Seizure, Motor, and Cognitive Outcomes After Epilepsy Surgery for Patients With Sturge-Weber Syndrome: Results From a Multicenter Study.

BACKGROUND AND OBJECTIVES: Surgery is widely performed for refractory epilepsy in patients with Sturge-Weber syndrome (SWS), but reports on its effectiveness are limited. This study aimed to analyze seizure, motor, and cognitive outcomes of surgery in these patients and to identify factors associated with the outcomes. METHODS: This was a multicenter retrospective observational study using data from patients with SWS and refractory epilepsy who underwent epilepsy surgery between 2000 and 2020 at 16 centers throughout China. Longitudinal postoperative seizures were classified by Engel class, and Engel class I was regarded as seizure-free outcome. Functional (motor and cognitive) outcomes were evaluated using the SWS neurologic score, and improved or unchanged scores between baseline and follow-up were considered to have stable outcomes. Outcomes were analyzed using Kaplan-Meier analyses. Multivariate Cox regression was used to identify factors associated with outcomes. RESULTS: A total of 214 patients with a median age of 2.0 (interquartile range 1.2-4.6) years underwent surgery (focal resection, FR [n = 87]; hemisphere surgery, HS [n = 127]) and completed a median of 3.5 (1.7-5.0) years of follow-up. The overall estimated probability for being seizure-free postoperatively at 1, 2, and 5 years was 86.9% (95% CI 82.5-91.6), 81.4% (95% CI 76.1-87.1), and 70.7% (95% CI 63.3-79.0), respectively. The overall estimated probability of being motor stable at the same time post operatively was 65.4% (95% CI 58.4-71.2), 80.2% (95% CI 73.8-85.0), and 85.7% (95% CI 79.5-90.1), respectively. The overall probability for being cognition stable at 1, 2, and 5 years was 80.8% (95% CI 74.8-85.5), 85.1% (95% CI 79.3-89.2), and 89.5% (95% CI 83.8-93.2), respectively. Both FR and HS were effective at ensuring seizure control. For different HS techniques, modified hemispherotomy had comparable outcomes but improved safety compared with anatomical hemispherectomy. Regarding FR, partial resection (adjusted hazard ratio [aHR] 11.50, 95% CI 4.44-29.76), acute postoperative seizure (APOS, within 30 days of surgery; aHR 10.33, 95% CI 3.94-27.12), and generalized seizure (aHR 3.09, 95% CI 1.37-6.94) were associated with seizure persistence. For HS, seizure persistence was associated with APOS (aHR 27.61, 9.92-76.89), generalized seizure (aHR 7.95, 2.74-23.05), seizure frequency ≥30 times/month (aHR 4.76, 1.27-17.87), and surgical age ≥2 years (aHR 3.78, 1.51-9.47); motor stability was associated with severe motor defects (aHR 5.23, 2.27-12.05) and postoperative seizure-free status (aHR 3.09, 1.49-6.45); and cognition stability was associated with postoperative seizure-free status (aHR 2.84, 1.39-5.78) and surgical age <2 years (aHR 1.76, 1.13-2.75). DISCUSSION: FR is a valid option for refractory epilepsy in patients with SWS and has similar outcomes to those of HS, with less morbidity associated with refractory epilepsy. Early surgical treatment (under the age of 2 years) leads to better outcomes after HS, but there is insufficient evidence that surgical age affects FR outcomes. These findings warrant future prospective multicenter cohorts with international cooperation and prolonged follow-up in better exploring more precise outcomes and developing prognostic predictive models. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in children with SWS and refractory seizures, surgical resection-focal, hemispherectomy, or modified hemispherotomy-leads to improved outcomes.

Clinical and pathologic features of Sturge-Weber syndrome in patients with refractory epilepsy.

