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Introduction: Mental health comorbidities such as depression and anxiety are common in epilepsy, especially among people with pharmacoresistant epilepsy who are candidates for epilepsy surgery. The Psychology Task Force of the International League Against Epilepsy advised that psychological interventions should be integrated into comprehensive epilepsy care. Methods: To better understand the psychological impact of epilepsy and epileptic seizures in epilepsy surgery candidates, we analysed interviews with this subgroup of patients using Karl Jaspers’ concept of limit situations, which are characterised by a confrontation with the limits and challenges of life. These are especially chance, randomness, and unpredictability, death and finitude of life, struggle and self-assertion, guilt, failure, and falling short of one’s aspirations. Results: In 43 interviews conducted with 15 people with drug-resistant epilepsy who were candidates for epilepsy surgery, we found that these themes are recurrent and have a large psychosocial impact, which can result in depression and anxiety. For some people, epileptic seizures appear to meet the criteria for traumatic events. Conclusion: Understanding epilepsy and seizures as existential challenges complements the neurobiological explanations for psychological comorbidities and can help tailor psychological interventions to the specific needs of people with epilepsy, especially those who are candidates for surgical treatment.

Cenobamate (CNB) is a new antiseizure medication (ASM) for the treatment of focal epilepsy in adults. While efficacy of CNB was confirmed in controlled clinical trials, its effects on cognition are unclear. Cognitive adverse effects of ASM affect quality of life and retention rate. Therefore, we investigated whether the adjunctive treatment with CNB is associated with changes in cognitive performance.Efficacy and tolerability of CNB were investigated in an observational study. Fifty patients with pharmacoresistant focal epilepsy aged 18 to 71 years (Mdn = 37.5 years) were tested before (T0) and after reaching the first target dose of CNB, usually after three months (T1). Cognitive performance was assessed using the EpiTrack©, a change-sensitive screening tool for attention and executive functions.The median CNB dose at T1 was 125 mg/day (range: 50 - 250 mg/day). Most patients received 2-3 concomitant ASMs. Individual test scores remained stable in 72%, significantly improved in 16%, and significantly deteriorated in 12% of the patients from T0 to T1. The total group showed a significant improvement in EpiTrack scores (p .01). Changes in EpiTrack performance from T0 to T1 occurred independently of CNB dose, changes in the total drug load or reduction in seizure frequency.Most of the patients showed stable or improved cognitive performance. Thus, there is preliminary evidence that adjunctive CNB is not associated with an increased risk of cognitive side effects for the majority of patients. These findings need to be confirmed in controlled trials encompassing higher doses.

Objectives: High counts of averaged interictal epileptiform discharges (IEDs) are key components of accurate interictal electric source imaging (ESI) in patients with focal epilepsy. Automated detections may be time-efficient, but they need to identify the correct IED types. Thus we compared semiautomated and automated detection of IED types in long-term video-EEG (electroencephalography) monitoring (LTM) using an extended scalp EEG array and short-term high-density EEG (hdEEG) with visual detection of IED types and the seizure-onset zone (SOZ). Methods: We prospectively recruited consecutive patients from four epilepsy centers who underwent both LTM with 40-electrode scalp EEG and short-term hdEEG with 256 electrodes. Only patients with a single circumscribed SOZ in LTM were included. In LTM and hdEEG, IED types were identified visually, semiautomatically and automatically. Concordances of semiautomated and automated detections in LTM and hdEEG, as well as visual detections in hdEEG, were compared against visually detected IED types and the SOZ in LTM. Results: Fifty-two of 62 patients with LTM and hdEEG were included. The most frequent IED types per patient, detected semiautomatically and automatically in LTM and visually in hdEEG, were significantly concordant with the most frequently visually identified IED type in LTM and the SOZ. Semiautomated and automated detections of IED types in hdEEG were significantly concordant with visually identified IED types in LTM, only when IED types with more than 50 detected single IEDs were selected. The threshold of 50 detected IED in hdEEG was reached in half of the patients. For all IED types per patient, agreement between visual and semiautomated detections in LTM was high. Significance: Semiautomated and automated detections of IED types in LTM show significant agreement with visually detected IED types and the SOZ. In short-term hdEEG, semiautomated detections of IED types are concordant with visually detected IED types and the SOZ in LTM if high IED counts were detected.

To determine the diagnostic yield of in-hospital video-electroencephalography (EEG) monitoring to document seizures in patients with epilepsy.Retrospective analysis of electronic seizure documentation at the University Hospital Freiburg (UKF) and at King's College London (KCL). Statistical assessment of the role of the duration of monitoring, and subanalyses on presurgical patient groups and patients undergoing reduction of antiseizure medication.Of more than 4800 patients with epilepsy undergoing in-hospital recordings at the two institutions since 2005, seizures with documented for 43% (KCL) and 73% (UKF).. Duration of monitoring was highly significantly associated with seizure recordings (p .0001), and presurgical patients as well as patients with drug reduction had a significantly higher diagnostic yield (p .0001). Recordings with a duration of5 days lead to additional new seizure documentation in only less than 10% of patients.There is a need for the development of new ambulatory monitoring strategies to document seizures for diagnostic and monitoring purposes for a relevant subgroup of patients with epilepsy in whom in-hospital monitoring fails to document seizures.

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.

Mental health comorbidities are frequent in epilepsy. Consequently, psychotherapy is becoming increasingly important. To address the psychological needs of people with epilepsy (PwE) it is essential to understand the subjective experiences of seizures better. There is little research on how people report seizures, and which psychological representations they have. We conducted a thematic analysis based on 42 (micro-phenomenological) interviews with 15 participants on their experiences of seizures. In these interviews, we identified three categories of seizure descriptions: (1) phenomena related to the body and emotions; (2) the moments that are difficult to describe; and (3) the use of figurative language and metaphors. Paroxysmal physical and psychological sensations were often reported spontaneously by the participants. The moments that were difficult to describe were expressed, among other things, through the use of paradoxes or the report of a 'strange' feeling and led participants to use figurative language. As these metaphors can reveal important information about people's subjective experiences, they were analyzed in detail. We identified the three main types of metaphors that the participants used most frequently: (1) perception, (2) nature, and (3) battle. The theme of battle was most frequently used in different forms and was closely related to the metaphors from the fields of perception and nature, thus representing a key point in the personal experience of seizures. These findings can contribute to developing psychotherapeutic approaches for the treatment of seizure disorders.

