Has recording of seizures become obsolete?

Some patients with medically intractable epilepsy are considered for surgical treatment. In some surgical candidates, the investigation includes the placement of intracerebral electrodes and long-term monitoring to find the region of seizure onset. This region is the primary determinant of the surgical resection but about one-third of patients are not offered surgery after electrode implantation and among those operated only about 55% are seizure free after five years. This paper discusses why the primary reliance on the seizure onset maybe suboptimal and may be in part responsible for the relatively low surgical success rate. It also proposes to consider some interictal markers that may have advantages over seizure onset and may be easier to obtain.

Scalp EEG is not a blur: it can see high frequency oscillations although their generators are small.

High frequency oscillations (HFOs) are emerging as biomarkers of epileptogenicity. They have been shown to originate from small brain regions. Surprisingly, spontaneous HFOs can be recorded from the scalp. To understand how is it possible to observe these small events on the scalp, one avenue is the analysis of the cortical correlates at the time of scalp HFOs. Using simultaneous scalp and intracranial recordings of 11 patients, we studied the spatial distribution of scalp events on the cortical surface. For typical interictal epileptiform discharges the subdural distributions were, as expected, spatially extended. On the contrary, for scalp HFOs the subdural maps corresponded to focal sources, consisting of one or a few small spatial extent activations. These topographies suggest that small cortical areas generated the HFOs seen on the scalp. Similar scalp distributions corresponded to distinct distributions on a standard 1 cm subdural grid and averaging similar scalp HFOs resulted in focal subdural maps. The assumption that a subdural grid "sees" everything that contributes to the potential of nearby scalp contacts was not valid for HFOs. The results suggest that these small extent events are spatially undersampled with standard scalp and grid inter-electrode distances. High-density scalp electrode distributions seem necessary to obtain a solid sampling of HFOs on the scalp. A better understanding of the influence of spatial sampling on the observation of high frequency brain activity on the scalp is important for their clinical use as biomarkers of epilepsy.

Targeted density electrode placement achieves high concordance with traditional high-density EEG for electrical source imaging in epilepsy.

OBJECTIVE: High-density (HD) electroencephalography (EEG) is increasingly used in presurgical epilepsy evaluation, but it is demanding in time and resources. To overcome these issues, we compared EEG source imaging (ESI) solutions with a targeted density and HD-EEG montage. METHODS: HD-EEGs from patients undergoing presurgical evaluation were analyzed. A low-density recording was created by selecting the 25 electrodes of a standard montage from the 83 electrodes of the HD-EEG and adding 8-11 electrodes around the electrode with the highest amplitude interictal epileptiform discharges. The ESI solution from this "targeted" montage was compared to that from the HD-EEG using the distance between peak vertices, sublobar concordance and a qualitative similarity measure. RESULTS: Fifty-eight foci of forty-three patients were included. The median distance between the peak vertices of the two montages was 13.2 mm, irrespective of focus' location. Tangential generators (n = 5/58) showed a higher distance than radial generators (p = 0.04). We found sublobar concordance in 54/58 of the foci (93%). Map similarity, assessed by an epileptologist, had a median score of 4/5. CONCLUSIONS: ESI solutions obtained from a targeted density montage show high concordance with those calculated from HD-EEG. SIGNIFICANCE: Requiring significantly fewer electrodes, targeted density EEG allows obtaining similar ESI solutions as traditional HD-EEG montage.

Detection of epileptic activity in fMRI without recording the EEG.

EEG-fMRI localizes epileptic foci by detecting cerebral hemodynamic changes that are correlated to epileptic events visible in EEG. However, scalp EEG is insensitive to activity restricted to deep structures and recording the EEG in the scanner is complex and results in major artifacts that are difficult to remove. This study presents a new framework for identifying the BOLD manifestations of epileptic discharges without having to record the EEG. The first stage is based on the detection of epileptic events for each voxel by sparse representation in the wavelet domain. The second stage is to gather voxels according to proximity in time and space of detected activities. This technique was evaluated on data generated by superposing artificial responses at different locations and responses amplitude in the brain for 6 control subject runs. The method was able to detect effectively and consistently for responses amplitude of at least 1% above baseline. 46 runs from 15 patients with focal epilepsy were investigated. The results demonstrate that the method detected at least one concordant event in 37/41 runs. The maps of activation obtained from our method were more similar to those obtained by EEG-fMRI than to those obtained by the other method used in this context, 2D-Temporal Cluster Analysis. For 5 runs without event read on scalp EEG, 3 runs showed an activation concordant with the patient's diagnostic. It may therefore be possible, at least when spikes are infrequent, to detect their BOLD manifestations without having to record the EEG.

