Study of the microstructure of brain white matter in medial temporal lobe epilepsy based on diffusion tensor imaging.

OBJECTIVES: To compare the white matter (WM) asymmetry in left and right medial temporal lobe epilepsy (mTLE) with and without hippocampal sclerosis (HS+, HS-) and assess the correlation of preoperative asymmetry and the dynamics of WM fibers with surgical outcomes. MATERIALS AND METHODS: Preoperative MRI scans were collected from 58 mTLE patients (40 HS+, 18 HS-); 15 (11 HS+, 4 HS-) then underwent postoperative MRI scans. DTI parameters, including the fractional anisotropy (FA), mean diffusion coefficient (MD), axial diffusion coefficient (AD), and radial diffusion coefficient (RD), were extracted from 20 paired WM tracts by PANDA based on the JHU WM tractography atlas. The bilateral cerebral parameters and the pre- to postoperative changes in the DTI parameters of specific fiber tracts were compared. The asymmetry indexes (AIs) of paired fibers were also analyzed. RESULTS: There were fewer asymmetrical WM fibers in HS- patients than in HS+ patients. The pattern of WM asymmetry differed between left and right mTLE patients. Differences in the FA AI of the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus (ILF) were found in left HS+ patients with different surgical outcomes. All mTLE patients exhibited decreases in FA and increases in MD and RD in specific ipsilateral WM fibers. In International League Against Epilepsy (ILAE) grade 1 patients, the MD values in the ipsilateral CGH increased over time, whereas the RD values in the ipsilateral ILF and the AD values in the ipsilateral ILF and UNC decreased. In ILAE grade 2-5 patients, the FA values in the ipsilateral cingulate gyrus part of the cingulum (CGC) increased over time. CONCLUSION: The WM tract asymmetry was more extensive in HS+ patients than in HS- patients. The preoperative WM fiber AIs in left HS+ patients may be useful for surgical prognosis. Additionally, pre- to postoperative changes in WM fibers may help predict surgical outcomes.

An Independent Seizure-Onset Zone in Medial Temporal Lobe Found by 18 F-FDG PET Imaging Besides Epileptogenic Periventricular Nodular Heterotopia.

ABSTRACT: A 23-year-old man with drug-resistant epilepsy was admitted for presurgical evaluation. The epileptogenic zone could not be derived from seizure semiology and scalp electroencephalographic monitoring definitely. MRI showed periventricular nodular heterotopia in occipital horn of left lateral ventricle with high FDG uptake on interictal 18 F-FDG PET scan, whereas the hypometabolic zone in the left medial temporal lobe was also found on PET with no abnormality on MRI. Stereoelectroencephalographic implantation was performed to identify the seizure-onset zone. Two independent epileptogenic foci located in periventricular nodular heterotopia and left hippocampus were validated by stereoelectroencephalographic monitoring and the outcome of subsequent thermocoagulation.

Brain volume and perfusion asymmetry in temporal lobe epilepsy with and without hippocampal sclerosis.

Objectives: To detect and compare the features of interictal perfusion and volume asymmetry between temporal lobe epilepsy (TLE) patients with and without hippocampal sclerosis (HS).Methods: Sixty-one TLE patients (mean age 28.4 ± 9.3 years; 28 female/33 male) with unilateral signs of HS (TLE-HS+) and 25 TLE patients (mean age 29.8 ± 8.0 years; 17 female/8 male) without HS (TLE-HS-) were included. Thirty healthy volunteers served as controls (mean age 26.0 ± 8.7 years; 22 female/8 male). Brain segmentation and volume calculation were performed. Quantitative cerebral blood flow (CBF) values were measured based on arterial spin labeling (ASL). The asymmetry indices (AIs) of volume and perfusion were calculated.Results: TLE-HS+ (adjusted P = 0.001) and TLE-HS- patients (adjusted P = 0.006) had significantly higher hippocampal perfusion AIs than controls. TLE-HS+ and TLE-HS- had similar hippocampal perfusion AIs (adjusted P = 1.00). TLE-HS+ had higher hippocampal volume AIs than TLE-HS- and controls (adjusted P < 0.001). TLE-HS- and controls had similar hippocampal volume AIs (adjusted P = 1.00). All (100%) TLE-HS+ patients had positive hippocampal perfusion or volume AIs. No significant correlation between the AIs of hippocampal perfusion and volume was found in both TLE-HS+(P = 0.894) and TLE-HS- (P = 0.106) patients. TLE-HS+ patients demonstrated more extensive whole-brain asymmetry of both perfusion and volume than TLE-HS- patients.Conclusion: TLE-HS+ and TLE-HS- patients have different patterns of whole-brain perfusion and volume asymmetry. Hippocampal perfusion asymmetry was revealed in both TLE-HS+ and TLE-HS- patients.

