Interpretable functional specialization emerges in deep convolutional networks trained on brain signals.

Objective.Functional specialization is fundamental to neural information processing. Here, we study whether and how functional specialization emerges in artificial deep convolutional neural networks (CNNs) during a brain-computer interfacing (BCI) task.Approach.We trained CNNs to predict hand movement speed from intracranial electroencephalography (iEEG) and delineated how units across the different CNN hidden layers learned to represent the iEEG signal.Main results.We show that distinct, functionally interpretable neural populations emerged as a result of the training process. While some units became sensitive to either iEEG amplitude or phase, others showed bimodal behavior with significant sensitivity to both features. Pruning of highly sensitive units resulted in a steep drop of decoding accuracy not observed for pruning of less sensitive units, highlighting the functional relevance of the amplitude- and phase-specialized populations.Significance.We anticipate that emergent functional specialization as uncovered here will become a key concept in research towards interpretable deep learning for neuroscience and BCI applications.

Gray-White Matter Blurring of the Temporal Pole Associated With Hippocampal Sclerosis: A Microstructural Study Involving 3 T MRI and Ultrastructural Histopathology.

Hippocampal sclerosis (HS) is often associated with gray-white matter blurring (GMB) of the anterior temporal lobe. In this study, twenty patients with unilateral temporal lobe epilepsy and HS were studied with 3 T MRI including T1 MP2RAGE and DTI/DMI sequences. Anterior temporal lobe white matter T1 relaxation times and diffusion measures were analyzed on the HS side, on the contralateral side, and in 10 normal controls. Resected brain tissue of three patients without GMB and four patients with GMB was evaluated ultrastructurally regarding axon density and diameter, the relation of the axon diameter to the total fiber diameter (G-ratio), and the thickness of the myelin sheath. Hippocampal sclerosis GMB of the anterior temporal lobe was related to prolonged T1 relaxation and axonal loss. A less pronounced reduction in axonal fraction was also found on imaging in GMB-negative temporal poles compared with normal controls. Contralateral values did not differ significantly between patients and normal controls. Reduced axonal density and axonal diameter were histopathologically confirmed in the temporopolar white matter with GMB compared to temporal poles without. These results confirm that GMB can be considered an imaging correlate for disturbed axonal maturation that can be quantified with advanced diffusion imaging.

Alterations of intracerebral connectivity in epilepsy patients with secondary bilateral synchrony.

INTRODUCTION: The aim of our study was to evaluate intracerebral network changes in epilepsy patients demonstrating secondary bilateral synchrony (SBS) in EEG by applying a new Diffusion Tensor Imaging (DTI) method using an energy-based global tracking algorithm. MATERIALS AND METHODS: 10 MRI negative epilepsy patients demonstrating SBS in 10-20 surface EEG were included. EEG findings were analyzed for irritative zones characterized by focal interictal epileptiform discharges (IEDs) triggering SBS. In addition, DTI including an energy-based global tracking algorithm was applied to analyze fiber tract alterations in irritative zones. To measure the deviation of a certain cortical connection in comparison to healthy controls, normalized differences of fiber tract streamline counts (SC) and their p-values were evaluated in comparison to corresponding fibers of the control group. RESULTS: In 6 patients the irritative zone initiating SBS was located in the frontal lobe, in 3 patients in the temporal lobe and in 1 patient in the region surrounding the right central sulcus. All patients demonstrated significantly altered SC in brain lobes where the irritative zone triggering SBS was located (p ≤ 0.05). Seven out of 10 patients demonstrated SC alterations in tracts connecting brain lobes between the ipsilateral and the contralateral hemisphere (p ≤ 0.05). CONCLUSION: Our data demonstrate that alterations in fiber tracts in irritative zones triggering SBS are not necessarily associated with intracerebral lesions visible in high resolution MRI. Our study gives evidence that diffusion tensor imaging is a promising non-invasive additive tool for intracerebral network analyses even in MRI-negative epilepsy patients.

Morphometric MRI Analysis: Improved Detection of Focal Cortical Dysplasia Using the MP2RAGE Sequence.

