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Introduction: Rehabilitation and exercise interventions are beneficial for the physical and psychological health of cancer survivors. Current clinic-based performance status measures do not accurately capture the survivor's functioning, or rehabilitation and exercise needs. Our primary objective was to explore the feasibility of performing a performance-based functional assessment with brain tumour survivors as a means to inform needs for rehabilitation and exercise., Methods: A feasibility study was conducted with survivors of brain and other neurological cancers attending new patient or follow-up clinics. Survivors were assessed using the Short Physical Performance Battery (SPPB), grip strength and Rosow-Breslau Physical Activity Self-Assessment (RSB)., Results: We approached 40 survivors with brain tumours, and 30 agreed to participate in the study. The SPPB was inversely correlated with Eastern Cooperative Oncology Group (ECOG) scores (r = -.73; p < .01), but scores on the SPPB for individuals classified as ECOG 1 ranged from 5 to 12 out of 12, indicating a large variability in functional scores within this ECOG grade., Conclusion: Implementation of objective functional testing is feasible in the neuro-oncology outpatient clinic. The SPPB appears to best inform the functional status of survivors with brain tumours, facilitating more individualised exercise and rehabilitation referrals., (© 2020 John Wiley & Sons Ltd.)

Objective: This prospective case-control study was conducted to examine whether spherical deconvolution (SD) can unveil microstructural abnormalities in the corticospinal tract (CST) caused by IDH-mutant gliomas. To determine the significance of abnormal microstructure, the authors investigated the correlation between diffusion parameters and neurophysiological data collected with navigated transcranial magnetic stimulation (nTMS)., Methods: Twenty participants (10 patients and 10 healthy controls) were recruited. Diffusion-weighted images were acquired on a 3-T MRI scanner using a cardiac-gated single-shot spin echo echo-planar imaging multiband sequence (TE 80 msec, TR 4000 msec) along 90 diffusion directions with a b-value of 2500 sec/mm2 (FOV 256 × 256 mm). Diffusion tensor imaging tractography and SD tractography were performed with deterministic tracking. The anterior portion of the ipsilateral superior peduncle and the precentral gyrus were used as regions of interest to delineate the CST. Diffusion indices were extracted and analyzed for significant differences between hemispheres in patients and between patient and control groups. A navigated brain stimulation system was used to deliver TMS pulses at hotspots at which motor evoked potentials (MEPs) for the abductor pollicis brevis, first digital interosseous, and abductor digiti minimi muscles are best elicited in patients and healthy controls. Functional measurements such as resting motor threshold (rMT), amplitude of MEPs, and latency of MEPs were noted. Significant differences between hemispheres in patients and between patients and controls were statistically analyzed. The Spearman rank correlation was used to investigate correlations between diffusion indices and functional measurements., Results: The hindrance modulated orientational anisotropy (HMOA), measured with SD tractography, is lower in the hemisphere ipsilateral to glioma (p = 0.028). The rMT in the hemisphere ipsilateral to a glioma is significantly greater than that in the contralateral hemisphere (p = 0.038). All measurements contralateral to the glioma, except for the mean amplitude of MEPs (p = 0.001), are similar to those of healthy controls. Mean diffusivity and axial diffusivity from SD tractography are positively correlated with rMT in the hemisphere ipsilateral to glioma (p = 0.02 and 0.006, respectively). The interhemispheric difference in HMOA and rMT is correlated in glioma patients (p = 0.007)., Conclusions: SD tractography can demonstrate microstructural abnormality within the CST of patients with IDH1-mutant gliomas that correlates to the functional abnormality measured with nTMS.

Background: Navigated transcranial magnetic stimulation (nTMS) is being used for different purposes in patients with brain tumors. However, the procedure requires a positive electrophysiological response. For patients with negative response in rest conditions, active motor threshold (AMT) may be used. However, sometimes it is difficult to obtain AMT measures owing to inability of the patient to sustain steady muscle contraction. Herein, we describe a simple method by using a hand dynamometer to obtain AMT measures during nTMS session., Case Description: A woman aged 68 years underwent total removal of a right frontal lobe oligodendroglioma World Health Organization grade II 15 years ago. Cranial magnetic resonance imaging during follow-up revealed local recurrence. In the postoperative period, she developed left upper limb paresis. A postoperative nTMS session was performed for motor electrophysiological evaluation. However, using the standard technique for AMT measurement, the patient was unable to perform sustained muscle contraction as required. A hand dynamometer was used. It allowed sustained muscle contraction for AMT measurement. A counter force for the index finger flexion, the hand support to stabilize hand joints, and a numerical screen serving for both the examiner and the patient as a feedback parameter may explain the success obtained with this simple device., Conclusions: Although more studies are necessary to validate the method, the hand dynamometer should be considered for patients unable to sustain muscle contraction during AMT measurement., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tumefactive appearing lesions on brain imaging can cause a diagnostic dilemma. We report a middle-aged man who presented with right-sided optic neuritis. A brain MRI showed enhancement of the right optic nerve, and non-enhancing white matter lesions including a 3 cm right frontal lesion with adjacent gyral expansion. Cerebrospinal fluid analysis showed five oligoclonal bands not present in serum. Glatiramer acetate was started for suspected tumefactive multiple sclerosis (MS). A follow-up brain MRI 6 months later showed persistence of the frontal gyral expansion. A brain biopsy led to the diagnosis of an oligodendroglioma, isocitrate dehydrogenase-mutant and 1 p/19q co-deleted (WHO grade II), managed with surgical resection and radiotherapy. Postoperative brain MRI showed a new enhancing periventricular lesion, making the choice of optimal disease-modifying therapy for MS challenging. This case highlights the possibility of coexistence of MS and oligodendroglioma, and emphasises the importance of a tissue diagnosis when atypical MS imaging features are present., Competing Interests: Competing interests: AS is funded through a clinician scientist development award from the USA National Multiple Sclerosis Society, and a clinical research training scholarship from the American Academy of Neurology. GFW has been a paid consultant for: EMD-Serono and Genzyme/Sanofi and is on the speaker bureau for EMD-Serono and Genzyme/Sanofi. GFW has received research grant funding from Genetech/Roche, the NIH, and the Doris Duke Foundation. CG reports no conflicts of interest. AHC has been a paid consultant for: Biogen, EMD-Serono, Genzyme/Sanofi, Genentech/Roche, and Novartis. AHC was funded in part by the Manny & Rosalyn Rosenthal – Dr John L Trotter MS Center Chair in Neuroimmunology of Barnes-Jewish Hospital Foundation., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Studies comparing intraventricular oligodendroglioma (IVO) and central neurocytoma (CN) in terms of their clinical, radiological and pathological features are scarce. We, therefore, investigated the similarities and differences between these types of tumors to get a better understanding of how they may be more properly diagnosed and treated. The clinical manifestations, CT/MRI findings, pathological characteristics and clinical outcomes of 8 cases of IVOs and 12 cases of CNs were analyzed retrospectively. Both IVO and CN occurred most commonly in young adults and manifested with symptoms of increased intracranial pressure secondary to obstructive hydrocephalus. However, they were radiologically different in location (p = 0.007), diffusion-weighted imaging (p = 0.001), "scalloping" appearance (p = 0.006), flow void sign (p = 0.006) and ventricular wall invasion (p = 0.000). Histologically, significant differences in mitotic count (p = 0.008) and parenchymal infiltration (p = 0.01) were noted. Immunohistochemically, significant differences in the expression of Olig2 (p = 0.000), Syn (p = 0.01) and NeuN (p = 0.000) were observed. In addition, MIB-1 labeling index (p = 0.035) and case fatality rate (p = 0.021) of IVO were much higher than those of CN, while survival rate of IVO was much lower than that of CN (p = 0.028). IVO and CN are similar in onset age and clinical manifestations, but have different imaging and pathological features. Patients with IVOs may have a relatively poorer prognosis compared to those with CNs.

