Effect of Training on Visual Identification of High Frequency Oscillations-A Delphi-Style Intervention.

OBJECTIVE: We examined the effect of a simple Delphi-method feedback on visual identification of high frequency oscillations (HFOs) in the ripple (80-250 Hz) band, and assessed the impact of this training intervention on the interrater reliability and generalizability of HFO evaluations. METHODS: We employed a morphology detector to identify potential HFOs at two thresholds and presented them to visual reviewers to assess the probability of each epoch containing an HFO. We recruited 19 board-certified epileptologists with various levels of experience to complete a series of HFO evaluations during three sessions. A Delphi-style intervention was used to provide feedback on the performance of each reviewer relative to their peers. A delayed-intervention paradigm was used, in which reviewers received feedback either before or after the second session. ANOVAs were used to assess the effect of the intervention on the reviewers' evaluations. Generalizability theory was used to assess the interrater reliability before and after the intervention. RESULTS: The intervention, regardless of when it occurred, resulted in a significant reduction in the variability between reviewers in both groups (p GroupDI = 0.037, p GroupEI = 0.003). Prior to the delayed-intervention, the group receiving the early intervention showed a significant reduction in variability (p GroupEI = 0.041), but the delayed-intervention group did not (p GroupDI = 0.414). Following the intervention, the projected number of reviewers required to achieve strong generalizability decreased from 35 to 16. SIGNIFICANCE: This study shows a robust effect of a Delphi-style intervention on the interrater variability, reliability, and generalizability of HFO evaluations. The observed decreases in HFO marking discrepancies across 14 of the 15 reviewers are encouraging: they are necessarily associated with an increase in interrater reliability, and therefore with a corresponding decrease in the number of reviewers required to achieve strong generalizability. Indeed, the reliability of all reviewers following the intervention was similar to that of experienced reviewers prior to intervention. Therefore, a Delphi-style intervention could be implemented either to sufficiently train any reviewer, or to further refine the interrater reliability of experienced reviewers. In either case, a Delphi-style intervention would help facilitate the standardization of HFO evaluations and its implementation in clinical care.

Localization of interictal discharge origin: A simultaneous intracranial electroencephalographic-functional magnetic resonance imaging study.

OBJECTIVE: Scalp electroencephalographic (EEG)-functional magnetic resonance imaging (fMRI) studies suggest that the maximum blood oxygen level-dependent (BOLD) response to an interictal epileptiform discharge (IED) identifies the area of IED generation. However, the maximum BOLD response has also been reported in distant, seemingly irrelevant areas. Given the poor postoperative outcomes associated with extra-temporal lobe epilepsy, we hypothesized this finding is more common when analyzing extratemporal IEDs as compared to temporal IEDs. We further hypothesized that a subjective, holistic assessment of other significant BOLD clusters to identify the most clinically relevant cluster could be used to overcome this limitation and therefore better identify the likely origin of an IED. Specifically, we also considered the second maximum cluster and the cluster closest to the electrode contacts where the IED was observed. METHODS: Maps of significant IED-related BOLD activation were generated for 48 different IEDs recorded from 33 patients who underwent intracranial EEG-fMRI. The locations of the maximum, second maximum, and closest clusters were identified for each IED. An epileptologist, blinded to these cluster assignments, selected the most clinically relevant BOLD cluster, taking into account all available clinical information. The distances between these BOLD clusters and their corresponding IEDs were then measured. RESULTS: The most clinically relevant cluster was the maximum cluster for 56% (27/48) of IEDs, the second maximum cluster for 13% (6/48) of IEDs, and the closest cluster for 31% (15/48) of IEDs. The maximum clusters were closer to IED contacts for temporal than for extratemporal IEDs (p = .022), whereas the most clinically relevant clusters were not significantly different (p = .056). SIGNIFICANCE: The maximum BOLD response to IEDs may not always be the most indicative of IED origin. We propose that available clinical information should be used in conjunction with EEG-fMRI data to identify a BOLD cluster representative of the IED origin.

Outcome of lesional epilepsy surgery: Report of the first comprehensive epilepsy program in Iran.

