Electrical brain-stimulation paradigm for estimating the seizure onset site and the time to ictal transition in temporal lobe epilepsy.

OBJECTIVE: To explore and validate a novel stimulation and analysis paradigm proposed to monitor spatial distribution and temporal changes of the excitability state in patients with temporal lobe epilepsy (TLE). METHODS: We use intermittent pulse stimulation in the frequency range 10-20Hz. A quantitative measure of spectral phase de-modulation, the relative phase clustering index (rPCI) was applied to the evoked EEG signals, measured from electrodes implanted in the hippocampal formation. RESULTS: We found that in the interictal periods, high values of rPCI recorded from specific sites were correlated with the most probable seizure onset sites (SOS). Furthermore we found that high values of rPCI from certain locations correlated with shorter time intervals to the next seizure. CONCLUSIONS: Our clinical findings indicate that although the precise moment of ictal transitions is in general unpredictable, it may be possible to estimate the probability of occurrence of some epileptic seizures. SIGNIFICANCE: The use of the rPCI for probabilistic forecasting of upcoming epileptic seizures is warranted. rPCI measurements may be used to guide interventions with the aim of modifying local tissue excitability that ultimately might prevent ictal transitions.

Spike cluster analysis in neocortical localization related epilepsy yields clinically significant equivalent source localization results in magnetoencephalogram (MEG).

OBJECTIVE: In magnetoencephalogram (MEG) recordings of patients with epilepsy several types of sharp transients with different spatiotemporal distributions are commonly present. Our objective was to develop a computer based method to identify and classify groups of epileptiform spikes, as well as other transients, in order to improve the characterization of irritative areas in the brain of epileptic patients. METHODS: MEG data centered on selected spikes were stored in signal matrices of C channels by T time samples. The matrices were normalized and euclidean distances between spike representations in vector space R(CxT) were input to a Ward's hierarchical clustering algorithm. RESULTS: The method was applied to MEG data from 4 patients with localization-related epilepsy. For each patient, distinct spike subpopulations were found with clearly different topographical field maps. Inverse computations to selected spike subaverages yielded source solutions in agreement with seizure classification and location of structural lesions, if present, on magnetic resonance images. CONCLUSIONS: With the proposed method a reliable categorization of epileptiform spikes is obtained, that can be applied in an automatic way. Computation of subaverages of similar spikes enhances the signal-to-noise ratio of spike field maps and allows for more accurate reconstruction of sources generating the epileptiform discharges.

Gamma-band phase clustering and photosensitivity: is there an underlying mechanism common to photosensitive epilepsy and visual perception?

Photosensitive epilepsy (PSE) is the most common form of human reflex epilepsy, appearing in up to 10% of epileptic children. It also offers a highly reproducible model to investigate whether changes in neuronal activity preceding the transition to an epileptic photoparoxysmal response (PPR) may be detected. We studied 10 patients with idiopathic PSE (eight female, mean age 26 years, range 9-51 years) using magnetoencephalography. In addition, we also studied the responses of five normal controls (mean age 24 years, age range 9-35 years) and three non-photosensitive epileptic patients (mean age 10 years, range 8-11 years). Spectral analysis of the MEG signals recorded during intermittent photic stimulation revealed relevant information in the phase spectrum. To quantify this effect, we introduced a second order response feature of the stimulus-triggered visual response preceding the PPR: the phase clustering index, which measures how close the phases of successive periods are grouped for each frequency component for all periods of the stimuli applied. We recorded a total of 86 PPRs, including several absence seizures, in nine of the 10 patients. We found that an enhancement of phase synchrony in the gamma-band (30-120 Hz), harmonically related to the frequency of stimulation, preceded the stimulation trials that evolved into PPRs, and differed significantly from that encountered in trials not followed by PPR or in control subjects. This novel finding leads us to postulate that a pathological deviation of normally occurring synchronization of gamma oscillations, underlying perceptional processes, mediates the epileptic transition in PSE.

