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Purpose: Diffuse midline gliomas are rare midline CNS malignancies that primarily affect children but can also affect adults. While radiation is standard treatment, prognosis remains fatal. Furthermore, due to its sensitive anatomic location, many physicians have been reluctant to perform biopsies without potential for improved prognosis. However, recent advancements in molecular-targeted therapeutics have encouraged greater tissue sampling. While the literature reflects this progress, the landscape of how clinicians actually manage these patients remains unclear. Our goal was to assess the attitudes of current practicing neurosurgical oncologists towards management of adult diffuse midline gliomas, reasons behind their practices, and factors that might influence these practices., Methods: We created and distributed a survey with 16 multiple choice and open-ended questions to members of the Tumor Section of the Congress of Neurological Surgeons., Results: A total of 81 physicians responded to the survey. Although time since training and volume of glioma patients did not significantly affect the decision to consider clinical trials or to offer biopsy, those that operated on fewer gliomas (< 25/year) were more likely to cite surgical morbidity as the primary reason not to biopsy these midline locations. Further, surgeons with access to more advanced molecular testing were significantly more likely to consider clinical trial eligibility when offering biopsies., Conclusion: Factors that affect the management of diffuse midline gliomas and the role of biopsy are relatively uniform across the field, however, there were a few notable differences that reflect the changes within the neuro-oncology field in response to clinical trials.

Hypnosis could extend the time of Intraoperative Neuropsychological Testing and Brain Mapping in Awake Surgery. A clinical validation for the Hypnosis aided AS (HAs) is still ongoing and further evidences are required. The objective of the present study is to compare two homogeneous cohorts of patients undergoing AS, the first with the aid of the hypnosis and the second according to a standard AS (SAs) protocols. The clinical, radiological and surgical data of two comparable procedures cohorts were retrospectively examined for the present study. All surgeries in Group A were performed with a HAs protocol. Procedures belonging to Group B were performed with a SAs protocol. Endpoints: to compare 1. Incidence of complications in the immediate postoperative period, 2. Clinical and neurological status in the immediate postoperative period and 30 days after surgery, 3. Duration of surgical interventions, 4. Extent of Resection (EOR). The final cohort is composed of 15 procedures; 6 belonging to Group A and 9 to Group B. The different methods outline statistically comparable results from the clinical (Neurological outcomes) both in the postoperative period and one month after surgery and from the surgical point of view (comparable EOR). The incidence of complications is comparable either. The duration of the procedures was significantly longer in HAs group. Hypnosis is a promising approach to increasing the duration of intraoperative "testability" of patients at the price of a longer operative time. A specific professional is needed to induce hypnosis in the difficult intraoperative setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap., Methods/design: This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor-patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care). In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services. Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor-patient consultation; as well as the length of the doctor-patient consultation., Discussion: Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient's distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases)., Trial Registration: German Clinical Trials Register, DRKS00018079. Registered on 3rd September 2019.

Objectives: This study aimed to investigate the association of high-sensitivity C-reactive protein (hsCRP) and N -terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations with cognitive functions of glioma and meningioma patients., Methods: 177 brain tumor patients awaiting for brain tumor surgery participated in the study. Patients were assessed preoperatively, using neuropsychological tests for verbal memory, psychomotor speed, mental flexibility, and verbal fluency. The functional status of patients was evaluated using the Karnofsky Performance Index. Blood samples were drawn for evaluation of serum hsCRP and NT-proBNP concentrations upon hospital admission., Results: The highest NT-proBNP concentration was observed in meningioma patients. Glioma and meningioma patients did not differ in hsCRB concentration. Patients in the highest hsCRP tertile were older and more frequently reported cardiovascular comorbidity. Patients in the highest NT-proBNP tertile were older, more frequently with cardiovascular comorbidity, females, and diagnosed with a meningioma. hsCRP was significantly related to slower psychomotor speed in high-grade glioma patients ( rho = 0.30, p < 0.05). In meningioma sample, NT-proBNP correlated with decreased psychomotor speed ( rho = 0.38, p < 0.01), mental flexibility ( rho = 0.33, p < 0.01), worse cumulative learning ( rho = -0.27, p < 0.05), and delayed recall ( rho = 0.30, p < 0.01). However, the relationship between the NT-proBNP and cognitive functions became nonsignificant when demographic and clinical covariates were included into analysis. Higher hsCRP concentration remained significantly related to slower psychomotor speed ( p = 0.02) and worse mental flexibility ( p = 0.05) in glioma patients, independently from demographic and clinical covariates. Preoperative cognitive functioning was also predicted by older age, gender, side and location of the tumor, and tumor malignancy, and general functional status of a patient., Conclusions: NT-proBNP was not associated with memory, language, and attention/executive cognitive domains of glioma and meningioma patients. Increased hsCRP was related to slower psychomotor speed and worse mental flexibility in glioma patients, indicating that inflammation processes are important for cognitive functioning in glial tumors., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Aiste Pranckeviciene et al.)

Purpose: Awake surgery is an established technique for resection of low-grade gliomas, while its possible benefit for resection of high-grade gliomas (HGGs) needs further confirmations. This retrospective study aims to compare overall survival, extent of resection (EOR) and cognitive outcome in two groups of HGGs patients submitted to asleep or awake surgery., Methods: Thirty-three patients submitted to Gross Total Resection of contrast-enhancing area of HGGs were divided in two homogeneous groups: awake (AWg; N = 16) and asleep surgery (ASg; N = 17). All patients underwent to an extensive neuropsychological assessment before surgery (time&#95;1), 1-week (time&#95;2) and 4-months (time&#95;3) after surgery. We performed analyses to assess differences in cognitive performances between groups, cognitive outcomes in each group and EOR. A comparison of overall survival (OS) between the two groups was conducted., Results: Statistical analyses showed no differences between groups at time&#95;2 and time&#95;3 in each cognitive domain, excluding selective attention that resulted higher in the AWg before surgery. Regarding cognitive outcomes, we found a reversible worsening of memory and constructional praxis, and a significant recovery at time&#95;3, similar for both groups. Assessment of time&#95;3 in respect to time&#95;1 never showed differences (all ps > .074). Moreover we found a significant lower level of tumor infiltration after surgery for AWg (p < .05), with an influence on OS (p < .05). Indeed, patients of AWg showed a significant longer OS in comparison to those in the ASg (p < .01). This result was confirmed even considering only wildtype Glioblastoma (p < .05)., Conclusion: These results indicate that awake surgery, and in general a supra-total resection of enhancing area, can improve OS in HGGs patients, preserving neuro-cognitive profile and quality of life.

Purpose: Gliomas are primary brain tumors with a life-limiting course of disease, and the last weeks of life are often characterized by neurological deficits that affect communication and personality. End-of-life treatment in this patient group therefore requires specific approaches. To date, little data is available on patients' and caregivers' needs and experiences in the last phase of the disease., Methods: In this observational study, relatives of patients treated at the University Hospital Zurich, Switzerland and deceased 2015-2017 due to glioma progression were contacted to complete a structured questionnaire assessing caregivers experience within the last weeks of the disease., Results: The survey was sent to 120 relatives of deceased patients with a glioma (WHO grades II-IV) (median patient age: 62 years; 73.8% male). Forty-three questionnaires were returned (37.7%). Approximately half of the patients were taken care of at home in the last 4 weeks of the disease, mainly with the assistance of in-home nursing care, of which eventually 14 patients (63.6%) died at home. While caregivers reported high satisfaction with medical and nursing care, psychological support was rated average to poor on a 10-point scale. Free comment fields were used widely, revealing open questions and needs of the relatives., Conclusions: This study illustrates the need for a more patient-centered end-of-life care including higher psychological support mechanisms, and a higher inclusion and consideration of relatives and caregivers into the care focus. Earlier discussion of end-of-life preferences could prevent hospitalizations in the last phase of life and could improve patients' and caregivers' quality of life.

Objective: Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)-negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance., Methods: Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN)., Results: Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1-8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1-6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus., Conclusions: Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.