BACKGROUND: We investigated the utility of epilepsy surgery and postoperative outcome in patients with lesional epilepsy in Iran, a relatively resource-poor setting. METHODS: This prospective longitudinal study was conducted during 2007-2017 in Kashani Comprehensive Epilepsy Center, Isfahan, Iran. Patients with a diagnosis of intractable focal epilepsy, with MRI lesions, who underwent epilepsy surgery and were followed up ≥ 24 months, were included and evaluated for postoperative outcome. RESULTS: A total of 214 patients, with a mean age of 26.90 ± 9.82 years (59.8% men) were studied. Complex partial seizure was the most common type of seizure (85.9%), and 54.2% of the cases had auras. Temporal lobe lesions (75.2%) and mesial temporal sclerosis (48.1%) were the most frequent etiologies. With a mean follow-up of 62.17 ± 19.33 months, 81.8% of patients became seizure-free postoperatively. Anticonvulsants were reduced in 86% of the cases and discontinued in 40.7%. In keeping with previous studies, we found that seizure freedom rates were lower among patients with longer follow-up periods. CONCLUSIONS: We found high rates of seizure freedom after surgery in lesional epilepsy patients despite limited facilities and infrastructure; antiepileptic medications were successfully tapered in almost half of the patients. Considering the favorable outcome of epilepsy surgery in our series, we believe that it is a major treatment option, even in less resource-intensive settings, and should be encouraged. Strategies to allow larger scale utility of epilepsy surgery in such settings in the developing world and dissemination of such knowledge may be considered an urgent clinical need, given the established mortality and morbidity in refractory epilepsy.

Focal epilepsy without interictal spikes on scalp EEG: A common finding of uncertain significance.

OBJECTIVE: Interictal epileptiform discharges (IEDs) are important to identify the epileptogenic zone and to define epileptic syndromes. However, not all patients show IEDs on scalp EEG. We evaluate the likelihood of not findings spikes on prolonged Video-EEG Monitoring (VEM) in patients with focal epilepsy, and explore clinical correlates. METHODS: We retrospectively reviewed the VEM reports for all the patients admitted to the seizure monitoring unit in the Calgary Epilepsy Program between July'10 and August'17. Adult focal epilepsy patients, using the diagnostic criteria of the International League Against Epilepsy, who had at least three consecutive VEM days and one recorded seizure were included. Patients were categorized as spikers or non-spikers if any or no spikes were seen on VEM. We compared demographic, neuroimaging, epilepsy risk factor and seizure data. RESULTS: Of 933 patients, 345 fulfilled our eligibility criteria, 17% [55% males] non-spikers and 83% [53% males] spikers. There were no statistically significant differences between non-spikers and spikers in the studied clinical variables at our epilepsy centre. Average age and average duration of epilepsy were 39 and 13 years for non-spikers and 38 and 16 years for spikers. The average duration of VEM was 8-9 days in both groups. The most frequent seizure focus was in the temporal lobe in both groups (53% in non-spikers vs. 64% in spikers, p = 0.06). An epileptogenic lesion on MRI was identified in 26 (46%) of non-spikers and 158 (57%) of spikers (p = 0.16). SIGNIFICANCE: Approximately one out of six patients with focal epilepsy showed no IEDs despite prolonged VEM. There was no significant difference among the investigated clinical variables between these two groups of patients in our epilepsy centre. We hypothesise that patients without IEDs on scalp EEG may have smaller, deeper generators with lower levels of neuronal synchrony, which precludes the expression of high amplitude spikes detectable on scalp EEG.

Generalizability of High Frequency Oscillation Evaluations in the Ripple Band.

