Category: Oncology

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Higher incidence of epilepsy in meningiomas located on the premotor cortex: a voxel-wise statistical analysis

Acta Neurochir (2012) 154:2241–2249

A substantial number of patients with brain tumors develop recurrent seizures, known as tumorassociated epilepsy. It is important to identify specific subgroups of brain tumor patients with higher incidences of epilepsy because a meta-analysis failed to certify the effectiveness of prophylactic anti-epileptic drugs (AEDs) to abort tumor-associated epilepsy as a whole.

Methods To investigate the relationship between tumor location and incidence of epilepsy, we performed voxel-wise comparison between 3D MRI scans obtained from patients with meningioma-associated epilepsy and those from control patients using spatial normalization techniques on neuroimaging data. Variables such as age, tumor size, the degree of edema, and pathological diagnosis were also compared between the two groups.

Results Our results showed the highest incidence of epilepsy when the tumor was located on the premotor cortex in the frontal lobe (Z-scores >2.0, Liebermeister’s quasi-exact test). The stepwise multiple regression analysis on the clinical data revealed that the tumor diameter (p<0.001) and the patient’s age (p=0.024) were positive and negative predictors, respectively, for the onset of epilepsy.

Conclusions The incidence of epilepsy was higher in meningiomas located on the premotor cortex than on the other cortex. Larger volume also contributed to the onset of epilepsy. We suggest that variations of epilepsy incidence dependent on tumor characteristics can be considered when treating tumor-associated epilepsy.

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Low-grade glioma surgery in eloquent areas

J Neurosurg 117:1039–1052, 2012

A growing number of published studies have recently demonstrated the role of resection in overall survival (OS) for patients with gliomas. In this retrospective study, the authors objectively investigated the role of the extent of resection (EOR) in OS in patients with low-grade gliomas (LGGs).

Methods. Between 1998 and 2011, 190 patients underwent surgery for LGGs. All surgical procedures were conducted under corticosubcortical stimulation. The EOR was established by analyzing the pre- and postoperative volumes of the gliomas on T2- weighted MRI studies. The difference between the preoperative tumor volumes was also investigated by measuring the volumetric difference between the T2- and T1-weighted MRI images (DVT2T1) to evaluate how the diffusive tumor-growing pattern affected the EOR achieved.

Results. The median preoperative tumor volume was 55 cm3, and in almost half of the patients the EOR was greater than 90%. In this study, patients with an EOR of 90% or greater had an estimated 5-year OS rate of 93%, those with EOR between 70% and 89% had a 5-year OS rate of 84%, and those with EOR less than 70% had a 5-year OS rate of 41% (p < 0.001). New postoperative deficits were noted in 43.7% of cases, while permanent deficits occurred in 3.16% of cases. There were 41 deaths (21.6%), and the median follow-up was 4.7 years. A further volumetric analysis was also conducted to compare 2 different intraoperative protocols (Series 1 [intraoperative electrical stimulation alone] vs Series 2 [intraoperative stimulation plus overlap of functional MRI/fiber tracking diffusion tensor imaging data on a neuronavigation system]). Patients in Series 1 had a median EOR of 77%, while those in Series 2 had a median EOR of 90% (p = 0.0001). Multivariate analysis showed that OS is influenced not only by EOR (p = 0.001) but also by age (p = 0.003), histological subtype (p = 0.005), and the DVT2T1 value (p < 0.0001). Progression-free survival is similarly influenced by histological subtype (fibrillary astrocytoma, p = 0.003), EOR (p < 0.0001), and DVT2T1 value (p < 0.0001), as is malignant progression– free survival (p = 0.003, p < 0.0001, and p < 0.0001, respectively). Finally, the study shows that the higher the DVT2T1 value, the less extensive the currently possible resection, highlighting an apparent correlation between the DVT2T1 value itself and EOR (p < 0.0001).

Conclusions. The EOR and the DVT2T1 values are the strongest independent predictors in improving OS as well as in delaying tumor progression and malignant transformation. Furthermore, the DVT2T1 value may be useful as a predictive index for EOR. Finally, due to intraoperative corticosubcortical mapping and the overlap of functional data on the neuronavigation system, major resection is possible with an acceptable risk and a significant increase in expected OS.