BACKGROUND AND PURPOSE: Focal cortical dysplasias are the most common resected epileptogenic lesions in children and the third most common lesion in adults, but they are often subtle and frequently overlooked on MR imaging. The purpose of this study was to evaluate whether MP2RAGE-based morphometric MR imaging analysis is superior to MPRAGE-based analysis in the detection of focal cortical dysplasia. MATERIALS AND METHODS: MPRAGE and MP2RAGE datasets were acquired in a consecutive series of 640 patients with epilepsy. Datasets were postprocessed using the Morphometric Analysis Program to generate morphometric z score maps such as junction, extension, and thickness images based on both MPRAGE and MP2RAGE images. Focal cortical dysplasia lesions were manually segmented in the junction images, and volumes and mean z scores of the lesions were measured. RESULTS: Of 21 focal cortical dysplasias discovered, all were clearly visible on MP2RAGE junction images, whereas 2 were not visible on MPRAGE junction images. In all except 4 patients, the volume of the focal cortical dysplasia was larger and mean lesion z scores were higher on MP2RAGE junction images compared with the MPRAGE-based images (P = .005, P = .013). CONCLUSIONS: In this study, MP2RAGE-based morphometric analysis created clearer output maps with larger lesion volumes and higher z scores than the MPRAGE-based analysis. This new approach may improve the detection of subtle, otherwise overlooked focal cortical dysplasia.

Flashbulb memory recall in healthy adults - a functional magnetic resonance imaging study.

The present study investigated neural activations related to flashbulb memory (FM) recall and examined whether the amygdala and hippocampus are involved in FM recall. 20 healthy adults completed a block design with an FM-condition, where the reception events for a number of potential FM events had to be recalled, and a control condition (FMC) comprising reception events lacking FM characteristics. A definition naming task was used as an implicit baseline. The individual emotional reaction to the FM events (EMO) and self-rated retrieval success were included in the SPM model as modulating parameters. The main contrast of interest were FM > FMC and activations associated with EMO. ROI-analyses on mesiotemporal regions were performed. FM > FMC yielded activations in line with the autobiographical memory network, with mostly left sided-activations. EMO was associated with a more bilateral activation pattern. ROI-analysis revealed activations for EMO in the right amygdala and HATA. FM > FMC was associated with right hippocampal activations. The present findings are compatible with previous research into autobiographical memory, but also show activations for FM recall different from ordinary, not highly emotional autobiographical memories, as EMO is associated with a more bilateral network. Moreover, the amygdala seems to be involved in FM recall.

[Mobile seizure monitoring in epilepsy patients]. / Mobiles Anfallsmonitoring bei Epilepsiepatienten.

Wearables are receiving much attention from both epilepsy patients and treating physicians, for monitoring of seizure frequency and warning of seizures. They are also of interest for the detection of seizure-associated risks of patients, for differential diagnosis of rare seizure types and prediction of seizure-prone periods. Accelerometry, electromyography (EMG), heart rate and further autonomic parameters are recorded to capture clinical seizure manifestations. Currently, a clinical use to document nocturnal motor seizures is feasible. In this review the available devices, data on the performance in the documentation of seizures, current options for clinical use and developments in data analysis are presented and critically discussed.

Simultaneously recorded intracranial and scalp high frequency oscillations help identify patients with poor postsurgical seizure outcome.

OBJECTIVE: High frequency oscillations (HFO) between 80-500 Hz are markers of epileptic areas in intracranial and maybe also scalp EEG. We investigate simultaneous recordings of scalp and intracranial EEG and hypothesize that scalp HFOs provide important additional clinical information in the presurgical setting. METHODS: Spikes and HFOs were visually identified in all intracranial scalp EEG channels. Analysis of correlation of event location between intracranial and scalp EEG as well as relationship between events and the SOZ and zone of surgical removal was performed. RESULTS: 24 patients could be included, 23 showed spikes and 19 HFOs on scalp recordings. In 15/19 patients highest scalp HFO rate was located over the implantation side, with 13 patients having the highest scalp and intracranial HFO rate over the same region. 17 patients underwent surgery, 7 became seizure free. Patients with poor post-operative outcome showed significantly more regions with HFO than those with seizure free outcome. CONCLUSIONS: Scalp HFOs are mostly located over the SOZ. Widespread scalp HFOs are indicative of a larger epileptic network and associated with poor postsurgical outcome. SIGNIFICANCE: Analysis of scalp HFO add clinically important information about the extent of epileptic areas during presurgical simultaneous scalp and intracranial EEG recordings.

High Frequency Oscillations in the Ripple Band (80-250 Hz) in Scalp EEG: Higher Density of Electrodes Allows for Better Localization of the Seizure Onset Zone.