The aim of this study is to determine whether regional homogeneity (ReHo) of resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (rsfMRI) data based on Kendall's coefficient of concordance (KCC-ReHo) and coherence (Cohe-ReHo) metrics may allow detection of brain tumor-induced neurovascular uncoupling (NVU) in the sensorimotor network similar to findings in standard motor task-based BOLD fMRI (tbfMRI) activation. Twelve de novo brain tumor patients undergoing clinical fMRI exams (tbfMRI and rsfMRI) were included in this Institutional Review Board (IRB)-approved study. Each patient displayed decreased/absent tbfMRI activation in the primary ipsilesional sensorimotor cortex in the absence of corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for motor tasks were obtained from the general linear model (GLM) analysis (reflecting motor activation vs. rest). KCC-ReHo and Cohe-ReHo maps were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and ipsilesional (IL) hemispheres were parcellated using an automated anatomical labeling (AAL) template for each patient. Similar region of interest (ROI) analysis was performed on tbfMRI, KCC-ReHo, and Cohe-ReHo maps to allow direct comparison of results. Voxel values in CL and IL ROIs of each map were divided by the corresponding global mean of KCC-ReHo and Cohe-ReHo in bihemispheric cortical brain tissue. Group analysis revealed significantly decreased IL mean KCC-ReHo (p = 0.02) and Cohe-ReHo (p = 0.04) metrics compared with respective values in the CL ROIs, consistent with similar findings of significantly decreased ipsilesional BOLD signal for tbfMRI (p = 0.0005). Ipsilesional abnormalities in ReHo derived from rsfMRI may serve as potential indicators of NVU in patients with brain tumors and other resectable brain lesions; as such, ReHo findings may complement findings on tbfMRI used for presurgical planning.

Objective: Patients with brain tumors are known to have deficits in cognitive, motor, and emotional domains. Comprehensive evaluation of the patient with brain tumor includes taking into account all these domains at baseline and throughout treatment. Standard neuropsychological assessment methods, however, are lengthy, expensive, and often are variable. The authors appraised the feasibility of using a brief, inexpensive, comprehensive, and standardized neuropsychological battery, the National Institutes of Health (NIH) Toolbox, to assess these domains in patients with diffuse glioma., Methods: Eighteen patients were recruited and completed the NIH Toolbox Cognitive Battery, 2 motor tests (Grip Strength and Grooved Pegboard), and the NIH Toolbox Emotional Battery. Fully corrected T scores are reported, as well as composite scores of fluid and crystallized cognition. Follow-up cognitive (n = 13) and motor assessment (n = 12) were performed at 1 month after surgery., Results: The total time to complete the battery was approximately 60 minutes. A total of 78% of patients demonstrated significant impairment on one or more cognitive test, whereas 37% had impaired fluid cognition. Crystallized and overall composite cognitive scores were relatively intact, with 16% of patients showing significant impairment. A total of 22% of patients had impaired strength in the left hand, and 22% had impaired dexterity in both hands. In addition, 50% of patients showed impairment in one or more emotional domain. At 1 month after surgery, a significant decrease in crystallized cognition was observed., Conclusions: The NIH Toolbox represents a feasible alternative to current neuropsychological batteries in the assessment of neurosurgical patients. It can be administered quickly, inexpensively, and will give the neurosurgical community a common currency when reporting neuropsychological results., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The initial aim of this study was to generate a transplantable glial tumour model of low-intermediate grade by disaggregation of a spontaneous tumour mass from genetically engineered models (GEM). This should result in an increased tumour incidence in comparison to GEM animals. An anaplastic oligoastrocytoma (OA) tumour of World Health Organization (WHO) grade III was obtained from a female GEM mouse with the S100β-v-erbB/inK4a-Arf (+/-) genotype maintained in the C57BL/6 background. The tumour tissue was disaggregated; tumour cells from it were grown in aggregates and stereotactically injected into C57BL/6 mice. Tumour development was followed using Magnetic Resonance Imaging (MRI), while changes in the metabolomics pattern of the masses were evaluated by Magnetic Resonance Spectroscopy/Spectroscopic Imaging (MRS/MRSI). Final tumour grade was evaluated by histopathological analysis. The total number of tumours generated from GEM cells from disaggregated tumour (CDT) was 67 with up to 100 % penetrance, as compared to 16 % in the local GEM model, with an average survival time of 66 ± 55 days, up to 4.3-fold significantly higher than the standard GL261 glioblastoma (GBM) tumour model. Tumours produced by transplantation of cells freshly obtained from disaggregated GEM tumour were diagnosed as WHO grade III anaplastic oligodendroglioma (ODG) and OA, while tumours produced from a previously frozen sample were diagnosed as WHO grade IV GBM. We successfully grew CDT and generated tumours from a grade III GEM glial tumour. Freezing and cell culture protocols produced progression to grade IV GBM, which makes the developed transplantable model qualify as potential secondary GBM model in mice.

Gliomas and glioneuronal tumors are histologically polymorphous tumors. They can harbor a clear cell "oligodendroglial-like" component that can be difficult to distinguish from tumor cells of oligodendrogliomas or neurons, particularly on small samples. Thus, knowledge of the pattern of molecular markers in different tumor cell components is essential to ensure reliable diagnosis. Here, we screened 14 pilocytic astrocytomas (PA), 12 gangliogliomas, and 13 oligodendrogliomas for the KIAA1549-BRAF fusion gene, IDH1/2 mutations, and 1p19q losses in various areas of interest representative of the different tumor cell components. Molecular patterns were analyzed according to histologic type, tumor cell components, and clinical data. The KIAA1549-BRAF fusion gene was detected only in 8 out of 11 PAs (73%) and in 3 out of 9 gangliogliomas (33%) (P=0.003). Interestingly, all of the studied areas of interest within the same tumor exhibited the same KIAA1549-BRAF fusion gene status. IDH1-R132H and 1p19q loss were found only in 12 out of the 13 oligodendrogliomas (P<0.0001). Our study shows that cellular polymorphism in PAs and gangliogliomas does not affect the results of molecular analysis investigating the status of the KIAA1549-BRAF fusion gene. Thus, this molecular analysis can be reliably used even if the sample size is limited and the selection of different tumor areas is not possible.

