Temporal Interictal Epileptiform Discharges Research Articles

The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy.

Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or "irritative" network. Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups. There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment. The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.

Mesial temporal lobe spiking reveals distinct patterns of blood oxygen level-dependent functional magnetic resonance imaging activation using simultaneous intracranial electroencephalography-functional magnetic resonance imaging.

Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography-functional MRI (iEEG-fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED-associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG-fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED-associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. Two patterns of IED-associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic-clonic seizures and had better postsurgical outcomes. Simultaneous iEEG-fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED-associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated-activation had fewer focal to bilateral tonic-clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events.

Clinical features and surgical outcomes in temporal lobe epilepsy with amygdala enlargement - a single tertiary center study

Objective: To analyze and summarize clinical features and surgical outcomes in temporal lobe epilepsy with amygdala enlargement (TLE-AE) in a single tertiary center. Methods: Patients with TLE-AE admitted to the Neurological Disease Center of Peking University International Hospital from January 2016 to September 2022 were continuously collected. The clinical data of TLE-AE patients were retrospectively analyzed. Results: A total of 19 patients with TLE-AE were included. The average age at onset was (29.0 ± 14.5) years and all patients had focal impairment awareness seizure (FIAS). Ten (52.6%) patients were in line with drug-resistant epilepsy and 8 cases received surgical treatment. Focal temporal interictal epileptiform discharges on scalp electroencephalography were exclusively present ipsilateral to AE in 15 (78.9%) patients. Stereo-electroencephalography analysis found the ictal onset zone involved not only the enlarged amygdala but also the hippocampus in 2 patients. Two patients who responded well to antiseizure medication exhibited AE remission on follow-up MRI. Histopathology of the amygdala showed focal cortical dysplasia (FCD) in 7 patients and ganglioglioma in 1 patient. The 8 surgical patients were followed up for 13-79 months after operation. Six (75.0%) patients achieved Engel class Ia or I outcome, whereas 2 cases did not fully respond to the surgery (Engel class II). Conclusions: Patients with TLE-AE had a later age of seizure onset and FIAS was common. The epileptogenic zone in TLE-AE patients may be located in the enlarged amygdala and ipsilateral hippocampus. AE might be a secondary seizure-induced change in a subset of patients with favorable responses to drugs. As for drug-resistant patients, FCD may be the most common pathological change and surgical treatment could be taken into consideration.

ATP1A2-related epileptic encephalopathy and movement disorder: Clinical features of three novel patients.

Variants in the ATP1A2 gene exhibit a wide clinical spectrum, ranging from familial hemiplegic migraine to childhood epilepsies and early infantile developmental epileptic encephalopathy (EIDEE) with movement disorders. This study aims to describe the epileptology of three unpublished cases and summarize epilepsy features of the other 17 published cases with ATP1A2 variants and EIDEE. Medical records of three novel patients with pathogenic ATP1A2 variants were retrospectively reviewed. Additionally, the PUBMED, EMBASE, and Cochrane databases were searched until December 2023 for articles on EIDEE with ATP1A2 variants, without language or publication year restrictions. Three female patients, aged 6 months-10 years, were investigated. Epilepsy onset occurred between 5 days and 2 years, accompanied by severe developmental delay, intellectual disability, drug-resistant epilepsy, severe movement disorder, and recurrent status epilepticus. All individuals had pathogenic variants of the ATP1A2 gene (ATP1A2 c.720_721del (p.Ile240MetfsTer9), ATP1A2c.3022C > T (p.Arg1008Trp), ATP1A2 c.1096G > T (p.Gly366Cys), according to ACMG criteria. Memantine was p) rescribed to three patients, one with a reduction in ictal frequency, one with improvement in gait pattern, coordination, and attention span, and another one in alertness without significant side effects. This study reinforces the association between ATP1A2 variants and a severe phenotype. All patients had de novo variants, focal motor seizures with impaired awareness as the primary type of seizure; of the 11 EEGs recorded, 10 presented a slow background rhythm, 7 multifocal interictal epileptiform discharges (IED), predominantly temporal IEDs, followed by frontal IED, as well as ten ictal recordings, which showed ictal onset from the same regions mentioned above. Treatment with antiseizure medication was generally ineffective, but memantine showed moderate improvement. Prospective studies are needed to enlarge the phenotype and assess the efficacy of NMDA receptor antagonist therapies in reducing seizure frequency and improving quality of life.

