Within and beyond the visual cortex: brain tumors induce highly sensitive plasticity of visual processing in whole-brain neural functional networks.

Vision is a key source of information input for humans, which involves various cognitive functions and a great range of neural networks inside and beyond the visual cortex. There has been increasing observation that the cognitive outcomes after a brain lesion cannot be well predicted by the attributes of the lesion itself but are influenced by the functional network plasticity. However, the mechanisms of impaired or preserved visual cognition have not been probed from direct function-execution conditions and few works have observed it on whole-brain dynamic networks. We used high-resolution electroencephalogram recordings from 25 patients with brain tumors to track the dynamical patterns of functional reorganization in visual processing tasks with multilevel complexity. By comparing with 24 healthy controls, increased cortical responsiveness as functional compensation was identified in the early phase of processing, which was highly localized to the visual cortex and functional networks and less relevant to the tumor position. Besides, a spreading wide enhancement in whole-brain functional connectivity was elicited by the visual word-recognition task. Enhanced early rapid-onset cortical compensation in the local functional networks may contribute to largely preserved basic vision functions, and higher-cognitive tasks are vulnerable to impairment but with high sensitivity of functional plasticity being elicited.

Germline ALK variations are associated with a poor prognosis in glioma and IDH-wildtype glioblastoma.

BACKGROUND: Glioma is the most common primary brain tumor. Clear classification is crucial for accurate diagnosis and individualized treatment. Histopathological characteristics and genetic alterations have shown to be related to prognosis and treatment response. Germline variants are important components of genetic alterations. However, the distribution of germline variations in glioma patients and their association with survival remain unknown. METHODS: We carried out whole-exome sequencing on 99 cases to explore germline variants in glioma. We also analyzed the association of germline variants with clinicopathological features and other prognostic indicators. RESULTS: All the glioma cases harbored rare germline variants. Germline ALK variants (gALK-Mut) were identified in 12/99 (12.12%) patients. The gALK-Mut patients had significantly shorter overall survival than germline ALK wildtype (gALK-WT) patients in the all glioma group (99 cases) and the subset of patients with IDH-wildtype glioblastoma (IDH-WT-GBM, 39 cases) (P = 0.013 and 0.027, respectively). The gALK-Mut patients also had higher frequency of BIRC5, PIK3CA and RPN1 somatic mutations than the gALK-WT patients in IDH-WT-GBM. Other confounding factors appeared to contribute to patient survival. The subgroup of patients in IDH-WT-GBM with gALK-Mut/TP53-Mut had worse prognosis than the gALK-WT/TP53-Mut subgroup (P = 0.031); The gALK-Mut/TERT-WT and gALK-Mut/TERT-Mut subgroups both had a worse prognosis than the gALK-WT/TERT-Mut subgroup (P = 0.031 and 0.018, respectively). CONCLUSIONS: Our study revealed ALK variation was an independent indicator of poor prognosis in glioma and IDH-WT-GBM. It could be a promising biomarker and tractable therapeutic target for this deadly disease.

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.

Diagnosis and surgical treatment of non-lesional temporal lobe epilepsy with unilateral amygdala enlargement.

OBJECTIVE: Exploring the role of amygdala enlargement (AE) in temporal lobe epilepsy (TLE) without ipsilateral mesial temporal sclerosis (MTS) using comprehensive presurgical workup tools including traditional tools, automatically volumetric analysis, high-density EEG (HD-EEG) source imaging (HD-ESI), and stereoelectroencephalography (SEEG). METHODS: Nine patients diagnosed with TLE-AE who underwent resective surgeries encompassing the amygdala were retrospectively studied. HD-ESI was obtained using 256-channel HD-EEG on the individualized head model. For automatic volumetric analysis, 48 matched controls were enrolled. Diagnosis and surgical strategies were based on a comprehensive workup following the anatomo-electro-clinical principle. RESULTS: At post-operative follow-up (average 30.9 months), eight patients had achieved Engel class I and one Engel class II recovery. HD-ESI yielded unifocal source estimates in anterior mesial temporal region in 85.7% of cases. Automatic volumetric analysis showed the AE sides were consistent with the values determined through other preoperative workup tools. Furthermore, the amygdala volume of the affected sides in AE was significantly greater than that of the larger sides in controls (p < 0.001). Meanwhile, the amygdala volume lateral index (LI) of AE was significantly higher than in controls (p < 0.001). SEEG analysis showed that ictal onsets arose from the enlarged amygdala (and hippocampus) in all cases. CONCLUSION: In addition to traditional workup tools, automatic volumetric analysis, HD-ESI on individualized head model, and invasive SEEG can provide evidence of epileptogenicity in TLE-AE. Resective surgical strategies encompassing the amygdala result in better prognosis. In suspected TLE cases, more attention should be focused on detecting enlargement of amygdala which sometimes is "hidden" in "MR-negative" non-MTS cases.