High frequency oscillations (HFO) are known as markers of epileptic areas in intracranial EEG and possibly scalp EEG. We compared distributions of HFO in the ripple band (80-250 Hz) in intracranial and scalp EEG with either a conventional 10-20-montage (10-20-EEG) or a high density recording using 128 electrodes (HD-EEG). HFO were visually identified, in all intracranial EEG channels (80-500 Hz) and all channels of the 10-20-EEG (scalp EEG 80-250 Hz). For the HD-EEG, HFO were analyzed in regions of interest using areas with HFO as seen on the 10-20-EEG as well as areas in the clinically-defined seizure onset zone (SOZ). 13 patients were included in the study, of whom 12 showed HFO in the ripple band. In 8 patients HD-EEG revealed additional regions of ripples compared to the 10-20-EEG. With HD-EEG, areas of highest ripple rates were corresponding between scalp and intracranial EEG in 7 patients (58%) and 8 (67%) patients showed highest ripple rates over the SOZ. In contrast, with 10-20-EEG only 2 patients (17%) had corresponding areas of highest ripple rates and only 3 patients (23%) showed highest ripple rates over the SOZ. HD-EEG proved to be better to identify scalp HFO in the ripple band compared to standard 10-20-EEG. Moreover, ripples in 10-20-EEG seem to lead to false localization of epileptic areas. In contrast ripples detected with HD-EEG were located over the seizure onset zone and maybe a promising tool to localize epileptic tissue in the future.

Bilateral cingulum fiber reductions in temporal lobe epilepsy with unilateral hippocampal sclerosis.

PURPOSE: To evaluate whether white matter tracts within the Papez circuit are altered in patients with unilateral hippocampal sclerosis (HS). METHODS: Twenty patients with histologically proven unilateral HS and 20 age-matched controls were studied with a 3T Epilepsy-dedicated MRI protocol including a MPRAGE sequence for hippocampus volumetry and a diffusion tensor imaging (DTI) sequence (61 diffusion-encoding directions, 2×2×2mm3 voxels) for diffusion tensor tractography (DTT). An energy-based global tracking algorithm was used to calculate streamline counts (SC) and fractional anisotropy (FA) of cingulate, fornix, and mammillo-thalamic tracts, respectively. RESULTS: Sclerotic hippocampi were significantly smaller compared to the contralateral side and to age-matched controls. Cingulum SC but not FA were reduced on the hippocampal sclerosis (258+81.0) and contralateral side (271+85.6) compared to age-matched controls (447+138). CONCLUSION: Focusing on white matter tracts of the Papez circuit we showed that in patients with intractable temporal lobe epilepsy unilateral hippocampal sclerosis is associated with a bilateral reduction of cingulum association fibers projecting from the cingulate gyrus to the parahippocampal gyrus.

The role of presurgical EEG parameters and of reoperation for seizure outcome in temporal lobe epilepsy.

PURPOSE: After surgery for intractable mesiotemporal lobe epilepsy (mTLE) seizures recur in 30-40%. One predictor for seizure recurrence is the distribution of seizure onset and interictal epileptiform discharges (IED). Our study focused on lateralization and extent of epileptiform activity regarding postoperative seizure persistence and the effect of reoperation. METHODS: This study comprises 426 consecutive patients operated for intractable mTLE. Impact of preoperative seizure onset and IED on the persistence of seizures and results of reoperation were analyzed. RESULTS: One year after surgery, 27% of patients with mTLE experienced persistent seizures (Engel II-IV). Preoperative bilateral seizure onset in EEG was predictive for postoperative seizure recurrence (Engel II-IV: 64%). Seizure foci and IED exceeding the temporal lobe in the ipsilateral hemisphere were not found to be associated with worse seizure outcome (Engel I: 72% and 75%) compared to patients with seizure foci confined to the ipsilateral temporal lobe (Engel I: 75% and 76%). Moreover, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED did not negatively affect seizure freedom if seizure onset was strictly limited to the affected temporal lobe (Engel I: 85% and 65%, respectively). 60% of patients reoperated in the ipsilateral temporal lobe for persistent seizures became seizure free. CONCLUSIONS: Preoperative bilateral ictal foci are a negative predictor for seizure outcome. Contrarily, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED had favorable seizure outcome if seizure onset is strictly limited to the affected temporal lobe. Reoperation for seizure persistence constitutes a promising therapeutic option.

