Complex observation of scalp fast (40-150 Hz) oscillations in West syndrome and related disorders with structural brain pathology.
ABSTRACT: We investigated the relationship between the scalp distribution of fast (40-150 Hz) oscillations (FOs) and epileptogenic lesions in West syndrome (WS) and related disorders. Subjects were 9 pediatric patients with surgically confirmed structural epileptogenic pathology (age at initial electroencephalogram [EEG] recording: mean 7.1 months, range 1-22 months). The diagnosis was WS in 7 patients, Ohtahara syndrome in 1, and a transitional state from Ohtahara syndrome to WS in the other. In the scalp EEG data of these patients, we conservatively detected FOs, and then examined the distribution of FOs. In five patients, the scalp distribution of FOs was consistent and concordant with the lateralization of cerebral pathology. In another patient, FOs were consistently dominant over the healthy cerebral hemisphere, and the EEG was relatively low in amplitude over the pathological atrophic hemisphere. In the remaining 3 patients, the dominance of FOs was inconsistent and, in 2 of these patients, the epileptogenic hemisphere was reduced in volume, which may result from atrophy or hypoplasia. The correspondence between the scalp distribution of FOs and the epileptogenic lesion should be studied, taking the type of lesion into account. The factors affecting scalp FOs remain to be elucidated.
Project description:We investigated temporal and spatial characteristics of ictal gamma and beta activity on scalp EEG during spasms in patients with West syndrome (WS) to evaluate potential focal cortical onset.A total of 1,033 spasms from 34 patients with WS of various etiologies were analyzed on video-electroencephalography (EEG) using time-frequency analysis. Ictal gamma (35-90 Hz) and beta (15-30 Hz) activities were correlated with visual symmetry of spasms, objective EMG (electromyography) analysis, and etiology of WS.Prior to the ictal motor manifestation, focal ictal gamma activity emerged from one hemisphere (71%, 24/34) or from midline (26%, 9/34), and was rarely simultaneously bilateral (3%, 1/34). Focal ictal beta activity emerged from either one hemisphere (68%, 23/34) or from midline (32%, 11/34). Onsets of focal ictal gamma and beta activity were most commonly observed around the parietal areas. Focal ictal gamma activity propagated faster than ictal beta activity to adjacent electrodes (median: 65 vs. 170 msec, p < 0.01), and to contralateral hemisphere (median: 100 vs. 170 msec, p = 0.01). Asymmetric peak amplitude of ictal gamma activity in the centroparietal areas (C3-P3 vs. C4-P4) correlated with asymmetric semiology. On the other hand, most of the visually symmetric spasms showed asymmetry in peak amplitude and interhemispheric onset latency difference in both ictal gamma and beta activity.Spasms may be a seizure with focal electrographic onset regardless of visual symmetry. Asymmetric involvement of ictal gamma activity to the centroparietal areas may determine the motor manifestations in WS. Scalp EEG ictal gamma and beta activity may be useful to demonstrate localized seizure onset in infants with WS.
Project description:We present a framework to detect fast oscillations (FOs) in magnetoencephalography (MEG) and to perform magnetic source imaging (MSI) to determine the location and extent of their generators in the cortex. FOs can be of physiologic origin associated to sensory processing and memory consolidation. In epilepsy, FOs are of pathologic origin and biomarkers of the epileptogenic zone. Seventeen patients with focal epilepsy previously confirmed with identified FOs in scalp electroencephalography (EEG) were evaluated. To handle data deriving from large number of sensors (275 axial gradiometers) we used an automatic detector with high sensitivity. False positives were discarded by two human experts. MSI of the FOs was performed with the wavelet based maximum entropy on the mean method. We found FOs in 11/17 patients, in only one patient the channel with highest FO rate was not concordant with the epileptogenic region and might correspond to physiologic oscillations. MEG FOs rates were very low: 0.02-4.55 per minute. Compared to scalp EEG, detection sensitivity was lower, but the specificity higher in MEG. MSI of FOs showed concordance or partial concordance with proven generators of seizures and epileptiform activity in 10/11 patients. We have validated the proposed framework for the non-invasive study of FOs with MEG. The excellent overall concordance with other clinical gold standard evaluation tools indicates that MEG FOs can provide relevant information to guide implantation for intracranial EEG pre-surgical evaluation and for surgical treatment, and demonstrates the important added value of choosing appropriate FOs detection and source localization methods.