Background: Patients affected by a high-grade glioma (HGG) have a poor prognosis with a median survival of 12-16 months. Such poor prognosis affects the perception of the remaining life by patients and the neuropsychological status can strongly affect every-day functioning of these patients. Monitoring changes of neuropsychological functioning (NPF) overtime may provide better clinical information and optimize the neuro-oncological management. The aims of our work were (1) to investigate the feasibility of a complex neuropsychological battery in HGG patients before and during follow-up after surgery; (2) to study the neuropsychological profile of patients affected by HGGs and their relation with the disease status (relapse/death) across time after surgery., Methods: One hundred two patients who received surgery for HGG between 2011 and 2017 were studied. All clinical data were prospectively recorded. NPF was assessed during the neuro-oncological follow-up through the Milano-Bicocca Battery (MIBIB). Statistical analysis was performed on the neuropsychological results of the tests administered., Results: First, MIBIB proved to be suitable for patients with HGG tumors before and after surgery, and during long-term follow-up; it also showed a cluster structure representative of the principal cognitive domains. Second, we found a steep decline in the neuropsychological profile before death and/or tumor relapse for the 52% of the neuropsychological tests administered., Conclusion: Complex neuropsychological batteries can be administered to HGG patients before and during follow-up after surgery. There is a correlation between neuropsychological deterioration and tumor relapse and/or death, which may reflect a progressive damage to cognitive functions due to tumor infiltration and progression.

Purpose: Fractionated radiotherapy as well as concomitant and adjuvant chemotherapy such as temozolomide for postoperative high-grade glioma (HGG) patients improves progression-free survival and overall survival. Multiple factors such as chemotherapy, radiotherapy, tumor grade, residual tumor volume, and genetic modifications might play a role in the formation of cognitive impairment. The risk factors of cognitive impairment in postoperative patients with HGG receiving radiotherapy and chemotherapy remains a concern in this population. The purpose of this study was to identify risk factors for cognitive impairment in patients of postoperative HGG., Materials and Methods: A total of 229 patients with HGG who underwent surgery were analyzed. Cognitive impairment was defined as a decrease of Cognitive Assessment Montreal (MoCA)'s score in at least two cognitive domains or any MoCA's score of less than 26 points at the time of study compared with baseline level. Multiple potential risk factors including methylated status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter, glioma World Health Organization (WHO) grade, residual tumor volume, education, and sex were analyzed. Cox univariate and multivariate regression analysis was used to detect the significant risk factors for cognitive impairment., Results: At the end of follow-up among the 229 patients, 147 patients (67%) developed cognitive impairment. 82 patients (36%) remained in normal cognitive condition. In multivariate analysis, unmethylated MGMT promoter (hazard ratio [HR], 1.679; 95% confidence interval [CI], 1.212 to 2.326; p=0.002), glioblastoma (HR, 1.550; 95% CI, 1.117 to 2.149; p=0.009), and residual tumor volume > 5.58 cm3 (HR, 1.454; 95% CI, 1.047 to 2.020; p=0.026) were independent risk factors for cognitive impairment., Conclusion: Methylated status of the MGMT promoter, glioma WHO grade, and residual tumor volume might be risk factors for the cognitive impairment in postoperative patients with HGG.

Background: Gliomas are associated with significant healthcare burden, yet reports of costs are scarce. While many costs are unavoidable there may be treatable symptoms contributing to higher costs. We describe healthcare and societal costs in glioma patients at high risk for depression and their family caregivers, and explore relationships between costs and treatable symptoms., Methods: Data from a multicenter randomized trial on effects of internet-based therapy for depressive symptoms were used (NTR3223). Costs of self-reported healthcare utilization, medication use, and productivity loss were calculated for patients and caregivers separately. We used generalized linear regression models to predict costs with depressive symptoms, fatigue, cognitive complaints, tumor grade (low-/high-grade), disease status (stable or active/progression), and intervention (use/non-use) as predictors., Results: Multiple assessments from baseline through 12 months from 91 glioma patients and 46 caregivers were used. Mean overall costs per year were M = €20,587.53 (sd = €30,910.53) for patients and M = €5,581.49 (sd = €13,102.82) for caregivers. In patients, higher healthcare utilization costs were associated with more depressive symptoms; higher medication costs were associated with active/progressive disease. In caregivers, higher overall costs were linked with increased caregiver fatigue, cognitive complaints, and lower patient tumor grade. Higher healthcare utilization costs were related to more cognitive complaints and lower tumor grade. More productivity loss costs were associated with increased fatigue (all P < 0.05)., Conclusions: There are substantial healthcare and societal costs for glioma patients and caregivers. Associations between costs and treatable psychological symptoms indicate that possibly, adequate support could decrease costs., Trial Registration: Netherlands Trial Register NTR3223.

We report a case series of four patients operated on for a glioma in awake conditions and in whom task-based functional magnetic resonance imaging (fMRI) demonstrated right-dominant activity during a language production task. Language functional sites were identified intraoperatively by electrical stimulations only in the patient with a right-sided lesion. Furthermore, the pre- or postoperative cognitive evaluations in the three patients operated on for a left-sided glioma revealed right spatial neglect and dysexecutive syndrome, hence demonstrating that, in patients with right-dominant activity on language fMRI, the left hemisphere is implicated in spatial consciousness and cognitive control. This study supports the interest of presurgical task-based language fMRI to identify patients with a reversed lateralization of cognitive functions and to make an adequate selection of the battery of intraoperative cognitive tasks to be monitored in those rare outliers., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Optic Pathway Glioma (OPG) is a relatively common brain tumour in childhood; however, there is scarce understanding of neuropsychological sequelae in these survivors. In this study, 12 children with diagnosis of OPG before 6 years of age received a comprehensive standardised assessment of visual perception, general intelligence and academic achievement, using adjustments to visual materials of the tests, to examine the extent of concurrent impairment in these functional domains. Information about vision, clinical and socio-demographic factors were extracted from medical records to assess the associations of neuropsychological outcomes with clinical and socio-demographic factors. Children with OPG exhibited high within-patient variability and moderate group-level impairment compared to test norms. Visual perception was the most impaired domain, while scholastic progression was age-appropriate overall. For cognition, core verbal and visuo-spatial reasoning skills were intact, whereas deficits were found in working memory and processing speed. Visual function was associated with tasks that rely on visual input. Children with OPG are at moderate risk of neuropsychological impairment, especially for visual perception and cognitive proficiency. Future research should elucidate further the relative contribution of vision loss and neurofibromatosis type 1 co-diagnosis within a large sample.

Objective: To determine if cognition can be used to identify persons with cancer at high risk for the impaired ability to understand treatment decisions., Methods: The association between understanding treatment decisions and cognition was examined using data from 181 participants across four groups: 67 with brain metastasis, 41 with metastatic cancer that has not spread to the brain, 27 with malignant glioma, and 46 healthy controls. All diagnoses were made by board-certified oncologists and were verified histologically., Results: Results indicated that numerous cognitive functions were associated with the ability to understand treatment decisions in persons with cancer. The following proportion of participants demonstrated impaired understanding of treatment decisions in our three patient groups: approximately 51% malignant glioma, approximately 46% brain metastasis, and approximately 24% metastatic cancer. In a combined brain cancer group, we were able to use cognitive performance to predict the impaired ability to understand treatment decisions., Conclusions: An impaired ability to understand treatment decisions is prevalent in persons with brain cancer and persons with metastatic cancer. Performance on a brief cognitive battery can be used to help clinicians identify patients at particular risk for impaired medical decision making., (© 2019 John Wiley & Sons, Ltd.)

