Predictors of postoperative complications and functional outcomes in pediatric patients with surgically treated fourth ventricle tumors.

BACKGROUND: Tumors of the fourth ventricle are frequently treated pathologies in pediatric neurosurgery. Data regarding predictors for permanent neurological deficits, long-term functional outcomes, cerebellar mutism (CM), the extent of resection (EOR), and oncological outcomes are scarce. We attempt to contribute to this topic with an analysis of our institutional cohort. METHODS: A retrospective single-center study of patients aged ≤ 19 years who underwent primary surgical resection of a fourth ventricular tumor over a 15-year period (2006-2021). Predictors analyzed included age, gender, surgical approach, anatomical pattern, tumor grade, EOR, tumor volume, and others as appropriate. RESULTS: One hundred six patients were included (64 males, mean age 7.3 years). The rate of permanent neurological deficit was 24.2%; lateral tumor extension (p = 0.036) and tumor volume greater than 38 cm3 (p = 0.020) were significant predictors. The presence of a deficit was the only significant predictor of reduced (less than 90) Lansky score (p = 0.005). CM occurred in 20.8% of patients and was influenced by medulloblastoma histology (p = 0.011), lateral tumor extension (p = 0.017), and male gender (p = 0.021). No significant difference between the transvermian and telovelar approach in the development of CM was detected (p = 0.478). No significant predictor was found for the EOR. EOR was not found to be a significant predictor of overall survival for both low-grade and high-grade tumors; however, gross total resection (GTR) was protective against tumor recurrence compared to near-total or subtotal resection (p < 0.001). In addition, survival was found to be better in older patients (≥ 7.0 years, p = 0.019). CONCLUSION: The overall rate of postoperative complications remains high due to the eloquent localization. Older patients (> 7 years) have been found to have better outcomes and prognosis. Achieving GTR whenever feasible and safe has been shown to be critical for tumor recurrence. CM was more common in patients with medulloblastoma and in patients with tumors extending through the foramen of Luschka. The telovelar approach uses a safe and anatomically sparing corridor; however, it has not been associated with a lower incidence of CM and neurological sequelae in our series, showing that each case should be assessed on an individual basis.

Automated Identification of Stereoelectroencephalography Contacts and Measurement of Factors Influencing Accuracy of Frame Stereotaxy.

OBJECTIVE: Stereoelectroencephalography (SEEG) is an established invasive diagnostic technique for use in patients with drug-resistant focal epilepsy evaluated before resective epilepsy surgery. The factors that influence the accuracy of electrode implantation are not fully understood. Adequate accuracy prevents the risk of major surgery complications. Precise knowledge of the anatomical positions of individual electrode contacts is crucial for the interpretation of SEEG recordings and subsequent surgery. METHODS: We developed an image processing pipeline to localize implanted electrodes and detect individual contact positions using computed tomography (CT), as a substitute for time-consuming manual labeling. The algorithm automates measurement of parameters of the electrodes implanted in the skull (bone thickness, implantation angle and depth) for use in modeling of predictive factors that influence implantation accuracy. RESULTS: Fifty-four patients evaluated by SEEG were analyzed. A total of 662 SEEG electrodes with 8,745 contacts were stereotactically inserted. The automated detector localized all contacts with better accuracy than manual labeling (p < 0.001). The retrospective implantation accuracy of the target point was 2.4 ± 1.1 mm. A multifactorial analysis determined that almost 58% of the total error was attributable to measurable factors. The remaining 42% was attributable to random error. CONCLUSION: SEEG contacts can be reliably marked by our proposed method. The trajectory of electrodes can be parametrically analyzed to predict and validate implantation accuracy using a multifactorial model. SIGNIFICANCE: This novel, automated image processing technique is a potentially clinically important, assistive tool for increasing the yield, efficiency, and safety of SEEG.

Current management in the treatment of intramedullary ependymomas in children.

PURPOSE: Current management of pediatric intramedullary ependymoma is extrapolated from adult series since large studies in children are unavailable. This has led us to share our experience with this rare tumor and compare it to the literature and to review and highlight important aspects of current management and point out inconsistencies. METHODS: This is a retrospective analysis of patients with intramedullary ependymoma managed at our institution between 2004 and 2021. RESULTS: During the study period, 5 patients were treated for intramedullary ependymoma. Cases of myxopapillary ependymoma were excluded. The mean age of our cohort was 11.2 years. We identified 4 cases of grade II ependymoma and 1 case of grade III ependymoma. Gross tumor removal (GTR) was achieved in two patients (40%) of patients. One patient was treated with radiotherapy for recurrence and two patients received chemotherapy. There were no cases of recurrence among patients treated with GTR, but in all patients treated with STR. Eighty percent of patients either improved or stayed stable neurologically. During follow-up (mean 73 months), 2 patients died of disease. CONCLUSION: GTR and tumor grade remain the key prognostic factor of long-term tumor-free survival. Many questions prevail regarding outcomes, correct use of adjuvant therapy, and prognostic factors.