[New developments in clinical neurophysiology: magnetoencephalography. Contributions of magnetoencephalography to the study of epilepsy]. / Nuevas técnicas en neurofisiología: magnetoencefalografía. Contribuciones de la magnetoencefalografía al estudio de la epilepsia.

INTRODUCTION: Magnetoencephalography (MEG) is a novel neurophysiological technique based on the detection of the tiny cerebral magnetic fields generated by the intracellular electrical currents. DEVELOPMENT: It offers several theoretical advantages to electroencephalography, like the transparency of the skull and soft tissues to the magnetic signal and the sensitivity to tangential fields generated in the cerebral sulci. Both properties allow an easier and more accurate modelling of the intracerebral sources. Furthermore, both techniques are complementary. On the other hand, its cost is the most limiting factor for its routine implementation in clinical practice. MEG is fully integrated with neuroimaging giving rise to the term magnetic source imaging. Integration with other neuroimaging modalities such us functional magnetic resonance imaging constitutes one of the major developments for the future. CONCLUSION: In this review, we present an overview of the physiological basis and technical aspects of magnetoencephalography, its comparison with electroencephalography, and its increasing number of clinical applications in the study of the different epilepsy syndromes as well as its role in epilepsy surgery.

Non-linear analysis of intracranial human EEG in temporal lobe epilepsy.

OBJECTIVE: Intracranial EEG recordings from patients suffering from medically intractable temporal lobe epilepsy were analyzed with the aim of characterizing the dynamics of EEG epochs recorded before and during a seizure and comparing the classification of the EEG epochs on the basis of visual inspection to the results of the numerical analysis. METHODS: The stationarity of the selected EEGs was assessed qualitatively. The coarse-grained correlation dimension and coarse-grained correlation entropy were used for the non-linear characterization of the EEG epochs. RESULTS: High-pass filtering was necessary in order to make the majority of the epochs appear stationarity beyond a time scale of about 2 s. It was found that the dimension of the ictal EEGs decreased with respect to the epochs containing ongoing (interictal) activity. The entropy of the ictal recordings however increased. A scaling of the entropy was applied and it was found that the scaled entropy of the ictal EEG decreased, consistent with the increased regularity of the ictal EEG. The coarse-grained quantities discriminated well between EEG epochs recorded prior to and during seizures at locations displaying ictal activity and classification improved by including the linear autocorrelation time in the analysis. CONCLUSIONS: It is concluded that ictal and non-ictal EEG can be well distinguished on the basis of non-linear analysis. The results are in good agreement with the visual analysis.

Comparison of combined versus subdural or intracerebral electrodes alone in presurgical focus localization.

PURPOSE: The yield of subdural versus intracerebral electrodes for ictal localization remains a point of controversy. We assessed the relative sensitivity of these two types of electrodes per case. METHODS: Eighty-three intracranial recordings obtained from 82 patients were retrospectively reviewed to establish which type of electrode performed best in which patients and which seizure types. RESULTS: Sixty (73%) of 82 patients had temporal lobe seizure onsets, eight frontal, nine widespread or multifocal/multilobar or both, whereas in five, seizure onset was not localized. Exclusive use of intracerebral electrodes would have been sufficient for accurate localization of the seizure-onset zone in all 35 patients with strictly mesial temporal seizure onsets. In only 20 (57%) of these 35 patients, the same decision would have been reached with exclusive use of subdural electrodes. In widespread neocortical and mesial temporal seizures (n = 25), yield of both electrode types was at about the same level, but neither was sufficient to identify the zone of ictal onset on its own. In frontal or multilobar seizures (n = 22), yield of subdural electrodes was slightly better then that of the intracerebral electrodes, but was not sufficient in all cases. CONCLUSIONS: This study indicates that, depending on the characteristics of the seizure disorder, exclusive use of either intracerebral or subdural electrodes may easily result in erroneous diagnosis because of insufficient sampling of the brain. These findings are in contrast with other studies emphasizing the high yield of reliable EEG findings in evaluations with a single type of electrode and corroborate the results of one of our previous studies.

