Electrocorticographic discharge patterns in glioneuronal tumors and focal cortical dysplasia.

PURPOSE: To determine whether highly epileptiform electrocorticographical discharge patterns occur in patients with glioneuronal tumors (GNTs) and focal cortical dysplasia (FCD) and whether specific histopathological features are related to such patterns. METHODS: The series consists of operated patients with pharmacoresistant epilepsy because of FCD or GNT between 1992 and 2003. Electrocorticography was reviewed for presence of continuous spiking, bursts, recruiting discharges, or sporadic spikes. Surgical specimens were reviewed for the presence of balloon cells, (coexisting) cortical dysplasia, and relative frequencies of neurons, glia, and microglia. RESULTS: Continuous spiking was seen in 55% versus 12% of patients with FCD and GNT, respectively (p = 0.005). Bursts and recruiting discharges were seen in a similar proportion of patients with FCD or GNT. Ninety-one percent of patients with continuous spiking showed (coexisting) cortical dysplasia in contrast to 42% of patients without this pattern (p = 0.004). The presence of balloon cells and glia or microglia content were not associated with discharge patterns. CONCLUSION: Continuous spiking, bursts, and recruiting discharges occur in patients with FCD and GNT. Continuous spiking was seen significantly more often in patients with FCD. When continuous spiking is found with GNT, it is likely to be associated with dysplastic regions with a high neuronal density.

Single pulse electrical stimulation for identification of structural abnormalities and prediction of seizure outcome after epilepsy surgery: a prospective study.

BACKGROUND: Abnormal late responses to single pulse electrical stimulation (SPES) in patients with intracranial recordings can identify epileptogenic cortex. We aimed to investigate the presence of neuropathological abnormalities in abnormal SPES areas and to establish if removal of these areas improved postsurgical seizure control. METHODS: We studied abnormal responses to SPES during chronic intracranial recordings in 40 consecutive patients who were thereafter operated on because of refractory epilepsy and had a follow-up period of at least 12 months. FINDINGS: 22 patients had abnormal responses to SPES exclusively located in resected regions (96% with favourable outcome), seven had abnormal responses to SPES located in resected and non-resected regions (71% with favourable outcome), three had abnormal responses to SPES exclusively outside the resected region (none with favourable outcome), and eight did not have abnormal responses to SPES (62.5% with favourable outcome). Surgical outcome was significantly better when areas with abnormal responses to SPES were completely resected compared with partial or no removal of abnormal SPES areas (p=0.006). Neuropathological examination showed structural abnormalities in the abnormal SPES areas in 26 of the 29 patients in whom these regions were resected, despite the absence of clear MRI abnormalities in nine patients. INTERPRETATION: Abnormal responses to SPES are functional markers of epileptogenic structural abnormalities, and can identify epileptogenic cortex and predict surgical outcome, especially when a frontal or temporal focus is suspected.

Treatment of interictal epileptiform discharges can improve behavior in children with behavioral problems and epilepsy.

OBJECTIVES: It is generally agreed that children should be treated for epilepsy only if they have clinical seizures. The aim of this study was to examine whether suppressing interictal discharges can affect behavior in children with epilepsy. STUDY DESIGN: In a double-blinded, placebo-controlled, crossover study, 61 children with well-controlled or mild epilepsy were randomly assigned to add-on therapy with either lamotrigine followed by placebo or placebo followed by lamotrigine. Ambulatory electroencephalographic recordings and behavioral scales were performed during baseline and at the end of placebo and drug phases. The primary hypothesis to be tested was that behavioral scales would improve specifically in patients with a reduction of electroencephalographic discharges during active drug treatment. RESULTS: Global rating of behavior significantly improved only in patients who showed a significant reduction in either frequency ( P < .05) or duration of discharges ( P < .05) during active treatment but not in patients with without a significant change in discharge rate. This improvement was mainly seen in patients with partial epilepsy ( P < .005). CONCLUSIONS: Our data suggest that suppressing interictal discharges can improve behavior in children with epilepsy and behavioral problems, particularly partial epilepsy. Focal discharges may be involved in the underlying mechanisms of behavioral problems in epilepsy.

Characteristics of scalp electrical fields associated with deep medial temporal epileptiform discharges.

OBJECTIVE: To determine scalp characteristics of epileptiform discharges arising from medial temporal structures (MT). METHODS: Signal-to-noise ratio was increased by averaging simultaneous recordings from intracranial and scalp electrodes synchronised on discharges recorded by foramen ovale (FO) electrodes. The topography, amplitude and distribution of averaged scalp signals were analysed. RESULTS: Four thousand three hundred and twenty-seven discharges from 20 patients were averaged into 77 patterns. Before averaging, only 9% of discharges were detectable on the scalp without the need of simultaneous FO recordings (SED). A further 72.3% of discharges fell into averaged patterns that could be detected on the scalp as small transients before or after averaging (STBA or STAA). In 18.7% of discharges, no scalp signal was seen after averaging. Whereas most SED patterns had largest amplitude on the scalp at anterior temporal electrodes, STBA and STAA patterns showed greater variability and more widespread scalp fields, suggesting a deeper source. Dipole source localisation modelled the majority of SED patterns as radial dipoles located just behind the eye. In contrast, dipoles corresponding to STBA or STAA patterns showed greater variability in location and orientation and tended to be located at MT. CONCLUSIONS: SED patterns seem to arise from widespread subtemporal and/or superficial neocortical activation, generating EEG fields that are distorted by the high electrical conductivity of anterior cranial foramina. In contrast, STBA and STAA patterns represent electrical fields from neuronal activity more restricted to MT, that reach the scalp highly attenuated by volume-conduction and less distorted by cranial foramina. SIGNIFICANCE: Low amplitude scalp signals can be related to MT activity and must be taken into consideration for the diagnosis of temporal lobe epilepsy, pre-surgical assessment and for valid modelling of deep sources from the scalp EEG and magnetoencephalogram.