Mapping the Scene and Object Processing Networks by Intracranial EEG.

Human perception and cognition are based predominantly on visual information processing. Much of the information regarding neuronal correlates of visual processing has been derived from functional imaging studies, which have identified a variety of brain areas contributing to visual analysis, recognition, and processing of objects and scenes. However, only two of these areas, namely the parahippocampal place area (PPA) and the lateral occipital complex (LOC), were verified and further characterized by intracranial electroencephalogram (iEEG). iEEG is a unique measurement technique that samples a local neuronal population with high temporal and anatomical resolution. In the present study, we aimed to expand on previous reports and examine brain activity for selectivity of scenes and objects in the broadband high-gamma frequency range (50-150 Hz). We collected iEEG data from 27 epileptic patients while they watched a series of images, containing objects and scenes, and we identified 375 bipolar channels responding to at least one of these two categories. Using K-means clustering, we delineated their brain localization. In addition to the two areas described previously, we detected significant responses in two other scene-selective areas, not yet reported by any electrophysiological studies; namely the occipital place area (OPA) and the retrosplenial complex. Moreover, using iEEG we revealed a much broader network underlying visual processing than that described to date, using specialized functional imaging experimental designs. Here, we report the selective brain areas for scene processing include the posterior collateral sulcus and the anterior temporal region, which were already shown to be related to scene novelty and landmark naming. The object-selective responses appeared in the parietal, frontal, and temporal regions connected with tool use and object recognition. The temporal analyses specified the time course of the category selectivity through the dorsal and ventral visual streams. The receiver operating characteristic analyses identified the PPA and the fusiform portion of the LOC as being the most selective for scenes and objects, respectively. Our findings represent a valuable overview of visual processing selectivity for scenes and objects based on iEEG analyses and thus, contribute to a better understanding of visual processing in the human brain.

Corrigendum: The Sub-Regional Functional Organization of Neocortical Irritative Epileptic Networks in Pediatric Epilepsy.

[This corrects the article DOI: 10.3389/fneur.2018.00184.].

The Sub-Regional Functional Organization of Neocortical Irritative Epileptic Networks in Pediatric Epilepsy.

Between seizures, irritative network generates frequent brief synchronous activity, which manifests on the EEG as interictal epileptiform discharges (IEDs). Recent insights into the mechanism of IEDs at the microscopic level have demonstrated a high variance in the recruitment of neuronal populations generating IEDs and a high variability in the trajectories through which IEDs propagate across the brain. These phenomena represent one of the major constraints for precise characterization of network organization and for the utilization of IEDs during presurgical evaluations. We have developed a new approach to dissect human neocortical irritative networks and quantify their properties. We have demonstrated that irritative network has modular nature and it is composed of multiple independent sub-regions, each with specific IED propagation trajectories and differing in the extent of IED activity generated. The global activity of the irritative network is determined by long-term and circadian fluctuations in sub-region spatiotemporal properties. Also, the most active sub-region co-localizes with the seizure onset zone in 12/14 cases. This study demonstrates that principles of recruitment variability and propagation are conserved at the macroscopic level and that they determine irritative network properties in humans. Functional stratification of the irritative network increases the diagnostic yield of intracranial investigations with the potential to improve the outcomes of surgical treatment of neocortical epilepsy.

The dynamics of error processing in the human brain as reflected by high-gamma activity in noninvasive and intracranial EEG.

Error detection in motor behavior is a fundamental cognitive function heavily relying on local cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a multiscale picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.

Predominance of Movement Speed Over Direction in Neuronal Population Signals of Motor Cortex: Intracranial EEG Data and A Simple Explanatory Model.

How neuronal activity of motor cortex is related to movement is a central topic in motor neuroscience. Motor-cortical single neurons are more closely related to hand movement velocity than speed, that is, the magnitude of the (directional) velocity vector. Recently, there is also increasing interest in the representation of movement parameters in neuronal population activity, such as reflected in the intracranial EEG (iEEG). We show that in iEEG, contrasting to what has been previously found on the single neuron level, speed predominates over velocity. The predominant speed representation was present in nearly all iEEG signal features, up to the 600-1000 Hz range. Using a model of motor-cortical signals arising from neuronal populations with realistic single neuron tuning properties, we show how this reversal can be understood as a consequence of increasing population size. Our findings demonstrate that the information profile in large population signals may systematically differ from the single neuron level, a principle that may be helpful in the interpretation of neuronal population signals in general, including, for example, EEG and functional magnetic resonance imaging. Taking advantage of the robust speed population signal may help in developing brain-machine interfaces exploiting population signals.