[Differential diagnosis of dissociative seizures]. / Differenzialdiagnose dissoziativer Anfälle.

Patient history taking and semiology provide seminal clues to the diagnosis of dissociative seizures. Openness and alertness of the treating physician are essential. Video-electroencephalogram(EEG)-based analyses of the events are crucial to establish the correct diagnosis, particularly in complex cases. The patient-doctor relationship is of particular importance in order to successfully motivate the patient for psychotherapeutic treatment. Coexisting psychiatric morbidity as well as other functional somatic symptoms must be actively explored. Current changes in the established diagnostic manuals, including ICD-11, reflect the ongoing vivid interest and controversial discussions in the field of dissociative disorders.

A realistic multimodal modeling approach for the evaluation of distributed source analysis: application to sLORETA.

OBJECTIVE: Electrical source localization (ESL) deriving from scalp EEG and, in recent years, from intracranial EEG (iEEG), is an established method in epilepsy surgery workup. We aimed to validate the distributed ESL derived from scalp EEG and iEEG, particularly regarding the spatial extent of the source, using a realistic epileptic spike activity simulator. APPROACH: ESL was applied to the averaged scalp EEG and iEEG spikes of two patients with drug-resistant structural epilepsy. The ESL results for both patients were used to outline the location and extent of epileptic cortical patches, which served as the basis for designing a spatiotemporal source model. EEG signals for both modalities were then generated for different anatomic locations and spatial extents. ESL was subsequently performed on simulated signals with sLORETA, a commonly used distributed algorithm. ESL accuracy was quantitatively assessed for iEEG and scalp EEG. MAIN RESULTS: The source volume was overestimated by sLORETA at both EEG scales, with the error increasing with source size, particularly for iEEG. For larger sources, ESL accuracy drastically decreased, and reconstruction volumes shifted to the center of the head for iEEG, while remaining stable for scalp EEG. Overall, the mislocalization of the reconstructed source was more pronounced for iEEG. SIGNIFICANCE: We present a novel multiscale framework for the evaluation of distributed ESL, based on realistic multiscale EEG simulations. Our findings support that reconstruction results for scalp EEG are often more accurate than for iEEG, owing to the superior 3D coverage of the head. Particularly the iEEG-derived reconstruction results for larger, widespread generators should be treated with caution.

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

OBJECT: The 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 METHODS: Our 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. RESULTS: Complete 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. CONCLUSION: Depending 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.

[Invasive stimulation procedures and EEG diagnostics in epilepsy]. / Invasive Stimulationsverfahren und EEG-Diagnostik bei Epilepsien.

Stimulation has been performed experimentally and in small case series to treat epilepsy since the 1970s. Since the introduction of vagus nerve stimulation in 1997 and intracranial stimulation methods in 2011 into patient care, invasive stimulation has become a rapidly developing but infrequently used therapeutic option in Europe. Whereas vagus nerve stimulation is frequently used, particularly in the USA, intracranial stimulation differs in its regional availability. In order to improve the efficacy of stimulation, develop criteria for its use and assure low complication rates, a concentration on experienced centers and multicenter data acquisition and sharing are needed.Invasive electroencephalographic (EEG) monitoring with subdural electrodes and especially with stereotactically implanted depth electrodes have been used increasingly more often for presurgical evaluation in recent years. They are applied when non-invasive diagnostics show insufficient results to exactly identify the location and extent of the epileptogenic zone or cannot be adequately distinguished from eloquent cortex areas. Complications include intracranial hemorrhage, infections and increased intracranial pressure but lasting deficits or even death are rare (≤2 %). The outcome of invasive monitoring is inferior to non-invasive monitoring because of the higher degree of complexity of the cases; however, it is far superior to the seizure-free rates achieved by anticonvulsant drug treatment alone.

[Perampanel as a therapy option in patients with epilepsy]. / Perampanel als Therapieoption bei Epilepsiepatienten.