OBJECTIVES: We aimed to investigate the clinicopathologic features of and genetic changes in Sturge-Weber syndrome (SWS) in patients with refractory epilepsy. METHODS: Clinical data were retrospectively analyzed. H&E and immunohistochemistry were performed to assess pathologic changes. Targeted amplicon sequencing was applied to investigate the somatic GNAQ (c.548G>A) mutation. The potential predictors of seizure outcomes were estimated by univariate and multivariate statistical analyses. RESULTS: Forty-eight patients with SWS and refractory epilepsy were enrolled. According to the imaging data and pathologic examination, ipsilateral hippocampal sclerosis (HS), calcification of leptomeningeal arteries, and focal cortical dysplasia were found in 14 (29.2%), 31 (64.6%), and 37 (77.1%) patients, respectively. A high frequency of GNAQ alteration was detected in both cerebral cortex (57.7%) and ipsilateral hippocampus (50.0%) from patients with SWS. During follow-up, 43 of 48 patients (85.4%) had achieved seizure control (Engel class I). Statistically, HS signs on imaging were found to be independent predictors of unfavorable seizure outcomes (P = .015). CONCLUSIONS: Calcification of leptomeningeal arteries, focal cortical dysplasia, and GNAQ alteration are common features in SWS pathology. Patients with refractory epilepsy caused by SWS can achieve satisfactory seizure control after surgery, but seizure control was compromised in patients with comorbid HS.

Local field potentials, spiking activity, and receptive fields in human visual cortex.

The concept of receptive field (RF) is central to sensory neuroscience. Neuronal RF properties have been substantially studied in animals, while those in humans remain nearly unexplored. Here, we measured neuronal RFs with intracranial local field potentials (LFPs) and spiking activity in human visual cortex (V1/V2/V3). We recorded LFPs via macro-contacts and discovered that RF sizes estimated from low-frequency activity (LFA, 0.5-30 Hz) were larger than those estimated from low-gamma activity (LGA, 30-60 Hz) and high-gamma activity (HGA, 60-150 Hz). We then took a rare opportunity to record LFPs and spiking activity via microwires in V1 simultaneously. We found that RF sizes and temporal profiles measured from LGA and HGA closely matched those from spiking activity. In sum, this study reveals that spiking activity of neurons in human visual cortex could be well approximated by LGA and HGA in RF estimation and temporal profile measurement, implying the pivotal functions of LGA and HGA in early visual information processing.

Relativistic-guided stable mode of few-cycle 20 µm level infrared radiation.

The generation of intense infrared radiation with a wavelength greater than 10 µm is limited by the optical materials in traditional methods or the laser-plasma parameters of plasma-bubble methods. In this study, we propose a new method for generating an intense longitudinal radiation field of tens of GV/m. By utilizing the oscillations of the electron film on the inner surface of the micro-tube, excited by the relativistic electron beam propagating within it, it is possible to obtain tunable long-wavelength few-cycle infrared radiation, ranging from 20 to 30 µm and even longer. The radiation source is guided entirely by a relativistic electron beam and formed a stable TM propagation mode in the micro-tube. This opens up new opportunities for applications of the relativistic intensity infrared radiation to high-field physics, shorter attosecond pulses generation and charged particle acceleration.

An artificial intelligence-based pipeline for automated detection and localisation of epileptic sources from magnetoencephalography.

Objective.Magnetoencephalography (MEG) is a powerful non-invasive diagnostic modality for presurgical epilepsy evaluation. However, the clinical utility of MEG mapping for localising epileptic foci is limited by its low efficiency, high labour requirements, and considerable interoperator variability. To address these obstacles, we proposed a novel artificial intelligence-based automated magnetic source imaging (AMSI) pipeline for automated detection and localisation of epileptic sources from MEG data.Approach.To expedite the analysis of clinical MEG data from patients with epilepsy and reduce human bias, we developed an autolabelling method, a deep-learning model based on convolutional neural networks and a hierarchical clustering method based on a perceptual hash algorithm, to enable the coregistration of MEG and magnetic resonance imaging, the detection and clustering of epileptic activity, and the localisation of epileptic sources in a highly automated manner. We tested the capability of the AMSI pipeline by assessing MEG data from 48 epilepsy patients.Main results.The AMSI pipeline was able to rapidly detect interictal epileptiform discharges with 93.31% ± 3.87% precision based on a 35-patient dataset (with sevenfold patientwise cross-validation) and robustly rendered accurate localisation of epileptic activity with a lobar concordance of 87.18% against interictal and ictal stereo-electroencephalography findings in a 13-patient dataset. We also showed that the AMSI pipeline accomplishes the necessary processes and delivers objective results within a much shorter time frame (∼12 min) than traditional manual processes (∼4 h).Significance.The AMSI pipeline promises to facilitate increased utilisation of MEG data in the clinical analysis of patients with epilepsy.