Alternate accesses for transcatheter aortic valve replacement: A network meta-analysis.

BACKGROUND: When transfemoral (TF) access is contraindicated in patients undergoing transcatheter aortic valve replacement (TAVR), alternate access strategies are considered. The choice of one alternate access over the other remains controversial. METHODS: Following a comprehensive literature search, studies comparing any combination of TF, transapical (TA), transaortic (TAo), transcarotid (TC), and trans-subclavian (TS) TAVR were identified. Data were pooled using fixed- and random-effects network meta-analysis. Rank scores with probability ranks of different treatment groups were calculated. RESULTS: Eighty-four studies (26,449 patients) were included. Compared to TF access, TA and TAo accesses were associated with higher 30-day mortality (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.31-1.94; OR 1.79, 95% CI 1.21-2.66, respectively), while the TC and TS showed no difference (OR 1.12, 95% CI 0.64-1.95; OR 1.23, 95% CI 0.67-2.27, respectively); TF access ranked best followed by TC. There was no significant difference in 30-day stroke; TC access ranked best followed by TS. At a weighted mean follow-up of 1.6 years, TA and TAo accesses were associated with higher long-term mortality versus TF (incidence rate ratio [IRR] 1.31, 95% CI 1.18-1.45; IRR 1.41, 95% CI 1.11-1.79, respectively); there was no difference between TC and TS versus TF access (IRR 1.02, 95% CI 0.70-1.47; IRR 1.16, 95% CI 0.82-1.66, respectively); TF access ranked best followed by TC. At a weighted mean follow-up of 1.4 years, only TA access was associated with higher long-term stroke compared to TF (IRR 3.01, 95% CI 1.15-7.87); TF access ranked as the best strategy followed by TAo. CONCLUSION: TC and TS approaches are associated with superior postoperative outcomes compared to other TAVR alternate access strategies. Randomized trials definitively assessing the safety and efficacy of alternate access strategies are needed.

Impact of a pandemic on surgical neuro-oncology-maintaining functionality in the early phase of crisis.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has extraordinarily impacted global healthcare. Neuro-oncological surgery units have peculiar features that make them highly relevant in the strategic reaction to the pandemic. In this Chinese Society of Neuro-Oncology (CSNO) initiated survey, we appraise the changes implemented in neuro-oncological surgery hospitals across different Asian countries and provide expert recommendations for responses at different stages of the pandemic. METHODS: We performed a 42-question survey of the early experience of neuro-oncological surgery practice in hospitals across different Asian countries on April 1, 2020, with responses closed on April 18, 2020. RESULTS: 144 hospitals completed the questionnaire. Most were in WHO post-peak phase of the pandemic and reported a median reduction in neuro-oncological surgery volume of 25-50%. Most (67.4%) resumed elective surgery in only COVID-19 negative patients;11.1% performed only emergency cases irrespective of COVID-19 status;2.1% suspended all surgical activity. Ninety-one (63.2%) relocated personnel from neurosurgery to other departments. Fifty-two (36.1%) hospitals suspended post-operative adjuvant therapy and 94 (65.2%) instituted different measures to administer post-operative adjuvant therapy. Majority (59.0%) of the hospitals suspended research activity. Most (70%) respondents anticipate that current neurosurgery restrictions will continue to remain for > 1 month. CONCLUSIONS: Majority of the respondents to our survey reported reduced neuro-oncological surgery activity, policy modification, personnel reallocation, and curtailment of educational/research activities in response to the COVID-19 pandemic. The persistent widespread interruption of surgical neuro-oncology in even post-peak phases of the pandemic raises serious concerns about the long-term impact of the pandemic on neuro-oncological patients and highlights the essence of timely measures for pandemic preparedness, patient triage, and workforce protection.