Intracranial EEG seizure-offset termination patterns: relation to outcome of epilepsy surgery in temporal lobe epilepsy.

PURPOSE: Studies using stereo-EEG (SEEG) and electrocorticography (ECoG) should not only identify a patient's epileptogenic zone, but also should provide prognostic information for surgical outcome. In this respect, seizure-offset patterns have so far been the subject of only one study, in which they were shown to be associated with poor outcome when recorded over cortical areas outside the temporal lobe of seizure onset. To clarify whether seizure-offset patterns are reliable in predicting seizure outcome, we studied SEEG/ECoG in a similar group of patients with temporal lobe epilepsy (TLE). METHODS: SEEG/ECoG records of 44 patients with refractory TLE were analyzed. The areas of seizure termination were classified as ipsilateral or contralateral (mesial and/or lateral) temporal, (temporal and) frontal, and diffuse/bilateral. Patients were classified with respect to seizure outcome as either seizure-free (UCLA class 1a) or not seizure free (UCLA class 2-4); both groups were correlated with specific seizure-offset categories using Fisher's exact probability test and analysis of variance (ANOVA). RESULTS: Of the 44 patients, the majority (n = 36) had at least part of their seizure offsets in the ipsilateral temporal lobe, whereas 8 patients manifested no seizure offsets in this lobe. Only 9 patients (20%) showed exclusive offsets in the ipsilateral temporal lobe. No statistically significant difference was evident between patients with all seizure offsets in the ipsilateral temporal lobe and those with offsets elsewhere. Similarly, no statistically significant difference was evident between patients with a diffuse seizure offset and those with seizure offsets of a different category. CONCLUSIONS: Seizure-offset patterns in SEEG/ECoG are unreliable in predicting seizure outcome after resective activity surgery for TLE.

Nonlinear dynamics of epileptic seizures on basis of intracranial EEG recordings.

PURPOSE: An understanding of the principles governing the behavior of complex neuronal networks, in particular their capability of generating epileptic seizures implies the characterization of the conditions under which a transition from the interictal to the ictal state takes place. Signal analysis methods derived from the theory of nonlinear dynamics provide new tools to characterize the behavior of such networks, and are particularly relevant for the analysis of epileptiform activity. METHODS: We calculated the correlation dimension, tested for irreversibility, and made recurrence plots of EEG signals recorded intracranially both during interictal and ictal states in temporal lobe epilepsy patients who were surgical candidates. RESULTS: Epileptic seizure activity often, but not always, emerges as a low-dimensional oscillation. In general, the seizure behaves as a nonstationary phenomenon during which both phases of low and high complexity may occur. Nevertheless a low dimension may be found mainly in the zone of ictal onset and nearby structures. Both the zone of ictal onset and the pattern of propagation of seizure activity in the brain could be identified using this type of analysis. Furthermore, the results obtained were in close agreement with visual inspection of the EEG records. CONCLUSIONS: Application of these mathematical tools provides novel insights into the spatio-temporal dynamics of "epileptic brain states". In this way it may be of practical use in the localization of an epileptogenic region in the brain, and thus be of assistance in the presurgical evaluation of patients with localization-related epilepsy.

Alpha rhythms: noise, dynamics and models.