Bilaterality of temporal EEG findings in limbic encephalitis compared to other mesiotemporal epilepsies – A retrospective cohort study

BackgroundThe current diagnostic criteria for autoimmune limbic encephalitis (LE) stress bilaterality of temporal MRI and EEG findings. This retrospective cohort study aimed to determine whether bilaterality is indeed more common in LE than in other mesiotemporal epilepsies. MethodsWe compared EEG findings mostly from long-term EEG monitoring in patients with LE (n=59), hippocampal sclerosis (HS, n=44), and mesiotemporal tumors (n=24). ResultsBilateral temporal EEG findings including temporal slowing, interictal epileptiform discharges (IED), and seizures were equally frequent with 37% in LE, 32% in HS, and 17% in tumor patients. Bilateral independent temporal seizures were infrequent with 3%, 9%, and 0%, respectively. Patients with seropositive LE more often showed an EEG without IED or seizure patterns than patients with seronegative LE (n=37) with a higher proportion of unilateral temporal findings. Patients with immunotherapy naïve LE (n=40) showed a higher proportion of bilateral temporal IED or slowing in comparison with tumor patients. ConclusionsWe conclude that unilateral or absent temporal EEG findings are common in LE and should not discourage this differential diagnosis.

Sparse Common Feature Analysis for Detection of Interictal Epileptiform Discharges From Concurrent Scalp EEG

Temporal interictal epileptiform discharges (IEDs) are often invisible in the scalp EEG (sEEG). However, due to within-electrode temporal correlation and between-electrode spatial correlation, they still have their signatures in the sEEG. Therefore, it is expected to have some common spatial and temporal features among the IEDs. In this paper, we first present a novel method, called common feature analysis (CFA)-based method, for IED detection via an existing common orthogonal basis extraction (COBE) algorithm. In the second approach, we benefit from the sparsity of IED waveforms in developing a new algorithm, namely sparse COBE, and based on that, a sparse CFA (SCFA)-based method for IED detection. The proposed CFA and SCFA models are compared with two state-of-the-art IED detection methods. Two types of approaches, namely within- and between-subject classification approaches, are employed for evaluating the methods. SCFA outperforms the others and achieves the accuracy values of 75.1% and 67.8% using within- and between-subject classification approaches, respectively. This enables the proposed techniques to capture the intracranial biomarkers of epilepsy and ameliorate the performance of a classifier in automatically detecting the scalp-invisible IEDs from sEEG.

Seizure in Patient with Neurofibromatosis and Amygdala Low-Grade Glioma

A 31-year-old male with history of bipolar disorder, suicidal attempts requiring inpatient hospitalization, and seizures on antiepileptic medications presented with increasing seizure frequency. He was neurologically intact yet had multiple facial, axillary, and inguinal flat pigmented macules (cafe au lait spots) and ophthalmologic examination with iris hamartomas (Lisch nodules) consistent with neurofibromatosis type1. Electroencephalogram was notable for multiple right temporal lobe seizures with anterior temporal interictal epileptiform discharges. Magnetic resonance imaging revealed a T2 hyperintense mass centered in the right amygdala, contiguous with the cystic area. Preoperative intracarotid sodium amobarbital testing showed left-sided language and memory dominance. The patient was operated on for right amygdalohippocampectomy, and initial pathology was consistent with a low-grade neuroepithelial neoplastic process. Further pathologic examination found hypercellular proliferation of predominantly bland, spindled cells with scattered, embedded neurocytic elements with dysplastic appearance, consistent with low-grade glioma. The patient was clinically diagnosed with neurofibromatosis type1.

Features of intracranial interictal epileptiform discharges associated with memory encoding.