Background: Little is known about the symptoms glioma patients experience in the year before diagnosis, either or not resulting in health care usage. This study aimed to determine the incidence of symptoms glioma patients experienced in the year prior to diagnosis, and subsequent visits to a general practitioner (GP)., Methods: Glioma patients were asked to complete a 30-item study-specific questionnaire focusing on symptoms they experienced in the 12 months before diagnosis. For each indicated symptom, patients were asked whether they consulted the GP for this issue., Results: Fifty-nine patients completed the questionnaires, 54 (93%) with input of a proxy. The median time since diagnosis was 4 months (range 1-12). The median number of symptoms experienced in the year before diagnosis was similar between gliomas with favourable and poor prognosis, i.e. 6 (range 0-24), as were the five most frequently mentioned problems: fatigue (n = 34, 58%), mental tiredness (n = 30, 51%), sleeping disorder (n = 24, 41%), headache (n = 23, 39%) and stress (n = 20, 34%). Twenty-six (44%) patients visited the GP with at least one issue. Patients who did consult their GP reported significantly more often muscle weakness (11 vs 3, p = 0.003) than patients who did not, which remained significant after correction for multiple testing, which was not the case for paralysis in hand/leg (10 vs 4), focussing (11 vs 6) or a change in awareness (9 vs 4)., Conclusions: Glioma patients experience a range of non-specific problems in the year prior to diagnosis, but only patients who consult the GP report more often neurological problems.

Purpose: This study aimed to investigate the preoperative predictive factors affecting return to work in patients with gliomas in the left cerebral hemisphere undergoing awake surgery., Methods: We retrospectively reviewed 50 consecutive glioma patients who underwent awake surgery from January 2012 to July 2017. Adult patients older than 18 years, who reported working prior to surgery, were recruited for this study., Results: Comparing sociodemographic, disease-related and preoperative neurocognitive variables of glioma patients who returned to work and those who did not, binomial logistic regression models for preoperative predictors affecting return to work revealed significant differences in age and sole breadwinner status as sociodemographic variables, tumour volume as a disease-related variable, and Verbal IQ, Performance IQ, general memory, attention/concentration, and working memory as neurocognitive variables. Multivariate logistic regression models demonstrated that the independent factors associated with propriety of returning to work 1 year after surgery was the sociodemographic variable sole breadwinner status (yes vs no; OR = 15.00, 95% CI 2.22-101.35, p = 0.01), the disease-related variable tumour volume (per 1 cm 3 ; OR = 0.98, 95% CI 0.96-0.99, p = 0.04), and the preoperative neurocognitive variable general memory (≥ 100 vs < 100; OR = 21.70, 95% CI 2.60-183.94, p = 0.01)., Conclusions: Our results suggest that three predictive factors including sole breadwinner status, tumour volume and general memory that can be assessed in the preoperative stage substantially contribute to returning to work in patients with gliomas in the left cerebral hemisphere, 1 year after awake surgery.

Objective: Brain tumours are relatively rare but hold a significant place in cancer rehabilitation due to their pronounced disabling capacity to promote physical, cognitive and psychosocial sequelae. This small-scale qualitative study used coping and motivational theories to gain understanding and knowledge of patients' experience of being diagnosed with a severe disease and of their view of a rehabilitation process., Design: Qualitative interview study., Setting: Odense University Hospital, Denmark., Informants: Five patients (men, aged 30-79 years) with primary glioma who had participated in a rehabilitation intervention., Methods: Semi-structured interviews were conducted. The phenomenological interpretive analysis was used to analyse the interviews., Results: The analysis revealed three main themes: (1) coping with a new life situation, (2) motivating and maintaining elements and (3) experience of the benefit of the rehabilitation programme., Conclusion: The study concluded that interviewed informants use problem-solving coping strategies, which make them more active in their health behaviour. However, passive and emotion-focused strategies related to confronting diagnosis may be used in some cases. The motivational aspect is multifaceted. Personal and interpersonal elements alongside a competitive setting are crucial to self-efficacy and benefit. The intervention's impact on health-related quality of life also has the potential to increase patients' resources to manage their situation., Trial Registration Number: NCT02221986., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Clinical significance of a decline in free T4 (FT4) concentrations across the reference range in children with brain tumors treated with radiation therapy (RT) is uncertain., Objectives: To study trends in FT4 in children after RT and risk factors and health outcomes associated with plasma FT4 concentrations., Design and Setting: Longitudinal, single-center retrospective cohort study., Patients: Low-grade glioma or ependymoma patients (n = 267; age ≤25 years) who received RT (50.4 to 59.4 Gy) at a single institution (1996 to 2016) and followed with serial FT4 measurements., Main Outcome Measure: A linear mixed-effects model with a random intercept was used to investigate risk factors for longitudinal changes in FT4 concentrations. A two-stage mixed-effects model examined associations between clinical outcomes and plasma FT4 concentrations., Results: FT4 concentrations declined over time after RT (P < 0.001). Females (P < 0.001) and younger patients (P < 0.001) demonstrated greater declines in FT4 concentrations over time. The rate of weight gain, but not of height loss, increased with a higher FT4 decline rate (P < 0.001). At last follow-up, patients with lower baseline FT4 concentrations had increased risk of glucose disorder (OR, 19.73; P = 0.002) or dyslipidemia (OR, 19.40; P = 0.003) but not high fat mass (P = 0.18). Lower baseline FT4 concentrations were not associated with impaired scores for intelligence, attention, memory, or psychosocial functioning., Conclusions: FT4 concentrations significantly decline in children with brain tumor after RT. Variation and trends in FT4 concentration are associated with physical health outcomes. Future studies should assess whether continuous FT4 concentrations and trends, rather than population-based cut-off values, can distinguish between euthyroid and hypothyroid states., (Copyright © 2019 Endocrine Society.)

Aim: This study aimed to assess the prevalence of symptoms glioma patients may present with to the general practitioner, and whether these can be distinguished from patients with other CNS disorders or any other condition. Methods: Glioma patients were matched to CNS patients and 'other controls' using anonymized general practitioner registries. Prevalences were evaluated in the 5 years prior to diagnosis. Result: CNS patients reported significantly more motor symptoms in the period 60-24 months, (p = 0.039). Moreover, <6 months before diagnosis CNS patients differed significantly in mood disorders/fear compared with 'other controls' (p = 0.012) but not glioma patients (p = 0.816). Conclusion: Glioma patients could not be distinguished from both control groups with respect to the number or type of prediagnostic symptoms.

In recent years, advances in cortical-subcortical mapping, intraoperative neurophysiology, and neuropsychology have increased the ability to remove intrinsic brain tumors, expanding indications and maximizing the extent of resection. This has provided a significant improvement in progression-free survival, time of malignant transformation (in low-grade gliomas), and overall survival. Although current techniques enable preservation of language and motor functions during surgery, the maintenance of a complex set of functions defined with the term cognition is not always achievable. Cognition is defined as every neural process underlying a high human function and includes motor haptic and visuospatial functions, memory, social interactions, empathy, and emotions. In this regard, an extensive preoperative and postoperative neuropsychological evaluation is strongly suggested to assess cognitive impairment due to tumor growth, to assess surgical result, and to plan cognitive rehabilitation. This article discusses the main recent innovations introduced for cognitive mapping with the aim to preserve cognitive functions, which are essential to maintain a high quality of life., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: This study investigated the levels of depression, subjective prospective memory (PM), and subjective retrospective memory (RM) among Chinese glioma patients and explored the bi-directional relationships between depression and memory impairment, including subjective PM and RM., Methods: Seventy-one participants with glioma were assessed for depression, PM, and RM at two time points (Time 1: within 48 h of being hospitalized; Time 2: two weeks after surgery). A cross-lagged path analysis was conducted to examine the bi-directional relationships between depression and memory., Main Results: Depression at T1 predicted memory impairment total scores (β = 0.22, P = 0.011) and RM (β = 0.29, P < 0.001) at T2. However, depression at TI could not predict PM at T2 (β = 0.15, P = 0.090). Memory, whether PM or RM, at T1 could not predict depression at T2 (β = 0.07, P = 0.497; β = 0.00, P = 0.978; β = 0.06, P = 0.321)., Conclusions: Depression can affect RM memory impairment among glioma patients. Oncology nurses should preoperatively screen for depression in glioma patients to identify high-risk groups, for whom emotional interventions and memory training should be carried out to reduce postoperative RM memory impairment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Patients with diffuse glioma often experience neurocognitive impairment already prior to surgery. Pertinent information on whether damage to a specific brain region due to tumor activity results in neurocognitive impairment or not, is relevant in clinical decision-making, and at the same time renders unique information on brain lesion location and functioning relationships. To examine the impact of tumor location on preoperative neurocognitive functioning (NCF), we performed MRI based lesion-symptom mapping., Methods: Seventy-two patients (mean age 40 years) with a radiologically suspected glioma were recruited preoperatively. For each of the six cognitive domains tested, we used tumor localization maps and voxel-based lesion-symptom mapping analyses to identify cortical and subcortical regions associated with NCF impairment., Results: Compared to healthy controls, preoperative NCF was significantly impaired in all cognitive domains. Most frequently affected were attention (30% of patients) and working memory (20% of patients). Deficits in attention were significantly associated with regions in the left frontal and parietal cortex, including the precentral and parietal-opercular cortex, and in left-sided subcortical fiber tracts, including the arcuate fasciculus and corticospinal tract. Surprisingly, no regions could be related to working memory capacity. For the other neurocognitive domains, impairments were mainly associated with regions in the left hemisphere., Conclusions: Prior to treatment, patients with diffuse glioma in the left hemisphere run the highest risk to have NCF deficits. Identification of a left frontoparietal network involved in NCF not only may optimize surgical procedures but may also be integrated in counseling and cognitive rehabilitation for these patients.

