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Background: Status epilepticus (SE) can occur in persons with or without epilepsy and is associated with high morbidity and mortality. Methods: This survey aimed to record self-reported frequency of SE in persons with epilepsy, its association with clinical characteristics and patient level of information on SE and rescue medication. 251 persons with epilepsy at a tertiary epilepsy center were included in the study. Results: 87 (35%) had a history of SE defined as seizure duration of more than 5 min. These patients were less likely to be seizure-free, and had a higher number of present and past anti-seizure medication. Female sex, cognitive disability, younger age at epilepsy onset, defined epilepsy etiology, and focal epilepsy were associated with a history of SE. On Cox regression analysis, female sex, defined etiology and focal classification remained significant. 67% stated that they had information about prolonged seizures, and 75% knew about rescue medication. 85% found it desirable to receive information about SE at the time of initial diagnosis of epilepsy, but only 16% had been offered such information at the time. Conclusion: SE is frequent among persons with epilepsy and there remain unmet needs regarding patient education. [ABSTRACT FROM AUTHOR]

Purpose: Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy. Methods: Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews. Results: Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic–clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only. Conclusion: Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome. [ABSTRACT FROM AUTHOR]

Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t -test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions. [ABSTRACT FROM AUTHOR]

Objectives To evaluate dose-response relationship of BGG492 as add-on therapy to 1-3 antiepileptic drugs in patients with partial-onset seizures and to investigate safety and tolerability of BGG492. Methods This was a 12-week, randomized, double-blind, placebo-controlled, phase II dose-titration study (core study) with a 30-week, flexible-dose, open-label extension. In the core study, patients were randomized (1:2) to placebo or BGG492 100 mg t.i.d. in cohort 1, and in cohort 2 patients were randomized (1:4) to placebo or BGG492 150 mg t.i.d. On completion of the core study, eligible patients entered the extension study. Primary outcome measures were total partial seizure frequency per 28 days (core study) and safety and tolerability (extension study). Results Overall, 93 patients were randomized (150 mg [n = 44]; 100 mg [n = 24]; placebo [n = 25]), and 81 (87.1%) completed the core study. Fifty-one patients entered and 43 (84.3%) completed the extension study. In the core study, no statistically significant dose-response trend among the BGG492 treatment groups (100 and 150 mg) was observed at the 4-week double-blind maintenance period (weeks 7-10); however, there was higher percent reduction in total partial seizure frequency in the BGG492 150 mg over placebo groups (37.32%; 95% confidence interval [CI] −18.90, 66.95). Dizziness, somnolence, and fatigue were the most common adverse events ( AEs), higher in the BGG492 150 mg group than in the 100 mg and placebo groups (dizziness: 14 [31.8%] vs. 3 [12.5%] and 1 [4.0%]; somnolence: 7 [15.9%] vs. 1 [4.2%] and 1 [4.0%]; fatigue: 5 [11.4%] vs. 1 [4.2%] and 1 [4.0%]). During the open-label extension study, 39 (76.5%) patients on BGG492 had AEs, and the most commonly experienced AEs were dizziness (14 [27.5%]) and somnolence (9 [17.6%]). Significance There was no significant dose-response trend in the BGG492 treatment groups (100 and 150 mg); however, higher percent reduction over placebo was observed in the BGG492 150 mg group. Safety and tolerability data were consistent with the known safety profile for BGG492, and no new safety risks were identified. [ABSTRACT FROM AUTHOR]

Recording extracellulary from neurons in the brains of animals in vivo is among the most established experimental techniques in neuroscience, and has recently become feasible in humans. Many interesting scientific questions can be addressed only when extracellular recordings last several hours, and when individual neurons are tracked throughout the entire recording. Such questions regard, for example, neuronal mechanisms of learning and memory consolidation, and the generation of epileptic seizures. Several difficulties have so far limited the use of extracellular multi-hour recordings in neuroscience: Datasets become huge, and data are necessarily noisy in clinical recording environments. No methods for spike sorting of such recordings have been available. Spike sorting refers to the process of identifying the contributions of several neurons to the signal recorded in one electrode. To overcome these difficulties, we developed Combinato: a complete data-analysis framework for spike sorting in noisy recordings lasting twelve hours or more. Our framework includes software for artifact rejection, automatic spike sorting, manual optimization, and efficient visualization of results. Our completely automatic framework excels at two tasks: It outperforms existing methods when tested on simulated and real data, and it enables researchers to analyze multi-hour recordings. We evaluated our methods on both short and multi-hour simulated datasets. To evaluate the performance of our methods in an actual neuroscientific experiment, we used data from from neurosurgical patients, recorded in order to identify visually responsive neurons in the medial temporal lobe. These neurons responded to the semantic content, rather than to visual features, of a given stimulus. To test our methods with multi-hour recordings, we made use of neurons in the human medial temporal lobe that respond selectively to the same stimulus in the evening and next morning. [ABSTRACT FROM AUTHOR]

