C.D. Binnie

Intracerebral propagation of interictal activity in partial epilepsy: implications for source localisation.

The hypothesis that focal scalp EEG and MEG interictal epileptiform activity can be modelled by single dipoles or by a limited number of dipoles was examined. The time course and spatial distribution of interictal activity recorded simultaneously by surface electrodes and by electrodes next to mesial temporal structures in 12 patients being assessed for epilepsy surgery have been studied to estimate the degree of confinement of neural activity present during interictal paroxysms, and the degree to which volume conduction and neural propagation take part in the diffusion of interictal activity. Also, intrapatient topographical correlations of ictal onset zone and deep interictal activity have been studied. Correlations between the amplitudes of deep and surface recordings, together with previous reports on the amplitude of scalp signals produced by artificially implanted dipoles suggest that the ratio of deep to surface activity recorded during interictal epileptiform activity on the scalp is around 1:2000. This implies that most such activity recorded on the scalp does not arise from volume conduction from deep structures but is generated in the underlying neocortex. Also, time delays of up to 220 ms recorded between interictal paroxysms at different recording sites show that interictal epileptiform activity can propagate neuronally within several milliseconds to relatively remote cortex. Large areas of archicortex and neocortex can then be simultaneously or sequentially active via three possible mechanisms: (1) by fast association fibres directly, (2) by fast association fibres that trigger local phenomena which in turn give rise to sharp/slow waves or spikes, and (3) propagation along the neocortex. The low ratio of deep-to-surface signal on the scalp and the simultaneous activation of large neocortical areas can yield spurious equivalent dipoles localised in deeper structures. Frequent interictal spike activities can also take place independently in areas other than the ictal onset zone and their interictal propagation to the surface is independent of their capacity to trigger seizures. It is concluded that: (1) the deep-to-surface ratios of electromagnetic fields from deep sources are extremely low on the scalp; (2) single dipoles or a limited number of dipoles are not adequate for surgical assessment; (3) the correct localisation of the onset of interictal activity does not necessarily imply the onset of seizures in the region or in the same hemisphere. It is suggested that, until volume conduction and neurophysiological propagation can be distinguished, semiempirical correlations between symptomatology, surgical outcome, and detailed presurgical modeling of the neocortical projection patterns by combined MEG, EEG, and MRI could be more fruitful than source localization with unrealistic source models.

Cognitive impairment during epileptiform discharges: is it ever justifiable to treat the EEG?

Epileptiform EEG discharges are not confined to people with epilepsy, and their frequency is only weakly related to severity. A fundamental principle of EEG practice is, therefore, to avoid overinterpretation of epileptiform activity. Epileptiform discharges not accompanied by obvious clinical events are generally regarded as subclinical or interictal. However, in many patients sensitive methods of observation, notably continuous psychological testing, show brief episodes of impaired cognitive function during such discharges. This phenomenon of transitory cognitive impairment (TCI) is found in about 50% of patients who show discharges during testing. TCI is not simple inattention. The effects are material and site specific: lateralised discharges are associated with deficits of functions mediated by the hemisphere in which the discharges occur. Conversely, specific tasks can activate or suppress focal discharges over the brain regions that mediate the cognitive activity in question. TCI clearly contributes to the cognitive problems of some people with epilepsy and may cause deficits that pass unrecognised. TCI is demonstrable in many cases of benign partial epilepsy of childhood, a disorder once thought to have no adverse psychological effects. TCI can contribute to abnormalities of psychological test profiles and interferes with daily tasks, such as reading and driving. In children it may be associated with behavioural disorders. An important practical issue is whether TCI materially impairs psychosocial function and, if so, whether drug treatment is desirable or effective. Uncontrolled reports and two preliminary randomised controlled trials of antiepileptic treatment of TCI have suggested that suppression of discharges is associated with significant improvement in psychosocial function.

Power spectrum and intracranial EEG patterns at seizure onset in partial epilepsy.