Proteomic changes in the hippocampus and motor cortex in a rat model of cerebral palsy: Effects of topical treatment.

Cerebral palsy (CP) is a non-progressive motor-impairment disorder related to brain injury early in development. To gain new insights into the mechanisms of CP and the therapeutic efficacy of Baimai ointment, we used a high-throughput quantitative proteomic approach to evaluate proteomic changes in the hippocampus and motor cortex in a rat model of CP induced by lipopolysaccharide (LPS) combined with hypoxia/ischemia (H/I). More than 2000 proteins were identified in each brain region with high confidence. Quantitative analysis demonstrated profound disturbances in the proteomes of the hippocampus and motor cortex after LPS + H/I, in addition to the disruption of the motor system. In contrast, the topical application of Baimai ointment not only alleviated the motor deficit in the CP model rats, but also restored the proteomes in the brain cortex. Furthermore, astrocytes in the hippocampus were strongly activated in the Baimai-treated CP rat brains, associated with an increase in neurotrophic factors. Proteomic analysis demonstrated that the CP model induced neuroinflammatory responses in the brain which were reversed by the topical application of Baimai ointment. This study highlights the unexpected roles of hippocampus and motor cortex neurons in CP progress and treatment, thus providing potentially novel therapeutic targets for CP.

Proteomic profiling of sclerotic hippocampus revealed dysregulated packaging of vesicular neurotransmitters in temporal lobe epilepsy.

PURPOSE: Temporal lobe epilepsy (TLE) is the most common type of epilepsy. Hippocampal sclerosis is the most distinctive pathological feature of TLE; however, its role in the pathogenesis of TLE remains to be clarified. We performed global protein expression analysis of hippocampus from TLE patients and controls, aiming to reveal the molecular signaling pathways related to TLE. METHOD: Proteomic and bioinformatic analyses of the hippocampus were performed on 4 TLE and 4 control samples. High-resolution liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in combination with TMT-6plex quantification, was applied for global protein expression analysis. The proteomics results were validated by Western blot with 25 TLE and 25 control individuals and Immunohistochemistry analysis with 33 TLE and 10 control individuals. RESULTS: Bioinformatics analysis demonstrated differentially expressed proteins in the synaptic vesicle pathway, the prostaglandin synthesis and regulation pathway and endocannabinoids and retrograde modulation of synaptic transmission pathway. Among these, excitatory amino acid transporter 1 (EAAT1) and Vesicular glutamate transporter 1 (VGLUT1) are critical for TLE and dysregulated expression might be closely related to the uptake of extracellular glutamate and contribute to the pathophysiology of TLE. Ras-related protein Rab-3A (RAB3A) downregulation might indicate the TLE-induced compensatory deficit in glutamate release. CONCLUSION: Our study indicates that expression of some proteins involved in the packaging of vesicular neurotransmitters is altered in TLE. In addition, upregulated expression of annexin family proteins, which are also related to TLE, might play an important role in protection against TLE.

A quantitative MRI index for assessing the severity of hippocampal sclerosis in temporal lobe epilepsy.

