Interictal estimation of intracranial seizure onset in temporal lobe epilepsy.

OBJECTIVES: To evaluate the lateralizing and localizing values of interictal focal slow activity (IFSA), single pulse electrical stimulation (SPES) and (18)FDG PET, in order to estimate their potential to complement ictal intracranial recordings and reduce prolonged monitoring in patients with temporal lobe epilepsy. METHODS: The study includes 30 consecutive patients with bilateral temporal subdural electrodes and focal seizure onset. IFSA, SPES and (18)FDG PET when available, were visually assessed and their combined lateralization was based on the majority of the individual lateralizing tests. RESULTS: In the 18 patients who had all three tests, lateralization was congruent with seizure onset areas in 15 (83%). When lateralized (15 patients), (18)FDG PET was always congruent with intracranial seizure onset. In all 12 patients without (18)FDG PET, lateralization combining IFSA and SPES was congruent with seizure onset, including two with bilateral independent seizure onset on subdural monitoring. 22 out of the 23 patients who had surgery enjoyed favorable outcome (Engel I or II). CONCLUSION: Intracranial IFSA and SPES can reliably predict the side and site (mesial versus lateral temporal) of seizure onset when they lateralize to the same side. SIGNIFICANCE: (18)FDG PET can be useful in planning electrode implantation. During intracranial recordings, IFSA and SPES have the potential to reduce telemetry time, risks and costs.

In vivo neuronal firing patterns during human epileptiform discharges replicated by electrical stimulation.

OBJECTIVE: To describe neuronal firing patterns observed during human spontaneous interictal epileptiform discharges (IEDs) and responses to single pulse electrical stimulation (SPES). METHODS: Activity of single neurons was recorded during IEDs and after SPES in 11 consecutive patients assessed with depth EEG electrodes and attached microelectrodes. RESULTS: A total of 66 neurons were recorded during IEDs and 151 during SPES. We have found essentially similar patterns of neuronal firing during IEDs and after SPES, namely: (a) a burst of high frequency firing lasting less than 100 ms (in 39% and 25% of local neurons, respectively for IED and SPES); (b) a period of suppression in firing lasting around 100-1300 ms (in 19% and 14%, respectively); (c) a burst followed by suppression (in 10% and 12%, respectively); (d) no-change (in 32% and 50%, respectively). CONCLUSIONS: The similarities in neuronal firing patterns associated with IEDs and SPES suggest that, although both phenomena are initiated differently, they result in the activation of a common cortical mechanism, probably initiated by brief synchronised burst firing in some cells followed by long inhibition. SIGNIFICANCE: The findings provide direct in vivo human evidence to further comprehend the pathophysiology of human focal epilepsy.

Single-pulse electrical stimulation helps to identify epileptogenic cortex in children.

PURPOSE: The usefulness of single-pulse electrical stimulation (SPES) during intracranial recordings was evaluated in a pediatric population. This method is useful in identifying epileptogenic cortex in adult subjects. METHODS: We studied 35 children who were undergoing intracranial electroencephalography (EEG) recordings from two hospitals (King's College Hospital and Great Ormond Street Hospital for Sick Children, London, United Kingdom). In each patient we studied all available contacts using a series of 10 or more single, brief (1ms) electrical stimuli. The cortical responses were reviewed in detail. The data were examined for associations between response type, ictal onset zone, lesion boundary, and seizure outcome. RESULTS: We identified cortical responses to SPES that were similar to those reported in adults. In agreement with previous studies we found that two types of responses ("delayed" and "repetitive" responses) were associated with the ictal onset zone and the area of the presumed epileptogenic lesion. When these responses were present (54% of cases), the removal of the entire area responsible for the abnormal responses to SPES was associated with good outcome. CONCLUSION: Cortical responses to SPES in children provide new and additional information in the investigation of epileptogenic cortex in children during assessment for epilepsy surgery. This may improve the outcome for this difficult but important group.

Late EEG responses triggered by transcranial magnetic stimulation (TMS) in the evaluation of focal epilepsy.

PURPOSE: To evaluate the use of EEG responses to transcranial magnetic stimulation (TMS-EEG responses) as a noninvasive tool for the diagnosis of focal epilepsy. METHODS: Fifteen patients and 15 healthy subjects were studied. TMS at an intensity set at resting corticomotor threshold were delivered at the standard EEG electrode positions. For each position, EEG responses to TMS were evaluated before and after averaging EEG recordings synchronized with the TMS pulse. RESULTS: Two types of TMS-EEG responses were seen: (A) early responses: consisting of a single slow wave seen after the TMS pulse; and (B) late TMS-EEG responses, which were subclassified into (b.1) delayed responses: waveforms resembling interictal epileptiform discharges induced by TMS; or (b.2) repetitive responses: onset of a new rhythym induced by TMS. Early responses were observed in patients and healthy subjects when stimulating at various sites and were considered normal responses to TMS. Late TMS-EEG responses were not seen in healthy subjects, whereas they were seen in 11 of the 15 epileptic patients. Late TMS-EEG responses occurred when stimulating the epileptogenic side in eight out of the nine patients who had lateralized late TMS-EEG responses. The combined use of late TMS-EEG responses and interictal scalp EEG would have suggested the diagnosis of focal epilepsy in all patients, despite the absence of late TMS-EEG responses in four patients and the presence of normal interictal scalp EEG in three. CONCLUSIONS: TMS-EEG responses can identify epileptogenic cortex and may substantially improve the diagnosis of focal epilepsy, particularly, if combined with standard EEG studies.

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.

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.

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.