Purpose: Progressive disease in patients with high-grade glioma may be reflected in cognitive decline. However, the cognitive functions most sensitive to progression may differ between patients. We investigated whether decline on a personalized selection of tests predicted progressive disease according to RANO criteria in high-grade glioma patients., Methods: Starting one day before surgery, patients underwent neuropsychological assessment every three months during standard treatment and clinical follow-up. We first made a personalized selection of three tests that showed the highest Reliable Change Index (RCI) values, i.e., most positive change, at the first post-surgical assessment for each patient. In subsequent follow up, a decline of RCI ≤ - 1 on at least two of the three tests in the selection was considered cognitive decline. We performed a discrete Cox proportional hazards model including a time-dependent coefficient cognitive decline (vs. stability) and covariate age to predict progressive disease., Results: Twenty five patients were included. Cognitive decline on the personalized test selection preceded or had occurred by the time progression was established in 9/15 patients with RANO confirmed progressive disease (60%). Decline was absent in 8/10 patients (80%) with stable disease during participation. The independent hazard ratio for progression in case of cognitive decline was 5.05 (p < 0.01) compared to stable performance., Conclusions: Using only three patient-specific neuropsychological tests, we found a fivefold increased chance of disease progression in case of cognitive decline as compared to stable performance. Brief, patient-tailored cognitive assessment may be a noninvasive addition to disease monitoring without overburdening patients and clinical care.

Background: Current estimates suggest that 75% of children diagnosed with a central nervous system (CNS) tumor will become 5-year survivors. However, survivors of childhood CNS tumors are at increased risk for long-term morbidity., Methods: To determine long-term neuropsychological and socioeconomic status (SES) outcomes, adult survivors of pediatric low-grade gliomas (n = 181) in the Childhood Cancer Survivor Study and a sibling comparison group that was frequency-matched by age and sex (n = 105) completed a comprehensive battery of standardized neuropsychological tests and an SES assessment. Multivariable regression models compared treatment-specific groups for neuropsychological and SES outcomes and evaluated associations with tumor location, age at diagnosis, sex, and age at evaluation., Results: In adjusted models, survivors treated with surgery and radiotherapy (surgery+RT; median age at diagnosis, 7 years; median age at assessment, 41 years) scored lower on estimated IQ than survivors treated with surgery only, who scored lower than siblings (surgery+RT, 93.9; surgery only, 101.2; siblings, 108.5; all P values <.0001). Survivors diagnosed at younger ages had low scores for all outcomes (P < .05) except for attention/processing speed. For SES outcomes, survivors treated with surgery+RT had lower occupation scores (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.1-5.9), lower income (OR, 2.6; 95% CI, 1.3-5.0), and less education (OR, 2.1; 95% CI, 1.1-4.0) than those treated with surgery only., Conclusions: Decades after treatment, survivors treated with radiotherapy and at younger ages had poorer neuropsychological and SES outcomes. Lifelong surveillance of survivors of pediatric low-grade gliomas may be warranted as life events, stages, and transitions (employment, family, and aging) present new challenges and risks., (© 2019 American Cancer Society.)

Background: Patients with frontal glioma might experience cognition alterations together with potential dysfunction of resting-state networks (RSNs). To understand the altered patterns of the intrinsic activity and underlying network interactions between the cognitive-related RSNs is of great importance., Objective: This study aimed to investigate the characteristics of the altered RSNs, including default mode network, executive control network, and salience network and further elucidate the possible functional reorganization of RSNs in patients with frontal glioma., Methods: Thirteen patients with frontal glioma and 10 healthy controls (HCs) were enrolled in this study. Independent component analysis was performed to identify the characteristics of the selected RSNs activity. Further, functional connectivity analysis was applied to investigate the relationship between the altered regions. Subsequently, partial correlation analysis was performed to examine associations between the neural activity of RSNs and neurocognitive characteristics., Results: Compared with the HCs group, the patient group exhibited significant differences in functional connectivity among default mode network, executive control network, and salience network. In addition, the number of the significant functional connectivities between the paired seeds observed in the patients was greater than that in HCs and significantly increased functional connectivity was detected between left posterior cingulate cortex and right angular gyrus. Furthermore, altered neural activities in the RSNs of patients with frontal glioma were positively associated with certain aspects of cognitive function., Conclusions: Our results suggested underlying network functional reorganization of the triple unifying RSNs in patients with frontal glioma, providing novel insights for improving understanding of brain function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Prognostic value of health-related quality of life (HRQoL) data may be important to inform patients in clinical practice and to guide clinical decision-making. Our study investigated the added prognostic value of HRQoL for overall survival (OS) and progression-free survival (PFS) in a large heterogeneous sample of glioma patients, besides known prognostic factors., Methods: We included individual baseline data from previously published randomised controlled trials (RCTs) in glioma patients in which HRQoL was assessed through the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BN20 questionnaires. Multivariable Cox regression models (stratified for newly diagnosed versus recurrent disease) were constructed, first with clinical variables (age, sex, tumour type, performance status, allocated treatment and extent of resection) only and subsequently with HRQoL variables added, separately for OS and PFS. The added prognostic value of HRQoL was calculated using C-indices., Results: Baseline HRQoL and clinical data from 15 RCTs were included, comprising 5217 patients. In the model including both clinical and HRQoL variables, better cognitive and role functioning and less motor dysfunction were independently associated with longer OS, whereas better role and cognitive functioning, less nausea and vomiting and more appetite loss were independently associated with prolonged PFS. However, C-indices indicated only a small prognostic improvement of the models for OS and PFS when adding HRQoL to the clinical prognostic variables (+1.1% for OS and +.7% for PFS)., Conclusion: Our findings demonstrate that several baseline HRQoL variables are independently prognostic for OS and PFS, yet the added value of HRQoL to the known clinical prognostic variables was small., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The present study attempted to explore the moderating effect of depression on the association between posttraumatic growth (PTG) and quality of life (QoL) in low-grade glioma patients in China. A prospective study design was conducted. Patients completed the survey approximately 1 month and 1 year after surgery. A hierarchical linear model was used to examine the linear and the quadratic relationships between PTG and QoL. The interaction term of PTG and depression was included in the model to explore the moderating effect of depression. A quadratic relationship was found between PTG and QoL in the patients who had significant depressive symptoms. A linear relationship between PTG and QoL was found in the patients without significant depressive symptoms. In conclusion, PTG improved the patients' quality of life to some extent. The relationship between PTG and QoL in LGG patients depends on the level of depression.