[Seizure prediction: from myth to reality]. / Prédiction des crises d'épilepsie: du mythe à la réalité.

INTRODUCTION: Clinical, metabolic and electrophysiologic studies suggest the existence of a preictal state, a transition between the interictal state and seizure. STATE OF THE ART: Analysis of the intracranial EEG by mathematical methods shows changes of the brain dynamics several minutes before the occurrence of partial seizures. These modifications can be widespread and not restricted to the epileptogenic focus, which would explain why they can also be detected from scalp EEG. Several scenarios could underlie the preictal state: a progressive recruitment of neurons or a facilitating state with a high probability of seizure occurrence. Because of the high rate of false predictions, no satisfactory method for seizure prediction has been currently proposed. PERSPECTIVES: A European multicenter study (Evolving platform for improving living expectation of patients suffering from IctAl events [EPILEPSIAE]) is currently evaluating a combination of 44 methods applied for EEG and ECG analysis on long-term recordings obtained from a large multicenter database (www.epilepsiae.eu). CONCLUSION: Combining analyses of multi-level signals including intracranial EEG and microelectrodes, scalp EEG and in vitro electrophysiological studies of post-operative tissues should help clarify brain dynamics during the pre-ictal state.

Different structures involved during ictal and interictal epileptic activity in malformations of cortical development: an EEG-fMRI study.

Malformations of cortical development (MCDs) are commonly complicated by intractable focal epilepsy. Epileptogenesis in these disorders is not well understood and may depend on the type of MCD. The cellular mechanisms involved in interictal and ictal events are notably different, and could be influenced independently by the type of pathology. We evaluated the relationship between interictal and ictal zones in eight patients with different types of MCD in order to better understand the generation of these activities: four had nodular heterotopia, two focal cortical dysplasia and two subcortical band heterotopia (double-cortex). We used the non-invasive EEG-fMRI technique to record simultaneously all cerebral structures with a high spatio-temporal resolution. We recorded interictal and ictal events during the same session. Ictal events were either electrical only or clinical with minimal motion. BOLD changes were found in the focal cortical dysplasia during interictal and ictal epileptiform events in the two patients with this disorder. Heterotopic and normal cortices were involved in BOLD changes during interictal and ictal events in the two patients with double cortex, but the maximum BOLD response was in the heterotopic band in both patients. Only two of the four patients with nodular heterotopia showed involvement of a nodule during interictal activity. During seizures, although BOLD changes affected the lesion in two patients, the maximum was always in the overlying cortex and never in the heterotopia. For two patients intracranial recordings were available and confirm our findings. The dysplastic cortex and the heterotopic cortex of band heterotopia were involved in interictal and seizure processes. Even if the nodular gray matter heterotopia may have the cellular substrate to produce interictal events, the often abnormal overlying cortex is more likely to be involved during the seizures. The non-invasive BOLD study of interictal and ictal events in MCD patients may help to understand the role of the lesion in epileptogenesis and also determine the potential surgical target.

Value of ictal and interictal epileptiform discharges and high frequency oscillations for delineating the epileptogenic zone in patients with focal cortical dysplasia.

OBJECTIVES: There are different neurophysiological markers of the Epileptogenic Zone (EZ), but their sensitivity and specificity for the EZ is not known in Focal Cortical Dysplasia (FCD) patients. METHODS: We studied patients with FCD who underwent stereoelectroencephalography (SEEG) and surgery. We marked in the SEEG: (a) typical and atypical interictal epileptiform patterns, (b) ictal onset patterns, and (c) rates of ripples (80-250 Hz) and fast ripples (FRs) (>250 Hz). High frequency oscillations were marked automatically during one hour of deep sleep. Surgical outcome was defined as good (Engel I) or poor (Engel II-IV). We computed the sensitivity and, as a measure of specificity, the false positive rate to identify the EZ, and compared them across the different neurophysiological markers. RESULTS: We studied 21 patients, 19 with FCD II. Ictal and typical interictal pattern were the markers with highest sensitivity, while the atypical interictal pattern had the lowest. We found no significant difference in specificity among markers. However, there is a tendency that FRs had the lowest false positive rate. CONCLUSION: The typical interictal pattern has the highest sensitivity. The clinical use of FRs is limited by their low sensitivity. SIGNIFICANCE: We suggest to analyze the typical interictal pattern first. FRs should be analyzed in a second step. If, for instance, a focus with FRs and no typical interictal pattern is found, this area could be considered for resection.