Objective: We examined the interrater reliability and generalizability of high-frequency oscillation (HFO) visual evaluations in the ripple (80-250 Hz) band, and established a framework for the transition of HFO analysis to routine clinical care. We were interested in the interrater reliability or epoch generalizability to describe how similar the evaluations were between reviewers, and in the reviewer generalizability to represent the consistency of the internal threshold each individual reviewer. Methods: We studied 41 adult epilepsy patients (mean age: 35.6 years) who underwent intracranial electroencephalography. A morphology detector was designed and used to detect candidate HFO events, lower-threshold events, and distractor events. These events were subsequently presented to six expert reviewers, who visually evaluated events for the presence of HFOs. Generalizability theory was used to characterize the epoch generalizability (interrater reliability) and reviewer generalizability (internal threshold consistency) of visual evaluations, as well as to project the numbers of epochs, reviewers, and datasets required to achieve strong generalizability (threshold of 0.8). Results: The reviewer generalizability was almost perfect (0.983), indicating there were sufficient evaluations to determine the internal threshold of each reviewer. However, the interrater reliability for 6 reviewers (0.588) and pairwise interrater reliability (0.322) were both poor, indicating that the agreement of 6 reviewers is insufficient to reliably establish the presence or absence of individual HFOs. Strong interrater reliability (≥0.8) was projected as requiring a minimum of 17 reviewers, while strong reviewer generalizability could be achieved with <30 epoch evaluations per reviewer. Significance: This study reaffirms the poor reliability of using small numbers of reviewers to identify HFOs, and projects the number of reviewers required to overcome this limitation. It also provides a set of tools which may be used for training reviewers, tracking changes to interrater reliability, and for constructing a benchmark set of epochs that can serve as a generalizable gold standard, against which other HFO detection algorithms may be compared. This study represents an important step toward the reconciliation of important but discordant findings from HFO studies undertaken with different sets of HFOs, and ultimately toward transitioning HFO analysis into a meaningful part of the clinical epilepsy workup.

Interrater reliability of visually evaluated high frequency oscillations.

OBJECTIVE: High frequency oscillations (HFOs) and interictal epileptiform discharges (IEDs) have been shown to be markers of epileptogenic regions. However, there is currently no 'gold standard' for identifying HFOs. Accordingly, we aimed to formally characterize the interrater reliability of HFO markings to validate the current practices. METHODS: A morphology detector was implemented to detect events (candidate HFOs, lower-threshold events, and distractors) from the intracranial EEG (iEEG) of ten patients. Six electroencephalographers visually evaluated these events for the presence of HFOs and IEDs. Interrater reliability was calculated using pairwise Cohen's Kappa (κ) and intraclass correlation coefficients (ICC). RESULTS: The HFO evaluation distributions were significantly different for most pairs of reviewers (p<0.05; 11/15 pairs). Interrater reliability was poor for HFOs alone (κmean=0.403; ICC=0.401) and HFO+IEDs (κmean=0.568; ICC=0.570). CONCLUSIONS: The current practice of using two visual reviewers to identify HFOs is prone to bias arising from the poor agreement between reviewers, limiting the extrinsic validity of studies using these markers. SIGNIFICANCE: The poor interrater reliability underlines the need for a framework to reconcile the important findings of existing studies. The present epoched design is an ideal candidate for the implementation of such a framework.

Prognostic value of ictal onset patterns in postsurgical outcome of temporal lobe epilepsy.

Background: To investigate ictal onset patterns (IOP) in scalp electroencephalography (EEG) of patients with temporal lobe epilepsy (TLE) and their prognostic effect on the postoperative outcome. Methods: We conducted a retrospective cohort study between 2011 and 2015 in our referral Epilepsy Surgery Center enrolling adult patients with refractory TLE and a visible epileptogenic lesion in magnetic resonance imaging (MRI), who underwent epilepsy surgery. Demographic, clinical and MRI findings were collected and ictal findings during video-EEG monitoring were reviewed in detail. The correlation between preoperative findings and the postsurgical outcome was analyzed. Results: We reviewed 303 seizures in 93 patients. Rhythmic theta and rhythmic spike/sharp and wave were respectively the most common initial ictal pattern and late significant discharges. Engel class I outcome was observed in 88.2% of patients. Female sex, aura, the absence of secondary generalization, rhythmic theta as initial ictal pattern and concordance of ictal-interictal EEG findings were correlated with favorable 1-year postsurgical outcome. Conclusion: Preoperative clinical and EEG findings can provide valuable information regarding postsurgical prognosis in TLE patients.