Project description:Routine scalp EEG is essential in the clinical diagnosis and management of epilepsy. However, a normal scalp EEG (based on expert visual review) recorded from a patient with epilepsy can cause delays in diagnosis and clinical care delivery. Here, we investigated whether normal EEGs might contain subtle electrophysiological clues of epilepsy. Specifically, we investigated (i) whether there are indicators of abnormal brain electrophysiology in normal EEGs of epilepsy patients, and (ii) whether such abnormalities are modulated by the side of the brain generating seizures in focal epilepsy. We analysed awake scalp EEG recordings of age-matched groups of 144 healthy individuals and 48 individuals with drug-resistant focal epilepsy who had normal scalp EEGs. After preprocessing, using a bipolar montage of eight channels, we extracted the fraction of spectral power in the alpha band (8-13 Hz) relative to a wide band of 0.5-40 Hz within 10-s windows. We analysed the extracted features for (i) the extent to which people with drug-resistant focal epilepsy differed from healthy subjects, and (ii) whether differences within the drug-resistant focal epilepsy patients were related to the hemisphere generating seizures. We then used those differences to classify whether an EEG is likely to have been recorded from a person with drug-resistant focal epilepsy, and if so, the epileptogenic hemisphere. Furthermore, we tested the significance of these differences while controlling for confounders, such as acquisition system, age and medications. We found that the fraction of alpha power is generally reduced (i) in drug-resistant focal epilepsy compared to healthy controls, and (ii) in right-handed drug-resistant focal epilepsy subjects with left hemispheric seizures compared to those with right hemispheric seizures, and that the differences are most prominent in the frontal and temporal regions. The fraction of alpha power yielded area under curve values of 0.83 in distinguishing drug-resistant focal epilepsy from healthy and 0.77 in identifying the epileptic hemisphere in drug-resistant focal epilepsy patients. Furthermore, our results suggest that the differences in alpha power are greater when compared with differences attributable to acquisition system differences, age and medications. Our findings support that EEG-based measures of normal brain function, such as the normalized spectral power of alpha activity, may help identify patients with epilepsy even when an EEG does not contain any epileptiform activity, recorded seizures or other abnormalities. Although alpha abnormalities are unlikely to be disease-specific, we propose that such abnormalities may provide a higher pre-test probability for epilepsy when an individual being screened for epilepsy has a normal EEG on visual assessment.
Project description:<h4>Objective</h4>To alert about the wide margin of unpredictability that distribution of somatic <i>MTOR</i> mosaicism may have in the brain and the risk for independent epileptogenesis arising from the seemingly healthy contralateral hemisphere after complete removal of epileptogenic focal cortical dysplasia (FCD).<h4>Methods</h4>Clinical, EEG, MRI, histopathology, and molecular genetics in 2 patients (1 and 2) treated with focal resections and subsequent complete hemispherectomy for epileptogenic FCD due to somatic <i>MTOR</i> mutations. Autoptic brain study of bilateral asymmetric hemispheric dysplasia and identification of alternative allele fraction (AAF) rates for <i>AKT1</i> (patient 3).<h4>Results</h4>The strongly hyperactivating p.Ser2215Phe (patient 1) and p.Leu1460Pro (patient 2) <i>MTOR</i> mutations were at low-level AAF in the dysplastic tissue. After repeated resections and eventual complete hemispherectomy, both patients manifested intractable seizures arising from the contralateral, seemingly healthy hemisphere. In patient 3, the p.Glu17Lys <i>AKT1</i> mutation exhibited random distribution and AAF rates in different tissues with double levels in the more severely dysplastic cerebral hemisphere.<h4>Conclusions</h4>Our understanding of the distribution of somatic mutations in the brain in relation to the type of malformation and its hypothesized time of origin may be faulty. Large studies may reveal that the risk of a first surgery being disappointing might be related more to the specific somatic mammalian target of rapamycin mutation identified than to completeness of resection and that the advantages of repeated resections after a first unsuccessful operation should be weighed against the risk of the contralateral hemisphere becoming in turn epileptogenic.