High-frequency oscillations during human focal seizures.

Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.

A system for automatic artifact removal in ictal scalp EEG based on independent component analysis and Bayesian classification.

OBJECTIVE: To devise an automated system to remove artifacts from ictal scalp EEG, using independent component analysis (ICA). METHODS: A Bayesian classifier was used to determine the probability that 2s epochs of seizure segments decomposed by ICA represented EEG activity, as opposed to artifact. The classifier was trained using numerous statistical, spectral, and spatial features. The system's performance was then assessed using separate validation data. RESULTS: The classifier identified epochs representing EEG activity in the validation dataset with a sensitivity of 82.4% and a specificity of 83.3%. An ICA component was considered to represent EEG activity if the sum of the probabilities that its epochs represented EEG exceeded a threshold predetermined using the training data. Otherwise, the component represented artifact. Using this threshold on the validation set, the identification of EEG components was performed with a sensitivity of 87.6% and a specificity of 70.2%. Most misclassified components were a mixture of EEG and artifactual activity. CONCLUSIONS: The automated system successfully rejected a good proportion of artifactual components extracted by ICA, while preserving almost all EEG components. The misclassification rate was comparable to the variability observed in human classification. SIGNIFICANCE: Current ICA methods of artifact removal require a tedious visual classification of the components. The proposed system automates this process and removes simultaneously multiple types of artifacts.

Independent component analysis identifies ictal bitemporal activity in intracranial recordings at the time of unilateral discharges.

OBJECTIVE: To apply independent component analysis (ICA) in intracranial recordings to analyze interactions during temporal lobe seizures. METHODS: Seizures from 20 patients with bitemporal implantation were classified as unilateral or bilateral and analyzed with ICA. During the period preceding bilateral activity, correlation coefficients were calculated between ICA components having ictal activity during the unilateral seizure phase (early ICA components) and every channel of the original EEG. ICA components were classified as unilateral if the correlation was >0.2 exclusively with channels in one hemisphere; and bilateral if both hemispheres were involved. RESULTS: One hundred twenty-three seizures were analyzed. Thirty-two percent of visually classified unilateral seizures and 64% of bilateral seizures (during the unilateral phase) had bilateral ICA components. The proportion of early ICA components that were bilateral and the proportion of channels contralateral to the visually identified seizure with correlation higher than 0.2 with at least one early ICA component were significantly lower in seizures that stayed unilateral than in seizures that later became bilateral by visual inspection (11 and 10%, respectively, in unilateral seizures; 33 and 28% in bilateral seizures; P=0.001). CONCLUSIONS: In patients with bitemporal epilepsy, approximately 20% of the components extracted using ICA have a bitemporal distribution even at the time when the seizures are apparently unilateral. The presence of early contralateral ictal activity is more frequent and extensive in seizures that later become evidently bilateral. SIGNIFICANCE: Minimal contralateral seizure activity is present even when the discharge appears unilateral and this is more frequent in seizures which later spread to the contralateral temporal lobe.

Cortical and thalamic fMRI responses in partial epilepsy with focal and bilateral synchronous spikes.

OBJECTIVE: To determine the blood oxygen level-dependent (BOLD) responses to epileptic discharges in the thalamus and cerebral cortex in patients with partial epilepsy. METHODS: Among 64 tested patients, 40 had EEG spikes during scanning and were divided in two groups: unilateral or bilateral independent spikes (29 patients) and bilaterally synchronous spikes (11 patients). Each spike topography was analyzed separately, yielding 40 studies in the first group and 17 in the second. RESULTS: Forty-five percent of focal spike studies showed significant BOLD responses. Cortical activation (positive BOLD) represented the dominant response and had a better correlation with spike location than cortical deactivation (negative BOLD). In the second group, all patients had significant BOLD responses; they were more widespread compared to the first group, and deactivated areas were as important as activated regions. A thalamic response was seen in 12.5% of studies in the first group and 55% in the second. CONCLUSIONS: The thalamus is involved in partial epilepsy during interictal discharges. This involvement and also cortical deactivation are more commonly seen with bilateral spikes than focal discharges. SIGNIFICANCE: These findings show evidence for a role for the thalamus and a more important role for inhibition in secondary bilateral synchrony.