Objective Recent reports define temporal lobe epilepsy with amygdala enlargement ( TLE- AE) as a distinct electroclinical syndrome comparable to TLE with hippocampal sclerosis. In this retrospective observational study, we present the largest consecutive series of patients with new-onset TLE- AE to date and describe clinical characteristics and seizure outcome, and we aim to explore underlying autoimmune mechanisms within this syndrome. Methods We reviewed all consecutive patients between 2004 and 2014 at our tertiary epilepsy center at the University of Bonn, Germany, with new-onset (<5 years) TLE- AE, negative serum antibody (ab) test results, and with available follow-up data for at least 12 months. Results We identified 40 patients (23 male) with TLE- AE with a median age at epilepsy onset of 51 years (range 10-73) and a median disease duration of 11 months (range 0.5-55) at first presentation. At follow-up, 50% of the entire cohort achieved seizure freedom. Of interest, patients with remittent features of AE at follow-up (N = 24) had a superior outcome compared to those with stable magnetic resonance imaging ( MRI) features of AE (N = 16): 17 (71%) of 24 were seizure-free for at least 6 months compared to 3 (19%) of 16, respectively (p = 0.003). MRI volumetry confirmed significantly enlarged amygdalae in TLE- AE in relation to healthy controls, and additionally showed significantly greater volume reductions in patients with remittent AE compared to those with stable AE. Significance TLE- AE is a clinical syndrome beginning mostly in middle age, and in addition to its known association with ab-positive limbic encephalitis, it occurs in an ab-negative condition. Remission of AE in the course of the disease could be identified as a predictor for a favorable clinical outcome and is suspicious of an autoimmune etiology, although we could not confirm this hypothesis unequivocally with currently available noninvasive diagnostic tools. [ABSTRACT FROM AUTHOR]

Object: Resective surgery is a safe and effective treatment of drug-resistant epilepsy. If surgery has failed reoperation after careful re-evaluation may be a reasonable option. This study was to summarise the risks and benefits of reoperation in patients with epilepsy.Methods: This is a retrospective single centre study comprising clinical data, long-term seizure outcome, neuropsychological outcome and postoperative complications of patients, who had undergone a second resective epilepsy surgery from 1989 to 2009.Results: A total of 66 patients with median follow-up of 10.3 years were included into the study. Fifty-one patients (77%) had surgery for temporal lobe epilepsy, the remaining 15 cases for extra-temporal lobe epilepsies. The most frequent histological findings were tumours (n=33, 50%), followed by dysplasia, gliosis (n=11, each) and hippocampus sclerosis (n=9). The main reasons for seizure recurrence were incomplete resection (59.1%) of the putative epileptogenic lesion. After reoperation 46 patients (69.7%) were completely seizure-free International League Against Epilepsy 1 (ILAE 1) at the last available follow-up. The neuropsychological evaluation demonstrated that repeated losses in the same cognitive domain, that is, successive changes from better to worse performance categories, were rare and that those losses after first surgery were followed by improvement rather than decline. However, reoperations lead to an increased rate of permanent neurological deficits (9%), overall surgical complications (9%) and visual field deficits (67%).Conclusions: Reoperation after failed resective epilepsy surgery led to approximately 70% long-time seizure freedom and reasonable neuropsychological outcome. There is an increased risk of permanent postoperative neurological deficits, which should be taken into consideration when counselling for reoperation. [ABSTRACT FROM AUTHOR]