Background Intracranial recordings with stereoelectroencephalography (SEEG) aims at defining the epileptogenic zone in patients with pharmacoresistant epilepsy. Currently used techniques for depth electrode implantation include stereotactic frame-based and navigated frameless applications, both either conventional or robot-assisted. Safety and diagnostic effectiveness depend on accuracy of implantation. Objective To evaluate the planning experience, accuracy of stereotactic electrode placement as well as accuracy predictors with the use of latest generation planning software. Methods Retrospective study of 15 consecutive patients who received depth electrodes using the Leksell stereotactic frame, after planning with Elements (Brainlab, Munich, Germany). For each electrode, we calculated the entry point error (EPE) as lateral deviation and target point error (TPE) both as lateral deviation and distance to tip. Multivariate regression analysis and computation of 95% confidence intervals using the bootstrap method were applied for statistical analysis and evaluation of accuracy predictors. Results The mean EPE, lateral deviation at TP and distance to tip at TP were 0.6 0.5 mm, 1.1 0.7 mm and 1.5 0.8 mm respectively. Order of implantation (1-6 vs. >6) is predictor for distance to tip at TP and length of electrode predictor for the lateral deviation at TP. Localization of electrode generally did not correlate to error, but insular electrodes were significantly less accurate than lobar ones. Conclusion Combination of frame-based stereotaxy with latest generation planning software may offer a better planning and implantation experience. Accuracy predictors should be analyzed and be considered for the improvement of accuracy and safety of SEEG implantation methods.

Because oral pharmacological treatment of neocortical focal epilepsy is limited due to common systemic side effects and relatively low drug concentrations reached at the epileptic foci locally, application of antiepileptic agents directly onto the neocortical focus may enhance treatment tolerability and efficacy. We describe the effects of cortically applied sodium valproate (VPA) in two patients with pharmacoresistant neocortical focal epilepsy who were selected for epilepsy surgery after a circumscribed epileptic focus had been determined by invasive presurgical evaluation using subdural electrodes. Local VPA modified epileptic activity as electrocorticographically recorded from the chronic focus in both patients. In addition, VPA induced local increase of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in cortical tissue samples, whereas the excitatory glutamate was possibly decreased. In this clinical pilot study, we could show antiepileptic effects of cortically applied VPA in humans by electrocorticographic and neurochemical parameters.

Background Information about the histopathology in 3 Tesla MRI negative extratemporal epilepsies is relatively limited. Most common histopathological findings in earlier (mixed 1.5 or 3 Tesla) MRI-negative series are focal cortical dysplasia (FCD), gliosis or normal findings. These series mostly use the older Palmini criteria for classification and grading. We focus on histopathology of only 3 Tesla MRI-negative extratemporal epilepsies according to the current ILAE criteria and investigate potential correlation to seizure outcome 1 year postoperatively. Materials and methods Sixteen substrates of 3 Tesla MRI-negative extratemporal epilepsies were examined in two steps. Standard stains and immunohistochemical reactions and Palmini criteria were used prospectively during the initial examination. Retrospectively, all specimens were re-examined and re-evaluated. Phospho-6 and calretinin stains and ILAE criteria were used during the review examination. Results Initial examination revealed 5 FCDs Palmini 1b, two 1a, five 2a and 4 cases of gliosis. The review examination according to ILAE criteria revealed 6 FCDs type IIa, 2 FCDs Ib and 7 mild malformations of cortical development (mMCD) type II. None of our cases was labelled as isolated gliosis after the review examination. The incidence of FCD, after the review examination per ILAE criteria, was reduced to 56%; versus 75% per Palmini. Conclusions In “true” 3 Tesla MRI-negative extratemporal epilepsies, incidence of FCD may be lower than in earlier MRI-negative series that included weaker MRI-field. Furthermore, consistent review examination may confirm the diagnosis of mMCD type II as substrate in cases diagnosed as “gliosis” or “normal” in the past.

Introduction Histopathology of MRI-negative temporal lobe epilepsies (TLE) shows heterogeneous findings. The use of either 1.5 or 3 Tesla MRI for the selection of MRI-negative cases and use of older classification systems instead of the current ILAE classification system may account for this heterogeneity. We focus on histopathology of 3 Tesla MRI-negative TLE according to ILAE criteria and investigate potential correlation to seizure outcome 1 year postoperatively. Materials and methods Twenty specimens (9 neocortical, 11 hippocampal) from eleven 3 Tesla MRI-negative patients with TLE were examined in two steps. Standard stains and immunohistochemical reactions as well as Palmini and Wyler criteria were used prospectively during the initial examination. Retrospectively, all specimens were re-examined and re-evaluated. Phospho-6 and calretinin stains and the ILAE criteria were used during the review examination. Results Initial examination revealed 7 focal cortical dysplasias (FCDs) Palmini type 1, two cases of cortical gliosis, 4 cases of hippocampal sclerosis (HS) Wyler grade 1 and seven cases of hippocampal gliosis. The review examination according to ILAE criteria revealed 4 FCDs type I and 5 mild malformations of cortical development. All hippocampal specimens showed “no HS/gliosis only” after the review examination. Histopathology showed no correlation to seizure outcome. Discussion This is the first histopathological study to include only 3 Tesla MRI-negative cases. The use of ILAE criteria lead to the diagnosis of “no HS/gliosis only” of all hippocampal specimens, a finding not in line with previously reported series. The spectrum of diagnoses within neocortical specimens showed accordingly more mild findings.

