[Show abstract][Hide abstract] ABSTRACT: In contrast to the abundance of seizure outcome reports in epilepsy surgery for glioneuronal tumors in childhood and adolescence, there is a dearth of information regarding cognitive outcomes.
To investigate the seizure and cognitive outcome of children and adolescents that underwent resective surgery for glioneuronal tumor-associated refractory epilepsy and, determine their predictive factors.
We retrospectively analyzed the presurgical findings, resection types and outcomes over 1.3-12.3 years (mean 7.3) of 29 consecutive patients, who underwent resection in 2000-2011. The mean age at epilepsy onset was 7.9 years (range 0-15.4), the mean age at surgery was 11.7 years (range 2.6-17.3), and the mean epilepsy duration to surgery was 3.8 years (range 0.3-15.3). Etiology comprised 13 dysembryoplastic neuroepithelial tumors and 16 gangliogliomas, with additional focal cortical dysplasia in 5 cases.
86% of children were seizure-free 12 months after surgery; at final follow-up 76% remained seizure-free and 62% had discontinued antiepileptic drugs. Gross-total resection was related to significantly higher rates of seizure-freedom. Higher presurgical cognitive functioning (full scale IQ, verbal IQ) was related to shorter epilepsy duration to surgery independent of age at epilepsy onset, thus determining postsurgical functioning. Improvements in verbal IQ, performance IQ and visual memory as well as a trend towards improvement in full scale IQ were established after surgery. Despite individual losses in full scale IQ, verbal or visual memory, no deterioration was noted in any cognitive variable on a group level.
Completeness of resection predisposes to favorable outcomes regarding seizure alleviation. Whereas cognitive functioning deteriorates with time in glioneuronal tumor-related refractory epilepsy, surgery is linked to improvement rather than to deterioration on a group level.
[Show abstract][Hide abstract] ABSTRACT: To assess the visibility and detectability in scalp electroencephalography (EEG) of cortical sources in frontal lobe epilepsy (FLE) as to their localization, and the extent and amplitude of activation.
We analyzed the simultaneous subdural and scalp interictal EEG recordings of 14 patients with refractory frontal lobe epilepsy (FLE) associated with focal cortical dysplasia. Subdural spike types were identified and averaged for source localization and detection of their scalp EEG correlates. Both raw and averaged scalp EEG segments were reviewed for spikes, blinded to subdural segments. We further analyzed the correlation of spike-to-background amplitude ratios in subdural and scalp EEG.
We identified 36 spike types in subdural EEG, corresponding to 29 distinct sources. Four of 29 sources were visible by visual evaluation of scalp EEG and six additional sources were detectable after averaging: four in the medial frontal, two in the dorsolateral gyri, two in the depth of dorsolateral sulci, and two in the basal frontal region. Cortical sources generating scalp-detectable spikes presented a median of 6 cm(2) of activated cortical convexity surface and a subdural spike-to-background-amplitude ratio >8. These sources were associated with a higher number of activated subdural grid contacts and a higher subdural spike-to-background amplitude ratio than sources generating non-scalp-detectable spikes.
Not only dorsolateral but also basal and medial sources can be detectable in FLE. This is the first in vivo demonstration derived from simultaneous subdural and scalp EEG recordings of the complementary significance of extensive source activation and higher subdural spike-to-background amplitude ratio in the detection of cortical sources in FLE.
[Show abstract][Hide abstract] ABSTRACT: In many species, spatial navigation is supported by a network of place cells that exhibit increased firing whenever an animal is in a certain region of an environment. Does this neural representation of location form part of the spatiotemporal context into which episodic memories are encoded? We recorded medial temporal lobe neuronal activity as epilepsy patients performed a hybrid spatial and episodic memory task. We identified place-responsive cells active during virtual navigation and then asked whether the same cells activated during the subsequent recall of navigation-related memories without actual navigation. Place-responsive cell activity was reinstated during episodic memory retrieval. Neuronal firing during the retrieval of each memory was similar to the activity that represented the locations in the environment where the memory was initially encoded.