Patient specific hemodynamic response functions associated with interictal discharges recorded via simultaneous intracranial EEG-fMRI.

Simultaneous collection of scalp EEG and fMRI has become an important tool for studying the hemodynamic changes associated with interictal epileptiform discharges (IEDs) in persons with epilepsy, and has become a standard presurgical assessment tool in some centres. We previously demonstrated that performing EEG-fMRI using intracranial electrodes (iEEG-fMRI) is of low risk to patients in our research centre, and offers unique insight into BOLD signal changes associated with IEDs recorded from very discrete sources. However, it is unknown whether the BOLD response corresponding to IEDs recorded by iEEG-fMRI follows the canonical hemodynamic response. We therefore scanned 11 presurgical epilepsy patients using iEEG-fMRI, and assessed the hemodynamic response associated with individual IEDs using two methods: assessment of BOLD signal changes associated with isolated IEDs at the location of the active intracranial electrode, and by estimating subject-specific impulse response functions to isolated IEDs. We found that the hemodynamic response associated with the intracranially recorded discharges varied by patient and by spike location. The observed shape and timing differences also deviated from the canonical hemodynamic response function traditionally used in many fMRI experiments. It is recommended that future iEEG-fMRI studies of IEDs use a flexible hemodynamic response model when performing parametric tests to accurately characterize these data.

Co-localization between the BOLD response and epileptiform discharges recorded by simultaneous intracranial EEG-fMRI at 3 T.

OBJECTIVES: Simultaneous scalp EEG-fMRI can identify hemodynamic changes associated with the generation of interictal epileptiform discharges (IEDs), and it has the potential of becoming a standard, non-invasive technique for pre-surgical assessment of patients with medically intractable epilepsy. This study was designed to assess the BOLD response to focal IEDs recorded via simultaneous intracranial EEG-functional MRI (iEEG-fMRI). METHODS: Twelve consecutive patients undergoing intracranial video EEG monitoring were recruited for iEEG-fMRI studies at 3 T. Depth, subdural strip, or grid electrodes were implanted according to our standard clinical protocol. Subjects underwent 10-60 min of continuous iEEG-fMRI scanning. IEDs were marked, and the most statistically significant clusters of BOLD signal were identified (Z-score 2.3, p value < 0.05). We assessed the concordance between the locations of the BOLD response and the IED. Concordance was defined as a distance <1.0 cm between the IED and BOLD response location. Negative BOLD responses were not studied in this project. RESULTS: Nine patients (7 females) with a mean age of 31 years (range 22-56) had 11 different types of IEDs during fMR scanning. The IEDs were divided based on the location of the active electrode contact into mesial temporal, lateral temporal, and extra-temporal. Seven (5 left) mesial temporal IED types were recorded in 5 patients (110-2092 IEDs per spike location). Six of these IEDs had concordant BOLD response in the ipsilateral mesial temporal structures, <1 cm from the most active contact. One of the two subjects with left lateral temporal IEDs had BOLD responses concordant with the location of the most active contact, as well other ipsilateral and contralateral sites. Notably, the remaining two subjects with extratemporal discharges showed no BOLD signal near the active electrode contact. CONCLUSIONS: iEEG-fMRI is a feasible and low-risk method for assessment of hemodynamic changes of very focal IEDs that may not be recorded by scalp EEG. A high concordance rate between the location of the BOLD response and IEDs was seen for mesial temporal (6/7) IEDs. Significant BOLD activation was also seen in areas distant from the active electrode and these sites exhibited maximal BOLD activation in the majority of cases. This implies that iEEG-fMRI may further describe the areas involved in the generation of IEDs beyond the vicinity of the electrode(s).

Epilepsy surgery in patients with bilateral temporal lobe seizures: a systematic review.