Epilepsy surgery is currently the only way to cure drug-resistant epilepsy (DRE). The loss of epileptic activity or its propagation in the developing brain may not only result in seizure freedom but also be associated with further positive effects. Here, we analyzed the cognitive development of children and adolescents with DRE after epilepsy surgery. We evaluated retrospectively the cognitive development of children and adolescents before and after epilepsy surgery. Fifty-three children and adolescents underwent epilepsy surgery at a median age of 7.62 years. Overall seizure freedom was 86.8% at a current median observation period of 20 months. Presurgically, 81.1% had the clinical diagnosis of cognitive impairment, which was confirmed by standardized tests in 43 of 53 patients (76.7%). Further 10 patients had severe cognitive impairment rendering a standardized test impossible. The median intelligence quotient (IQ)/development quotient value was 74. After surgery, caretakers reported developmental progress in all patients, whereas the median IQ decreased slightly (P = 0.404). In eight patients the IQ points decreased after surgery; however, their individual raw scores increased in line with their reported increase in cognitive abilities. We did not detect any cognitive deterioration in children following epilepsy surgery. A loss of IQ points did not correspond to a real loss of cognitive abilities. These patients developed more slowly than age-matched peers with an average development speed but profited individually as seen in their raw scores. Therefore, an individual analysis of raw scores is relevant to assess the cognitive development after surgery. [ABSTRACT FROM AUTHOR]

Purpose Precise outcome data about the surgical therapy of cerebral cavernous malformation (CCM)-associated epilepsy is scarce regarding different epilepsy types, surgical approach, and outcome. Long-term outcome in patients with CCM-associated epilepsy is analyzed in a large single-center series. Methods Seizure outcome data >24 months was available in 118 patients. The influence of different parameters of preoperative workup and surgical technique was analyzed with regard to seizure outcome. Key Findings The study cohort comprised 76 patients with drug-resistant epilepsy (DRE), 20 patients with chronic epilepsy that did not meet the definition of DRE, as well as 22 patients with sporadic seizures. Temporal localization of CCMs predisposed to develop DRE. Detailed epileptologic workup was performed in 85 patients; invasive monitoring was done in 23 (37%) of 76 DRE cases. In 84% of DRE cases more extensive resections were performed. Mean follow-up varied between 107 and 137 months for the three groups. Seizure freedom in DRE was 88%, in chronic epilepsy 80%, and in sporadic seizures was 91%. Longer symptom duration was associated with worse seizure outcome. Outcome of patients who underwent invasive monitoring was not worse. The outcome in CCM-associated DRE can be good if more extensive resections are used and if noninvasive and/or invasive presurgical epileptologic workup is used whenever indicated. DRE was considerably more frequent in the temporal lobe, suggesting that temporal localization predisposes development of DRE. Seizure freedom rates were stable over a long period. Significance Surgical therapy of CCM-associated seizures and epilepsy can be successful if different surgical techniques according to presurgical evaluation are realized. To prevent clinical worsening into DRE, surgical intervention in CCM-associated epilepsy may be considered early. [ABSTRACT FROM AUTHOR]

Which neural processes underlie our conscious experience? One theoretical view argues that the neural correlates of consciousness (NCC) reside in local activity in sensory cortices. Accordingly, local category-specific gamma band responses in visual cortex correlate with conscious perception. However, as most studies manipulated conscious perception by altering the amount of sensory evidence, it is possible that they reflect prerequisites or consequences of consciousness rather than the actual NCC. Here we directly address this issue by developing a new experimental paradigm in which conscious perception is modulated either by sensory evidence or by previous exposure of the images while recording intracranial EEG from the higher-order visual cortex of human epilepsy patients. A clear prediction is that neural processes directly reflecting conscious perception should be present regardless of how it comes about. In contrast, we observed that although subjective reports were modulated both by sensory evidence and by previous exposure, gamma band responses solely reflected sensory evidence. This result contradicts the proposal that local gamma band responses in the higher-order visual cortex reflect conscious perception. [ABSTRACT FROM AUTHOR]

Not only poststimulus, but also prestimulus neural activity has been shown to be predictive for later successful memory encoding. However, it is still not clear which medial temporal lobe processes precede effective memory formation. Here, our aim was to investigate whether such prestimulus markers for successful memory encoding can be specified based on intracranial recordings directly from the hippocampus and rhinal cortex. For this purpose, we analyzed subsequent memory effects during a continuous word recognition paradigm in 31 presurgical epilepsy patients. We found that rhinal and hippocampal theta and successive alpha power enhancement before word presentation predicted successful memory encoding. Previous studies suggest that stimulus-triggered hippocampal theta activity is particularly related to memory retrieval and activation of a mnemonic context, whereas the alpha rhythm reflects inhibitory top-down control of task processing and executive functioning. In line with these suggestions, we propose that the observed medial temporal theta and alpha power increases before stimulus presentation reflect activation of contextual information and inhibitory top-down control processes preparing for stimulus-triggered memory processing. [ABSTRACT FROM AUTHOR]

The article offers information on a study conducted to analyze whether antiepilectic drugs (AEDs) have affect on serum levels of vitamin B12 and folate. The study included patients who suffered from epilepsy of the Department for Epileptology of the University Hospital Bonn in Germany. It mentions that the study conducted in Germany concluded that AEDS other than benzodiazepines and levetiracetam are associated with lower serum levels.