Project description:Simultaneous scalp EEG/functional MRI measures non-invasively haemodynamic responses to interictal epileptic discharges, which are related to the epileptogenic zone. High frequency oscillations are also an excellent indicator of this zone, but are primarily recorded from intracerebral EEG. We studied the spatial overlap of these two important markers in patients with drug-resistant epilepsy to assess if their combination could help better define the extent of the epileptogenic zone. We included patients who underwent EEG-functional MRI and later intracerebral EEG. Based on intracerebral EEG findings, we separated patients with unifocal seizures from patients with multifocal or unknown onset seizures. Haemodynamic t-maps were coregistered with the intracerebral electrode positions. Each EEG channel was classified as pertaining to one of the following categories: primary haemodynamic cluster (maximum t-value), secondary cluster (t-value > 90% of the primary cluster) or outside the primary and secondary clusters. We marked high frequency oscillations (ripples: 80-250 Hz; fast ripples: 250-500 Hz) during 1 h of slow wave sleep, and compared their rates in each haemodynamic category. After classifying channels as high- or low-rate, the proportion of high-rate channels within the primary or primary plus secondary clusters was compared to the proportion expected by chance. Twenty-five patients, 11 with unifocal and 14 with multifocal/unknown seizure onsets, were studied. We found a significantly higher median high frequency oscillation rate in the primary cluster compared to secondary cluster and outside these two clusters for the unifocal group (P < 0.0001), but not for the multifocal/unknown group. For the unifocal group, the number of high-rate channels within the primary or primary plus secondary clusters was significantly higher than expected by chance. This held only for the high-ripple-rate channels in the multifocal/unknown group. At the patient level, most patients (18/25, or 72%) had at least one high-rate channel within a primary cluster. In patients with unifocal epilepsy, the maximum haemodynamic response (primary cluster) related to scalp interictal discharges overlaps with the tissue generating high frequency oscillations at high rates. If intracranial EEG is warranted, this response should be explored. As a tentative clinical use of the combination of these techniques we propose that higher high frequency oscillation rates inside than outside the maximum response indicates that the patient has indeed a focal epileptogenic zone demarcated by this response, whereas similar rates inside and outside may indicate a widespread epileptogenic zone or an epileptogenic zone not covered by the implantation.
Project description:Volumetric and morphometric studies have demonstrated structural abnormalities related to chronic epilepsies on a cohort- and population-based level. On a single-patient level, specific patterns of atrophy or cortical reorganization may be widespread and heterogeneous but represent potential targets for further personalized image analysis and surgical therapy. The goal of this study was to compare morphometric data analysis in 37 patients with temporal lobe epilepsies with expert-based image analysis, pre-informed by seizure semiology and ictal scalp EEG. Automated image analysis identified abnormalities exceeding expert-determined structural epileptogenic lesions in 86% of datasets. If EEG lateralization and expert MRI readings were congruent, automated analysis detected abnormalities consistent on a lobar and hemispheric level in 82% of datasets. However, in 25% of patients EEG lateralization and expert readings were inconsistent. Automated analysis localized to the site of resection in 60% of datasets in patients who underwent successful epilepsy surgery. Morphometric abnormalities beyond the mesiotemporal structures contributed to subtype characterisation. We conclude that subject-specific morphometric information is in agreement with expert image analysis and scalp EEG in the majority of cases. However, automated image analysis may provide non-invasive additional information in cases with equivocal radiological and neurophysiological findings.
Project description:Brain connectivity analysis plays an essential role in the research of working memory that involves complex coordination of various brain regions. In this research, we present a comprehensive view of trans-states brain connectivity variation based on continuous scalp EEG, extending beyond traditional stimuli-lock averaging or restriction to short time scales of hundreds of milliseconds after stimulus onset. The scalp EEG was collected under three conditions: quiet, memory, and control. The only difference between the memory and control conditions was that in the memory condition, subjects made an effort to retain information. We started our investigation with calibrations of Pearson correlation in EEG analysis and then derived two indices, link strength and node connectivity, to make comparisons between different states. Finally, we constructed and studied trans-state brain connectivity variation topography. Comparing memory and control states with quiet state, we found that the beta topography highlights links between T5/T6 and O1/O2, which represents the visual ventral stream, and the gamma topography conveys strengthening of inter-hemisphere links and weakening of intra-hemisphere frontal-posterior links, implying parallel inter-hemisphere coordination combined with sequential intra-hemisphere coordination when subjects are confronted with visual stimuli and a motor task. For comparison between memory and control states, we also found that the node connectivity of T6 stands out in gamma topography, which provides strong proof from scalp EEG for the information binding or relational processing function of the temporal lobe in memory formation. To our knowledge, this is the first time for any method to effectively capture brain connectivity variation associated with working memory from a relatively large scale both in time (from a second to a minute) and in space (from the scalp). The method can track brain activity continuously with minimal manual interruptions; therefore, it has promising potential in applications such as brain computer interfaces and brain training.