BACKGROUND: Hippocampal sclerosis (HS) is associated with post-surgery outcome in patients with temporal lobe epilepsy (TLE), and an automated method that quantifies HS severity is still lacking. Here, we aim to propose an MRI-based HS index (HSI) that integrates hippocampal volume and FLAIR signal to measure the severity of HS. METHODS: Forty-two pre-surgery TLE patients were included retrospectively, with T1-weighted (T1W) and FLAIR images acquired from each subject. Two experienced neurosurgeons (W.D. and C.S.) and one neurologist (Q.L.) rated HS severity with a four-class grading scale (normal, mild, moderate and severe) based on both hippocampal volume loss and increased FLAIR signal. A consensus of HS severity for each subject was made by voting among the three visual rating results. Regarding the automatic quantification, the hippocampal volume was quantified by AccuBrain on T1W image, and the FLAIR signal of hippocampus was calculated as the mean intensity of hippocampal region on the FLAIR image (normalized by the mean intensity of gray matter). To fit the HSI from visual rating, we applied ordinal regression with the voted visual rating as the dependent variable, and hippocampal volume and FLAIR signal as the independent variables. The HSI was calculated by weighting the predicted probabilities of the four-class grading scales from ordinal regression. RESULTS: The intra-class correlation coefficient (single measure) of the three raters was 0.806. The generated HSI was significantly correlated with the visual rating scales of the three raters (W.D.: 0.823, Q.L.: 0.817, C.S.: 0.717). HSI scores well differentiated the different HS categories as defined by the agreed HS visual rating (normal vs. mild: p < 0.001, mild vs. moderate: p < 0.001, moderate vs. severe: p = 0.001). CONCLUSIONS: The proposed HSI was consistent with visual rating scales from epileptologists and sensitive to HS severity. This MRI-based index may help to evaluate HS severity in clinical practice. Further validations are needed to associate HSI with post-surgery outcomes.

Comparison of seizure outcomes and safety between anterior temporal lobotomy and lobectomy in patients with temporal lobe epilepsy.

Objectives: To compare the efficacy and safety of anterior temporal lobotomy (ATLo) and anterior temporal lobectomy (ATLe) in drug-resistant temporal lobe epilepsy.Methods: Patients diagnosed with pharmacoresistant temporal lobe epilepsy who underwent anterior temporal lobotomy (ATLo) or anterior temporal lobectomy (ATLe) performed by a single surgeon were retrospectively included. Every patient was followed up annually after surgery. The postoperative seizure outcome evaluation was based on the Engel and ILAE classifications. We compared postoperative complications and 2-year follow-up seizure outcomes between the ATLo group and the ATL group.Results: A total of 42 individuals (21 ATLo and 20 ATLe) were included. At the two-year follow-up, more patients in the ATLo group than the ATLe group had reached Engel class I (20 versus 14) and ILAE I (19 versus 13). However, these differences were not significant. One patient in the ATLo group had intraparenchymal hematoma and fully recovered. The two groups had similar incidences of other short-term complications, and no patients died or had any permanent complications.Discussion: ATLo is not inferior to ATLe for patients with drug-resistant temporal epilepsy. There was no significant difference in seizure outcomes or the rate of postoperative complications between the two groups. A large sample randomized control study is needed.

Type IIB focal cortical dysplasia with balloon cells in medial temporal lobe epilepsy: Clinical, neuroimaging, and histopathological findings.

PURPOSE: Type IIB focal cortical dysplasia (FCD) is an important cause of drug-resistant epilepsy. However, balloon cells located in the medial temporal lobe have been seldom reported. We aimed to discuss the clinical and pathological features of Type IIB FCD with balloon cells in the medial temporal lobe (MTLE-FCDIIB) and the differential diagnosis with other types of mesial temporal lobe epilepsy. METHODS: Three MTLE-FCDIIB cases were enrolled from Peking Union Medical College Hospital. Clinical and neuroimaging data were analyzed and histology features observed on hematoxylin-eosin (H&E) staining and immunochemical staining, including vimentin, nestin, S-100, CD34, neuronal nuclei antigen (Neun), glial fibrillary acidic protein (GFAP), neurofilament heavy chain (SMI32), were discussed. RESULTS: All cases involved drug-resistant epilepsy patients with childhood onset. The semiology of the epileptic seizure was a highly frequent partial seizure with or without generalized tonic-clonic seizures. Magnetic resonance imaging showed hyper-intensity in the medial temporal lobe without atrophy, different from mesial temporal sclerosis. Histological examination indicated the presence of balloon cells in the white matter of the para-hippocampal gyrus, subiculum, and cornu ammonis with cortical disorganization, and SMI32 positive dysmorphic neurons in the gray matter. Balloon cells were immunohistochemically stained with vimentin and nestin. Granular cell dispersion and pyramidal cell loss were not found. CONCLUSIONS: The presence of balloon cells in the medial temporal lobe is observed in a rare subgroup of FCD, named MTLE-FCDIIB. It has distinct clinical manifestations, neuroimaging features, pathological changes, and prognosis, which should be differentiated from mesial temporal lobe sclerosis and mesial temporal lobe tumors. Our findings enable more accurate diagnosis of mesial temporal lobe epilepsy.

