Comprehensive molecular characterization of long-term glioblastoma survivors.

Fewer than 5 % glioblastoma (GBM) patients survive over five years and are termed long-term survivors (LTS), yet their molecular background is unclear. The present cohort included 72 isocitrate dehydrogenase (IDH)-wildtype GBM patients, consisting of 35 LTS and 37 short-term survivors (STS), and we employed whole exome sequencing, RNA-seq and DNA methylation array to delineate this largest LTS cohort to date. Although LTS and STS demonstrated analogous clinical characters and classical GBM biomarkers, CASC5 (P = 0.002) and SPEN (P = 0.013) mutations were enriched in LTS, whereas gene-to-gene fusions were concentrated in STS (P = 0.007). Importantly, LTS exhibited higher tumor mutation burden (P < 0.001) and copy number (CN) increase (P = 0.013), but lower mutant-allele tumor heterogeneity score (P < 0.001) and CN decrease (P = 0.026). Additionally, LTS demonstrated hypermethylated genome (P < 0.001) relative to STS. Differentially expressed and methylated genes both enriched in olfactory transduction. Further, analysis of the tumor microenvironment revealed higher infiltration of M1 macrophages (P = 0.043), B cells (P = 0.016), class-switched memory B cells (P = 0.002), central memory CD4+ T cells (P = 0.031) and CD4+ Th1 cells (P = 0.005) in LTS. We also separately analyzed a subset of patients who were methylation class-defined GBM, contributing 70.8 % of the entire cohort, and obtained similar results relative to prior analyses. Finally, we demonstrated that LTS and STS could be distinguished using a subset of molecular features. Taken together, the present study delineated unique molecular attributes of LTS GBM.

Effect of high-field iMRI guided resection in cerebral glioma surgery: A randomized clinical trial.

BACKGROUND: Extent of resection (EOR) in glioma contributes to longer survival. The purpose of NCT01479686 was to prove whether intraoperative magnetic resonance imaging (iMRI) increases EOR in glioma surgery and benefit survival. METHODS: Patients were randomized (1:1) to receive the iMRI (n = 161) or the conventional neuronavigation (n = 160). The primary endpoint was gross total resection (GTR); secondary outcomes reported were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: 188 high-grade gliomas (HGGs) and 133 low-grade gliomas (LGGs) were enrolled. GTR was 83.85% in the iMRI group vs. 50.00% in the control group (P < 0.0001). In 321 patients, the median PFS (mPFS) was 65.12 months in the iMRI group and 61.01 months in the control group (P = 0.0202). For HGGs, mPFS was improved in the iMRI group (19.32 vs. 13.34 months, P = 0.0015), and a trend of superior OS compared with control was observed (29.73 vs. 25.33 months, P = 0.1233). In the predefined eloquent area HGG subgroup, mPFS, and mOS were 20.47 months and 33.58 months in the iMRI vs. 12.21 months and 21.16 months in the control group (P = 0.0098; P = 0.0375, respectively). From the exploratory analyses of HGGs, residual tumor volume (TV) < 1.0 cm3 decreased the risk of survival (mPFS: 18.99 vs. 9.43 months, P = 0.0055; mOS: 29.77 vs. 18.10 months, P = 0.0042). LGGs with preoperative (pre-OP) TV > 43.1 cm3 and postoperative (post-OP) TV > 4.6 cm3 showed worse OS (P= 0.0117) CONCLUSIONS: It showed that iMRI significantly increased EOR and indicated survival benefits for HGGs, particularly eloquent HGGs. Residual TV in either HGGs or LGGs is a prognostic factor for survival.

Development and validation of clinical-radiomics analysis for preoperative prediction of IDH mutation status and WHO grade in diffuse gliomas: a consecutive L-[methyl-11C] methionine cohort study with two PET scanners.

