Influence of resective extent of epileptogenic tuber on seizure outcome in patients with tuberous sclerosis complex-related epilepsy: A systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis to identify whether tuberectomy and tuberectomy plus are associated with different postoperative seizure outcomes in patients with tuberous sclerosis complex (TSC) -related epilepsy. METHODS: Electronic databases (PubMed, Embase, Cochrane, Proquest, Web of Science, Scopus, Biosis Previews) were searched without date restriction. Retrospective cohort studies of participants with TSC-associated epilepsy undergoing resective surgery that reported demographics, presurgical evaluation, extent of resection and postoperative seizure outcomes were included. Title, abstract and the full text were checked independently and in duplicate by two reviewers. Disagreements were resolved through discussion. One author extracted data which was verified by a second author using identified common standard in advance, including using a risk of bias tool we agreed on to evaluate study quality. RESULTS: Five studies, with a total of 327 participants, were included. One hundred and sixty patients received tuberectomy, and 93 of them (58.1%) achieved postoperative seizure freedom, while the other 167 patients underwent tuberectomy plus, and 128 of them (76.6%) achieved seizure freedom after adequate follow-ups (RR=0.72, 95% CI [0.60, 0.87], P<0.05). Subgroup analysis found that 40 of 63 (63.5%) patients after tuberectomy and 66 of 78 (84.6%) patients after tuberectomy plus of a single tuber achieved seizure freedom (RR = 0.71, 95% CI [0.56,0.91], P<0.05). In the multituber subrgroup, 16 of 42 (38.1%) and 21 of 31 (67.7%) patients achieved seizure freedom, after tuberectomy and tuberectomy plus, respectively (RR = 0.57, 95% CI [0.32,1.03], P = 0.06). CONCLUSIONS: Tuberectomy plus is a more effective treatment than tuberectomy for patients with TSC-related intractable epilepsy.

Factors that Influence Subdural Hemorrhage Secondary to Intracranial Arachnoid Cysts in Children.

OBJECTIVE: This study aimed to investigate factors that influence subdural haemorrhage (SDH) secondary to intracranial arachnoid cysts (IACs) in children. METHODS: Data of children with unruptured IACs (IAC group) and those with SDH secondary to IACs (IAC-SDH group) were analyzed. Nine factors, sex, age, birth type (vaginal or caesarean), symptoms, side (left, right, or midline), location (temporal or nontemporal), image type (I, II, or III), volume, and maximal diameter, were selected. IACs were classified as types I, II, and III according to their morphological changes observed on computed tomography images. RESULTS: There were 117 boys (74.5%) and 40 girls (25.5%); 144 (91.7%) patients comprised the IAC group and 13 (8.3%) comprised the IAC-SDH group. There were 85 (53.8%) IACs on the left side, 53 (33.5%) on the right side, 20 (12.7%) in the midline region, and 91 (58.0%) in the temporal region. The univariate analysis showed significant differences in age, birth type, symptoms, cyst location, cyst volume, and cyst maximal diameter (P < 0.05) between the 2 groups. Logistic regression using the synthetic minority oversampling technique model showed that image type III and birth type were independent factors that influenced SDH secondary to IACs (ß0 = 4.143; ß for image type = -3.979; ß for birth type = -2.542) and that the representative area under the receiver-operating characteristic curve value was 0.948 (95% confidence interval, 0.898-0.997). CONCLUSIONS: IACs are more common in boys than in girls. They can be divided into 3 groups according to their morphological changes on computed tomography images. Image type III and caesarean delivery were independent factors that influenced SDH secondary to IACs.

Effect of current conduction for local epileptiform discharges in patients with temporal lobe epilepsy.

