Feasibility of performance-based functional assessment in brain tumour survivors.

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.

Clinical, radiological, pathological and prognostic aspects of intraventricular oligodendroglioma: comparison with central neurocytoma.

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.

Development of a transplantable glioma tumour model from genetically engineered mice: MRI/MRS/MRSI characterisation.

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 S100ß-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.

Treatment of large low-grade oligodendroglial tumors with upfront procarbazine, lomustine, and vincristine chemotherapy with long follow-up: a retrospective cohort study with growth kinetics.

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.

Paradoxical perfusion metrics of high-grade gliomas with an oligodendroglioma component: quantitative analysis of dynamic susceptibility contrast perfusion MR imaging.

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.

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

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.

rTMS stimulation to induce plastic changes at the language motor area in a patient with a left recidivant brain tumor affecting Broca's area.

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.

Pregnancy increases the growth rates of World Health Organization grade II gliomas.

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.

Oligodendroglial hamartoma: a potential source of misdiagnosis for oligodendroglioma.

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.

Dissecting tumor maintenance requirements using bioluminescence imaging of cell proliferation in a mouse glioma model.

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.

Prognostic value of perfusion MR imaging in patients with oligodendroglioma: A survival study.

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.

Assessment of tumor angiogenesis as a prognostic factor of survival in patients with oligodendroglioma.

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.

MR imaging characteristics of oligodendroglial tumors with assessment of 1p/19q deletion status.

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.

Measurement of Active Motor Threshold Using a Dynamometer During Navigated Transcranial Magnetic Stimulation in a Patient with Postoperative Brain Tumor: Technical Note.

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.

Altered corticospinal microstructure and motor cortex excitability in gliomas: an advanced tractography and transcranial magnetic stimulation study.

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.

Oncogenic role of microRNAs in brain tumors.

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.

Group independent component analysis of language fMRI from word generation tasks.

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.

Influence of MDM2 SNP309 alone or in combination with the TP53 R72P polymorphism in oligodendroglial tumors.

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.

Preoperative functional magnetic resonance imaging assessment of higher-order cognitive function in patients undergoing surgery for brain 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.

A case of oligodendroglioma and multiple sclerosis: Occam's razor or Hickam's dictum?

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.