Source localization of mesial temporal interictal epileptiform discharges: Correlation with intracranial foramen ovale electrode recordings

OBJECTIVE: We have investigated the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) on a statistical basis by using clinical electroencephalographic (EEG) data of simultaneous scalp and intracranial foramen ovale (FO) electrode recordings. METHODS: We retrospectively analyzed the IED of 15 patients who underwent presurgical assessment for intractable temporal lobe epilepsy. All patients have subsequently undergone amygdalohippocampectomy. The scalp signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. Source modeling was carried out by using statistical non-parametric mapping (SNPM) of LORETA values and by calculating raw LORETA values of averaged IED. The results were compared to intracranial data obtained from FO electrode recordings. RESULTS: Two thousand six hundred and fifteen discharges could be attributed to 19 different patterns of intracranial mesial temporal IED. SNPM of LORETA revealed confined ipsilateral mesial temporal solutions for 14 (73.7%) and no significant solutions for five (26.3%) of these patterns. Raw LORETA current density distributions of the 19 averaged IED patterns revealed ipsilateral basal to lateral temporal solutions for the 14 IED patterns with a sufficient signal to noise ratio (SNR), but spurious results for those five IED with a low SNR. CONCLUSIONS: SNPM of LORETA but not LORETA analysis of averaged IED patterns accurately localizes the source generators of mesial temporal IEDs. SIGNIFICANCE: SNPM of raw LORETA values might be appropriate for localizing restricted mesial temporal lobe sources.     

Mesial temporal versus lateral temporal interictal epileptiform activity: comparison of chronic and acute intracranial recordings

Intracranial interictal epileptiform activity (EA) was recorded by chronic stereotactic depth electroencephalography (SDEEG) and acute electrocorticography (ECOG) in 22 patients with complex partial seizures of temporal lobe origin. Chronic SDEEG recordings defined two groups of patients with respect to the presence of absence of lateral temporal EA; 13 patients showed independent lateral temporal EA during chronic recordings and 9 patients did not. All patients had EA recorded from mesial temporal structures during SDEEG. The presence of lateral temporal EA was correlated with a higher pre-operative seizures frequency but not with ictal onset zones, structural pathology, age at onset of epilepsy, or duration of epilepsy. Results of acute ECOG recordings performed on the same patients 1–24 months after SDEEG accurately reproduced the mesial versus lateral distribution of EA within patients (P < 0.0003). Though ECOG was less sensitive than SDEEG in demonstrating EA confined to mesial structures, positive findings at ECOG were 100% specific with respect to SDEEG. These results suggest that, at least with respect to mesial temporal versus lateral temporal structures, there is a constancy within patients in the distribution of interictal EA recorded with chronic intracranial electrodes. In addition, acute ECOG provides an accurate representation of individual patients' interictal EA.     

EEG source localization of interictal epileptiform activity in patients with partial complex epilepsy: comparison between dipole modeling and brain distributed source models.

The precision between dipole Brain Electric Source Analysis (BESA) and brain distributed Variable Resolution Electromagnetic Tomography (VARETA) models for the localization of brain sources of interictal epileptiform discharges in patients with partial complex epilepsy was compared. The localization of brain sources calculated with dipole analysis and variable resolution electromagnetic tomography in 20 interictal recordings was analyzed. The origin of the dipoles was temporal in 18 cases, frontal in 1 and occipital in another. One dipole was enough in 7 cases, whereas two dipoles were necessary in 13 cases. The localization of paroxysmal activity was the same with BESA and VARETA in 17 patients. BESA and VARETA are useful methods for EEG sources analysis; BESA has more precision for the localization of punctate epileptogenic regions, and VARETA provides more information concerning the extension of the epileptic zone.     