Alpha rhythms appear as sinusoidal-like oscillations in the electroencephalogram (EEG) within the frequency range 8-12 Hz that waxe and wane in a more or less irregular way. The irregularity may have various origins. It may be due to noise or the oscillations may have an intrinsic irregular character, e.g. they may be generated by chaotic processes [Jansen (1991) Quantitative analysis of electroencephalograms: is there chaos in the future? Int. J. Biomed. Comput., 27: 95-123; Pradham, N. and Dutt, D.N. (1993) A nonlinear perspective in understanding the neurodynamics of EEG. Comput. Biol. Med., 23: 425-442; Pritchard et al. (1995) Dimensional analysis of resting human EEG II: Surrogate-data testing indicates nonlinearily but not low-dimensional chaos. Psychophysiology. 32: 486]. The term noise is often used in neurophysiology with different connotations as pointed out by Bullock (1990), either meaning an unwanted signal from the point of view of the receiver of a message, or a signal with intrinsic random fluctuations, i.e. with a stochastic character. Here we consider noise in this sense, as random or quasi-random neural activity. In this overview, we concentrate on the question of whether alpha rhythms should be considered generated in neuronal networks (1) as forms of filtered noise, (2) as deterministic oscillations influenced by noise or (3) as the result of chaotic dynamics. A clear answer to this question can have theoretical value because it may lead to a general model of the generation of this important EEG signal. Such a model, of course, would be a macroscopic one, since it would primarily account for the properties of the alpha rhythms at the neuronal network level. A translation of these properties to the microscopic, i.e. neuronal, level will not be easy to achieve without more direct knowledge of the membrane and synaptic basic properties of the neurons involved. Here we consider the question formulated above by presenting some relevant experimental evidence and theoretical arguments. The consideration whether alpha rhythms may have noise or chaotic sources implies examining how and where such sources can occur in the neuronal networks of the brain. Therefore we present, first, some basic data regarding the possible origin of noise and of chaos in neuronal networks. Second, the signal analysis methods that have to be applied in order to discriminate between filtered noise activities and chaotic oscillations are introduced. Third, the implications of these signal analyses regarding the possible answer to the initial question are discussed.

Regional brain glucose metabolism in patients with complex partial seizures investigated by intracranial EEG.

We performed interictal 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) studies in 57 patients with complex partial epilepsy (CPE), not controlled by medical treatment and considered for surgical resection of their epileptic focus. A precise localization of the epileptic focus was obtained in 37 of these patients with a combination of subdural and depth electrodes. We visually inspected the metabolic images; we also measured glucose consumption in a number of brain regions and compared the values with those obtained in 17 normal controls. Eighty-two percent of the 57 patients had an area of glucose hypometabolism on the 18FDG-PET images. Six patients had a frontal epileptic focus, 3 of them had a frontal lobe hypometabolism. Twenty-six patients had a unilateral temporal lobe focus and all of them displayed a temporal lobe hypometabolism. The asymmetry was more pronounced in the lateral temporal cortex (-20%) than in the mesial part of the temporal lobe (-9.6%). In each cortical brain region on the side of the epileptic focus (except the sensorimotor cortex), glucose consumption rate was lower than in the contralateral region or than in controls. No differences could be found between patients with a seizure onset restricted to the hippocampus and patients with a seizure onset involving the hippocampus and the adjacent neocortex. Divergent metabolic patterns were obtained in 5 patients with bilateral temporal seizure foci. Combined with other non invasive techniques (EEG, neuroradiology), PET contributes increasingly to the selection of patients with CPE who could benefit from surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

On-line detection of transient neuropsychological disturbances during EEG discharges in children with epilepsy.

Short-term memory tasks (visual-spatial and verbal) were devised to identify the influence of transient EEG discharges, without clinically manifest disturbances, on neuropsychological performance. 53 children with subclinical focal and generalized EEG discharges were tested 72 times and 16-channel telemetered EEG and video-recordings were made. 36 per cent of test sessions showed a significant preponderance of errors when discharges were recorded. Children with right-sided discharges had impaired performance in 50 per cent of their test sessions, with performance on the visual-spatial task most affected: left-sided discharges appeared to exert greater influence on the verbal task. These tests can easily be used to monitor six- to 15-year-old children.

Combined use of subdural and intracerebral electrodes in preoperative evaluation of epilepsy.