OBJECTIVES: The effects of current conduction were researched to confirm that it can decrease focal epileptogenicity in patients with temporal lobe epilepsy (TLE). METHODS: Data from 13 patients with mesial TLE were collected. After no less than two habitual seizures were captured during stereo-electroencephalogram monitoring, current conduction was measured in the hippocampus to a homemade, zero potential circuit board. The interictal spike, ripple, fast ripple, and ictal epileptogenicity index (EI) changes were analyzed in the hippocampus, amygdala, and anterior and middle temporal neocortex regions. RESULTS: Significant differences were found in the percentage of patients without spikes in the temporal neocortex between pre- and post-current conduction. Significant decreases in average ripple rates were found in the hippocampus and amygdala after current conduction. The percentage of fast ripple rate decrease in the hippocampus and amygdala was significantly higher than that in the temporal neocortex, and significant decreases were found in the fast ripple rate in the hippocampus from post- to pre-current conduction. Significant decreases were found in the EI values after current conduction in the amygdala and middle temporal lobe compared to the EI values before current conduction. CONCLUSION: After current conduction in patients with TLE, the spike rate decreases in the hippocampus, amygdala, and anterior and middle temporal neocortex, the ripple rate decreases in the hippocampus and amygdala, the fast ripple decreases in the hippocampus, and the EI decreases in the amygdala and middle temporal neocortex. Current conduction can reduce epileptogenicity in the hippocampus in mesial TLE.

Preliminary study on pathogenic mechanism of first Chinese family with PNKD.

Background: The first Chinese family with paroxysmal non-kinesigenic dystonia (PNKD) was confirmed to harbour a PNKD mutation. However, the pathogenic mechanism of the PNKD-causing gene mutation was unclear. Methods: Wild-type and mutant PNKD-L plasmids were prepared and transfected into the C6 cell line to study the distribution and stability of PNKD protein in C6 cells and its effect on the glutathione content. The blood and cerebrospinal fluid (CSF) of 3 PNKD patients and 3 healthy controls were collected. The differentially expressed proteins were identified using isobaric tags for relative and absolute quantitation. Furthermore, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed, and the protein-protein interaction network was constructed. Results: Wild-type PNKD protein was mainly distributed in the membranes, whereas mutant PNKD protein was distributed throughout the C6 cells. After transfection with mutant PNKD-L plasmid, the glutathione content decreased significantly in C6 cells; the stability of the mutant PNKD protein was significantly low. There were 172 and 163 differentially expressed proteins in CSF and plasma, respectively, of PNKD patients and healthy controls. For these proteins, blood microparticle and complex activation (classical pathway) were the common GO enrichment term, and complex and coordination cascade pathway were the common KEGG enrichment pathway. Recombinant mothers against decapentaplegic homolog 4 (SMAD4) was one of the differentially expressed proteins; it exhibited a relationship with the aforementioned enrichment GO terms and KEGG pathway. Conclusion: PNKD protein was mainly distributed in cell membranes. PNKD-L mutation affected subcellular localisation, PNKD protein stability, and glutathione content. SMAD4 was found to be a potential biomarker for PNKD diagnosis.

Interictal Discharge Pattern in Preschool-Aged Children With Tuberous Sclerosis Complex Before and After Resective Epilepsy Surgery.

Objective: To analyze the interictal discharge (IID) patterns on pre-operative scalp electroencephalogram (EEG) and compare the changes in IID patterns after removal of epileptogenic tubers in preschool children with tuberous sclerosis complex (TSC)-related epilepsy. Methods: Thirty-five preschool children who underwent resective surgery for TSC-related epilepsy were enrolled retrospectively, and their EEG data collected before surgery to 3 years after surgery were analyzed. Results: Twenty-three (65.7%) patients were seizure-free post-operatively at 1-year follow-up, and 37-40% of post-operative patients rendered non-IID on scalp EEGs, and patients with focal IIDs or generalized IID patterns on pre-operative EEG presented a high percentage of normal post-operative scalp EEGs. IID patterns on pre-operative scalp EEGs did not influence the outcomes of post-operative seizure controls, while patients with non-IID and focal IID on post-operative EEGs were likely to achieve post-operative seizure freedom. Patients with new focal IIDs presented a significantly lower percentage of seizure freedom than those without new focal IIDs on post-operative EEGs at 3-year follow-up. Conclusion: Over 1/3 children with TSC presented normal scalp EEGs after resective epileptsy surgery. Patients with post-operative seizure freedom were more likely to have non-IIDs on post-operative EEGs. New focal IIDs were negative factors for seizure freedom at the 3-year follow-up.

Diagnostic value of high-frequency oscillations for the epileptogenic zone: A systematic review and meta-analysis.