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Brain Tumor Surgery With 3-Dimensional Surface Navigation

Neurosurgery 71[ONS Suppl 2]:ons286–ons295, 2012

Precise lesion localization is necessary for neurosurgical procedures not only during the operative approach, but also during the preoperative planning phase. OBJECTIVE: To evaluate the advantages of 3-dimensional (3-D) brain surface visualization over conventional 2-dimensional (2-D) magnetic resonance images for surgical planning and intraoperative guidance in brain tumor surgery.

METHODS: Preoperative 3-D brain surface visualization was performed with neurosurgical planning software in 77 cases (58 gliomas, 7 cavernomas, 6 meningiomas, and 6 metastasis). Direct intraoperative navigation on the 3-D brain surface was additionally performed in the last 20 cases with a neurosurgical navigation system. For brain surface reconstruction, patient-specific anatomy was obtained from MR imaging and brain volume was extracted with skull stripping or watershed algorithms, respectively. Threedimensional visualization was performed by direct volume rendering in both systems. To assess the value of 3-D brain surface visualization for topographic lesion localization, a multiple-choice test was developed. To assess accuracy and reliability of 3-D brain surface visualization for intraoperative orientation, we topographically correlated superficial vessels and gyral anatomy on 3-D brain models with intraoperative images.

RESULTS: The rate of correct lesion localization with 3-D was significantly higher (P = .001, x2), while being significantly less time consuming (P , .001, x2) compared with 2-D images. Intraoperatively, visual correlation was found between the 3-D images, superficial vessels, and gyral anatomy.

CONCLUSION: The proposed method of 3-D brain surface visualization is fast, clinically reliable for preoperative anatomic lesion localization and patient-specific planning, and, together with navigation, improves intraoperative orientation in brain tumor surgery and is relatively independent of brain shift.

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Meningiomas in Pregnancy

Neurosurgery 71:951–961, 2012

Dramatic growth of meningiomas is occasionally encountered during pregnancy. While cell proliferation is often assumed, hemodynamic changes have also been touted as a cause.

OBJECTIVE: We identified 17 meningiomas resected during pregnancy or within 3 weeks post-partum and characterized them to determine the cause of occasional rapid growth in pregnancy.

METHODS: Seventeen tumors were identified from searches at 4 university centers. All available clinical records, radiology images, and tissue specimens were reviewed, with immunohistochemical studies performed as needed.

RESULTS: Sixteen patients underwent tumor resection and 1 died of complications prior to surgery. Average patient age was 32 years. Nine experienced onset of symptoms in the third trimester or within 8 days post-partum. Principle physical findings included visual complaints (59%) and cranial nerve palsies (29%). Ten tumors (59%) were located in the skull base region. The Ki-67 labeling index was low (0.5-3.6%) in 11 of 13 benign (grade I) tumors and elevated (11-23.2%) in 3 of 4 atypical (grade II) meningiomas. Eight (50%) tumors featured hypervascularity with at least focal CD34- positive hemangioma-like microvasculature. Fourteen (82%) showed evidence of intraand/ or extracellular edema, 1 so extensive that its meningothelial nature was not apparent. Five tumors (29%) exhibited intratumoral hemorrhage and/or necrosis.

CONCLUSION: Our series suggests that pregnancy-associated meningiomas located in the skull base are likely to require surgical intervention for visual complaints and cranial nerve palsies. The rapid tumor growth is more often due to potentially reversible hemodynamic changes rather than hormone-induced cellular proliferation.

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Extent of resection in glioblastoma

J Neurosurg 117:851–859, 2012

The extent of resection (EOR) is a known prognostic factor in patients with glioblastoma. However, gross-total resection (GTR) is not always achieved. Understanding the factors that prevent GTR is helpful in surgical planning and when counseling patients. The goal of this study was to identify demographic, tumor-related, and technical factors that influence EOR and to define the relationship between the surgeon’s impression of EOR and radiographically determined EOR.