PURPOSE: Determination of isocitrate dehydrogenase (IDH) genotype is crucial in the stratification of diagnosis and prognostication in diffuse gliomas. We sought to build and validate radiomics models and clinical features incorporated nomogram for preoperative prediction of IDH mutation status and WHO grade of diffuse gliomas with L-[methyl-11C] methionine ([11C]MET) PET/CT imaging according to the 2016 WHO classification of tumors of the central nervous system. METHODS: Consecutive 178 preoperative [11C]MET PET/CT images were retrospectively studied for radiomics analysis. One hundred six patients from PET scanner 1 were used as training dataset, and 72 patients from PET scanner 2 were used for validation dataset. [11C]MET PET and integrated CT radiomics features were extracted, respectively; three independent predictive models were built based on PET features, CT features, and combined PET/CT features, respectively. The SelectKBest method, Spearman correlation analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and machine learning algorithms were applied for feature selection and model building. After filtering the satisfactory predictive model, key clinical features were incorporated for the nomogram establishment. RESULTS: The combined [11C]MET PET/CT radiomics model, which consisted of four PET features and eight integrated CT features, was significantly associated with IDH genotype (p < 0.0001 for both training and validation datasets). Nomogram based on the [11C]MET PET/CT radiomics score, patients' age, and dichotomous tumor location status showed satisfactory discrimination capacity, and the AUC was 0.880 (95% CI, 0.726-0.998) in the training dataset and 0.866 (95% CI, 0.777-0.956) in the validation dataset. In IDH stratified WHO grade prediction, the final radiomics model consists of four PET features and two CT features had reasonable and stable differential efficacy of WHO grade II and III patients from grade IV patients in IDH-wildtype patients, and the AUC was 0.820 (95% CI, 0.541-1.000) in the training dataset and 0.766 (95% CI, 0.612-0.921) in the validation dataset. CONCLUSION: [11C]MET PET radiomics features could benefit non-invasive IDH genotype prediction, and integrated CT radiomics features could enhance the efficacy. Radiomics and clinical features incorporation could establish satisfactory nomogram for clinical application. This non-invasive predictive investigation based on our consecutive cohort from two PET scanners could provide the perspective to observe the differential efficacy and the stability of radiomics-based investigation in untreated diffuse gliomas.

Distinct aneuploid evolution of astrocytoma and glioblastoma during recurrence.

Astrocytoma and glioblastoma (GB) are reclassified subtypes of adult diffuse gliomas based on distinct isocitrate dehydrogenase (IDH) mutation in the fifth edition of the WHO Classification of Tumors of the Central Nervous System. The recurrence of gliomas is a common and inevitable challenge, and analyzing the distinct genomic alterations in astrocytoma and GB could provide insights into their progression. This study conducted a longitudinal investigation, utilizing whole-exome sequencing, on 65 paired primary/recurrent gliomas. It examined chromosome arm aneuploidies, copy number variations (CNVs) of cancer-related genes and pathway enrichments during the relapse. The veracity of these findings was verified through the integration of our data with multiple public resources and by corroborative immunohistochemistry (IHC). The results revealed a greater prevalence of aneuploidy changes and acquired CNVs in recurrent lower grade astrocytoma than in relapsed grade 4 astrocytoma and GB. Larger aneuploidy changes were predictive of an unfavorable prognosis in lower grade astrocytoma (P < 0.05). Further, patients with acquired gains of 1q, 6p or loss of 13q at recurrence had a shorter overall survival in lower grade astrocytoma (P < 0.05); however, these prognostic effects were confined in grade 4 astrocytoma and GB. Moreover, acquired gains of 12 genes (including VEGFA) on 6p during relapse were associated with unfavorable prognosis for lower grade astrocytoma patients. Notably, elevated VEGFA expression during recurrence corresponded to poorer survival, validated through IHC and CGGA data. To summarize, these findings offer valuable insights into the progression of gliomas and have implications for guiding therapeutic approaches during recurrence.

Evidence-based expert consensus on the management of primary central nervous system lymphoma in China.