Ectopic expression of neuronal adenosine kinase, a biomarker in mesial temporal lobe epilepsy without hippocampal sclerosis.

AIMS: Mesial temporal lobe epilepsy without hippocampal sclerosis (no-HS MTLE) refers to those MTLE patients who have neither magnetic resonance imaging (MRI) lesions nor definite pathological evidence of hippocampal sclerosis. They usually have resistance to antiepileptic drugs, difficulties in precise seizure location and poor surgical outcomes. Adenosine is a neuroprotective neuromodulator that acts as a seizure terminator in the brain. The role of adenosine in no-HS MTLE is still unclear. Further research to explore the aetiology and pathogenesis of no-HS MTLE may help to find new therapeutic targets. METHODS: In surgically resected hippocampal specimens, we examined the maladaptive changes of the adenosine system of patients with no-HS MTLE. In order to better understand the dysregulation of the adenosine pathway in no-HS MTLE, we developed a rat model based on the induction of focal cortical lesions through a prenatal freeze injury. RESULTS: We first examined the adenosine system in no-HS MTLE patients who lack hippocampal neuronal loss and found ectopic expression of the astrocytic adenosine metabolising enzyme adenosine kinase (ADK) in hippocampal pyramidal neurons, as well as downregulation of neuronal A1 receptors (A1 Rs) in the hippocampus. In the no-HS MTLE model rats, the transition of ADK from neuronal expression to an adult pattern of glial expression in the hippocampus was significantly delayed. CONCLUSIONS: Ectopic expression of neuronal ADK might be a pathological hallmark of no-HS MTLE. Maladaptive changes in adenosine metabolism might be a novel target for therapeutic intervention in no-HS MTLE.

Protocol of a prospective multicenter randomized controlled trial of robot-assisted stereotactic lesioning in the treatment of focal drug-resistant epilepsy.

BACKGROUND: This protocol describes the design of a multicenter randomized controlled trial of robot-assisted stereotactic lesioning versus epileptogenic foci resection. Typical causes of focal epilepsy include hippocampal sclerosis and focal cortical dysplasia. These patients usually present with drug resistance and require surgical treatment. Although epileptogenic foci resection is still the most commonly used treatment for such focal epilepsy, there is increasing evidence that epileptogenic focus resection may lead to neurological impairment. The treatment of epilepsy with a robot-assisted stereotactic lesioning mainly includes two new minimally invasive surgical methods: radiofrequency thermocoagulation (RF-TC) and laser interstitial thermal therapy (LITT). Seizure-free is less likely to be achieved by these two procedures, but neurologic preservation is better. In this study, we aimed to compare the safety and efficacy of RF-TC, LITT, and epileptogenic foci resection for focal drug-resistant epilepsy. METHODS: This is a multicenter, three-arm, randomized controlled clinical trial. The study will include patients older than 3 years of age with epilepsy who have had medically refractory seizures for at least 2 years and are eligible for surgical treatment with an epileptogenic focus as determined by multidisciplinary evaluation prior to randomization. The primary outcome measure is seizure outcome (quantified by seizure remission rate) at 3-month, 6-month, and 1-year follow-up after treatment. Postoperative neurologic impairment, spectrum distribution change of video electroencephalogram, quality of life, and medical costs will also be assessed as secondary outcomes. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR2200060974. Registered on June 14, 2022. The status of the trial is recruiting, and the estimated study completion date is December 31, 2024.