Familial temporal lobe epilepsy due to focal cortical dysplasia type IIIa.

PURPOSE: Focal cortical dysplasia (FCD) represents a common cause of refractory epilepsy. It is considered a sporadic disorder, but its occasional familial occurrence suggests the involvement of genetic mechanisms. METHODS: Siblings with intractable epilepsy were referred for epilepsy surgery evaluation. Both patients were examined using video-EEG monitoring, MRI examination and PET imaging. They underwent left anteromedial temporal lobe resection. RESULTS: Electroclinical features pointed to left temporal lobe epilepsy and MRI examination revealed typical signs of left-sided hippocampal sclerosis and increased white matter signal intensity in the left temporal pole. PET examination confirmed interictal hypometabolism in the left temporal lobe. Histopathological examination of resected tissue demonstrated the presence FCD type IIIa, i.e. hippocampal sclerosis and focal cortical dysplasia in the left temporal pole. CONCLUSION: We present a unique case of refractory mesial temporal lobe epilepsy in siblings, characterized by an identical clinical profile and histopathology of FCD type IIIa, who were successfully treated by epilepsy surgery. The presence of such a high concordance between the clinical and morphological data, together with the occurrence of epilepsy and febrile seizures in three generations of the family pedigree points towards a possible genetic nature of the observed FCD type IIIa.

Detection of interictal epileptiform discharges using signal envelope distribution modelling: application to epileptic and non-epileptic intracranial recordings.

Interictal epileptiform discharges (spikes, IEDs) are electrographic markers of epileptic tissue and their quantification is utilized in planning of surgical resection. Visual analysis of long-term multi-channel intracranial recordings is extremely laborious and prone to bias. Development of new and reliable techniques of automatic spike detection represents a crucial step towards increasing the information yield of intracranial recordings and to improve surgical outcome. In this study, we designed a novel and robust detection algorithm that adaptively models statistical distributions of signal envelopes and enables discrimination of signals containing IEDs from signals with background activity. This detector demonstrates performance superior both to human readers and to an established detector. It is even capable of identifying low-amplitude IEDs which are often missed by experts and which may represent an important source of clinical information. Application of the detector to non-epileptic intracranial data from patients with intractable facial pain revealed the existence of sharp transients with waveforms reminiscent of interictal discharges that can represent biological sources of false positive detections. Identification of these transients enabled us to develop and propose secondary processing steps, which may exclude these transients, improving the detector's specificity and having important implications for future development of spike detectors in general.

Ictal and postictal semiology in patients with bilateral temporal lobe epilepsy.

Bilateral temporal lobe epilepsy is characterized by evidence of seizure onset independently in both temporal lobes. The main aim of the present study was to determine whether patients with evidence of independent bilateral temporal lobe epilepsy (biTLE) can be identified noninvasively on the basis of seizure semiology analysis. Thirteen patients with biTLE, as defined by invasive EEG, were matched with 13 patients with unilateral temporal lobe epilepsy (uniTLE). In all 26 patients, the frequency of predefined clusters of ictal and periictal signs were evaluated: ictal motor signs (IMSs), periictal motor signs (PIMSs), periictal vegetative signs (PIVSs), the frequency of early oroalimentary automatisms (EOAs), and the duration of postictal unresponsiveness (PU). Some other noninvasive and clinical data were also evaluated. A lower frequency of IMSs was noted in the group with biTLE (patients = 46.2%, seizures = 20.7%) than in the group with uniTLE (patients = 92.3%, seizures = 61.0%) (p = 0.030; p < 0.001, respectively). The individual IMS average per seizure was significantly lower in the group with biTLE (0.14; range = 0-1.0) than in the group with uniTLE (0.80; range = 0-2.6) (p = 0.003). Postictal unresponsiveness was longer than 5 min in more patients (75.0%) and seizures (42.9%) in the group with biTLE than in the group with uniTLE (patients = 30.8%, seizures = 18.6%) (p = 0.047; p = 0.002). The frequency of EOAs, PIMSs, PIVSs, and other clinical data did not differ significantly. There is a lower frequency of ictal motor signs and longer duration of postictal unresponsiveness in patients with biTLE.