Recent findings indicate that the hippocampus supports not only longterm memory encoding but also plays a role in working memory MM) maintenance of multiple items; however, the neural mechanism underlying multi-item maintenance is still unclear. Theoretical work suggests that multiple items are being maintained by neural assemblies synchronized in the gamma frequency range (25-100 Hz) that are locked to consecutive phase ranges of oscillatory activity in the theta frequency range (4-8 Hz). Indeed, cross-frequency coupling of the amplitude of high-frequency activity to the phase of slower oscillations has been described both in animals and in humans, but has never been linked to a theoretical model of a cognitive process. Here we used intracranial EEG recordings in human epilepsy patients to test pivotal predictions from theoretical work. First, we show that simultaneous maintenance of multiple items in WM is accompanied by cross-frequency coupling of oscillatory activity in the hippocampus, which is recruited dunng multiitem WM. Second, maintenance of an increasing number of items is associated with modulation of beta/gamma amplitude with theta band activity of lower frequency, consistent with the idea that longer cycles are required for an increased number of representations by gamma cycles. This effect cannot be explained by a difference in theta or beta! gamma power. Third, we describe how the precision of cross-frequency coupling predicts individual WM performance. These data support the idea that working memory in humans depends on a neural code using phase information. [ABSTRACT FROM AUTHOR]

The face inversion effect (FIE) refers to a disproportionate disruption of the processing of face information by inverting faces. We investigated the FIE in epilepsy patients by simultaneous intracranial and scalp recordings of event-related potentials (ERPs). In scalp recordings, a typical FIE on ERPs was observed with increased latencies and amplitudes of the positive counterpart of the occipito-temporal N170, namely, the vertex positive potential (VPP), in response to inverted faces. Similar amplitude and latency increases were revealed for the intracranial N200 recorded over face-sensitive and non-face-sensitive areas in the lateral occipital cortex, but not in the ventral temporal cortex. Peak latencies did not differ between the scalp VPP and intracranial N200. Findings indicate that the lateral occipital cortex but not the ventral temporal cortex contributes primarily to the FIE observed in scalp recordings. [ABSTRACT FROM AUTHOR]

Summary: Analysis of ictal semiology is essential to presurgical evaluation of epilepsy patients providing information on seizure origin. To assess the significance of hypersalivation and postictal coughing for seizure origin in temporal lobe epilepsy (TLE), we analyzed video/EEG monitoring documented seizures of 107 adult patients for these seizure elements with respect to frequency and sequence of occurrence in relation to epileptogenic origin, comparing mesial versus extra-mesial and left versus right. Hypersalivation was rare, but occurred exclusively in seizures of mesial origin (9.4%). Comparison between left (11.4%) and right (6.9%) mesial origin was statistically insignificant. Postictal coughing also occurred exclusively in seizures of mesial onset (6.3%). Again, comparison between left (5.7%) and right (6.9%) mesial seizure onset was statistically insignificant. Thus, hypersalivation and postictal coughing are rare seizure phenomena in TLE, but their occurrence strongly support mesial seizure origin. [Copyright &y& Elsevier]

We apply the method of frequency-selective excitation waves in excitable media to characterize synchronization phenomena in interacting complex dynamical systems by measuring coincidence rates of induced excitations. We relax the frequency-selectivity of excitable media and demonstrate two applications of the method to signals with broadband spectra. Findings obtained from analyzing time series of coupled chaotic oscillators as well as electroencephalographic (EEG) recordings from an epilepsy patient indicate that this method can provide an alternative and complementary way to estimate the degree of phase synchronization in noisy signals. [ABSTRACT FROM AUTHOR]

We assess electrical brain dynamics before, during, and after 100 human epileptic seizures with different anatomical onset locations by statistical and spectral properties of functionally defined networks. We observe a concave-like temporal evolution of characteristic path length and cluster coefficient indicative of a movement from a more random toward a more regular and then back toward a more random functional topology. Surprisingly, synchronizability was significantly decreased during the seizure state but increased already prior to seizure end. Our findings underline the high relevance of studying complex systems from the viewpoint of complex networks, which may help to gain deeper insights into the complicated dynamics underlying epileptic seizures. [ABSTRACT FROM AUTHOR]