SEEG-based reevaluation of epileptogenic networks and the predictive role for reoperation in MTLE patients with surgical failure.

OBJECTIVE: Approximately 20%-30% of mesial temporal lobe epilepsy (MTLE) patients got unfavorable seizure control after surgery, and there was a discrepancy about the reasons for the surgical failure. The functional connectivity (FC) patterns obtained from stereo-electroencephalography (SEEG) reveal information about the dynamics of the epileptic brain and the added value of extracting information that was not identifiable in the SEEG data using FC analysis. This study aims to find out the patterns of the potential epileptogenic network of failure patients and the electrophysiological predictors of reoperation. METHODS: From January 2012 to December 2019, the MTLE patients with surgical failure were reviewed, and all patients underwent SEEG-guided reoperation. The epileptogenic network was quantified by calculating FC indicators, including phase slope index (PSI), mutual information (MI) strength, imaginary coherence (icoh), and Granger causality. RESULTS: Ten patients with 13 seizures were included in the analysis, and 7 of them achieved a favorable outcome after the SEEG-guided reoperation. The surgical zone (SZ) with a favorable prognosis showed greater outward information flow than the non-SZ, whereas the SZ with an unfavorable prognosis showed greater inward information flow. The recurrent patients with favorable prognosis had strong connectivity between the posterior hippocampus, temporal neocortex, and insula, whereas the patients with unfavorable prognosis showed strong functional connectivity between the insula and temporal-parietal-occipital junction. The power spectrum of patients with favorable prognosis was significantly lower than that of patients with unfavorable prognosis, especially showing a more oscillation power of low frequency. SIGNIFICANCE: The SEEG-guided reoperation could achieve favorable seizure control outcomes for recurrent patients. The FCs were a potential indicator to help construct the temporal epileptic network and predictor for the reoperative prognosis in the recurrent patients.

Deep brain stimulation suppresses epileptic seizures in rats via inhibition of adenosine kinase and activation of adenosine A1 receptors.

AIMS: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug-resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A1 Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms. METHODS: Control group, SE (status epilepticus) group, SE-DBS group, and SE-sham-DBS group were included in this study. One week after a pilocarpine-induced status epilepticus, rats in the SE-DBS group were treated with DBS for 4 weeks. The rats were monitored by video-EEG. ADK and A1 Rs were tested with histochemistry and western blot, respectively. RESULTS: Compared with the SE group and SE-sham-DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A1 R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A1 Rs. CONCLUSION: The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A1 Rs. A1 Rs might be a potential target of DBS for the treatment of epilepsy.

Neural Network Design for Impedance Modeling of Power Electronic Systems Based on Latent Features.

Data-driven approaches are promising to address the modeling issues of modern power electronics-based power systems, due to the black-box feature. Frequency-domain analysis has been applied to address the emerging small-signal oscillation issues caused by converter control interactions. However, the frequency-domain model of a power electronic system is linearized around a specific operating condition. It thus requires measurement or identification of frequency-domain models repeatedly at many operating points (OPs) due to the wide operation range of the power systems, which brings significant computation and data burden. This article addresses this challenge by developing a deep learning approach using multilayer feedforward neural networks (FNNs) to train the frequency-domain impedance model of power electronic systems that is continuous of OP. Distinguished from the prior neural network designs relying on trial-and-error and sufficient data size, this article proposes to design the FNN based on latent features of power electronic systems, i.e., the number of system poles and zeros. To further investigate the impacts of data quantity and quality, learning procedures from a small dataset are developed, and K-medoids clustering based on dynamic time warping is used to reveal insights into multivariable sensitivity, which helps improve the data quality. The proposed approaches for the FNN design and learning have been proven simple, effective, and optimal based on case studies on a power electronic converter, and future prospects in its industrial applications are also discussed.