We explored the association between magnetic resonance imaging (MRI) lesion, degree of seizure laterality on intracranial electroencephalography (iEEG), and seizure outcome in patients with ambiguous or presumed bilateral temporal lobe epilepsy (BiTLE) on scalp EEG. We systematically reviewed the literature using Embase and MEDLINE up to May 31, 2012. Patients with bilateral iEEG, temporal lobe surgery, and follow-up ≥1 year were included. We undertook three separate analyses on patients whose scalp EEG showed ambiguous onset or BiTLE (1) group data of those whose iEEG demonstrated unilateral TLE, (2) group data of those whose iEEG demonstrated BiTLE, (3) individual patient analysis in those with BiTLE for whom iEEG seizure laterality data were provided. Of 1,403 patients with ambiguous or presumed BiTLE on scalp EEG, 1,027 (73%) proved to have unilateral TLE on iEEG and contributed to the first analysis. Of these, 58% had Engel class I and 9% Engel class II outcomes. Of 132 patients in the second analysis (true BiTLE), Engel class I and II outcomes were achieved in 23% and 14%, respectively. Of 41 patients in the third analysis, 66% and 2% had Engel class I and II outcomes, respectively. The median proportion of seizures ipsilateral to the resection on iEEG did not differ between BiTLE patients with Engel class I-II (76%) and Engel III-IV (78%) outcomes (p = 0.87). Patients with ambiguous or independent bitemporal seizure onset on scalp EEG achieved good surgical outcomes. Overall, a significantly higher proportion of patients achieved good outcomes when iEEG showed unilateral TLE (67%) than when it showed true BiTLE (45%). However, the degree of seizure lateralization in those with BiTLE was not associated with seizure outcome, and it has a limited role in selecting the side of surgery.

Alpha-[11C]methyl-L-tryptophan uptake in patients with periventricular nodular heterotopia and epilepsy.

BACKGROUND: Alpha-[11C]methyl-L-tryptophan (alpha-MTrp) positron emission tomography (PET) is a promising tool in the localization of the epileptogenic area in selected group of focal epilepsy patients. Electrophysiological evidence suggests the involvement of the neocortex in periventricular nodular heterotopia (PVNH). PURPOSE: To determine whether alpha-MTrp PET can detect neocortical changes in patients with PVNH. METHODS: Four patients (2 male, mean age 28, range 23-35 years) with PVNH and intractable seizures were studied. The functional image in each patient was compared with those from 21 healthy controls (mean age 34.6 +/- 14.2 years) by using statistical parametric mapping (SPM). The location of increased alpha-MTrp uptake was compared with the location of the EEG focus. A significant cluster was defined as a cluster with a height p = 0.005 and an extent threshold 100. RESULTS: Alpha-MTrp PET revealed increased cortical uptake in two of four patients. The area of increased alpha-MTrp uptake in one patient was widespread. In the other patient, the area of increased uptake did not include the region where most seizures were generated on EEG. alpha-MTrp PET did not show increased uptake in the heterotopic nodules in any of the patients. CONCLUSIONS: Alpha-MTrp PET suggests abnormal metabolism of tryptophan in the neocortex. The increased uptake may be diffuse and may not co-localize with the EEG focus. This preliminary study suggests that alpha-MTrp PET may be useful, in conjunction with other evaluations, in localizing epileptic focus in patients with PVNH and refractory seizures.

A method for detecting nonlinear determinism in normal and epileptic brain EEG signals.

A robust method of detecting determinism for short time series is proposed and applied to both healthy and epileptic EEG signals. The method provides a robust measure of determinism through characterizing the trajectories of the signal components which are obtained through singular value decomposition. Robustness of the method is shown by calculating proposed index of determinism at different levels of white and colored noise added to a simulated chaotic signal. The method is shown to be able to detect determinism at considerably high levels of additive noise. The method is then applied to both intracranial and scalp EEG recordings collected in different data sets for healthy and epileptic brain signals. The results show that for all of the studied EEG data sets there is enough evidence of determinism. The determinism is more significant for intracranial EEG recordings particularly during seizure activity.

Temporal and extratemporal BOLD responses to temporal lobe interictal spikes.