The prognosis of glioblastoma: a large, multifactorial study.

OBJECTIVE: Glioblastoma is the most common and fatal primary brain tumor in adults. Even with maximal resection and a series of postoperative adjuvant treatments, the median overall survival (OS) of glioblastoma patients remains approximately 15 months. The Huashan Hospital glioma bank contains more than 2000 glioma tissue samples with long-term follow-up data; almost half of these samples are from glioblastoma patients. Several large glioma databases with long-term follow-up data have reported outcomes of glioblastoma patients from countries other than China. We investigated the prognosis of glioblastoma patients in China and compared the survival outcomes among patients from different databases. METHODS: The data for 967 glioblastoma patients who underwent surgery at Huashan Hospital and had long-term follow-up records were obtained from our glioma registry (diagnosed from 29 March 2010, through 7 June 2017). Patients were eligible for inclusion if they underwent surgical resection for newly diagnosed glioblastomas and had available data of survival and personal information. Data of 778 glioblastoma patients were collected from three separate online databases (448 patients from The Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov), 191 from REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) database (GSE108476) and 132 from data set GSE16011(Hereafter called as the French database). We compared the prognosis of glioblastoma patients from records among the different databases and the changes in survival outcomes of glioblastoma patients from Huashan Hospital over an 8-year period. RESULTS: The median OS of glioblastoma patients was 16.3 (95% CI: 15.4-17.2) months for Huashan Hospital, 13.8 (95% CI: 12.9-14.9) months for TCGA, 19.3 (95% CI: 17.0-20.0) months for the REMBRANDT database, and 9.1 months for the French database. The median OS of glioblastoma patients from Huashan Hospital improved from 15.6 (2010-2013, 95% CI: 14.4-16.6) months to 18.2 (2014-2017, 95% CI: 15.8-20.6) months over the study period (2010-2017). In addition, the prognosis of glioblastoma patients with total resection was significantly better than that of glioblastoma patients with sub-total resection or biopsy. CONCLUSIONS: Our study confirms that treatment centered around maximal surgical resection brought survival benefits to glioblastoma patients after adjusting to validated prognostic factors. In addition, an improvement in prognosis was observed among glioblastoma patients from Huashan Hospital over the course of our study. We attributed it to the adoption of a new standard of neurosurgical treatment on the basis of neurosurgical multimodal technologies. Even though the prognosis of glioblastoma patients remains poor, gradual progress is being made.

Silencing expression of PHF14 in glioblastoma promotes apoptosis, mitigates proliferation and invasiveness via Wnt signal pathway.

BACKGROUND: The plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families. Abnormal expression of PHF14 has been identified in various cancers and is known to be implicated in the pathogenesis of tumors. This study investigates the role and the underlying mechanisms of PHF14 in GBM (glioblastoma multiforme). METHODS: Tissue microarrays and public databases interrogation were used to explore the relationship between the expression of PHF14 and GBM. Three stable PHF14-silenced cell lines (U251, U87MG and A172) were constructed to assess the biological functions changes of GBM cells in vitro. In addition, tumorigenicity in vivo was also performed using U87MG cell line. To understand the mechanism of action of PHF14, RNA-Seq, qRT-PCR, Western blot, IC50 assay and subsequent pathway analysis were performed. RESULTS: Our results showed that the expression of PHF14 was upregulated in glioma, especially in GBM. Overexpression of PHF14 translated to poor prognosis in glioma patients. In vitro assays revealed that silencing expression of PHF14 in glioma cells inhibited migration, invasiveness and proliferation and promoted cell apoptosis. Animal assay further confirmed that over-expression of PHF14 was a dismal prognostic factor. Analysis based on RNA-Seq suggested a PHF14-dependent regulation of Wnt signaling networks, which was further validated by qRT-PCR, Western blot and IC50 analysis. In addition, the mRNA expression of several key markers of EMT (epithelial-mesenchymal transition) and angiogenesis was found to change upon PHF14 silencing. CONCLUSIONS: Our data provide a new insight into the biological significance of PHF14 in glioma and its potential application in therapy and diagnosis.