Consistent localization of interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex

PURPOSE: We addressed consistent localization of focal interictal epileptiform activity on EEGs of patients with tuberous sclerosis complex (TSC) and epilepsy. METHODS: Twenty-one patients with TSC with a 10-year history of epilepsy and interictal epileptiform activity in three or more EEG recordings were included. None of the patients had undergone epilepsy surgery. Local maxima of interictal epileptiform activity were measured from 76 EEG traces and 33 EEG reports. Information about the patients' clinical course was extracted from their medical records. Magnetic resonance imaging (MRI) and neuropsychological examinations were performed. Statistical analysis was performed with the Mann-Whitney U test. RESULTS: In eight patients, interictal epileptiform activity was consistently detected in one or two regions (group 1), and in 13 patients, epileptiform activity was detected in three or more regions (group 2). The number of foci increased throughout the disease course in both groups. Age at seizure onset and IQ were significantly higher in group 1. Complex partial seizures occurred more often in the patients of group 1. In 19 of the 21 patients, the most consistent epileptiform activity was localized in the frontotemporal region. CONCLUSIONS: Ninety percent of patients with TSC showed at least one region of consistent interictal epileptiform activity. Patients with one or two regions of epileptiform activity were older at seizure onset, often experienced complex partial seizures, and had mild or no mental deficits. These patients may be candidates for epilepsy surgery.     

Dipole source localization of interictal epileptiform activity in temporal lobe epilepsy with medial temporal lesion

Dipole sources of interictal epileptiform activities recorded by conventional electroencephalogram (EEG) were estimated using the dipole tracing method. Four cases of temporal lobe epilepsy with medial temporal lesions were studied. Two patients with hippocampal sclerosis, one patient with granulation in the hippocampus and one patient with cavernous angioma were involved in the study. Interictal epileptiform activities were classified into two patterns according to the topography of spikes. They were widespread spikes over the parasagittal electrodes (parasagittal spikes) and restricted spikes at the temporal electrodes (temporal spikes). Dipole sources of parasagittal spikes were localized in the medio-basal temporal lobe with vertically orientated vector moment. Dipole sources of temporal spikes were localized in the medio-basal temporal lobe with horizontally orientated vector moment. Locations of dipoles and directions of vector moments were consistent with topography and polarity of spikes. The difference in the two patterns of interictal epileptiform activities was derived from the difference in the direction of the vector moment of dipole sources. There was no difference in the location of dipole sources. Both the dipole sources and the lesions were localized in the same medio-basal temporal lobe. Dipole tracing was very useful in localizing the dipole sources of interictal epileptiform activities and in understanding the neurophysiological background.     

Clinical application of dipole models in the localization of epileptiform activity.

SUMMARY: Routine clinical interpretation of EEG using visual inspection of traces is a time-honored, but simplistic, form of analysis. This is particularly true in attempts to localize an epileptogenic focus by means of EEG spike or seizure waveforms. Improved understanding of the cortical substrates of these potentials has allowed us to identify their likely cerebral origins through spatio-temporal analysis of scalp voltage fields. Equivalent dipole modeling is one such technique. Although an imperfect representation of spike or seizure sources, proper interpretation of dipole models can lead to a far better characterization of their localization and propagation. Modern techniques of 3-D MRI reconstruction and realistic head models have both improved localization accuracy and provided a means of displaying results in an image of the individual's brain.     

The circadian distribution of interictal epileptiform EEG activity

Eighteen continuous 48 h monitoring studies are reported from 17 patients with epilepsy. The numbers of epileptiform discharges over corresponding epochs of the 2 days were significantly positively correlated in 16 studies. However, this was explicable by masking due to the sleep/wake cycle and when waking and sleep were considered separately a minority of studies showed significant correlations. The difference in total 24 h production of discharges between the 2 days ranged from 1.3 to 30.3%, mean 15.1%. The maximum discharge rate in 75% of the studies occurred during sleep; during waking the distribution of discharges was random. Even in the waking state the 0.5 h discharge rate was extremely variable and in few patients could a single 30 min epoch be regarded as a reliable sample of the mean rate over the waking day. The intervals between events showed a Poisson distribution during 9 days and 5 nights, but there was no within-patient consistency between the first and second 24 h period. The occurrence of discharges was periodic significantly more often at night than during the day, but the periodicities did not clearly correspond to the REM cycle. Discharges increased overall during sleep in 14 studies, were unchanged in 2 and decreased in 4. The time of occurrence of maximal discharge rate during sleep was consistent from night I to night II only in patients exhibiting generalized regular spike-wave activity but random in the others. A negative correlation between antiepileptic drug levels and discharge rate was rarely observed.     

