Mentalizing can be Impaired in Patients with Meningiomas Originating in the Anterior Skull Base.

OBJECTIVE: Mentalizing is an essential function of our social lives. Impairment of mentalizing due to meningiomas has not received attention because most patients return to their social lives after surgical treatment. We investigated the influence of meningiomas and their surgical resection on mentalizing. METHODS: Low- and high-level mentalizing were retrospectively examined in 61 patients with meningiomas and 14 healthy volunteers. Mentalizing was assessed using the facial expression recognition test and picture arrangement test of the Wechsler Adult Intelligence Scale, third edition, before and after surgery. We examined the influence of tumor localization on mentalizing and recovery from mentalizing disorders after tumor resection. Voxel-based lesion-symptom mapping was performed to investigate the relationship between impairments in mentalizing and tumor location. RESULTS: Before surgery, mentalizing was impaired significantly in patients with meningiomas compared to those in the control group (low-level: P = 0.015, high-level: P = 0.011). This impairment was associated with contact between the tumor and frontal lobe (low-level: P = 0.036, high-level: P = 0.047) and was severe in patients with tumors arising in the anterior skull base (low-level: P = 0.0045, high-level: P = 0.043). Voxel-based lesion-symptom mapping revealed that when the basal cortex of the frontal lobe was compressed by the tumor, the risk of impaired mentalizing was high. The region responsible for high-level mentalizing was located deeper than that responsible for low-level mentalizing. After the surgical removal of the tumor, the test scores significantly improved (low-level: P = 0.035, high-level: P = 0.045). CONCLUSIONS: Mentalizing was impaired by meningiomas arising from the anterior skull base, but it can improve after surgical resection of the tumors.

Glioblastomas at the white matter of temporo-parietal junction cause a poor postoperative independence level.

INTRODUCTION: Right cerebral hemispheric glioblastomas (GBMs) often decrease the Karnofsky performance status (KPS) score postoperatively, despite the patient having sufficient patient function while performing daily living. This study aimed to evaluate the factors that could cause poor KPS scores during the postoperative chronic phase in patients with right cerebral hemispheric GBMs. METHODS: Data of 47 patients with newly diagnosed right cerebral hemispheric GBMs were analyzed. All patients were assessed preoperatively and 3 months postoperatively to determine KPS and brain function. To determine tumor location related to the postoperative KPS scores, we used voxel-based lesion symptom mapping (VLSM). The patients were divided into two groups (involvement and non-involvement groups) based on whether their lesion involved a significant region identified by VLSM. We then compared functional factors and prognosis between the groups using the chi-squared and log-rank tests, respectively. RESULTS: The KPS score significantly decreased after surgery compared to that preoperatively measured (p = 0.023). VLSM revealed that tumors in the white matter of temporo-parietal junction (WM-TPJ) caused a significant decline in the KPS score at three months postoperatively. The patients in the involvement group had a higher probability of impaired attention, visuospatial cognition, emotion recognition, and visual field than did those in the non-involvement group. In addition, tumor in the WM-TPJ were associated with shorter progression-free survival and overall survival (p = 0.039 and 0.023, respectively). CONCLUSIONS: GBMs involving the right WM-TPJ are more likely to result in poor postoperative KPS scores and prognoses. Impairments of several kinds of brain functions caused by tumor invasion to the WM-TPJ may be associated with lower KPS scores.

Nuclear transport surveillance of p53 by nuclear pores in glioblastoma.

Nuclear pore complexes (NPCs) are the central apparatus of nucleocytoplasmic transport. Disease-specific alterations of NPCs contribute to the pathogenesis of many cancers; however, the roles of NPCs in glioblastoma (GBM) are unknown. In this study, we report genomic amplification of NUP107, a component of NPCs, in GBM and show that NUP107 is overexpressed simultaneously with MDM2, a critical E3 ligase that mediates p53 degradation. Depletion of NUP107 inhibits the growth of GBM cell lines through p53 protein stabilization. Mechanistically, NPCs establish a p53 degradation platform via an export pathway coupled with 26S proteasome tethering. NUP107 is the keystone for NPC assembly; the loss of NUP107 affects the integrity of the NPC structure, and thus the proportion of 26S proteasome in the vicinity of nuclear pores significantly decreases. Together, our findings establish roles of NPCs in transport surveillance and provide insights into p53 inactivation in GBM.

