BACKGROUND: Multiple hippocampal transection (MHT) is a surgical technique used for the treatment of drug-resistant mesial temporal lobe epilepsy in situations where standard procedures would pose a high risk for memory deterioration. During MHT, the longitudinal fibers of the hippocampus, implicated in epilepsy spreading, are interrupted, while the transverse memory circuits are spared. The extent of MHT is governed by intraoperative electrocorticography; abolition of epileptic discharges serves as an end point to terminate the transection. In other words, the aim of MHT is not the anatomical completeness of hippocampal transection. In contrast, we hypothesize that only the complete transection of hippocampal cross-section is needed to durably terminate epilepsy, avoiding possible postoperative reorganization of longitudinal pathways. Here, we report an anatomical study designed to evaluate the feasibility of complete transection of hippocampus with the aid of ultrasound neuronavigation and we propose new instruments to reach this goal. METHODS: Five cadaveric brains were analyzed in this study. MHT was performed on both sides of each brain either with or without ultrasound neuronavigation. The percentage of transected cross-section of the hippocampus was measured using magnetic resonance imaging (MRI) and both sides were compared. RESULTS: The ultrasound-guided MHTs were more likely to achieve complete hippocampal transection compared with the nonnavigated MHT transection (73 vs 58%; p < 0.01). Our study also allowed us to propose specialized transectors to minimize invasivity of this procedure. CONCLUSION: Completeness of MHT can be better reached with the aid of an ultrasound neuronavigation system; modified instruments for this procedure were also designed.

• MeSH
• epilepsie temporálního laloku * chirurgie   diagnostické zobrazování   MeSH
• hipokampus * diagnostické zobrazování   chirurgie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mrtvola MeSH
• neurochirurgické výkony metody   MeSH
• neuronavigace * metody   MeSH
• refrakterní epilepsie chirurgie   diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Despite extensive temporal lobe epilepsy (TLE) research, understanding the specific limbic structures' roles in seizures remains limited. This weakness can be attributed to the complex nature of TLE and the existence of various TLE subsyndromes, including non-lesional TLE. Conventional TLE models like kainate and pilocarpine hinder precise assessment of the role of individual limbic structures in TLE ictogenesis due to widespread limbic damage induced by the initial status epilepticus. In this study, we used a non-lesional TLE model characterized by the absence of initial status and cell damage to determine the spatiotemporal profile of seizure initiation and limbic structure recruitment in TLE. Epilepsy was induced by injecting a minute dose of tetanus toxin into the right dorsal hippocampus in seven animals. Following injection, animals were implanted with bipolar recording electrodes in the amygdala, dorsal hippocampus, ventral hippocampus, piriform, perirhinal, and entorhinal cortices of both hemispheres. The animals were video-EEG monitored for four weeks. In total, 140 seizures (20 seizures per animal) were analyzed. The average duration of each seizure was 53.2+/-3.9 s. Seizure could initiate in any limbic structure. Most seizures initiated in the ipsilateral (41 %) and contralateral (18 %) ventral hippocampi. These two structures displayed a significantly higher probability of seizure initiation than by chance. The involvement of limbic structures in seizure initiation varied between individual animals. Surprisingly, only 7 % of seizures initiated in the injected dorsal hippocampus. The limbic structure recruitment into the seizure activity wasn't random and displayed consistent patterns of early recruitment of hippocampi and entorhinal cortices. Although ventral hippocampus represented the primary seizure onset zone, the study demonstrated the involvement of multiple limbic structures in seizure initiation in a non-lesional TLE model. The study also revealed the dichotomy between the primary epileptogenic lesion and main seizure onset zones and points to the central role of ventral hippocampi in temporal lobe ictogenesis.

• MeSH
• elektroencefalografie MeSH
• epilepsie temporálního laloku * chemicky indukované   patofyziologie   patologie   MeSH
• hipokampus účinky léků   patologie   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech * MeSH
• potkani Sprague-Dawley MeSH
• tetanový toxin * toxicita   MeSH
• záchvaty * chemicky indukované   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• tetanový toxin * MeSH