Intracranial electroencephalographic patterns of seizure onset during preoperative assessment with intracerebral and subdural electrodes have been correlated with surgical outcome in 15 patients with partial epilepsy assessed for surgery. The presence and topography of electrodecremental events, high frequency activity, irregular sharp waves intermixed with slow activity, spike-wave activity and rhythmic ictal transformation at seizure onset were studied in a total of 78 complex partial seizures. Raw traces from intracerebral and subdural recordings were assessed visually in conjunction with changes in the following spectral variables (calculated for consecutive 1.28 sec epochs): amplitude (sum of amplitude of all components within a frequency band), activity, mobility, and complexity. The time course of these variables during preictal and ictal periods was displayed and assessed. This technique proved effective for detecting low-amplitude high-frequency activity and subtle electrodecremental events. It was concluded that: (a) most patients (12/15) showed early electrodecremental events, generalised or local, mainly involving frequencies below 40 Hz; (b) generalised electrodecremental events at onset did not imply poor outcome; (c) localised high-frequency activity, between 20 and 80 Hz, was associated with a good outcome.

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.

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.

Surgical treatment of epilepsy due to cortical dysplasia: clinical and EEG findings.

Seventeen patients with cortical dysplasia who had surgical resection for medically intractable partial epilepsy were studied. Compared with two groups of surgically treated patients with intractable epilepsy due to tumour (n = 20) and mesial temporal sclerosis (n = 40), patients with cortical dysplasia showed significantly more frequent extratemporal lesions, more frequent non-epileptiform EEG abnormalities and less favourable surgical outcome for seizure control. Patients with cortical dysplasia were younger at onset of seizures and had a lower detection rate of CT abnormalities compared with the tumour group, and lower IQ compared with the mesial temporal sclerosis group. MRI was abnormal in five of seven patients. Six patients became seizure-free or almost seizure-free but eight did not experience relief of seizures. Surgical outcome related to the extent of pathology but not to the histological abnormality. Lesions outside the temporal and frontal lobes were correlated with poor surgical outcome, as were generalised interictal EEG abnormalities, which may reflect extensive or multiple lesions. Ictal intracranial recordings were not useful for presurgical evaluation of cortical dysplasia.

Electrical impedance tomography of human brain function using reconstruction algorithms based on the finite element method

Electrical impedance tomography (EIT) is a recently developed technique which enables the internal conductivity of an object to be imaged using rings of external electrodes. In a recent study, EIT during cortical evoked responses showed encouraging changes in the raw impedance measurements, but reconstructed images were noisy. A simplified reconstruction algorithm was used which modelled the head as a homogeneous sphere. In the current study, the development and validation of an improved reconstruction algorithm are described in which realistic geometry and conductivity distributions have been incorporated using the finite element method. Data from computer simulations and spherical or head-shaped saline-filled tank phantoms, in which the skull was represented by a concentric shell of plaster of Paris or a real human skull, have been reconstructed into images. There were significant improvements in image quality as a result of the incorporation of accurate geometry and extracerebral layers in the reconstruction algorithm. Image quality, assessed by blinded subjective expert observers, also improved significantly when data from the previous evoked response study were reanalysed with the new algorithm. In preliminary images collected during epileptic seizures, the new algorithm generated EIT conductivity changes which were consistent with the electrographic ictal activity. Incorporation of realistic geometry and conductivity into the reconstruction algorithm significantly improves the quality of EIT images and lends encouragement to the belief that EIT may provide a low-cost, portable functional neuroimaging system in the foreseeable future.

Vagal nerve stimulation in epileptic encephalopathies.