Association Between Risperidone Use and Kidney Function Decline in Patients with Schizophrenia: A Retrospective Cohort Study.

PURPOSE: Several D-amino acids have been shown to be protective against kidney injury in mice. Risperidone, a currently used atypical antipsychotic agent for schizophrenia, is also known to inhibit the activity of D-amino acid oxidase, which degrades certain D-amino acids. Based on the hypothesis that risperidone would prevent kidney disease progression, this study investigated the association between risperidone use and kidney function decline in patients with schizophrenia. METHODS: This retrospective cohort study included patients who were diagnosed with schizophrenia and had data available from two or more serum creatinine measurements between April 1, 2010, and March 31, 2020. Patients who used risperidone for at least 30 days were included in the risperidone group, whereas those who had no record of risperidone use were included in the control group. Cox regression models were used to evaluate the risk for 40% decline in estimated glomerular filtration rate (eGFR) in patients treated with risperidone compared to that in the control group. FINDINGS: Overall, 212 patients used risperidone and 1468 patients had no record of risperidone use. The mean age was 55 years, 759 (45%) of the patients were male, and the mean eGFR at baseline was 88 mL/min/1.73 m2. The mean age in the risperidone group was less than that in the control group (52 vs 56 years); other baseline characteristics were comparable between the two groups. During a mean follow-up of 1.6 years, 267 patients (16%) had a 40% eGFR decline. The incidence rate of 40% eGFR decline was lower in the risperidone group than in the control group (60 vs 104 per 1000 person-years). After adjustment for baseline age, sex, and eGFR, risperidone use was associated with a decreased risk for 40% eGFR decline (hazard ratio = 0.54; 95% CI, 0.33-0.87; P = 0.01). IMPLICATIONS: Risperidone use may be associated with decreased risk for kidney function decline in patients with schizophrenia. Further studies are warranted to validate these findings.

Therapeutic potential of pentamidine for glioma-initiating cells and glioma cells through multimodal antitumor effects.

Glioma-initiating cells, which comprise a heterogeneous population of glioblastomas, contribute to resistance against aggressive chemoradiotherapy. Using drug reposition, we investigated a therapeutic drug for glioma-initiating cells. Drug screening was undertaken to select candidate agents that inhibit proliferation of two different glioma-initiating cells lines. The alteration of proliferation and stemness of the two glioma-initiating cell lines, and proliferation, migration, cell cycle, and survival of these two differentiated glioma-initiating cell lines and three different glioblastoma cell lines treated with the candidate agent were evaluated. We also used a xenograft glioma mouse model to evaluate anticancer effects of treated glioma cell lines. Among the 1301 agents, pentamidine-an antibiotic for Pneumocystis jirovecii-emerged as a successful antiglioma agent. Pentamidine treatment suppressed proliferation and stemness in glioma-initiating cell lines. Proliferation and migration were inhibited in all differentiated glioma-initiating cells and glioblastoma cell lines, with cell cycle arrest and caspase-dependent apoptosis induction. The in vivo study reproduced the same findings as the in vitro studies. Pentamidine showed a stronger antiproliferative effect on glioma-initiating cells than on differentiated cells. Western blot analysis revealed pentamidine inhibited phosphorylation of signal transducer and activator of transcription 3 in all cell lines, whereas Akt expression was suppressed in glioma-initiating cells but not in differentiated lines. In the present study, we identified pentamidine as a potential therapeutic drug for glioma. Pentamidine could be promising for the treatment of glioblastomas by targeting both glioma-initiating cells and differentiated cells through its multifaceted antiglioma effects.

Intra-Brain and Plasma Levels of L-Serine Are Associated with Cognitive Status in Patients with Chronic Kidney Disease.