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 .

Microsurgery resection of giant cervicothoracic spinal ependymoma: Two-dimensional operative video.

Background: Ependymomas, rare glial brain tumors, account for <5% of all brain tumors. Interestingly, over 60% of ependymomas occur in the spinal cord of adults, including those originating from the filum terminale, while the rest are found within the brain. The World Health Organization (WHO) categorizes ependymomas into three grades: subependymomas and myxopapillary ependymomas ([MEPNs]; WHO grade I), classic ependymomas (WHO grade II), and anaplastic ependymomas (WHO grade III). Spinal ependymomas generally exhibit a more favorable prognosis compared to their intracranial counterparts and are primarily treated through gross total resection, which is considered the most effective surgical approach. As such, they are recognized as a distinct clinical entity that demands tailored management strategies. MEPNs, which constitute 13% of ependymomas, typically occur in the cauda equina and sometimes extend into the conus medullaris. Most other spinal ependymomas are of the classic type and predominantly arise in the cervical and thoracic regions of the spine. The mean age at diagnosis is 45 years of age. While prognosis varies based on molecular subtypes, complete resection is associated with improved survival. Case Description: Here, we demonstrate the technical nuances to safely achieve gross total resection of a giant spinal ependymoma in a 29-year-old female with a medical history notable for sept-optic dysplasia, and panhypopituitarism. The patient presented with progressive neck pain, upper and lower extremity weakness, and numbness for 1 year. On physical examination, she demonstrated mild weakness in her left arm. The preoperative magnetic resonance imaging revealed a cervicothoracic intramedullary mass extending from C4 to T2 with an associated syrinx at C4. Under intraoperative neural monitoring (somatosensory evoked potentials, motor-evoked potentials, and epidural direct wave recordings), the patient underwent a C4 - T2 laminectomy. In addition, spinal ultrasonography helped differentiate solid tumor mass from syrinx formation, thus guiding the focus and extent of the decompression . Conclusion: Gross total resection was achieved; at 18 postoperative months, the patient had mild residual motor deficit. The pathological evaluation revealed a WHO grade II ependymoma. Subsequent sequential enhanced MR studies at 3, 6, and 12 months confirmed no tumor recurrence.

Radiotherapy Is Associated With Improved Overall Survival in Adult Pineoblastoma: A SEER Database Analysis.

OBJECTIVE: Pineoblastomas (PBLs) are rare high-grade tumors treated variably with surgery and/or radiation. The role of surgical extent of resection and radiotherapy (RT) in adult PBL remains unclear. We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess these variables' effects on overall survival (OS) in adult PBL. METHODS: The SEER (1975-2016) database was queried for adult patients with diagnosis of PBL (ICD-0-3: 9362/3). Variables extracted included age, sex, race, geographical region, extent of tumor resection, RT, chemotherapy (CT), and OS data. Comparisons were performed with the χ2 test for categorical variables, Cox proportional hazards models to assess the association of clinical variables on OS, and Kaplan-Meier curves were generated. RESULTS: A total of 201 patients with PBL were identified with mean age 40.0 years (interquartile range 27.0-51.0) and most patients being male (53%) and Caucasian (77%). 101 (50%) patients received RT, and gross total resection was achieved in 83 (41%). Age stratification by decade revealed statistically significant poorer OS in patients aged ≥70 years. In bivariate analysis, RT with or without surgery was associated with improved 5-year OS compared with no RT (77.3% vs. 63.2%, P = 0.020). In multivariate analysis, age was a poor prognostic factor for OS (P < 0.001) and RT did appear to improve survival (P = 0.020). Extent of surgical resection was not significantly associated with improved survival. CONCLUSIONS: In adult patients with PBL, RT may offer an OS benefit irrespective of surgery or extent of surgical resection. Patients ≥70 years of age are associated with poorer OS.

Fractionated Radiotherapy After Gross Total Resection of Clival Chordoma: A Systematic Review of Survival Outcomes.