Methods. The authors performed a retrospective review of the electronic medical records to identify all patients who underwent craniotomy for glioblastoma resection between 2006 and 2009 and who had both preoperative and postoperative MRI studies. Forty-six patients were identified and were included in the study. Image analysis software (FIJI) was used to perform volumetric analysis of tumor size and EOR based on preoperative and postoperative MRI. Using multivariate analysis, the authors assessed factors associated with EOR and residual tumor volume. Perception of resectability was described using bivariate statistics, and survival was described using the log-rank test and Kaplan-Meier curves.

Results. The EOR was less for tumors in eloquent areas (p = 0.014) and those touching ventricles (p = 0.031). Left parietal tumors had significantly greater residual volume (p = 0.042). The average EOR was 91.0% in this series. There was MRI-demonstrable residual tumor in 69.6% of cases (16 of 23) in which GTR was perceived by the surgeon. Expert reviewers agreed that GTR could be safely achieved in 37.0% of patients (17 of 46) in this series. Among patients with safely resectable tumors, radiographically complete resection was achieved in 23.5% of patients (4 of 17). An EOR greater than 90% was associated with a significantly greater 1-year survival (76.5%) than an EOR less than 90% (p = 0.005).

Conclusions. The authors’ findings confirm that tumor location affects EOR and suggest that EOR may also be influenced by the surgeon’s ability to judge the presence of residual tumor during surgery. The surgeon’s ability to judge completeness of resection during surgery is commonly inaccurate. The authors’ study confirms the impact of EOR on 1-year survival.

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Cognitive functioning early after surgery of gliomas in eloquent areas

J Neurosurg 117:831–838, 2012

Patients with gliomas frequently have cognitive deficits, and surgery can exacerbate these deficits. Preoperative assessment is therefore crucial in patients undergoing surgery for glioma in eloquent areas, because the proximity of functional areas increases the risk of permanent postoperative cognitive disturbances. Although pre- and postoperative language and motor function in patients with glioma have been investigated frequently, data on good cognition studies are scarce. Most studies have focused on clinical neurological functioning or have only used brief neurological instruments. The authors investigated whether surgery for glioma in eloquent areas influences cognition early after surgery, by using an elaborate test protocol.

Methods. Twenty-eight patients with gliomas of the left hemisphere in language and nonlanguage areas were assessed before and 3 months after surgery with a comprehensive neuropsychological test protocol. The authors performed a correlation analysis between change in cognitive performance and tumor characteristics (that is, location, volume, pathological features, and histological grade) and between cognitive change and treatment-related factors (the extent of the resection and postoperative treatment with chemo- and radiotherapy).

Results. Both pre- and postoperatively, the mean performance of the patients was worse than the performance of the normal population in the language domain, the memory domain, and the executive functions (p < 0.05). Postoperatively, a decline was found in the language domain (t = 2.34, p = 0.027) and in the executive functions (t = 2.45, p = 0.022). However, cognitive change postsurgery was influenced by the location of the tumor; the decrease of cognitive score in the language domain was only observed in patients with tumors in or close to language areas (t = 2.33, p = 0.029). No effect on cognitive change was found for the other tumor characteristics and treatment-related factors.

Conclusions. This study underlines the importance of the use of a neuropsychological test protocol before and after surgery in patients with glioma, because several tasks in the domains of language, memory, and executive functions appeared to deteriorate after surgery. Tumor resection in language areas increases the risk of cognitive deficits in the language domain postoperatively.

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Assessing the functional status of the motor system in brain tumor patients using transcranial magnetic stimulation

Acta Neurochir (2012) 154:2075–2081

Transcranial magnetic stimulation (TMS) is being used in the pre-operative diagnostics of patients with tumors in or near the motor cortex. Although the main purpose of TMS in such patients is to map the functional areas of the motor cortex in spatial relation to the tumor, TMS also provides some numerical neurophysiological measurements of the functional status of the patient’s motor system. The aim of this paper is to provide reference values for these neurophysiological measurements from a large and varied clinical sample.

Methods TMS was used in the pre-operative work-up of patients with various types of tumors in or near the motor cortex during a 3-year period. Data was collected prospectively in 100 patients, yet this is a post hoc report.