Objective To investigate presurgical diagnostic modalities, clinical and seizure outcome as well as predictive factors after resective epilepsy surgery in 3 Tesla MRI-negative focal epilepsies. Patients and methods This retrospective study comprises 26 patients (11 males/15 females, mean age 34 ± 12 years, range 13–50 years) with 3 Tesla MRI-negative focal epilepsies who underwent resective epilepsy surgery. Non-invasive and invasive presurgical diagnostic modalities, type and localization of resection, clinical and epileptological outcome with a minimum follow-up of 1 year (range 1–11 years, mean 2.5 ± 2.3 years) after surgery as well as outcome predictors were evaluated. Results All patients underwent invasive video-EEG monitoring after implantation of intracerebral depth and/or subdural electrodes. Ten patients received temporal and 16 extratemporal or multilobar (n = 4) resections. There was no perioperative death or permanent morbidity. Overall, 12 of 26 patients (46%) were completely seizure-free (Engel IA) and 65% had a favorable outcome (Engel I–II). In particular, seizure-free ratio was 40% in the temporal and 50% in the extratemporal group. In the temporal group, long duration of epilepsy correlated with poor seizure outcome, whereas congruent unilateral FDG-PET hypometabolism correlated with a favorable outcome. Conclusions In almost two thirds of temporal and extratemporal epilepsies defined as “non-lesional” by 3 Tesla MRI criteria, a favorable postoperative seizure outcome (Engel I–II) can be achieved with accurate multimodal presurgical evaluation including intracranial EEG recordings. In the temporal group, most favorable results were obtained when FDG-PET displayed congruent unilateral hypometabolism.

Antero-inferior temporal lobe meningoencephaloceles are a rare, but increasingly recognized cause of drug-resistant temporal lobe epilepsy (TLE). In order to evaluate whether these lesions are related to idiopathic intracranial hypertension (IIH), we analyzed clinical and MRI findings of a cohort of patients undergoing presurgical work-up. Seizure onset in the anterior temporal lobe was proven by EEG electrodes in 22 patients, and in 21 patients, anterior temporal lobectomy (mostly with sparing of the hippocampus) was performed. MRI signs of IIH (in particular empty sella) and the volumes of the ventricles and external CSF spaces were determined and related to the body mass index (BMI) and clinical outcome. Six of seven obese (BMI > 30 kg/m2) compared to four of 15 non-obese patients had partial empty or empty sella (p = 0.007). Bilateral lesions were found in all obese and 11 patients. Seizure freedom (Engel class 1A) was achieved in 12 of 21 patients (5 obese compared to 7 non-obese patients). BMI was related to the volume of the external CSF spaces (r = 0.467), and age at seizure onset was higher in obese patients. Roughly a third of patients with temporal lobe epilepsy due to antero-inferior meningoencephaloceles is obese and has MRI signs of idiopathic intracranial hypertension.

Background and Study Aims In complex cases of drug-resistant focal epilepsy, the precise localization of the epileptogenic zone requires simultaneous implantation of depth and subdural grid electrodes. This study describes a new simple frame-assisted method that facilitates the simultaneous placement of both types of intracranial electrodes. Material and Methods Ten consecutive patients were evaluated and divided into two groups. Group A included patients with simultaneous frame-assisted placement of depth and subdural grid electrodes. In group B, depth electrodes were implanted stereotactically; grid electrodes were implanted in a separate surgery. Results The placement of the subdural grid was accurate as individually designed by the epileptologists in all five patients from group A. In group B, one patient showed a slight and another one a significant deviation of the subdural grid position postoperatively. The mean surgical time in group A was shorter (280±62 minutes) compared with the mean duration of the surgical procedures in group B (336±51 minutes). Conclusion The frame-assisted placement of subdural grid electrodes facilitates the surgical procedure for invasive video-electroencephalography monitoring in complex cases of drug-resistant focal epilepsy in which a combination of depth electrodes and subdural grid electrodes is needed, by reducing the surgical time and guaranteeing highly accurate electrode localizations.

Electroencephalography (EEG) is a core element in the diagnosis of epilepsy syndromes and can help to monitor antiseizure treatment. Mobile EEG (mEEG) devices are increasingly available on the consumer market and may offer easier access to EEG recordings especially in rural or resource-poor areas. The usefulness of consumer-grade devices for clinical purposes is still underinvestigated. Here, we compared EEG traces of a commercially available mEEG device (Emotiv EPOC) to a simultaneously recorded clinical video EEG (vEEG). Twenty-two adult patients (11 female, mean age 40.2 years) undergoing noninvasive vEEG monitoring for clinical purposes were prospectively enrolled. The EEG recordings were evaluated by 10 independent raters with unmodifiable view settings. The individual evaluations were compared with respect to the presence of abnormal EEG findings (regional slowing, epileptiform potentials, seizure pattern). Video EEG yielded a sensitivity of 56% and specificity of 88% for abnormal EEG findings, whereas mEEG reached 39% and 85%, respectively. Interrater reliability coefficients were better in vEEG as compared to mEEG (ϰ = 0.50 vs. 0.30), corresponding to a moderate and fair agreement. Intrarater reliability between mEEG and vEEG evaluations of simultaneous recordings of a given participant was moderate (ϰ = 0.48). Given the limitations of our exploratory pilot study, our results suggest that vEEG is superior to mEEG, but that mEEG can be helpful for diagnostic purposes. We present the first quantitative comparison of simultaneously acquired clinical and mobile consumer-grade EEG for a clinical use-case.