Interictal epileptiform discharges (IEDs) were shown to be associated with cognitive impairment in persons with epilepsy. Previous studies indicated that IED rate, location, timing, and spatial relation to the seizure onset zone could predict an IED's impact on memory encoding and retrieval if they occurred in lateral temporal, mesial temporal, or parietal regions. In this study, we explore the influence that other IED properties (e.g., amplitude, duration, white matter classification) have on memory performance. We were specifically interested in investigating the influence that lateral temporal IEDs have on memory encoding. Two hundred sixty-one subjects with medication-refractory epilepsy undergoing intracranial electroencephalographic monitoring performed multiple sessions of a delayed free-recall task (n=671). Generalized linear mixed models were utilized to examine the relationship between IED properties and memory performance. We found that increased IED rate, IEDs propagating in white matter, and IEDs localized to the left middle temporal region were associated with poorer memory performance. For lateral temporal IEDs, we observed a significant interaction between IED white matter categorization and amplitude, where IEDs with an increased amplitude and white matter propagation were associated with reduced memory performance. Additionally, changes in alpha power after an IED showed a significant positive correlation with memory performance. Our results suggest that IED properties may be useful for predicting the impact an IED has on memory encoding. We provide an essential step toward understanding pathological versus potentially beneficial interictal epileptiform activity.

O-EG003. Can spike voltage topography predict the ictal patterns in temporal lobe epilepsy?

Introduction . To study whether voltage topographic analysis of interictal epileptiform discharges (IEDs) in temporal lobe epilepsy (TLE) help to predict the type of scalp ictal onset pattern. Methods . IEDs from 74 patients with drug resistant TLE and unilateral mesial temporal sclerosis (MTS) who underwent presurgical evaluation were categorized according to dipolar fields into Types A and B temporal IEDs. Type A IEDs were defined as those with dipolar fields (tangential/ vertical) with sharply defined negativity over the infero-lateral temporal scalp and positivity over contra lateral centro-parietal scalp. Type B IEDs included all other IEDs other than Type A. Scalp ictal electrographic patterns were classified into rhythms confined to temporal lobe ipsilateral to MTS (“focal”), lateralized to the hemisphere (“regional”), and diffuse, nonlateralized and non-localized rhythms (“diffuse”) and ictal onset to the contra lateral side of MTS (“discordant”). Results . A total of 5476 IEDs and 377 seizures were analyzed. They were divided into four categories based on the side of MTS: 1) Type A IEDs ipsilateral to MTS (44 patients); 2) bilateral Type A IEDs (16 patients); 3) Type B IEDs ipsilateral and Type A IEDs contra laterally (7 patients); 4) Bilateral type B IEDs (7 patients). In 51 of 60 (85%) patients with Type A IEDs (either ipsilateral and/or bilateral to MTS), the ictal pattern was either focal or regional and only in 9 patients (15%) it was “diffuse”.12 of 14 (86%) patients with either ipsilateral or bilateral Type B IEDs showed a diffuse ictal onset, whereas 2 (14%) showed a contralateral ictal onset. Conclusion . In MTS, Type A IEDs are associated with clearly localized ictal onset and Type B IEDs with diffuse ictal onset. A spikevoltage topographic analysis is sufficient for selection of cases for antero-medial temporal lobe resection. Additional home-video recordings of seizures can rule out psychogenic non-epileptiform events.

Unilateral temporal interictal epileptiform discharges correctly predict the epileptogenic zone in lesional temporal lobe epilepsy.

To evaluate the necessity of recording ictal electroencephalography (EEG) in patients with temporal lobe epilepsy (TLE) considered for resective surgery who have unilateral temporal interictal epileptiform discharges (IEDs) and concordant ipsitemporal magnetic resonance imaging (MRI) pathology. To calculate the necessary number of recorded EEG seizure patterns (ESPs) to achieve adequate lateralization probability. In a retrospective analysis, the localization and lateralization of interictal and ictal EEG of 304 patients with lesional TLE were analyzed. The probability of further contralateral ESPs was calculated based on a total of 1967 recorded ESPs, using Bayes' theorem. Two hundred seventy-one patients had unilateral TLE, and in 98% of them (265 of 271), IEDs were recorded during video-EEG monitoring. Purely unilateral temporal IEDs were present in 61% (166 of 271 patients). Ipsilateral temporal MRI pathology was found in 83% (138 of 166). Ictal EEG was concordant with the clinical side of TLE in 99% (136 of 138) of these patients. Two patients had discordant ictal EEG with both ipsilateral and contralateral ESPs. Epilepsy surgery with resection in the lesioned temporal lobe was still performed, and both patients remain seizure-free. Probability calculations demonstrate that at least 6 recorded unilateral ESPs result in a >95% probability for a concordance of >0.9 of any further ESPs. The combination of purely unilateral temporal IED with ipsitemporal MRI pathology is sufficient to identify the epileptogenic zone, and the recording of ictal ESP did not add any surgically relevant information in these 138 patients. Rarely, discordant ESPs might be recorded, but the surgical outcome remains excellent after surgery on the lesioned side.