Results Patient characteristics had no influence on the neurophysiological parameters. The response latency time was almost never different in the tumorous versus healthy hemisphere, so clinicians should be suspicious if they find interhemispheric differences for latency. A high interhemispheric ratio of resting motor threshold (RMT) or a low interhemispheric ratio of motor evoked potential (MEP) amplitude appear to suggest immanent deterioration of the patient’s motor status.

Conclusion In addition to topographic cortical mapping, TMS also serves as a neurophysiological assessment of the functional status of the patient’s motor system. The results presented here provide clinicians with a set of reference values to contextualize findings in their own tumor patients. Further research is still needed to better understand the full clinical relevance of these neurophysiological parameters.

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Arcuate fasciculus in brain tumor surgery

J Neurosurg 117:839–843, 2012 

Disturbance of the arcuate fasciculus in the dominant hemisphere is thought to be associated with language- processing disorders, including conduction aphasia. Although the arcuate fasciculus can be visualized in vivo with diffusion tensor imaging (DTI) tractography, its involvement in functional processes associated with language has not been shown dynamically using DTI tractography. In the present study, to clarify the participation of the arcuate fasciculus in language functions, postoperative changes in the arcuate fasciculus detected by DTI tractography were evaluated chronologically in relation to postoperative changes in language function after brain tumor surgery.

Methods. Preoperative and postoperative arcuate fasciculus area and language function were examined in 7 right-handed patients with a brain tumor in the left hemisphere located in proximity to part of the arcuate fasciculus. The arcuate fasciculus was depicted, and its area was calculated using DTI tractography. Language functions were measured using the Western Aphasia Battery (WAB).

Results. After tumor resection, visualization of the arcuate fasciculus was increased in 5 of the 7 patients, and the total WAB score improved in 6 of the 7 patients. The relative ratio of postoperative visualized area of the arcuate fasciculus to preoperative visualized area of the arcuate fasciculus was increased in association with an improvement in postoperative language function (p = 0.0039).

Conclusions. The role of the left arcuate fasciculus in language functions can be evaluated chronologically in vivo by DTI tractography after brain tumor surgery. Because increased postoperative visualization of the fasciculus was significantly associated with postoperative improvement in language functions, the arcuate fasciculus may play an important role in language function, as previously thought. In addition, postoperative changes in the arcuate fasciculus detected by DTI tractography could represent a predicting factor for postoperative language-dependent functional outcomes in patients with brain tumor.

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Surgical treatment of parasagittal and falcine meningiomas of the posterior third

Acta Neurochir (2012) 154:1987–1995

To the authors’ knowledge, meningiomas of the posterior third of the falx and the parasagittal sinus have never been specifically described to date and correlated visual outcome remains unclear. With this retrospective study we describe the clinical characteristics of these tumours, their surgical management, and the improvement in visual disturbances after surgery.

Methods Twenty-six consecutive patients (22 females, 4 males; mean age, 54 years) operated on for parasagittal (n022) and falcine (n04) meningioma between 1990 and 2010 were analysed retrospectively. Preoperative planning included magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) or angiography. Sinus invasion was classified as normal, stenotic or occluded from the imaging findings and according to the Sindou classification from the intraoperative notes.

Results Visual disturbances and headache (in 21 and 14 cases, respectively) were the most commonly referred symptoms; visual field deficit was present in 19 patients. Simpson grade I was obtained in four patients, grade II in 15, grade III in three, and grade IV in four. The main limiting factor for total removal was sinus involvement. No perioperative deaths or relevant postoperative complications occurred. The mean follow-up was 107 months. Visual field deficit improved or resolved in almost half of the patients during the follow-up period. Three (12%) patients relapsed, two were treated with Gamma Knife surgery (stable at current writing) and the third died of disease progression.

Conclusions Outcome after surgery compares favourably with other parasagittal meningioma localisations and overall morbidity is negligible. Visual function is crucial for clinical outcome. Since an improvement of the deficit might still be possible, every effort should be undertaken to preserve the visual cortex.