Introduction: The aim of this study is to investigate perfusion characteristics of glioblastoma with an oligodendroglioma component (GBMO) compared with conventional glioblastoma (GBM) using dynamic susceptibility contrast (DSC) perfusion magnetic resonance (MR) imaging and microvessel density (MVD)., Methods: The study was approved by the institutional review board. Newly diagnosed high-grade glioma patients were enrolled (n = 72; 20 GBMs, 14 GBMOs, 19 anaplastic astrocytomas (AAs), 13 anaplastic oligodendrogliomas (AOs), and six anaplastic oligoastrocytomas (AOAs)). All participants underwent preoperative MR imaging including DSC perfusion MR imaging. Normalized cerebral blood volume (nCBV) values were analyzed using a histogram approach. Histogram parameters were subsequently compared across each tumor subtype and grade. MVD was quantified by immunohistochemistry staining and correlated with perfusion parameters. Progression-free survival (PFS) was assessed according to the tumor subtype., Results: GBMO displayed significantly reduced nCBV values compared with GBM, whereas grade III tumors with oligodendroglial components (AO and AOA) exhibited significantly increased nCBV values compared with AA (p < 0.001). MVD analyses revealed the same pattern as nCBV results. In addition, a positive correlation between MVD and nCBV values was noted (r = 0.633, p < 0.001). Patients with oligodendroglial tumors exhibited significantly increased PFS compared with patients with pure astrocytomas in each grade., Conclusion: In contrast to grade III tumors, the presence of oligodendroglial components in grade IV tumors resulted in paradoxically reduced perfusion metrics and MVD. In addition, patients with GBMO exhibited a better clinical outcome compared with patients with GBM.

We treated patients with newly diagnosed and large low-grade oligodendroglial tumors with upfront procarbazine, CCNU and vincristine (PCV) in order to delay radiotherapy. Patients were treated with PCV for a maximum of 6 cycles. The response to treatment was defined according to the RANO criteria; in addition change over time of mean tumor diameters (growth kinetics) was calculated. Thirty-two patients were treated between 1998 and 2006, 18 of which were diagnosed with 1p/19q co-deleted tumors. Median follow-up duration was 8 years (range 0.5-13 years). The median overall survival (mOS) was 120 months and the median progression-free survival (mPFS) was 46 months. Growth kinetics showed an ongoing decrease of the mean tumor diameter after completion of chemotherapy, during a median time of 35 months, but an increase of the mean tumor diameter did not herald progression as detected by RANO criteria. 1p/19q co-deletion was associated with a significant increase in OS (mOS 83 months versus not reached for codeleted tumors; p = 0.003)) and PFS (mPFS 35 months versus 67 months for codeleted tumors; p = 0.024). Patients with combined 1p/19q loss had a 10 year PFS of 34 % and the radiotherapy in these patients was postponed for a median period of more than 6 years. This long-term follow-up study indicates that upfront PCV chemotherapy is associated with long PFS and OS and delays radiotherapy for a considerable period of time in patients with low-grade oligodendroglial tumors, in particular with combined 1p/19q loss.

Unlabelled: Oligodendrogliomas are a type of glioma that lack detailed investigation because of an inability to cultivate oligodendroglioma cells that faithfully recapitulate their salient qualities. We have successfully isolated and propagated glioma stem-like cells from multiple clinical oligodendroglioma specimens. These oligodendroglioma-propagating cells (OligPC) are multipotent and form xenografts with oligodendroglioma features. Bone morphogenetic proteins (BMP) are considered potent inhibitors of oligodendrogliogenesis during development; therefore, the effects of BMP signaling in OligPCs were characterized. BMP pathway components are expressed by OligPCs and canonical signaling via Smad proteins is intact. This signaling potently depletes CD133-positive OligPCs, decreasing proliferation, and inducing astrocytic differentiation. Furthermore, analyses revealed that cytoplasmic sequestration of the oligodendrocyte differentiation factors OLIG1/2 by the BMP signaling effectors ID2 and ID4 is a plausible underlying mechanism. These findings elucidate the molecular pathways that underlie the effects of BMP signaling on oligodendroglioma stem-like cells., Implications: Stem-like cells are capable of propagating oligodendrogliomas, and BMP signaling potently diminishes their stemness by inducing astrocytic differentiation, suggesting that BMP activation may be effective as a cancer stem cell-targeted therapy.

Background: Point mutations in genes encoding NADP+-dependent isocitrate dehydrogenases (especially IDH1) are common in lower grade diffuse gliomas and secondary glioblastomas and occur early during tumor development. The contribution of these mutations to gliomagenesis is not completely understood and research is hampered by the lack of relevant tumor models. We previously described the development of the patient-derived high-grade oligodendroglioma xenograft model E478 that carries the commonly occurring IDH1-R132H mutation. We here report on the analyses of E478 xenografts at the genetic, histologic and metabolic level., Results: LC-MS and in situ mass spectrometric imaging by LESA-nano ESI-FTICR revealed high levels of the proposed oncometabolite D-2-hydroxyglutarate (D-2HG), the product of enzymatic conversion of α-ketoglutarate (α-KG) by IDH1-R132H, in the tumor but not in surrounding brain parenchyma. α-KG levels and total NADP+-dependent IDH activity were similar in IDH1-mutant and -wildtype xenografts, demonstrating that IDH1-mutated cancer cells maintain α-KG levels. Interestingly, IDH1-mutant tumor cells in vivo present with high densities of mitochondria and increased levels of mitochondrial activity as compared to IDH1-wildtype xenografts. It is not yet clear whether this altered mitochondrial activity is a driver or a consequence of tumorigenesis., Conclusions: The oligodendroglioma model presented here is a valuable model for further functional elucidation of the effects of IDH1 mutations on tumor metabolism and may aid in the rational development of novel therapeutic strategies for the large subgroup of gliomas carrying IDH1 mutations.

Background: For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES)., Methods and Materials: The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR., Results: Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 ± 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients., Conclusion: The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

Introduction: Extent of resection is one of the most powerful predictors of outcome in surgery of gliomas. Tumors located within areas governing eloquence may impede a total tumor resection. Functional plasticity may be induced by therapeutic means, such as cortical stimulation with repetitive transcranial magnetic stimulation (rTMS). Thus, rTMS is a potential tool to induce an improvement of functions of eloquence menaced by brain tumors., Material and Methods: We report a case of a 59-year-old woman operated for a left sided precentral oligodendroglioma with awake intraoperative stimulation, whose tumor could not be completely removed because it affected areas governing language. Nine months later the tumor progressed and the motor language functions worsened. We submitted the patient to rTMS directed to Broca's area, next to the anterior pole of the tumor, with the aim of improving motor language function before a new tumor resection attempt. We performed 12 daily sessions of theta-burst rTMS followed by intensive language rehabilitation for 10 minutes, and 5 different aspects of language were measured before, immediately after and 10 minutes after each session., Results: Repetition and nomination worsened immediately after each rTMS session, and improved after 10 min of rehabilitation. However, basal values improved globally along the experiment. Also, the impact of rTMS on motor language was increasingly less along the procedure., Conclusions: rTMS induces changes in Broca's area and this effect can be potentially used to improve language function in tumors located at or close to eloquent cortical areas.