Objective. To study the effect of vagal nerve stimulation (VNS) in children with epileptic encephalopathies. Methods and Materials. All children receiving VNS during a 2-year period at our center were studied prospectively for changes in seizure frequency, electroencephalogram (EEG), adaptive behavior, quality of life, and where appropriate, verbal/nonverbal performance. Assessments were made before and for at least 1 year after implant. Results. Sixteen children were studied. One device was removed because of infection. Of the remaining 15 children, 4 had a >50% reduction and 2 had a >50% increase in seizure frequency at 1 year after implant. Median reduction in seizure frequency was 17%. There was no trend toward improvement of the EEG or adaptive behavior. Quality of life was unchanged in most areas, except in perceived treatment side effects and general behavior that were improved. In 6 children undergoing further assessment, there was a significant improvement in verbal performance; this did not correlate with reduction in seizure frequency. Conclusion. VNS did not significantly improve seizure frequency, severity, adaptive behavior, or the EEG during the first year of treatment for the group as a whole, although 4 children (27%) had a worthwhile reduction in seizure frequency. There were significant improvements in perceived treatment side effects and general behavior.

Predictors of outcome and pathological considerations in the surgical treatment of intractable epilepsy associated with temporal lobe lesions.

OBJECTIVES To evaluate the influence of clinical, investigative, and pathological factors on seizure remission after temporal lobectomy for medically intractable epilepsy associated with focal lesions other than hippocampal sclerosis. METHODS From a series of 234 consecutive “en bloc” temporal resections for medically intractable epilepsy performed between 1976 and 1995, neuropathological examination disclosed a focal lesion in 80. The preoperative clinical, neuropsychological, interictal EEG, and neuroimaging characteristics of these patients were assembled in a computerised database. The original neuropathological material was re-examined for lesion classification and completeness of removal. The presence of additional cortical dysplasia and mesial temporal sclerosis was also noted. Survival analysis was performed using Kaplein-Meier curves and actuarial statistics. Logistic regression analysis was used to establish the independent significance of the clinical variables. RESULTS The probability of achieving a 1 year seizure remission was 71% by 5 years of follow up. Factors predicting a poor outcome on multivariate analysis included the need for special schooling and a long duration of epilepsy. Generalised tonic-clonic seizures, interictal EEG discharges confined to the resected lobe, demonstration of the lesion preoperatively on CT, and complete histological resection of the lesion were not predictive of outcome. Neuropsychological tests correctly predicted outcome in left sided cases but apparently congruent findings in right sided resections were associated with a poor outcome. Pathological reclassification established the dysembryoplastic neuroepithelial tumour as the commonest neoplasm (87%) in this series, with a significantly better seizure outcome than for developmental lesions, such as focal cortical dysplasia. CONCLUSIONS The findings highlight the importance of dysembryoplastic neuroepithelial tumour in the pathogenesis of medically refractory lesional temporal lobe epilepsy and the prognostic significance of preoperative duration of epilepsy emphasises the need for early recognition and surgical treatment. Cognitive and behavioural dysfunction, however, is associated with a lower seizure remission rate, independent of duration of epilepsy.

Multiple subpial transection: a review of 21 cases.

Multiple subpial transection (MST) is a novel technique in surgery for epilepsy, employed in patients where some or all of the epileptogenic zone cannot be resected because it lies in a vital cortical area. Twenty one patients subjected to MST were reviewed. Eighteen patients had medically intractable epilepsy and three patients had Landau-Kleffner syndrome. Their ages ranged from 6 to 47 (mean 15-9) and duration of epilepsy ranged from 0.33 to 42 (mean 8.6) years. Preoperative MRI showed focal abnormalities in eight cases. Detailed electrophysiological examination was carried out on all patients. Brain resection was performed in addition to MST in 12 patients. A further six patients underwent brain biopsy. Three patients with Landau-Kleffner syndrome were subjected neither to resection nor to biopsy. Histopathological examination showed Rasmussens syndrome in six patients, cortical dysplasia in six, cerebral tumour in one, and non-specific changes in five. Multiple subpial transection was carried out mainly in precentral and postcentral regions. Eighteen patients have been followed up for one to five years, and three for 10 months. The three patients with Landau-Kleffner syndrome were mute before operation and have shown substantial recovery of speech. Of the other 18, 11 showed a worthwhile decrease in seizure frequency. None of the patients developed chronic neurological deficits attributable to MST. It is concluded that MST leads to worthwhile seizure control without major neurological deficit in patients who would otherwise be inoperable.