BACKGROUND: Delineation of the epileptogenic zone (EZ) is crucial during resective surgery in patients with epilepsy. In recent years, high-frequency oscillations, including fast ripples and ripples, have been considered promising biomarkers of the EZ. The objective of this study was to perform a systematic review and meta-analysis to evaluate the diagnostic accuracy of fast ripples and ripples in identifying EZs. METHODS: The PubMed, Embase, and Cochrane databases were searched systematically. The review process followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A bivariate mixed-effects regression approach was used to obtain summary estimates of the sensitivity and specificity of fast ripples and ripples. RESULTS: Thirteen studies were included in this review (12 for fast ripples and eight for ripples). Fast ripples had a pooled sensitivity of 0.80 (95% confidence interval [CI], 0.62-0.91), a specificity of 0.72 (95% CI, 0.55-0.85), and a summary area under the curve of 0.82 (95% CI, 0.79-0.86). The threshold effect was detected for ripples, and the summary area under the curve was 0.75 (95% CI, 0.71-0.79), with a sensitivity of 0.38 (95% CI, 0.18-0.64) and specificity of 0.90 (95% CI, 0.70-0.97). CONCLUSIONS: Fast ripples are a biomarker of the EZ with moderate diagnostic accuracy; in contrast, ripples are not as effective.

Independent temporal lobe epilepsy in patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare disease that involves multiple organs, including the brain; approximately 80%-90% of TSC patients exhibit TSC-associated epilepsy. Independent temporal lobe epilepsy (TLE), TSC-unrelated epilepsy, is particularly rare in patients with TSC. Here, we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography (EEG), postoperative pathological findings, and seizure outcome at follow-up. The patients were retrospectively enrolled at two centers; their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG. The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery. Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients. Furthermore, postoperative intelligence quotient improvement was evident in one patient, while the quality of life was improved in two patients at 12 months after surgery.

Fast Ripples as a Biomarker of Epileptogenic Tuber in Tuberous Sclerosis Complex Patients Using Stereo-Electroencephalograph.

Objectives: To evaluate the value of fast ripples (FRs) (200-500 Hz) recorded with stereo-electroencephalograph (SEEG) in the localization of epileptogenic tubers in patients with tuberous sclerosis complex (TSC). Methods: Seventeen TSC patients who underwent preoperative SEEG examination and resective epilepsy surgery were retrospectively enrolled. They were divided into two groups according to the seizure control at 1-year postoperative follow-up. The occurrence frequencies of FRs were automatically counted, and the FR rate was calculated. The high FR rate was defined as FR rate ≧0.5. According to different positions, the contacts' locations were divided into three groups: inner of the tubers, the junction region of the tubers, and out of the tubers. The influence factors of postoperative seizure freedom were also analyzed. Results: Twelve patients reached postoperative seizure freedom at 1-year follow-up. In total, FRs were found in 24.2% of the contacts and 67.1% of the tubers in all assessed patients. There were 47 high FR rate contacts localized in the junction region of the tubers, which was 62.7% of the 75 high FR rate contacts in total and was 8.4% of the total 561 contacts localized in the junction region of the tubers. Total removal of epileptogenic tubers and total resection of the high FR rate tubers/contacts were associated with postoperative seizure freedom (P < 0.05). Conclusion: FRs could be extensively detected in TSC patients using SEEG, and high FR rate contacts were mostly localized in the junction region of the epileptogenic tuber, which could aid in the localization of epileptogenic tubers.

Clinical Application of 7T Magnetic Resonance Imaging in Patients with Focal Cortical Dysplasia IIa and Epilepsy.

