ to 15‐year‐old children.

Sharp transients in the sleep EEG of healthy adults: a possible pitfall in the diagnostic assessment of seizure disorders

The use of sleep EEG recordings is a routine procedure in the diagnostic work up of patients with suspected epilepsy. With respect to the diagnostic significance of paroxysmal EEG phenomena it is of importance to be informed about the incidence of such paroxysms in EEGs of healthy subjects. Several benign paroxysmal EEG phenomena during drowsiness or sleep have been identified (benign epileptiform transients of sleep (BETS), 14 and 6 positive spikes). Recent studies have shown that other, apparently aspecific, paroxysmal sharp transients may be recorded during drowsiness or sleep in healthy subjects. In order to obtain more data on such paroxysmal EEG phenomena during sleep, a qualitative and semi quantitative analysis was performed on full night sleep recordings from 60 carefully selected healthy volunteers. Only 4 recordings were completely without the studied phenomena, all others showed some suspicious paroxysmal transients and some rare yet true specific epileptiform discharges were recorded in 8 subjects (13%), predominantly during transient periods of light non-REM sleep in the first two sleep cycles. The presence of some sharp transients during drowsiness or light sleep thus should be considered as a non-specific and non-pathological finding. Moreover these findings indicate the limited diagnostic specificity of the presence of a few epileptiform discharges during sleep, especially in patients with an ambiguous clinical history of epilepsy.

Non-linear analysis of intracranial human EEG in temporal lobe epilepsy

OBJECTIVE Intracranial EEG recordings from patients suffering from medically intractable temporal lobe epilepsy were analyzed with the aim of characterizing the dynamics of EEG epochs recorded before and during a seizure and comparing the classification of the EEG epochs on the basis of visual inspection to the results of the numerical analysis. METHODS The stationarity of the selected EEGs was assessed qualitatively. The coarse-grained correlation dimension and coarse-grained correlation entropy were used for the non-linear characterization of the EEG epochs. RESULTS High-pass filtering was necessary in order to make the majority of the epochs appear stationarity beyond a time scale of about 2 s. It was found that the dimension of the ictal EEGs decreased with respect to the epochs containing ongoing (interictal) activity. The entropy of the ictal recordings however increased. A scaling of the entropy was applied and it was found that the scaled entropy of the ictal EEG decreased, consistent with the increased regularity of the ictal EEG. The coarse-grained quantities discriminated well between EEG epochs recorded prior to and during seizures at locations displaying ictal activity and classification improved by including the linear autocorrelation time in the analysis. CONCLUSIONS It is concluded that ictal and non-ictal EEG can be well distinguished on the basis of non-linear analysis. The results are in good agreement with the visual analysis.

Comparison of Combined Versus Subdural or Intracerebral Electrodes Alone in Presurgical Focus Localization

Summary: purpose: The yield of subdural versus intracerebra1 electrodes for ictal localization remains a point of controversy. We assessed the relative sensitivity of these two types of electrodes per case.

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.

Seven day administration of lamotrigine in epilepsy: placebocontrolled add-on trial

A double-blind placebo-controlled trial of 7 days administration of lamotrigine as add-on therapy was performed in 10 patients with frequent therapy-resistant, chiefly partial, seizures. Dosage was adjusted on the basis of estimated half-life. Six patients showed a 50% seizure reduction on lamotrigine and two an increase. Side effects (ataxia, dizziness and apathy) occurred in 3 patients, but only at blood levels above 3 micrograms/ml, and were rapidly relieved when the dose was reduced in two. EEG spike counts were significantly reduced on lamotrigine. There was no evidence of interactions with co-medication.

Mesial temporal versus neocortical temporal lobe seizures: Demonstration of different electroencephalographic spreading patterns by combined use of subdural and intracerebral electrodes

Abstract We investigated differences between spatiotemporal intracranial EEG characteristics of temporal lobe seizures with mesiolimbic versus neocortical onset, using both subdural and intracerebral electrodes. In 37 patients we analyzed 128 seizures, assessing time intervals from initial onset of a seizure in either mesial or neocortical temporal (NT) lobe structures to sequential ictal involvement of the contralateral mesiolimbic structures and the ipsi- and contralateral temporal and frontal neocortical areas. We noted significantly more rapid seizure spread from mesiolimbic temporal (MT) structures ipsilateral to contralateral in patients with NT versus MT seizure onset. Time values for total seizure duration and time of spread from ipsilateral limbic to contralateral limbic reliably discriminate between individual seizures of either type. Three different spreading patterns were noted in the MT group and two more were noted in the NT group. Theoretical considerations concerning routes of spread are presented. In neither the MT nor the NT group could a correlation be established between pattern of seizure spread and outcome of surgery.