Hector Berlioz (1803–1869) war einer der schillerndsten franzosischen Kunstlerpersonlichkeiten des 19. Jahrhunderts. Die detaillierte Analyse historischer Quellen aus epileptologischem Blickwinkel unterstutzt die Hypothese, dass der Komponist an einem idiopathischen generalisierten Epilepsiesyndrom mit Fotosensibilitat litt. Da sich unter den verschiedenen Anfallstypen auch myoklonische Anfalle identifizieren lassen, scheint die retrospektive Diagnose einer juvenilen Myoklonusepilepsie (Janz-Syndrom) plausibel.

Summary Objective Information on the relative timing of electroencephalography (EEG) seizure onset, ictal tachycardia (ITC), and first other clinical seizure manifestations is crucial for an understanding of the potential benefit of ITC-detection based closed-loop intervention systems for epilepsy treatment. This study analyzes the temporal relation of ITC, other clinical signs, and seizure onset in relation to intracranial and surface EEG. Methods Seventy-eight seizures with ITC from 13 patients undergoing invasive EEG recordings with simultaneous recordings of electrocardiography (ECG), intracranial EEG (iEEG) and surface EEG, and video recordings to determine clinical onset were analyzed. Latencies for ITC were calculated for thresholds of 100 bpm and for a 20% heart rate increase above baseline obtained 60 s prior to seizure onset on iEEG. Patient-based, seizure-based, and seizure origin–based analyses were performed. Results Mean latencies between seizure onset in invasive EEG and the following onset of ITC in the seizure- and patient-based analysis for both thresholds varied between 21.6 and 23.7 s, showing that ITC is an ictal rather a preictal phenomenon. In 10 of 13 patients and in 56 of 78 seizures, at least one of the thresholds for ITC was crossed before any other clinical sign. In the majority of cases, ITC also preceded ictal onset as determined in surface EEG. Latencies to ictal tachycardia were shorter for hippocampal than for extrahippocampal temporal seizure onset. ITC occurred earlier in right than in left temporal seizures. Significance iEEG preceded other seizure manifestations, but ictal tachycardia was an early sign particularly in mesial temporal and in right temporal seizure onset and often preceded not only other clinical manifestations but also first visible patterns in surface EEG. Detection of ictal tachycardia was thus the best noninvasively assessed marker for closed-loop interventions in this multimodally assessed patient group.

Purpose Pharmacotherapy of epilepsies is limited due to low concentrations at epileptogenic foci, side effects of high systemic doses and that some potentially efficient substances do not pass the blood–brain barrier. To overcome these limitations, we tested the efficacy of local valproate (VPA)-containing polymer implants in a model of necocortical injected tetanus toxin (TeT) in the rat. Methods Tetanus toxin was injected intracortically and cobalt (II) chloride (CoCl 2 ) was applied on the cortical surface. Video-electrocorticography recordings with intracortical electrodes were performed. VPA-containing polymers were implanted above the cortical focus. Antiepileptic effects were evaluated as reductions of epileptiform potentials (EPs) per hour in comparison to saline (NaCl)-containing polymer implants. Results Triple 50ng TeT injections plus CoCl 2 application (20/10mg) showed consistent EPs. NaCl-implanted animals ( n =6) showed a mean of 10.5EPs/h after the first week, the EP frequency increased to 53.5EPs/h after the second week. VPA-implant animals ( n =5) showed a reduction in EP frequency from 71.6 to 4.8EPs/h after the second week. The EP frequency after the second week was higher in the NaCl-implanted animals than in the VPA-implanted ( p =0.0303). The mean EPs/h increase in NaCl-implanted rats (+42.9EPs/h) was different ( p =0.0087) from the mean EPs/h decrease in VPA-implanted rats (−66.8EPs/h). Conclusion Despite former publications no clear seizures could be reproduced but it was possible to establish focal EPs, which proved to be a reliable marker for epileptic activity. Local antiepileptic therapy with VPA has shown efficacy in decreasing EP frequency.

Objective We share our experience with extratemporal MRI-negative epilepsies that received “image-guided” resection with the use of neuronavigation after invasive presurgical video-EEG monitoring. We describe and discuss our technique of image generation, navigation system registration, and surgical resection. In addition, we evaluate seizure outcome with respect to the preoperatively planned versus achieved resection. Patients and Methods Seven patients with 3 T MRI-negative extratemporal epilepsy received navigation-guided resective surgery. The resection plan was based on electrophysiological data from intracranial EEG recordings. For each case a resection segment was created in the neuronavigation device in a systematic manner. We compared the preoperatively planned segment to the achieved resection and looked for correlation with postoperative seizure outcome according to Engel classification, at last follow-up (mean 2.4 years, range 1–4 years). Results Mean volume of planned resections was 23.8 ± 15.3 cm3 and of achieved resections 17 ± 10.4 cm3. There was complete overlap with planned resection in 4 patients and partial overlap in 3. Postoperative seizure outcome was class I in 4 patients (57%), IIIA in 1 patient and IVB in 2 patients. Three patients reached seizure-freedom (Engel IA). Volume of planned resection, volume difference of planned versus achieved resection and level of overlap (complete versus partial) did not significantly correlate to seizure outcome. Conclusion The use of neuronavigation for planning and executing a tailored resection in MRI-negative extratemporal epilepsy is elaborate but can be an effective procedure.

Background Schizophrenia-like disorders can be divided into endogenic or primary, idiopathic, polygenetic forms, and different secondary, organic subgroups [e.g., (para)epileptic, immunological, degenerative]. Epileptic and paraepileptic explanatory approaches have a long tradition due to the high rate of electroencephalography (EEG) alterations in patients with schizophrenia. Case presentation We present the case of a 23-year-old female patient suffering, since the age of 14 years, from a fluctuating paranoid-hallucinatory syndrome with formal thought disorder, fear, delusions of persecution, auditory, visual, and tactile hallucinations, as well as negative and cognitive symptoms. Laboratory measurements showed increased titers of antinuclear antibodies (ANAs) in the context of ulcerative colitis. While there was no clear history or evidence of epileptic seizures, the EEG showed generalized 3 Hz polyspike wave complexes. Under treatment with levetiracetam, the symptoms disappeared and the patient was able to complete vocational training. Conclusion The schizophrenia-like symptoms associated with epileptiform discharges but not overt seizures and the good response to antiepileptic treatment could be interpreted in the context of a (para)epileptic pathomechanism. The EEG alterations might be due to a polygenetic effect due to different genes. Mild immunological mechanisms in the framework of ulcerative colitis and increased ANA titers might have supported the network instability. This case report illustrates (1) the importance of EEG screenings in schizophrenia, (2) a potential pathogenetic role of epileptiform discharges in a subgroup of patients with schizophrenia-like symptoms, and (3) that antiepileptic medication with levetiracetam could be a successful treatment alternative in schizophrenia-like disorders with EEG alterations.

