EEG-fMRI study of the interictal epileptic activity in patients with partial epilepsy

PURPOSE: To investigate Blood Oxygen Level Dependent (BOLD) responses to interictal epileptic discharges (IEDs) during EEG-correlated functional MRI (EEG-fMRI) in patients with partial epilepsy. METHODS: We studied eight patients who had a diagnosis of partial epilepsy and active spiking on routine scalp EEG recording. Sessions of continuous EEG-fMRI were recorded, and spikes (identified after online artifact removal) were used as events in the fMRI analysis. Regions of BOLD signal change in response to interictal epileptic discharge were assessed and epileptogenic zone localization was electroclinically identified. RESULTS: Eight patients with partial epilepsy were recruited (6 males, 2 females, mean age 18.5, mean onset age range 0.5-29). Two who underwent EEG-fMRI were excluded from further analysis: one due to absence of epileptic discharges, the other due to excessive head motion. Eight sessions of EEG-fMRI scanning in 6 patients were obtained: 6 with activation and deactivation, one with activation only, and one with deactivation only. Focal activations corresponding to electroclinical localization occurred in 7 sessions, 5 of which were maximal. CONCLUSIONS: Maximally activated areas detected by EEG-fMRI in patients with partial epilepsy appear to be concordant with epileptogenic areas as defined by electroclinical localization data. In most patients with focal epilepsy, positive BOLD responses seem to be mainly in epileptogenic zones and the corresponding contralateral areas. Responses to deactivation seem less associated with IEDs. So EEG-fMRI is a useful tool to study the pathophysiological mechanisms of epilepsy and may assist in presurgical evaluation of epilepsy.     

Magnetoencephalography with temporal spread imaging to visualize propagation of epileptic activity

Objective

We describe temporal spread imaging (TSI) that can identify the spatiotemporal pattern of epileptic activity using Magnetoencephalography (MEG).

EEG-fMRI study of the ictal and interictal epileptic activity in patients with eyelid myoclonia with absences

Purpose: To investigate the blood oxygenation level‐dependent (BOLD) signal changes correlated with ictal and interictal epileptic discharges using electroencephalography‐correlated functional magnetic resonance imaging (EEG‐fMRI) in patients with eyelid myoclonia with absences (EMA) and then to explore the pathophysiological mechanisms of epileptic discharges and their effect on brain function. Methods: Four patients with EMA were investigated through the method of EEG‐fMRI. The characteristics of BOLD signal changes linked to ictal and interictal epileptic discharges under different states of consciousness were explored. Results: Seven sessions of EEG‐fMRI scanning in the four patients were obtained. The main regions of activation included thalamus, mesial frontal cortex, middle parietal lobe, temporal lobe, insula, midline structures, and cerebellum. Deactivations were mainly in the anterior frontal lobe, posterior parietal lobe, and posterior cingulate gyrus. Thalamic BOLD change was predominantly activation in most of our cases. The distribution of activation associated with ictal epileptic discharges was wider, and the distribution of deactivation was closer to pericortex compared with the BOLD change linked with interictal epileptic discharges. Conclusions: The activation in the thalamus may be associated with generalized spike wave in EMA; the combination of different patterns of activation with consistent pattern of deactivations (“default” pattern) in patients with EMA may prognosticate different states of consciousness in response to ictal and interictal epileptic discharges.     

fMRI activation in continuous and spike-triggered EEG-fMRI studies of epileptic spikes