Primary central nervous system lymphoma (PCNSL) is a type of central nervous system restricted non-Hodgkin lymphoma, whose histopathological diagnosis is majorly large B cell lymphoma. To provide specific, evidence-based recommendations for medical professionals and to promote more standardized, effective and safe treatment for patients with PCNSL, a panel of experts from the Chinese Neurosurgical Society of the Chinese Medical Association and the Society of Hematological Malignancies of the Chinese Anti-Cancer Association jointly developed an evidence-based consensus. After comprehensively searching literature and conducting systematic reviews, two rounds of Delphi were conducted to reach consensus on the recommendations as follows: The histopathological specimens of PCNSL patients should be obtained as safely and comprehensively as possible by multimodal tomography-guided biopsy or minimally invasive surgery. Corticosteroids should be withdrawn from, or not be administered to, patients with suspected PCNSL before biopsy if the patient's status permits. MRI (enhanced and DWI) should be performed for diagnosing and evaluating PCNSL patients where whole-body PET-CT be used at necessary time points. Mini-mental status examination can be used to assess cognitive function in the clinical management. Newly diagnosed PCNSL patients should be treated with combined high-dose methotrexate-based regimen and can be treated with a rituximab-inclusive regimen at induction therapy. Autologous stem cell transplantation can be used as a consolidation therapy. Refractory or relapsed PCNSL patients can be treated with ibrutinib with or without high-dose chemotherapy as re-induction therapy. Stereotactic radiosurgery can be used for PCNSL patients with a limited recurrent lesion who were refractory to chemotherapy and have previously received whole-brain radiotherapy. Patients with suspected primary vitreoretinal lymphoma (PVRL) should be diagnosed by vitreous biopsy. PVRL or PCNSL patients with concurrent VRL can be treated with combined systemic and local therapy.

Tumor treating fields: a comprehensive overview of the underlying molecular mechanism.

INTRODUCTION: As a novel treatment modality, tumor treating fields (TTFields) exert low-intensity, medium-frequency electric fields on tumor cells. TTFields' effectiveness and safety have been demonstrated clinically and in the real world for treating glioblastoma, the most common and aggressive primary central nervous system tumor. TTFields therapy has also been approved for the management of malignant mesothelioma, and clinical trials are ongoing for NSCLC, gastric cancer, pancreatic cancer, and other solid tumors. AREAS COVERED: This article comprehensively reviews the currently described evidence of TTFields' mechanism of action. TTFields' most evident therapeutic effect is to induce cell death by disrupting mitosis. Moreover, evidence suggests at additional mechanistic complexity, such as delayed DNA repair and heightened DNA replication stress, reversible increase in cell membrane and blood-brain barrier permeability, induction of immune response, and so on. EXPERT OPINION: TTFields therapy has been arising as the fourth anti-tumor treatment besides surgery, radiotherapy, and antineoplastic agents in recent years. However, the precise molecular mechanisms underlying the effects of TTFields are not fully understood and some concepts remain controversial. An in-depth understanding of TTFields' effects on tumor cell and tumor microenvironment would be crucial for informing research aimed at further optimizing TTFields' efficacy and developing new combination therapies for clinical applications.

UCP2 silencing in glioblastoma reduces cell proliferation and invasiveness by inhibiting p38 MAPK pathway.

Uncoupling protein-2 (UCP2) is a mitochondrial inner membrane anion carrier and is emerging as a negative regulator of ROS production. Overexpression of UCP2 has been detected in various tumors, but its role in glioblastoma remains unclear. Using tissue microarrays and interrogations of public databases, we explored that the expression of UCP2 is upregulated in glioma, especially in GBM, and overexpression of UCP2 correlates with poor prognosis in glioma patients. To further reveal the role of UCP2 in glioma, UCP2-slienced cell lines (U251, U87MG and A172) by lentivirus were constructed to study how silenced UCP2 expression affects cellular functions in vitro, and tumorigenicity in vivo. RNA-Seq based genome and pathway analysis were performed to elucidate the underlying mechanisms of action of UCP2. Our results revealed that UCP2 silenced glioma cells show inhibited migration, invasiveness, clonogenicity, proliferation, promoted cell apoptosis in vitro, and weaker tumorigenicity in nude mice. Transcriptome analysis suggested a UCP2-dependent regulation of p38 MAPK (Mitogen-activated protein kinase) signaling networks, which was further validated by qRT-PCR and Western blot. Our research provides a new insight into the biological significance of UCP2 in glioma and its potential application in treatment and diagnosis.

Combination of Magnetic Resonance Spectroscopy and ¹¹C-Methionine Positron Emission Tomography for the Accurate Diagnosis of Non-Enhancing Supratentorial Glioma.