Interregional interactions of oscillatory activity are crucial for the integrated processing of multiple brain regions. However, while the EEG in virtually all brain structures passes through substantial modifications during sleep, it is still an open question whether interactions between neocortical and medial temporal EEG oscillations also depend on the state of alertness. Several previous studies in animals and humans suggest that hippocampal-neocortical interactions crucially depend on the state of alertness (i.e., waking state or sleep). Here, we analyzed scalp and intracranial EEG recordings during sleep and waking state in epilepsy patients undergoing presurgical evaluation. We found that the amplitudes of oscillations within themedial temporal lobe and the neocortex were more closely correlated during sleep, in particular during non-REM sleep, than during waking state. Possibly, the encoding of novel sensory inputs, which mainly occurs during waking state, requires that medial temporal dynamics are rather independent from neocortical dynamics, while the consolidation of memories during sleep may demand closer interactions between MTL and neocortex. [ABSTRACT FROM AUTHOR]

Purpose: It is difficult to validly assess the long-term effect of epilepsy surgery. Here, this is attempted by comparing the outcome of surgically treated pharmacoresistant epilepsy patients to three different nonoperated comparison groups regarding seizure control, antiepilepsy drug (AED) usage, and health related quality of life (QOL). Methods: One hundred thirty-one operated patients (group 1, mean follow-up since presurgical assessment 6.9 years), 105 patients awaiting presurgical assessment (group 2, mean follow-up after assignment to waiting list 0.8 years), 99 patients considered to be presurgical candidates who chose to withdraw from waiting for presurgical assessment (group 3, mean follow-up after assignment to waiting list 5.5 years), and 49 patients who were not deemed to be eligible for surgery after comprehensive assessment (group 4, mean follow-up since presurgical assessment 6.5 years) were studied. The patients completed a questionnaire on seizures, AED usage, and QOL (ESI-55). Results: The surgical patients had a better outcome than all three comparison groups regarding seizure frequency, seizure freedom rate, and number of AEDs used. They scored higher than groups 2, 3, and 4 on 7/11, 6/11, and 3/11 ESI-55 domains, respectively. Conclusions: The superior long-term outcome of the operated patients was most marked if compared to the patients awaiting surgery. This is compatible with the assumption that patients present for presurgical candidacy selection and assessment at a “nadir” of their disease course. After several years, a regression to the mean occurs which reduces (but does not abolish) the differences between nonoperated and operated patients. [ABSTRACT FROM AUTHOR]

Purpose: Intellectual disabilities are often associated with bilateral or diffuse morphologic brain damage. The chances of becoming seizure free after focal surgery are therefore considered to be worse in patients with intellectual disabilities. The risk of postoperative cognitive deficits could increase because diffuse brain damage lowers the patient's ability to compensate for surgically induced deficits. Several studies in adult patients have indicated that IQ alone is not a good predictor of postoperative cognitive and seizure outcome. Our study evaluated this subject in children and adolescents. Methods: Pediatric patients with intellectual disabilities (IQ ≤ 70), subaverage intelligence (IQ between 71 and 85), or average-range intelligence (IQ > 85) were matched according to several clinical and etiologic criteria to determine the influence of IQ (N = 66). Results: No dependency of seizure outcome, postoperative cognitive development, and behavioral outcome on the IQ level was found. All groups slightly improved in attention while memory functions tended to decrease and executive functions were stable. School placement remained unchanged for the majority of patients. Between 67 and 78% were seizure free 1 year after surgery (Engel outcome class I). Conclusions: IQ alone is not a good predictor of postoperative outcome in pediatric patients with epilepsy. As with patients of average-range intelligence, the decision to operate on patients with a low level of intelligence should depend on the results of the presurgical diagnostics. If the results of the neuropsychological examination indicate diffuse functional impairment, this should not hinder further steps, if all other findings are consistent. [ABSTRACT FROM AUTHOR]