PURPOSE: To evaluate functional magnetic resonance imaging (fMRI) with simultaneous EEG for finding metabolic sources of epileptic spikes. To find the localizing value of activated regions and factors influencing fMRI responses. METHODS: Patients with focal epilepsy and frequent spikes were subjected to spike-triggered or continuous fMRI with simultaneous EEG. Results were analyzed in terms of fMRI activation, concordance with the location of EEG spiking and anatomic MRI abnormalities, and other EEG and clinical variables. In four patients, results also were compared with those of intracerebral EEG. RESULTS: Forty-eight studies were performed on 38 patients. Seventeen studies were not analyzed, primarily because no spikes occurred during scanning. Activation was obtained in 39% of 31 studies, with an activation volume of 2.55 +/- 4.84 cc. Activated regions were concordant with EEG localization in almost all studies and confirmed by intracerebral EEG in four patients. Forty percent of patients without an MRI lesion showed activation; 37.5% of patients with a lesion had an activation; the activation was near or inside the lesion. Bursts of spikes were more likely to generate an fMRI response than were isolated spikes (76 vs. 11%; p < 0.05). CONCLUSIONS: Combining EEG and fMRI in focal epilepsy yields regions of activation that are presumably the source of spiking activity. These regions are highly linked with epileptic foci and epileptogenic lesions in a significant number of patients. Activation also is found in patients with no visible MRI lesion. Intracerebral recordings largely confirm that these activation regions represent epileptogenic areas. It is still unclear why many patients show no activation.     

Representation and propagation of epileptic activity in absences and generalized photoparoxysmal responses

Although functional imaging studies described networks associated with generalized epileptic activity, propagation patterns within these networks are not clear. In this study, electroencephalogram (EEG)‐based coherent source imaging dynamic imaging of coherent sources (DICS) was applied to different types of generalized epileptiform discharges, namely absence seizures (10 patients) and photoparoxysmal responses (PPR) (eight patients) to describe the representation and propagation of these discharges in the brain. The results of electrical source imaging were compared to EEG‐functional magnetic resonance imaging (fMRI) which had been obtained from the same data sets of simultaneous EEG and fMRI recordings. Similar networks were described by DICS and fMRI: (1) absence seizures were associated with thalamic involvement in all patients. Concordant results were also found for brain areas of the default mode network and the occipital cortex. (2) Both DICS and fMRI identified the occipital, parietal, and the frontal cortex in a network associated with PPR. (3) However, only when PPR preceded a generalized tonic‐clonic seizure, the thalamus was involved in the generation of PPR as shown by both imaging techniques. Partial directed coherence suggested that during absences, the thalamus acts as a pacemaker while PPR could be explained by a cortical propagation from the occipital cortex via the parietal cortex to the frontal cortex. In conclusion, the electrical source imaging is not only able to describe similar neuronal networks as revealed by fMRI, including deep sources of neuronal activity such as the thalamus, but also demonstrates interactions interactions within these networks and sheds light on pathogenetic mechanisms of absence seizures and PPR. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

EEG-fMRI as an useful tool to detect epileptic foci associated with secondary bilateral synchrony

IntroductionTailoring the epileptic cortex is the key issue in the pre-surgical work-up of patients with pharmacoresistant focal epilepsy. Not always, however, the conventional MRI and the scalp EEG are able to provide the information needed to address this issue since the imaging may be normal (criptogenetic epilepsy) and the EEG, even ictal, poorly localizing.Patient and methodsWe present a case of focal criptogenetic epilepsy with speech arrest seizures and bilateral synchronous spike and wave scalp EEG pattern (secondary bilateral synchrony). The patient underwent an EEG-fMRI continuous co-registration.ResultsThe EEG-fMRI showed a clear cut activation of a BOLD signal during the epileptic discharge over the left Supplementary Motor Area (SMA) and, on lesser degree, over the homolateral motor strip.DiscussionKnowledge and expertise about this technique has greatly increased over the last few years making it an useful tool for localizing purposes specially in patients with ambiguous scalp EEG and normal MRI just like the one we presented.     