SISCOM and FDG-PET in patients with non-lesional extratemporal epilepsy: correlation with intracranial EEG, histology, and seizure outcome.

AIMS: To assess the practical localising value of subtraction ictal single-photon emission computed tomography (SISCOM) coregistered with MRI and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with extratemporal epilepsy and normal MRI. METHODS: We retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome. RESULTS: Two patients underwent one-stage multimodal image-guided surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. No correlation between histopathological FCD subtype and seizure outcome was observed. CONCLUSION: Complete resection of the dysplastic cortex localised by SISCOM, FDG-PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non-lesional extratemporal epilepsy.

1H MR spectroscopy in histopathological subgroups of mesial temporal lobe epilepsy.

The aim of the study was to analyze the lateralizing value of proton magnetic resonance spectroscopy ((1)H MRS) in histopathologically different subgroups of mesial temporal lobe epilepsies (MTLE) and to correlate results with clinical, MRI and seizure outcome data. A group of 35 patients who underwent resective epilepsy surgery was retrospectively studied. Hippocampal (1)H MR spectra were evaluated. Metabolite concentrations were obtained using LCModel and NAA/Cr, NAA/Cho, NAA/(Cr+Cho), Cho/Cr ratios and coefficients of asymmetry were calculated. MRI correctly lateralized 89% of subjects and (1)H MRS 83%. MRI together with (1)H MRS correctly lateralized 100% of patients. Nineteen subjects had "classical" hippocampal sclerosis (HS), whereas the remaining 16 patients had "mild" HS. Nineteen patients had histopathologically proven malformation of cortical development (MCD) in the temporal pole; 16 subjects had only HS. No difference in (1)H MRS findings was found between patients in different histopathological subgroups of MTLE. Our results support the hypothesis that (1)H MRS abnormalities do not directly reflect histopathological changes in MTLE patients. Subjects with non-lateralized (1)H MRS abnormalities did not have a worse postoperative seizure outcome. We found no significant impact of contralateral (1)H MRS abnormality on post-surgical seizure outcome.

Clinical impact of a high-frequency seizure onset zone in a case of bitemporal epilepsy.

High-frequency activity has been described as having a role in the initiation of epileptic seizures. The case of a patient with refractory bitemporal epilepsy is presented. Extraoperative monitoring with depth and subdural electrodes revealed an ictal pattern with a build-up of high-frequency (> 80 Hz) activity originating in the cortex, with spread to both hippocampi. This observation was only revealed with the use of high-pass filtering, and represented crucial information that significantly influenced the decision about the side, localization and extent of resection. Removal of the cortex generating high-frequency activity, led to cessation of seizures in this patient. Current knowledge about the role of high-frequency activity and the case presented here support the importance of recording with equipment capable of detecting fast activity during the presurgical invasive monitoring. An active search for a high-frequency seizure onset zone in patients with structurally-unaffected hippocampi may improve the outcome beyond that possible with conventional bandwidth, invasive EEG recordings.

Clinical characteristics in patients with hippocampal sclerosis with or without cortical dysplasia.

BACKGROUND: Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) constitutes a distinct clinical syndrome with variable pathogenesis. Extrahippocampal regions may be affected in MTLE/HS, association with cortical dysplasia is common and temporal polar cortex is frequently involved in seizure onset. Patients with dual pathology may have favourable outcome from the surgery provided that both pathologies are removed. The aim of the study was to review clinical variables of MTLE/HS patients in order to distinguish preoperatively patients with associated microscopic cortical dysplasia in the temporal pole. METHODS: A series of 38 patients with the clinical diagnosis of MTLE and histopathologically proven HS were analysed. Patients were divided into two groups on the basis of histopathological finding in the temporal polar cortex: HS associated with malformation of cortical development (group HS+, n = 19) and a group with isolated HS (group HS, n = 19). Demographic, clinical, electrographic and seizure semiology variables were obtained and their prevalence compared between both groups. RESULTS: At least one insult was identified in early childhood history of 18 patients in the HS group in comparison to 10 patients in the HS+ group (p < 0.01). Complicated febrile seizures were found in both groups with similar prevalence, the history of early childhood CNS infection prevailed in the HS group (p < 0.01). Absence of aura was reported in HS group only. Patients in the the HS+ group had earlier surgery (p < 0.05) but the seizure outcome was comparable between groups. CONCLUSIONS: Microscopic dual pathology is common in MTLE/HS patients. This group of patients is difficult to distinguish preoperatively on the basis of noninvasive electrographic features or ictal clinical semiology. Detailed information regarding the possible precipitating insult in the history may be of critical importance.