[Show abstract][Hide abstract] ABSTRACT: Reoperations account for >10% in pediatric epilepsy surgery cohorts and they are especially relevant in young children with catastrophic epilepsy.
To determine surgical outcomes and their predictive factors in reoperations for refractory epilepsy in childhood.
We retrospectively analyzed presurgical findings, resections and outcomes of 23 consecutive children that underwent reoperations from 2000-2011.
Etiology included cortical dysplasia with/without glioneuronal tumor in 19 patients (83%), sole glioneuronal tumor in 2, and tuberous sclerosis and Rasmussen's encephalitis in one each. Reasons for failure of initial surgery were functional considerations in 8 (35%), incorrect delineation of the epileptogenic zone in 8 (35%), and resection not performed as initially planned in 7 (30%) cases. Final procedures included 8 (35%) intralobar, 8 (35%) multilobar resections and 7 (30%) hemispherotomies. Following reoperations, 14 (61%) patients were seizure-free, 6 (26%) showed significant or worthwhile improvement, and 3 (13%) failed to respond to surgery. Six of 8 patients that underwent the first resection before the age of 3 years, 6 of 8 whose first resection was limited by functional considerations, and all 7 with hemispherotomy as the final resection achieved seizure freedom after reoperation.
Reoperation is particularly beneficial for selected children with refractory epilepsy associated with cortical dysplasia that failed to respond to an initial limited and/or early resection but achieved seizure freedom after extensive procedures. When indicated, reoperation should be performed at the youngest possible age to profit from higher functional plasticity in compensating for neurologic deficit.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND:: Intracranial in vivo recordings of individual neurons in humans are increasingly performed for a better understanding of the mechanisms of epileptogenesis and of the neurobiological basis of cognition. So far, information about the safety of stereotactic implantations and of MR imaging with hybrid depth electrodes is scarce. OBJECTIVE:: To assess neurosurgical safety of implantations, recordings, and imaging using hybrid electrodes in humans. METHODS:: Perioperative and long-term safety of implantation of a total of 88 hybrid depth electrodes with integrated microwires was assessed retrospectively in 25 consecutive epilepsy patients implanted from 2007 to 2011 based on electronically stored charts. Safety aspects of MR imaging are reported from both in vitro and in vivo investigations. Precision of electrode implantation is evaluated based on intraoperative computerized tomography (CT) and pre- and postoperative magnetic resonance imaging (MRI). RESULTS:: There was no clinically relevant morbidity associated with the use of hybrid electrodes in any of the patients. Precision of recordings from the targets aimed at was similar to standard depth electrodes. In vitro studies demonstrated the absence of relevant heating of hybrid electrodes with newly designed connectors with MR imaging at 1.5 T, corresponding to well tolerated clinical MR imaging in patients. CONCLUSION:: Given the technical approach described here, precise targeting and safe use is possible with hybrid electrodes containing microwires for in vivo recording of human neuronal units.