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Correlation between language function and the left arcuate fasciculus detected by diffusion tensor imaging tractography after brain tumor surgery

J Neurosurg 117:839–843, 2012

Disturbance of the arcuate fasciculus in the dominant hemisphere is thought to be associated with language-processing disorders, including conduction aphasia. Although the arcuate fasciculus can be visualized in vivo with diffusion tensor imaging (DTI) tractography, its involvement in functional processes associated with language has not been shown dynamically using DTI tractography. In the present study, to clarify the participation of the arcuate fasciculus in language functions, postoperative changes in the arcuate fasciculus detected by DTI tractography were evaluated chronologically in relation to postoperative changes in language function after brain tumor surgery.

Methods. Preoperative and postoperative arcuate fasciculus area and language function were examined in 7 right-handed patients with a brain tumor in the left hemisphere located in proximity to part of the arcuate fasciculus. The arcuate fasciculus was depicted, and its area was calculated using DTI tractography. Language functions were measured using the Western Aphasia Battery (WAB).

Results. After tumor resection, visualization of the arcuate fasciculus was increased in 5 of the 7 patients, and the total WAB score improved in 6 of the 7 patients. The relative ratio of postoperative visualized area of the arcuate fasciculus to preoperative visualized area of the arcuate fasciculus was increased in association with an improvement in postoperative language function (p = 0.0039).

Conclusions. The role of the left arcuate fasciculus in language functions can be evaluated chronologically in vivo by DTI tractography after brain tumor surgery. Because increased postoperative visualization of the fasciculus was significantly associated with postoperative improvement in language functions, the arcuate fasciculus may play an important role in language function, as previously thought. In addition, postoperative changes in the arcuate fasciculus detected by DTI tractography could represent a predicting factor for postoperative language-dependent functional outcomes in patients with brain tumor.

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Gross Total Resection Rates in Contemporary Glioblastoma Surgery: Results of an Institutional Protocol Combining 5-Aminolevulinic Acid Intraoperative Fluorescence Imaging and Brain Mapping

Neurosurgery 71:927–936, 2012

Complete resection of contrast-enhancing tumor has been recognized as an important prognostic factor in patients with glioblastoma and is a primary goal of surgery. Various intraoperative technologies have recently been introduced to improve glioma surgery.

OBJECTIVE: To evaluate the impact of using 5-aminolevulinic acid and intraoperative mapping and monitoring on the rate of complete resection of enhancing tumor (CRET), gross total resection (GTR), and new neurological deficits as part of an institutional protocol.

METHODS: One hundred three consecutive patients underwent resection of glioblastoma from August 2008 to November 2010. Eligibility for CRET was based on the initial magnetic resonance imaging assessed by 2 reviewers. The primary end point was the number of patients with CRET and GTR. Secondary end points were volume of residual contrast-enhancing tissue and new postoperative neurological deficits. RESULTS: Fifty-three patients were eligible for GTR/CRET (n = 43 newly diagnosed glioblastoma, n = 10 recurrent); 13 additional patients received surgery for GTR/CRET-ineligible glioblastoma. GTR was achieved in 96% of patients (n = 51, no residual enhancement . 0.175 cm3); CRET was achieved in 89% (n = 47, no residual enhancement). Postoperatively, 2 patients experienced worsening of preoperative hemianopia, 1 patient had a new mild hemiparesis, and another patient sustained sensory deficits.

CONCLUSION: Using 5-aminolevulinic acid imaging and intraoperative mapping/ monitoring together leads to a high rate of CRET and an increased rate of GTR compared with the literature without increasing the rate of permanent morbidity. The combination of safety and resection-enhancing intraoperative technologies was likely to be the major drivers for this high rate of CRET/GTR.

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Surgical management of intraventricular central neurocytoma: 92 cases

Acta Neurochir (2012) 154:1951–1960 

Objective To analyse the clinical characteristics of intraventricular central neurocytomas and gain a better understanding of the surgical management and treatment strategies.

Methods A total of 92 cases of intraventricular central neurocytomas with initial treatment using surgical resection were studied retrospectively.