This study aimed to explore the effects of radiochemotherapy on the neurocognitive function of patients with high-grade gliomas (HGG). The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), event-related potential P300 (ERP-P300), and specific MRI parameters were compared, and the associations between specific MRI parameters and different doses of radiation were determined for before and up to 12 months after radiotherapy. There were no significant differences in MMSE, MoCA, or ERP-P300 before and after radiotherapy. Compared with pre-radiochemotherapy, fractional anisotropy (FA) in the contralateral hippocampus decreased at 6 and 9 months after radiotherapy. FA in the ipsilateral hippocampus before radiochemotherapy decreased compared with 6 months after radiotherapy. Compared to the end of radiotherapy, as well as 3- and 6-months post-radiotherapy, the regional cerebral blood volume (rCBV) in the genu of the corpus was significantly lower at 12 months post-radiotherapy. Some MRI parameters in different regions of the brain were negatively correlated with the mean and maximum dose. There was no significant effect of radiochemotherapy on the neurocognitive functioning of patients with HGGs found before radiochemotherapy until 12 months after radiotherapy. The radiation-induced FA decrease in the bilateral hippocampus preceded cognitive dysfunction, and DTI of the hippocampus may provide a useful biomarker for predicting radiation-induced neurocognitive impairment in patients with HGGs.

Introduction: Cognitive deficits occur frequently in diffuse glioma patients, but are limitedly understood. An important marker for survival in these patients is isocitrate dehydrogenase (IDH) mutation (IDH-mut). Patients with IDH-mut glioma have a better prognosis but more often suffer from epilepsy than patients with IDH-wildtype (IDH-wt) glioma, who are generally older and more often have cognitive deficits. We investigated whether global brain functional connectivity differs between patients with IDH-mut and IDH-wt glioma, and whether this measure reflects variations in cognitive functioning in these subpopulations beyond the associated differences in age and presence of epilepsy., Methods: We recorded magnetoencephalography and tested cognitive functioning in 54 diffuse glioma patients (31 IDH-mut, 23 IDH-wt). Global functional connectivity between 78 atlas regions spanning the entire cortex was calculated in two frequency bands (theta and alpha). Group differences in global functional connectivity were tested, as was their association with cognitive functioning, controlling for age, education, and presence of epilepsy., Results: Patients with IDH-wt glioma had lower functional connectivity in the alpha band than patients with IDH-mut glioma (p = 0.040, corrected for age and presence of epilepsy). Lower alpha band functional connectivity was associated with poorer cognitive performance (p < 0.034), corrected for age, education, and presence of epilepsy., Conclusion: Global functional connectivity is lower in patients with IDH-wt diffuse glioma compared to patients with IDH-mut diffuse glioma. Moreover, having lower functional alpha connectivity relates to poorer cognitive performance in patients with diffuse glioma, regardless of age, education, and presence of epilepsy., (© 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Purpose: The primary objective of this study was to investigate the incidence of PTSD at 3 months postoperatively in patients who were newly diagnosed with LGGs, and its association with 5-year survival. Moreover, QoL and other psychiatric disorders like depression and anxiety were also evaluated., Methods: From February 2011 to April 2013, patients who underwent low-grade glioma surgery at our hospital and come back for reexamination at 3-month follow-up were considered for this study. Interviews, HADS-A, HADS-D, and SF-36 scales were used for evaluating PTSD, anxiety, depression, and quality of life. Participants were asked to complete these assessments at 3 months after surgery. Followed-ups on survival status were made for 5 years., Results: A total of 219 subjects comprising 83 women and 136 men with a mean age of 41.5 years were included in this study. At 3 months after surgery, 35 (16%) patients were diagnosed with PTSD. Younger age (OR = 2.23, [95% CI 1.02-4.84], P = 0.04) and frontal lobe involvement of tumor (OR = 2.57, [95% CI 1.06-6.23], P = 0.04) predicted PTSD. Patients with PTSD had higher anxiety and depression level, and had worse QoL in all eight dimensions of SF-36. Kaplan-Meier analyses demonstrated that diagnosis of PTSD was associated with shorter overall survival in LGG patients (Log-rank = 7.45, P = 0.01). After adjusting for other variables, PTSD remained associated with elevated 5-year overall mortality risk of LGG patients (HR = 2.98 [95% CI 1.10-8.05], P = 0.03)., Conclusions: The results showed that newly diagnosed LGG patients suffering from PTSD at 3 months after surgery had lower rates of 5-year survival. In clinical practice, psychological evaluation is suggested for LGG patients and proper psychotherapy should be considered for those with PTSD.

Clinical trial accrual is vital to advancing care. A single study elucidated demographic data correlating with glioma patients' clinical trial enrollment. However, it did not investigate the underlying decision-making process for non-participation. In this study, we seek to understand this key aspect of patient accrual. All notes for glioma patients seen by a single neuro-oncologist from July 2010 to May 2017 were examined for mention of clinical trial offerings. When a trial was declined, the patient's reasoning was recorded along with the following: diagnosis, KPS, extent of resection, age, gender, race, marital status, income group, religion, trial offered at initial visit versus subsequent, and distance from trial site. Of 279 consecutive glioma patients, 88 were eligible for and offered a clinical trial. Fifty-seven accepted (65%), and 31 (35%) declined participation (Fig. 1). Of those offered a clinical trial, patients with glioblastoma (GBM) were significantly more likely to accept (44 out of 57 (77%) vs. 13 out of 57 (23%), p =0.03). After we adjusted for gender and travel distance, GBM was the only significant predictor of clinical trial acceptance, with an odds ratio of 3.18 (95% CI 1.17, 8.61, p =0.02). Reasons cited for non-participation included: travel distance (39%), lack of interest (39%), visit frequency (16%), and fear of randomization (6%). This study clarified for the first time individual glioma patient rationale for non-participation and potential areas for improving enrollment. Allowing off-site treatment centers or telemedicine visits may entice rural patients to participate. Visit frequency should be carefully considered and minimized whenever possible. Further prospective study of rationale for non-participation may improve enrollment over time.

Objective: Although the parietal lobe is a common site for glioma formation, current literature is scarce, consists of retrospective studies, and lacks consistency with regard to the incidence, nature, and severity of parietal association deficits (PADs). The aim of this study was to assess the characteristics and incidence of PADs in patients suffering from parietal lobe gliomas through a prospective study and a battery of comprehensive neuropsychological tests., Methods: Between 2012 and 2016 the authors recruited 38 patients with glioma confined in the parietal lobe. Patients were examined for primary and secondary association deficits with a dedicated battery of neuropsychological tests. The PADs were grouped into 5 categories: visuospatial attention, gnosis, praxis, upper-limb coordination, and language. For descriptive analysis tumors were divided into high- and low-grade gliomas and also according to patient age and tumor size., Results: Parietal association deficits were elicited in 80% of patients, thus being more common than primary deficits (50%). Apraxia was the most common PAD (47.4%), followed by anomic aphasia and subcomponents of Gerstmann's syndrome (34.2% each). Other deficits such as hemineglect, stereoagnosia, extinction, and visuomotor ataxia were also detected, albeit at lower rates. There was a statistically nonsignificant difference between PADs and sex (72.2% males, 85% females) and age (77.8% at ≤ 60 years, 80% at age > 60 years), but a statistically significant difference between the > 4 cm and the ≤ 4 cm diameter group (p = 0.02, 94.7% vs 63.2%, respectively). There was a tendency (p = 0.094) for low-grade gliomas to present with fewer PADs (50%) than high-grade gliomas (85.7%). Tumor laterality showed a strong correlation with hemineglect (p = 0.004, predilection for right hemisphere), anomia (p = 0.001), and Gerstmann's symptoms (p = 0.01); the last 2 deficits showed a left (dominant) hemispheric preponderance., Conclusions: This is the first study to prospectively evaluate the incidence and nature of PADs in patients with parietal gliomas. It could be that the current literature may have underestimated the true incidence of deficits. Dedicated neuropsychological examination detects a high frequency of PADs, the most common being apraxia, followed by anomia and subcomponents of Gerstmann's syndrome. Nevertheless, a direct correlation between the clinical deficit and its anatomical substrate is only possible to a limited extent, highlighting the need for intraoperative cortical and subcortical functional mapping.