BACKGROUND AND OBJECTIVE: Patients with presumed nonlesional focal epilepsy-based on either MRI or histopathologic findings-have a lower success rate of epilepsy surgery compared with lesional patients. In this study, we aimed to characterize a large group of patients with focal epilepsy who underwent epilepsy surgery despite a normal MRI and had no lesion on histopathology. Determinants of their postoperative seizure outcomes were further studied. METHODS: We designed an observational multicenter cohort study of MRI-negative and histopathology-negative patients who were derived from the European Epilepsy Brain Bank and underwent epilepsy surgery between 2000 and 2012 in 34 epilepsy surgery centers within Europe. We collected data on clinical characteristics, presurgical assessment, including genetic testing, surgery characteristics, postoperative outcome, and treatment regimen. RESULTS: Of the 217 included patients, 40% were seizure-free (Engel I) 2 years after surgery and one-third of patients remained seizure-free after 5 years. Temporal lobe surgery (adjusted odds ratio [AOR]: 2.62; 95% CI 1.19-5.76), shorter epilepsy duration (AOR for duration: 0.94; 95% CI 0.89-0.99), and completely normal histopathologic findings-versus nonspecific reactive gliosis-(AOR: 4.69; 95% CI 1.79-11.27) were significantly associated with favorable seizure outcome at 2 years after surgery. Of patients who underwent invasive monitoring, only 35% reached seizure freedom at 2 years. Patients with parietal lobe resections had lowest seizure freedom rates (12.5%). Among temporal lobe surgery patients, there was a trend toward favorable outcome if hippocampectomy was part of the resection strategy (OR: 2.94; 95% CI 0.98-8.80). Genetic testing was only sporadically performed. DISCUSSION: This study shows that seizure freedom can be reached in 40% of nonlesional patients with both normal MRI and histopathology findings. In particular, nonlesional temporal lobe epilepsy should be regarded as a relatively favorable group, with almost half of patients achieving seizure freedom at 2 years after surgery-even more if the hippocampus is resected-compared with only 1 in 5 nonlesional patients who underwent extratemporal surgery. Patients with an electroclinically identified focus, who are nonlesional, will be a promising group for advanced molecular-genetic analysis of brain tissue specimens to identify new brain somatic epilepsy genes or epilepsy-associated molecular pathways.

• MeSH
• elektroencefalografie MeSH
• epilepsie parciální * diagnostické zobrazování   chirurgie   MeSH
• epilepsie temporálního laloku * chirurgie   MeSH
• epilepsie * diagnostické zobrazování   chirurgie   MeSH
• kohortové studie MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• záchvaty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Interictal very high-frequency oscillations (VHFOs, 500-2000 Hz) in a resting awake state seem to be, according to a precedent study of our team, a more specific predictor of a good outcome of the epilepsy surgery compared to traditional interictal high-frequency oscillations (HFOs, 80-500 Hz). In this study, we retested this hypothesis on a larger cohort of patients. In addition, we also collected patients' sleep data and hypothesized that the occurrence of VHFOs in sleep will be greater than in resting state. We recorded interictal invasive electroencephalographic (iEEG) oscillations in 104 patients with drug-resistant epilepsy in a resting state and in 35 patients during sleep. 21 patients in the rest study and 11 patients in the sleep study met the inclusion criteria (interictal HFOs and VHFOs present in iEEG recordings, a surgical intervention and a postoperative follow-up of at least 1 year) for further evaluation of iEEG data. In the rest study, patients with good postoperative outcomes had significantly higher ratio of resected contacts with VHFOs compared to HFOs. In sleep, VHFOs were more abundant than in rest and the percentage of resected contacts in patients with good and poor outcomes did not considerably differ in any type of oscillations. In conclusion, (1) our results confirm, in a larger patient cohort, our previous work about VHFOs being a specific predictor of the area which needs to be resected; and (2) that more frequent sleep VHFOs do not further improve the results.