Objective: To assess whether surgery to reduce or control epileptic seizures is safe and effective in patients known to have additional psychogenic seizures. Design: We reviewed our computerized database of 1342 patients examined for epilepsy surgery and identified 13 patients with both epileptic and psychogenic seizures on whom postoperative outcome data were available. Data were gathered from the patients' records. Mean postoperative follow-up was 56 months. Results: Epilepsy surgery led to clinically relevant improvements in 11 of 13 patients. Seven patients became free of epileptic and psychogenic seizures, 2 patients became free of epileptic seizures but continued to have infrequent psychogenic seizures, 1 patient reported more than an 80% improvement in epileptic seizure frequency and an abolishment of psychogenic attacks, and in 1 patient nondisabling epileptic seizures persisted at lower frequency but psychogenic seizures stopped. In 2 of 13 patients, epilepsy surgery failed to produce notable improvements. Although 1 patient became free of epileptic attacks and the other had fewer than 3 epileptic seizures per year, the severity or frequency of psychogenic seizures and pseudo–status epilepticus increased postoperatively. One of these patients had a preoperative diagnosis of somatization disorder; in the other, pathological illness behavior had been noted. Conclusion: A diagnosis of additional psychogenic seizures should not be considered an absolute contraindication to epilepsy surgery, although patients should undergo careful preoperative psychiatric evaluation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To test whether epileptic seizure prediction algorithms have true predictive power, their performance must be compared with the one expected under well-defined null hypotheses. For this purpose, analytical performance estimates and seizure predictor surrogates were introduced. We here extend the Monte Carlo framework of seizure predictor surrogates by introducing alarm times surrogates. Methods: We construct artificial seizure time sequences and artificial seizure predictors to be consistent or inconsistent with various null hypotheses to determine the frequency of null hypothesis rejections obtained from analytical performance estimates and alarm times surrogates under controlled conditions. Results: Compared to analytical performance estimates, alarm times surrogates are more flexible with regard to the testable null hypotheses. Both approaches have similar, high statistical power to indicate true predictive power. For Poisson predictors that fulfill the null hypothesis of analytical performance estimates, the frequency of false positive null hypothesis rejections can exceed the significance level for long mean inter-alarm intervals, revealing an intrinsic bias of these analytical estimates. Conclusions: Alarm times surrogates offer important advantages over analytical performance estimates. Significance: The key question in the field of seizure prediction is whether seizures can in principle be predicted or whether algorithms which have been presumed to perform better than chance actually are unable to predict seizures and simply have not yet been tested against the appropriate null hypotheses. Alarm times surrogates can help to answer this question. [Copyright &y& Elsevier]

Background There is evidence that the sudden unexpected death in epilepsy (SUDEP) risk can be reduced by good seizure control, nocturnal supervision, and by early cardiopulmonary resuscitation if cardiorespiratory arrest occurs in the aftermaths of generalized tonic–clonic seizures (GTCS). These measures, however, may critically depend on the knowledge of patients and relatives on SUDEP. Here, we assessed the basic knowledge on SUDEP of people with epilepsy at a tertiary epilepsy center in Germany. Methods Adult patients with epilepsy and relatives or caregivers of patients with epilepsy aged 16 years or older attending our outpatient clinic from January to March 2014 were given the opportunity to participate in a (assisted or unassisted) written survey. In the anonymized questionnaire, people were asked if they had already heard about SUDEP, by what means and if they wish to learn (more) about SUDEP. Furthermore, age, sex, epilepsy duration, highest degree of education, number of GTCS during the last year, and estimation of subjective impairment by their disease were assessed. Statistics were done using mixed linear or logistic regression models. Results A total of 372 patients' questionnaires were included in this survey. More than 87% of the participants had never heard of SUDEP before. Whereas about 50% of the participants wanted to learn more about SUDEP, about 40% did not. Only the age at survey was significantly associated with both being informed and the desire of learning more about SUDEP: Younger patients had more often heard (p = 0.022) and wanted to know more about SUDEP (p = 0.020). Thirty-nine patients were considered at high risk for SUDEP. Of these, only 6 patients (15%) knew about SUDEP prior to this survey, but 18 patients (46%) wanted to learn more about this fatal complication. Conclusion Our data suggest that the level of information on SUDEP among people with epilepsy is poor in Germany regardless of sex, school education, or epilepsy severity. Additionally, a considerable proportion of people with epilepsy seems to prefer not getting detailed information on SUDEP. More efforts are required to understand the potential barriers of the education of patients and relatives on sudden death with the ultimate goal of decreasing the risk of SUDEP. [ABSTRACT FROM AUTHOR]