OBJECTIVE: To evaluate whether the combination of magnetic resonance spectroscopy (MRS) and ¹¹C-methionine positron emission tomography (¹¹C-MET PET) could increase accurate diagnostic sensitivity for non-enhancing supratentorial gliomas. MATERIALS AND METHODS: Between February 2012 and December 2017, 109 patients with non-enhanced supratentorial lesions on contrast-enhanced MRI were enrolled. Each patient underwent MRS and ¹¹C-MET PET before treatment. A lesion was considered to be a glioma when either the MRS or ¹¹C-MET PET results reached the diagnostic threshold. The radiological diagnosis was compared with the pathological diagnosis or medical diagnostic criteria. RESULTS: The sensitivity and specificity were 60.0% and 50.0% for MRS and 75.8% and 50.0% for ¹¹C-MET PET, respectively. Upon combining the two modalities, the sensitivity and specificity of the imaging-based diagnosis prior to surgery reached 89.5% and 42.9%, respectively. Statistically significant differences in the sensitivities were observed between the combined and individual approaches (MRS alone, 89.5% vs. 60.0%, p < 0.001; ¹¹C-MET PET alone, 89.5% vs. 75.8%, p = 0.001). However, no significant differences in specificity were observed between the combined and individual modalities. CONCLUSION: The combination of MRS and ¹¹C-MET PET findings significantly increases accurate diagnostic sensitivity for non-enhancing supratentorial gliomas without significantly lowering the specificity. This finding suggests the potential of the combined MRS and ¹¹C-MET PET approach in clinical applications.

The role of ABCB1 polymorphism as a prognostic marker for primary central nervous system lymphoma.

To investigate the possible role of functional single nucleotide polymorphism (SNP) in circadian genes as prognostic markers of primary central nervous system lymphoma (PCNSL). We conducted a prospective study using data from Huashan Hospital 2006-2015 and followed up 91 PCNSL patients until June 30, 2016. The survival of patients with different prognostic factors was compared by log-rank test. Univariate and multivariate analyses were performed by Cox regression. During a long-term follow-up (6-110 months), overall survival (OS) was 32 months (95% CI, 13.3-91.1) and progression-free survival (PFS) was 23 months (95% CI, 9.0-41.0) for the entire cohort. Age (P = 0.046, P = 0.001) and performance status (PS) score (P = 0.013, P = 0.003) showed differences in OS and PFS. ABCB1 rs1045642 variant showed significant difference in PFS between patients with CC genotype and those with CT/TT genotypes (P = 0.020). In multivariate analysis, age (HR = 2.3; 95% CI, 1.2-4.2, P = 0.008), PS (HR = 2.4; 95% CI, 1.3-4.4, P = 0.007), and ABCB1 rs1045642 (HR = 1.9; 95% CI, 1.0-3.3, P = 0.036) were the independent risk factors for PFS. In our results, the most important prognostic factors associated with higher risk of progression were ABCB1 rs1045642 CC genotype, PS > 2, and older age.

The Analysis of Risk Factors and Survival Outcome for Chinese Patients with Epilepsy with High-Grade Glioma.

OBJECTIVE: To evaluate the risk factors of tumor-related epilepsy (TRE) and the relationship between TRE and functional/survival outcomes in patients with high-grade glioma (HGG). METHODS: The clinical data of 587 patients with HGG were retrospectively analyzed. A χ2 test and logistic multiple-regression analysis were used to analyze factors associated with TRE. Logistic and Cox regression were used to analyze factors that may influence functional and survival outcomes. RESULTS: Glioma location in temporal (odds ratio [OR], 0.439; P = 0.04) and parietal lobes (OR, 0.092; P = 0.02) were independent protective factors of preoperative epilepsy, compared with gliomas of frontal lobe. Preoperative epilepsy (OR, 9.290; P < 0.001) and dominant hemispheric location (OR, 2.616; P = 0.04) were independent risk factors of postoperative epilepsy. On univariate analysis, patients with preoperative epilepsy had longer progression-free survival (PFS) (P = 0.001) and overall survival (OS) (P < 0.001). Multivariate analysis further confirmed that preoperative epilepsy was an independent protective factor of OS (hazard ratio, 0.587; P = 0.008). CONCLUSIONS: In patients with HGG, preoperative epilepsy is significantly associated with tumor involvement of the frontal lobe, whereas postoperative epilepsy is associated with preoperative epilepsy and dominant hemispheric location. Also, patients with HGG with preoperative epilepsy have better PFS and OS.