BACKGROUND: Current treatment guidelines for clival chordomas recommend surgical resection followed by high-dose radiotherapy (RT). However, in patients in whom gross total resection (GTR) is achieved, the benefits of additional RT remain unclear. OBJECTIVE: To investigate whether RT offers any benefit to progression-free survival (PFS) in patients undergoing GTR of clival chordoma by performing a systematic review of all currently published literature. METHODS: A total of 5 databases were searched to include all studies providing data on GTR ± RT for clival chordomas (January 1990-June 2021). Qualitative assessment was performed with Newcastle-Ottawa Scale guidelines for assessing quality of nonrandomized studies. Statistical analysis using individualized patient data of PFS was performed. RESULTS: The systematic search yielded 2979 studies, weaned to 22 full-text articles containing 108 patients. All patients underwent GTR of clival chordoma, with 46 (43%) patients receiving adjuvant RT. Mean PFS for RT patients was 31.09 months (IQR: 12.25-37.75) vs 54.92 months (IQR: 14.00-85.75) in non-RT patients. Overall, RT did not increase PFS (HR 0.320, P = .069) to a value that achieved statistical significance. Stratifying by photon therapy vs particle beam therapy yielded no statistically significant benefit for particle beam therapy for PFS ( P = .300). Of patients with age ≥65 years, RT did not improve outcomes to statistical significance for PFS (HR 0.450, P = .481). Patients age ≥65 years had lower PFS on both bivariate analysis (HR 3.708, P = .007) and multivariate analysis (HR 3.322, P = .018). CONCLUSION: After achieving GTR of clival chordoma, fractionated RT offers unclear benefit upon survival outcomes.

Robustness of Randomized Control Trials Supporting Current Neurosurgery Guidelines.

BACKGROUND: Treatment guidelines in neurosurgery are often based on evidence obtained from randomized controlled trials (RCTs). OBJECTIVE: To evaluate the robustness of RCTs supporting current central nervous tumor and cerebrovascular disease guidelines by calculating their fragility index (FI)-the minimum number of patients needed to switch from an event to nonevent outcome to change significant trial primary outcome. METHODS: We analyzed RCTs referenced in the Congress of Neurological Surgeons and American Association of Neurological Surgeons guidelines on central nervous tumor and cerebrovascular disease management. Trial characteristics, finding of a statistically significant difference in the primary endpoint favoring the experimental intervention, the FI, and FI minus number lost to follow-up were assessed. RESULTS: Of 312 RCTs identified, 158 (50.6%) were published from 2000 to 2010 and 106 (34%) after 2010. Sixty-three trials (19.2%) were categorized as surgical trials, and the rest studied medical treatment (82.0%) or percutaneous intervention (8.33%). The trials had a median power of 80.0% (IQR 80.0-90.0). Of these, 120 trials were eligible for FI calculation. The median FI was 7.0 (IQR 2.0-16.25). Forty-four (36.6%) trials had FI ≤ 3 indicating very low robustness. After adjusting for covariates, recently published trials and trials studying percutaneous interventions were associated with significantly higher FI compared with older trials and trials comparing surgical approaches, respectively. Trials limited to single centers were associated with significantly lower FI. CONCLUSION: Trials supporting current guidelines on neuro-oncological and neurovascular surgical interventions have low robustness. While the robustness of trials has improved over time, future guidelines must take into consideration this metric in their recommendations.

Surgical management of metastatic Hürthle cell carcinoma to the skull base, cortex, and spine: illustrative case.

BACKGROUND: Hürthle cell carcinoma (HCC) is an unusual and aggressive variant of the follicular type of differentiated thyroid cancer (DTC), accounting for less than 3% of DTCs but posing the highest risk of metastasis. Brain metastases are uncommonly reported in the literature but pose a poor prognosis. The low rate of brain metastases from HCC coupled with ambiguous treatment protocols for the extracranial disease complicate successful disease management and definitive treatment strategy. The authors present the case of a patient with HCC metastasis to the skull base, cortex, and spine with recent tibial metastasis. OBSERVATIONS: Despite the presence of metastasis to the cortex, skull base, and spine, the patient responded very well to radiation therapy, sellar mass resection, and cervical spine decompression and fixation and has made a remarkable recovery. LESSONS: The authors' multidisciplinary approach to the patient's care, including a diverse team of specialists from oncology, neurosurgery, orthopedic surgery, radiology, endocrinology, and collaboration with clinical trial researchers, was fundamental to her successful outcome, demonstrating the utility of intersecting specialties in successful outcomes in neuro-oncological patient care.