BACKGROUND: This article describes a monocentric retrospective analysis of clinical experience with the latest antiepileptic drug perampanel with non-competitive modulation of postsynaptic AMPA receptors. MATERIAL AND METHODS: Evaluation of electronic medical charts of patients newly treated with perampanel between 2012 and 2014 at the epilepsy center of the University Hospital Freiburg regarding effectiveness and tolerability. RESULTS: A total of 85 patients (45 male, mean age 37.4 years, range 14-80 years) with therapy resistance to an average of 6 antiepileptic medications were newly treated with add-on perampanel. Of the patients 35 % experienced a relevant reduction in seizures. The most commonly reported side effects were tiredness (32.5 %), dizziness (24.5 %) and irritability (10.5 %). The dosages resulting in a significant reduction in seizures which varied between patients from 4 to 12 mg/day. Even multidrug-resistant patients who had not benefited from vagus nerve and deep brain stimulation, profited from add-on treatment with perampanel. CONCLUSION: In this cohort, even epilepsy patients who did not respond to multiple previous antiepileptic treatment profited from add-on therapy with the new mode of action of perampanel.

Transcutaneous Vagus Nerve Stimulation (tVNS) for Treatment of Drug-Resistant Epilepsy: A Randomized, Double-Blind Clinical Trial (cMPsE02).

BACKGROUND: Various brain stimulation techniques are in use to treat epilepsy. These methods usually require surgical implantation procedures. Transcutaneous vagus nerve stimulation (tVNS) is a non-invasive technique to stimulate the left auricular branch of the vagus nerve at the ear conch. OBJECTIVE: We performed a randomized, double-blind controlled trial (cMPsE02) to assess efficacy and safety of tVNS vs. control stimulation in patients with drug-resistant epilepsy. METHODS: Primary objective was to demonstrate superiority of add-on therapy with tVNS (stimulation frequency 25 Hz, n = 39) versus active control (1 Hz, n = 37) in reducing seizure frequency over 20 weeks. Secondary objectives comprised reduction in seizure frequency from baseline to end of treatment, subgroup analyses and safety evaluation. RESULTS: Treatment adherence was 84% in the 1 Hz group and 88% in the 25 Hz group, respectively. Stimulation intensity significantly differed between the 1 Hz group (1.02 ± 0.83 mA) and the 25 Hz group (0.50 ± 0.47 mA; p = 0.006). Mean seizure reduction per 28 days at end of treatment was -2.9% in the 1 Hz group and 23.4% in the 25 Hz group (p = 0.146). In contrast to controls, we found a significant reduction in seizure frequency in patients of the 25 Hz group who completed the full treatment period (20 weeks; n = 26, 34.2%, p = 0.034). Responder rates (25%, 50%) were similar in both groups. Subgroup analyses for seizure type and baseline seizure frequency revealed no significant differences. Adverse events were usually mild or moderate and comprised headache, ear pain, application site erythema, vertigo, fatigue, and nausea. Four serious adverse events were reported including one sudden unexplained death in epilepsy patients (SUDEP) in the 1 Hz group which was assessed as not treatment-related. CONCLUSIONS: tVNS had a high treatment adherence and was well tolerated. Superiority of 25 Hz tVNS over 1 Hz tVNS could not be proven in this relatively small study, which might be attributed to the higher stimulation intensity in the control group. Efficacy data revealed results that justify further trials with larger patient numbers and longer observation periods.

The role of blood vessels in high-resolution volume conductor head modeling of EEG.

Reconstruction of the electrical sources of human EEG activity at high spatio-temporal accuracy is an important aim in neuroscience and neurological diagnostics. Over the last decades, numerous studies have demonstrated that realistic modeling of head anatomy improves the accuracy of source reconstruction of EEG signals. For example, including a cerebro-spinal fluid compartment and the anisotropy of white matter electrical conductivity were both shown to significantly reduce modeling errors. Here, we for the first time quantify the role of detailed reconstructions of the cerebral blood vessels in volume conductor head modeling for EEG. To study the role of the highly arborized cerebral blood vessels, we created a submillimeter head model based on ultra-high-field-strength (7T) structural MRI datasets. Blood vessels (arteries and emissary/intraosseous veins) were segmented using Frangi multi-scale vesselness filtering. The final head model consisted of a geometry-adapted cubic mesh with over 17×10(6) nodes. We solved the forward model using a finite-element-method (FEM) transfer matrix approach, which allowed reducing computation times substantially and quantified the importance of the blood vessel compartment by computing forward and inverse errors resulting from ignoring the blood vessels. Our results show that ignoring emissary veins piercing the skull leads to focal localization errors of approx. 5 to 15mm. Large errors (>2cm) were observed due to the carotid arteries and the dense arterial vasculature in areas such as in the insula or in the medial temporal lobe. Thus, in such predisposed areas, errors caused by neglecting blood vessels can reach similar magnitudes as those previously reported for neglecting white matter anisotropy, the CSF or the dura - structures which are generally considered important components of realistic EEG head models. Our findings thus imply that including a realistic blood vessel compartment in EEG head models will be helpful to improve the accuracy of EEG source analyses particularly when high accuracies in brain areas with dense vasculature are required.