Study of the hippocampal internal architecture in temporal lobe epilepsy using 7 T and 3 T MRI.

PURPOSE: To compare the hippocampal internal architecture (HIA) between 3 and 7 Tesla (T) magnetic resonance imaging (MRI) in patients with temporal lobe epilepsy (TLE), and to investigate the relationship between HIA and hippocampal volume, and postoperative outcomes. MATERIALS AND METHODS: Thirty-nine TLE patients were recruited with 3 and 7 T MRI scans and a semi-quantitative assessment of the HIA was performed. Differences in HIA scores between 3 and 7 T MRI were evaluated. HIA and hippocampal volume asymmetry were also calculated and compared. The utility of HIA and hippocampal volume asymmetry in epilepsy lateralization, and the predictive value between these two indicators were compared. The relationship between HIA and postoperative outcomes was investigated in 25 patients with amygdalohippocampectomy. RESULTS: HIA scores of epileptogenic hippocampi were lower than those of non-epileptogenic hippocampi at 3 and 7 T MRI. Higher HIA scores were observed at 7 T MRI. The HIA asymmetry and hippocampal volume asymmetry were both strong predictors for epilepsy lateralization and did not show difference in predictive value. No statistical differences in HIA asymmetry were observed between seizure-free patients (ILAE 1) compared to patients with seizures (ILAE 2-5). CONCLUSIONS: Visualization of hippocampal internal architecture (HIA) may be improved at 7 T MRI. HIA asymmetry is a significant predictor of laterality of seizure onset in TLE patients and has similar predictive value as hippocampal volume asymmetry, however, HIA asymmetry at 7 T does not have extra value in determining epilepsy lateralization and neither does predict surgical outcomes.

The interactome and proteomic responses of ALKBH7 in cell lines by in-depth proteomics analysis.

BACKGROUND: ALKBH7 is a mitochondrial protein, involved in programmed necrosis, fatty acid metabolism, cell cycle regulation, and prostate cancer disease. However, the exact roles of ALKBH7 and the underlying molecular mechanisms remain mysterious. Thus, investigations of the interactome and proteomic responses of ALKBH7 in cell lines using proteomics strategies are urgently required. METHODS: In the present study, we investigated the interactome of ALKBH7 in mitochondria through immunoprecipitation-mass spectrometry/mass spectrometry (IP-MS/MS). Additionally, we established the ALKBH7 knockdown and overexpression cell lines and further identified the differentially expressed proteins (DEPs) in these cell lines by TMT-based MS/MS. Two DEPs (UQCRH and HMGN1) were validated by western blotting analysis. RESULTS: Through bioinformatic analysis the proteomics data, we found that ALKBH7 was involved in protein homeostasis and cellular immunity, as well as cell proliferation, lipid metabolism, and programmed necrosis by regulating the expression of PTMA, PTMS, UQCRH, HMGN1, and HMGN2. Knockdown of ALKBH7 resulted in upregulation of UQCRH and HMGN1 expression, and the opposite pattern of expression was detected in ALKBH7 overexpression cell lines; these results were consistent with our proteomics data. CONCLUSION: Our findings indicate that the expression of UQCRH and HMGN1 is regulated by ALKBH7, which provides potential directions for future studies of ALKBH7. Furthermore, our results also provide comprehensive insights into the molecular mechanisms and pathways associated with ALKBH7.

