The impact of a history of status epilepticus for epilepsy surgery outcome.

OBJECTIVE: Patients with focal drug resistant epilepsy are excellent candidates for epilepsy surgery. Status epilepticus (SE) and seizure clusters (SC), described in a subset of patients, have both been associated with extended epileptogenic cerebral networks within one or both hemispheres. In this retrospective study, we were interested to determine if a history of SE or SC is associated with a worse surgical outcome. METHODS: Data of 244 patients operated between 2000 to 2018 were reviewed, with a follow-up of at least 2 years. Patients with a previous history of SE or SC were compared to operated patients without these conditions (control group, CG). RESULTS: We identified 27 (11%) and 38 (15.5%) patients with history of SE or SC, respectively. No difference in post-operative outcome was found for SE and SC patients. Compared to the control group, patients with a history of SE were diagnosed and operated significantly at earlier age(p = 0.01), and after a shorter duration of the disease (p = 0.027), but with a similar age of onset. SIGNIFICANCE: A history of SE or SC was not associated with a worse post-operative prognosis. Earlier referral of SE patients for surgery suggests a heightened awareness regarding serious complications of recurrent SE by the referring neurologist or neuropediatrician. While the danger of SE is evident, policies to underline the impact for SC or very frequent seizures might be an efficient approach to accelerate patient referral also for this patient group.

Network alterations in temporal lobe epilepsy during non-rapid eye movement sleep and wakefulness.

OBJECTIVE: Investigate sleep and temporal lobe epilepsy (TLE) effects on brain networks derived from electroencephalography (EEG). METHODS: High-density EEG was recorded during non-rapid eye movement (NREM) sleep stage 2 (N2) and wakefulness in 23 patients and healthy controls (HC). Epochs without epileptic discharges were source-reconstructed in 72 brain regions and connectivity was estimated. We calculated network integration and segregation at global (global efficiency, GE; average clustering coefficient, avgCC) and hemispheric level. These were compared between groups across frequency bands and correlated with the individual proportion of wakefulness- or sleep-related seizures. RESULTS: At the global level, patients had higher delta GE, delta avgCC and theta avgCC than controls, irrespective of the vigilance state. During wakefulness, theta GE of patients was higher than controls and, for patients, theta GE during wakefulness was higher than during N2. Wake-to-sleep differences in TLE were notable only in the ipsilateral hemisphere. Only measures from wakefulness recordings correlated with the proportion of wakefulness- or sleep-related seizures. CONCLUSIONS: TLE network alterations are more prominent during wakefulness and at lower frequencies. Increased integration and segregation suggest a pathological 'small world' configuration with a possible inhibitory role. SIGNIFICANCE: Network alterations in TLE occur and are easier to detect during wakefulness.

Structure-function coupling increases during interictal spikes in temporal lobe epilepsy: A graph signal processing study.

OBJECTIVE: Structure-function coupling remains largely unknown in brain disorders. We studied this coupling during interictal epileptic discharges (IEDs), using graph signal processing in temporal lobe epilepsy (TLE). METHODS: We decomposed IEDs of 17 patients on spatial maps, i.e. network harmonics, extracted from a structural connectome. Harmonics were split in smooth maps (long-range interactions reflecting integration) and coarse maps (short-range interactions reflecting segregation) and were used to reconstruct the part of the signal coupled (Xc) and decoupled (Xd) from the structure, respectively. We analysed how Xc and Xd embed the IED energy over time, at global and regional level. RESULTS: For Xc, the energy was smaller than for Xd before the IED onset (p < .001), but became larger around the first IED peak (p < .05, cluster 2, C2). Locally, the ipsilateral mesial regions were significantly coupled to the structure over the whole epoch. The ipsilateral hippocampus increased its coupling during C2 (p < .01). CONCLUSIONS: At whole-brain level, segregation gives way to integrative processes during the IED. Locally, brain regions commonly involved in the TLE epileptogenic network increase their reliance on long-range couplings during IED (C2). SIGNIFICANCE: In TLE, integration mechanisms prevail during the IED and are localized in the ipsilateral mesial temporal regions.