Aberrant adenosine signaling in patients with focal cortical dysplasia.

Focal cortical dysplasia (FCD), a common malformation of cortical development, is frequently associated with pharmacoresistant epilepsy in both children and adults. Adenosine is an inhibitory modulator of brain activity and a prospective anti-seizure agent with potential for clinical translation. Our previous results demonstrated that the major adenosine-metabolizing enzyme adenosine kinase (ADK) was upregulated in balloon cells (BCs) within FCD type IIB lesions, suggesting that dysfunction of the adenosine system is implicated in the pathophysiology of FCD. In our current study, we therefore performed a comprehensive analysis of adenosine signaling in surgically resected cortical specimens from patients with FCD type I and type II via immunohistochemistry and immunoblot analysis. Adenosine enzyme signaling was assessed by quantifying the levels of the key enzymes of adenosine metabolism, i.e., ADK, adenosine deaminase (ADA), and ecto-5'-nucleotidase (CD73). Adenosine receptor signaling was assessed by quantifying the levels of adenosine A2A receptor (A2AR) and putative downstream mediators of adenosine, namely, glutamate transporter-1 (GLT-1) and mammalian target of rapamycin (mTOR). Within lesions in FCD specimens, we found that the adenosine-metabolizing enzymes ADK and ADA, as well as the adenosine-producing enzyme CD73, were upregulated. We also observed an increase in A2AR density, as well as a decrease in GLT-1 levels and an increase in mTOR levels, in FCD specimens compared with control tissue. These results suggest that dysregulation of the adenosine system is a common pathologic feature of both FCD type I and type II. The adenosine system might therefore be a therapeutic target for the treatment of epilepsy associated with FCD.

The clinicopathological features of ganglioglioma with CD34 expression and BRAF mutation in patients with epilepsy.

Objective: The aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated gangliogliomas (GG) with CD34 expression and BRAFV600E mutation. Methods: Clinical data of patients who underwent epilepsy surgery for GG were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAFV600E mutation in GG. Results: A total of 208 patients with GG had immunohistochemical detection of CD34 expression (positive/negative: 184/24), and among them, 89 patients had immunohistochemical detection of BRAFV600E mutation (positive/negative: 54/35). By univariate and multivariate analyses, seizure aura (p = 0.025), concordance of ictal electroencephalogram (EEG) findings (p = 0.045) and medial temporal tumor (p = 0.030) were found to be related to CD34 expression, but only hospitalization time (p = 0.042) was different for BRAF-mutated status. In addition, drug-resistant epilepsy (p = 0.040) and concordance of interictal EEG findings (p = 0.009) were found to be associated with tumor progression-free survival (PFS) in univariate analysis, but only concordance of interictal EEG findings was with significance in multivariate analysis. However, CD34 expression or BRAFV600E mutation in GG was not found to be associated with surgical outcomes of seizure control and tumor PFS. Conclusion: The CD34 expression or BRAFV600E mutation in GG may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence.

Rapid Processing of Invisible Fearful Faces in the Human Amygdala.