Project description:In the present study, we used expression microarray to establish a transcriptome on epileptogenic zone versus irritative zone from removed brain tissues of patients affected with intractable neocortical epilepsies. Our results showed that expression profiling of a total of 30,968 human genes in 10 patients brain samples. Overall design: A total of 10 patients were recruited in this study. Mean age and period of intractable neocortical epilepsy were 19.8±2.5 and 13.7±2.3 years, respectively. After clinical evaluatng by EEG, SPEC, MRI, and v-EEG, patients were performed with surgical removal of epileptogenic zone and irritative zone. Removed surgical samples were obtained snap-frozen on dry ice for total RNA extraction commissined to Phalanx Biotech Group, Taiwan. RNA samples were evaluated using Human OneArray TM with 30,968 human genome probes.
Project description:<h4>Objective</h4>To report clinical experience with presurgical evaluation in patients with insulo-opercular epilepsy. Quantitative analysis on PET imaging and stereoelectroencephalography (SEEG) signals was used to summarize their electroclinical features.<h4>Methods</h4>Twenty-two patients with focal epilepsy arising from the insular and/or opercular cortex according to SEEG were retrospectively analyzed. Presurgical noninvasive data were analyzed in detail. Interictal PET data of patients were then statistically compared with those of healthy controls to identify the interictal hypometabolic network. The epileptogenicity index (EI) of ictal SEEG signal was computed to identify areas of spread at the beginning of seizure onset.<h4>Results</h4>Focal tonic seizures of the face and/or neck (16/22, 73%) were the most prevalent early objective signs. Epileptic discharges in the interictal and ictal scalp-EEG mostly showed an ipsilateral perisylvian distribution. Statistical analysis of interictal PET showed significant hypometabolism in the insular lobe, central operculum, supplementary motor area, middle cingulate cortex, bilateral caudate nuclei, and putamen. According to the EI analysis, insulo-opercular epilepsy could be classified as insulo-opercular epilepsy (50%), opercular epilepsy (41%), and insular cortex epilepsy (9%).<h4>Significance</h4>Clinical diagnosis of insulo-opercular epilepsy is challenging because of its complex seizure semiology and nonlocalizing discharges on scalp-EEG. A common hypometabolic network involving the insulo-opercular cortex, mesial frontal cortex and subcortical nuclei may be involved in the organization of the insulo-opercular epilepsy network. Furthermore, quantified SEEG analysis suggested that pure insular epilepsy is rare, and the close connection between insular and opercular cortex necessitates SEEG implantation to define the epileptogenic zone.
Project description:Resection of the seizure generating tissue can be highly beneficial in patients with drug-resistant epilepsy. However, only about half of all patients undergoing surgery get permanently and completely seizure free. Investigating the dependences between intracranial EEG signals adds a multivariate perspective largely unavailable to visual EEG analysis, which is the current clinical practice. We examined linear and nonlinear interrelations between intracranial EEG signals regarding their spatial distribution and network characteristics. The analyzed signals were recorded immediately before clinical seizure onset in epilepsy patients who received a standardized electrode implantation targeting the mesiotemporal structures. The linear interrelation networks were predominantly locally connected and highly reproducible between patients. In contrast, the nonlinear networks had a clearly centralized structure, which was specific for the individual pathology. The nonlinear interrelations were overrepresented in the focal hemisphere and in patients with no or only rare seizures after surgery specifically in the resected tissue. Connections to the outside were predominantly nonlinear. In all patients without worthwhile improvement after resective treatment, tissue producing strong nonlinear interrelations was left untouched by surgery. Our findings indicate that linear and nonlinear interrelations play fundamentally different roles in preictal intracranial EEG. Moreover, they suggest nonlinear signal interrelations to be a marker of epileptogenic tissue and not a characteristic of the mesiotemporal structures. Our results corroborate the network-based nature of epilepsy and suggest the application of network analysis to support the planning of resective epilepsy surgery.