Long-term outcome characteristics in mesial temporal lobe epilepsy with and without associated cortical dysplasia

ObjectThe intention of our study was to identify predictive characteristics for long-term seizure control and running down phenomenon after surgical treatment of pharmacoresistant mesiotemporal lobe epilepsy (mTLE) with and without associated cortical dysplasia. Materials and methodsOur study comprises a consecutive series of 458 patients who underwent surgical treatment for intractable mTLE at the Epilepsy Center Freiburg. Data evaluated included semiology, duration and frequency of seizures, results of presurgical diagnostics including video-EEG monitoring, MRI, PET and SPECT as well as postoperative seizure outcome. Results were evaluated forming two groups: Group A consisted of isolated mesiotemporal lesions. Group B comprised patients with mTLE and additional focal cortical dysplasia (FCD). Statistical evaluation was based on the Kaplan Meier survival analysis, using log-rank-tests and a multivariate regression model. Postoperative running down phenomenon was defined as seizure freedom after a period of gradual reduction of postoperative seizure frequency. This was compared to patients with ongoing epilepsy. ResultsComplete seizure freedom was achieved in 65.0% of investigated patients at 1year and in 56.5% at long-term follow-up of ≥5 years after surgery. Corresponding results were 64.2% and 56.8% at 1 and ≥5 years, respectively in group A and 66.4% and 56.0%, respectively in group B. Predictive for favorable postoperative outcome in the total group were younger age at surgery, shorter duration of epilepsy, absence of secondarily generalized tonic-clonic seizures (SGTCS), presence of strictly ipsilateral temporal interictal epileptiform discharges (IEDs), complete resection of the lesion as well as absence of postoperative epileptiform activity and of early postoperative seizures. In subgroup analyses, patients of group A demonstrated longer postoperative seizure-free intervals with adolescent age at surgery, short duration of epilepsy before surgery and absence of SGTCS, whereas in patients of group B ipsilateral temporal seizure onset and strictly unilateral IEDs in EEG as well as complete resection were predictors for favorable seizure outcome. Furthermore, absence of early postoperative seizures and of spikes in EEG were predictive factors for long-term seizure-freedom in both subgroups.The running down phenomenon was found in 33 (7.2%) patients. None of the parameters evaluated demonstrated significant predictive power. Only late seizure onset and neoplastic lesions showed a trend for postoperative gradual seizure reduction in multivariate analyses. ConclusionDepending on the presence or absence of focal cortical dysplasia in addition to mesiotemporal structural alterations, predictors of long-term seizure control differed regarding the relevant clinical and electrophysiological features. This is important for specific patient counseling in respective groups.

PET imaging in extratemporal epilepsy requires consideration of electroclinical findings

ObjectiveThe study aimed to assess the relevance of interictal temporal glucose hypometabolism in patients with extratemporal epilepsy (ETE) by analyzing its association with a seizure semiology suggestive for temporal seizure involvement and the presence of temporal interictal epileptiform discharges (IEDs). MethodsWe retrospectively reviewed the database of our epilepsy monitoring unit for patients with ETE, in whom long-term EEG-video-monitoring and [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) had been performed. The localization of IEDs and the glucose hypometabolism were compared. ResultsAlmost half (46%) of the 63 ETE patients had IEDs localized in the temporal lobe. Most patients (87.5%; 7/8) with temporal IEDs and an ipsitemporal hypometabolism showed seizure semiology suggestive of temporal or limbic system involvement in contrast to only 31.0% (9/29, p=0.01) in patients without temporal IEDs nor temporal hypometabolism. Those patients also showed an ictal seizure pattern spread into the ipsitemporal lobe, compared with 75.9% (22/29, n.s.) in patients without temporal IEDs nor temporal hypometabolism. Both, extratemporal (ipsilateral in 82.1%; 23/28 patients) and temporal (ipsilateral in 78.6%; 11/14 patients) hypometabolism significantly (p<0.05) lateralized to the epileptogenic hemisphere. ConclusionThe common temporal glucose hypometabolism in ETE patients reflects a remote epileptic dysfunction arising from extratemporal epileptogenic zones. Thus, interpretation of interictal FDG-PET results requires consideration of EEG results and seizure semiology to avoid false localization particularly in non-lesional epilepsy.

