"Semi-invasive" vs. invasive approaches for intracranial EEG and seizure monitoring in epilepsy.

When non-invasive studies fail to provide sufficient localising data to permit resective epilepsy surgery, intracranial seizure monitoring may have to be performed. Various techniques are available with specific advantages as well as disadvantages. "Semi-invasive" techniques, despite their name, remain essentially "invasive". The choice for a specific approach therefore should depend on the clinical problem in each individual patient rather than on theoretical preference.

Ring chromosome 20 epilepsy syndrome in children: electroclinical features.

Ring chromosome 20 mosaicism is associated with dysmorphic features, mental retardation, and intractable seizures, including recurrent episodes of nonconvulsive status epilepticus. The authors' findings in four children, all without dysmorphic features, indicate that mental deterioration and frequent subtle nocturnal frontal lobe seizures, associated with a characteristic EEG pattern, represent prominent additional clinical features not previously described in this syndrome. This emphasizes the importance of full-night video-EEG in children with frontal lobe seizures and cognitive deterioration.

Pilot study to determine the interaction of oxiracetam with antiepileptic drugs.

Oxiracetam, a nootropic drug, could be of potential use in the treatment of memory disturbances in patients with epilepsy who are using antiepileptic drugs. The half-life of oxiracetam appears to be influenced by the concomitant use of carbamazepine or valproic acid, necessitating more frequent administration of oxiracetam than is recommended for other conditions. No effect was observed on the serum concentrations of these antiepileptic drugs by oxiracetam. Long term concurrent use of oxiracetam and antiepileptic agents does not appear to be contraindicated.

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.

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.

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.

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)

Seven day administration of lamotrigine in epilepsy: placebo-controlled 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.

[Paroxysmal and bizarre motor agitation as manifestation of partial frontal lobe epileptic seizures]. / Paroxismale en bizarre motorische onrust als uiting van partiële frontale epileptische aanvallen.

Three patients, two men of 21 and 38 years and a woman of 20 years old, showed atypical seizures with motor agitation without tongue bite, incontinence or postictal confusion. After extensive video-EEG registration frontal lobe epilepsia was diagnosed. This is a relatively recently recognized disease entity.

[Dutch Collaborative Epilepsy Surgery Program: reduction of seizures, operative complications and tapering of medication in 338 patients, 1973-1998]. / Het Nederlandse epilepsiechirurgieprogramma: aanvalsreductie, operatieve complicaties en vermindering van medicatie bij 338 patiënten, 1973-1998.

OBJECTIVE: To determine the results of surgical treatment in patients with drug-resistant epilepsy, referred to the Dutch Epilepsy Surgery Program, who were treated in the University Medical Centre Utrecht, the Netherlands, in the period January 1973-December 1998. DESIGN: Retrospective descriptive. METHOD: A total of 338 patients were operated on; 269 underwent temporal lobe resection, 41 extratemporal resection, 12 a functional hemispherectomy and 10 callosotomy. Six patients were treated with vagus nerve stimulation. For seven of the patients no follow-up data was available. RESULTS: After a minimum follow-up of 1 year class I or class II results (in accordance with the University of California in Los Angeles classification (UCLA) where class I = seizure-free and class II < or = 3 seizures per year) were obtained in 91% of patients who underwent temporal lobe resections, 67% of patients who underwent extratemporal resections, 81% of patients who underwent functional hemispherectomy and 10% of patients who underwent anterior callosotomy. In five of these patients an improvement in their behaviour occurred. Of the 6 patients who underwent vagus nerve stimulation only I experienced a beneficial seizure reduction (UCLA class III). Transient physical complications occurred in 4% of the patients treated and permanent damage in 1%. Postoperative psychiatric complications occurred almost exclusively following temporal resections; in 11% of which 7% de novo. After 4 postoperative years this had decreased to 5%. In a group of 143 patients who were seizure-free for 2 or more years, post-surgery medication was tapered in 75 cases, stopped in 33 cases and remained unchanged in 35 cases. The relapse rate following a tapering or stopping of the medication was 30% and with unchanged medication 17%. Although the majority of patients were once again seizure-free upon restarting the medication, a significant number continued to experience seizures. CONCLUSION: For a number of carefully selected epilepsy patients with intractable seizures, surgery is a successful treatment with few serious complications.