Objective: Caregivers to patients with primary malignant brain tumours neglect their own physical and emotional needs during the disease trajectory. The aim of the systematic review was to explore how informal caregivers of patients with primary malignant brain tumour (high-grade glioma (HGG)) experience and manage their life situation after the death of the patient., Methods: A systematic literature search was carried out in December 2016 and revised in September 2017. The following six databases were searched: PubMed, Cumulative Index of Nursing and Allied Health Literature, Excerpta Medica database, Scopus, PsycINFO and The Social Sciences Citation Index. Studies eligible for inclusion met the following criteria: (1) included bereaved caregivers to patients diagnosed with HGG ≥18 years, (2) described the caregiver's perspective at post bereavement (3) had been peer-reviewed. The papers included were assessed for methodological quality using the Critical Appraisal Skills Programme., Results: Four qualitative articles, published from 2004 to 2015, met the eligibility criteria. Bereaved informal caregivers expressed profound grief and had unmet needs and questions related to the disease and their role as caregiver. Moreover, they experienced depressive symptoms and fatigue, resulting in a reduced work capability and social network., Conclusions: We conclude that bereaved informal caregivers experience psychosocial consequences and emotional reactions after bereavement, resulting in feelings of isolation and loneliness. This review identified limited evidence on how the bereaved caregivers prefer to be supported, and further study is warranted. We suggest incorporating systematic information on bereavement in clinical practice and a cooperation across sectors., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Purpose: Low-grade gliomas (LGG) are a heterogeneous group of brain tumors, which are often assumed to have a benign course. Yet, children diagnosed and treated for LGG in infancy are at increased risk for neurodevelopmental disruption. We sought to investigate neuropsychological outcomes of infants diagnosed with LGG., Methods: Between 1986 and 2013, 51 patients were diagnosed with LGG before 12 months of age and managed at St. Jude Children's Research Hospital. Twenty-five of the 51 patients received a cognitive assessment (68% male; 6.8 ± 3.3 months at diagnosis; 10.5 ± 4.8 years at latest assessment). Approximately half the patients received radiation therapy (n = 12; aged 4.0 ± 3.0 years at radiation therapy), with a median of 2 chemotherapy regimens (range = 0-5) and 1 tumor directed surgery (range = 0-5)., Results: The analyses revealed performance below age expectations on measures of IQ, memory, reading, mathematics, and fine motor functioning as well as parent-report of attention, executive, and adaptive functioning. Following correction for multiple comparisons, a greater number of chemotherapy regimens was associated with lower scores on measures of IQ and mathematics. More tumor directed surgeries and presence of visual field loss were associated with poorer dominant hand fine motor control. Radiation therapy exposure was not associated with decline in neuropsychological performance., Conclusions: Children diagnosed with LGG in infancy experience substantial neuropsychological deficits. Treatment factors, including number of chemotherapy regimens and tumor directed surgeries, may increase risk for neurodevelopmental disruption and need to be considered in treatment planning.

Language deficits following brain tumors should consider the dynamic interactions between different tumor growth kinetics and functional network reorganization. We measured the resting-state functional connectivity of 126 patients with left cerebral gliomas involving language network areas, including 77 patients with low-grade gliomas (LGG) and 49 patients with high-grade gliomas (HGG). Functional network mapping for language was performed by construction of a multivariate machine learning-based prediction model of individual aphasia quotient (AQ), a summary score that indicates overall severity of language impairment. We found that the AQ scores for HGG patients were significantly lower than those of LGG patients. The prediction accuracy of HGG patients (R 2  = 0.27, permutation P = 0.007) was much higher than that of LGG patients (R 2  = 0.09, permutation P = 0.032). The rsFC regions predictive of LGG's AQ involved the bilateral frontal, temporal, and parietal lobes, subcortical regions, and bilateral cerebro-cerebellar connections, mainly in regions belonging to the canonical language network. The functional network of language processing for HGG patients showed strong dependence on connections of the left cerebro-cerebellar connections, limbic system, and the temporal, occipital, and prefrontal lobes. Together, our findings suggested that individual language processing of glioma patients links large-scale, bilateral, cortico-subcortical, and cerebro-cerebellar functional networks with different network reorganizational mechanisms underlying the different levels of language impairments in LGG and HGG patients., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This study aims to identify the neuropsychological tests commonly used for assessment in each neurocognitive domain, and quantify the post-operative changes in neurocognitive function in the immediate post-operation and follow-up., Methods: With the use of the PubMed, a comprehensive search of the English literature was performed following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. There were 1021 publications identified for screening. Standardized mean differences (SMD) in neuropsychological task performance were calculated both for immediate post-operation (up to 1 week) and follow-up (up to 6 months)., Results: Out of 12 studies which met the inclusion criteria, 11 studies were analyzed in this meta-analysis, with a total of 313 patients (age range 18-82, 50% males) with intracranial gliomas (45% high-grade, 55% low-grade). Complex attention, language and executive function were the most frequently tested neurocognitive domains. Surgery had a positive impact in the domains of complex attention, language, learning and memory tasks in the immediate post-operative period and sustained improvement at follow-up. In contrast, surgery was found to negatively impact performance for executive function in the immediate post-operative period with sustained decline in performance in the long term., Conclusions: This meta-analysis suggests that surgery for glioma confers a benefit for the domains of complex attention, language, learning and memory, while negatively affecting executive function, in the periods immediately after surgery and at 6 months follow-up. In addition, awake surgery seemed to confer a beneficial effect on neurocognitive functions. Future research should attempt to standardize a battery of neuropsychological tests for patients undergoing surgical resection for glioma, perhaps with a particular focus on executive function.

Background: Adaptive behavior, i.e., the performance on daily activities required for personal and social independence, is essential to estimate in children with low-grade glioma (LGG) since most of them are long-term survivors. Our aim was to investigate adaptive behavior in children with LGG., Methods: In a cross-sectional study, adaptive behavior was assessed using the paper pencil version of the Parent Form of the Vineland Adaptive Behavior Scales 2nd edition (VABS-II) testing communication, daily living skills, social skills, and motor skills. Scores of children with LGG, younger than 20 years, and diagnosed between 2004 and 2014 were compared with family controls. Correlations between clinical variables and adaptive behavior were explored., Results: Fifty-six children with LGG (median age, 12.1 years; 52% male) and 46 controls (median age, 11.0 years; 43% male) were included in the analyses. Compared with controls, the LGG group was more impaired on total adaptive behavior, communication, and motor skills and in the subdomain gross motor skills (effect sizes d, 0.64-0.86, P < 0.003). Younger age at diagnosis (r = -0.357, P < 0.01) and chemotherapy (r = -0.342, P < 0.05) were associated with poorer motor skills. Residual disease was associated with poorer total adaptive behavior (r = -0.282, P < 0.05). No other significant correlations were found., Conclusion: At the group level, adaptive functioning of children with LGG is impaired compared with family controls. Regular structured monitoring of adaptive behavior is recommended to be able to define the needs for tailored rehabilitation in daily life at home as well as at school., (© 2018 Wiley Periodicals, Inc.)

Objectives: To describe the adaptability to the patterns in symptoms and quality of life (QoL) during 6 months post low-grade glioma diagnosis by valid and reliable tools; to identify through qualitative interviews patient/provider adaptive techniques and strategies; and to assess associations among patient characteristics, symptoms and QoL, and adaptive techniques or strategies., Data Sources: Demographic, clinical and pathologic data from medical records. Validated instruments that assess QoL, fatigue, depression, and distress were completed at 2, 4, and 6 months post diagnosis. Qualitative interviews identifying the symptoms, challenges, adaptive techniques and strategies were conducted at 4 and 6 months., Conclusion: The most frequently used adaptive strategies included: obtaining community support (87%), managing expectations (73%) and support systems (67%), and seeking out knowledge about physical (67%) and behavioral symptoms (53%). Seizures were reported with IDH1 mut (11%) but not IDH1 wildtype . Patients with either IDH1 mut or TERT mut consistently reported lower QoL and higher distress, depression, and fatigue scores. IDH1/TERT mut may be related to lower QoL because of IDH1 mut -related seizures., Implications for Nursing Practice: Findings provide a list of adaptive strategies and characteristics to address the problems and symptoms that may improve overall QoL in patients with low-grade glioma., (Copyright © 2018. Published by Elsevier Inc.)