Material-specific recognition memory deficits elicited by unilateral hippocampal electrical stimulation.

Although the medial temporal lobe is thought to be critical for recognition memory (RM), the specific role of the hippocampus in RM remains uncertain. We investigated the effects of transient unilateral hippocampal electrical stimulation (ES), subthreshold for afterdischarge, on delayed item RM in epilepsy patients implanted with bilateral hippocampal depth electrodes. RM was assessed using a novel computer-controlled test paradigm in which ES to left or right hippocampus was either absent (baseline) or synchronized with item presentation. Subsequent yes-no RM performance revealed a double dissociation between material-specific RM and the lateralization of ES. Left hippocampal ES produced word RM deficits, whereas right hippocampal ES produced face RM deficits. Our findings provide the first demonstration in humans that selective unilateral stimulation-induced hippocampal disruption is sufficient to produce impairments on delayed RM tasks and provide support for the material-specific laterality of hippocampal function with respect to RM.

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.

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.

Presurgical assessment of memory-related brain structures: the Wada test and functional neuroimaging.

Medial temporal lobe structures are known to play a major role in memory processing. Recent work has revealed that extratemporal structures (e.g. the frontal lobe and thalamus) may also be important in memory function. In candidates for epilepsy surgery, particularly in those with temporal lobe seizures, presurgical evaluation of memory function is essential, since seizures may originate in the neural substrate that is critical for memory. In this article, we review the tools used for presurgical evaluation and their contribution to the understanding of memory function, focusing on the Wada test, [18F]fluorodeoxy-glucose positron emission tomography ([18F]FDG-PET) and functional magnetic resonance imaging (fMRI). We also explore perspectives on future studies that may elucidate the role of the temporal and extratemporal structures in memory function and the mechanisms of cerebral plasticity.

Lateralising value of neuropsychological protocols for presurgical assessment of temporal lobe epilepsy.

PURPOSE: To estimate the value of neuropsychological measurements in determining the side of seizure onset for presurgical assessment in patients with temporal lobe epilepsy. The lateralising value of neuropsychological protocols was evaluated for all patients and in subpopulations depending on surgical outcome with regard to seizure control, speech dominance, neuropathology, and need for intracranial EEG recordings. METHODS: A battery of neuropsychological procedures was carried out preoperatively in 125 patients who underwent left (n = 66) or right (n = 59) temporal lobectomies. Binary logistic regression analysis was performed to find sets of variables that allowed the best prediction of the side of seizure onset (assumed to be the operated-on side). RESULTS: Combinations of noninvasive neuropsychological tests and Wada subscores showed the highest lateralising values: 80.8% for all patients, 79.4% in seizure-free patients, 86.0% in patients not rendered seizure free, 85.7% in left speech patients, 77.8% in non-left speech patients, 89.3% in patients with mesial temporal sclerosis (MTS), 78.1% in non-MTS patients, 80.3% in patients who underwent intracranial EEG recordings, and 77.3% in those who did not. CONCLUSIONS: The lateralising value (80-90%) of neuropsychological protocols appears similar to that of other tests widely accepted for lateralisation (ictal and interictal scalp EEG and neuroimaging). Attention should be paid to neuropsychological results, particularly from the Wada test, during presurgical assessment of temporal lobe epilepsy, as they can provide strong support for findings from other lateralising tests, particularly in patients with presumed MTS or in left-speech patients.

A hole in the skull distorts substantially the distribution of extracranial electrical fields in an in vitro model.

The purpose of this study was to quantify the distortion of electrical fields by skull foramina using an in vitro model. Extracranial voltage generated by current dipoles located inside a human calva immersed in saline were measured when a 4-mm hole was open and when it was blocked with paraffin wax. Dipoles were located either along the internal surface of the bone (superficial dipoles) or at increasing distances from the bone (deep dipoles). With the hole open, extracranial signals had a substantially greater amplitude than with the hole blocked. The locations of the largest voltage values recorded outside the skull depended on the distance of the recording electrode from the hole rather than on the location of the internal dipole. For superficial dipoles, voltage values with the hole open were as much as 116 times greater than when the hole was blocked. Furthermore, when the hole was open, the largest extracranial signals were seen at the hole even when the dipole was 5 to 6 cm away from the hole. The effects of skull holes were less prominent for deep dipoles than for superficial dipoles. Skull discontinuities can be major determinants for the distribution of extracranial EEG signals. These results have implications for EEG interpretation and for source localization.