Modulation of epileptic networks by transient interictal epileptic activity: A dynamic approach to simultaneous EEG-fMRI.

Epileptic networks, defined as brain regions involved in epileptic brain activity, have been mapped by functional connectivity in simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) recordings. This technique allows to define brain hemodynamic changes, measured by the Blood Oxygen Level Dependent (BOLD) signal, associated to the interictal epileptic discharges (IED), which together with ictal events constitute a signature of epileptic disease. Given the highly time-varying nature of epileptic activity, a dynamic functional connectivity (dFC) analysis of EEG-fMRI data appears particularly suitable, having the potential to identify transitory features of specific connections in epileptic networks. In the present study, we propose a novel method, defined dFC-EEG, that integrates dFC assessed by fMRI with the information recorded by simultaneous scalp EEG, in order to identify the connections characterised by a dynamic profile correlated with the occurrence of IED, forming the dynamic epileptic subnetwork. Ten patients with drug-resistant focal epilepsy were included, with different aetiology and showing a widespread (or multilobar) BOLD activation, defined as involving at least two distinct clusters, located in two different lobes and/or extended to the hemisphere contralateral to the epileptic focus. The epileptic focus was defined from the IED-related BOLD map. Regions involved in the occurrence of interictal epileptic activity; i.e., forming the epileptic network, were identified by a general linear model considering the timecourse of the fMRI-defined focus as main regressor. dFC between these regions was assessed with a sliding-window approach. dFC timecourses were then correlated with the sliding-window variance of the IED signal (VarIED), to identify connections whose dynamics related to the epileptic activity; i.e., the dynamic epileptic subnetwork. As expected, given the very different clinical picture of each individual, the extent of this subnetwork was highly variable across patients, but was but was reduced of at least 30% with respect to the initially identified epileptic network in 9/10 patients. The connections of the dynamic subnetwork were most commonly close to the epileptic focus, as reflected by the laterality index of the subnetwork connections, reported higher than the one within the original epileptic network. Moreover, the correlation between dFC timecourses and VarIED was predominantly positive, suggesting a strengthening of the dynamic subnetwork associated to the occurrence of IED. The integration of dFC and scalp IED offers a more specific description of the epileptic network, identifying connections strongly influenced by IED. These findings could be relevant in the pre-surgical evaluation for the resection or disconnection of the epileptogenic zone and help in reaching a better post-surgical outcome. This would be particularly important for patients characterised by a widespread pathological brain activity which challenges the surgical intervention.

The network integration of epileptic activity in relation to surgical outcome.

OBJECTIVE: Epilepsy 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: Abnormal network patterns in epilepsy are related to seizure outcome after surgery. SIGNIFICANCE: Our 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.

What to do in failed hemispherotomy? Our clinical series and review of the literature.

Hemispherotomy is an established surgical technique to cure or palliate selected, mostly young patients suffering from refractory epilepsy. However, a few patients continue to have seizures despite the surgical hemispherical disconnection. We present a case series of patients who underwent redo hemispherotomy after a first unsuccessful hemispherical disconnection and provide a roadmap for subsequent workup and treatment. The institutional database of epilepsy surgery was reviewed. Twenty-four patients who underwent hemispherotomies for refractory epilepsy were identified between 2007 and 2016. Patients' notes were checked for demographics, history, clinical presentation, preoperative workup, medical treatment, age at first hemispherotomy, and surgical technique. Complications, histopathology, postoperative antiepileptic drug, and postoperative neurological follow-up were documented. Engel class was used to determine the outcome after surgery. Three patients (one hemimegalencephaly, one perinatal stroke, and one Rasmussen's disease) underwent redo hemispherotomy after electroencephalography and MRI studies with particular importance given to diffusion tensor imaging (DTI) to demonstrate residual connection between hemispheres. In one case, redo disconnection followed by a frontal lobectomy rendered the patient seizure-free (Engel class I). In one case, the seizure frequency remained the same but generalized seizures disappeared (Engel class III), and in one case, seizure frequency was considerably reduced after the redo disconnection (Engel class II), with a minimum follow-up of 2 years. Surgical aspects, possible reasons of failure of first hemispherotomy, and rationale that led to second-look surgery are presented. Reasons for failure can be related to patient's selection and/or surgical aspects. Hemispherotomy is a technically demanding procedure and requires accurate preoperative workup. Redo hemispherotomy is a valid option on the basis of further epileptological and radiological workup to demonstrate residual interhemispheric connections and/or rule out bi-hemispheric epileptic activity.