Aim of Study: The survival rate in high-grade glioma (HGG) patients receiving a combined regimen of radiotherapy (RT) and temozolomide after tumor resection was increased. However, cognitive deficits and depression after the treatments challenge the treatments. The aim of this study was to evaluate the cognition and depression in postoperative patients with HGG following RT and chemotherapy., Materials and Methods: Six-five eligible patients were included in the study. Cognition and depression were examined at baseline (after surgery before RT), every 3 months during follow-up using mini-mental state examination and Zung Self-Rating Depression Scale (SDS), respectively., Results: Our results showed that cognition was not significantly affected after treatments (F = 1.19, P = 0.32). However, significant differences between baseline and follow-ups were found regarding SDS scores (F = 3.26, P =0.0.01). SDS score at the 3 rd month was significantly higher than that at baseline (t = -3.16, P = 0.002)., Conclusion: This prospective study showed that although cognition was not significantly affected, the treatment caused depression, particularly at the 3 rd month. These data implicated that interventions should be designed to deal with depression in the 3 rd month., Competing Interests: None

Introduction: Glioma is the most common intracranial primary brain tumor. Patients with glioma often suffer from epilepsy, anxiety and depression. Aims of this study were to identify risk factors for drug-treated anxiety and depression, and to determine the use of psychiatric medication in a national glioma cohort., Methods: Data from the Cancer Registry of Norway on all persons diagnosed with glioma WHO grade II-IV 2004-2010 were linked with data from the Norwegian Prescription Database. Cox regression analysis was used to assess risk factors for drug-treated anxiety and depression. Standardized incidence ratios were calculated for psychiatric medication dispensed to glioma patients and compared to the general population., Results: The glioma cohort consisted of 1056 males and 772 females. Of the 1828 patients, 565 had glioma grade II-III, and 1263 had grade IV. The patients with glioma grade II-III who were treated with levetiracetam had an increased risk for drug-treated anxiety compared to patients without levetiracetam; hazard ratio 2.8 (95% confidence interval 1.7-4.9). Female gender increased the risk for drug-treated anxiety compared to males in patients with glioma grade IV; hazard ratio 1.5 (95% confidence interval 1.2-2.0). Antidepressants were less frequently dispensed to patients with glioma grade II-III and epilepsy than to the general population., Conclusions: Patients with glioma grade II-III on levetiracetam had an increased risk for drug-treated anxiety. The subgroup of patients with glioma grade II-III and epilepsy received less antidepressants than the general population.

Objective: Memory complaints are common in patients after brain tumor, but is difficult to map memory functions during awake surgery, to preserve them. Thus we analyzed one of the largest data sets on clinical, surgical, and anatomical correlates of memory in patients with brain tumor to date, providing anatomical hotspots for short and long-term memory functions., Methods: A total of 260 patients with brain tumor (130 high-grade gliomas; 76 low-grade gliomas [LGG]; 54 meningiomas) were tested on 2 commonly used short-term memory (Digit Span Forward and Corsi Spatial Span) and 2 long-term memory tasks (Narrative Memory and Delayed Recall of Rey Figure). Patients were evaluated before and immediately after surgery and (for LGG) after 4 months and data analyzed by means of analysis of covariance and the voxel-based lesion-symptom mapping technique., Results: As expected, patients with high-grade gliomas were already impaired before surgery, whereas patients with meningioma were largely unimpaired. Patients with LGG were unimpaired before surgery, but showed significant performance drop immediately after, with good recovery within few months. Voxel-based lesion-symptom mapping analyses identified specific anatomical correlates for verbal memory tasks, whereas visuospatial tasks provided good sensitivity to cognitive damage but failed to show anatomical specificity. Anatomical hotspots identified were in line with both previous functional magnetic resonance imaging and clinical studies on other neurological populations., Conclusions: Verbal memory tasks revealed a set of specific anatomical hotspots that might be considered "eloquent" for verbal memory functions, unlike visuospatial tasks, suggesting that commonly used spatial memory tasks might not be optimal to localize the damage, despite an otherwise good sensitivity to cognitive damage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

High-grade gliomas (HGGs; grades III and IV) are the most common and aggressive adult primary brain tumors, and their invasive nature ranks them the fourth in the incidence of cancer death. In our previous study, we found that AG-1031 and AG-1503 showed inhibitory effects on several cancer cell lines. In this study, C6 glioma-bearing rats were treated with AG-1031 or AG-1503. Western blot results of autophagy-associated protein (LC3 II/I, Beclin-1) and apoptosis-associated proteins (caspase-3, Bcl-2, Bax) revealed that AG-1031 could activate apoptotic signal pathway via inhibiting autophagy process in cancer cells. HE staining indicated that the tumor volumes were significantly decreased in AG-1031 and AG-1503 treated rats compared to non-treated C6 glioma-bearing rats. Meanwhile, AG-1031 and AG-1503 significantly decreased the expression of VEGF, a marker of invasion ability of tumor, in tumor tissue. The novel object recognition test showed that cognitive functions in C6 glioma-bearing rats were considerably damaged, whereas AG-1031 and AG-1503 significantly impeded the cognitive impairment. AG-1031 and AG-1503 efficiently alleviated the glioma-induced impairments of long-term potentiation (LTP), which was damaged in C6 glioma-bearing rats. Furthermore, AG-1031 and AG-1503 augmented the expression of synaptophysin (SYP), which were decreased in glioma rats. In conclusion, our results suggest that AG-1031 and AG-1503 can inhibit the expansion of glioma, and improve the cognitive impairment caused by glioma in glioma-bearing rats., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Extended margin tumor resection beyond the abnormal area detected by magnetic resonance imaging, defined as supratotal resection, could improve the outcomes of patients with lower grade gliomas (LGGs). The aim of the present study was to assess the surgical outcomes of awake brain mapping to achieve supratotal resection with determination of the normal brain tissue boundaries beyond the tumor of frontal LGGs, in both dominant and nondominant hemispheres., Methods: We analyzed the data from 9 patients with diffuse frontal LGGs who had undergone supratotal resection with awake surgery from January 2016 to November 2017., Results: The frontal aslant tract was identified as the functional boundary in 4 of 5 left frontal tumor cases (80%). Working memory impairments during dorsolateral prefrontal cortex stimulation with digit span and/or visual N-back tasks were detected in all 4 patients (100%) with right-frontal tumor. The neurocognitive outcomes were significantly improved after surgery, as shown by the mean Wechsler adult intelligence scale III scores for verbal intelligence quotient (P = 0.04) and verbal comprehension (P = 0.03) and the mean Wechsler memory scale-revised scores for generalized memory (P = 0.04) and delayed recall (P = 0.04)., Conclusions: The results of the present study have provided evidence that awake mapping can enable the preservation of higher neurocognitive function, including working memory and spatial cognition in patients with nondominant right frontal tumors. Despite the small number of cases, our findings suggest the surgical benefit of awake surgery for supratotal resection of diffuse frontal LGGs., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Patients who are diagnosed with high-grade gliomas (HGG) have poor prognoses and often experience rapid declines in functional and cognitive status, which makes caring for them particularly stressful. We conducted a prospective study to investigate the factors influencing the quality of life of HGG patients and their informal caregivers and analyzed their reciprocal impacts. Based on our results, we elaborated a screening model to identify patients and caregivers in need of psychooncological support., Methods: A total of 45 matched HGG patient-caregiver dyads completed the Multidimensional Mood State Questionnaire, the 12-Item Short Form Medical Outcome Questionnaire and the Center for Epidemiology Studies Depression Scale. A subsequent semi-structured interview was performed with each individual., Results: We found a significant relationship between the mood and depression scores of patients and caregivers, with a third of them displaying symptoms of a major depressive episode. Our screening model showed that 73% of the dyads exhibited signs of severe emotional strain with the need of psychooncological support. Beneficial factors that helped patients and caregivers cope with the illness included mutual respect, good communication, caregiver mastery and resilience., Conclusions: For a more comprehensive understanding of patient-caregiver interactions, we recommend using a combination of standardized psychometric tests and a semi-structured interview. The high percentage of emotional strain and depression found in patients and their caregivers facing HGG highlights the necessity of methodical screening for warning signs and consequent initiation of psycho-oncological interventions.