The stability of spike counts in children with interictal epileptiform activity

PurposeLittle is known about the stability of serial measures of spike counts in children or whether spike counts are an inherently stable or unstable measure. We investigated the variation in first- and second-night spike counts in children undergoing 48-h ambulatory EEG recording.MethodsWe analyzed 40 consecutive 48-h ambulatory EEGs performed at Boston Children's Hospital that manifested spikes but no seizures. Distinct spike foci in the same child were counted separately. We visually counted all spikes in the first 20 min after the first sleep spindle during nighttime sleep, comparing the first and second nights.ResultsFifty-five unique spike foci were counted in 40 children (age range: 9 months to 19 years; median: 8.4 years). Considerable variation was seen when comparing Night 1 and Night 2 spike counts: for all foci, Night 1 mean and median spike counts were 304.5 and 126 and Night 2 counts were 309.5 and 148, respectively. For each focus, the mean change in spike frequency between Night 1 and Night 2 was 42.1% (median = 28.3%, IQR 19.0–50.0%). The coefficient of variation of 0.94 suggested a large amount of variation. The percentage change weighted according to high or low spike frequency was 25.1%.ConclusionIn 40 children with 55 unique spike foci, significant variability in spike frequency was seen between consecutive nights of sleep, suggesting significant natural variation in spike frequency. A quarter of spike foci varied by 50% or more. Spike counts separated by longer intervals may show even more dramatic natural variation.     

Visual and automatic investigation of epileptiform spikes in intracranial EEG recordings

PURPOSE: Performance of automatic spike-detection algorithms and interrater reliability of human EEG reviewers were investigated previously by using scalp EEG recordings. However, it is not known, whether the findings of these studies hold for intracranial recordings. To address this question, we analyzed spike detection in intracranial recordings by two human reviewers and three automatic systems covering major lines in the development of automatic spike-detection systems. METHODS: Intracranial recordings from subdural and intrahippocampal depth electrode contacts in seven patients were analyzed by two reviewers and three spike-detection systems: (a) The rule-based system by Gotman, (b) a two-stage system consisting of a linear predictor and a second rule-based stage, and (c) a system using wavelet coefficients of the intracranial EEG data. RESULTS: Agreement between the two human reviewers with respect to spike identification was <50%. The automatic systems achieved agreements of 24% (Gotman), 26% (wavelet detector), and 32% (two-stage system) with the individual human reviewers. In spite of the small proportion of agreements, the same anatomic regions were identified by human and automatic EEG analysis as generators for the majority of spikes. CONCLUSIONS: The poor agreement between the human EEG reviewers suggests that the definition of spikes and spike-like episodes in intracranial electrodes is far from unequivocal. Nevertheless, localizing information is highly consistent by either visual or automatic spike detection, independent of the algorithm used for automatic spike detection.     

Controversies in neurophysiology. MEG is superior to EEG in localization of interictal epileptiform activity: Pro.