Results Among 48 male and 44 female patients, 65 underwent gross total resection and 27 underwent subtotal resection. Transcortical or transcallosal approaches were performed, and there was no significant difference between the two approaches in terms of effects and complications. Tumours with calcification or adhesion had a significant lower gross total resection rate. Three patients died after surgery. During follow-up, 55 patients underwent postoperative radiotherapy and four patients had a recurrence of the tumour.

Conclusion Central neurocytomas mostly occur in the lateral ventricle system near the foramen of Monro. Therefore, total resection is the best treatment. Two surgical approaches are possible as treatment. Calcifications or adhesions affect the gross total resection of the tumour. Radiation therapy or radiosurgery therapy can be chosen as a salvage treatment in case of recurrence.

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Intracystic Bleomycin for Cystic Craniopharyngiomas in Children

 Neurosurgery 71:909–915, 2012

Craniopharyngiomas are the most common benign histological tumors to involve the hypothalamopituitary region in childhood. When the tumor location is unfavorable, a gross total or partial resection followed by radiotherapy is the main treatment option in adults. However, it presents the risk of morbidity, especially for children. Intracystic bleomycin has been used to potentially delay the use of radiotherapy or radical resection to decrease morbidity.

OBJECTIVE: To determine the benefit and harm of intracystic bleomycin vs other treatments for cystic craniopharyngiomas in children. METHODS: We searched the electronic databases of CENTRAL, MEDLINE/PubMed, and EMBASE/Ovid with prespecified terms. In addition, we searched reference lists of relevant articles and reviews, conference proceedings, and ongoing trial databases.

RESULTS: We could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. We did identify a randomized, controlled trial comparing intracystic bleomycin with intracystic 32P (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference in cyst reduction, neurological status, third nerve paralysis, fever, or total adverse effects between the treatment groups. There was a significant difference in favor of the 32P group for the occurrence of headache and vomiting.

CONCLUSION: Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality randomized, controlled trials are needed.

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Intermittent General Anesthesia With Controlled Ventilation for Asleep-Awake-Asleep Brain Surgery

Neurosurgery 71:764–772, 2012

Awake brain tumor surgery is a unique opportunity for mapping sensorimotor and cognitive functions, allowing the operator to optimize the resection while preserving the patient’s quality of life. During this type of procedure, active participation of the patient is necessary.

OBJECTIVE: To assess the efficacy and safety of a method of intermittent general anesthesia with controlled ventilation for performing invasive cerebral mapping. METHODS: We report our prospective and observational single-center study with an asleep-awake-asleep protocol. Aspects of feasibility, airway management, timing of each phase, and occurrence of adverse events were detailed.

RESULTS: During a 35-month period, 140 patients underwent resection of a glioma in an eloquent area. During the asleep phases, controlled ventilation with a laryngeal mask was always efficient. Orotracheal intubation was performed for some patients for the second asleep period. The patients remained fully awake for a mean time of 98 minutes. Postural discomfort was reported in 17.8% of cases. There was 1 case of aspiration of gastric contents with a favorable outcome and no mortality.

CONCLUSION: Intermittent general anesthesia with controlled ventilation for this type of neurosurgical procedure remains an anesthesiological challenge. However, the results of this study suggest that it may be feasible, reproducible, and relatively safe in the context of a standardized protocol involving members of both anesthesiology and surgery teams. Such a technique has a great potential to improve the surgical results, from both oncological and functional perspectives.

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Prognosis of patients with multifocal glioblastoma

J Neurosurg 117:705–711, 2012

The prognosis of patients with glioblastoma who present with multifocal disease is not well documented. The objective of this study was to determine whether multifocal disease on initial presentation is associated with worse survival.

Methods. The authors retrospectively reviewed records of 368 patients with newly diagnosed glioblastoma and identified 47 patients with multifocal tumors. Each patient with a multifocal tumor was then matched with a patient with a solitary glioblastoma on the basis of age, Karnofsky Performance Scale (KPS) score, and extent of resection, using a propensity score matching methodology. Radiation and temozolomide treatments were also well matched between the 2 cohorts. Kaplan-Meier estimates and log-rank tests were used to compare patient survival.