Rapid detection of a threat or its symbol (e.g., fearful face), whether visible or invisible, is critical for human survival. This function is suggested to be enabled by a subcortical pathway to the amygdala independent of the cortex. However, conclusive electrophysiological evidence in humans is scarce. Here, we explored whether the amygdala can rapidly encode invisible fearful faces. We recorded intracranial electroencephalogram (iEEG) responses in the human (both sexes) amygdala to faces with fearful, happy, and neutral emotions rendered invisible by backward masking. We found that a short-latency intracranial event-related potential (iERP) in the amygdala, beginning 88 ms poststimulus onset, was preferentially evoked by invisible fearful faces relative to invisible happy or neutral faces. The rapid iERP exhibited selectivity to the low spatial frequency (LSF) component of the fearful faces. Time-frequency iEEG analyses further identified a rapid amygdala response preferentially for LSF fearful faces at the low gamma frequency band, beginning 45 ms poststimulus onset. In contrast, these rapid responses to invisible fearful faces were absent in cortical regions, including early visual areas, the fusiform gyrus, and the parahippocampal gyrus. These findings provide direct evidence for the existence of a subcortical pathway specific for rapid fear detection in the amygdala and demonstrate that the subcortical pathway can function without conscious awareness and under minimal influence from cortical areas.SIGNIFICANCE STATEMENT Automatic detection of biologically relevant stimuli, such as threats or dangers, has remarkable survival value. Here, we provide direct intracranial electrophysiological evidence that the human amygdala preferentially responds to fearful faces at a rapid speed, despite the faces being invisible. This rapid, fear-selective response is restricted to faces containing low spatial frequency information transmitted by magnocellular neurons and does not appear in cortical regions. These results support the existence of a rapid subcortical pathway independent of cortical pathways to the human amygdala.

Long-term ANT-DBS effects in pilocarpine-induced epileptic rats: A combined 9.4T MRI and histological study.

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures in animals and humans however, its therapeutic mechanisms remain elusive. This study aimed to combine 9.4T multimodal magnetic resonance imaging (MRI) with histology to investigate the longitudinal effects of long-term ANT-DBS in pilocarpine-induced epileptic rats. Status epilepsy (SE) was induced by LiCl-pilocarpine injection in 11 adult male Sprague-Dawley rats. Four weeks after SE, chronic epileptic rats underwent either ANT-DBS (n = 6) or sham-DBS (n = 5) surgery. Electroencephalography (EEG) and spontaneous recurrent seizures (SRS) were recorded for 1 week. The T2-weighted image and images from resting-state functional MRI (rs-fMRI) were acquired at three states: before SE, at 4 weeks post-SE, and at 5 weeks post-DBS. Volumes of the hippocampal subregions and hippocampal-related functional connectivity (FC) were compared longitudinally. Finally, antibodies against neuronal nuclei (NeuN) and glial fibrillary acidic proteins were used to evaluate neuronal loss and astrogliosis in the hippocampus. Long-term ANT-DBS significantly reduced seizure generalization in pilocarpine-induced epileptic rats. By analyzing the gray matter volume using T2-weighted images, long-term ANT-DBS displayed morphometric restoration of the hippocampal subregions. Neuronal protection of the hippocampal subregions and inhibition of astrogliosis in the hippocampal subregions were observed in the ANT-DBS group. ANT-DBS caused reversible regulation of FC in the insula-hippocampus and subthalamic nucleus-hippocampus. Long-term ANT-DBS provides comprehensive protection of hippocampal histology, hippocampal morphometrics, and hippocampal-related functional networks.

Periventricular nodular heterotopia is coupled with the neocortex during resting and task states.

Periventricular nodular heterotopia (PVNH) is a well-defined developmental disorder characterized by failed neuronal migration, which forms ectopic neuronal nodules along the ventricular walls. Previous studies mainly focus on clinical symptoms caused by the PVNH tissue, such as seizures. However, little is known about whether and how neurons in the PVNH tissue functionally communicate with neurons in the neocortex. To probe this, we applied magnetoencephalography (MEG) and stereo-electroencephalography (sEEG) recordings to patients with PVNH during resting and task states. By estimating frequency-resolved phase coupling strength of the source-reconstructed neural activities, we found that the PVNH tissue was spontaneously coupled with the neocortex in the α-ß frequency range, which was consistent with the synchronization pattern within the neocortical network. Furthermore, the coupling strength between PVNH and sensory areas effectively modulated the local neural activity in sensory areas. In both MEG and sEEG visual experiments, the PVNH tissue exhibited visual-evoked responses, with a similar pattern and latency as the ipsilateral visual cortex. These findings demonstrate that PVNH is functionally integrated into cognition-related cortical circuits, suggesting a co-development perspective of ectopic neurons after their migration failure.