3D-ASL perfusion correlates with VEGF expression and overall survival in glioma patients: Comparison of quantitative perfusion and pathology on accurate spatial location-matched basis.

BACKGROUND: There is a need for an imaging-based tool for measuring vascular endothelial growth factor (VEGF) expression and overall survival (OS) in patients with glioma. PURPOSE: To assess the correlation between cerebral blood flow (CBF), measured by 3D pseudo-continuous arterial spin-labeling (3D-ASL), and VEGF expression in gliomas on the basis of coregistered localized biopsy, and investigate whether CBF correlated with survival month (SM) in glioma patients. STUDY TYPE: Prospective cohort. SUBJECTS: Thirty-seven patients with gliomas from whom 63 biopsy specimens were obtained. SEQUENCE: 3D-ASL acquired with a 3.0T MR unit. ASSESSMENT: Biopsy specimens were grouped as high-grade (HGG) or low-grade glioma (LGG). CBF measurements were spatially matched with VEGF expression by coregistered localized biopsies, and the CBF value was correlated with quantitative VEGF expression for each specimen. Patients' survival information was derived and connected with CBF. STATISTICAL TESTS: Patients' OS was analyzed by Kaplan-Meier and Cox-regression methods. VEGF expression and CBF were compared in both LGG and HGG. The Spearman rank correlation was calculated for CBF and VEGF expression, SM. Significance level, P < 0.05. RESULTS: CBF-derived 3D-ASL positively correlated significantly with VEGF expression in both LGG (31 specimens) and HGG (32 specimens), r = 0.604 (P < 0.001) and r = 0.665 (P < 0.001), respectively. LGG and HGG together gave a correlation coefficient r = 0.728 (P < 0.001). Median survival for LGG and HGG patients was 34.19 and 17.17 months, respectively (P = 0.037); CBF value negatively correlated significantly with SM with r = -0.714 (P < 0.001) regardless of glioma grade. CBF was an independent risk factor for OS with HR = 1.027 (P = 0.044), 1.028 (P = 0.010) for univariate/multivariate regression analysis. DATA CONCLUSION: CBF determined by 3D-ASL correlates with VEGF expression in glioma and is an independent risk factor for OS in these patients. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:209-220.

The Relationship Between IDH1 Mutation Status and Metabolic Imaging in Nonenhancing Supratentorial Diffuse Gliomas: A 11C-MET PET Study.

PURPOSE: We evaluated the relationship between isocitrate dehydrogenase 1 (IDH1) mutation status and metabolic imaging in patients with nonenhancing supratentorial diffuse gliomas using 11C-methionine positron emission tomography (11C-MET PET). MATERIALS AND METHODS: Between June 2012 and November 2017, we enrolled 86 (38 women and 48 men; mean age, 41.9 ± 13.1 years [range, 8-67 years]) patients with newly diagnosed supratentorial diffuse gliomas. All patients underwent preoperative 11C-MET PET. Tumor samples were obtained and immunohistochemically analyzed for IDH1 mutation status. RESULTS: The mutant and wild-type IDH1 diffuse gliomas had significantly different mean maximum standardized uptake value values (2.73 [95% confidence interval, CI: 2.32-3.16] vs 3.85 [95% CI: 3.22-4.51], respectively; P = .004) and mean tumor-to-background ratio (1.90 [95% CI: 1.65-2.16] vs 2.59 [95% CI: 2.17-3.04], respectively; P = .007). CONCLUSIONS: 11C-methionine PET can noninvasively evaluate the IDH1 mutation status of patients with nonenhancing supratentorial diffuse gliomas.

Transcortical insular glioma resection: clinical outcome and predictors.