同步脑电图-功能磁共振成像技术在癫痫灶定位中的应用研究

目的 探讨同步脑电图-功能磁共振成像技术(EEG-fMRI)在癫痫灶定位中的作用.方法 13例难治性癫痫患者接受同步EEG-fMRI检查,根据EEG出现癫痫波的时间点作为事件相关时间曲线对fMRI数据进行分析,了解发作间期癫痫样放电时血氧水平依赖信号变化所引起的脑部激活情况,并分析这些区域与神经电生理记录所确定的癫痫灶之间的吻合程度.结果 9例患者癫痫样放电在fMRI上的激活区与皮质电极确定的癫痫灶一致;4例患者癫痫样放电在fMRI上的激活区范围大于皮质电极确定的癫痫灶范围,但最强激活区的位置仍与皮质电极确定的癫痫灶一致.结论 同步EEG-fMRI技术将癫痫灶的功能定位与解剖定位相结合,是一种无创、精确度较高的癫痫灶定位方法 .     

The neocortico to mesio-basal limbic propagation of focal epileptic activity during the spike-wave complex.

In order to localize epileptogenic electrophysiological sources, a multichannel MEG system was used in 3 patients with partial epilepsy during presurgical evaluation. MEG and EEG (including scalp, sphenoidal and intracranial foramen ovale electrodes) were recorded simultaneously during a period of intensive video-EEG monitoring in order to observe single spontaneous spikes. In addition to MRI, SPECT and PET investigations were performed. Electrical activity subsequent to the activity of the epileptic focus could be localized by the MEG after noise reduction using a temporal correlation technique. Simultaneous registration of the magnetic field and the electrical field showed that the source of the primary focal epileptic activity (first period during the total spike wave complex where a dipolar magnetic field pattern is found) is localized in neocortical lateral regions, whereas another focal epileptic activity in a later phase of propagation occurs in temporal mesial regions. In 1 patient (case 1) the primary focal epileptic activity was localized in the surrounding neocortical tissue of an angioma and the middle and inferior temporal gyrus. The second phase of propagation is localized in temporo-basal-mesial regions, including para- and hippocampal structures. The latest center of activity occurred in posterior parts of the gyrus cinguli. In 2 other patients, the primary focal epileptogenic activity was localized at the insula and also spread into temporal basal mesial regions. A multi-modal approach to research of focal epilepsy, combining metabolic, electrical potential, magnetoencephalographic and morphological data, recorded by non-invasive techniques, offers new perspectives for the detection of involved brain regions. The 3-D and time-resolved localization of focal epileptic activity, correlated with the individual anatomy of the human brain, may improve the determination of neuronal populations involved in the individual epileptogenic process, especially in the interaction between temporal or extratemporal neocortex and limbic system.     

Site and propagation of focal epileptic activity: multichannel MEG/EEG analysis]

Electrophysiological examinations provide the basis for a deeper pathophysiological understanding of focal epileptic activity. In addition to electroencephalography, magnetoencephalography from field measurements is now available for biomagnetic diagnosis. As magnetoencephalography (MEG) is basically better suited for the localization of focal epileptic activity than EEG, an increase in MEG measurements has taken place over the last years. In this study we discuss magnetic source localization which was combined with anatomical 3-D-MR-images and compared with the results of EEG-registration carried out simultaneously and with other investigative procedures of presurgical diagnosis. The results of investigation show that simultaneous magnetic field measurements over one hemisphere of the skull allow localization of sources both in the temporal lobe and in deeper areas of the brain. Furthermore, propagation of epileptic activity can be registered not only in neighbouring areas of the epileptogenic source but also in regions localized deeper in the temporal lobe. This opens new possibilities for presurgical evaluation as well as an understanding of partial and generalized epilepsies. The results of investigation show primary focal epileptic activity neocortex laterally or surrounding a mesio-temporal lesion in all investigated patients with partial (temporal, frontal) and secondary generalized epilepsies. Furthermore, a pattern of propagation of focal epileptic activity which is directed from neocortical-lateral to mediobasal-limbic brain structures is found in most of these patients.     