BACKGROUND: Focal cortical dysplasia (FCD) is one of the most important pathogenic findings in patients with extratemporal lobe epilepsy. Magnetic resonance imaging (MRI)-negative is the most important negative factor to predict postoperative seizure freedom; however, FCD-I and part of FCD-IIa are MRI-negative on routine MRI. OBJECTIVES: To explore the diagnostic values of 7T MRI and its new scan sequences in epilepsy patients with FCD-IIa. METHODS: To include patients with focal seizure and suspicious focal abnormal imaging on 3T MRI during preoperative evaluation and perform a 7T MRI scan with white matter-suppressed (WMS) and gray-white matter tissue border enhancement (GWBE) sequences, resective epilepsy surgery, and postoperative pathological finding of FCD-IIa. The preoperative qualitative and localization significance of 7T MRI and 3T MRI in lesions with FCD-IIa was compared, and then, the imaging characteristics of lesions with FCD-IIa on 7T MRI were analyzed. RESULTS: Ten cases were enrolled in this study. Seven tesla MRI presented high spatial resolutions and a high signal-to-noise ratio. WMS and GWBE could selectively suppress the signal of special tissue and improved the possibility of FCD findings. FCD-IIa showed abnormal thickness of gray matter and a blurring border and was hypointense on 7T MRI compared with 3T MRI. Seven patients showed improvement in the qualitative diagnosis strength grade of FCD, and 6 subjects showed improvement in the localization strength grade of the lesion border after careful reading of the 7T MR images. Significant differences were found in the qualitative diagnosis of FCD (p < 0.05) and localization of the lesion border (p < 0.05) between the neuroimaging diagnoses based on 3T MRI and the findings based on 7T MRI. CONCLUSION: 7T MRI with WMS and GWBE sequences shows application value in the preoperative imaging diagnosis of lesions with FCD-IIa in epilepsy patients.

Magnetic resonance-guided laser interstitial thermal therapy versus stereoelectroencephalography-guided radiofrequency thermocoagulation for drug-resistant epilepsy: A systematic review and meta-analysis.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is a minimally invasive treatment for drug-resistant epilepsies (DRE), and stereoelectroencephalography-guided radiofrequency thermocoagulation (SEEG-RFTC) is also reported as a minimally invasive treatment in some cases with DRE. This study aimed to undertake a meta-analysis to assess the effectiveness and safety of the two approaches in treating DRE. METHODS: Databases, including PubMed, Embase, and Cochrane, were searched systematically up to November 2019. Our primary objective was to estimate the percentage of postoperative freedom from seizures and complications after MRgLiTT and SEEG-RFTC. The secondary objective was to estimate the rate of freedom from seizure after dividing the patients into groups according to the etiology of the epilepsy. RESULTS: Twenty-six studies, with a total number of 804 patients, were identified, 16 studies with MRgLiTT (414 patients) and 10 with SEEG-RFTC (390 patients). In total, significant difference was found in the postoperative rate of freedom from seizure between patients with MRgLiTT (65 %; 95 % CI 56-74 %) and those with SEEG-RFTC (23 %; 95 % CI 10-39 %) (P = 0.00), and there was high heterogeneity across groups. After dividing the patients according to etiology, those with MRgLiTT in both the hypothalamic hamartoma group (99 %; 95 % CI 92 %-100 %) and the temporal lobe epilepsy group (59 %; 95 % CI 53 %-65 %) achieved great efficacy and low heterogeneity, and patients with temporal lobe epilepsy and mesial temporal sclerosis (MTS) did not achieve better seizure control than non-MTS patients did (OR = 1.46; 95 % CI [0.88, 2.41]; P = 0.142). For the patients treated with SEEG-RFTC, those in the periventricular nodular heterotopias group obtained the highest percentage of freedom from seizure (56 %; 95 % CI 23 %-86 %). The overall complication rate across all samples was low in the two approaches (5%; 95 % CI 3%-8%). CONCLUSIONS: MRgLiTT and SEEG-RFTC are both safe, minimally invasive treatments for patients with DRE. Patients treated with MRgLiTT had an overall higher postoperative rate of freedom from seizure than those treated with SEEG-RFTC.

MAP30 promotes apoptosis of U251 and U87 cells by suppressing the LGR5 and Wnt/ß-catenin signaling pathway, and enhancing Smac expression.