Pallidal Deep Brain Stimulation in Patients With Chorea-Acanthocytosis.

INTRODUCTION: Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disorder caused by the mutation of gene VPS13A. Deep brain stimulation of ChAc has made substantial progress in the recent decades. However, the reports were scattered across centers and performed by different neurosurgeons. Here, we report a case series consisting of six patients diagnosed with ChAc, receiving bilateral high-frequency stimulation of globus pallidus internus (GPi) in a single center. METHODS: We report six consecutive patients diagnosed with ChAc and present a review of the literature. All patients received neurological evaluations using the Unified Huntington's Disease Rating Scale (UHDRS) motor score before surgery and during clinical follow-ups. One patient was observed over six months, while five patients were seen over 12 months. RESULTS: All patients underwent high-frequency stimulation ranging from 130 Hz to 175 Hz. In the follow-up period, a general trend was found toward higher amplitude and broader pulse widths, with a mean current range of 2.08 mA to 3.06 mA and a mean pulse width range of 75 µsec to 98 µsec. On preoperative evaluation, the mean UHDRS motor score was 35.7 ± 16.3 and the chorea subscore was 11.3 ± 4.7. At the three-month postoperative follow-up, both UHDRS motor score (13.5 ± 5.8) and chorea subscore (3.0 ± 1.2) reached valley values. Thereafter, the UHDRS motor score and chorea subscore showed a gradual rise, reaching 19.2 ± 5.9 and 4.8 ± 1.7, respectively, at the 12-month follow-up. In addition, adverse events were also seen. Patient 1 developed dysarthria six months after surgery, whereas Patient 6 had a generalized tonic-clonic seizure attack one day after surgery CONCLUSION: High frequency stimulation of the GPi is an effective and safe modality for the treatment of ChAc, with both rapid symptomatic improvements and steady chronic outcomes.

Transcriptome profiling of the subventricular zone and dentate gyrus in an animal model of Parkinson's disease.

Adult neurogenesis in the subventricular zone (SVZ), as well as in the subgranular zone contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells within these two regions, while a DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not yet been fully characterized, particularly following DA depletion. In thi study, we performed RNA sequencing to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This analysis identified differentially expressed genes which were involved in the regulation of transcription, immune response, extracellular region, cell junction and myelination. These genes partially displayed different temporal profiles of expression, some of which may participate in the metabolic switch related to neurogenesis. Additionally, the mitogen­activated protein kinase (MAPK) signaling pathway was shown to be been positively regulated in the SVZ, while it was negatively affected in the DG following MPTP administration. Overall, our findings indicate that exposure to MPTP may exert different effects on transcriptome profiling between the SVZ and DG.

Subthalamic Nuclei Stimulation in Patients With Pantothenate Kinase-Associated Neurodegeneration (PKAN).

INTRODUCTION: Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive genetic disease that leads to extrapyramidal symptoms, such as dystonia, ataxia, dysarthria, and involuntary movements. Treatment of PKAN with deep brain stimulation (DBS) has been reported, but mainly focuses on targeting the globus pallidus internus (GPi). Subthalamic nuclei (STN) may also be a potential target for treatment of PKAN. METHODS: In this study, we reviewed three patients with PKAN (two with typical PKAN and one with atypical PKAN) treated by bilateral STN stimulation and present a review of the literature. All patients received neurological evaluation using the Burke-Fahn-Marsden Dystonia Rating Scale-movement (BFMDRS) scoring system before and after surgery. Patients were then subject to regular clinical follow-ups (ranging from 22 to 44 months). RESULTS: The mean stimulation amplitude, pulse width and frequency was 2.65 ± 0.45 V, 91.7 ± 21.9 µs, and 146.7 ± 12.5 Hz, respectively. BFMDRS scores were improved in all patients after surgery, ranging from 41.6 to 73.1%. Improvements of appendicular symptoms ranged from 46.2 to 94.1%, and improvements of axial symptoms ranged from 27.3 to 33.3%. No side effects were reported in patients 1 and 2; whereas patient 3 exhibited a mild decline in verbal fluency one year after surgery. CONCLUSION: STN stimulation could serve as a candidate DBS target in the treatment of PKAN, especially for patients with prominent appendicular symptoms.