Summary Objective Focal cortical dysplasia (FCD) is currently recognized as the most common cause of neocortical pharmacoresistant epilepsy. Epilepsy surgery has become an increasingly successful treatment option. Herein, the largest patient cohort reported to date is analyzed regarding long-term outcome and factors relevant for long-term seizure control. Methods Two hundred eleven children and adults undergoing epilepsy surgery for histologically proven FCD and a follow-up period of 2–12 years were analyzed regarding the longitudinal course of seizure control, effects of FCD type, localization, magnetic resonance imaging (MRI), timing of surgery, and postoperative antiepileptic treatment. Results After 1 year, Engel class I outcome was achieved in 65% of patients and the percentage of seizure-free patients remained stable over the following (up to 12) years. Complete resection of the assumed epileptogenic area, lower age at surgery, and unilobar localization were positive prognostic indicators of long-term seizure freedom. Seizure recurrence was 12% after the first year, whereas 8% achieved late seizure freedom either following additional introduction of antiepileptic drugs (AEDs) (4%), a reoperation (2%), or a running down phenomenon (2%). Thirty-nine percent of patients had a reduction of AED from polytherapy to monotherapy or a complete cessation of AED treatment. Late seizure relapse was seen in nine patients during reduction of AEDs (i.e., in 12% of all patients with AED tapering); in four of them seizures persisted after reestablishment of antiepileptic medication. Significance Postoperative long-term seizure outcome was favorable in patients with FCD and remained stable in 80% of patients after the first postoperative year. Several preoperative factors revealed to be predictive for the postoperative outcome and may help in the preoperative counseling of patients with FCD and in the selection of ideal candidates for epilepsy surgery.

Objectives Postictal generalized EEG suppression (PGES) frequently occurs after generalized convulsive seizures (GCS) and may be involved in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). It is usually determined using conventional scalp EEG which is likely to miss cerebral activity in deeper brain structures. Here, we examined intracranial EEG activity after GCS to unravel the pattern and extent of local brain activity during apparent PGES on scalp EEG (s-PGES). Methods We retrospectively reviewed electroencephalographic data of people with chronic epilepsy who had GCS during presurgical video-EEG monitoring using simultaneous intracranial and scalp EEG (10–20 system) electrodes. Results Twenty-five GCS (20 with s-PGES) of 15 patients with an average number of 88 ± 42 intracranial electrode contacts were included. The majority of GCS with s-PGES (18 of 20) displayed persisting or reemerging intracranial EEG activity during apparent PGES on scalp EEG. Three patterns were identified: Pattern 1 (11 GCS, 6 patients) consisted of continuous local interictal activity; Pattern 2 (5 GCS, 5 patients) displayed suppressed EEG activity at all intracranial contacts in the early phase of s-PGES, but reemerging local brain activity before s-PGES dissolved; and Pattern 3 (2 GCS, 2 patients) showed persistent local ictal activity during s-PGES. Persisting intracranial EEG activity at PGES onset on scalp EEG was present in 10 ± 14% (range: 0 to 42%) of all intracranial contacts and mostly in the temporal lobe. Conclusions Our results reveal that, during apparently generalized postictal EEG suppression, local brain activity persists or reemerges in most GCS. Possible implications of this localized neuronal activity in the context of SUDEP are discussed in the paper.

Pathological findings in electroencephalography (EEG) are discussed as a possible marker of organic mental disorders and a therapeutic response to anticonvulsive medication under these conditions.We compared the prevalence of EEG abnormalities in 100 patients with schizophrenia, 100 patients with schizoaffective disorder, 51 patients with acute polymorphic psychotic disorder, 100 patients with bipolar disorder, 100 patients with unipolar major depression and 76 healthy control subjects with the findings of a previous study using well-diagnosed, large control samples (13,658 pilots and aircrew personnel).We detected an increased number of pathological EEG findings with intermittent rhythmic delta or theta activity in 7% of patients with schizophrenia, 7% of patients with schizoaffective disorder, 5.9% of patients with acute polymorphic psychosis, 6% of patients with bipolar disorder, 4% of unipolar depressed patients and 3.9% of the own control group, compared to 1% of strictly controlled healthy subjects. One-sided logistic regression revealed an association between pathological EEGs and the diagnosis of schizophrenia (Wald W = 3.466, p = 0.0315), schizoaffective disorder (W = 3.466, p = 0.0315) and bipolar disorder (W = 2.862, p = 0.0455).We suggest that the previously developed local area network inhibition model for a potential paraepileptic pathomechanism can explain the relevance of such findings in different psychiatric disorders.