Both EEG and magnetoencephalography (MEG), with a time resolution of 1 ms or less, provide unique neurophysiologic data not obtainable by other neuroimaging techniques. MEG and EEG have often been compared to each other now although the two are complementary. Now that MEG has emerged as a mature clinical technology, it is worthwhile to compare the relative strengths of each for the localization of interictal epileptiform activity and to describe the strengths of MEG relative to EEG in the localization of interictal epileptiform activity. The sources of MEG and EEG signals will first be reviewed. Issues relevant to solving the forward problem and the inverse problem in MEG and EEG will be addressed followed by a comparison of research concerning the detection and localization of interictal epileptiform activity by MEG and EEG. The emphasis will be upon techniques and software routinely used in clinical applications but some emerging areas of MEG research which are entering clinical practice will also be reviewed. SIGNIFICANCE: MEG is a new noninvasive neurophysiologic technique which provides unique information for the clinical evaluation of patients with epilepsy, revealing aspects of neuronal function that previously could only be obtained by invasive EEG monitoring, and giving a new window for research of neuronal activity.     

Ictal and interictal SPECT findings in childhood absence epilepsy.

The purpose of this study was to investigate the informative value of single photon emission tomography (SPECT) in relation to the pathophysiological functioning of the brain during absence seizures and the origin of ictal discharges in idiopathic generalized epilepsies (IGEs). Six patients with childhood absence epilepsy (CAE) were selected for the study and two consecutive SPECT sessions were performed concomitant with EEG recordings revealing normal results and during hyperventilation (HV) studies where the ictal discharges were induced either alone or accompanied by clinical absence seizures. All six patients had ictal discharges in their EEGs during HV and two of them also had clinical absences. SPECT findings during HV revealed an overall increase in the cerebral blood flow (CBF) with significantly higher values as compared to the baseline data. There was no indication for any focal origin in either the interictal or the ictal SPECT findings. Results of the study were supportive for the concept of subcortical origin for the absence seizures and they were also promising for the diagnostic value of ictal SPECT in epileptic cases with undetermined origin as to whether they were localization-related or generalized.     

Accuracy of electroencephalographic dipole localization of epileptiform activities associated with focal brain lesions

We evaluated the accuracy of an electroencephalographic (EEG) localization technique (dipole inverse solution) in a consecutive series of 12 focal intracerebral lesions of divrse etiologies whose EEGs showed interictal spike activity or rhythmic activity at seizure onset. The calculated equivalent dipole was plotted on three axes in the patients' magnetic resonance image, and the distance between the dipole and the lesion margin was measured assuming that the shell of the lesion constituted an epileptognic region. In all cases the dipole localized closer than 0.8 cm to the nearest lesion margin. In addition, we compared the postsurgical outcome of 6 patients to the dipole localization and the resection margins. In all 6 patients in whom the dipole, and hence the estimated seizure generator, was removed the surgical outcome was favorable. We conclude that the inverse solution algorithm is a promising method for using the scalp EEG to localize the sources of electrical activity in the human brain in routine clinical electroencephalography and provides three-dimensional data not available from conventional analysis.     

Non-supervised spatio-temporal analysis of interictal magnetic spikes: comparison with intracerebral recordings.

OBJECTIVE: Our main goal was to evaluate the accuracy of an original non-supervised spatio-temporal magnetoencephalography (MEG) localization method used to characterize interictal spikes generators. METHODS: MEG and stereotactic intracerebral recordings (stereo-electro-encephalographic exploration, SEEG) data were analyzed independently in 4 patients. MEG localizations were performed with and without anatomical constraints. RESULTS: We analyzed 1326 interictal spikes recorded using MEG. For each patient, 2-3 typical source patterns were described. These source configurations were compared with SEEG. SEEG findings and MEG spatio-temporal localization results were remarkably coherent in our 4 patients. Most of the MEG patterns were similar to interictal SEEG patterns from a spatio-temporal point of view. CONCLUSIONS: We were able to evaluate the usefulness of our non-invasive localization method. This approach described correctly the part of the epileptogenic network involved in the generation of interictal events. Our results demonstrate the potential of MEG in the non-invasive spatio-temporal characterization of generators of interictal spikes.     