• MeSH
• bdění MeSH
• elektroencefalografie metody   MeSH
• epilepsie * MeSH
• lidé MeSH
• refrakterní epilepsie * chirurgie   MeSH
• spánek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Verbal memory dysfunction is common in focal, drug-resistant epilepsy (DRE). Unfortunately, surgical removal of seizure-generating brain tissue can be associated with further memory decline. Therefore, localization of both the circuits generating seizures and those underlying cognitive functions is critical in presurgical evaluations for patients who may be candidates for resective surgery. We used intracranial electroencephalographic (iEEG) recordings during a verbal memory task to investigate word encoding in focal epilepsy. We hypothesized that engagement in a memory task would exaggerate local iEEG feature differences between the seizure onset zone (SOZ) and neighboring tissue as compared to wakeful rest ("nontask"). METHODS: Ten participants undergoing presurgical iEEG evaluation for DRE performed a free recall verbal memory task. We evaluated three iEEG features in SOZ and non-SOZ electrodes during successful word encoding and compared them with nontask recordings: interictal epileptiform spike (IES) rates, power in band (PIB), and relative entropy (REN; a functional connectivity measure). RESULTS: We found a complex pattern of PIB and REN changes in SOZ and non-SOZ electrodes during successful word encoding compared to nontask. Successful word encoding was associated with a reduction in local electrographic functional connectivity (increased REN), which was most exaggerated in temporal lobe SOZ. The IES rates were reduced during task, but only in the non-SOZ electrodes. Compared with nontask, REN features during task yielded marginal improvements in SOZ classification. SIGNIFICANCE: Previous studies have supported REN as a biomarker for epileptic brain. We show that REN differences between SOZ and non-SOZ are enhanced during a verbal memory task. We also show that IESs are reduced during task in non-SOZ, but not in SOZ. These findings support the hypothesis that SOZ and non-SOZ respond differently to task and warrant further exploration into the use of cognitive tasks to identify functioning memory circuits and localize SOZ.

• Klíčová slova
• cognitive task, epilepsy, functional connectivity, seizure onset zone, spikes,
• MeSH
• elektroencefalografie MeSH
• elektrokortikografie MeSH
• epilepsie parciální * chirurgie   MeSH
• lidé MeSH
• mozek MeSH
• refrakterní epilepsie * chirurgie   MeSH
• záchvaty MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Many methods applied to data acquired by various imaging modalities have been evaluated for their benefit in localizing lesions in magnetic resonance (MR) negative epilepsy patients. No approach has proven to be a stand-alone method with sufficiently high sensitivity and specificity. The presented study addresses the potential benefit of the automated fusion of results of individual methods in presurgical evaluation. We collected electrophysiological, MR, and nuclear imaging data from 137 patients with pharmacoresistant MR-negative/inconclusive focal epilepsy. A subgroup of 32 patients underwent surgical treatment with known postsurgical outcomes and histopathology. We employed a Gaussian mixture model to reveal several classes of gray matter tissue. Classes specific to epileptogenic tissue were identified and validated using the surgery subgroup divided into two disjoint sets. We evaluated the classification accuracy of the proposed method at a voxel-wise level and assessed the effect of individual methods. The training of the classifier resulted in six classes of gray matter tissue. We found a subset of two classes specific to tissue located in resected areas. The average classification accuracy (i.e., the probability of correct classification) was significantly higher than the level of chance in the training group (0.73) and even better in the validation surgery subgroup (0.82). Nuclear imaging, diffusion-weighted imaging, and source localization of interictal epileptic discharges were the strongest methods for classification accuracy. We showed that the automatic fusion of results can identify brain areas that show epileptogenic gray matter tissue features. The method might enhance the presurgical evaluations of MR-negative epilepsy patients.

• Klíčová slova
• data fusion, neuroimaging, nonlesional epilepsy, seizure onset zone,
• MeSH
• dospělí MeSH
• elektroencefalografie metody   MeSH
• epilepsie parciální diagnostické zobrazování   MeSH
• jednofotonová emisní výpočetní tomografie metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• multimodální zobrazování MeSH
• neurozobrazování metody   MeSH
• pozitronová emisní tomografie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Debates on six controversial topics on the network theory of epilepsy were held during two debate sessions, as part of the International Conference for Technology and Analysis of Seizures, 2019 (ICTALS 2019) convened at the University of Exeter, UK, September 2-5 2019. The debate topics were (1) From pathologic to physiologic: is the epileptic network part of an existing large-scale brain network? (2) Are micro scale recordings pertinent for defining the epileptic network? (3) From seconds to years: do we need all temporal scales to define an epileptic network? (4) Is it necessary to fully define the epileptic network to control it? (5) Is controlling seizures sufficient to control the epileptic network? (6) Does the epileptic network want to be controlled? This article, written by the organizing committee for the debate sessions and the debaters, summarizes the arguments presented during the debates on these six topics.