Introduction: The number of patients with chronic kidney disease (CKD) is increasing worldwide. Cognitive impairment is one of the comorbidities of CKD. With the increased number of aged population, novel biomarkers of impaired cognitive function are required. Intra-body profile of amino acid (AA) is reportedly altered in patients with CKD. Although some AAs act as neurotransmitters in the brain, it is not clear whether altered AA profile are associated with cognitive function in patients with CKD. Therefore, intra-brain and plasma levels of AAs are evaluated with respect to cognitive function in patients with CKD. Methods: Plasma levels of AAs were compared between 14 patients with CKD, including 8 patients with diabetic kidney disease, and 12 healthy controls to identify the alteration of specific AAs in CKD. Then, these AAs were evaluated in the brains of 42 patients with brain tumor using non-tumor lesion of the resected brain. Cognitive function is analyzed with respect to intra-brain levels of AAs and kidney function. Moreover, plasma AAs were analyzed in 32 hemodialyzed patients with/without dementia. Results: In patients with CKD, plasma levels of asparagine (Asn), serine (Ser), alanine (Ala), and proline (Pro) were increased as compared to patients without CKD. Among these AAs, L-Ser, L-Ala, and D-Ser show higher levels than the other AAs in the brain. Intra-brain levels of L-Ser was correlated with cognitive function and kidney function. The number of D-amino acid oxidase or serine racemase-positive cells was not correlated with kidney function. Moreover, the plasma levels of L-Ser are also decreased in patients with declined cognitive function who are treated with chronic hemodialysis. Conclusion: The decreased levels of L-Ser are associated with impaired cognitive function in CKD patients. Especially, plasma L-Ser levels may have a potential for novel biomarker of impaired cognitive function in patients with hemodialysis.

The effect of damage to the white matter network and premorbid intellectual ability on postoperative verbal short-term memory and functional outcome in patients with brain lesions.

Cognitive reserve is the capacity to cope with cognitive decline due to brain damage caused by neurological diseases. Premorbid IQ has been investigated as a proxy for cognitive reserve. To date, no study has focused on the effects of premorbid IQ in patients with brain tumors, considering the damage to white matter tracts. We investigated whether a higher premorbid IQ has a beneficial impact on postoperative verbal short-term memory and functional outcomes in patients with brain tumors. A total of 65 patients with brain tumors (35 right and 30 left hemisphere lesions) and 65 healthy subjects participated in the study. We used multiple regression analysis to examine whether white matter tract damage and premorbid IQ affect postoperative verbal short-term memory, and the interaction effects of premorbid IQ with damage to white matter tract on postoperative verbal short-term memory. Path analysis was used to investigate the relationship between damage to the white matter tract and premorbid IQ on postoperative functional ability. Our results showed that damage to the left arcuate fasciculus affected postoperative functional ability through verbal short-term memory, working memory, and global cognition in patients with left hemisphere lesions. In the right hemisphere lesion group, high premorbid IQ had a positive effect on functional ability by mediating verbal short-term memory, verbal working memory, and global cognition. We found that damage to the eloquent pathway affected postoperative verbal short-term memory regardless of the premorbid IQ level. However, a higher premorbid IQ was associated with better postoperative verbal short-term memory and functional outcomes when the brain lesions were not located in a crucial pathway. Our findings suggest that premorbid IQ and damage to the white matter tracts should be considered predictors of postoperative functional outcomes.

Patterns of failure in glioblastoma multiforme following Standard (60 Gy) or Short course (40 Gy) radiation and concurrent temozolomide.