THE RELATION BETWEEN CLINICAL, EPILEPTIFORM DISCHARGES, AND NEUROMETABOLIC DYSFUNCTION IN TEMPORAL LOBE EPILEPSY

Background: Temporal lobe epilepsy (TLE) is the most frequent cause of focal and refractory seizures. Magnetic Resonance Spectroscopy (MRS) is a potentially useful tool in the investigation of brain metabolites in TLE. Objective: to clarify the role of MRS in the TLE epilepsy and to evaluate the relationship between the results of MRS, Electroencephalography (EEG), and the clinical data of TLE patients with negative Magnetic Resonance imaging (MRI). Patients & Methods: Thirty patients with TLE and negative MRI were investigated by EEG, MRS and neuropsychological tests that assessed memory function of temporal lobe. By using temporal metabolite identified on MRS, we could detect metabolic disturbance that occur in TLE and tried to lateralize epileptic focus. We correlated MRS results with, EEG results, and the patient's scores on memory function tests. Twenty age-matched volunteers were used as control subjects. Result(s): Ipsilateral temporal N-acetyl-aspartate (NAA)/ Creatine+Choline (Cr+Cho) and NAA/Cr ratios of the patients were significantly reduced compared with the mean ratios of contralateral hippocampus (p <0.001) and control subjects (p <0.001). EEG could detect epileptic focus in 17 (56.7%) patients, while MRS could detect epileptic focus in 27 (90%) patients and could lateralize about 76.9% of patients with bitemporal interictal epileptiform discharges (IEDs). Significant negative correlation between ipsilateral temporal NAA/Cr+Cho, NAA/Cr ratios and ipsilateral IEDs ratio (p < 0.05). Left temporal NAA/Cr ratio correlated significantly with patient's scores on Rey Auditory Verbal Learning Test (RAVLT) (p< 0.05) and right temporal NAA/Cr ratio correlated significantly with patient's scores on Rey Complex Figure Test (RCFT) (p < 0.05). Conclusion(s): These findings suggested that the temporal metabolite ratios identified on MRS could lateralize epileptic focus in TLE patients and they are closely related to the temporal IEDs and the cognitive function of temporal lobe. Key Words: temporal lobe epilepsy, Magnetic resonance spectroscopy, EEG, memory.

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

ObjectivesSimultaneous 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).MethodsTwelve 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.ResultsNine 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.ConclusionsiEEG-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).

Congruence and discrepancy of interictal and ictal EEG with MRI lesions in focal epilepsies

To compare the occurrence and localization of interictal epileptiform discharges (IEDs) and epileptic seizure patterns (ESPs) with the localization of MRI lesions. We retrospectively analyzed the EEG and MRI data of a series of patients with focal epilepsies that had been studied from 1991 to 2009. In patients with temporal lesions, the localization of IEDs was most congruent (58.6% with IEDs exclusively over the lesional lobe and 29.7% with a majority of temporal IEDs). This differed (p < 0.001) from frontal lesions (27.5% with exclusively frontal IEDs, 24.6% with a majority of frontal IEDs). In parieto-occipital lobe lesions, only 12.1% had IEDs exclusively over the lesional lobe compared to 48.5% with no parieto-occipital IEDs at all. Patients with central lesions often lacked any IEDs (54.5%, p < 0.001). The occurrence and localization of ESPs also differed between the regions. They were most congruent in temporal lesions (63.5% of patient had ESPs only over the lesional lobe, 23.4% had the majority of ESPs over the lesional lobe), which differed from frontal and parieto-occipital lesions (37.7% and 30.3% of patients with ESPs only over the lesional lobe). Patients with central lesions had ESPs very frequently only outside the lesional lobe (63.6%). Surgery outcome did not differ between the regions. The occurrence and localization of interictal and ictal EEG findings differs vastly for lesions in different brain regions. These findings should be used to carefully weigh the results from EEG studies particularly in patients with extratemporal epilepsies considered for epilepsy surgery.

EEG and MEG in mesial temporal lobe epilepsy: Where do the spikes really come from?