For intracranial recording of partial seizures considered to originate from one of the temporal or frontal lobes, the team in the Utrecht Academic Hospital has used subdural, multicontact, flexible electrodes since 1972. These are introduced through bilateral, frontocentral trephine holes and are manipulated under fluoroscopy to cover most of the cerebral convexity. It became evident that in many patients, additional placements to record from intracerebral structures were indispensable. Therefore, using the same trephine holes, an additional 2 to 4 depth electrodes were stereotactically implanted in the mesial temporal and/or frontal structures, as appropriate. An extensive intra- and extracerebral spatial representation of the epileptogenic zone was thus obtained. We report here the methods for manufacturing and applying these electrodes and our clinical experience with 28 patients. The results obtained so far stress the value of combining subdural and depth electroencephalographic monitoring in the presurgical selection of patients suffering from medically refractory complex partial seizures. By miniaturizing the electrodes, extensive areas of the brain can be investigated without craniotomy or multiple burr holes.

Quantitative analysis of 18/FDG-PET in the presurgical evaluation of patients suffering from refractory partial epilepsy. Comparison with CT, MRI, and combined subdural and depth. EEG.

CT, MRI, 18/FDG-PET and Depth. EEG, performed with subdural and depth electrodes were part of the presurgical evaluation in 22 patients. Statistical analysis of 18/FDG-PET was performed to compare cerebral utilization of glucose to that of normal age matched controls. The findings of CT, MRI, and quantitative analysis of PET are compared with those of ictal Depth. EEG. A positive correlation between CT and Depth. EEG was obtained in 23% of the patients and between MRI and Depth. EEG. in 50%. For both imaging techniques a negative correlation was found in 5%. Regional abnormalities were found with quantified PET in 95% of the patients and were concordant with Depth. EEG. for side of onset in 77% of the patients and for lobe of onset in 59%. A possibly false localising PET result for lobe of onset was obtained in 8 patients (36%). Limitations of PET were most apparent in patients with regional mesiolimbic or bilateral seizure onset. A favourable outcome of surgery was associated usually with positive convergence of both methods. PET may be a valuable contribution to the research and management of partial complex epilepsy, but at present cannot be considered a reliable alternative to invasive EEG methods in patients without clear unilateral focus localization on surface EEG.

Identification of the side of epileptic focus with 123I-Iomazenil SPECT. A comparison with 18FDG-PET and ictal EEG findings in patients with medically intractable complex partial seizures.

123I-Iomazenil SPECT was performed in 17 patients who were considered candidates for surgery of epilepsy because of medically intractable complex partial seizures. In addition to this examination their presurgical evaluation consisted of long term ictal EEG-CCTV monitoring, CT, MRI and 18FDG PET. In eight patients intracranial ictal EEG recordings were performed. SPECT was assessed visually while PET data were analyzed quantitatively. Both SPECT and PET were compared to ictal EEG data and showed asymmetries in over 80% of patients in agreement with EEG findings. These three methods were in agreement in 65% of patients. SPECT showed abnormality contralateral to the EEG focus in one patient (6%) while PET always demonstrated ipsilateral dysfunction. It is concluded that 123I-Iomazenil SPECT may be considered a more economical and more widely available alternative to 18FDG PET in the presurgical evaluation of patients with medically intractable complex partial seizures. In this respect 123I-Iomazenil specifically reflects functional changes in the membranes of neurons while 18FDG is related to glucose metabolism not only of neurons but also of glial cells.

Relationship between blood viscosity and cerebral ischemia after surgical treatment of ruptured intracranial aneurysms.

To determine the role of blood viscosity after surgical treatment of ruptured intracranial aneurysms, the relationship between blood viscosity and clinical condition was examined in 17 patients. A total of 213 blood samples were analyzed. An inverse correlation was found between blood viscosity and level of consciousness; in addition, blood viscosity was higher when focal neurologic deficit was observed. Hematocrit was similarly related to clinical condition, although the correlations observed were less strong. Postoperative plasma viscosity was higher in patients with focal neurologic deficit. Regular blood viscosity measurements are of value in patients at risk for developing cerebral ischemia.