Juhn A. Wada and the sodium amytal test in the first (and last?) 50 years.

Fifty years ago Juhn A. Wada developed the intracarotid amobarbital procedure (IAP), a test in which first one and then the other cerebral hemisphere is temporarily anaesthetised through direct intracarotid application of sodium amytal. The IAP was devised initially as a method to allow unilateral electroconvulsive shock therapy for psychosis. The method subsequently proved its value for the lateralisation of language and, following adaption of the test protocol, for the assessment of memory functions. Thus the IAP became the standard test in the presurgical evaluation for resective surgical treatment of medically intractable epilepsy. This paper will briefly review the history of the IAP, the controversies concerning its current applications and its expected eventual replacement by less invasive and more easily repeatable methods, notably functional magnetic resonance imaging.

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 EEG's 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.

Geniculate spikes during epileptic seizures induced in dogs by pentylenetetrazol and bicuculline.

Previous studies have indicated that in cats generalized seizures induced by pentylenetetrazol (PTZ) or bicuculline (BIC) may be preceded by high frequency multi-unit activity in brain-stem structures. This activity is not readily demonstrable using conventional EEG recording bandwidths and precedes the onset of spikes and spikes-wave activity in thalamo-cortical systems. Recording with chronic subdural and depth electrodes during PTZ and BIC-induced seizures in 18 dogs essentially replicated these results. However, a new and consistent finding was that the high frequency discharges accompanying seizure onset were most often seen, and most often appeared first, in the lateral geniculate body, neocortex and hippocampus being involved later. The findings are considered to suggest a significant role for subcortical structures in this particular model of generalized cortico-reticular epilepsy.

Preliminary assessment of the efficacy of Org 6370 in photosensitive epileptic patients: paradoxical enhancement of photosensitivity and provocation of myoclonic seizures.

Photosensitivity has proved to be a useful model to study the acute effects of experimental antiepileptic drugs (AEDs). The photosensitivity range is usually diminished or even abolished after administration of a known or experimental AED. An increase in photosensitivity, an unexpected reaction, was found in four photosensitive epileptic patients after oral ingestion of 500, 100, or 50 mg of Org 6370. Moreover, the three patients receiving doses of 100 and 500 mg reported nausea, dizziness, restlessness, and an increase in spontaneous epileptic seizures (myoclonus and in one patient a generalized tonic-clonic convulsion). The side effects coincided with peak Org 6370 serum levels. Our findings indicate that in the photosensitivity model experimental drugs with proven anticonvulsant properties in animals may increase rather than decrease the degree of patient photosensitivity. Photosensitive patients may represent a special subgroup of epileptic patients and therefore need to be classified as such.

Dissociation in temporal lobe epilepsy and pseudo-epileptic seizure patients.

Patients with epileptic seizures (ES) and especially those with temporal lobe epilepsy (TLE) share many symptoms with patients with pseudo-epileptic seizures (PES), and the differentiation between them is often difficult There is growing evidence that a subgroup of PES patients suffer from a dissociative disorder. It is recognized that dissociative symptoms pertain to both psychological and somatoform components of experience. Questionnaires assessing dissociation might provide positive criteria for the diagnosis of PES. In this study, the Dissociation Questionnaire (DIS-Q) and the Somatoform Dissociation Questionnaire (SDQ-20) were administered to patients with ES (TLE, non-TLE) and PES. To control for the influence of general psychoneurotic complaints, the SCL-90 was administered. Apart from this, answers on a trauma questionnaire were related to the diagnosis. Results showed that PES patients scored significantly higher on the SDQ-20, also after correction with the SCL-90, and no difference was found on the DIS-Q. Also, PES patients significantly more often reported sexual traumatic experiences. A logistic regression revealed that results on the SDQ-20 have no independent value in addition to the contribution of gender, age, age at seizure onset, and the presence of sexual abuse in the prediction of the diagnosis. In conclusion, somatoform and not psychological dissociative symptoms are characteristic for PES patients in comparison to ES patients. Other measures are needed within the framework of the differential diagnosis between PES and ES.

Classification of epileptic seizures: a comparison of two systems.