Widespread interictal epileptic discharge more likely than focal discharges to unveil the seizure onset zone in EEG-fMRI

ObjectiveWe hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI.Methods157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient.ResultsThe number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ.ConclusionsThe number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ.SignificanceWidespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.     

Origin and propagation of epileptic spasms delineated on electrocorticography

PURPOSE: Ictal electrographic changes were analyzed on intracranial electrocorticography (ECoG) in children with medically refractory epileptic spasms to assess the dynamic changes of ictal discharges associated with spasms and their relation to interictal epileptiform activity and neuroimaging findings. METHODS: We studied a consecutive series of 15 children (age 0.4 to 13 years; nine girls) with clusters of epileptic spasms recorded on prolonged intracranial subdural ECoG recordings, which were being performed for subsequent cortical resection, and in total, 62 spasms were analyzed by using quantitative methods. RESULTS: Spasms were associated with either a "leading" spike followed by fast-wave bursts (type I: 42 events analyzed quantitatively) or fast-wave bursts without a "leading" spike (type II: 20 events analyzed quantitatively). Twenty-three of the 42 type I spasms but none of the 20 type II spasms were preceded by a focal seizure. A "leading" spike had a focal origin in all 42 type I spasms and involved the pre- or postcentral gyrus within 0.1 s in 37 of these spasms. A leading spike was associated with interictal spike activity >1/min in 40 of 42 type I spasms and originated within 2 cm from a positron emission tomography glucose hypometabolic region in all but two type I spasms. Failure to resect the cortex showing a leading spike was associated with poor surgical outcome (p = 0.01; Fisher's exact probability test). Fast-wave bursts associated with spasms involved neocortical regions extensively at least in two lobes within 1.28 s in all 62 spasms and involved the pre- or postcentral gyrus in 53 of 62 spasms. CONCLUSIONS: Epileptic spasms may be triggered by a focal neocortical impulse in a subset of patients, and a leading spike, if present, might be used as a marker of the trigger zone for epileptic spasms. Rapidly emerging widespread fast-wave bursts might explain the clinical semiology of epileptic spasms.     

EEG-fMRI of focal epileptic spikes: analysis with multiple haemodynamic functions and comparison with gadolinium-enhanced MR angiograms

Combined EEG-fMRI has recently been used to explore the BOLD responses to interictal epileptiform discharges. This study examines whether misspecification of the form of the haemodynamic response function (HRF) results in significant fMRI responses being missed in the statistical analysis. EEG-fMRI data from 31 patients with focal epilepsy were analysed with four HRFs peaking from 3 to 9 sec after each interictal event, in addition to a standard HRF that peaked after 5.4 sec. In four patients, fMRI responses were correlated with gadolinium-enhanced MR angiograms and with EEG data from intracranial electrodes. In an attempt to understand the absence of BOLD responses in a significant group of patients, the degree of signal loss occurring as a result of magnetic field inhomogeneities was compared with the detected fMRI responses in ten patients with temporal lobe spikes. Using multiple HRFs resulted in an increased percentage of data sets with significant fMRI activations, from 45% when using the standard HRF alone, to 62.5%. The standard HRF was good at detecting positive BOLD responses, but less appropriate for negative BOLD responses, the majority of which were more accurately modelled by an HRF that peaked later than the standard. Co-registration of statistical maps with gadolinium-enhanced MRIs suggested that the detected fMRI responses were not in general related to large veins. Signal loss in the temporal lobes seemed to be an important factor in 7 of 12 patients who did not show fMRI activations with any of the HRFs.     

Taurine- and penicillin-induced epileptic activity

The present study has been performed to investigate the effect of i.v. administration of taurine on the electrical activity of the epileptogenic focus induced by penicillin applied to the right sensory motor cortex of adult rats. Taurine (100 mg/kg body weight) was administered 15, 30, 60, and 120 min before the application of penicillin. The EEG was unipolarly recorded by means of electrodes applied to the pia. Taurine caused a decrease of the frequency as well as the spike amplitude of epileptic discharge. The spread of epileptogenic foci to the opposite hemisphere was retarded when compared to that of control animals. The maximal antiepileptic effect of taurine was observed when the amino acid was administered 30-60 min previous to penicillin. It is suggested that high concentrations of taurine in the brain might be necessary to inhibit the epileptic activity.     