Significant antitumor activity of Momordica anti-human immunodeficiency virus protein of 30 kDa (MAP30) purified from Momordica charantia has been the subject of previous research. However, the effective mechanism of MAP30 on malignant glioma cells has not yet been clarified. The aim of the present study was to investigate the effects and mechanism of MAP30 on U87 and U251 cell lines. A Cell Counting Kit-8 assay, wound healing assay and Transwell assay were used to detect the effects on U87 and U251 cells treated with different concentrations of MAP30 (0.5, 1, 2, 4, 8 and 16 µM) over different periods of time. Proliferation, migration and invasion of each cell line were markedly inhibited by MAP30 in a dose- and time-dependent manner. Flow cytometry and fluorescence staining demonstrated that apoptosis increased and the cell cycle was arrested in S-phase in the two investigated cell lines following MAP30 treatment. Western blot analysis demonstrated that leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5) expression and key proteins in the Wnt/ß-catenin signaling pathway were apparently decreased, whereas second mitochondria-derived activator of caspase (Smac) protein expression significantly increased with MAP30 treatment in the same manner. These results suggest that MAP30 markedly induces apoptosis in U87 and U251 cell lines by suppressing LGR5 and the Wnt/ß-catenin signaling pathway, and enhancing Smac expression in a dose- and time-dependent manner.

Influence of antithrombotic agents on the recurrence of chronic subdural hematomas and the quest about the recommencement of antithrombotic agents: A meta-analysis.

Antithrombotic agents (AT), including anticoagulants and antiplatelets, are risk factors of chronic subdural hematomas (CSDHs). However, the use of AT has not been clearly associated with postoperative recurrence (PR) in the literature before. Furthermore, the association between the resumption of AT and postoperative complications also requests research. Databases including Pubmed, Embase and Cochrane were searched for patients presenting with CSDH on anticoagulant or antiplatelet medication. Ten studies were included to analyze the association between the use of AT and PR: The meta-analysis showed that the use of AT, both anticoagulants (OR=2.20, 95%CI [1.45, 3.33]; P=0.0002) and antiplatelets (OR=1.64, 95%CI [1.17, 2.30]; P=0.004), could increase the PR rate. Two studies were included to analyze the relationship between the resumption of AT and postoperative complications. The meta-analysis showed that after the patients on AT resumed their medication, the risk of PR did not increase (OR=0.33, 95%Cl [0.13, 0.80]; P=0.01), and the occurrence of thromboembolism events had no statistical significance (OR=1.30, 95%CI [0.26, 6.50]; P=0.75). This meta-analysis demonstrated that AT were risk factors for the recurrence of CSDH. Recommencement of AT did not appear to increase the risk of postoperative hemorrhage, and could reduce the risk of thromboembolism. Thus, appropriate postoperative resumption of anticoagulants or antiplatelets may be safe. Still, more evidence is needed to answer the question about whether and how to resume AT.

Trichosanthin suppresses the proliferation of glioma cells by inhibiting LGR5 expression and the Wnt/ß-catenin signaling pathway.

Studies have indicated that trichosanthin (TCS), a bioactive protein extracted and purified from the tuberous root of Trichosanthes kirilowii (a well­known traditional Chinese medicinal plant), produces antitumor effects on various types of cancer cells. However, the effects of TCS on glioma cells are poorly understood. The objective of this study was to investigate the antitumor effects of TCS on the U87 and U251 cell lines. The in vitro effects of TCS on these two cell lines were determined using a Cell Counting Kit­8 (CCK­8) assay, Annexin V­FITC staining, DAPI staining, Transwell assays, terminal deoxynucleotidyl transferase­mediated dUTP nick end­labeling (TUNEL) assays, 5,5',6,6'­tetrachloro­1,1',3,3'­tetraethyl­imidacarbocyanine iodide (JC­1) staining and western blotting, which was utilized to assess the expression of leucine­rich repeat­containing G protein­coupled receptor 5 (LGR5) and key proteins in the Wnt/ß­catenin signaling pathway. Our data indicated that TCS inhibited the proliferation of glioma cells in a dose­ and time­dependent manner and played a role in inhibiting glioma cell invasion and migration. Additional investigation revealed that the expression levels of LGR5 and of key proteins in the Wnt/ß­catenin signaling pathway were markedly decreased after TCS treatment. The results suggest that TCS may induce apoptosis in glioma cells by targeting LGR5 and repressing the Wnt/ß­catenin signaling pathway. In the future, in vivo experiments should be conducted to examine the potential use of this compound as a novel therapeutic agent for gliomas.