Early specialized care after a first unprovoked epileptic seizure.

A first seizure is a life-changing event with physical and psychological consequences. We aimed to assess the role of early comprehensive patient care after a first unprovoked seizure to improve diagnostic accuracy and follow-up adherence. From April 2011 to March 2012, patients presenting a first unprovoked epileptic seizure received standard patient care (SPC), i.e., a consultation in the ED, an EEG and a CT scan. The patients were notified of the follow-ups. We compared this protocol to subsequently acquired "early comprehensive patient care" (ECPC), which included a consultation by an epileptologist in the emergency department (ED), a routine or long-term monitoring electroencephalogram (LTM-EEG), magnetic resonance imaging and three follow-up consultations (3 weeks, 3 months, 12 months). 183 patients were included (113 ECPC, 70 SPC). LTM-EEG and MRI were performed in 51 and 85 %, respectively, of the patients in the ECPC group vs in 7 and 52 % of the patients in the SPC group (p < 0.001). A final diagnosis was obtained in 64 vs 43 % of the patients in the ECPC vs SPC group (p < 0.01). Patient attendance at 3-month was 84 % in the ECPC group vs 44 % in the SPC group (p < 0.001). At 12-month follow-up, the delay until the first recurrence was longer in the ECPC group (p = 0.008). An early epileptologist-driven protocol is associated with clinical benefit in terms of diagnostic accuracy, follow-up adherence and recurrence. This study highlights the need for epilepsy experts in the early assessment of a first epileptic seizure, starting already in the ED.

Comparison of high gamma electrocorticography and fMRI with electrocortical stimulation for localization of somatosensory and language cortex.

OBJECTIVE: We investigated the contribution of electrocortical stimulation (ECS), induced high gamma electrocorticography (hgECoG) and functional magnetic resonance imaging (fMRI) for the localization of somatosensory and language cortex. METHODS: 23 Epileptic patients with subdural electrodes underwent a protocol of somatosensory stimulation and/or an auditory semantic decision task. 14 Patients did the same protocol with fMRI prior to implantation. RESULTS: ECS resulted in the identification of thumb somatosensory cortex in 12/16 patients. Taking ECS as a gold standard, hgECoG and fMRI identified 53.6/33% of true positive and 4/12% of false positive contacts, respectively. The hgECoG false positive sites were all found in the hand area of the post-central gyrus. ECS localized language-related sites in 7/12 patients with hgECoG and fMRI showing 50/64% of true positive and 8/23% of false positive contacts, respectively. All but one of the hgECoG/fMRI false positive contacts were located in plausible language areas. Four patients showed post-surgical impairments: the resection included the sites positively indicated by ECS, hgECoG and fMRI in 3 patients and a positive hgECoG site in one patient. CONCLUSIONS: HgECoG and fMRI provide additional localization information in patients who cannot sufficiently collaborate during ECS. SIGNIFICANCE: HgECoG and fMRI make the cortical mapping procedure more flexible not only by identifying priority cortical sites for ECS or when ECS is not feasible, but also when ECS does not provide any result.

[Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version]. / Qualitätsleitlinien für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie : 1. Neufassung.

In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory.

Effects of amygdala-hippocampal stimulation on synchronization.

Changes in EEG synchronization, i.e., spatio-temporal correlation, with amygdala-hippocampal stimulation were studied in patients with temporal lobe epilepsy. Synchronization was evaluated for high frequency, 130 Hz, pseudo-monophasic or biphasic charge-balanced pulses. Desynchronization was most frequently induced by stimulation. There was no correlation between the changes in synchronization and the changes in interictal epileptiform discharge rates. Changes in synchronization do not appear yet to be a marker of stimulation efficiency in reducing seizures.

A multi-center study: intra-scan and inter-scan variability of diffusion spectrum imaging.

The objective of this study was to investigate whether it is possible to pool together diffusion spectrum imaging data from four different scanners, located at three different sites. Two of the scanners had identical configuration whereas two did not. To measure the variability, we extracted three scalar maps (ADC, FA and GFA) from the DSI and utilized a region and a tract-based analysis. Additionally, a phantom study was performed to rule out some potential factors arising from the scanner performance in case some systematic bias occurred in the subject study. This work was split into three experiments: intra-scanner reproducibility, reproducibility with twin-scanner settings and reproducibility with other configurations. Overall for the intra-scanner and twin-scanner experiments, the region-based analysis coefficient of variation (CV) was in a range of 1%-4.2% and below 3% for almost every bundle for the tract-based analysis. The uncinate fasciculus showed the worst reproducibility, especially for FA and GFA values (CV 3.7-6%). For the GFA and FA maps, an ICC value of 0.7 and above is observed in almost all the regions/tracts. Looking at the last experiment, it was found that there is a very high similarity of the outcomes from the two scanners with identical setting. However, this was not the case for the two other imagers. Given the fact that the overall variation in our study is low for the imagers with identical settings, our findings support the feasibility of cross-site pooling of DSI data from identical scanners.

Effects of amygdala-hippocampal stimulation on interictal epileptic discharges.

Deep brain stimulation (DBS) of different nuclei is being evaluated as a treatment for epilepsy. While encouraging results have been reported, the effects of changes in stimulation parameters have been poorly studied. Here the effects of changes of pulse waveform in high frequency DBS (130 Hz) of the amygdala-hippocampal complex (AH) are presented. These effects were studied on interictal epileptic discharge rates (IEDRs). AH-DBS was implemented with biphasic versus pseudo monophasic charge balanced pulses, in two groups of patients: six with temporal lobe epilepsy (TLE) associated with hippocampal sclerosis (HS) and six with non lesional (NLES) temporal epilepsy. In patients with HS, IEDRs were significantly reduced with AH-DBS applied with biphasic pulses in comparison with monophasic pulse. IEDRs were significantly reduced in only two patients with NLES independently to stimulus waveform. Comparison to long-term seizure outcome suggests that IEDRs could be used as a neurophysiological marker of chronic AH-DBS and they suggest that the waveform of the electrical stimuli can play a major role in DBS. We concluded that biphasic stimuli are more efficient than pseudo monophasic pulses in AH-DBS in patients with HS. In patients with NLES epilepsy, other parameters relevant for efficacy of DBS remain to be determined.

Diffusion tensor imaging analysis with tract-based spatial statistics of the white matter abnormalities after epilepsy surgery.