PURPOSE: The purpose of this study was to analyze the patterns of failure in patients with glioblastoma multiforme (GBM) treated using chemoradiotherapy in the Standard radiotherapy (60 Gy/30 fractions; Standard) or Short course (40 Gy/15 fractions: Short). MATERIALS AND METHODS: Ninety-three consecutive patients with newly diagnosed glioblastoma treated at our hospital between April 2007 and December 2016, and 68 patients who could be followed up were included. All patients underwent surgical resection followed by radiotherapy with concurrent temozolomide. We retrospectively analyzed treatment outcomes and recurrence patterns. RESULTS: The median follow-up period of the surviving patients was 82.8 months (range: 46.0-158.9 months). Of the 68 patients, 58 patients (85%) had recurrences, 34 underwent the Standard and 24 Short course. The Standard course was seen in younger age groups and had a better Karnofsky performance status (KPS) than the Short course. The median survival time (MST) was 25.8 months for the Standard and 15.4 months with the Short in all cases. Standard course had significantly longer MST than the Short (p = 0.001) course. For recurrent cases only, there was no significant difference between Standard and Short courses in OS (p = 0.06). The recurrences occurred at the radiation fields alone (Standard/Short: 85%/83%), only at distant sites (Standard/Short: 12%/13%), and at both the radiation fields and distant sites (Standard/Short: 3%/4%). There was no significant difference in recurrence pattern and frequency between the two protocols (p = 0.11). CONCLUSIONS: Standard course tended to be significant in younger age groups and have a better KPS than the Short course; therefore, the Standard course has a longer OS, but the recurrence pattern of the Short course is similar to that of the Standard treatment.

COL1A2 inhibition suppresses glioblastoma cell proliferation and invasion.

OBJECTIVE: An extracellular matrix such as collagen is an essential component of the tumor microenvironment. Collagen alpha-2(I) chain (COL1A2) is a chain of type I collagen whose triple helix comprises two alpha-1 chains and one alpha-2 chain. The authors' proteomics data showed that COL1A2 is significantly higher in the blood of patients with glioblastoma (GBM) compared with healthy controls. COL1A2 has many different functions in various types of cancers. However, the functions of COL1A2 in GBM are poorly understood. In this study, the authors analyzed the functions of COL1A2 and its signaling pathways in GBM. METHODS: Surgical specimens and GBM cell lines (T98, U87, and U251) were used. The expression level of COL1A2 was examined using GBM tissues and normal brain tissues by quantitative real-time polymerase chain reaction. The clinical significance of these levels was evaluated using Kaplan-Meier analysis. Small interfering RNA (siRNA) and small hairpin RNA of COL1A2 were transfected into GBM cell lines to investigate the function of COL1A2 in vitro and in vivo. Flow cytometry was introduced to analyze the alteration of cell cycles. Western blot and immunohistochemistry were performed to analyze the underlying mechanisms. RESULTS: The expression level of COL1A2 was upregulated in GBM compared with normal brain tissues. A higher expression of COL1A2 was correlated with poor progression-free survival and overall survival. COL1A2 inhibition significantly suppressed cell proliferation in vitro and in vivo, likely due to G1 arrest. The invasion ability was notably deteriorated by inhibiting COL1A2. Cyclin D1, cyclin-dependent kinase 1, and cyclin-dependent kinase 4, which are involved in the cell cycle, were all downregulated after blockade of COL1A2 in vitro and in vivo. Phosphoinositide 3-kinase inhibitor reduced the expression of COL1A2. Although downregulation of COL1A2 decreased the protein kinase B (Akt) phosphorylation, Akt activator can phosphorylate Akt in siRNA-treated cells. This finding suggests that Akt phosphorylation is partially dependent on COL1A2. CONCLUSIONS: COL1A2 plays an important role in driving GBM progression. COL1A2 inhibition attenuated GBM proliferation by promoting cell cycle arrest, indicating that COL1A2 could be a promising therapeutic target for GBM treatment.

Recovery of Visual Field After Awake Stimulation Mapping of the Optic Pathway in Glioma Patients.