Objective: Few studies have assessed patient-reported quality of life (QoL) in patients with glioma undergoing surgery, and even fewer have provided longitudinal data. Accordingly, there is little knowledge about the changes of QoL over time in patients with glioma. We sought to explore perioperative and postoperative development of generic QoL during the first 6 months after primary glioma surgery., Methods: A total of 136 adult patients undergoing primary surgery for high-grade glioma (HGG) or low-grade glioma (LGG) were prospectively included in this explorative longitudinal study. Patient-reported QoL was measured with the generic tool EQ-5D 3L preoperatively and at 1 and 6 months after surgery., Results: At group level, there was no difference in EQ-5D index values in patients with HGG compared with patients with LGG at baseline or at 1 month. At 6 months, EQ-5D index values in patients with HGG had deteriorated significantly (P < 0.001) but remained stable in patients with LGG. Individual level QoL development was more diverse. American Society of Anesthesiologists class ≥3, resection grades other than gross total resection, and HGG were identified as independent predictors for negative development of QoL between 1 and 6 months after surgery., Conclusions: At group level, development of generic QoL between baseline and 1 and 6 months postoperatively seems to follow the natural disease trajectories of LGG and HGG, with deterioration in patients with HGG at 6 months. Individual development of QoL is heterogeneous. HGG, resection grades other than gross total resection, and preoperative comorbidity are predictors of postoperative impairment of QoL., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The use of X-ray for therapeutics always raises the problem of radiation hazards to living beings. In this research, we explored the radioprotective activity of glutathione (GSH) on cognitive ability of X-ray radiated tumor-bearing mice., Methods: Forty C57BL/6 mice were chosen to establish the GL261 glioma model and randomly divided into four groups: Model group, X-ray group, Pre-GSH group and Pos-GSH group. Morris water maze test was used to test cognitive ability. Moreover, histopathological observation of hippocampus was observed by hematoxylin and eosin (HE) staining. The protein expression of choline acetyl transferase (ChAT) was measured by western blot, simultaneously the contents of acetylcholinesterase (Ach), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA),TNF-α and IL-6 were detected by the respective kit., Results: There was a significant difference in X-ray group of the escape latency from the Model group (P<0.05). Besides, HE staining revealed that nucleus in hippocampus cells were pyknotic, glial cells were hyperplastic and the nerve cells were swelling in X-ray group. In X-ray group the expression of ChAT and Ache were decreased versus Model group. Finally, the cognitive ability in Pre-GSH and Pos-GSH group was enhanced than X-ray group, in which the cognitive ability of Pos-GSH group was higher than the Pre-GSH group., Discussion: X-ray impaired the brain tissues and cognitive ability of tumor-bearing mice. The damages of brain tissues were alleviated by Pre-GSH and Pos-GSH protection and the efficacy of Pos-GSH protection was superior to Pre-GSH protection. Abbreviation Ach: Acetylcholinesterase; GSH: Glutathione; HE: Hematoxylin and eosin; MDA: methane dicarboxylic aldehyde; SOD: Superoxide dismutase; TV: Tumor volume; TW: Tumor weight.

Background: The relationship between spontaneous speech and formal language testing in people with brain tumors (gliomas) has been rarely studied. In clinical practice, formal testing is typically used, while spontaneous speech is less often evaluated quantitatively. However, spontaneous speech is quicker to sample and may be less prone to test/retest effects, making it a potential candidate for assessing language impairments when there is restricted time or when the patient is unable to undertake prolonged testing., Aim: To assess whether quantitative spontaneous speech analysis and formal testing detect comparable language impairments in people with gliomas. Specifically, we addressed (a) whether both measures detected comparable language impairments in our patient sample; and (b) which language levels, assessment times, and spontaneous speech variables were more often impaired in this subject group., Method: Five people with left perisylvian gliomas performed a spontaneous speech task and a formal language assessment. Tests were administered before surgery, within a week after surgery, and seven months after surgery. Performance on spontaneous speech was compared with that of 15 healthy speakers., Results: Language impairments were detected more often with both measures than with either measure independently. Lexical-semantic impairments were more common than phonological and grammatical impairments, and performance was equally impaired across assessment time points. Incomplete sentences and phonological paraphasias were the most common error types., Conclusions: In our sample both spontaneous speech analysis and formal testing detected comparable language impairments. Currently, we suggest that formal testing remains overall the better option, except for cases in which there are restrictions on testing time or the patient is too tired to undergo formal testing. In these cases, spontaneous speech may provide a viable alternative, particularly if automated analysis of spontaneous speech becomes more readily available in the future. These results await replication in a bigger sample and/or other populations.

Background: Patients with cancer need high-quality information about disease stage, treatment options, and side effects. High-quality information can also improve health literacy, shared decision making, and satisfaction. We created patient-specific three-dimensional (3D) models of tumors including surrounding functional areas and assessed what patients with glioma value (or fear) about the models when they are used to educate them about the relationship between their tumor and specific brain parts, the surgical procedure, and risks., Methods: This exploratory study included adult patients with glioma who underwent functional magnetic resonance imaging and diffusion tensor imaging as part of preoperative work-up. All participants received an actual-size 3D model printed based on functional magnetic resonance imaging and diffusion tensor imaging. Semistructured interviews were conducted to identify facilitators and barriers for using the model and perceived effects., Results: Models were successfully created for all 11 participants. There were 18 facilitators and 8 barriers identified. The model improved patients' understanding about their situation; patients reported that it was easier to ask their neurosurgeon questions based on their model and that it supported their decision about preferred treatment. A perceived barrier for using the 3D model was that it could be emotionally confronting, particularly in an early phase of the disease. Positive effects were related to psychological domains, including coping, learning effects, and communication., Conclusions: Patient-specific 3D models are promising and simple tools that could help patients with glioma better understand their situation, treatment options, and risks. These models have the potential to improve shared decision making., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Despite their high symptom burden and poor prognosis, evidence-based supportive care interventions for adults with high-grade glioma (HGG) and their caregivers are lacking. Thus, we aimed to establish feasibility of a patient-caregiver dyadic yoga program (DYP) for newly diagnosed HGG patients and their family caregivers targeting quality-of-life (QOL) outcomes., Method: In this single-arm pilot trial, dyads participated in a 12-session DYP program across the course of patients' radiotherapy. The intervention focused on breathing exercises, gentle movements, and guided meditations. We tracked feasibility data and assessed levels of cancer-related symptoms (MD Anderson Symptom Inventory [MDASI]), depressive symptoms (Centers for Epidemiological Studies-Depression scale), fatigue (Brief Fatigue Inventory), sleep disturbances (Pittsburgh Sleep Quality Index [PSQI]), and overall mental and physical QOL (36-item Short-Form Survey [SF-36]) at baseline and post-DYP, which was at the end of radiotherapy., Results: We approached 6 dyads of which 5 dyads (86%) consented and completed all 12 sessions and pre/post assessments. All patients (mean age: 52 years, 80% female, 80% grade IV) and caregivers (mean age: 58 years, 80% female, 60% spouses) perceived benefit from the program. Paired t tests revealed a marginally significant, yet clinically meaningful, decrease in patient's cancer symptoms ( t = 2.32, P = .08; MDASI mean; pre = 1.75, post = 1.04). There were clinically significant reductions in patient sleep disturbances (PSQI mean: pre = 10.75, post = 8.00) and improvements in patient and caregiver mental QOL (MCS of SF-36 mean: pre = 42.35, post = 52.34, and pre = 45.14, post = 51.43, respectively)., Conclusions: This novel supportive care program appears to be safe, feasible, acceptable, and subjectively useful for HGG patients and their caregivers. There was also preliminary evidence regarding QOL treatment gains for both patients and caregivers.

Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.