[Show abstract][Hide abstract] ABSTRACT: AIMS: To investigate seizure and developmental outcomes following epilepsy surgery in very young children and determine their predictive factors. METHODS: We retrospectively reviewed the clinical data, surgical variables, and outcomes of 30 children under 3 years of age that underwent resection for refractory focal epilepsy in our institution in 2001-2011. RESULTS: Seizure onset was in the first year of life in 27 (90%) cases and mean age at surgery was 20 months (range 5-33.6). Pathology consisted of cortical malformations in 24 (80%) cases, glioneuronal tumour and infarction with or without cortical dysplasia in three (10%) cases each. Morbidity was comparable with older paediatric cohorts. At 1-11.6 year follow-up (mean 4.1) 21 of 30 (70%) children achieved seizure freedom (Engel I), six (20%) demonstrated worthwhile improvement (Engel II/III) and three (10%) did not benefit from surgery (Engel IV). Intralobar lesionectomy more often resulted in seizure freedom than multilobar or hemispheric surgery. The abundance of non-regional interictal and ictal EEG findings did not preclude seizure freedom. Presurgical developmental impairment was established in 25 of 28 (89%) children; its severity correlated with longer epilepsy duration and determined postoperative developmental outcome. Developmental progress was established in 26 out of 28 (93%) children following surgery, showing stabilized trajectories rather than catch-up. CONCLUSIONS: Resective surgery in very young children is safe and effective in terms of seizure control and developmental progress. Our findings underline the importance of early intervention in order to timely stop seizures and their deleterious effects on the developing brain.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 04/2013; · 2.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To evaluate the seizure control and developmental outcomes after hemispherotomy for refractory epilepsy in childhood and to identify their predictive factors. METHODS: We retrospectively studied the clinical courses and outcomes of 52 children with refractory epilepsy who underwent hemispherotomy in the Epilepsy Center Freiburg between 2002 and 2011. KEY FINDINGS: Mean age at epilepsy onset was 1.8 years (range 0-8 years) and mean age at surgery was 6.7 years (range 6 months-18 years). The underlying etiology was congenital in 22 (42%) children, acquired in 24 (46%), and progressive in 6 (12%). At final follow-up of 1-9.8 years (mean 3.3), 43 children (83%) were seizure-free. Seizure outcome was not correlated to etiology, with the exception of hemimegalencephaly that was linked to poor seizure control. Presurgical development was impaired in all but one child. Postsurgical development highly correlated with presurgical development. Patients with acquired or progressive etiology, later epilepsy onset, and subsequent later surgery exhibited higher presurgical developmental status that substantially determined postoperative developmental outcome. Improved postsurgical development was determined by acquired etiology and seizure freedom off antiepileptic drugs. SIGNIFICANCE: In our study, most of the selected children and adolescents achieved seizure freedom, including those with congenital etiology. Developmental outcomes, however, were superior in patients with acquired etiology and older age at surgery, underscoring that it is never too late to reap the benefits of this procedure in terms of both epilepsy and development.
[Show abstract][Hide abstract] ABSTRACT: Introduction
Cortical spreading depression (CSD) – initially considered a correlate for migraine auras – has also been related to other neurologic diseases in vitro. In vivo it has been shown in stroke and trauma patients and was considered to be a sign of poor outcome (Strong, 2002; Fabricius 2006; Dreier et al., 2012). The aim of our study was to investigate CSD in epilepsy patients undergoing invasive presurgical video-EEG-monitoring, allowing to collect CSD-data in patients without severe brain damage.
Data of 18 patients with pharmacoresistant epilepsy undergoing invasive video-EEG-monitoring with 44 up to 106 subdural electrodes and with a high pass filter of 0,02 Hz filter settings were evaluated. CSD was defined as a slow wave in the range of 1–5 mm/min with suppression of the normal EEG-activity. Data were related to the extent of periprocedural hemorrhage, the origin and number of seizures and histopathologic findings.
In 7/18 patients we could detect CSD. Two of them developed a clinically symptomatic subdural hematoma (SDH), paralleled by an increase of CSD-frequency; in 4/7 subclinical hemorrhage or minor lesions could be demonstrated on MRI, while one patient showed no abnormality on MRI. In comparison, minor hemorrhage was documented in 5/11 patients without CSD. There was no obvious spatial or temporal relation of CSD to seizure onset. The main histopathological finding both in patients with and without CSD was focal cortical dysplasia.
Our data show CSD for the first time in vivo in patients without major brain trauma in patients with epilepsy. The main finding was that CSD is not limited to major brain damage but might also appear after mild trauma without clinical relevance or even without detectable trauma. Out data did not show a temporal or spatial correlation of CSD to seizure onset or histopathological findings. However, larger numbers and a longer follow-up are necessary to draw conclusions about the clinical relevance of CSD in epilepsy patients.