Results. The incidence of multifocal tumors was 12.8% (47/368). The median age of patients with multifocal tumors was 61 years, 76.6% had KPS scores ≥ 70, and 87.2% underwent either a biopsy or partial resection of their tumors. The 47 patients with multifocal tumors were almost perfectly matched on the basis of age (p = 0.97), extent of resection (p = 1.0), and KPS score (p = 0.80) compared with 47 patients with a solitary glioblastoma. Age (> 65 years), partial resection or biopsy, and low KPS score (< 70) were associated with worse median survival within the multifocal group. In the multifocal group, 19 patients experienced tumor progression on postradiation therapy MRI, compared with 11 patients (26.8%) with tumor progression in the unifocal group (p = 0.08). Patients with multifocal tumors experienced a significantly shorter median overall survival of 6 months (95% CI 4–10 months), compared with the 11-month median survival (95% CI 10–19 months) of the matched solitary glioblastoma group (p = 0.02, log-rank test). Two-year survival rates were 4.3% for patients with multifocal tumors and 29.0% for the unifocal cohort. Patients with newly diagnosed multifocal tumors were found to have an almost 2-fold increase in the hazard of death compared with patients with solitary glioblastoma (hazard ratio 1.8, 95% CI 1.1–3.1; p = 0.02). Tumor samples were analyzed for expression of phosphorylated mitogen-activated protein kinase, phosphatase and tensin homolog, O6-methylguanine-DNA methyltransferase, laminin b1 and b2, as well as epidermal growth factor receptor amplification, and no significant differences in expression profile between the multifocal and solitary glioblastoma groups was found.

Conclusions. Patients with newly diagnosed multifocal glioblastoma on presentation experience significantly worse survival than patients with solitary glioblastoma. Patients with multifocal tumors continue to pose a therapeutic challenge in the temozolomide era and magnify the challenges faced while treating patients with malignant gliomas.

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Intraoperative subcortical electrical mapping of optic radiations in awake surgery for glioma involving visual pathways

J Neurosurg 117:466–473, 2012

Preservation of the visual field in glioma surgery, especially avoidance of hemianopia, is crucial for patients’ quality of life, particularly for driving. Recent studies used tractography or cortical occipital stimulation to try to avoid visual deficit. However, optic radiations have not been directly mapped intraoperatively. The authors present, for the first time to their knowledge, a consecutive series of awake surgeries for cerebral glioma with intrasurgical identification and preservation of visual pathways using subcortical electrical mapping.

Methods. Fourteen patients underwent awake resection of a glioma (1 WHO Grade I, 11 WHO Grade II, 2 WHO Grade III) involving the optic radiations. The patients had no presurgical visual field deficit. Intraoperatively, a picture-naming task was used, with presentation of 2 objects situated diagonally on a screen divided into 4 quadrants. An image was presented in the quadrant to be saved and another image was presented in the opposite quadrant. Direct subcortical electrostimulation was repeatedly performed without the patient’s knowledge, until optic radiations were identified (transient visual disturbances). All patients underwent an objective visual field assessment 3 months after surgery.

Results. All patients experienced visual symptoms during stimulation. These disturbances led the authors to stop the tumor resection at that level. Postoperatively, only 1 patient had a permanent hemianopia, despite an expected quadrantanopia in 12 cases. The mean extent of resection was 93.6% (range 85%–100%).

Conclusions. Online identification of optic radiations by direct subcortical electrostimulation is a reliable and effective method to avoid permanent hemianopia in surgery for gliomas involving visual pathways.

 

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Visual Outcomes After Surgical Treatment of Adult Craniopharyngiomas

Neurosurgery 71:715–721, 2012 DOI: 10.1227/NEU.0b013e318262146b

Craniopharyngiomas (CRPs) often cause visual deterioration (VD) due to the close vicinity of the optic apparatus.

OBJECTIVE: To evaluate longitudinal visual outcomes after surgery of CRP and determine the prognostic factors thereof.

METHODS: One hundred forty-six adult patients who underwent surgery for newly diagnosed CRP were retrospectively reviewed. There were 87 male patients (60%), and the median age was 41 years (range, 18-75). The mean follow-up duration was 88.7 months (range, 24-307). A visual impairment score was used to assess the short-term (,1 month) and long-term (.2 years) visual outcomes.