OBJECTIVE: Insular lobe gliomas continue to challenge neurosurgeons due to their complex anatomical position. Transcortical and transsylvian corridors remain the primary approaches for reaching the insula, but the adoption of one technique over the other remains controversial. The authors analyzed the transcortical approach of resecting insular gliomas in the context of patient tumor location based on the Berger-Sinai classification, achievable extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome. METHODS: The authors studied 255 consecutive cases of insular gliomas that underwent transcortical tumor resection in their division. Tumor molecular pathology, location, EOR, postoperative neurological outcome for each insular zone, and the accompanying OS were incorporated into the analysis to determine the value of this surgical approach. RESULTS: Lower-grade insular gliomas (LGGs) were more prevalent (63.14%). Regarding location, giant tumors (involving all insular zones) were most prevalent (58.82%) followed by zone I+IV (anterior) tumors (20.39%). In LGGs, tumor location was an independent predictor of survival (p = 0.003), with giant tumors demonstrating shortest patient survival (p = 0.003). Isocitrate dehydrogenase 1 (IDH1) mutation was more likely to be associated with giant tumors (p < 0.001) than focal tumors located in a regional zone. EOR correlated with survival in both LGG (p = 0.001) and higher-grade glioma (HGG) patients (p = 0.008). The highest EORs were achieved in anterior-zone LGGs (p = 0.024). In terms of developing postoperative neurological deficits, patients with giant tumors were more susceptible (p = 0.038). Postoperative transient neurological deficit was recorded in 12.79%, and permanent deficit in 15.70% of patients. Patients who developed either transient or permanent postsurgical neurological deficits exhibited poorer survival (p < 0.001). CONCLUSIONS: The transcortical surgical approach can achieve maximal tumor resection in all insular zones. In addition, the incorporation of adjunct technologies such as multimodal brain imaging and mapping of cortical and subcortical eloquent brain regions into the transcortical approach favors postoperative neurological outcomes, and prolongs patient survival.

Intraoperative awake brain mapping and multimodal image-guided resection of dominant side insular glioma.

Resection of insular tumors in the dominant hemisphere poses a significant risk of postoperative motor and language deficits. The authors present a case in which intraoperative awake mapping and multi-modal imaging was used to help preserve function while resecting a dominant insular glioma. The patient, a 55-year-old man, came to the clinic after experiencing sudden onset of numbness in the right limbs for 4 months. Preoperative MRI revealed a nonenhancing lesion in the left insular lobe. Gross-total tumor resection was achieved through the transcortical approach, and the patient recovered without language or motor deficits. Informed patient consent was obtained. The video can be found here: https://youtu.be/gFky09ekmzw .

Long-Term Functional and Oncologic Outcomes of Glioma Surgery with and without Intraoperative Neurophysiologic Monitoring: A Retrospective Cohort Study in a Single Center.

OBJECTIVE: To evaluate long-term functional and survival outcomes of patients with glioma after intraoperative neurophysiologic monitoring (IONM) application. METHODS: A total of 856 patients with glioma, who underwent tumor resection between October 2010 and March 2016, were included in this retrospective cohort study. All patients were stratified into IONM (439 patients) and non-IONM groups (417 patients). The primary outcome measured was overall survival (OS), and the secondary outcome measured was rate of late neurologic deficits. Analyses were performed using univariate tests and multivariate logistic regression and Cox proportional hazard model. RESULTS: The 2 cohorts were well balanced with respect to baseline characteristics. Univariate survival analysis showed longer OS in the IONM group than that in the non-IONM group (P = 0.036), especially in patients with high-grade astrocytic tumor (P = 0.034). The IONM group showed a lower rate of neurologic deficits than did the non-IONM group. Multivariate analysis showed that IONM was a favorable factor of OS (odds ratio, 0.776; P = 0.046) and late neurologic function (odds ratio, 0.583; P = 0.039). Dominant hemispheric and eloquent location of glioma had no association with OS. CONCLUSIONS: Application of IONM is beneficial to long-term functional and oncologic outcomes of patients with glioma.

Reorganization of cerebro-cerebellar circuit in patients with left hemispheric gliomas involving language network: A combined structural and resting-state functional MRI study.