[Show abstract][Hide abstract] ABSTRACT: Despite general agreement on shared syntactic resources in music and language, the neuroanatomical underpinnings of this overlap remain largely unexplored. While previous studies mainly considered frontal areas as supramodal grammar processors, the domain-general syntactic role of temporal areas has been so far neglected. Here we capitalized on the excellent spatial and temporal resolution of subdural EEG recordings to co-localize low-level syntactic processes in music and language in the temporal lobe in a within-subject design. We used Brain Surface Current Density mapping to localize and compare neural generators of the early negativities evoked by violations of phrase structure grammar in both music and spoken language. The results show that the processing of syntactic violations relies in both domains on bilateral temporo-fronto-parietal neural networks. We found considerable overlap of these networks in the superior temporal lobe, but also differences in the hemispheric timing and relative weighting of their fronto-temporal constituents. While alluding to the dissimilarity in how shared neural resources may be configured depending on the musical or linguistic nature of the perceived stimulus, the combined data lend support for a co-localization of early musical and linguistic syntax processing in the temporal lobe.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Ictal-related cardiac asystole is supposed to be a risk factor for sudden unexpected death in epilepsy (SUDEP). We retrospectively analyzed the occurrence of ictal asystole in 2003 epilepsy patients undergoing long-term video EEG/ECG monitoring from 1/1999 to 6/2010 at the Freiburg epilepsy centre. Seven patients had cardiac arrest with a duration of at least 3s; 6 ictal, one postictal. In all patients, the temporal lobe was involved in ictal activity based on neurophysiological investigations or morphological lesion. Whereas asystole was self-limited in six cases, one patient with insular seizure origin had to undergo cardiopulmonary resuscitation. Interestingly, also patients with a short history of epilepsy, low seizure frequency and under treatment in monotherapy showed episodes of asystole. In all cases, even with brief cardiac arrest, asystole was associated with subsequent EEG flattening. In conclusion, ictal asystole is a rare event even in a population undergoing major changes in antiepileptic medication. Temporal lobe epilepsy was associated with a risk for asystole; cardiac arrest also occurred in patients who, based on their history, might have not been considered at elevated risk for SUDEP.
[Show abstract][Hide abstract] ABSTRACT: Characterization of seizure semiology in patients with hypothalamic hamartoma (HH) based on video-electroencephalography (EEG) monitoring (VEM).
We retrospectively analyzed seizure semiology of 31 patients (20 male, mean age 23.5 years) who underwent VEM at the University Hospitals Freiburg or Heidelberg, Germany. Inclusion criteria were magnetic resonance evidence of an HH, no prior surgical or radiosurgical treatment, and at least two video-documented seizures. A total of 263 seizures were included (mean number of seizures/patient 8.5, range 2-10). To analyze age-dependent changes in seizure semiology, patients were grouped into "children" (3-11 years, n = 5), "adolescents" (12-17 years, n = 4), and "adults" (≥18 years, n = 22).
According to patient history, gelastic seizures had occurred in all patients, in 74% as the initial seizure type at epilepsy onset. In VEM, epileptic laughter varied from facial grinning to intense contractions of the diaphragm and body shaking. Unilateral motor signs were seen ipsi- and contralaterally to the HH. Tonic seizures were frequent and did not depend on the state of vigilance. Children, in contrast to adults and adolescents, did not show secondarily generalized tonic-clonic seizures, the gelastic component was the dominating and initial semiologic element, and seizures were significantly shorter.
Seizure semiology is highly variable and age dependent. This may reflect network modulations with different propagation of ictal activity and/or secondary epileptogenesis. Detailed knowledge about such changes may contribute to both earlier recognition of seizures during childhood and better assignment of seizure types to a hypothalamic origin.