[Epilepsy-associated tumors of the central nervous system: Epilepsy surgery and oncological aspects]. / Epilepsieassoziierte Tumoren des Zentralnervensystems : Epilepsiechirurgische und onkologische Aspekte.

BACKGROUND: Among the tumors associated with chronic epilepsy, dysembryoplastic neuroepithelial tumor and ganglioglioma are the most common besides angiocentric glioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma. These tumors are usually considered as being benign. OBJECTIVE: To determine the best conservative and surgical treatment of tumors associated with epilepsy. MATERIAL AND METHODS: This article presents case reports of malignant transformation of a dysembryoplastic neuroepithelial tumor and of a tumor initially diagnosed as a ganglioglioma based on magnetic resonance imaging (MRI) criteria. Description of references in the literature on epilepsy surgery and the neuro-oncology of epilepsy-associated tumors. RESULTS: In the case of the initially histopathologically diagnosed dysembryoplastic neuroepithelial tumor, a malignant transformation occurred 5 years after incomplete resection. The differentiation from a glioblastoma was possible through the analysis of the methylation profile. In another case a tumor assumed to be a ganglioglioma showed an increase in size after 6 years. Initial histopathological results revealed a glioblastoma. The analysis of the methylation profile suggested the diagnosis of an anaplastic pleomorphic xanthoastrocytoma and as a differential diagnosis an anaplastic ganglioglioma. Tumor progress correlated with the worsening of seizures. CONCLUSION: Recent studies have shown that in the treatment of predominantly benign epilepsy-associated tumors neuro-oncological aspects should also be taken into account in addition to the epileptological considerations. In the case of malignant transformation epigenetic screening (methylation profiles) can help to classify the tumor entity more precisely.

Slow modulations of high-frequency activity (40-140-Hz) discriminate preictal changes in human focal epilepsy.

Recent evidence suggests that some seizures are preceded by preictal changes that start from minutes to hours before an ictal event. Nevertheless an adequate statistical evaluation in a large database of continuous multiday recordings is still missing. Here, we investigated the existence of preictal changes in long-term intracranial recordings from 53 patients with intractable partial epilepsy (in total 531 days and 558 clinical seizures). We describe a measure of brain excitability based on the slow modulation of high-frequency gamma activities (40-140 Hz) in ensembles of intracranial contacts. In prospective tests, we found that this index identified preictal changes at levels above chance in 13.2% of the patients (7/53), suggesting that results may be significant for the whole group (p < 0.05). These results provide a demonstration that preictal states can be detected prospectively from EEG data. They advance understanding of the network dynamics leading to seizure and may help develop novel seizure prediction algorithms.

Verbal fluency in focal epilepsy: a systematic review and meta-analysis.

Testing of verbal fluency is currently part of standard presurgical neuropsychological assessment for patients with focal epilepsy. However, to date no systematic review has been conducted on semantic (SVF) and phonemic verbal fluency (PVF) in this patient group. The present review compares verbal fluency between healthy control subjects and subgroups of adult presurgical patients with focal epilepsy according to lateralisation and localisation of the dysfunction. PubMed was searched with a comprehensive search string. Abstracts of all studies and full-texts of potentially relevant studies were screened. Study quality was assessed by independent raters according to predefined criteria. 39 studies were included. Meta-analyses were performed to compare SVF and PVF across groups of patients with temporal (TLE) and frontal lobe epilepsy (FLE) as well as healthy controls (HC). Both patients with left- and right sided TLE were impaired on SVF and PVF compared to HC. Patients with left-sided TLE were slightly more impaired than patients with right-sided TLE. Patients with FLE showed a larger impairment in PVF than patients with TLE, whereas on SVF there was no difference between FLE and TLE. For TLE comparisons the study pool seems to have been sufficient, whereas more studies are needed to verify results for FLE. Semantic verbal fluency might not differentiate between FLE and TLE. While verbal fluency impairment was anticipated, especially in left-sided TLE and FLE patients, the impairment in patients with right-sided TLE was larger than expected. Results are discussed with regard to neuropsychological theory and practice.