The role of cerebellum and cerebro-cerebellar system in neural plasticity induced by cerebral gliomas involving language network has long been ignored. Moreover, whether or not the process of reorganization is different in glioma patients with different growth kinetics remains largely unknown. To address this issue, we utilized preoperative structural and resting-state functional MRI data of 78 patients with left cerebral gliomas involving language network areas, including 46 patients with low-grade glioma (LGG, WHO grade II), 32 with high-grade glioma (HGG, WHO grade III/IV), and 44 healthy controls. Spontaneous brain activity, resting-state functional connectivity and gray matter volume alterations of the cerebellum were examined. We found that both LGG and HGG patients exhibited bidirectional alteration of brain activity in language-related cerebellar areas. Brain activity in areas with increased alteration was significantly correlated with the language and MMSE scores. Structurally, LGG patients exhibited greater gray matter volume in regions with increased brain activity, suggesting a structure-function coupled alteration in cerebellum. Furthermore, we observed that cerebellar regions with decreased brain activity exhibited increased functional connectivity with contralesional cerebro-cerebellar system in LGG patients. Together, our findings provide empirical evidence for a vital role of cerebellum and cerebro-cerebellar circuit in neural plasticity following lesional damage to cerebral language network. Moreover, we highlight the possible different reorganizational mechanisms of brain functional connectivity underlying different levels of behavioral impairments in LGG and HGG patients.

Perioperative Multimodal Evaluation and Surgical Tactics of Tumor-Related Epilepsy: 2-Dimensional Operative Video.

Treatment of tumor-related epilepsy (TRE), especially for tumors near critical areas, requires surgeons to strike a balance between the epileptic benefit and functional outcome after surgery. Here, we present a case in which multimodal evaluation facilitated the achievement of such surgical balance. Informed patient consent was obtained. A 17-yr-old female presented with seizure attacks for 2 yr. Magnetic resonance imaging (MRI) revealed a right parietal mass lesion with hypointense signal on T1W imaging, hyperintense signal on T2W imaging, and homogeneous enhancement. Carbamazepine and valproate administration were unable to control the intermittent seizures. From the patient's history and imaging, the initial diagnosis was refractory TRE. Whether lesionectomy would achieve seizure freedom in this case was not certain. Therefore, dESI (dense array EEG source imaging) was used to localize the epileptic zone preoperatively; results showed that the epileptic zone was very close to the lesion in the primary motor cortex. Surgery was carried out under awake-anesthesia, with the aid of multimodal neuronavigation, intraoperative neurophysiological monitoring, and intraoperative MRI evaluation. A gross total lesion resection was achieved while preserving critical motor areas. Histopathology revealed ganglioglioma grade I diagnosis. No motor deficits following surgery were detected except slight increase of muscle tension in the right lower limb. At 6-mo follow-up, the patient was without any motor impairment or any other neurological deficits and completely seizure-free with the antiepileptic drug Carbamazepine 1200 mg/day.

Intraoperative Multi-Information-Guided Resection of Dominant-Sided Insular Gliomas in a 3-T Intraoperative Magnetic Resonance Imaging Integrated Neurosurgical Suite.

OBJECTIVE: To evaluate the clinical application of 3-T intraoperative magnetic resonance imaging (iMRI), awake craniotomy, multimodal functional mapping, and intraoperative neurophysiologic monitoring (IONM) for resection of dominant-sided insular gliomas. METHODS: From March 2011 to June 2013, 30 gliomas involving the dominant insular lobe were resected in the IMRIS 3.0-T iMRI integrated neurosurgical suite. For 20 patients, awake craniotomy with cortical electrical stimulation mapping was performed to locate the language areas. For 10 patients who were not suitable for awake surgery, general anesthesia and functional navigation were performed. Diffusion tensor imaging tractography-based navigation, continuous motor evoked potential monitoring, and subcortical electrical stimulation mapping were applied to localize and monitor the motor pathway in all cases. iMRI was used to assess the extent of resection. The results of intraoperative imaging, IONM, and the surgical consequences were analyzed. RESULTS: Intraoperative imaging revealed residual tumor in 26 cases and led to further resection in 9 cases. As a result, the median extent of resection was increased from 90% to 93% (P = 0.008) in all cases, and from 88% to 92% (P = 0.018) in low-grade gliomas. The use of iMRI also resulted in an increase in the percentage of gross and near total resection from 53% to 77% (P = 0.016). The rates of permanent language and motor deficits resulting from tumor removal were 11% and 7.1%, respectively. CONCLUSIONS: The combination of iMRI, awake craniotomy, multimodal brain mapping, and IONM tailored for each patient permits the maximal safe resection of dominant-sided insular glioma.