Introduction: An increased prevalence of pathological electroencephalography (EEG) signals has been reported in patients with borderline personality disorder (BPD). In an elaborative case description of such a patient with intermittent rhythmic delta and theta activity (IRDA/IRTA), the BPD symptoms where linked to the frequency of the IRDAs/IRTAs and vanished with the IRDAs/IRTAs following anticonvulsive therapy. This observation raised a question regarding the prevalence of such EEG abnormalities in BPD patients. The aim of this retrospective study was to identify the frequency of EEG abnormalities in a carefully analyzed psychiatric collective. Following earlier reports, we hypothesized an increased prevalence of EEG abnormalities in BPD patients. Participants and Methods: We recruited 96 consecutive patients with BPD from the archive of a university clinic for psychiatry and psychotherapy, and compared the prevalence of EEG abnormalities to those of 76 healthy controls subjects. The EEGs were rated by three different blinded clinicians, including a consultant specializing in epilepsy from the local epilepsy center. Results: We found a significant increase in the prevalence of IRDAs and IRTAs in BPD patients (14.6%) compared to the control subjects (3.9%; p = 0.020). Discussion: In this blinded retrospective case-control study, we were able to confirm an increased prevalence of pathological EEG findings (IRDAs/IRTAs only) in BPD patients. The major limitation of this study is that the control group was not matched on age and gender. Therefore, the results should be regarded as preliminary findings of an open uncontrolled, retrospective study. Future research performing prospective, controlled studies is needed to verify our findings and answer the question of whether such EEG findings might predict a positive response to anticonvulsive pharmacological treatment.

Ictal fear is a semiological feature which is commonly associated with mesial temporal lobe epilepsy. Here, we describe fear as a leading symptom in cryptogenic occipital lobe epilepsy. In a patient with negative MRI findings, intracranial EEG recordings documented a strict correlation between habitual ictal anxiety attacks and both spontaneous and stimulation-induced epileptic activity in a right occipital epileptogenic area with subsequent spreading to the symptomatogenic zone in the amygdala. Circumscribed occipital topectomy led to seizure freedom. Episodes of non-epileptic fear ceased shortly afterwards. This report provides insight into pathways of propagation of epileptic activity, illustrates different etiologies of pathologic fear and underlines the importance of ictal EEG recordings.

Summary Purpose: To assess the efficacy and tolerability of chronic high-frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes. Methods: Five adult patients (four male, 28–39 years) with PME underwent chronic high-frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow-up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation-induced myoclonic jerks and daily life performance 8 weeks prior to implantation. Key Findings: Follow-up periods ranged from 12–42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side-effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic–clonic seizures increased after 3 months of stimulation following extensive trauma-related surgery. The best effect was seen in the least impaired patient. Significance: DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly.

Im deutschsprachigen Raum erfolgt die invasive Abklarung pharmakoresistenter fokaler Epilepsien traditionell unter Verwendung subduraler Elektroden, die gelegentlich mit einzelnen intrakraniellen Tiefenelektroden kombiniert werden. Demgegenuber steht die insbesondere in Frankreich und Italien verbreitete Methode der Stereoelektroenzephalographie (SEEG), bei der zur Bestimmung des epileptogenen Areals multiple Tiefenelektroden stereotaktisch implantiert werden. Anhand einer Kasuistik werden im vorliegenden Beitrag mogliche methodische Vorteile der SEEG exemplarisch veranschaulicht. Die seit Mitte 2008 erfolgte Etablierung der SEEG am Epilepsiezentrum Freiburg hat das Potenzial fur eine differenzierte prachirurgische Epilepsiediagnostik erweitert.

Einer 25-jahrigen Patientin wurde basierend auf dem magnetresonanztomographischen Nachweis eines links frontalen Kavernoms und anamestisch berichteten epileptischen Anfallen mit Kloni des rechten Armes ein epilepsiechirugischer Eingriff empfohlen. Nach Vorstellung im Epilepsiezentrum wies ein prolongiertes Video-EEG-Monitoring nach vollstandigem Absetzen von Valproat generalisierte Spike-wave-Komplexe (3/s) und bilaterale myoklonische Anfalle nach. Der bildgebende Nachweis einer Lasion kann zu einer falschen Interpretation der Anfallssemiologie verfuhren, die wiederum in eine falsche Klassifikation der Epilepsie sowie fehlerhafte und potenziell gefahrliche therapeutische Interventionen mundet. Der Nachweis eines kausalen Zusammenhanges zwischen Lasion und Epilepsie durch iktale Video-EEG-Aufzeichnungen vor einem epilepsiechirurgischen Eingriff ist unerlasslich.

Despite recent technological advancements in magnetencephalography and neuroimaging, the "old-fashioned” EEG continues to play a crucial role in the presurgical evaluation of epilepsies. This review highlights the unique features of non-invasive and invasive EEG techniques as well as their strengths and limitations in defining the epileptogenic zone.

Cardiac bradyarrhythmias may play a pivotal role in the pathophysiology of sudden unexpected death in epilepsy (SUDEP). We describe a patient with left temporal lobe epilepsy in whom high-grade atrioventricular conduction blocks were triggered by both spontaneous and stimulation-induced epileptic activity in the left temporal lobe. Electrophysiological data obtained by surface and intracranial electrodes point to a cerebral cardioarrhythmogenesis in the left amygdala and anterior hippocampus.

The epileptologically informed in-depth analysis of auto- and heteroanamnestic historical sources supports the hypothesis that Hector Berlioz (1803–1869) might have suffered from a photosensitive idiopathic generalized epilepsy syndrome with absences, absence status, myoclonic seizures, and bilateral tonic–clonic seizures. The study outlines the possible influence of the composer's probable epilepsy on his literary and musical oeuvre, including the Symphonie fantastique en cinq parties .