RESULTS: Gross total removal was performed in 53 patients (36%), and tumor recurrence occurred in 40 patients (27%). The average preoperative, short- and longterm visual impairment scores were 44.4, 38.5, and 38.1, respectively, on a 0- to 100-point scale (with 100 indicating the worst vision). Short- and long-term VD occurred in 28 (19%) and 39 patients (27%), respectively. Subtotal removal (STR) alone (P = .010; OR = 4.8), short-termVD (P<.001; OR = 39.7), and tumor recurrence (P<.001; OR = 28.2) were significant risk factors for long-term VD in the multivariate analysis. Patients undergoing STR alone had higher tumor recurrence rates in comparison with those who underwent gross total removal or STR with adjuvant therapy (P < .001).

CONCLUSION: Short-term VD secondary to the surgical insult and the recurrence of the tumor were strong predictors of long-term visual outcomes after surgical treatment for CRP. STR alone may be an ineffective strategy for achieving tumor control and optimal visual outcomes in patients with CRP.

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High-Definition Fiber Tractography of the Human Brain: Neuroanatomical Validation and Neurosurgical Applications

Neurosurgery 71:430–453, 2012

High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution.

OBJECTIVE: To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications.

METHODS: Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography.

RESULTS: HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers.

CONCLUSION: Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed.

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Cancer Immunoediting in Malignant Glioma

Neurosurgery 71:201–223, 2012

Significant work from many laboratories over the last decade in the study of cancer immunology has resulted in the development of the cancer immunoediting hypothesis. This contemporary framework of the naturally arising immune system–tumor interaction is thought to comprise 3 phases: elimination, wherein immunity subserves an extrinsic tumor suppressor function and destroys nascent tumor cells; equilibrium, wherein tumor cells are constrained in a period of latency under immune control; and escape, wherein tumor cells outpace immunity and progress clinically.

In this review, we address in detail the relevance of the cancer immunoediting concept to neurosurgeons and neuro-oncologists treating and studying malignant glioma by exploring the de novo immune response to these tumors, how these tumors may persist in vivo, the mechanisms by which these cells may escape/attenuate immunity, and ultimately how this concept may influence our immunotherapeutic approaches.

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Preoperative multimodal motor mapping: a comparison of magnetoencephalography imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation

J Neurosurg 117:354–362, 2012

Direct cortical stimulation (DCS) is the gold-standard technique for motor mapping during craniotomy. However, preoperative noninvasive motor mapping is becoming increasingly accurate. Two such noninvasive modalities are navigated transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) imaging. While MEG imaging has already been extensively validated as an accurate modality of noninvasive motor mapping, TMS is less well studied. In this study, the authors compared the accuracy of TMS to both DCS and MEG imaging.

Methods. Patients with tumors in proximity to primary motor cortex underwent preoperative TMS and MEG imaging for motor mapping. The patients subsequently underwent motor mapping via intraoperative DCS. The loci of maximal response were recorded from each modality and compared. Motor strength was assessed at 3 months postoperatively.

Results. Transcranial magnetic stimulation and MEG imaging were performed on 24 patients. Intraoperative DCS yielded 8 positive motor sites in 5 patients. The median distance ± SEM between TMS and DCS motor sites was 2.13 ± 0.29 mm, and between TMS and MEG imaging motor sites was 4.71 ± 1.08 mm. In no patients did DCS motor mapping reveal a motor site that was unrecognized by TMS. Three of 24 patients developed new, early neurological deficit in the form of upper-extremity paresis. At the 3-month follow-up evaluation, 2 of these patients were significantly improved, experiencing difficulty only with fine motor tasks; the remaining patient had improvement to 4/5 strength. There were no deaths over the course of the study.

Conclusions. Maps of the motor system generated with TMS correlate well with those generated by both MEG imaging and DCS. Negative TMS mapping also correlates with negative DCS mapping. Navigated TMS is an accurate modality for noninvasively generating preoperative motor maps.

 

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