Objective Limbic encephalitis (LE) is defined by mesiotemporal lobe structure abnormalities, seizures, memory, and psychiatric disturbances. This study aimed to identify the long-term clinical and neuropsychological outcome of selective amygdalohippocampectomy (sAH) in drug-resistant patients with temporal lobe epilepsy due to known or later diagnosed subacute LE not responding to immunotherapy associated with neuronal autoantibodies. Methods In seven patients with temporal lobe epilepsy due to antibody positive LE (glutamic acid decarboxylase (GAD65): n = 5; voltage-gated potassium channel complex (VGKC), N -methyl d -aspartate receptor (NMDAR): n = 1; Ma-2/Ta: n = 1) sAH (6 left, 1 right) was performed. Those patients underwent repeated electroencephalography (EEG) recordings, magnetic resonance imaging (MRI) volumetry of the amygdala and hippocampus, and neuropsychological examinations and were followed up for 6–7 years on average. Results Verbal memory and figural memory were affected in 57% of patients at baseline and 71% at the last follow-up. At the last follow-up, 14% of the patients had declined in verbal memory and figural memory. We observed improved memory in 43% of patients regarding figural memory, but not in a single patient regarding verbal memory. Repeated evaluations across the individual courses reveal cognitive and MRI dynamics that appear to be unrelated to surgery and drug treatment. Three of the seven patients with LE with different antibodies (NMDAR: n = 1, Ma-2/Ta: n = 1 and GAD65: n = 1) achieved persistent seizure freedom along with no accelerated memory decline after surgery. Two of the five GAD65-antibody patients positive with LE showed progressive memory decline and a long-term tendency to contralateral hippocampus atrophy. Conclusions While memory demonstrated some decline in the long run, what is most important is that a progressive decline in memory is seldom found after sAH in patients with LE. Moreover, the dynamics in performance and MRI before and after surgery reveal disease dynamics independent of surgery. Selective amygdalohippocampectomy can lead to seizure freedom, but should be considered as a last resort treatment option for drug-resistant patients with temporal lobe epilepsy due to LE. Particular caution is recommended in patients with GAD65-LE. [ABSTRACT FROM AUTHOR]

Objective To better understand the mechanisms that lead to the sudden and unexpected occurrence of seizures, with the neuronal correlate being abnormally synchronous discharges that disrupt neuronal function. Methods To address this problem, we recorded single neuron activity in epilepsy patients during the transition to seizures to uncover specific changes of neuronal firing patterns. We focused particularly on neurons repeatedly firing discrete groups of high-frequency action potentials (so called bursters) that have been associated with ictogenesis. We analyzed a total of 459 single neurons and used the mean autocorrelation time as a quantitative measure of burstiness. To unravel the intricate roles of excitation and inhibition, we also examined differential contributions from putative principal cells and interneurons. Results During interictal recordings, burstiness was significantly higher in the seizure onset hemisphere, an effect found only for principal cells, but not for interneurons, and which disappeared before seizures. Conclusion These findings deviate from conventional views of ictogenesis that propose slowly-increasing aggregates of bursting neurons which give rise to seizures once they reach a critical mass. Significance Instead our results are in line with recent hypotheses that bursting may represent a protective mechanism by preventing direct transmission of postsynaptic high-frequency oscillations. [ABSTRACT FROM AUTHOR]

Summary In the recent years, several neurological syndromes related to defects of the glucose transporter type 1 (Glut1) have been descried. They include the glucose transporter deficiency syndrome (Glut1-DS) as the most severe form, the paroxysmal exertion-induced dyskinesia (PED), a form of spastic paraparesis (CSE) as well as the childhood (CAE) and the early-onset absence epilepsy (EOAE). Glut1, encoded by the gene SLC2A1 , is the most relevant glucose transporter in the brain. All Glut1 syndromes respond well to a ketogenic diet (KD) and most of the patients show a rapid seizure control. Ketogenic Diet developed to an established treatment for other forms of pharmaco-resistant epilepsies. Since we were interested in the question if those patients might have an underlying Glut1 defect, we sequenced SLC2A1 in a cohort of 28 patients with different forms of pharmaco-resistant epilepsies responding well to a KD. Unfortunately, we could not detect any mutations in SLC2A1 . The exact action mechanisms of KD in pharmaco-resistant epilepsy are not well understood, but bypassing the Glut1 transporter seems not to play an important role. [ABSTRACT FROM AUTHOR]