Objective: The purpose of this study was to evaluate retrospectively whether cerebral blood volume measurement based on pretreatment perfusion MRI is a prognostic biomarker for survival in patients with oligodendroglioma or mixed oligoastrocytoma., Patients and Methods: Between 1998 and 2004, 54 patients (23 females and 31 males), aged 21-73 years, with oligodendroglioma (or mixed tumour) were examined prior to beginning treatment with dynamic susceptibility-weighted contrast (DSC) perfusion MRI during gadolinium first-pass. The relative cerebral blood volume (rCBV) was calculated by dividing the measurement within the tumour by the measurement of the normal-appearing contralateral region. Patients were classified in two groups, grade A and grade B, according to the Saint-Anne Hospital classification and followed-up clinically and by means of MRI until their death or for a minimum of 5 years. Patients were also classified in grade II and grade III-IV, according to the World Health Organisation (WHO) classification, and were analysed with the same methods. Age, sex, treatment, tumour grade, contrast agent uptake, and rCBV were tested using survival curves with Kaplan-Meier's method, and their differences were analysed using the log-rank test., Results: In this population, median survival was 3 years. A rCBV threshold value of 2.2 was validated as a prognostic factor, for survival in these patients with oligodendrogliomas. Age, sex, contrast uptake, and maximum rCBV were found to be prognostic factors in univariate analysis. Multivariate analysis revealed that tumour grade (grade A/grade B), rCBV, age, and sex were prognostic factors independent of the other factors. The tumour grade according to the WHO classification (II versus III-IV) was also detected as an independent prognostic factor., Conclusion: Pretreatment rCBV measured by DSC perfusion MRI was found to be a prognostic factor for survival in patients with oligodendroglioma or mixed tumour, by using the Saint-Anne Hospital classification, which separate the IIB from the IIA., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Various subtypes of intracerebral hamartomas, associated with seizure disorders, have long been described. We describe a cerebral hamartoma placed in the left frontal lobe, associated with drug-resistant epilepsy, composed exclusively of mature oligodendroglial cells. The patient was a 27-year-old right-handed male presenting with severe epileptic encephalopathy and symptoms of behavior dysfunction (disinhibition, rage attacks) associated with a left frontal lesion. Magnetic resonance imaging revealed a small area iso-hypointense compared to the gray matter in T1-weighted sequences not enhancing after gadolinium contrast injection in the left frontal site. On histology, a cortical lesion composed of large aggregates of oligodendroglial cells, with round central nuclei and clear perinuclear halos, was observed. Neither mitotic figures nor necrosis were present. Reactivity for Ki67 and P53 was not found. The lesion was well demarcated from the adjacent brain parenchyma and perineuronal satellitosis was not observed in the cortex. In conclusion, albeit extremely rare, recognition of oligodendroglial hamartoma and its distinction from other epileptogenic lesions as dysembryoplastic neuroepithelial tumor or above all oligodendroglioma have important therapeutic and prognostic implications.

Purpose: Patients with oligodendrogliomas with allelic loss of chromosomal arm 1p and 19q have been shown, especially with anaplastic oligodendrogliomas, to have both a better initial and long-term response to chemotherapy as well as an improved overall survival. Effective treatment of patients with brain tumors requires accurate diagnostic techniques. MR imaging can be used to help differentiate between low- and high-grade tumors. We hypothesize that certain MR imaging characteristics can be used to differentiate between patients with and without 1p and 19q deletion., Methods: Using the clinical database at the University of Virginia Neuro-Oncology Center, we identified adult patients with grade II and III oligodendroglial tumors who underwent treatment from 2002 to 2007. Age at diagnosis, gender, tumor grade, chromosomal deletion status, duration of follow-up, and MR imaging characteristics were analyzed; the latter was read by a blinded neuroradiologist., Results: One hundred and four patients met the inclusion criteria. Of these patients, 44 manifested 1p/19q co-deletion and 60 patients lacked this deletion. The greatest cross-sectional area (mean) of the tumor measured 23.4 cm(2) for patients with the co-deletion and 31.7 cm(2) for patients with intact alleles (p = 0.008). In addition, inner table thinning was noted directly adjacent to seven tumors with intact 1p and 19q alleles and in no tumors with the 1p/19q co-deletion (p = 0.020). Amongst patients with pure oligodendrogliomas, those with 1p/19q co-deletion had tumors more often confined to a single lobe as compared with those patients without the co-deletion (p = 0.023). Finally, tumors with intact alleles were more often found in the temporal lobe (45.0%) as compared with co-deleted tumors (22.7%) (p = 0.011)., Conclusion: MR imaging is a valuable imaging modality for differentiating between oligodendrogliomas with or without the 1p/19q deletion. While imaging will never replace definitive tissue diagnosis, imaging characteristics such as tumor size, location, and overlying skull thinning can assist clinicians in assessing patients with oligodendroglial tumors prior to surgical or medical intervention.

Object: Mammalian heparanase has been shown to function in tumor progression, invasion, and angiogenesis. However, heparanase expression in gliomas has not been well analyzed. To clarify its expression in gliomas, human glioma tissues and glioma animal models were investigated., Methods: The expression of heparanase mRNA was determined in 33 resected human glioma tissues by semiquantitative real-time polymerase chain reaction. Heparanase expression was verified with a Western blot assay and immunohistochemistry (IHC) staining. Primary neurospheres from human glioblastoma multiforme (GBM) were developed in vitro. Heparanase expression in murine astrocytoma and human primary neurosphere animal models was examined using IHC., Results: The authors found that heparanase mRNA is greatly increased in gliomas including oligodendroglioma (9 samples), anaplastic astrocytoma (11 samples), and GBM (13 samples) as compared with healthy brain mRNA (3 samples). Note, however, that no significant difference was observed among the 3 tumor groups. Increased heparanase expression was also found in tumor tissues on Western blotting. Immunohistochemistry staining demonstrated that heparanase was expressed by neovessel endothelial cells, infiltrated neutrophils, and in some cases, by neoplastic cells. Heparanase-expressing cells, including GBM tumor cells and neovessel endothelial cells, exhibited decreased expression of CD44, a cell adhesion molecule on the cell membrane that is important for regulating tumor invasion. In addition, heparanase-expressing tumor cells showed an elevated density of the cell proliferation marker Ki 67, as compared with its density in non-heparanase-expressing tumor cells, suggesting that heparanase expression is correlated with enhanced tumor proliferation. Two animal glioma models were tested for heparanase expression. Both murine astrocytoma cells (Ast11.9-2) and cultured primary human GBM neurospheres expressed heparanase when grown in animal brain tissue., Conclusions: Glioma tissues contain increased levels of heparanase. Multiple cell types contribute to the expression of heparanase, including neovessel endothelial cells, tumor cells, and infiltrated neutrophils. Heparanase plays an important role in the control of cell proliferation and invasion. Animal models using Ast11.9-2 and primary neurospheres are suitable for antitumor studies targeting heparanase.

Twelve pregnancies in 11 adult women harboring World Health Organization (WHO) grade II gliomas (GIIGs) prior to pregnancy were reviewed to address whether pregnancy affects tumor growth using a quantitative approach of the radiological velocity of diametric expansion (VDE) on successive magnetic resonance images. VDE was significantly increased during pregnancy as compared to prepregnancy (p < 0.001) and to postdelivery (p = 0.012) periods. Pregnancy increases the radiological growth rates of GIIGs. An increase in seizure frequency was observed concomitantly in 40% of cases and further oncological treatment was started after delivery in 25% of cases.

We report a 37-year-old man with a primary intracranial oligodendroglioma presenting later with symptomatic multiple cerebrospinal fluid (CSF) intradural drop spinal metastases. This patient initially presented in 2006 with complex partial seizures. Initial histology demonstrated World Health Organization (WHO) grade 2 oligodendroglioma. The patient had further generalised seizures 7 months after initial tumour resection. MRI at that time confirmed tumour recurrence. The patient underwent a repeat craniotomy. Histology showed anaplastic transformation to a WHO grade 3 oligodendroglioma. About 30 months after his initial presentation, the patient developed a focal neurological deficit in the left leg with associated retention of urine. MRI of the neuraxis demonstrated widespread leptomeningeal metastatic drop deposits within the spinal canal. We discuss the mechanisms involved in tumour dissemination throughout the CSF. We also review the relevant literature regarding this phenomenon., (Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.)

According to World Health Organization (WHO) and Daumas-Duport grading systems, progression of oligodendrogliomas (ODGs) to a higher grade (WHO grade III, grade B) is associated with increased angiogenesis. Based on multivariate assessment of molecular, pathological, and radiological parameters, we further assessed the influence of tumor angiogenesis on tumor progression and patient survival. Patients with a diagnosis of ODG, consecutively treated in a single institution, were reviewed and reclassified according to WHO and Daumas-Duport grading systems. MRI scans were reviewed to assess contrast enhancement and necrosis. Tissue sections were used for pathology review and to evaluate immunostaining of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGF-R), Ki-67, and CD34. Multivariate analysis was performed to assess the impact of tumor angiogenesis-related pathological and radiological factors on patient survival. One hundred thirty-four patients with pure ODG were included in this study. Multivariate analysis identified four independent poor prognostic factors: necrosis, absence of seizure, increased vascularization, and age >55 years. A subgroup of patients with tumor necrosis, increased vascularization, and absence of seizures had a significantly worse outcome than predicted, with a median overall survival of 14.2 months. VEGF expression was significantly higher in this subgroup and correlated with disease progression regardless of histologic grade. Based on the presence of radiological or pathological necrosis, contrast enhancement or endothelial hyperplasia, and absence of seizures, a high risk group of ODG can be identified with significantly worse overall survival. Also, VEGF over-expression in ODG constitutes an early marker for predicting tumor progression.

Background: For the last one and a half decade, it has been found that platelet-derived growth factor (PDGF) promotes glial tumor growth through autocrine and paracrine loops, by expression of PDGFalpha receptor (PDGFRalpha) on glioma cells and PDGFbeta receptor (PDGFRbeta) on proliferating endothelial cells. However, studies on oligodendrogliomas, correlating expression of PDGF and its receptor with tumor grade and proliferative activity, through MIB-1 labeling index (LI) are relatively few as compared to astroglial counterpart., Methods: Formalin-fixed paraffin-embedded tissues from 55 cases of oligodendrogliomas (34 World Health Organization [WHO] grade II and 21 WHO grade III tumors) were subjected to immunohistochemistry. MIB-1 LI was calculated, and a semiquantitative scoring system for expression of PDGF and PDGFRalpha was used., Results: MIB-1 LI and PDGF expression increased with histologic grades of malignancy ("t" test, P < .001 and Mann Whitney test, U = 109, P < .001 respectively). The PDGF expression scores had a positive correlation with MIB-1 LI, irrespective of tumor grade (Pearson's correlation coefficient, r = 0.566; P < .001). However, there was no significant difference of PDGFRalpha expression between 2 grades of tumors., Conclusions: The results of this study showed that MIB-1 LI is a rapid and cost-effective modality for predicting tumor grade in oligodendrogliomas. Immunohistochemistry for PDGF was found to be useful in differentiating various grades of oligodendroglioma, and therefore, it may be involved in tumor cell proliferation and malignant transformation. Platelet-derived growth factor receptor alpha, although expressed in oligodendroglial neoplasms, was not found to be useful in predicting tumor grade.

MicroRNAs (miRNAs) are short non-protein-coding RNAs that function as key regulators of diverse biological processes through negative control on gene expression at the post-transcriptional level. Emerging evidence indicates that miRNAs play an important role in the development of human cancers, with their deregulation resulting in altered activity of downstream tumor suppressors, oncogenes and other signaling molecules. Recent years have seen considerable progress in miRNA research in brain tumors, particularly in glioblastomas and medulloblastomas, providing novel insights into the pathogenesis of these malignant lesions. Expression profiling has unveiled miRNA signatures that not only distinguish brain tumors from normal tissues, but can also differentiate histotypes or molecular subtypes with altered genetic pathways. Moreover, specific miRNA subsets may have potential diagnostic and prognostic values in some brain tumors. Several deregulated miRNAs uncovered in glioblastomas and medulloblastomas have their gene targets and the associated genetic pathways identified. This review summarizes recent findings of miRNA study in brain tumors.

Background: Treatment with a regimen of bevacizumab-irinotecan has been shown to be effective in recurrent grade 3 and 4 gliomas, but the effect of this regimen against recurrent oligodendroglial tumors has not been specifically studied., Methods: The bevacizumab-irinotecan regimen was retrospectively evaluated in a consecutive series of 25 patients with recurrent oligodendroglial tumors. All patients had not responded to previous treatment with radiation therapy and at least one line of temozolomide chemotherapy. Bevacizumab (10 mg/kg) and irinotecan (125 or 340 mg/m(2) according to the antiepileptic regimen) were administered every 14 days. Response was measured clinically and on monthly MRI., Results: The objective response rate was 72% (20% complete response, 52% partial response). After a median follow up of 202 days, the median progression-free survival was 140 days (95% confidence interval [CI] 116-infinity), and overall survival had not been reached. The 6-month progression-free survival was 42% (95% CI 26%-67%). Among the 17 patients in whom the status of the main molecular alterations of gliomas could be evaluated (search for deletions of chromosomes 1p, 19q, 9p, and 10q and amplification of epidermal growth factor receptor, mouse double-minute gene, and cyclin-dependent kinase 4 gene), no relation could be found between the response rate and the type of genetic change (including 1p-19q codeletion). The profile of tolerance was fair, with treatment discontinuation in 20% of patients. Intratumoral hemorrhages occurred in 6 patients (24%), but the treatment had to be discontinued because of symptomatic bleeding in only 1 patient (4%)., Conclusions: This regimen is effective in recurrent oligodendrogliomas, and the overall tolerance is acceptable.

Language fMRI has been used to study brain regions involved in language processing and has been applied to pre-surgical language mapping. However, in order to provide clinicians with optimal information, the sensitivity and specificity of language fMRI needs to be improved. Type II error of failing to reach statistical significance when the language activations are genuinely present may be particularly relevant to pre-surgical planning, by falsely indicating low surgical risk in areas where no activations are shown. Furthermore, since the execution of language paradigms involves cognitive processes other than language function per se, the conventional general linear model (GLM) method may identify non-language-specific activations. In this study, we assessed an exploratory approach, independent component analysis (ICA), as a potential complementary method to the inferential GLM method in language mapping applications. We specifically investigated whether this approach might reduce type II error as well as generate more language-specific maps. Fourteen right-handed healthy subjects were studied with fMRI during two word generation tasks. A similarity analysis across tasks was proposed to select components of interest. Union analysis was performed on the language-specific components to increase sensitivity, and conjunction analysis was performed to identify language areas more likely to be essential. Compared with GLM, ICA identified more activated voxels in the putative language areas, and signals from other sources were isolated into different components. Encouraging results from one brain tumor patient are also presented. ICA may be used as a complementary tool to GLM in improving pre-surgical language mapping.

The transcription factor p53 and its negative regulator MDM2 are pivotal in normal and cancer cells biology. Recently, a functional single-nucleotide polymorphism in the promoter region of MDM2 (MDM2 SNP309), alone or in combination with TP53 R72P, was shown to be associated with the risk, prognosis, age at onset, molecular markers, and response to chemotherapy of various cancers. This SNP has never been specifically investigated in a large series of oligodendroglial tumors. In a comparison with 232 healthy controls, we retrospectively analyzed blood samples of 293 oligodendroglial tumor patients for MDM2 SNP309. In addition, the TP53 R72P polymorphism and chromosome 1p/19q status, a major biomarker in oligodendroglial tumors, were investigated. The frequencies of T/T, T/G, and G/G genotypes in patients and controls did not suggest an increased risk of oligodendroglial tumor formation correlating with MDM2 SNP309. A borderline association was found between MDM2 SNP309 and overall survival (p=0.05), but in multivariate analysis, MDM2 SNP309 did not provide prognostic information complementary to age, tumor phenotype, grade, and 1p/19q status in oligodendroglial tumors. Finally, MDM2 SNP309, alone or in combination with TP53 R72P, was not associated with oligodendroglial tumors.

Object: Resection of brain tumors has been shown to increase patient survival. The extent of the possible resection, however, depends on whether the tumor has invaded brain regions important for motor, sensory, or cognitive processes and whether the brain tissue surrounding the tumor maintains its functional role. The goal of the present study was to develop new pre- and intraoperative tools to specifically assess the function of the rostral part of the dorsal premotor cortex (PMdr) in 4 patients with brain tumors close to this region., Methods: Using functional magnetic resonance (fMR) imaging and a task developed to assess accurate selection between competing responses based on conditional rules, the authors preoperatively assessed the function of the PMdr in 4 patients with brain tumors close to this region. In 1 patient, the authors developed an intraoperative procedure to assess performance on the task during the tumor resection., Results: Preoperative fMR imaging data showed specific activity increases in the vicinity of the tumors, that is, in the PMdr. As confirmed by postoperative structural MR imaging, the extent of the tumor resection was optimal and the functional region within the PMdr was preserved. Furthermore, patients exhibited no postoperative deficits during task performance, demonstrating that the function was preserved. Intraoperative behavioral results demonstrated that the cognitive processes underlying performance on the task remained intact throughout the tumor resection., Conclusions: These findings suggest that preoperative fMR imaging, together with intraoperative behavioral evaluation, may be a useful paradigm to assist neurosurgeons in preserving cognitive function in patients with brain tumors.

Objective and Importance: Oligodendroglial tumors rarely occur after radiation therapy. Here, we report a rare case of anaplastic oligodendroglioma arising after radiation therapy, in which genetic analysis was performed., Clinical Presentation and Intervention: A 41-year-old man who had received radiation therapy for a tumor of the suprasellar and pineal regions 31 years previously, presented with headache and progressive right hemiparesis. Magnetic resonance (MR) images revealed a ring-enhanced mass lesion in the left frontal lobe. Total removal of the tumor was performed through left frontoparietal craniotomy, and the histologic diagnosis was anaplastic oligodendroglioma. Using 23 microsatellite markers, the allelic status of chromosomes 1p, 10, 17p and 19q was evaluated by a PCR-based loss of heterozygosity (LOH) assay. Markers on chromosomes 1p, 17p and 19q revealed LOH, but none of the markers on chromosome 10 showed LOH. Based on the genetic analysis, this tumor was considered to be sensitive to chemotherapy. Two courses of chemotherapy, with procarbazine, ACNU and vincristine, were performed. However, tumor recurrence was detected only 3 months after the surgery. Despite additional radiochemotherapy, the tumor aggressively increased in size and the patient died with multiple recurrent tumors 1 year after surgery., Conclusion: The anaplastic oligodendroglioma presented in this report showed a more aggressive clinical course than was expected from the genetic analysis. The significance of 1p and 19q LOH in radiation-induced oligodendroglial tumors might differ from that in spontaneous counterparts.

Allelic losses on 19q are found in the majority of oligodendroglial tumors and approximately one-third of diffuse astrocytomas. However, the tumor suppressor genes (TSG) on 19q are still elusive. Using cDNA microarray expression profiling, EMP3 at 19q13.3 was among those genes showing the most pronounced expression differences. In line with this, other authors reported EMP3 as being epigenetically silenced in neuroblastomas and astrocytomas. To further investigate EMP3 as a TSG candidate on 19q13.3, we performed molecular analysis of this gene in 162 human gliomas. Mutation analysis did not reveal EMP3 alteration in 132 gliomas. In oligodendroglial tumors, we found that aberrant methylation in the 5'-region of EMP3 was significantly associated with reduced mRNA expression and LOH 19q. In astrocytomas, EMP3 hypermethylation was also paralleled by reduced expression but was independent of the 19q status. EMP3 hypermethylation was detected in more than 80% of diffuse, anaplastic astrocytomas and secondary glioblastomas. Primary glioblastomas, however, mostly lacked EMP3 hypermethylation and frequently overexpressed EMP3. Our data corroborate that oligodendroglial and astrocytic gliomas often show EMP3 hypermethylation and aberrant expression. Furthermore, our findings suggest that primary and secondary glioblastomas are not only characterized by distinct genetic profiles but also differ in their epigenetic aberrations.

Object: Treatment of patients with oligodendrogliomas relies on histopathological grade and characteristic cytogenetic deletions of 1p and 19q, shown to predict radio- and chemosensitivity and prolonged survival. Perfusion weighted magnetic resonance (MR) imaging allows for noninvasive determination of relative tumor blood volume (rTBV) and has been used to predict the grade of astrocytic neoplasms. The aim of this study was to use perfusion weighted MR imaging to predict tumor grade and cytogenetic profile in oligodendroglial neoplasms., Methods: Thirty patients with oligodendroglial neoplasms who underwent preoperative perfusion MR imaging were retrospectively identified. Tumors were classified by histopathological grade and stratified into two cytogenetic groups: 1p or 1p and 19q loss of heterozygosity (LOH) (Group 1), and 19q LOH only on intact alleles (Group 2). Tumor blood volume was calculated in relation to contralateral white matter. Multivariate logistic regression analysis was used to develop predictive models of cytogenetic profile and tumor grade., Results: In World Health Organization Grade II neoplasms, the rTBV was significantly greater (p < 0.05) in Group 1 (mean 2.44, range 0.96-3.28; seven patients) compared with Group 2 (mean 1.69, range 1.27-2.08; seven patients). In Grade III neoplasms, the differences between Group 1 (mean 3.38, range 1.59-6.26; four patients) and Group 2 (mean 2.83, range 1.81-3.76; 12 patients) were not significant. The rTBV was significantly greater (p < 0.05) in Grade III neoplasms (mean 2.97, range 1.59-6.26; 16 patients) compared with Grade II neoplasms (mean 2.07, range 0.96-3.28; 14 patients). The models integrating rTBV with cytogenetic profile and grade showed prediction accuracies of 68 and 73%, respectively., Conclusions: Oligodendroglial classification models derived from advanced imaging will improve the accuracy of tumor grading, provide prognostic information, and have potential to influence treatment decisions.

Introduction: Oligodendrogliomas constitute a group of infiltrating gliomas with a good response to radio and chemotherapy, which makes it important to distinguish them from the other gliomas and more especially from astrocytomas. Although oligodendrogliomas generally present typical histological features and are easy to diagnose, they sometimes have a mixed or hybrid morphology that makes their classification difficult and ambiguous. In these cases immunohistochemistry is of little use, since to date no markers have been found that enable a reliable distinction to be made between oligodendrogliomas and astrocytomas., Development: Here we review the histological criteria of oligodendroglial tumours and how to distinguish them from other morphologically similar brain tumours. We also discuss how alterations to the short arm of chromosome 1 and to the long arm of chromosome 19 (co-deletion of 1p/19q), which can be detected using FISH or PCR, enable us to classify mixed oligoastrocytic tumours and to define subgroups of oligodendrogliomas with different prognoses and responses to treatment., Conclusions: In daily practice, the status of 1p and 19q should be analysed in all tumours with an oligodendroglial histological phenotype, because this makes it possible to define subgroups each having different prognoses and responses to therapy.

It is reasonable to suggest that working memory (WM; Baddeley & Hitch, 1974) is involved in decision making, as decision making is dependent on the ability to remember and update past choices and outcomes. However, contradictory results have been reported in the literature concerning the role of two of its components, namely the central executive and the phonological loop. In order to investigate the role of these components in the decision-making process, we tested a patient with intact central executive but impaired phonological loop on a laboratory decision-making task involving hypothetical gambles (gambling task, GT). When tested in a no-load condition (simple keypress task), her performance was not significantly different from that of matched controls. We also verified whether her performance would be affected differently by memory-load when compared with control subjects. The memory task (holding a string of letters in memory) loaded WM without incurring number-number interference. When the memory-load was imposed during the GT, both the patient and the controls showed a decline in performance, but the strategy they adopted differed. Possible explanations are discussed. In conclusion, our results suggest that the phonological loop is not directly involved in decision making.

Objective: Nogo-A is an axon regeneration inhibitor, and its function in central nervous system (CNS) is still unknown. The present study is to explore the relationship between the expression of Nogo-A and the malignancy of oligodendroglial tumors in patients., Methods: Tumor tissue samples with different malignancy grade were obtained from the hospitals. The samples used for detection had been diagnosed as oligodendroglial tumors (oligodendroglioma or anaplastic oligodendroglioma). The expression of Nogo-A was detected by immunohistochemistry and western-blot analysis. The correlation test between the Nogo-A expression and the morphological changes (the percentages of atypical cells and mitotic cells in the tumors) related to the malignancy of tumor tissues was performed., Results: There was significant negative correlation between the Nogo-A expression and the morphological change of tumor tissues according to immunohistochemistry. Western-blot analysis also indicated that the gray value of Nogo-A protein band in the oligodendroglioma group was significantly higher than that in the anaplastic oligodendroglioma group., Conclusion: Nogo-A expression was negatively correlated with the malignancy grade of oligodendroglial tumors.

Introduction: The biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the -1p/-19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy., Methods: Pretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12-15, and 10q22-26 and p53 mutation (exons 5-8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33)., Results: 1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student's t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The -1p/-19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss., Conclusion: rCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the -1p/-19q genotype.

The optimal treatment for patients with oligodendrogliomas is unknown, and current management strategies remain controversial. This past year, further exploration of the molecular genetics of the tumors and its prognostic implications for outcome, evaluation of the utility of positron emission tomography imaging, and the role of radiation and chemotherapy in the treatment of oligodendrogliomas have been reported. It is becoming increasingly apparent that oligodendrogliomas are several distinct diseases on a molecular level, and that key genetic derangements can signify a response to treatment and favorable outcome. The added contributions of recent publications consolidates these emerging impressions. Ultimately, the combination of improved imaging techniques, molecular profiling, and new therapies should result in improved outcome with reduced treatment-related toxicity for patients with newly diagnosed, progressive, and recurrent oligodendrogliomas.

Assessment of eloquent functions during brain mapping usually relies on testing reading, speech, and comprehension to uncover transient deficits during electrical stimulation. These tests stem from findings predicted by the Geschwind-Wernicke hypothesis of receptive and expressive cortices connected by white matter tracts. Later work, however, has emphasized cortical mechanisms of language function. The authors report two cases that demonstrate that conduction aphasia is cortically mediated and can be inadequately assessed if not specifically evaluated during brain mapping. To determine the distribution of language on the dominant cortex, electrical cortical stimulation was performed in two cases by using implanted subdural electrodes during brain mapping before epilepsy surgery. A transient isolated deficit in repetition of language was reported during stimulation of the posterior portion of the dominant superior temporal gyrus in one patient and during stimulation of the supramarginal gyrus in the other patient. These cases demonstrate a localization of language repetition to the posterior perisylvian cortex. Brain mapping of this region should include assessment of verbal repetition to avoid potential deficits resembling conduction aphasia.

The localization of functional areas obtained from functional MRI (fMRI) is useful for patients suffering from tumors contiguous to eloquent brain areas. fRMI is an efficient tool in the strategy of treatment of low grade oligodendroglioamas in the rolandic area in intact or slightly impaired patients. It can be used preoperatively to assess motor functional areas. Indeed there is a good correlation for motor cortex lesions when using comparison between fMRI and intraoperative findings. Direct integration of fMRI data into neuronavigation enables to better visualize and preserve eloquent brain areas. One must be aware of fMRI limits. It is still often used with the control of direct cortical stimulations.

Loss of 1p heterozygosity is one of the most characteristic events in oligodendrogliomas. Several genes located in this region have been previously studied to find the target gene implicated in the development of this tumor without success. Patched-2, RIZ1 and KIF1B are novel oncosuppressor genes located at 1p and involved in different kinds of tumors. We have studied these genes and p18(ink4c) using PCR/SSCP methods to detect sequence variations in a series of 40 oligodendrogliomas in which the allelic status at 1p was analyzed. Polymorphisms or no sequence changes were detected in all four genes analyzed. None of the genes analyzed seem to be the target-gene mapped at 1p involved by mutation in oligodendroglioma development.

Six patients with brain tumors within or near the primary motor cortex underwent preoperative functional magnetic resonance imaging (fMRI) and intraoperative cortical mapping, and the accuracy of those techniques for localization of the primary motor cortex and motor function beside the tumor were determined by comparison against neuroanatomical correlates from pre-, intra- and postoperative neurological observations. The location of the primary motor cortex was detected by intraoperative cortical mapping in 5 of 6 cases and by fMRI in all 6 cases. Brain mapping provided equivocal information on the cortical representation of motor territories, and with the technique used in close proximity to the tumor, the motor territories were not detected in all but 1 case. In contrast, the areas controlling motor function in close proximity to the tumor were detected by fMRI in 4 of 6 cases. These data indicate that intraoperative cortical mapping has a low sensitivity for the detection of motor function in the area beside the tumor. Therefore, this technique may not be sufficient to prevent compromise of motor areas during tumor resection., (Copyright 2005 S. Karger AG, Basel.)

Objective: This study addresses the potential utility of preoperative functional imaging with magnetoencephalography (MEG) for the selection of glioma patients who are likely to benefit from resective surgical treatment regarding postoperative morbidity., Methods: One hundred and nineteen patients with gliomas adjacent to sensorimotor, visual and speech related brain areas were investigated preoperatively with a MAGNES II biomagnetometer. In each patient the pre-surgical evaluation was focussed on the visual, sensorimotor cortex and/or of the speech related brain areas. A grading system was then used according to the distance of the MEG activation sources to the nearest tumour border to determine the further treatment. The therapeutic options consisted in conservative treatment, stereotactic biopsy and/or a radiation and chemotherapy, substantial cytoreduction and the gross total removal of the lesion., Results: From 119 investigated patients, 55 patients (46.2%) were not considered for surgery due to tumour invasion to functional cortex. Sixty four patients (53.8%) were chosen for resective surgery. In the surgical group only four patients (6.2%) suffered from neurological deterioration., Conclusions: Magnetic source imaging (MSI) proved to be a valuable help in the clinical decision making process of lesions adjacent to functional important brain areas. The relative high number of patients in whom MSI warns of the postoperative crippling sequelae may lead to a better selection of patients who benefit from resective surgery. This method may help to find the patients for whom conservative treatment seems to be more favourable concerning quality of life in the surviving time.

Purpose of Review: The sensitivity of oligodendroglioma to chemotherapy and the prognostic significance of combined loss of 1p/19q in these tumors are now well established. This review discusses recent molecular, genetic and clinical advances made in studies on oligodendroglioma and mixed oligoastrocytoma., Recent Findings: Methylation of genes is a frequent event in oligodendroglioma (OD), but no specific methylation sites have been discovered. In contrast to earlier reports, the expression of the basic helix-loop-helix transcription factors is not specific for OD, but may occur in glial tumors of all lineages. In a number of studies, the prognostic relevance of 1p/19q loss has been confirmed, and several studies have shown that loss of 1p/19q are early events in OD. No candidate genes have so far been identified on 1p36 and 19q13. Gene expression profiling using gene arrays allows the separation of glial tumors according to histology, tumor grade and prognosis. A number of genes have been identified that are significantly more highly expressed in OD. On MRI imaging, OD with combined 1p/19q loss has typical characteristics, including indistinct borders and a mixed signal intensity on T2-weighted images. Despite the large increase in knowledge on the molecular abnormalities in OD, the therapeutic options for these tumors have not improved significantly since the introduction of temozolomide. The increased survival after chemotherapy has been clearly established, but the timing of chemotherapy seems less critical. It is clear that temozolomide is a good alternative to procarbazine, CCNU and vincristine (PCV) chemotherapy, in particular, because it is better tolerated. No randomized trials, however, have compared PCV-chemotherapy to temozolomide. New agents--and probably more targeted therapies--are needed to further improve treatment. Chemo-irradiation deserves further study in anaplastic OD., Summary: The progress in the understanding of genetic and molecular abnormalities of OD has improved the recognition of treatment-sensitive OD, although this has not yet been mirrored in improved therapies or new treatment options. While chemotherapy improves the outcome of OD, further improvements will likely require new drugs or new treatment concepts.

Bioluminescence imaging has previously been used to monitor the formation of grafted tumors in vivo and measure cell number during tumor progression and response to therapy. The development and optimization of successful cancer therapy strategies may well require detailed and specific assessment of biological processes in response to mechanistic intervention. Here, we use bioluminescence imaging to monitor the cell cycle in a genetically engineered, histologically accurate model of glioma in vivo. In these platelet-derived growth factor (PDGF)-driven oligodendrogliomas, G1 cell-cycle arrest is generated by blockade of either the PDGF receptor or mTOR using small-molecule inhibitors.

The dielectric properties of various cancers, namely brain tumor, breast cancer, gastric carcinoma, and colon cancer, were measured in the frequency range of 500 MHz to 5 GHz. Cancers were cultivated applying the xenograft model of growing human cancerous tissues using the specific pathogen free, homo inbred mouse (a nude mouse). The complex permittivity was measured using an open-ended coaxial probe (HP85070B) and a computer controlled network analyzer (HP8510C). For the measurement of the dielectric properties, a total of 58 xenografted specimens was used. The results showed that measured values of complex permittivity for all four cancerous tissues were similar, with little variations over the frequency range used. It might be agreed that components and characteristics of different cancerous tissues would be similar despite their different occurrences in the human body. It is necessary to investigate this result further., (2004 Wiley-Liss, Inc.)

The conventional MR imaging appearance of gangliogliomas is often variable and nonspecific. Conventional MR images, relative cerebral blood volume (rCBV) and vascular permeability (K(trans)) measurements were reviewed in 20 patients with pathologically proven grade 1 and 2 gangliogliomas (n = 20) and compared to a group of grade 2 low-grade gliomas (n = 30). The conventional MRI findings demonstrated an average lesion size of 4.1 cm, contrast enhancement (n = 19), variable degree of edema, variable mass effect, necrosis/cystic areas (n = 8), well defined (n = 12), signal heterogeneity (n = 9), calcification (n = 4). The mean rCBV was 3.66 +/- 2.20 (mean +/- std) for grade 1 and 2 gangliogliomas. The mean rCBV in a comparative group of low-grade gliomas (n = 30), was 2.14 +/- 1.67. p Value < 0.05 compared with grade 1 and 2 ganglioglioma. The mean K(trans) was 0.0018 +/- 0.0035. The mean K(trans) in a comparative group of low-grade gliomas (n = 30), was 0.0005 +/- 0.001. p Value = 0.14 compared with grade 1 and 2 ganglioglioma. The rCBV measurements of grade 1 and 2 gangliogliomas are elevated compared with other low-grade gliomas. The K(trans), however, did not demonstrate a significant difference. Gangliogliomas demonstrate higher cerebral blood volume compared with other low-grade gliomas, but the degree of vascular permeability in gangliogliomas is similar to other low-grade gliomas. Higher cerebral blood volume measurements can help differentiate gangliogliomas from other low-grade gliomas.

Objective: The aim of this study was to analyze the usefulness of preoperative language functional magnetic resonance imaging (fMRI), by correlating fMRI data with intraoperative cortical stimulation results for patients with brain tumors., Methods: Naming and verb generation tasks were used, separately or in combination, for 14 right-handed patients with tumors in the left hemisphere. fMRI data obtained were analyzed with SPM software, with two standard analysis thresholds (P < 0.005 and then P < 0.05). The fMRI data were then registered in a frameless stereotactic neuronavigational device and correlated with direct brain mapping results. We used a statistical model with the fMRI information as a predictor, spatially correlating each intraoperatively mapped cortical site with fMRI data integrated in the neuronavigational system (site-by-site correlation). Eight patients were also studied with language fMRI postoperatively, with the same acquisition protocol., Results: We observed high variability in signal extents and locations among patients with both tasks. The activated areas were located mainly in the left hemisphere in the middle and inferior frontal gyri (F2 and F3), the superior and middle temporal gyri (T1 and T2), and the supramarginal and angular gyri. A total of 426 cortical sites were tested for each task among the 14 patients. In frontal and temporoparietal areas, poor sensitivity of the fMRI technique was observed for the naming and verb generation tasks (22 and 36%, respectively) with P < 0.005 as the analysis threshold. Although not perfect, the specificity of the fMRI technique was good in all conditions (97% for the naming task and 98% for the verb generation task). Better correlation (sensitivity, 59%; specificity, 97%) was achieved by combining the two fMRI tasks. Variation of the analysis threshold to P < 0.05 increased the sensitivity to 66% while decreasing the specificity to 91%. Postoperative fMRI data (for the cortical brain areas studied intraoperatively) were in accordance with brain mapping results for six of eight patients. Complete agreement between pre- and postoperative fMRI studies and direct brain mapping results was observed for only three of eight patients., Conclusion: With the paradigms and analysis thresholds used in this study, language fMRI data obtained with naming or verb generation tasks, before and after surgery, were imperfectly correlated with intraoperative brain mapping results. A better correlation could be obtained by combining the fMRI tasks. The overall results of this study demonstrated that language fMRI could not be used to make critical surgical decisions in the absence of direct brain mapping. Other acquisition protocols are required for evaluation of the potential role of language fMRI in the accurate detection of essential cortical language areas.