PURPOSE: Extensive experience with video-EEG seizure monitoring, notably in the setting of epilepsy surgery programs, has exposed the limited value of the current International Classification of Epileptic Seizures (ICES) for providing relevant localizing information. To overcome this limitation, a Semiologic Seizure Classification (SSC) has recently been proposed. This study aimed to assess and to compare the usefulness and reliability of both systems in the setting of a tertiary epilepsy center. METHODS: Three epileptologists independently reviewed video-taped seizures, randomly selected from the archive of the Epilepsy Monitoring Unit. They were blinded to the EEG findings and final diagnosis and classified all seizures according to both classifications. RESULTS: One hundred thirty-eight seizures from 60 patients (age range, 2-59 years) were reviewed (maximum, three seizures per patient). Fifty-five seizures from 20 patients were recorded in the setting of presurgical evaluations, and the remainder as part of regular diagnostic evaluations. The average interobserver agreement was higher for SSC (63.3%, kappa = 0. 56) than for ICES (38.6%, kappa = 0.41). Some categories of SSC, such as hypermotor or automotor, had the best interobserver agreement, and were strongly correlated with the anatomic localization of the seizures (frontal and temporal lobe, respectively). All reviewers agreed that SSC provided a better description of the seizures than did ICES, in 60% of the patients. CONCLUSIONS: SSC provides a more comprehensive picture of epileptic seizures than does ICES, notably in patients with localized epilepsy syndromes, and appears to be very useful and reliable, particularly in the setting of specialized epilepsy centers.

Light diffusion in photosensitive epilepsy.

Photosensitivity is usually tested by intermittent photic stimulation. Photoparoxysmal responses in the EEG are enhanced when the eyes remain closed during stimulation. We tested the hypothesis that this is due to diffusion of light by the eyelids. In 25 photosensitive patients, conditions 'eye closure', 'eyes closed', 'eyes open' and 'eyes open with diffuser' were tested for frequencies of 2-60 Hz. Additional influences of a red filter and fixation were also examined. The photosensitivity range was maximal in the condition 'eyes open with diffuser', due to an increase of the upper limit to a median 60 Hz (range 25-60), from 35 (15-50) Hz with eyes open, 37.5 (25-60) Hz with eyes closed and 40 (23-60) Hz with eye closure (P = 0.0002). This effect was attenuated in patients on valproic acid and with the use of a red or white filter. Testing with a diffuser was more sensitive than without, except for one patient who was photosensitive only in the eye closure condition. The influence of the eyelids on photosensitivity can be explained by diffusion of light, attentuated by an intensity loss. Use of a diffuser may simplify testing for photosensitivity in the EEG laboratory. The diffusion effect may explain seizure susceptibility in front of 50 and 60 Hz television screens.

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.

Comparison of combined versus subdural or intracerebral electrodes alone in presurgical focus localization.

PURPOSE: The yield of subdural versus intracerebral electrodes for ictal localization remains a point of controversy. We assessed the relative sensitivity of these two types of electrodes per case. METHODS: Eighty-three intracranial recordings obtained from 82 patients were retrospectively reviewed to establish which type of electrode performed best in which patients and which seizure types. RESULTS: Sixty (73%) of 82 patients had temporal lobe seizure onsets, eight frontal, nine widespread or multifocal/multilobar or both, whereas in five, seizure onset was not localized. Exclusive use of intracerebral electrodes would have been sufficient for accurate localization of the seizure-onset zone in all 35 patients with strictly mesial temporal seizure onsets. In only 20 (57%) of these 35 patients, the same decision would have been reached with exclusive use of subdural electrodes. In widespread neocortical and mesial temporal seizures (n = 25), yield of both electrode types was at about the same level, but neither was sufficient to identify the zone of ictal onset on its own. In frontal or multilobar seizures (n = 22), yield of subdural electrodes was slightly better then that of the intracerebral electrodes, but was not sufficient in all cases. CONCLUSIONS: This study indicates that, depending on the characteristics of the seizure disorder, exclusive use of either intracerebral or subdural electrodes may easily result in erroneous diagnosis because of insufficient sampling of the brain. These findings are in contrast with other studies emphasizing the high yield of reliable EEG findings in evaluations with a single type of electrode and corroborate the results of one of our previous studies.