[Show abstract][Hide abstract] ABSTRACT: Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we recorded electrocorticographic activity from widespread cortical and subcortical sites as 20 neurosurgical patients performed working memory tasks. These recordings revealed significant increases in 48-90 Hz gamma oscillatory power with memory load for two classes of stimuli: letters and faces. Sites exhibiting gamma increases with memory load appeared primarily in the hippocampus and medial temporal lobe. These findings implicate gamma oscillatory activity in the maintenance of both letters and faces in working memory and provide the first direct evidence for modulation of hippocampal gamma oscillations as humans perform a working memory task.
Journal of Neuroscience 02/2010; 30(7):2694-9. · 6.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess latencies to the first typical generalized spike-wave discharge (GSWD) and clinically manifest seizure during long-term video-EEG monitoring (VEM) in patients with idiopathic generalized epilepsy (IGE). This is a retrospective analysis of continuous long-term VEM of 39 patients (25 women; mean age, 28.7 years). Mean duration of VEM was 3 days (1-11 days). Latencies from start of VEM to the first appearance of GSWD and the first clinically manifest seizure were analyzed for IGE subsyndrome. Overall, mean latency from the beginning of VEM to the first typical GSWD was 853 minutes (range, 3-7,305 minutes). In 38.5% of the patients, the first typical GSWD occurred during the first hour of VEM and in 87.2% during the first day. Latencies were significantly shorter in juvenile absence epilepsy than in juvenile myoclonic epilepsy, epilepsy with generalized tonic-clonic seizures only, and IGE not further classified (P = 0.001). In 38.5% of the patients, clinically manifest seizures were recorded. Overall, mean latency to the first seizure was 1,984 minutes (range, 3-8,123 minutes). There were no significant differences in latencies to the first seizure between IGE syndromes. One day of VEM is sufficient for classification as IGE in the majority of patients. Patients with juvenile absence epilepsy had particularly low latencies to the appearance of the first typical GSWD. There is, however, a group of patients (12.8% in our sample) requiring a prolonged VEM period to achieve sufficient electroclinical evidence for syndromatic classification.
Journal of clinical neurophysiology: official publication of the American Electroencephalographic Society 02/2010; 27(1):1-6. · 1.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the hippocampus plays a crucial role in encoding and retrieval of contextually mediated episodic memories, considerable controversy surrounds the role of the hippocampus in short-term or working memory. To examine both hippocampal and neocortical contributions to working memory function, we recorded electrocorticographic activity from widespread cortical and subcortical sites as 20 neurosurgical patients performed working memory tasks. These recordings revealed significant increases in 48 –90 Hz gamma oscil-latory power with memory load for two classes of stimuli: letters and faces. Sites exhibiting gamma increases with memory load appeared primarily in the hippocampus and medial temporal lobe. These findings implicate gamma oscillatory activity in the maintenance of both letters and faces in working memory and provide the first direct evidence for modulation of hippocampal gamma oscillations as humans perform a working memory task.
Journal of Neuroscience 01/2010; 30(7):2694-2699. · 6.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent research has pointed to the possibility of a bidirectional relationship between seizure frequency in epilepsy and depressive symptoms. The study described here investigated the relationship between preoperative depressive symptomatology and postoperative seizure outcome in a sample of patients with temporal (TLE) and frontal (FLE) lobe epilepsy.
A retrospective analysis was conducted on the data from 115 eligible patients with TLE (N=97) and FLE (N=18) and resections limited to one cortical lobe who were evaluated preoperatively and 1year after epilepsy surgery with respect to depressive symptoms (Beck Depression Inventory, BDI) and seizure outcome. The latter was assessed in terms of actual total seizure frequency as well as a dichotomous variable (seizure free vs. not seizure free) for the 1-year outcome. Repeated-measures analyses of variance and regression analyses were applied.