Application of Preoperative CT/MRI Image Fusion in Target Positioning for Deep Brain Stimulation.

Objective To explore the efficacy of target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation.Methods We retrospectively analyzed the clinical data and images of 79 cases (68 with Parkinson's disease, 11 with dystonia) who received preoperative CT/MRI image fusion in target positioning of subthalamic nucleus in deep brain stimulation. Deviation of implanted electrodes from the target nucleus of each patient were measured. Neurological evaluations of each patient before and after the treatment were performed and compared. Complications of the positioning and treatment were recorded.Results The mean deviations of the electrodes implanted on X, Y, and Z axis were 0.5 mm, 0.6 mm, and 0.6 mm, respectively. Postoperative neurologic evaluations scores of unified Parkinson's disease rating scale (UPDRS) for Parkinson's disease and Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) for dystonia patients improved significantly compared to the preoperative scores (P<0.001); Complications occurred in 10.1% (8/79) patients, and main side effects were dysarthria and diplopia.Conclusion Target positioning by preoperative CT/MRI image fusion technique in deep brain stimulation has high accuracy and good clinical outcomes.

Quantitative protein profiling of hippocampus during human aging.

The hippocampus appears commonly affected by aging and various neurologic disorders in humans, whereas little is known about age-related change in overall protein expression in this brain structure. Using the 4-plex tandem mass tag labeling, we carried out a quantitative proteomic study of the hippocampus during normal aging using postmortem brains from Chinese subjects. Hippocampal samples from 16 subjects died of non-neurological/psychiatric diseases were divided into 4 age groups: 22-49, 50-69, 70-89, and >90. Among 4582 proteins analyzed, 35 proteins were significantly elevated, whereas 25 proteins were downregulated, along with increasing age. Several upregulated proteins, including transgelin, vimentin, myosin regulatory light polypeptide 9, and calcyphosin, were further verified by quantitative Western blot analysis of hippocampal tissues from additional normal subjects. Bioinformatic analysis showed that the upregulated and downregulated proteins were largely involved in several important protein-protein interaction networks. Proteins in the electron transport chain and synaptic vesicle fusion pathway were consistently downregulated with aging, whereas proteins associated with Alzheimer's disease showed little change. Our study demonstrates substantial protein profile changes in the human hippocampus during aging, which could be of relevance to age-related loss of hippocampal functions.

Schwannoma in Sellar Region Mimics Invasive Pituitary Macroadenoma: Literature Review With One Case Report.

In central nervous system, schwannomas, as ubiquitous tumors, mostly originate from sensory nerves like auditory and trigeminal nerves. However, intrasellar schwannomas are extremely rare. They are often misdiagnosed as pituitary adenomas. We report a rare case of schwannoma in the sellar region--a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological test. We represent a 65-year-old woman who had suffered from headaches, hypothyroidism, and visual disturbance. Her MRI revealed an abnormal sellar region mixed-signal mass lesion with suprasellar, left parasellar, and sellar floor invasiveness. We present detailed analysis of the patient's disease course and review relevant literatures. Written informed consent was obtained from the patient for publication of this article. A copy of the written consent is available for review by the editors of MEDICINE. Because this article does not involve any human or animal trials, there is no need to conduct special ethic review and the ethical approval is not necessary. When surgically treated, her specimen revealed a typical histopathology pattern of schwannoma. The patient's symptoms improved a lot after surgery and he continues to be under observation. Despite its rarity, intrasellar schwannoma should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas.

CD34 Over-Expression is Associated With Gliomas' Higher WHO Grade.