Objective There is persistent debate as to whether or not EEG and MEG recordings in patients with mesial temporal lobe epilepsy (MTLE) can detect mesial temporal interictal epileptiform discharges (spikes), and this issue is particularly relevant for source localization studies. With the aim of providing direct evidence pertinent to this debate we present detailed examples of the intracranial sources of spikes recorded with EEG and MEG in MTLE. Methods Spikes recorded in five different patients with MTLE during intracranial EEG ( n = 2), intraoperative electrocorticography (ECOG; n = 1), combined scalp-intracranial EEG ( n = 2) and combined EEG-MEG ( n = 1) were analyzed and the intracranial sources of the spike foci were matched with their corresponding extracranial EEG and/or MEG fields. EEG and MEG dipole source localization was performed on six independent spike foci identified in one representative patient with bilateral MTLE. Results Spikes with an electrical field maximal at F7/8, F9/10 ⩾ T3/4 were generated in the anterolateral temporal neocortex. The absence of coincident spiking at mesial locations indicated that these were not propagated from or to the hippocampus. Spikes with an electrical field maximal at T3/4 ⩾ T9/10 were generated in the lateral temporal neocortex and likewise did not involve the hippocampus. Individual spikes generated in the mesiobasal temporal neocortex, including the fusiform gyrus, were difficult to detect with EEG (low amplitude diphasic waves most apparent after spike averaging at T3/4, T9/10 ⩾ T5/6, P9/10) and only slightly more identifiable with MEG. Spikes generated within and confined to the mesial temporal structures, as confirmed by intracranial recordings, could not be detected with EEG or MEG. Notably, such spikes could not be detected even at intracranial recording sites on the lateral surface of the temporal lobe. Conclusions We present detailed evidence in a small case series showing that typical anterior temporal spikes recorded with EEG and MEG in MTLE arose from the anterolateral temporal neocortex and were neither propagated from nor to the hippocampus. Mid temporal EEG spikes were localized to the lateral temporal neocortex. Intracranially detected mesial temporal spikes were not detected with EEG or MEG. Significance The spikes recorded with EEG and MEG in MTLE are localized to neocortical foci, and not to the mesial temporal structures. Current noninvasive EEG and MEG source localization studies cannot accurately identify true mesial temporal spikes.

Extent of initial injury determines language lateralization in mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE‐HS)

To assess the prevalence and attributes of atypical language lateralization (ALL) in patients with left mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS). We recruited consecutive patients with left MTLE-HS, who had undergone resective surgery and had pathologically proven HS. Based on the Wada test, language lateralization was classified into typical (left hemispheric) or atypical (right hemispheric or codominant). We assessed the attributes of patients with ALL using univariate and multivariate analyses. Of 124 patients with left MTLE-HS, 23 (18.5%) had ALL. ALL occurred more frequently in patients with severe initial precipitating injury (IPI), early onset of epilepsy, and a short latent period between IPI and onset of habitual seizures. ALL was more common in patients with bitemporal and extratemporal interictal epileptiform discharges (IEDs) on electroencephalogram (EEG) and extratemporal changes on magnetic resonance imaging (MRI). On multivariate analyses, the age at onset of habitual seizures <6 years, atypical IPI, nonunilateral temporal IEDs, and extratemporal MRI abnormalities independently predicted ALL. The likelihood of ALL was very low ( approximately 1%) when all of these four risk factors were absent, whereas it was very high (>95%), if any three or all four of them were present. ALL occurs in one-fifth of patients with left MTLE-HS. ALL is more frequent in those with structural or functional extrahippocampal involvement and early onset of epilepsy interrupting the development of normal language networks. Because ALL is uncommon in those with damage/dysfunction restricted to the hippocampus, the hippocampus itself may have only a limited role in determining language lateralization.

Ictal EEG remains the prominent predictor of seizure-free outcome after temporal lobectomy in epileptic patients with normal brain MRI