• Klíčová slova
• Edges, Epileptic network, Epileptogenesis, Ictogenesis, Nodes, Seizure control,
• MeSH
• epilepsie diagnóza   farmakoterapie   patofyziologie   MeSH
• kongresy jako téma MeSH
• lidé MeSH
• nervová síť účinky léků   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: When considering all patients with focal drug-resistant epilepsy, as high as 40-50% of patients suffer seizure recurrence after surgery. To achieve seizure freedom without side effects, accurate localization of the epileptogenic tissue is crucial before its resection. We investigate an automated, fast, objective mapping process that uses only interictal data. METHODS: We propose a novel approach based on multiple iEEG features, which are used to train a support vector machine (SVM) model for classification of iEEG electrodes as normal or pathologic using 30 min of inter-ictal recording. RESULTS: The tissue under the iEEG electrodes, classified as epileptogenic, was removed in 17/18 excellent outcome patients and was not entirely resected in 8/10 poor outcome patients. The overall best result was achieved in a subset of 9 excellent outcome patients with the area under the receiver operating curve = 0.95. CONCLUSION: SVM models combining multiple iEEG features show better performance than algorithms using a single iEEG marker. Multiple iEEG and connectivity features in presurgical evaluation could improve epileptogenic tissue localization, which may improve surgical outcome and minimize risk of side effects. SIGNIFICANCE: In this study, promising results were achieved in localization of epileptogenic regions by SVM models that combine multiple features from 30 min of inter-ictal iEEG recordings.

• Klíčová slova
• Connectivity, Drug resistant epilepsy, Epileptogenic zone localization, High frequency oscillations, Machine learning, Multi-feature approach,
• MeSH
• dospělí MeSH
• elektroencefalografie přístrojové vybavení   metody   MeSH
• epilepsie parciální diagnóza   patofyziologie   MeSH
• implantované elektrody MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

OBJECTIVE: This study investigates high-frequency oscillations (HFOs; 65-600 Hz) as a biomarker of epileptogenic brain and explores three barriers to their clinical translation: (1) Distinguishing pathological HFOs (pathHFO) from physiological HFOs (physHFO). (2) Classifying tissue under individual electrodes as epileptogenic (3) Reproducing results across laboratories. METHODS: We recorded HFOs using intracranial EEG (iEEG) in 90 patients with focal epilepsy and 11 patients without epilepsy. In nine patients with epilepsy putative physHFOs were induced by cognitive or motor tasks. HFOs were identified using validated detectors. A support vector machine (SVM) using HFO features was developed to classify tissue under individual electrodes as normal or epileptogenic. RESULTS: There was significant overlap in the amplitude, frequency, and duration distributions for spontaneous physHFO, task induced physHFO, and pathHFO, but the amplitudes of the pathHFO were higher (P < 0.0001). High gamma pathHFO had the strongest association with seizure onset zone (SOZ), and were elevated on SOZ electrodes in 70% of epilepsy patients (P < 0.0001). Failure to resect tissue generating high gamma pathHFO was associated with poor outcomes (P < 0.0001). A SVM classified individual electrodes as epileptogenic with 63.9% sensitivity and 73.7% specificity using SOZ as the target. INTERPRETATION: A broader range of interictal pathHFO (65-600 Hz) than previously recognized are biomarkers of epileptogenic brain, and are associated with SOZ and surgical outcome. Classification of HFOs into physiological or pathological remains challenging. Classification of tissue under individual electrodes was demonstrated to be feasible. The open source data and algorithms provide a resource for future studies.

• Publikační typ
• časopisecké články MeSH

Focal cortical dysplasias (FCDs) are a range of malformations of cortical development each with specific histopathological features. Conventional radiological assessment of standard structural MRI is useful for the localization of lesions but is unable to accurately predict the histopathological features. Quantitative MRI offers the possibility to probe tissue biophysical properties in vivo and may bridge the gap between radiological assessment and ex-vivo histology. This review will cover histological, genetic and radiological features of FCD following the ILAE classification and will explain how quantitative voxel- and surface-based techniques can characterise these features. We will provide an overview of the quantitative MRI measures available, their link with biophysical properties and finally the potential application of quantitative MRI to the problem of FCD subtyping. Future research linking quantitative MRI to FCD histological properties should improve clinical protocols, allow better characterisation of lesions in vivo and tailored surgical planning to the individual.

• Klíčová slova
• Biophysical tissue properties, Epilepsy surgery, Focal cortical dysplasia, Histology, MRI, Malformation of cortical development, Quantitative MRI, Quantitative mapping, Radiology, qMRI,
• MeSH
• fenotyp * MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   statistika a číselné údaje   MeSH
• malformace mozkové kůry diagnostické zobrazování   genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH