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Abstract   Purpose In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. Patient and methods Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. Results LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. Conclusion LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits. [ABSTRACT FROM AUTHOR]

ABSTRACT: Knowledge of the level of resistance of weed populations and the herbicides to which they survive is important for recommending suitable advice to farmers and allowing the selection of appropriate management strategies. Whole-plant dose response experiments were carried out to assess the resistance status of eight putative resistant Galium spurium L. populations and one G. aparine L. population, originating from northern Greece. High levels of resistance of both species to the ALS-inhibiting herbicides chlorsulfuron and tribenuron were found, while their susceptible populations were controlled. Three G. spurium (GS) populations showed additional cross-resistance to [florasulam + 2,4-D], whereas the remaining five resistant GS populations were controlled with [tribenuron + mecoprop-p], [florasulam + 2,4-D], and [florasulam + aminopyralid]. Also, [florasulam + fluroxypyr] was very effective against two resistant GS populations tested. DNA sequence alignment of the three GS populations (GS 1, GS 6, and GS 8) with cross-resistance to chlorsulfuron, tribenuron, and florasulam revealed a point mutation at Trp-574 (tryptophan-574), causing amino acid substitution by Leu (leucine). The G. aparine (GA) population showed cross-resistance to chlorsulfuron and tribenuron, but it was controlled with [tribenuron + mecoprop-p], [florasulam + aminopyralid], [florasulam + 2,4-D], and [florasulam + fluroxypyr]. The confirmed cross-resistance of both GS and GA species to chlorsulfuron and tribenuron in northern Greece is the first report of Galium spp. resistance to ALS-inhibiting herbicides in Europe. Finally, all populations (8 GS and 1 GA) that showed resistance to chlorsulfuron and tribenuron were controlled with the mixtures [tribenuron + mecoprop-p] and [florasulam + fluroxypyr].

Background: Diffusion weighted imaging (DWI) is used for monitoring purposes for lower-grade glioma (LGG). While the apparent diffusion coefficient (ADC) is clinically used, various DWI models have been developed to better understand the micro-environment. However, the validity of these models and how they relate to each other is currently unknown. Therefore, this study assesses the validity and agreement of these models. Methods: Fourteen post-treatment LGG patients and six healthy controls (HC) underwent DWI MRI on a 3T MRI scanner. DWI processing included diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), white matter tract integrity (WMTI), neurite orientation dispersion and density imaging (NODDI), and fixel-based analysis (FBA). Validity was assessed by delineating surgical cavity, peri-surgical cavity, and normal-appearing white matter (NAWM) in LGG patients, and white matter (WM) in HC. Spearman correlation assessed the agreement between DWI parameters. Results: All obtained parameters differed significantly across tissue types. Remarkably, WMTI showed that intra-axonal diffusivity was high in the surgical cavity and low in NAWM and WM. Most DWI parameters correlated well with each other, except for WMTI-derived intra-axonal diffusivity. Conclusion: This study shows that all parameters relevant for tumour monitoring and DWI-derived parameters for axonal fibre-bundle integrity (except WMTI-IAS-D a ) could be used interchangeably, enhancing inter-DWI model interpretability.

Purpose: Diffuse low-grade gliomas (dLGG) often have a frontal location, which may negatively affect patients' executive functions (EF). Being diagnosed with dLGG and having to undergo intensive treatment can be emotionally stressful. The ability to cope with this stress in an adaptive, active and flexible way may be hampered by impaired EF. Consequently, patients may suffer from increased mental distress. The aim of the present study was to explore profiles of EF, coping and mental distress and identify characteristics of each profile., Methods: 151 patients with dLGG were included. Latent profile analysis (LPA) was used to explore profiles. Additional demographical, tumor and radiological characteristics were included., Results: Four clusters were found: 1) overall good functioning (25% of patients); 2) poor executive functioning, good psychosocial functioning (32%); 3) good executive functioning, poor psychosocial functioning (18%) and; 4) overall poor functioning (25%). Characteristics of the different clusters were lower educational level and more (micro)vascular brain damage (cluster 2), a younger age (cluster 3), and a larger tumor volume (cluster 4). EF was not a distinctive factor for coping, nor was it for mental distress. Maladaptive coping, however, did distinguish clusters with higher mental distress (cluster 3 and 4) from clusters with lower levels of mental distress (cluster 1 and 2)., Conclusion: Four distinctive clusters with different levels of functioning and characteristics were identified. EF impairments did not hinder the use of active coping strategies. Moreover, maladaptive coping, but not EF impairment, was related to increased mental distress in patients with dLGG., (© 2024. The Author(s).)

Background: Patients with low-grade gliomas (LGG) treated with surgery, generally function well and have a favorable prognosis. However, LGG can affect neurocognitive functioning. To date, little is known about social cognition (SC) in these patients, although impaired SC is related to social-behavioral problems and poor societal participation. Frontal brain areas are important for SC and LGG frequently have a frontal location. Therefore, the aim of the present study was to investigate whether emotion recognition, a key component of SC, was impaired, and related to general cognition, tumor location, laterality, tumor volume, and histopathological characteristics in patients with LGG, postsurgery, and before start of adjuvant therapy., Methods: A total of 121 patients with LGG were matched with 169 healthy controls (HC). Tumor location [including (frontal) subregions; insula, anterior cingulate cortex, lateral prefrontal cortex (LPFC), orbitofrontal-ventromedial PFC] and tumor volume were determined on MRI scans. Emotion recognition was measured with the Ekman 60 faces test of the Facial Expressions of Emotion-Stimuli and Tests (FEEST)., Results: Patients with LGG performed significantly lower on the FEEST than HC, with 33.1% showing impairment compared to norm data. Emotion recognition was not significantly correlated to frontal tumor location, laterality, and histopathological characteristics, and significantly but weakly with general cognition and tumor volume., Conclusions: Emotion recognition is impaired in patients with LGG but not (strongly) related to specific tumor characteristics or general cognition. Hence, measuring SC with individual neuropsychological assessment of these patients is crucial, irrespective of tumor characteristics, to inform clinicians about possible impairments, and consequently offer appropriate care., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Introduction: A 27-year-old man presented due to unilateral leg pain. He had a history of diabetes insipidus and panhypopituitarism. Laboratory analysis revealed hormonal undersupply. MRI showed a large contrast medium-absorbing mass in the pituitary gland extending into the hypothalamus. FDG-PET/CT examination revealed a hypermetabolic soft tissue lesion around the left femoral shaft. After biopsy of the lesion, a diagnosis of multisystemic Langerhans cell histiocytosis was made., Competing Interests: Es bestehen keine Interessenskonflikte., (© 2024 Aerzteverlag medinfo AG.)

Introduction: Brain tumours frequently cause language impairments and are also likely to co-occur with localised abnormal slow-wave brain activity. However, it is unclear whether this applies specifically to low-grade brain tumours. We investigate slow-wave activity in resting-state electroencephalography (EEG) in low-grade glioma and meningioma patients, and its relation to pre- and postoperative language functioning., Method: Patients with a glioma ( N = 15) infiltrating the language-dominant hemisphere and patients with a meningioma ( N = 10) with mass effect on this hemisphere underwent extensive language testing before and 1 year after surgery. EEG was registered preoperatively, postoperatively (glioma patients only), and once in healthy individuals. Slow-wave activity in delta- and theta- frequency bands was evaluated visually and quantitatively by spectral power at three levels over the scalp: the whole brain, the affected hemisphere, and the affected region., Results: Glioma patients had increased delta activity (affected area) and increased theta activity (all levels) before and after surgery. In these patients, increased preoperative theta activity was related to the presence of language impairment, especially to poor word retrieval and grammatical performance. Preoperative slow-wave activity was also related to postoperative language outcomes. Meningioma patients showed no significant increase in EEG slow-wave activity compared to healthy individuals, but they presented with word retrieval, grammatical, and writing problems preoperatively, as well as with writing impairments postoperatively., Discussion: Although the brain-tumour pathology in low-grade gliomas and meningiomas has a different effect on resting-state brain activity, patients with low-grade gliomas and meningiomas both suffer from language impairments. Increased theta activity in glioma patients can be considered as a language-impairment marker, with prognostic value for language outcome after surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wolthuis, Bosma, Bastiaanse, Cherian, Smits, Veenstra, Wagemakers, Vincent and Satoer.)

Background: Effective systemic treatments have revolutionized the management of patients with metastatic melanoma, including those with brain metastases. The extent to which these treatments influence disease trajectories close to death is unknown. Therefore, this study aimed to gain insight into provided treatments and healthcare consumption during the last 3 months of life in patients with melanoma brain metastases., Methods: Retrospective, single-center study, including consecutive patients with melanoma brain metastases diagnosed between June-2015 and June-2018, referred to the medical oncologist, and died before November-2019. Patient and tumor characteristics, anti-tumor treatments, healthcare consumption, presence of neurological symptoms, and do-not-resuscitate status were extracted from medical charts., Results: 100 patients were included. A BRAF-mutation was present in 66 patients. Systemic anti-tumor therapy was given to 72% of patients during the last 3 months of life, 34% in the last month, and 6% in the last week. Patients with a BRAF-mutation more frequently received systemic treatment during the last 3 (85% vs. 47%) and last month (42% vs. 18%) of life than patients without a BRAF-mutation. Furthermore, patients receiving systemic treatment were more likely to visit the emergency room (ER, 75% vs. 36%) and be hospitalized (75% vs. 36%) than those who did not., Conclusion: The majority of patients with melanoma brain metastases received anti-tumor treatment during the last 3 months of life. ER visits and hospitalizations occurred more often in patients on anti-tumor treatment. Further research is warranted to examine the impact of anti-tumor treatments close to death on symptom burden and care satisfaction., (© 2022. The Author(s).)

Introduction: Preservation of language functioning in patients undergoing brain tumor surgery is essential because language impairments negatively impact the quality of life. Brain tumor patients have alterations in functional connectivity (FC), the extent to which brain areas functionally interact. We studied FC networks in relation to language functioning in glioma and meningioma patients. Method: Patients with a low-grade glioma ( N = 15) or meningioma ( N = 10) infiltrating into/pressing on the language-dominant hemisphere underwent extensive language testing before and 1 year after surgery. Resting-state EEG was registered preoperatively, postoperatively (glioma patients only), and once in healthy individuals. After analyzing FC in theta and alpha frequency bands, weighted networks and Minimum Spanning Trees were quantified by various network measures. Results: Pre-operative FC network characteristics did not differ between glioma patients and healthy individuals. However, hub presence and higher local and global FC are associated with poorer language functioning before surgery in glioma patients and predict worse language performance at 1 year after surgery. For meningioma patients, a greater small worldness was related to worse language performance and hub presence; better average clustering and global integration were predictive of worse outcome on language function 1 year after surgery. The average eccentricity, diameter and tree hierarchy seem to be the network metrics with the more pronounced relation to language performance. Discussion: In this exploratory study, we demonstrated that preoperative FC networks are informative for pre- and postoperative language functioning in glioma patients and to a lesser extent in meningioma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wolthuis, Satoer, Veenstra, Smits, Wagemakers, Vincent, Bastiaanse, Cherian and Bosma.)

Background: Novel treatments make long-term survival possible for subsets of patients with melanoma brain metastases. Brain magnetic resonance imaging (MRI) may aid in early detection of brain metastases and inform treatment decisions. This study aimed to determine the impact of screening MRI scans in patients with metastatic melanoma and follow-up MRI scans in patients with melanoma brain metastases., Methods: This retrospective cohort study included patients diagnosed with metastatic melanoma or melanoma brain metastases between June 2015 and January 2018. The impact of screening MRI scans was evaluated in the first 2 years after metastatic melanoma diagnosis. The impact of follow-up MRI scans was examined in the first year after brain metastases diagnosis. The number of MRI scans, scan indications, scan outcomes, and changes in treatment strategy were analyzed., Results: In total, 116 patients had no brain metastases at the time of the metastatic melanoma diagnosis. Twenty-eight of these patients (24%) were subsequently diagnosed with brain metastases. Screening MRI scans detected the brain metastases in 11/28 patients (39%), of which 8 were asymptomatic at diagnosis. In the 96 patients with melanoma brain metastases, treatment strategy changed after 75/168 follow-up MRI scans (45%). In patients treated with immune checkpoint inhibitors, the number of treatment changes after follow-up MRI scans was lower when patients had been treated longer., Conclusion(s): Screening MRI scans aid in early detection of melanoma brain metastases, and follow-up MRI scans inform treatment strategy. In patients with brain metastases responding to immune checkpoint inhibitors, treatment changes were less frequently observed after follow-up MRI scans. These results can inform the development of brain imaging protocols for patients with immune checkpoint inhibitor sensitive tumors., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Knowledge regarding cognitive problems in metastatic non-small cell lung cancer (mNSCLC) is limited. Such problems may include both patient-reported cognitive concerns and demonstrable cognitive impairment. Greater understanding of these outcomes is needed to inform rehabilitation strategies for these difficulties. We aimed to identify the frequency of cognitive problems and associated factors in patients with mNSCLC., Methods: In this cross-sectional study, adults with mNSCLC completed validated neuropsychological tests and self-report questionnaires measuring cognitive concerns, neurobehavioral concerns, depression, demoralization, illness intrusiveness, self-esteem, and physical symptoms. Cognitive impairment (performance based) was defined according to International Cancer and Cognition Task Force criteria. Clinically significant cognitive concerns were defined by a score ≥1.5 SD below the normative mean on the Functional Assessment of Cancer Therapy-Cognitive Function Perceived Cognitive Impairment (FACT-Cog PCI). Univariate and multivariate logistic regression analyses were performed to identify associated factors., Results: Of 238 patients approached, 77 participated (median age: 62 years; range: 37-82). Brain metastases were present in 41 patients (53%), and 23 (29%) received cranial irradiation. Cognitive impairment and cognitive concerns were present in 31 (40%) and 20 patients (26%), respectively. Cognitive impairment and cognitive concerns co-occurred in 10 patients (13%), but their severity was unrelated. Cognitive impairment was associated with cranial irradiation (odds ratio [OR] = 2.89; P = .04), whereas cognitive concerns were associated with greater illness intrusiveness (OR = 1.04; P = .03) and lower self-esteem (OR = 0.86; P = .03)., Conclusions: Cognitive impairment and cognitive concerns are both common in patients with mNSCLC but are not necessarily related, and their risk factors differ. The association of illness intrusiveness and self-esteem with cognitive concerns can inform therapeutic interventions in this population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Context: Death anxiety is common in patients with metastatic cancer, but its relationship to brain metastases and cognitive decline is unknown. Early identification of death anxiety and its determinants allows proactive interventions to be offered to those in need., Objectives: To identify psychological, physical, and disease-related (including brain metastases and cognitive impairment) factors associated with death anxiety in metastatic non-small cell lung cancer (mNSCLC) patients., Methods: A cross-sectional pilot study with mNSCLC outpatients completing standardized neuropsychological tests and validated questionnaires measuring death anxiety, cognitive concerns, illness intrusiveness, depression, demoralization, self-esteem, and common cancer symptoms. We constructed a composite for objective cognitive function (mean neuropsychological tests z-scores)., Results: Study measures were completed by 78 patients (50% females; median age 62 years [range 37-82]). Median time since mNSCLC diagnosis was 11 months (range 0-89); 53% had brain metastases. At least moderate death anxiety was reported by 43% (n = 33). Objective cognitive impairment was present in 41% (n = 32) and perceived cognitive impairment in 27% (n = 21). Death anxiety, objective, and perceived cognitive impairment did not significantly differ between patients with and without brain metastases. In univariate analysis, death anxiety was associated with demoralization, depression, self-esteem, illness intrusiveness, common physical cancer symptoms, and perceived cognitive impairment. In multivariate analysis, demoralization (P < 0.001) and illness intrusiveness (P = 0.001) were associated with death anxiety., Conclusion: Death anxiety and brain metastases are common in patients with mNSCLC but not necessarily linked. The association of death anxiety with both demoralization and illness intrusiveness highlights the importance of integrated psychological and symptom management. Further research is needed on the psychological impact of brain metastases., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Anti-NMDA-receptor-encephalitis is a progressive autoimmune disease with significant mortality if left untreated., Case Description: A 58-year-old man without previous psychiatric or neurologic history presented at the emergency department after brief loss of consciousness at work. Within a few hours, the patient developed acute neuropsychiatric symptoms, including altered levels of consciousness, aggression, incoherence, change in behaviour, and psychomotor agitation. Initially, additional blood, cerebrospinal fluid and EEG tests showed no abnormalities. Over the course of the following days, catatonia, orofacial dyskinesia and autonomic-function disorder developed, eventually with respiratory insufficiency, necessitating transfer to the intensive-care unit. At this stage, the EEG did show abnormalities, and cerebrospinal fluid analysis showed marginal pleocytosis. The patient was treated with intravenous methylprednisolone and immunoglobins. Anti-NMDA-receptor antibodies were present in the blood and cerebrospinal fluid. Screening for malignancy identified small-cell lung carcinoma, for which the patient was treated with cytostatic agents., Conclusion: Acute neuropsychiatric symptoms in a middle-aged patient with no psychiatric medical history are suggestive of an underlying somatic cause. Timely recognition and treatment of anti-NMDA-receptor encephalitis is essential to improve the prognosis.

To provide an appropriate method to systematically analyze the hospital discharge of terminally ill patients especially the cooperation between hospital and community nurses and the quality of the discharge handovers. To evaluate the hospital discharge process of terminally ill patients in an academic hospital in the Netherlands using the proposed method.Data were collected from a prospective cohort of all terminally ill patients discharged from the University Medical Center Groningen, the Netherlands, between June and November 2014. The hospital discharges were assessed using 2 questionnaires: an inventory questionnaire, to determine the required care, and an evaluation questionnaire, to evaluate the care actually organized and the discharge handovers. The inventory questionnaire was completed prior to discharge and the evaluation questionnaire between 3 to 7 days after discharge.Around 130 consecutive patients were included. The discharge took place on the desired date in 86% of cases and the average overall discharge grade on a 10-point scale was 7.4 (range: 3-9.5). In 23% of cases discrepancies between required and provided care were identified and medication queries existed in 29%.This study provides a methodology to analyze the hospital discharge procedure of terminally ill patients that can be utlized in any hospital. Structured analysis of the discharge process is valuable and identifies where improvements can be made. Within the study cohort the home care could be arranged at short notice and was considered sufficient. However, in a significant proportion of patients a discrepancy between required and arranged care and queries about medication were identified.

Depressive symptoms are common in glioma patients, and can negatively affect health-related quality of life (HRQOL). We performed a nation-wide randomized controlled trial to evaluate the effects of an online guided self-help intervention for depressive symptoms in adult glioma patients. Glioma patients with depressive symptoms were randomized to a 5-week online course based on problem-solving therapy, or a waiting list control group. After having received the intervention, the glioma patient groups combined were compared with patients with cancer outside the central nervous system (non-CNS cancer controls), who also received the intervention. Sample size calculations yielded 63 participants to be recruited per arm. The primary outcome [depressive symptoms (CES-D)] and secondary outcomes [fatigue (Checklist Individual Strength (CIS)) and HRQOL (Short Form-36)], were assessed online at baseline, post-intervention, and 3 and 12 months follow-up. In total, 89 glioma patients (intervention N = 45; waiting list N = 44) and 26 non-CNS cancer controls were included, of whom 35 and 54% completed the intervention, respectively. Recruitment could not be extended beyond 3.5 years due to funding. On depression, no statistically significant differences between the groups were found. Fatigue decreased post-treatment in the glioma intervention group compared with the waiting list group (p = 0.054, d = 0.306). At 12 months, the physical component summary (HRQOL) remained stable in glioma patients, while scores improved in non-CNS cancer controls (p = 0.035, d = 0.883). In this underpowered study, no evidence for the effectiveness of online guided self-help for depression or HRQOL in glioma patients was found, but it may improve fatigue. Trial registration Netherlands Trial Register NTR3223.

Following tumor resection, the majority of high-grade glioma (HGG) patients are treated with a combined modality regimen of radiotherapy and temozolomide. As a result of the tumor itself or as treatment-related neurotoxic side-effects, these patients may experience cognitive deficits. Additionally, radiological abnormalities expressed as white matter hyperintensities (WMH) and cerebral atrophy (CA) can develop. In this study, these functional and morphological parameters are evaluated, and their relation is investigated. After surgery, HGG patients underwent chemo-irradiation for six weeks, followed by six cycles of temozolomide. Assessments were performed before chemo-irradiation, post-concomitantly, after the third and sixth adjuvant cycle, and 3 and 7 months after treatment. Degree of WMH and CA was scored on MRI. Patients' neuropsychological performance was compared to healthy matched controls, yielding six cognitive domain z-scores. Development or progression of pre-existing WMH and CA during follow-up was observed in 36 and 45 % of the patients (n = 39) respectively. Cognitive functioning remained stable or improved in 70 % of the patients and deteriorated in 30 % of the patients (n = 33). Of the cognitive decliners, 80 % had tumor progression within 4 months thereafter. No clear association between cognitive functioning and WMH or CA was found. Central neurotoxic effects of combined modality treatment in HGG patients expressed by radiological abnormalities are encountered in approximately 40 % of patients. However, functional impact as indexed by cognitive functioning was found to be limited. Furthermore, development or progression of pre-existing WMH and CA does not consistently result in functional impairment as measured by cognitive tests.

Background: Treatment of high-grade glioma (HGG) patients with anti-epileptic drugs (AEDs) has met with various side effects, such as cognitive deterioration. The cognitive effects of both older and newer AEDs in HGG patients are largely unknown. The aim of this study was to determine the effect of older and newer AEDs on cognitive performance in postoperative HGG patients., Methods: We selected HGG patients from 3 separate cohorts for use of older, newer, or no AEDs, as they represented distinct treatment eras and provided the opportunity to compare older and newer AEDs. In all 3 cohorts, patients were included within 6 weeks following neurosurgery before the start of postoperative treatment. Cognitive functioning was evaluated by an extensive neuropsychological assessment, executed in 6 cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed)., Results: One hundred seventeen patients met the inclusion criteria; 44 patients used no AED, 35 were on monotherapy with a newer AED (all levetiracetam), and 38 were on monotherapy with an older AED (valproic acid or phenytoin). Patients on older and newer AEDs performed equally well as patients not on an AED, and patients on levetiracetam performed even better on verbal memory tests than patients not on an AED. Post-hoc analyses revealed that within the group using older AEDs, patients on valproic acid performed better than patients on phenytoin., Conclusions: Neither levetiracetam nor valproic acid was associated with additional cognitive deficits in HGG patients. Both AEDs even appeared to have a beneficial effect on verbal memory in these patients.

Introduction: This paper aims to study the value of MRI and Thallium 201 ((201)Tl) single-photon emission computed tomography (SPECT) in the prediction of overall survival (OS) in glioma patients treated with temozolomide (TMZ) and to evaluate timing of radiological follow-up., Methods: We included patients treated with TMZ chemoradiotherapy for newly diagnosed glioblastoma multiforme (GBM) and with TMZ for recurrent glioma. MRIs and (201)Tl SPECTs were obtained at regular intervals. The value of both imaging modalities in predicting OS was examined using Cox regression analyses., Results: Altogether, 138 MRIs and 113 (201)Tl SPECTs in 46 patients were performed. Both imaging modalities were strongly related to OS (P ≤ 0.02). In newly diagnosed GBM patients, the last follow-up MRI (i.e., after six adjuvant TMZ courses) and SPECT (i.e., after three adjuvant TMZ courses) were the strongest predictors of OS (P = 0.01). In recurrent glioma patients, baseline measurements appeared to be the most predictive of OS (P < 0.01). The addition of one imaging modality to the other did not contribute to the prediction of OS., Conclusions: Both MRI and (201)Tl SPECT are valuable in the prediction of OS. It is adequate to restrict to one of both modalities in the radiological follow-up during treatment. In the primary GBM setting, MRI after six adjuvant TMZ courses contributes significantly to the prediction of survival. In the recurrent glioma setting, baseline MRI appears to be a powerful predictor of survival, whereas follow-up MRIs during TMZ seem to be of little additional value.

The aim of this study was to evaluate cognitive functioning in newly-diagnosed glioblastoma multiforme (GBM) patients during treatment with radiotherapy (RT) plus concomitant and adjuvant temozolomide (TMZ). Cognitive assessment took place following surgery, but prior to the start of RT (baseline), after 6 weeks of RT and concomitant TMZ (1st follow-up), and after three cycles of adjuvant TMZ (2nd follow-up). Standardized cognitive summary measures and delta scores for six cognitive domains were calculated at the individual level. Cognitive functioning of progression-free GBM patients was compared to that of matched healthy controls. Analyses were performed on a group of 13 GBM patients that were progression-free during follow-up. The results showed that the majority of patients had deficits in multiple cognitive domains at baseline. Between baseline and 1st follow-up, four patients improved in one cognitive domain, four patients deteriorated in one domain, one patient improved in one domain and deteriorated in another, and four patients remained stable in all six domains. Between 1st and 2nd follow-up, the majority of patients (11) remained stable in all six cognitive domains, whereas one patient declined in one domain, and one patient showed a deterioration in two domains. Overall, between baseline and 2nd follow-up, three patients improved in one cognitive domain, two patients deteriorated in two domains, one patient improved in one domain and deteriorated in another, and seven patients remained stable in all six cognitive domains. In conclusion, preceding treatment, the majority of GBM patients show clear-cut deficits in cognitive functioning. In the course of the first 6 months of their disease, however, progression-free GBM patients undergoing radiotherapy plus concomitant and adjuvant temozolomide treatment do not deteriorate in cognitive functioning.

Background: To understand neurophysiological mechanisms underlying cognitive dysfunction in low-grade glioma (LGG) patients by evaluating the spatial structure of 'resting-state' brain networks with graph theory., Methods: Standardized tests measuring 6 neurocognitive domains were administered in 17 LGG patients and 17 healthy controls. Magnetoencephalography (MEG) recordings were conducted during eyes-closed 'resting state'. The phase lag index (PLI) was computed in seven frequency bands to assess functional connectivity between brain areas. Spatial patterns were characterized with graph theoretical measures such as clustering coefficient (local connectivity), path length (global integration), network small world-ness (ratio of clustering coefficient/path length) and degree correlation (the extent to which connected nodes have similar degrees)., Results: Compared to healthy controls, patients performed poorer on psychomotor functioning, attention, information processing, and working memory. Patients displayed higher short- and long-distance synchronization and clustering coefficient in the theta band, whereas a lower clustering coefficient and small world-ness were observed in the beta band. A lower degree correlation was found in the upper gamma band. LGG patients with higher clustering coefficient, longer path length, and lower degree correlations in delta and lower alpha band were characterized by poorer neurocognitive performance., Conclusion: LGG patients display higher short- and long-distance synchronization within the theta band. Network analysis revealed changes (in particularly the theta, beta, and upper gamma band) suggesting disturbed network architecture. Moreover, correlations between network characteristics and neurocognitive performance were found, Widespread changes in the strength and spatial organization of brain networks may be responsible for cognitive dysfunction in glioma patients.

Background: Glioblastoma multiforme (GBM) cells secrete large amounts of glutamate that can trigger AMPA-type glutamate receptors (AMPARs). This commonly results in Na(+) and Ca(2+)-permeability and thereby in excitotoxic cell death of the surrounding neurons. Here we investigated how the GBM cells themselves survive in a glutamate-rich environment., Methods and Findings: In silico analysis of published reports shows down-regulation of all ionotropic glutamate receptors in GBM as compared to normal brain. In vitro, in all GBM samples tested, mRNA expression of AMPAR subunit GluR1, 2 and 4 was relatively low compared to adult and fetal total brain mRNA and adult cerebellum mRNA. These findings were in line with primary GBM samples, in which protein expression patterns were down-regulated as compared to the normal tissue. Furthermore, mislocalized expression of these receptors was found. Sequence analysis of GluR2 RNA in primary and established GBM cell lines showed that the GluR2 subunit was found to be partly unedited., Conclusions: Together with the lack of functional effect of AMPAR inhibition by NBQX our results suggest that down-regulation and afunctionality of AMPARs, enable GBM cells to survive in a high glutamate environment without going into excitotoxic cell death themselves. It can be speculated that specific AMPA receptor inhibitors may protect normal neurons against the high glutamate microenvironment of GBM tumors.

The objective of this study was to compare the health-related quality of life (HRQOL) of long-term to short-term high-grade glioma (HGG) survivors, determine the prognostic value of HRQOL for overall survival, and determine the effect of tumor recurrence on HRQOL for long-term survivors. Following baseline assessment (after surgery, before radiotherapy), self-perceived HRQOL (using the Medical Outcomes Study Short Form 36 [SF-36]) and brain tumor-specific symptoms (using the 20-item Brain Cancer Module) were assessed every 4 months until 16 months after histological diagnosis. Kaplan-Meier survival analysis and the Cox proportional hazards model were performed to estimate overall survival of patients with impaired scores on the aggregated SF-36 higher-order summary scores measuring physical functioning on a physical component scale and on a mental component scale (MCS). Sixteen patients with a short-term survival (baseline and 4-month follow-up) and 16 with a long-term survival (follow-up until 16 months after diagnosis) were selected out of 68 initially recruited HGG patients. At baseline, the short-term and long-term survivors did not differ in their HRQOL. Between baseline and the 4-month follow-up, HRQOL of short-term survivors deteriorated, whereas the long-term survivors improved to a level comparable to healthy controls. Patients with impaired mental functioning (MCS) at baseline had a shorter median survival than patients with normal functioning. After accounting for differences in patient and tumor characteristics, however, mental functioning was not independently related to poorer overall survival. Not surprisingly, in the group of long-term survivors, the five patients with recurrence had a more compromised HRQOL at the 16-month follow-up compared to the 11 patients without recurrence. We concluded that baseline HRQOL is not related to duration of survival and that long-term survivors show improvement of HRQOL to a level comparable to that of the healthy.

We investigated the mechanisms underlying neurocognitive dysfunction in patients with low-grade glioma (LGG) by relating functional connectivity revealed by magnetoencephalography to neurocognitive function. We administered a battery of standardized neurocognitive tests measuring six neurocognitive domains to a group of 17 LGG patients and 17 healthy controls, matched for age, sex, and educational level. Magnetoencephalography recordings were conducted during an eyes-closed "resting state," and synchronization likelihood (a measure of statistical correlation between signals) was computed from the delta to gamma frequency bands to assess functional connectivity between different brain areas. We found that, compared with healthy controls, LGG patients performed more poorly in psychomotor function, attention, information processing, and working memory. LGG patients also had significantly higher long-distance synchronization scores in the delta, theta, and lower gamma frequency bands than did controls. In contrast, patients displayed a decline in synchronization likelihood in the lower alpha frequency band. Within the delta, theta, and lower and upper gamma bands, increasing short- and long-distance connectivity was associated with poorer neurocognitive functioning. In summary, LGG patients showed a complex overall pattern of differences in functional resting-state connectivity compared with healthy controls. The significant correlations between neurocognitive performance and functional connectivity in various frequencies and across multiple brain areas suggest that the observed neurocognitive deficits in these patients can possibly be attributed to differences in functional connectivity due to tumor and/or treatment.

Widespread disturbances in resting state functional connectivity between remote brain areas have been demonstrated in patients with brain tumors. Functional connectivity has been associated with neurocognitive deficits in these patients. Thus far, it is unknown how (surgical) treatment affects functional connectivity. Functional connectivity before and after tumor resection was compared in primary brain tumor patients. Data from 15 newly diagnosed brain tumor patients were analyzed. Patients underwent tumor resection, and both preoperative (up to five months prior to surgery) and postoperative (up to ten months following surgery) resting state magnetoencephalography (MEG) recordings. Seven of the patients (47%) underwent radiotherapy after neurosurgery. Functional connectivity was assessed by the phase lag index (PLI), a measure of the correlation between MEG sensors that is not sensitive to volume conduction. PLIs were averaged to one short-distance and two long-distance (interhemispheric and intrahemispheric) scores in seven frequency bands. We found that functional connectivity changed in a complex manner after tumor resection, depending on frequency band and functional connectivity type. Post-hoc analyses yielded a significant decrease of interhemispheric PLI in the theta band after tumor resection. This result proved to be robust and was not influenced by radiotherapy or a variety of tumor- and patient-related factors.

Purpose: In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction., Patient and Methods: Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered., Results: LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory., Conclusion: LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits.

We evaluated the course of neurocognitive functioning in newly diagnosed high-grade glioma patients and specifically the effect of tumor recurrence. Following baseline assessment (after surgery and before radiotherapy), neurocognitive functioning was evaluated at 8 and 16 months. Neurocognitive summary measures were calculated to detect possible deficits in the domains of (1) information processing, (2) psychomotor function, (3) attention, (4) verbal memory, (5) working memory, and (6) executive functioning. Repeated-measures analyses of covariance were used to evaluate changes over time. Thirty-six patients were tested at baseline only. Follow-up data were obtained for 32 patients: 14 had a follow-up at 8 months, and 18 had an additional follow-up at 16 months. Between baseline and eight months, patients deteriorated in information-processing capacity, psychomotor speed, and attentional functioning. Further deterioration was observed between 8 and 16 months. Of 32 patients, 15 suffered from tumor recurrence before the eight-month follow-up. Compared with recurrence-free patients, not only did patients with recurrence have lower information-processing capacity, psychomotor speed, and executive functioning, but they also exhibited a more pronounced deterioration between baseline and eight-month follow-up. This difference could be attributed to the use of antiepileptic drugs in the patient group with recurrence. This study showed a marked decline in neurocognitive functioning in HGG patients in the course of their disease. Patients with tumor progression performed worse on neurocognitive tests than did patients without progression, which could be attributed to the use of antiepileptic drugs. The possibility of deleterious effects is important to consider when prescribing antiepileptic drug treatment.

Objective: Cerebral functions are based on the functional interactions between multiple distinct specialized regions of the brain. Functional interactions require anatomical connections as well as the synchronization of brain oscillations. The present work aims at evaluating the impact of brain tumours on spatial patterns of functional connectivity of the brain measured at rest by MEG., Methods: We analyzed the statistical dependency (by computing the synchronization likelihood (SL, a measure of generalized synchronization)) between MEG signals at rest, in 17 patients with a brain tumour and in 15 healthy controls. Following an approach that derives from graph theory, we also analyzed the architectural properties of the networks by computing two parameters from the SL matrix, the cluster coefficient C and the characteristic path length L., Results: Alterations in synchronization levels were found in the patients and were not focal but involved intra-hemispheric connectivity. Effects were different considering the frequencies sub-bands, predominating in a decrease in high frequencies bands for long-distance connections and an increase in slower bands for local connectivity. In addition, graph analysis reveals changes in the normal "small-world" network architecture in addition to changes in synchronization levels with some differences according to the studied frequency sub-bands., Conclusions: Brain tumours alter the functional connectivity and the "network" architecture of the brain. These alterations are not focal and effects are different considering the frequencies sub-bands., Significance: These neurophysiological changes may contribute to the cognitive alterations observed in patients with brain tumours.

Objective: This study was undertaken to test the hypothesis that brain tumors interfere with normal brain function by disrupting functional connectivity of brain networks., Methods: Functional connectivity was assessed by computing the synchronization likelihood in a broad band (0.5-60Hz) or in the gamma band (30-60Hz) between all pairwise combinations of magnetoencephalography signals. Magnetoencephalography recordings were made at rest in 17 brain tumor patients and 15 healthy control subjects. For a given threshold of synchronization likelihood values, graphs of the suprathreshold connections between each magnetoencephalography channel and the others channels were built., Results: In some regions, a variable number of channels without connectivity (missing connective points) at this threshold was found. The number of missing connective points was higher in patients with brain tumors than in control subjects (p < 0.0001, broad and gamma band) and was higher for left-sided than right-sided tumors (p = 0.008, broad band; p < 0.0001, gamma band). Individual results analysis indicates that the majority of brain tumor patients display several regions with missing connective point alterations in the affected and in the contralateral hemisphere., Interpretation: Our findings suggest that brain tumors induce a loss of functional connectivity that affects multiple brain regions, and that left side brain tumors have the more severe consequences in this respect.

Compared with conventional transfusion regimes a strong reduction in HLA alloimmunization and refractoriness to platelet transfusions is obtained when both red blood cell concentrates (RBCs) and platelet concentrates (PCs) are depleted of leukocytes by filtration. Because most of the leukocyte contamination is introduced by transfusion of RBCs, filtration of RBCs appears rational, but uncertainty exists regarding the degree of leukocyte-depletion of PCs needed for the prevention of HLA alloimmunization and refractoriness. We conducted a prospective trial and randomized patients with acute leukemia to receive leukocyte-depleted PCs prepared either by centrifugation (mean leukocyte count 35 x 10(6)/PC of 6 U) or by filtration (mean leukocyte count less than 5 x 10(6)/PC of 6 U). Both groups received RBCs that were filtered after prior removal of the buffy coat. Clinical refractoriness occurred in 46% (12 of 26) of the evaluable patients that were transfused with centrifuged PCs and only in 11% (3 of 27) in the filtered group (P less than .005). De novo anti-HLA antibodies were detected in 42% (11 of 26) patients in the centrifuged group and only in 7% (2 of 27) of the patients receiving filtered PCs (P less than .004). In 8 of 11 alloimmunized patients in the centrifuged group antibodies were detected in the first 4 weeks of transfusion therapy while none of the patients in the filtered group became immunized against HLA antigens during that period. We conclude that for the prevention of HLA alloimmunization and refractoriness to platelet transfusions from random donors, both RBCs and PCs have to be leukocyte-depleted by filtration.