Brain mapping during awake craniotomy for gliomas can help preserve neurological functions, including maintenance of central and peripheral vision. However, the consecutive changes in the visual field remain unknown. We retrospectively assessed 14 patients who underwent awake craniotomy for gliomas infiltrating into the optic radiation. Cortico-subcortical direct electrical stimulation (DES) was intraoperatively applied until transient visual symptoms were elicited and recorded. The visual fields were examined consecutively in the preoperative period and postoperative subacute and chronic periods. To evaluate the anatomo-functional validity of the recordings, all DES-elicited points were overlaid onto a three-dimensional template that included the optic radiation, using voxel-based morphometry (VBM) mapping. All patients experienced visual symptoms that were classified as phosphenes, blurred vision, or hallucinations during DES, and surgical resection was limited to within the functional boundaries. In VBM, almost all the subcortical positive mapping points overlapped with the surface of the optic radiation, and the distribution of sites that induced visual phenomena in the upper or lower visual fields could be differentiated in the anatomical space. We observed no postoperative visual deficit in four patients (29%), time-dependent improvements in five out of eight patients that presented transient quadrantanopia or partial visual defect (36% out of 57%), and permanent hemianopsia (14%) in two patients with occipital lesions. Intraoperative DES that identifies and preserves optic radiation in awake craniotomy for gliomas is a reliable and effective technique to reduce risk of permanent deficits, but has a low success rate in patients with occipital involvement.

Non-occlusive mesenteric ischemia during bevacizumab treatment for glioblastoma: a case report.

Glioblastoma is one of the most aggressive brain tumors in adults. The standard treatment is radiotherapy and chemotherapy based on the Stupp regimen after maximal safe resection. One effective chemotherapeutic drug is bevacizumab, which can prolong progression-free survival in glioblastoma patients but not overall survival. Adverse events of bevacizumab include hypertension, proteinuria, delayed wound healing, bleeding of the nose and gums, and thromboembolism resulting in gastrointestinal perforation. Herein, we describe an autopsy case of a patient with glioblastoma who died from non-occlusive mesenteric ischemia that was presumably caused by bevacizumab.

Posterior-prefrontal and medial orbitofrontal regions play crucial roles in happiness and sadness recognition.

The core brain regions responsible for basic human emotions are not yet fully understood. We investigated the key areas responsible for emotion recognition of facial expressions of happiness and sadness using data obtained from patients who underwent local brain resection. A total of 44 patients with right cerebral hemispheric brain tumors and 33 healthy volunteers were enrolled and subjected to a facial expression recognition test. Voxel-based lesion-symptom mapping was performed to investigate the relationship between the accuracy of emotion recognition and the resected regions. Consequently, trade-off relationships were discovered: the posterior-prefrontal region was related to a low score of happiness recognition and a high score of sadness recognition (disorder-of-happiness group), whereas the medial orbitofrontal region was related to a low score of sadness recognition and a high score of happiness recognition (disorder-of-sadness group). The emotion recognition score in both the happiness and sadness disorder groups was significantly lower than that in the control group (p = 0.0009 and p = 0.021, respectively). Interestingly, the deficit in happiness recognition was temporary, whereas the deficit in sadness recognition persisted during the chronic phase. Using graph theoretical analysis, we identified structural connectivity between the posterior-prefrontal and medial orbitofrontal regions. When either of these regions was damaged, the tract volume connecting them was significantly reduced (p = 0.013). These results indicate that the posterior-prefrontal and medial orbitofrontal regions may be crucial for maintaining a balance between happiness and sadness recognition in humans. Investigating the clinical impact of certain area resections using lesion studies combined with connectivity analysis is a useful neuroimaging method for understanding neural networks.

Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter.

BACKGROUND: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587). METHODS: Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients. RESULTS: As of December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO + RT + TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO + RT + TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively. CONCLUSIONS: NIVO added to RT + TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.

Intraoperative rupture of intracerebral aneurysm immediately after meningioma resection: a case report.

BACKGROUND: Meningiomas and unruptured cerebral aneurysms (UCAs) rarely coexist. However, the treatment strategy remains to be fully elucidated. This report is a first report that UCA related to the tumor feeder intraoperatively ruptured when the meningioma was resected. CASE PRESENTATION: Herein, we present a case of meningioma coexisting with contralateral UCA related to a tumor feeder. Immediately after the meningioma was resected, intraoperative acute brain swelling due to rupture of the contralateral aneurysm appeared. The swollen brain protruding into the epidural space was resected, following contralateral ruptured aneurysm was performed by endovascular surgery. Intensive neurological treatment was administered and the patient gradually recovered. CONCLUSION: This report highlights the possibility of intraoperative UCA rupture related to the tumor feeder when the meningioma is resected.