Purpose. In neocortical epilepsies not satisfactorily responsive to systemic antiepileptic drug therapy, local application of antiepileptic agents onto the epileptic focus may enhance treatment efficacy and tolerability. We describe the effects of focally applied valproate (VPA) in a newly emerging rat model of neocortical epilepsy induced by tetanus toxin (TeT) plus cobalt chloride (CoCl2).Methods. In rats, VPA (n=5) or sodium chloride (NaCl) (n=5) containing polycaprolactone (PCL) implants were applied onto the right motor cortex treated before with a triple injection of 75 ng TeT plus 15 mg CoCl2. Video-EEG monitoring was performed with intracortical depth electrodes.Results. All rats randomized to the NaCl group died within one week after surgery. In contrast, the rats treated with local VPA survived significantly longer (P<0.01). In both groups, witnessed deaths occurred in the context of seizures. At least3/4of the rats surviving the first postoperative day developed neocortical epilepsy with recurrent spontaneous seizures.Conclusions. The novel TeT/CoCl2approach targets at a new model of neocortical epilepsy in rats and allows the investigation of local epilepsy therapy strategies. In this vehicle-controlled study, local application of VPA significantly enhanced survival in rats, possibly by focal antiepileptic or antiepileptogenic mechanisms.

Precise delineation of pathological and eloquent cortices is essential in pre-neurosurgical diagnostics of epilepsy. A limitation of existing experimental procedures, however, is that they critically require active cooperation of the patient, which is not always achievable, particularly in infants and in patients with insufficient cognitive abilities. In the present study, we evaluated the potential of electrocorticographic recordings of high gamma activity during natural, non-experimental behavior of epilepsy patients to localize upper- and lower-extremity motor and language functions, and compared the results with those obtained using electrocortical stimulation. The observed effects were highly significant and functionally specific, and agreed well with the somatotopic organization of the motor cortex, both on the lateral convexity and in the supplementary motor area. Our approach showed a similar specificity and sensitivity for extremity movements as previously obtained from experimental data. We were able to quantify, for the first time, sensitivity and specificity of high gamma underlying non-experimental lower-extremity movements in four patients, and observed values in the same range as for upper extremities (analyzed in six patients). Speech-related responses in the three investigated patients, however, exhibited only a very low sensitivity. The present findings indicate that localization of not only upper- but also lower-extremity movements congruent with electrocortical stimulation mapping is possible based on event-related high gamma responses that can be observed during natural behavior. Thus, non-experimental mapping may be usefully applied as adjunct to established clinical procedures for identification of both upper- and lower-extremity motor functions.

To assess the efficacy and tolerability of chronic high-frequency deep brain stimulation (DBS) in adult patients with progressive myoclonic epilepsy (PME) syndromes.Five adult patients (four male, 28-39 years) with PME underwent chronic high-frequency DBS according to a study protocol that had been approved by the local ethics committee. Electrodes were implanted in the substantia nigra pars reticulata (SNr)/subthalamic nucleus (STN) region in the first patient and additionally in the ventral intermediate nucleus (VIM) bilaterally in the following four cases. Follow-up took place in intervals of 3 months and DBS effects were compared with baseline frequency of passive and activation-induced myoclonic jerks and daily life performance 8 weeks prior to implantation.Follow-up periods ranged from 12-42 months (median 24 months). The best clinical effects were seen with SNr/STN DBS in all patients. VIM stimulation failed to achieve acute therapeutic effects and revealed low side-effect thresholds and even triggering of myoclonia. In all patients the reduction of myoclonic seizures was observed and ranged between 30% and 100% as quantified by a standardized video protocol. All patients reported clinically relevant improvements of various capabilities such as free standing and walking or improved fine motor skills. In one patient with an excellent initial response generalized tonic-clonic seizures increased after 3 months of stimulation following extensive trauma-related surgery. The best effect was seen in the least impaired patient.DBS of the SNr/STN may be an effective treatment option for patients with PME. Less impaired patients may benefit more markedly.

Depth recordings in patients with Parkinson's disease on dopaminergic therapy have revealed a tendency for oscillatory activity in the basal ganglia that is sharply tuned to frequencies of approximately 70 Hz and increases with voluntary movement. It is unclear whether this activity is essentially physiological and whether it might be involved in arousal processes. Here we demonstrate an oscillatory activity with similar spectral characteristics and motor reactivity in the human thalamus. Depth signals were recorded in 29 patients in whom the ventral intermediate or centromedian nucleus were surgically targeted for deep brain stimulation. Thirteen patients with four different pathologies showed sharply tuned activity centred at approximately 70 Hz in spectra of thalamic local field potential (LFP) recordings. This activity was modulated by movement and, critically, varied over the sleep-wake cycle, being suppressed during slow wave sleep and re-emergent during rapid eye movement sleep, which physiologically bears strong similarities with the waking state. It was enhanced by startle-eliciting stimuli, also consistent with modulation by arousal state. The link between this pattern of thalamic activity and that of similar frequency in the basal ganglia was strengthened by the finding that fast thalamic oscillations were lost in untreated parkinsonian patients, paralleling the behaviour of this activity in the basal ganglia. Furthermore, there was sharply tuned coherence between thalamic and pallidal LFP activity at approximately 70 Hz in eight out of the 11 patients in whom globus pallidus and thalamus were simultaneously implanted. Subcortical oscillatory activity at approximately 70 Hz may be involved in movement and arousal.

We present a probabilistic epileptic seizure predictor and an according method for its statistical evaluation. The probabilistic predictor is based on a combination of feature channels, which are derived from the intracranial electroencephalogram (EEG), by a logistic regression map. The evaluation is done by the Brier score, an established assessment method in meteorology, which quantifies the prediction error. From the prediction features, the weights of the logistic regression are learned in a training phase and in a test phase the Brier score is assessed. A test for significance of the probabilistic predictor, based on seizure time surrogates, is computed. For 3 of 5 patients we obtained significant predictive power with the mean phase coherence and with the dynamical similarity index we obtained for 2 of the 5 patients significant results. The concept of probabilistic prediction can be a valuable tool for the development of future seizure intervention systems.