PURPOSE: Simultaneous EEG and functional MRI (fMRI) allows measuring metabolic changes related to interictal spikes. Our objective was to investigate blood oxygenation level-dependent (BOLD) responses to temporal lobe (TL) spikes by using EEG-fMRI recording. METHODS: We studied 35 patients who had a diagnosis of temporal lobe epilepsy (TLE) and active TL spiking on routine scalp EEG recording. Two-hour sessions of continuous EEG-fMRI were recorded, and spikes were identified after offline artifact removal and used as events in the fMRI analysis. Each type of spike was analyzed separately, as one EEG-fMRI study. We determined significant (p < 0.05) positive (activation) and negative (deactivation) BOLD responses for each study. RESULTS: Twenty-seven patients had spikes during scanning (19 unilateral and eight bilateral). From a total of 35 fMRI studies, 29 (83%) showed BOLD responses: 14 had both activations and deactivations; 12, activations only; and three, deactivations only. Six (17%) showed no responses. Nineteen studies had mainly neocortical TL activation: Sixteen (84%) of 19 concordant with spikes, 12 of 16 with concomitant activation of the contralateral TL, and 16 of 19 with additional extratemporal activation; few showed exclusively mesial TL activation. Seventeen studies showed deactivation, either extratemporal plus temporal (n = 8) or exclusively extratemporal (n = 9). CONCLUSIONS: BOLD responses to TL spikes occurred in 83% of studies, predominated in the spiking temporal lobe, and manifested as activation or deactivation. Responses often involved the contralateral homologous cortex at the time of unilateral spikes and were frequently observed in extratemporal regions, suggesting that TL epileptic spikes can affect neuronal activity at a distance through synaptic connections.

EEG-fMRI of epileptic spikes: concordance with EEG source localization and intracranial EEG.

Simultaneous EEG and fMRI recordings permit the non-invasive investigation of the generators of spontaneous brain activity such as epileptic spikes. Despite a growing interest in this technique, the precise relationship between its results and the actual regions of activated cortex is not clear. In this study, we have quantified for the first time the concordance between EEG-fMRI results and stereotaxic EEG (SEEG) recordings in 5 patients with partial epilepsy. We also compared fMRI and SEEG with other non-invasive maps based on scalp EEG alone. We found that SEEG measures largely validated the results of EEG and fMRI. Indeed, when there is an intracranial electrode in the vicinity of an EEG or fMRI peak (in the range 20-40 mm), then it usually includes one active contact. This was the case for both increases ('activations') and decreases ('deactivations') of the fMRI signal: in our patients, fMRI signal decrease could be as important in understanding the complete picture of activity as increase of fMRI signal. The concordance between EEG and fMRI was not as good as the concordance between either of these non-invasive techniques and SEEG. This shows that the two techniques can show different regions of activity: they are complementary for the localization of the areas involved in the generation of epileptic spikes. Moreover, we found that the sign of the fMRI response correlated with the low frequency content of the SEEG epileptic transients, this latter being a reflection of the slow waves. Thus, we observed a higher proportion of energy in the low frequencies for the SEEG recorded in regions with fMRI signal increase compared to the regions with fMRI signal decrease. This could reflect an increase of metabolism linked to the presence of slow waves, which suggests that fMRI is a new source of information on the mechanisms of spike generation.

Detecting determinism in EEG signals using principal component analysis and surrogate data testing.

A novel method is proposed here to determine whether a time series is deterministic even in the presence of noise. The method is the extension of an existing method based on smoothness analysis of the signal in state space with surrogate data testing. While classical measures fail to detect determinism when the time series is corrupted by noise, the proposed method can clearly distinguish between pure stochastic and originally deterministic but noisy time series. A set of measures is defined here named partial smoothness indexes corresponding to principal components of the time series in state space. It is shown that when the time series is not pure stochastic, at least one of the indexes reflects determinism. The method is first successfully tested through simulation on a chaotic Lorenz time series contaminated with noise and then applied on EEG signals. Testing results on both our experimental recorded EEG signals and a benchmark EEG database verifies this hypothesis that EEG signals are deterministic in nature while contain some stochastic components as well.

The role of periventricular nodular heterotopia in epileptogenesis.