Two different subcortical language networks supporting distinct Japanese orthographies: morphograms and phonograms.

Language systems worldwide are based on either morphograms or phonograms, but Japanese is unique in that uses a complicated combination of kanji (morphogram) and kana (phonogram) characters. The white matter networks associated with reading have been investigated previously but remain incompletely understood. In this study, we performed intraoperative language mapping under local anesthesia and postoperative language assessments of 53 consecutive patients who underwent awake craniotomy for surgical resection of cerebral glioma within the dominant temporal or parietal lobe. Six cases showing intraoperative dyslexia elicited by direct electrical stimulation (DES) were examined, and all cases showed transient symptoms of kanji or kana dyslexia during DES. We investigated the intraoperative positive mapping points localized near four white matter bundles: the arcuate fascicle, posterior superior longitudinal fascicle, inferior fronto-occipital longitudinal fascicle, and inferior longitudinal fascicle (ILF). The intraoperative DES distributions for kanji dyslexia were especially associated with the anterior-inferior side of the ILF. On the other hand, the DES points associated with kana dyslexia were localized on the posterior-superior side of the complex composed of these four tracts. These results suggest the presence of specific non-interfering networks that subserve the processes of reading morphograms and phonograms.

A Fiber Dissection Study of the Anterior Commissure: Correlations with Diffusion Spectrum Imaging Tractography and Clinical Relevance in Gliomas.

The anterior commissure, which connects bilateral temporal lobes and olfactive areas, remains elusive in many aspects of its structure and functional role. To comparatively describe anatomical details of the anterior commissure using cadaveric fiber dissection (FD) and diffusion spectrum imaging (DSI) thus refining our knowledge of the tract and exploring its clinical relevance in glioma migration. Twelve normal postmortem hemispheres were treated with Klingler's method and subjected to FD with medial, inferior, and lateral approaches. The FD findings were correlated with DSI tractography results. To illustrate the clinical relevance, two patients with recurrent temporal high-grade glioma are described. Our FD and DSI tractography of the anterior commissure disclosed a new anatomical paradigm. The FD confirmed that the anterior limb (absent sometimes and variable) and the lateral/temporal extension include the rostral portion and caudal portion, respectively, of the anterior commissure fibers. The shape of the lateral/temporal extension predominantly resembles an 'H'. The DSI tractography findings corresponded to these FD results. According to the FD, the Virchow-Robin space is continuous with the subarachnoid space and very close to the anterior commissure. The two clinical cases presented severe disturbances of consciousness and behavior despite good local tumor control. Subsequent magnetic resonance images showed new lesions infiltrating the contralateral temporal lobes. FD combined with DSI provided anatomical details facilitating a better understanding of the anterior commissure. Glioma migration routes to the contralateral temporal lobe included the anterior commissure, Virchow-Robin space, and subarachnoid space and were clinically relevant.

Quality of life following awake surgery depends on ability of executive function, verbal fluency, and movement.

INTRODUCTION: The outcome of awake surgery has been evaluated based on functional factors, return to work, and oncological aspects, and there have been no reports directly examining QOL. This study aimed to investigate the outcome of QOL following awake surgery and to determine the functional factors influencing QOL. METHODS: Seventy patients with WHO grade II/III gliomas were included. For the assessment of QOL, we used the SF-36 and calculated summary and sub-component scores. Three summary component scores, including physical (PCS), mental (MCS), and role/social summary (RCS) component scores, were computed based on sub-component scores. Additionally, various assessments of neurological/neuropsychological function were performed. We performed univariate and multiple regression analyses to investigate the functional factors influencing the SF-36. RESULTS: PCS and MCS were maintained, but only RCS was low to 42.0 ± 16.1. We then focused on the RCS and its sub-components: general health (GH), role physical (RP), social functioning (SF), and role emotional (RE). Multiple regression analysis showed following significant correlations between the sub-component scores and brain functions: GH to executive function and movement (p = 0.0033 and 0.032), RP to verbal fluency and movement (p = 0.0057 and 0.0010), and RE to verbal fluency (p = 0.020). Furthermore, when the sub-component scores were compared between groups with and without functional deficits related to GH, RP, and RE, each score was significantly lower in the groups with functional deficits (p = 0.012, 0.014, and 0.0049, respectively). CONCLUSIONS: In patients who underwent awake surgery, a subset of patients had low QOL because of poor RCS. Functional factors influencing QOL included executive function, verbal fluency, and movement.