Different SPECT findings before and after Capgras' syndrome in interictal psychosis

We herein report a case of Capgras' syndrome observed in interictal psychosis in which the single-photon emission computed tomography (SPECT) findings before and after the appearance of the psychotic symptoms differed. SPECT with 99mTc-hexamethyl propyleneamine oxine (HMPAO) revealed worsening of hypoperfusion in the entire right hemisphere after onset of the psychotic symptoms. The enhanced hypoperfusion demonstrated by SPECT in the present case seems to indicate a right interhemispheric disconnection resulting in the occurrence of Capgras' syndrome.     

Chronic intracranial recordings after resection for epilepsy reveal a "running down" of epileptiform activity

We describe an electrical "running down" phenomenon and also a consistent spectral change (in the aperiodic component of the power spectrum) derived from chronic interictal electrocorticography (ECoG) after surgery in a patient with drug-resistant epilepsy. These data were recorded using a closed-loop neurostimulation system that was implanted after resection. The patient has been seizure-free for 2.5 years since resection without requiring the neurostimulator to be turned on to stimulate. Concurrently, there was an exponential decrease in the number of epileptiform electrographic detections recorded by the device, particularly over the first 26 weeks, indicative of an electrical running down phenomenon as the brain adapted to an extended period of seizure freedom. We also find that the aperiodic exponent of the power spectrum gradually decreases over time. The aperiodic component of intracranial ECoG may represent a novel marker of epileptogenicity, independent of seizures.     

Controversies in clinical neurophysiology. MEG is superior to EEG in the localization of interictal epileptiform activity: Con.

OBJECTIVE: To assess whether MEG is superior to scalp-EEG in the localization of interictal epileptiform activity and to stress the 'con' part in this controversy. METHODS: Advantages and disadvantages of the two techniques were systematically reviewed. RESULTS: While MEG and EEG complement each other for the detection of interictal epileptiform discharges, EEG offers the advantage of long-term recording significantly increasing its diagnostic yield which is not feasible with MEG. Localization accuracies of EEG and MEG are comparable once inaccuracies for the solution of the forward problem are eliminated. MEG may be more sensitive for the detection of neocortical spike sources. EEG and MEG source localizations show comparable agreement with invasive electrical recordings, can clarify the spatial relationship between the irritative zone and structural lesions, guide the placement of invasive electrodes and attribute epileptic activity to lobar subcompartments in temporal lobe epilepsy and to a lesser extent in extratemporal epilepsy. CONCLUSIONS: A clear superiority of MEG over EEG for the localization of interictal epileptiform activity cannot be derived from the studies presently available. SIGNIFICANCE: The combination of EEG and MEG provides information for the localization of interictal epileptiform activity which cannot be obtained with either technique alone.     

Multi-feature localization of epileptic foci from interictal,intracranial EEG

ObjectiveWhen considering all patients with focal drug-resistant epilepsy, as high as 40–50% of patients suffer seizure recurrence after surgery. To achieve seizure freedom without side effects, accurate localization of the epileptogenic tissue is crucial before its resection. We investigate an automated, fast, objective mapping process that uses only interictal data.MethodsWe propose a novel approach based on multiple iEEG features, which are used to train a support vector machine (SVM) model for classification of iEEG electrodes as normal or pathologic using 30 min of inter-ictal recording.ResultsThe tissue under the iEEG electrodes, classified as epileptogenic, was removed in 17/18 excellent outcome patients and was not entirely resected in 8/10 poor outcome patients. The overall best result was achieved in a subset of 9 excellent outcome patients with the area under the receiver operating curve = 0.95.ConclusionSVM models combining multiple iEEG features show better performance than algorithms using a single iEEG marker. Multiple iEEG and connectivity features in presurgical evaluation could improve epileptogenic tissue localization, which may improve surgical outcome and minimize risk of side effects.SignificanceIn this study, promising results were achieved in localization of epileptogenic regions by SVM models that combine multiple features from 30 min of inter-ictal iEEG recordings.