The differential role of magnetic resonance imaging in predicting surgical outcomes between children versus adults with temporal lobe epilepsy.

Objective: This study aims to investigate the clinical discrepancies and the different predictors of anterior temporal lobectomy (ATL) in children (<18 years at surgery) and adults (>18 years at surgery) with temporal lobe epilepsy (TLE). Materials and methods: A total of 262 patients (56 children and 206 adults) with TLE who underwent ATL were included in this study. The clinical variables, including patients' characteristics, preoperative evaluations, pathology, surgical prognosis, and surgical predictors were assessed the discrepancies between TLE children versus adults using univariate and multivariate analyses. Kaplan-Meier survival analysis was used to calculate the probability of seizure freedom and AEDs withdrawal after ATL, and the difference between TLE children and adults was analyzed using the Log-Rank test. Results: There were significant differences including semiology, magnetic resonance imaging (MRI) examinations, numbers of preoperative AEDs, and pathologies between TLE children and adults (P < 0.05, Q < 0.05). The MRI-detected epileptic focus was the only independent predictor of seizure freedom (P = 0.002, Q = 0.036) in TLE children, and the concordance of MRI-detected focus with video-electroencephalography (video-EEG)-detected epileptic zone was the only variable associated with seizure freedom in TLE adults (OR = 2.686, 95% CI = 1.014-7.115, P = 0.047). The TLE children experienced a higher probability of AEDs withdrawal than adults after surgery (P = 0.005). Significance: There were remarkable differences in clinical manifestations, MRI examinations, number of preoperative AEDs, and pathologies between TLE children versus adults. TLE children had a higher possibility of AEDs withdrawal than adults after surgery. The favorable seizure outcome of ATL depended on the early complete resection of MRI-detected epileptogenic focus in TLE children, while the concordance of MRI-detected focus with EEG-detected epileptogenic zone was the only predictor of favorable seizure outcomes in TLE adults.

Translocation of High Mobility Group Box 1 From the Nucleus to the Cytoplasm in Depressed Patients With Epilepsy.

Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.

The clinical and pathological features of low-grade epilepsy-associated glioneuronal tumors.

The aim of the study was to evaluate the clinicopathological features, as well as the surgical prognosis, of epilepsy-associated glioneuronal tumors (GNT) with CD34 expression and BRAF mutation. Clinical data of patients who underwent epilepsy surgery for GNT were retrospectively studied. Univariate and multivariate analyses were performed to evaluate the correlations of clinical and pathological factors with molecular markers of CD34 expression and BRAFV600E mutation in GNT. A total of 247 patients with GNT had immunohistochemical detection of CD34 expression (CD34 positive vs. negative: 198/49), and among them, 102 patients had immunohistochemical detection of BRAFV600E mutation (BRAF positive vs. negative: 59/43). Univariate analysis found that tumor types (P < 0.001), patient population (P = 0.015), seizure aura (P = 0.007), drug-resistant epilepsy (P = 0.036), concordance of ictal electroencephalogram (EEG) findings (P = 0.032), surgical resection extent (P = 0.045), tumor location (P = 0.007) and duration of epilepsy (P = 0.027) were related to CD34 expression, and that concordance of ictal EEG findings (P = 0.031) and age at surgery (P = 0.015) were related to BRAFV600E mutation. In addition, history of generalized tonic-clonic seizure (HR 0.12; P = 0.035), drug-resistant epilepsy (HR 0.13; P = 0.030) and concordance of interictal EEG findings (HR 8.01; P = 0.039) were associated with tumor progression-free survival (PFS). However, CD34 expression or BRAFV600E mutation in GNT was not associated with surgical outcomes of seizure control and tumor PFS. The CD34 expression or BRAFV600E mutation in GNT may partly influence the distribution of clinicopathological features of patients with epilepsy, but they may be not able to predict the surgical prognosis of seizure outcome and tumor recurrence.