Introduction Spike-based magnetoencephalography (MEG) source localization is an established method in the presurgical evaluation of epilepsy patients. Focal cortical dysplasias (FCDs) are associated with focal epileptic discharges of variable morphologies in the beta frequency band in addition to single epileptic spikes. Therefore, we investigated the potential diagnostic value of MEG-based localization of spike-independent beta band (12-30 Hz) activity generated by epileptogenic lesions. Methods Five patients with FCD IIB underwent MEG. In one patient, invasive EEG (iEEG) was recorded simultaneously with MEG. In two patients, iEEG succeeded MEG, and two patients had MEG only. MEG and iEEG were evaluated for epileptic spikes. Two minutes of iEEG data and MEG epochs with no spikes as well as MEG epochs with epileptic spikes were analyzed in the frequency domain. MEG oscillatory beta band activity was localized using Dynamic Imaging of Coherent Sources. Results Intralesional beta band activity was coherent between simultaneous MEG and iEEG recordings. Continuous 14 Hz beta band power correlated with the rate of interictal epileptic discharges detected in iEEG. In cases where visual MEG evaluation revealed epileptic spikes, the sources of beta band activity localized within <2 cm of the epileptogenic lesion as shown on magnetic resonance imaging. This result held even when visually marked epileptic spikes were deselected. When epileptic spikes were detectable in iEEG but not MEG, MEG beta band activity source localization failed. Discussion Source localization of beta band activity has the potential to contribute to the identification of epileptic foci in addition to source localization of visually marked epileptic spikes. Thus, this technique may assist in the localization of epileptic foci in patients with suspected FCD. [ABSTRACT FROM AUTHOR]

Abstract: NeuroCog FX, a computerized neuropsychological screening instrument for serial examinations of patients with epilepsy and other neurological diseases, was developed to fill the gap between unspecific ratings and comprehensive assessments. Eight subtests address attention, working memory, verbal and figural memory, and language. The test duration is less than 30min. In research contexts, the test can be applied at multiple sites by nonacademic personnel. Normative data were recorded from healthy subjects (N =244, age range=16–75years; retest: N =44; validation: N =40) and unselected patients from an epileptology unit (N =212; retest: N =94; validation: N =126). Psychometric analyses confirmed sufficient reliability and concurrent validity, particularly in patients. NeuroCog FX memory and overall performance scores showed “fair” to “good” diagnostic utility with respect to deficits revealed by established tests. NeuroCog FX provides reliable and valid measures of cognitive performance and may be used in clinical and research contexts as a screening instrument. [Copyright &y& Elsevier]

Abstract: For patients with schizophrenia, a deficient gating (or filtering) of sensory input has been described. One major approach to study this sensory gating is to measure event-related potentials (ERPs) in response to paired clicks. In these experiments, sensory gating is quantified as amplitude reduction of the ERP components P50 and N100 from the 1st to the 2nd stimulus. In ERP studies brain electrical signals are averaged over single trials. Alterations in phase locking might be one factor contributing to the observed deficits in sensory gating, but findings have been inconclusive as yet. In particular, the contribution of different frequency bands to the deficit required further investigation. We studied N100 gating by intracranial recordings in a sample of epilepsy patients and subdivided the group into good and poor gators of the intracranial ERP component N100. Data were evaluated by frequency specific wavelet-based phase and power analyses. Poor N100 gators had an increased phase locking in the frequency range from 6.0–15.1 Hz after the 2nd stimulus, as compared to good gators. Other group differences were apparent already before the 2nd stimulus. Poor gators had less phase locked beta band activity (20.2–30.0 Hz) than good gators 200–315 ms after the onset of the 1st stimulus. Within the group of poor gators, lower values of phase locking in this frequency range were also associated with lower gating ratios. The reduced beta band response in response to the 1st stimulus may reflect poorer memory encoding of the 1st stimulus in poor gators. This in turn might lead to increased demands to process the 2nd stimulus. [Copyright &y& Elsevier]

: BackgroundFor the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain’s electrical responses to repeated clicks: the P50 potential is normally reduced to the second of two paired clicks but not in schizophrenia patients. To identify its neural correlates, we recorded electrical traces of sensory gating directly from the human hippocampus and neocortex.: MethodsIntracranial evoked potentials were recorded using hippocampal depth electrodes and subdural strip and grid electrodes in 32 epilepsy patients undergoing invasive presurgical evaluation.: ResultsWe found evidence of sensory gating only in the hippocampus, the temporo-parietal region (Brodmann’s areas 22 and 2), and the prefrontal cortex (Brodmann’s areas 6 and 24); however, whereas neocortical habituating responses to paired clicks were peaking around 50 msec, responses within the hippocampus proper had a latency of about 250 msec.: ConclusionsConsistent with data from animal studies, our findings show that the hippocampus proper contributes to sensory gating, albeit during a time window following neocortical habituation processes. Thus, sensory gating may be a multistep process, with an early phase subserved by the temporo-parietal and prefrontal cortex and a later phase mediated by the hippocampus. [Copyright &y& Elsevier]