INTRODUCTION: Diffusion tensor imaging (DTI) techniques demonstrated diffuse bilateral temporal and extra-temporal abnormalities of white matter in patients presenting mesial temporal lobe epilepsy with hippocampal sclerosis (HS). The aim of this study was to assess these diffusion changes following temporal lobe surgery, by applying a novel voxel-based tract-based spatial statistics (TBSS) technique for whole-brain analysis of fractional anisotropy (FA) and mean diffusivity (MD). Second, region-of-interest analysis (ROI) was performed to improve statistical power. MATERIAL AND METHODS: The study included 22 patients with unilateral HS. Twelve patients underwent temporal lobe surgery. Follow up MRI was done in a mean interval of 4 months. Voxelwise pre-operative FA asymmetry in all 22 patients was assessed within subjects between lesional and contralateral hemispheres. The whole-brain post-operative dataset of 10 seizure-free patients was compared with the corresponding pre-operative dataset using voxel-wise statistical analysis. Additionally, regional analysis at the fornices was done with skeleton-based region of interest (SROI). RESULTS: Within a mean interval time of 6.3 months after surgery, 10 of 12 patients were seizure free (83.3%). The voxelwise comparison between lesional and contralateral hemispheres was consistent with previous studies showing a more widespread diffusion alteration in the lesional hemisphere. Voxel-wise comparison between post and pre-operative dataset did not show supra-thresholded voxels. SROI statistical analysis showed significant decrease in FA and increase in MD in the ipsilateral fornix. Significant increase in FA was observed in the contralateral fornix after surgery. CONCLUSION: The ipsi-lesional fornix showed decreased FA and increased MD after surgery, consistent with Wallerian degeneration. In contrast, contra-lesional fornix demonstrated increase in FA. This observation is important for our understanding of the fate of the remaining brain tissue following removal of an epileptic focus. Postoperative increase in FA may reflect structural reorganization in response to epilepsy surgery. The discrepancy between SROI and voxelwise statistics emphasizes the difference of statistical sensitivity between voxelwise and ROI analyses.

[Current drug treatment for epilepsy]. / Traitement médicamenteux actuel de l'épiepsie.

If one patient is diagnosed with epilepsy, the first treatment line is represented by medications, which allow a seizure control in at least 2/3 of patients. Following the steady development of new compounds, there are currently more than 20 antiepileptic agents on the market, and several more will appear in the near future. This review, focusing on the indications and pitfalls of the most used drugs, with a particular attention to the new ones, aims at improving the orientation among this multitude of options. Since there is almost no difference regarding the efficacy on seizures, it is rather the profile of comorbidities and possible (positive and negative) side effects that will allow to select the best antiepileptic drug for each specific clinical situation, permitting a patient-tailored approach.

[Autoimmune epilepsy]. / Epilepsies d'origine auto-immune.

There is increasing recognition of an autoimmune origin of pharmacoresistant epileptic disorders. Besides the paraneoplastic limbic encephalopathies (LE), reports of syndromes of non-paraneoplastic LE are increasingly reported in the last 5-10 years. Three antibodies are now relatively well described: Voltage-gated potassium channels (VGKC), glutamic acid decarboxylase (GAD) and N-methyl-D-aspartate receptor-(NMDA) antibodies. We review clinical syndromes, associated imaging and laboratory findings. While most reports arise from adult populations, children and adolescents are also concerned as evidenced by increasing observations. Early recognition is mandatory, since early immunomodulatory treatment appears to be related to significantly better outcome.

Antiepileptic drugs modify power of high EEG frequencies and their neural generators.

BACKGROUND: The clinical and molecular effects of antiepileptic drugs (AEDs) have been extensively investigated. Much less is known about their effects on human electrophysiology. METHODS: Topographic analysis in the frequency domain has been used to analyze 104 electroencephalogram (EEG) epochs of 52 patients presenting with first-ever generalized seizure, with normal MRI and EEG. Patients were treated with valproate, arbamazepine, or lamotrigine in monotherapy (each group n = 13). Thirteen patients without medication served as a control group. RESULTS: Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50-60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30-40 Hz). No such changes were found in the control group. For all AEDs, the neural generators were shifted more anteriorly in medial temporal through to inferior frontal regions. CONCLUSION: Decreased gamma-power and anterior shift of neural generators after AED introduction reflect AED influence on human electrophysiology.