While an abnormal pre-operative high-resolution brain MRI portends a favorable outcome in patients undergoing resective epilepsy surgery for medically intractable localization-related epilepsy (LRE), a normal MRI is less favorable. Ascertaining desirable pre-operative predictors for successful anterior temporal lobectomy (ATL) in LRE patients with a normal brain MRI is essential to better anticipate surgical outcome. Patients with LRE and normal temporal structures on MRI underwent ATL at two epilepsy centers in the southeastern US (FL and NC). Outcome was separated into those patients that were seizure free (SF), and those that were not seizure free (NSF), and those NSF were stratified in accordance with the Engel classification system. Those with a pre-operative history of clinical risk factors, unilateral anterior temporal interictal epileptiform discharges (IEDs), well localized scalp ictal EEG with rhythmic temporal theta at onset, localized PET/ictal SPECT, and Wada asymmetry with >2.5/8, were evaluated for the purpose of predicting outcome. Where appropriate, data is presented as a median (mean +/- S.D.). Thirty-nine patients, median age 33 years, were followed up 2 years (3+/-1.2) after ATL. Overall, 22/39 (56.4%) patients were identified as SF, and 17/39 (43.6%) patients were NSF. Ictal EEG with rhythmic temporal theta at onset was the only predictive measure of seizure-free outcome (p=0.001, Fisher's exact test), and also favorably correlated with seizure reduction (p=0.0001, r(2)=0.34, multiple regression analysis). None of the other predictors examined added greater predictive value. ATL is a favorable option for patients with LRE even when high-resolution brain MRI reveals normal temporal structures. Normal brain MRI patients with localizing pre-operative scalp ictal EEG, have better outcomes following ATL.

Source localization of interictal epileptiform discharges: Comparison of three different techniques to improve signal to noise ratio

Objective To investigate the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) using a new relative averaging (RELAVG) technique for noise reduction. Methods We analyzed 19 patterns of mesial temporal IED recorded simultaneously with scalp and foramen ovale (FO) electrodes in 15 consecutive patients who underwent presurgical assessment for intractable temporal lobe epilepsy. The scalp signals were time-locked to the peak activity in the FO electrode recordings and source modeling was performed using the RELAVG technique. Random noise of various amounts was then applied. The results were compared to intracranial data obtained from the FO electrode recordings and to LORETA source solutions obtained using two other approaches to improve signal to noise ratio (SNR): statistical non-parametric mapping (SNPM) and the commonly applied averaging (AVG) technique. Results The RELAVG technique allowed for reasonable mesial temporal localization in 52.6% (10/19) of IED patterns, compared with 73.7% (14/19) using SNPM. The AVG technique provided no strictly mesial temporal solutions. Nine of the IED patterns revealed relative current density quotient changes >10; all of these were accurately localized by RELAVG into mesial temporal structures. Increasing amounts of white and physiological noise had no influence on the accuracy of RELAVG and SNPM solutions, whereas AVG source reconstructions became progressively spurious. Conclusion The RELAVG technique and SNPM, but not the commonly used AVG technique, allow for reasonable source localization of mesial temporal IED. SNPM is the most accurate but also the most time-consuming noise reduction technique. Significance The RELAVG LORETA technique might provide a simple and fast semi-quantitative alternative for localizing IED with low single to noise ratio.

Source localization of mesial temporal interictal epileptiform discharges: Correlation with intracranial foramen ovale electrode recordings

Objective We have investigated the localization accuracy of low-resolution electromagnetic tomography (LORETA) for mesial temporal interictal epileptiform discharges (IED) on a statistical basis by using clinical electroencephalographic (EEG) data of simultaneous scalp and intracranial foramen ovale (FO) electrode recordings. Methods We retrospectively analyzed the IED of 15 patients who underwent presurgical assessment for intractable temporal lobe epilepsy. All patients have subsequently undergone amygdalohippocampectomy. The scalp signals were averaged time-locked to the peak activity in bilateral 10-contact FO electrode recordings. Source modeling was carried out by using statistical non-parametric mapping (SNPM) of LORETA values and by calculating raw LORETA values of averaged IED. The results were compared to intracranial data obtained from FO electrode recordings. Results Two thousand six hundred and fifteen discharges could be attributed to 19 different patterns of intracranial mesial temporal IED. SNPM of LORETA revealed confined ipsilateral mesial temporal solutions for 14 (73.7%) and no significant solutions for five (26.3%) of these patterns. Raw LORETA current density distributions of the 19 averaged IED patterns revealed ipsilateral basal to lateral temporal solutions for the 14 IED patterns with a sufficient signal to noise ratio (SNR), but spurious results for those five IED with a low SNR. Conclusions SNPM of LORETA but not LORETA analysis of averaged IED patterns accurately localizes the source generators of mesial temporal IEDs. Significance SNPM of raw LORETA values might be appropriate for localizing restricted mesial temporal lobe sources.