Sex-specific molecular differences in glioblastoma: assessing the clinical significance of genetic variants.

Introduction: Glioblastoma multiforme (GBM) is one of the most aggressive types of brain cancer, and despite rigorous research, patient prognosis remains poor. The characterization of sex-specific differences in incidence and overall survival (OS) of these patients has led to an investigation of the molecular mechanisms that may underlie this dimorphism. Methods: We reviewed the published literature describing the gender specific differences in GBM Biology reported in the last ten years and summarized the available information that may point towards a patient-tailored GBM therapy. Results: Radiomics analyses have revealed that imaging parameters predict OS and treatment response of GBM patients in a sex-specific manner. Moreover, gender-based analysis of the transcriptome GBM tumors has found differential expression of various genes, potentially impacting the OS survival of patients in a sex-dependent manner. In addition to gene expression differences, the timing (subclonal or clonal) of the acquisition of common GBM-driver mutations, metabolism requirements, and immune landscape of these tumors has also been shown to be sex-specific, leading to a differential therapeutic response by sex. In male patients, transformed astrocytes are more sensitive to glutaminase 1 (GLS1) inhibition due to increased requirements for glutamine uptake. In female patients, GBM is more sensitive to anti-IL1ß due to an increased population of circulating granulocytic myeloid-derived suppressor cells (gMDSC). Conclusion: Moving forward, continued elucidation of GBM sexual dimorphism will be critical in improving the OS of GBM patients by ensuring that treatment plans are structured to exploit these sex-specific, molecular vulnerabilities in GBM tumors.

TP53-PTEN-NF1 depletion in human brain organoids produces a glioma phenotype in vitro.

Glioblastoma (GBM) is fatal and the study of therapeutic resistance, disease progression, and drug discovery in GBM or glioma stem cells is often hindered by limited resources. This limitation slows down progress in both drug discovery and patient survival. Here we present a genetically engineered human cerebral organoid model with a cancer-like phenotype that could provide a basis for GBM-like models. Specifically, we engineered a doxycycline-inducible vector encoding shRNAs enabling depletion of the TP53, PTEN, and NF1 tumor suppressors in human cerebral organoids. Designated as inducible short hairpin-TP53-PTEN-NF1 (ish-TPN), doxycycline treatment resulted in human cancer-like cerebral organoids that effaced the entire organoid cytoarchitecture, while uninduced ish-TPN cerebral organoids recapitulated the normal cytoarchitecture of the brain. Transcriptomic analysis revealed a proneural GBM subtype. This proof-of-concept study offers a valuable resource for directly investigating the emergence and progression of gliomas within the context of specific genetic alterations in normal cerebral organoids.

Mini-temporal approach as an alternative to the classical pterional approach for resective temporal region surgeries.

BACKGROUND: Classical pterional appoach for temporal surgeries may cause atrophy and dysfunction of temporalis, injury to the facial nerve, and unnecessary cortical exposure. As an alternative to the classical pterional approach for such surgeries, we hereby describe an mini-temporal approach which reduces these risks and proven to be practical in neurological surgeries. MATERIAL AND METHODS: In the mini-temporal incision design, the frontal end of the incision never surpassed the hairline at the level of temporal line, and a one-layer skin-galea-muscle flap was detached from the cranium, effectively avoiding the injuries of facial nerve. The surgical bone window was completely located underneath the temporalis muscle, allowing it to be completely repositioned postoperatively. RESULTS: We demonstrated the application of mini-temporal approach in a variety of temporal region tumors, which can be applied to complete successful resective surgeries while effectively reducing injuries to extra-temporal cortex, temporalis, and facial nerve. There were no postoperative complications related to extra-temporal cortical damage, atrophy of temporalis, or injury to the facial nerve. CONCLUSION: The mini-temporal approach can effectively shorten the time of craniotomy and closure, decrease the size of bony removal, increase the restoration of temporalis during closure, and lower the chance of facial nerve injury. Therefore, it improves cosmetic outcomes and reduces the risk of unintentional extra-temporal cortical injury, which fully embodies the minimally invasive principle in neurosurgery.

Navigated 3D ultrasound-guided resection of high-grade gliomas: A case series and review.