Background and aims: Recent data have revealed that clinically generalised tonic–clonic seizures do not involve all brain regions electrophysiologically. The hippocampus in particular could be protected from epileptic activity by putative filtering properties of the dentate gyrus. Here we investigated if simple or complex focal seizures (SFS/CFS) and in particular secondarily generalised tonic–clonic seizures (SGS) of extrahippocampal onset (EHO) spare the hippocampus and if there are promotive factors. Methods: We retrospectively assessed clinical, electrophysiological, imaging and histopathological data from patients undergoing presurgical evaluation of focal epilepsy with hippocampal depth and extrahippocampal subdural electrodes and selected those suffering from SGS of EHO. We further subdivided this patient sample according to qualitative MRI criteria into a HL(−) group, with an extrahippocampal lesion only, and a HL(+) group, displaying an extrahippocampal and additional hippocampal lesion. Results: 14 patients (seven in each group) fulfilling the inclusion criteria had a total of 43 SGS, of which 35 were of EHO. Whereas only 68% of SFS/CFS of EHO propagated into the hippocampus, all SGS of EHO invaded the hippocampi independently of the ictal propagation pattern or degree of hippocampal pathology. All hippocampi in the HL(−) group displayed interictal epileptiform activity and even seizure onset in two patients. Conclusions: In our patient sample, the human hippocampus was not spared during SGS of EHO, but was invariably invaded by epileptic activity. The presence of spontaneous epileptic activity in the HL(−) group revealed persistent modifications in hippocampal excitability that might be due to secondary epileptogenesis in the hippocampus following repeated seizures of EHO.

Benign focal epileptiform discharges of childhood are a genetically determined electroencephalographic trait. Assessment of their clinical relevance in children with epilepsy may be difficult if imaging reveals a lesion congruent or incongruous with the focus of the benign focal epileptiform discharges of childhood. This article reports a boy with parietooccipital benign focal epileptiform discharges of childhood in whom videoelectroencephalography and magnetic resonance imaging disclosed symptomatic frontal lobe epilepsy. Surgical removal of a focal cortical dysplasia in the left frontal lobe yielded freedom from seizures and positive behavioral and cognitive development. Nocturnal benign focal epileptiform discharges of childhood persisted until puberty (follow-up, 50 months). Early diagnostic differentiation of idiopathic syndromes such as idiopathic benign focal epilepsy of childhood from symptomatic focal epilepsies with a potentially less benign course is important. In symptomatic frontal lobe epilepsy, epilepsy surgery may yield an excellent outcome despite the presence of concurrent benign focal epileptiform discharges of childhood.

A total of 120 patients with histologically proven focal cortical dysplasias (FCD) were retrospectively analysed for prognostic factors for successful epilepsy surgery. Multivariate data analyses showed that older age at epilepsy surgery, occurrence of secondarily generalised seizures and a multilobar extent of the dysplasia were significant negative predictors. In univariate analyses, longer duration of epilepsy, need for intracranial EEG recordings and incomplete resection of the FCD were factors which significantly reduced the chance of becoming seizure free. Histological subtype of the FCD and age at epilepsy onset had no significant predictive value. These findings strongly suggest early consideration of epilepsy surgery in FCD patients.

Purpose Most common clinical studies with antiepileptic drugs do not reflect medical everyday practice due to their strict in- and exclusion criteria and specifications of treatment regimens. Here we present a large non-interventional registry with the intention to evaluate the spectrum of applications in daily use and the efficacy and tolerability of intravenously given levetiracetam (LEV-iv). Methods In a prospective approach of 17 neurological and neuropediatric centres in Germany LEV-iv treated patients of all ages were included over a period of 10 months. The observational period was 10 days with daily documentation of LEV-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events (AEs). In addition, treatment efficacy and tolerability were assessed by patients and physicians at study end as well as practicability of LEV-iv using a five-step scale. Results In 95 patients LEV-iv was administered, 93 were included into the analysis. The median LEV-iv dose was 1500mg (range 110–6000mg) per day. Median age was 66 years (range 0.7–90.3 years). The majority of patients ( n =70, 75%) suffered from status epilepticus (SE, n =55, 59%) and acute seizure clusters ( n =15, 16%). Of those with SE, 41 patients (75%) had SE for the first time. Acute seizure clusters and SE terminated in 83% after LEV-iv administration. A total of 29 adverse events were reported in 17 of the 95 patients from the safety set. Ten of these were at least possibly related to LEV-iv treatment. Slight decrease of blood pressure during the infusion (3 patients each) was captured most frequently. No serious side effect was observed. Physicians rated the efficacy and tolerability of LEV-iv treatment as good or very good in 78% and 82% of the cases, respectively. Conclusion In this large observational study of everyday practise the use of LEV-iv exhibited a remarkable good response and tolerability in patients with acute onset seizures (mostly SE). Further randomized controlled studies, like the established status epilepticus trial (ESET) are needed to confirm these findings.

Purpose Resective epilepsy surgery is the recommended treatment for a well-defined group of patients with drug-resistant epilepsy. Long-term outcome studies are an appropriate quality control to assess the value of elective surgical procedures ethically and economically. This paper reports the long-term post-surgical follow-up of adult patients of the Kork Epilepsy Centre. Method Data collection was performed by means of a questionnaire to obtain updated information about postsurgical outcome, frequency and postsurgical seizure semiology in case of relapse, postsurgical use of antiepileptic drugs, social issues and satisfaction rates. We classified seizure outcome according to the ILAE surgery outcome scale (OC 1–OC 6). Results Outcome data of 340 adult patients were obtained. Mean post-operative follow-up was 6.7 years (range 1.0–21.6 years). Seizure remission was 67% if comprising patients with postoperative auras only (OC 1+OC 2). Sixty-two per cent of patients were completely seizure free. The majority of patients (78%) underwent temporal lobe resections. Sixty-four per cent of these and 52% of the patients with extra-temporal resections became completely seizure-free (OC 1). Only 34% of the patients with negative MRI achieved complete seizure-freedom. Conclusion In line with others our huge cohort sample that covers decades of experience with epilepsy surgery revealed satisfying long-term outcome results. Best results were obtained in lesional temporal lobe epilepsy, least favourable results in MRI-negative epilepsy.