[Brain Functional Networks and Awake Craniotomy for Gliomas].

The sophisticated functional networks of the human brain are integral to life, controlling domains such as language understanding and production and social cognition, which are important for inter-personal communication. Glioma, a primary brain tumor, infiltrates into the brain tissue, forcing the normal brain to reorganize the neural networks(brain plasticity)to resist the invasion. Awake craniotomy for gliomas enables reliable intraoperative identification and preservation of not only the innate normal brain functional areas but also the brain functional networks that have adapted and changed in response to the tumor-invasive environment. Recent advances in neurosurgical techniques and anesthetics have enabled the performance of intraoperative mapping of various brain functions, while maintaining the patient at a high level of awake condition. Attempts have also been made to preserve not only the language functions in the left cerebral hemisphere but also the higher brain functions represented by the right frontal lobe. Herein, we introduce the neural networks of the brain that glioma surgeons need to be aware of, and further describe the indications, methods, and usefulness of awake craniotomy for preserving these networks. In addition, we will discuss topics expected to become the standard in the near future.

Disconnection of posterior part of the frontal aslant tract causes acute phase motor functional deficit.

The frontal aslant tract (FAT) mainly connects the supplementary motor area (SMA) and inferior frontal gyrus. The left FAT is involved in language-related functions, while the functional role of the right FAT is not fully understood. The aim of this study was to investigate the function of the right FAT by dividing it into three segments according to the anatomical structure. A total of 34 right frontal gliomas who had undergone surgery were studied. Participants were assessed for the acute and chronic phases of several neuropsychological and motor functions. FAT was reconstructed into the anterior, middle, and posterior segments according to the cortical connections as the medial prefrontal cortex, pre-SMA, and SMA proper, respectively. The relationships between the damaged severity of each FAT segment and behavioral scores were analyzed. A significant relationship was observed only in the acute phase motor function and posterior segment of the FAT. The middle segment was involved in motor function, but it did not have a sufficient significance level compared to the posterior segment. Our study revealed that the right FAT can be divided into three segments and that its posterior segment is related to acute phase motor function.

Functional anatomy of the frontal aslant tract and surgical perspectives.

The frontal aslant tract (FAT) is an intralobar white matter fasciculus providing dense connections between the medial part of the superior frontal gyrus, in particular the presupplementary motor area (SMA) and the SMA proper, and the lateral part of the frontal lobe, especially the inferior frontal gyrus. Although this tract has been characterized belatedly, it has received important attention in recent years due notably to its increasingly evidenced role in the speech and language networks. As cerebral tumors frequently affect the frontal lobe, an improved knowledge of the functional anatomy of the FAT is mandatory to refine the way neurosurgeries are performed and to give the patients the best opportunities to recover after surgery. In this work, we first describe the spatial arrangement of the FAT and detail its cortical projections. We then provide a comprehensive review of the functions supposedly mediated by this transverse frontal connectivity. It is structured following a tripartite organization where the linguistic (i.e. speech and language), supralinguistic (i.e. functions that interact with speech and language: executive functions, working memory, and social communication) and extralinguistic implications (i.e. functions outside the linguistic domain: visuospatial processing, praxis and motor skills) are successively addressed. We lastly discussed this knowledge in the context of wide-awake neurosurgeries for brain tumors. We emphasize the need to evaluate thoroughly the functions conveyed by FAT by means of longitudinally-designed studies to first estimate its plasticity potential and then to determine which tasks should be selected to avoid lasting impairments due to its disconnective breakdown.