Background: The crux in high-grade glioma surgery remains maximizing resection without affecting eloquent brain areas. Toward this, a myriad of adjunct tools and techniques has been employed to enhance surgical safety and efficacy. Despite intraoperative MRI and advanced neuronavigational techniques, as well as augmented reality, to date, the only true real-time visualization tool remains the ultrasound (US). Neuroultrasonography is a cost-efficient imaging modality that offers instant, real-time information about the changing anatomical landscape intraoperatively. Recent advances in technology now allow for the integration of intraoperative US with neuronavigation. Case Description: In this report, we present the resection technique for three cases of high-grade gliomas (two glioblastomas and one anaplastic astrocytoma). The patient presented with a variable clinical spectrum. All three cases have been performed using the Brainlab® neuronavigation system (BrainLAB, Munich, Germany) and the bk5000 US Machine® (BK Medical, Analogic Corporation, Peabody, Massachusetts, USA). Conclusion: Gross total resection was achieved in all three cases. The use of 3D navigated US was a reliable adjunct surgical tool in achieving favorable resection outcomes in these patients.

The Intraoperative Utilization of Multimodalities Could Improve the Prognosis of Adult Glioblastoma: A Single-Center Observational Study.

OBJECTIVE: In recent years, numerous neurosurgical multimodal techniques have been utilized to maximize tumor resection safely and effectively. However, the synergetic effects of neurosurgical multimodalities on the survival of glioblastoma patients remain unclear. This study evaluated the role of intraoperative utilization of multimodalities in glioblastoma patients. METHODS: Data of 912 adult patients with glioblastoma were obtained from the Huashan Glioma Registry. The utilization of fewer than 2 (multimodality value < 2) intraoperative multimodal techniques was defined as the nonmultimodal group. In contrast, the utilization of 2 or more (multimodality value ≥ 2) intraoperative multimodal techniques was regarded as the multimodal group. The prognosis of the 2 cohorts was compared and further stratified based on the diagnosis date (2010-2014 or 2015-2019) to reveal the role of the application of multimodal techniques. RESULTS: The median overall survival (OS) and progression-free survival of glioblastoma patients were 17.70 months and 12.03 months, respectively. The OS time of the multimodal group was noticeably longer than that of the nonmultimodal group (21.0 months vs. 16.0 months, P < 0.001). Multimodal techniques were more frequently applied in surgery in the 2015-2019 group than in the 2010-2014 group. The popularity of multimodal techniques contributed to significant improvement in the prognosis of glioblastoma patients from 2010-2014 to 2015-2019 (OS, 16.0 months vs. 22.0 months, P < 0.001). CONCLUSIONS: This study indicated that the utilization of intraoperative multimodal techniques improved the extent of resection and elevated the survival for adult glioblastoma patients.

Infraoccipital Supratentorial Approach Resection of a Left Mesiotemporal and Atrium Epidermoid Cyst.

Classically mesiotemporal lesions are approached from the lateral temporal approach, which frequently injures the visual and language tracts. We present the posterior approach through which the language tracts and visual tracts at the roof and lateral wall of the temporal horn (Meyer loop) can be avoided, minimizing the risk of neurologic injury. The patient, a 32-year-old man, presented with the chief complaint of experiencing seizures for 6 years with rare, generalized, tonic-clonic seizures. Physical examination showed no neurologic deficits and past medical history was not remarkable. Magnetic resonance imaging revealed a left mesiotemporal lesion, which showed no contrast enhancement and infiltrated the atrium. For surgery, the patient was laid in prone position and a tailored bone flap was lifted. Next the occipital lobe was retracted gently to expose the lesion. Penfield dissectors were used to gradually resect the lesion. The roof and inner wall of the atrium were exposed during resection. These structures were protected. Residues of the lesion and its capsule were seen attached to the lateral ventricle and were carefully coagulated and removed. The hippocampus was also exposed and a small segment resected. Exposure of the roof and inner wall of the atrium confirmed that the entire lesion has been resected. Intraoperative magnetic resonance imaging evaluation confirmed a total resection of the lesion. Pathological analysis confirmed the diagnosis of epidermoid cyst. Cognitive evaluation results showed no postoperative deficiencies and his visual field was also not affected by the surgery. Informed patient content was obtained (Video 1).