Seizure-free patients had significantly lower BDI scores preoperatively as well as postoperatively than patients who were not seizure free. In the regression analyses, the preoperative BDI score was a significant predictor of postoperative seizure frequency as well as seizure freedom. When only patients with TLE were analyzed, the results for the association between preoperative BDI and postoperative seizure frequency and seizure freedom remained consistent.
The present results provide evidence for a statistical bidirectionality of the relationship between depressive symptoms and postoperative seizure status in a mixed sample of patients with TLE and FLE. Possible reasons for this bidirectional association include an underlying common pathology in both depression and epilepsy, for example, structural changes or functional alterations in neurotransmitter systems.
[Show abstract][Hide abstract] ABSTRACT: Behavioral studies of visual recognition memory indicate that old/new decisions reflect both the similarity of the probe to the studied items (probe-item similarity) and the similarities among the studied items themselves (list homogeneity). Recording intracranial electroencephalography from 1,155 electrodes across 15 patients, we examined the oscillatory correlates of probe-item similarity and homogeneity effects in short-term recognition memory for synthetic faces. Frontal areas show increases in low-frequency oscillations with both probe-item and item-item similarity, whereas temporal lobe areas show distinct oscillatory correlates for probe-item similarity and homogeneity in the gamma band. We discuss these frontal low-frequency effects and the dissociation in the temporal lobe in terms of recent computational models of visual recognition memory.
Brain research 08/2009; 1299:33-44. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The present study investigated the co-localization of musical and linguistic syntax processing in the human brain. EEGs were recorded from subdural electrodes placed on the left and right perisylvian cortex. The neural generators of the early potentials elicited by syntactic errors in music and language were localized by means of distributed source modeling and compared within subjects. The combined results indicated a partial overlap of the sources within the bilateral superior temporal gyrus, and, to a lesser extent, in the left inferior frontal gyrus, qualifying these areas as shared anatomic substrates of early syntactic error detection in music and language.
Annals of the New York Academy of Sciences 08/2009; 1169:494-8. · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Behavioral studies of visual recognition memory indicate that old/new decisions reflect both the similarity of the probe to the studied items (probe–item similarity) and the similarities among the studied items themselves (list homogeneity). Recording intracranial electroencephalography from 1,155 electrodes across 15 patients, we examined the oscillatory correlates of probe–item similarity and homogeneity effects in short-term recognition memory for synthetic faces. Frontal areas show increases in low-frequency oscillations with both probe–item and item–item similarity, whereas temporal lobe areas show distinct oscillatory correlates for probe–item similarity and homogeneity in the gamma band. We discuss these frontal low-frequency effects and the dissociation in the temporal lobe in terms of recent computational models of visual recognition memory.
Brain Research 01/2009; 1299:33. · 2.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retrospective evaluation and comparison of performances of a multivariate method for seizure detection and prediction on simultaneous long-term EEG recordings from scalp and intracranial electrodes.
Two multivariate techniques based on simulated leaky integrate-and-fire neurons were investigated in order to detect and predict seizures. Both methods were applied and assessed on 423h of EEG and 26 seizures in total, recorded simultaneously from the scalp and intracranially continuously over several days from six patients with pharmacorefractory epilepsy.
Features generated from simultaneous scalp and intracranial EEG data showed a similar dynamical behavior. Significant performances with sensitivities of up to 73%/62% for scalp/invasive EEG recordings given an upper limit of 0.15 false detections per hour were obtained. Up to 59%/50% of all seizures could be predicted from scalp/invasive EEG, given a maximum number of 0.15 false predictions per hour. A tendency to better performances for scalp EEG was obtained for the detection algorithm.
The investigated methods originally developed for non-invasive EEG were successfully applied to intracranial EEG. Especially, concerning seizure detection the method shows a promising performance which is appropriate for practical applications in EEG monitoring. Concerning seizure prediction a significant prediction performance is indicated and a modification of the method is suggested.
This study evaluates simultaneously recorded non-invasive and intracranial continuous long-term EEG data with respect to seizure detection and seizure prediction for the first time.