Optical imaging of visual cortex epileptic foci and propagation pathways

Precise localization of neocortical epileptic foci is a complex problem that usually requires ictal video-electroencephalography (EEG) recordings; high-resolution magnetic resonance imaging (MRI), positron emission tomography (PET), and single photon emission computed tomography (SPECT) studies; and/or invasive monitoring with implanted grid array electrodes. The exact ictal-onset site must be identified and removed to obtain the best opportunity for a seizure-free outcome. The goal of this study was to determine if high-resolution optical imaging could precisely identify neocortical epileptic foci and what role underlying neuroanatomic pathways played in the seizure propagation. Small acute epileptic foci (0.5?×?0.5?mm(2) ) were created in the primate visual neocortex and single-unit and surface EEG recordings were combined with optical imaging of voltage-sensitive dye changes. Brief visual stimulation was used to evoke interictal bursts. In addition, different visually evoked epileptiform bursts were analyzed to determine the location of the epileptic focus. Spike-triggered averaging of the optical images associated with the surface EEG interictal bursts were analyzed to determine the exact location of the epileptic focus. Specific orientations of brief visual stimulation evoked different intensity optical changes and precisely localized the epileptic focus. Optical imaging identified individual epileptic foci that were <3?mm apart. The development of individual epileptic focus was monitored with optical imaging, which demonstrated excitatory activity at the focus with a surrounding zone of inhibitory-like activity. Propagation pathways outside of the inhibitory-like surround demonstrated alternating bands of excitation and inhibition with a pattern orthogonal to the ocular dominance columns. This experimental study demonstrates that optical imaging can precisely localize an epileptic focus, and provides excellent spatial resolution of the changes that occur in and around the site of the epileptic focus.     

抗癫痫药物对人癫痫病灶脑片癫痫样电活动的抑制作用

目的：探讨用手术切除的癫痫病灶进行抗癫痫药物研究的可行性。方法：将手术中切除大脑皮层病灶切成脑薄片,通过脑标本的降温通氧保存脑片活力,用低Ｍｇ＾２＋和４－氨基吡啶（４－ＡＰ）灌流诱导脑片自发性癫痫样放电,用自行研制的多孔溶槽实现对同一脑标本行４种药物实验,观察在抗癫痫药前后自发放电波幅度变化。结果：４例癫痫病灶及２例非癫痫脑组织（对照组）实施了药物敏感实验,常用的４种药物实验,观察在抗癫痫药前后自发放电波幅变化。结果：４例癫痫病灶及２例非癫痫组织（对照组）实验了药物敏感实验,常用的４种抗癫痫药在低浓度时（μｍｏｌ／Ｌ：苯妥英钠１００,苯巴比妥１０００,安定３０,卡马西平１００）对癫痫脑片自发放电的抑制作用较对非癫痫脑片的作用弱。药物浓度增大３倍后,对两组脑片均产生明显抑制作用。结论：癫痫病灶皮层脑片在体外可以用     

Cognitive functions and epileptic activity.

Epilepsy, and its treatment, can affect the development and use of language in a number of different ways. The seizures may be a symptom of a lesion in areas of the brain essential for language function, and the complications of both the seizures and of the drugs can interfere with learning. However, the purpose of this review is to consider the role of epileptic activity as demonstrated by electrical discharges in the electroencephalogram (EEG), whether these are accompanied by overt seizures or not, on cerebral function especially that of language. The Landau-Kleffner, the continuous spike-waves during sleep, and the benign epilepsy of childhood with Rolandic spikes syndromes are considered; as well as the evidence of epileptic discharges affecting language development. If there are doubts that a patient is suffering from epilepsy the diagnosis may be difficult; and anyone involved in the treatment of language disorders should keep this possibility in mind. Particularly during childhood an EEG, awake and asleep, should be an important part of the assessment of both developmental and acquired dysphasia. The control of overt fits may be relatively easy, but drugs are not so effective in controlling the epileptic activity in the EEG. The treatment of such discharges used to be discouraged, but the evidence is now strongly in favour of employing both medical and surgical treatment. The results in restoring language function are sometimes dramatic.     