A system to detect the onset of epileptic seizures in scalp EEG.

OBJECTIVE: A new method for automatic seizure detection and onset warning is proposed. The system is based on determining the seizure probability of a section of EEG. Operation features a user-tuneable threshold to exploit the trade-off between sensitivity and detection delay and an acceptable false detection rate. METHODS: The system was designed using 652 h of scalp EEG, including 126 seizures in 28 patients. Wavelet decomposition, feature extraction and data segmentation were employed to compute the a priori probabilities required for the Bayesian formulation used in training, testing and operation. RESULTS: Results based on the analysis of separate testing data (360 h of scalp EEG, including 69 seizures in 16 patients) initially show a sensitivity of 77.9%, a false detection rate of 0.86/h and a median detection delay of 9.8 s. Results after use of the tuning mechanism show a sensitivity of 76.0%, a false detection rate of 0.34/h and a median detection delay of 10 s. Missed seizures are characterized mainly by subtle or focal activity, mixed frequencies, short duration or some combination of these traits. False detections are mainly caused by short bursts of rhythmic activity, rapid eye blinking and EMG artifact caused by chewing. Evaluation of the traditional seizure detection method of using both data sets shows a sensitivity of 50.1%, a false detection rate of 0.5/h and a median detection delay of 14.3 s. CONCLUSIONS: The system performed well enough to be considered for use within a clinical setting. In patients having an unacceptable level of false detection, the tuning mechanism provided an important reduction in false detections with minimal loss of detection sensitivity and detection delay. SIGNIFICANCE: During prolonged EEG monitoring of epileptic patients, the continuous recording may be marked where seizures are likely to have taken place. Several methods of automatic seizure detection exist, but few can operate as an on-line seizure alert system. We propose a seizure detection system that can alert medical staff to the onset of a seizure and hence improve clinical diagnosis.

The relation of spike foci and of clinical seizure characteristics to different patterns of mesial temporal atrophy.

We reviewed clinical data and scalp electroencephalograms in 61 consecutive patients with temporal lobe epilepsy and mesial temporal atrophy assessed with volumetric magnetic resonance imaging: 39 patients had unilateral and 22 patients had bilateral atrophy. We attempted to determine whether any aspects of seizure symptoms and any electrographic features could be correlated to degree and anatomic pattern of mesial temporal atrophy. Spikes were always confined to temporal regions and were frequently bilateral without a statistically significant difference between patients with unilateral atrophy (33%) and those with bilateral atrophy (50%). Twenty-five of 40 foci associated with amygdala atrophy had maximum field over the anterior temporal regions. In contrast, 19 of 19 foci with isolated hippocampal formation atrophy were never maximum anteriorly. Secondarily generalized seizures and temporal lobe syncopes were correlated with anatomically extensive, particularly amygdala, atrophy. Prolonged postictal confusion was always associated with bitemporal abnormalities in the form of atrophy or spiking. These results explain some of the variability in the clinical and electrographic manifestations of temporal epilepsy and outline the specific role of amygdala involvement in addition to the commonly reported hippocampal atrophy.

Changes in seizure activity following anticonvulsant drug withdrawal.

We retrospectively studied the effects of changing antiepileptic drug levels on patterns of seizure discharge in 8 patients investigated with intracerebral electrodes during presurgical evaluation. We compared seizures recorded at high levels of medication to seizures recorded at low levels for changes in seizure duration, duration from unilateral onset to contralateral spread, inter- and intrahemispheric coherence, and morphology of EEG discharges. Seizures were more frequent with low medication, as was secondary generalization. Reduction in medication did not affect the morphology of discharges at onset, duration to contralateral spread, and coherence between EEG discharges. Seizures of similar type (eg, complex partial seizures without secondary generalization) were not longer with low than with high medication. Whereas medication clearly affects seizure frequency and generalization, it has little effect on the pattern of early parts of seizures. In particular, we found no evidence that seizure discharges become bilateral or generalized more quickly when medication is reduced.

A seizure warning system for long-term epilepsy monitoring.