A temporal resection in patients with periventricular nodular heterotopia (PNH) and intractable focal seizures yields poor results. To define the role of heterotopic grey matter tissue in epileptogenesis and to improve outcome, we performed stereoencephalography (SEEG) recordings in eight patients with uni- or bilateral PNH and intractable focal epilepsy. The SEEG studies aimed to evaluate the most epileptogenic areas and included the allo- and neocortex and at least one nodule of grey matter. Interictal spiking activity was found in ectopic grey matter in three patients, in the cortex overlying the nodules in five and in the mesial temporal structures in all. At least one heterotopion was involved at seizure onset in six patients, synchronous with the overlying neocortex or ipsilateral hippocampus. Two patients had their seizures originating in the mesial temporal structures only. Six patients had surgery and the resected areas included the seizure onset, with follow-up from 1 to 8 years. An amygdalo-hippocampectomy was performed in two (Engel class Id and III), an amygdalo-hippocampectomy plus removal of an adjacent heterotopion in two (class Ia), and a resection of two contiguous nodules plus a small rim of overlying occipital cortex in one patient (class Id). One patient with bilateral PNH had three adjacent nodules resected and an ipsilateral amygdalo-hippocampectomy resulting in a reduction of the number of seizures by 25-50%. The best predictor of surgical outcome is the presence of a focal epileptic generator; this generator may or may not include the PNH. Invasive recording is required in patients with PNH; it improves localization and is the key to better outcome.

Analysis of the EEG-fMRI response to prolonged bursts of interictal epileptiform activity.

The use of combined EEG-fMRI to study interictal epileptiform activity is increasing and has great potential as a clinical tool, but the haemodynamic response to epileptiform activity remains incompletely characterised. To this end, 19 data sets from 14 patients with prolonged bursts of focal or generalised interictal epileptiform activity lasting up to 15 s were analysed. To determine whether the inclusion of the durations of the epileptic events in the general linear model resulted in increased statistical significance of activated regions, statistical maps were generated with and without the event durations. The mean differences when including the durations were a 14.5% increase in peak t value and a 29.5% increase in volume of activation. This suggests that when analysing EEG-fMRI data from patients with prolonged bursts of interictal epileptiform activity, it is better to include the event durations. To determine whether the amplitudes and latencies of the measured responses were consistent with the general linear model, the haemodynamic response functions for bursts of different durations were calculated and compared with the model predictions. The measured amplitude of the response to the shortest duration events was consistently larger than predicted, which is consistent with studies in normal subjects. For the two data sets with the widest range of event durations, the measured amplitudes increased with the durations of the events without evidence of the plateau that was expected from the general linear model. There were no consistent differences between the measured and modelled latencies.

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.

Patients with temporoparietal ictal symptoms and inferomesial EEG do not benefit from anterior temporal resection.

PURPOSE: The role of posterior structural lesions leading to inadequate results after inferomesial temporal resection is well recognized. Here we present poor surgical outcome in six patients with nonlesional intractable epilepsy, well-defined focal anterior and inferomesial temporal epileptic discharges, and posterior temporoparietal symptoms. METHODS: We reviewed patient data including scalp video-EEG telemetry, intracranial EEG recording, magnetic resonance imaging (MRI) sequences (1.5 Tesla), and single-photon emission computed tomography (SPECT) findings. RESULTS: Ictal onset was uni- or bilateral diffuse with late preponderance over one temporal, or centrotemporoparietal regions. Four patients had preresection intracranial EEG monitoring, which suggested an epileptogenic zone in the posterior temporal and inferior parietal area in two, in the temporal lobe in one, and was inconclusive in the remaining one, who showed late epileptiform activity in the temporal neocortex. A second intracranial implantation was performed in three of them after a first anterior temporal resection. This led to posterior temporal neocortical localization in two and posterior temporal-inferior parietal localization in one. Including subpial transection, these six patients had one to four operations each, but only limited improvement occurred as a result of surgery in this group of individuals. CONCLUSIONS: We conclude that anterior and inferomesial interictal epileptiform temporal discharges and at times even intracranial EEG monitoring may be misleading. Anteromesial temporal resection is ineffective in patients with posterior temporoparietal clinical ictal features.