CD34 is a transmembrane phosphoglycoprotein that was first identified on hematopoietic stem and progenitor cells. CD34 is known as an optimum marker for microvascular density studies and it is positively stained in pathological and physiologic vessels. The use of CD34 for the prognosis, diagnosis, and treatment of neoplasms has been increasingly discussed. The implications and utilities of CD34 in WHO grades of gliomas and its prognosis have been reported rarely. Also, the WHO grades and prognosis researches remains unclear and controversial. A meta-analysis is the best choice for drawing a convincing conclusion. Several databases were searched. We carefully assess the relevant articles and standard mean differences (SMDs) with 95% confidence intervals (95% CIs) were estimated in terms of the relationship between CD34 expression levels with gliomas' WHO grades, patients' ages and gender. We used the Galbraith figure, the I test, and Cochran Q test to evaluate the heterogeneity of the included studies. A sensitivity analysis was conducted to assess the pooled results' stability. A Contour-enhanced funnel plot evaluation was made to assess potential publication bias. Ethics review and approval was not necessary because the meta-analysis did not involve any direct human trials or animal experiments. There were 12 eligible studies, including 684 patients who were considered in the present meta-analysis. All of them were conducted in China. CD34 overexpression in glioma tissues was associated closely, according to the pooled SMD, with higher WHO grade (III + IV) (SMD -1.503, 95% CI -1.685 to -1.321; P = 0.000). There were no significant associations between CD34 and age (SMD -0.223, 95% CI -0.602 to 0.156; P = 0.248) and CD34 and gender (SMD -0.059, 95% CI -0.439, 0.321; P = 0.761). No publication bias was detected according to Contour-enhanced funnel plot. Our results suggested that CD34 overexpression is associated with higher WHO grades of gliomas. CD34 may serve as a potential diagnostic and prognostic marker, or it could be a useful therapy target.

Does Tenascin have Clinical Implications in Pathological Grade of Glioma Patients?: A Systematic Meta-Analysis.

Tenascin (TN) is an extracellular oligomeric glycoprotein that participates in the adhesion of cells to extracellular matrixc (ECM). Studies have shown that the expression levels of TN are upregulated in a variety of cancers, including colon cancer, lung cancer, brain tumor, and breast cancer. However, the implications and utilities of TN in clinical grading and prognosis of glioma patients were seldom reported and the effects of its pathway are still unclear and controversial. Thus, it is essential to carry out a meta-analysis to draw a convincing conclusion.A literature search was carried out up to April 2015. Data was collected using a purpose-designed form including glioma's WHO grade, etc. Differences were expressed as odds ratios (ORs) or standard mean differences (SMDs) with 95% confidence intervals (CIs). Galbr figure, Cochran's Q test, and I test were all performed to judge the heterogeneity between included studies. To examine the stability of the pooled results, a sensitivity analysis was performed. Potential publication bias was assessed by visual inspection of funnel plot. As this meta-analysis, as a systematic review, does not involve animal experiments or direct human trials, there is no need to conduct special ethic review and the ethical approval is not necessary.In this meta-analysis, 8 eligible studies involving 456 patients were incorporated. Six studies with dichotomous data revealed TN overexpression in glioma tissues and/or surrounding neoplastic vessels was closely associated with high WHO grade (III + IV) (odds ratio 3.398, 95% confidence interval 1.933, 5.974; P = 0.000); three continuous data studies showed there were close statistical associations between TN and WHO grade (SMD -2.114, 95% CI -2.580, -1.649; P = 0.000) too. Sensitivity analysis indicated a statistically robust result. No publication bias was revealed.Our meta-analysis suggests that TN expression is potentially associated with higher WHO grade of gliomas. More evidences on the basis of the evidence-based medicine are needed to prove it.

Exome sequencing identifies SUCO mutations in mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is the main type and most common medically intractable form of epilepsy. Severity of disease-based stratified samples may help identify new disease-associated mutant genes. We analyzed mRNA expression profiles from patient hippocampal tissue. Three of the seven patients had severe mTLE with generalized-onset convulsions and consciousness loss that occurred over many years. We found that compared with other groups, patients with severe mTLE were classified into a distinct group. Whole-exome sequencing and Sanger sequencing validation in all seven patients identified three novel SUN domain-containing ossification factor (SUCO) mutations in severely affected patients. Furthermore, SUCO knock down significantly reduced dendritic length in vitro. Our results indicate that mTLE defects may affect neuronal development, and suggest that neurons have abnormal development due to lack of SUCO, which may be a generalized-onset epilepsy-related gene.