We developed a system to provide a warning early in the development of a seizure with a reasonably low false alarm rate. Such a warning will improve the close observation of seizures and interaction between observers and patients early in the seizure, even in seizures having no obvious clinical manifestation. The system relies on the availability of the EEG recording of one sample seizure, which is used as a template for subsequent detection. We evaluated the performance in 24 seizure types from scalp and intracerebral recordings. It yielded a 100% detection rate and a false alarm rate averaging one false alarm every 5 hours. The warning signal was given, on average, 9.6 seconds after EEG seizure onset. The system will be useful in improving the clinical observation of seizures and may allow ictal SPECT scans to be more widely performed.

The EEG in deep midline lesions.

We studied the electroencephalograms (EEGs) of 154 patients with well-defined diencephalic, mesencephalic, or posterior fossa lesions. Electrographic and clinical parameters were statistically evaluated. The results indicated considerable overlap of EEG abnormalities from different subcortical sites. Focal or lateralized abnormalities were relatively specific, suggesting a diencephalic lesion, whereas bilateral paroxysmal slow-wave disturbances were unspecific and not of precise diagnostic significance. There was no specific feature in this series to clearly distinguish the EEG pattern in deep midline lesions from that seen with diffuse cortical and subcortical encephalopathies.

Interictal spiking during wakefulness and sleep and the localization of foci in temporal lobe epilepsy.

We examined variations in interictal spiking during sleep and wakefulness to assess differences in reliability for localizing epileptic foci. Forty patients were studied prospectively. Spikes were assessed for rates, field, and appearance of new foci. Final localization was determined by surgery, electrocorticography, and seizure onset. Comparison of interictal EEG foci with final localization was made. In 39 patients, slow-wave sleep activated spiking compared with wakefulness. Most patients showed maximal spiking in sleep stages 3 or 4. Restriction of field in rapid eye movement (REM) sleep and wakefulness, and extension of field in slow-wave sleep occurred. New foci appeared in non-rapid eye movement sleep in 53% of patients. Similar but not identical spiking rates, foci, and field distributions were seen in wakefulness and REM sleep. All REM foci were unilateral. Our findings suggest that localization of the primary epileptogenic area is more reliable in REM sleep than in wakefulness, and in wakefulness more than in slow-wave sleep.

Intracranial EEG study of brain structures affected by internal carotid injection of amobarbital.

Hippocampal function, considered critical in memory processing, is supposedly tested in the intracarotid sodium amobarbital (ISA) procedure; however, since the hippocampus is not completely irrigated by the internal carotid artery, some believe the procedure may be invalid for memory testing. We quantified delta activity in intracerebral EEGs during ISA tests. There was increased delta in ipsilateral structures as follows: amygdala (6.4 minutes), anterior hippocampus (7.2), middle hippocampus (7.4), temporal neocortex (9.1), frontal lobe (8.4), central/parietal area (11.0), and occipital lobe (9.7). Contralateral structures usually (> 64%) showed increased delta lasting 4 to 5 minutes. The ipsilateral hippocampus had delta waves in over 90% of injections. We conclude that the hippocampus is clearly affected by the ISA injection. We argue that the slow waves may not be caused by a direct effect of the drug, but rather by a functional deafferentation due to the profound inactivation of structures surrounding the hippocampus. Similarly, slow waves contralateral to injection may be caused by sudden removal of neuronal input from the regions receiving the amobarbital.

Patterns of seizure activation after withdrawal of antiepileptic medication.

Effects of withdrawal of anticonvulsant drugs on the temporal profile of occurrence and the type of seizures were investigated in 40 intractable epileptic patients who were candidates for surgical treatment. EEG and behavior were monitored while drugs were reduced to allow localization of the epileptogenic region. The rapid withdrawal of drugs caused a rebound effect, triggering either generalized seizures during a brief period or a longer-lasting increase in partial seizures. These increases in seizure frequency appeared related to change in dosage rather than to dosage itself, since they remained largely confined to the early period following reduction of an anticonvulsant.

Excitatory amino acids are elevated in human epileptic cerebral cortex.

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)--epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)--temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (mumol/g protein, mean +/- SEM): glutamate--spiking 109.8 +/- 1.8, nonspiking 87.4 +/- 2.0 (p less than 0.001); aspartate--spiking 15.2 +/- 0.9, nonspiking 12.2 +/- 0.5 (p less than 0.05); GABA--spiking 15.0 +/- 1.0, nonspiking 13.9 +/- 1.4 (NS); taurine--spiking 14.5 +/- 0.8, nonspiking 12.2 +/- 0.8 (NS); and glycine--spiking 11.5 +/- 0.8, nonspiking 7.4 +/- 0.6 (p less than 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.