Measurement of small time differences between EEG channels: method and application to epileptic seizure propagation

Small time differences between the EEG activities of two channels were measured by a method based on the use of coherence and phase spectra over a certain frequency range. In many cases this method allowed to establish that time differences of the order of 5-50 msec were actually present between two channels which appeared synchronous on visual inspection. The method was applied to seizure activity from the penicillin and kindling models in the cat and to seizures recorded from scalp and intracerebral electrodes in epileptic patients. When the seizure activity was widespread but was known to be related to an epileptic focus, it was found that the area of the focus had a consistent time lead over the other recording sites. It was concluded that the method could frequently allow to: (1) assess the presence of an epileptic focus even when only widespread seizure activity could be recorded; (2) make inferences about the possible routes of propagation of seizure activity.     

Approaches to staging sleep in polysomnographic studies with epileptic activity

BACKGROUND: The Standardized Sleep Manual of Rechtschaffen and Kales is well established and reliable in scoring the majority of polysomnograms (PSGs) encountered in clinical practice. In patients with epilepsy, however, abnormal brain activity may confound the interpretation of sleep waveforms. Our goal is to identify features that are problematic in analyzing sleep stages in patients with epilepsy and to offer approaches to score these PSGs. METHODS: Ninety eight PSGs from 43 patients with epilepsy were scored using Rechtschaffen and Kales guidelines. Features interfering with sleep staging were noted. RESULTS: In scoring polysomnograms (PSGs) of patients with epilepsy we noted epileptic seizures, interictal epileptiform discharges (IEDs) and abnormal EEG background to be features of epilepsy that compromised sleep scoring. Overall, 48% of the studies in our sample contained one or more of these epileptic features to the extent that sleep scoring by standard criteria was compromised. Approaches for staging sleep in the setting of these abnormalities are outlined. CONCLUSIONS: The Rechtschaffen and Kales method of sleep scoring is useful in staging the majority of PSGs of patients with epilepsy. However, we advocate some modifications because the abnormal electrical activity of epilepsy may interfere with accurate scoring of sleep waveforms. These approaches to scoring PSGs of patients with epilepsy will require empirical testing.     

The network integration of epileptic activity in relation to surgical outcome

ObjectiveEpilepsy is a network disease with epileptic activity and cognitive impairment involving large-scale brain networks. A complex network is involved in the seizure and in the interictal epileptiform discharges (IEDs). Directed connectivity analysis, describing the information transfer between brain regions, and graph analysis are applied to high-density EEG to characterise networks.MethodsWe analysed 19 patients with focal epilepsy who had high-density EEG containing IED and underwent surgery. We estimated cortical activity during IED using electric source analysis in 72 atlas-based cortical regions of the individual brain MRI. We applied directed connectivity analysis (information Partial Directed Coherence) and graph analysis on these sources and compared patients with good vs poor post-operative outcome at global, hemispheric and lobar level.ResultsWe found lower network integration reflected by global, hemispheric, lobar efficiency during the IED (p < 0.05) in patients with good post-surgical outcome, compared to patients with poor outcome. Prediction was better than using the IED field or the localisation obtained by electric source imaging.ConclusionsAbnormal network patterns in epilepsy are related to seizure outcome after surgery.SignificanceOur finding may help understand networks related to a more “isolated” epileptic activity, limiting the extent of the epileptic network in patients with subsequent good post-operative outcome.