Strategies to maximize resection of complex, or high surgical risk, low-grade gliomas

2013 ◽  
Vol 34 (2) ◽  
pp. E5 ◽  
Author(s):  
Jessica A. Wilden ◽  
Jason Voorhies ◽  
Kristine M. Mosier ◽  
Darren P. O'Neill ◽  
Aaron A. Cohen-Gadol
Keyword(s):  
Seizure Control ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Awake Craniotomy ◽  
Low Grade ◽  
Normal Brain ◽  
Surgical Risk ◽  
Motor Mapping ◽  
Low Grade Gliomas ◽  
High Surgical Risk

Object Early and aggressive resection of low-grade gliomas (LGGs) leads to increased overall patient survival, decreased malignant progression, and better seizure control. This case series describes the authors' approach to achieving optimal neurological and surgical outcomes in patients referred by outside neurosurgeons for stereotactic biopsy of tumors believed to be complex or a high surgical risk, due to their diffuse nature on neuroimaging and their obvious infiltration of functional cortex. Methods Seven patients underwent individualized neuroimaging evaluation preoperatively, which included routine brain MRI with and without contrast administration for intraoperative neuronavigation, functional MRI with speech and motor mapping, diffusion tensor imaging to delineate white matter tracts, and MR perfusion to identify potential foci of higher grade malignancy within the tumor. Awake craniotomy with intraoperative motor and speech mapping was performed in all patients. Tumor removal was initiated through a transsylvian approach for insular lesions, and through multiple corticotomies in stimulation-confirmed noneloquent areas for all other lesions. Resection was continued until neuronavigation indicated normal brain, cortical or subcortical stimulation revealed functional cortex, or the patient began to experience a minor neurological deficit on intraoperative testing. Results Gross-total resection was achieved in 1 patient and subtotal resection (> 80%) in 6 patients, as assessed by postoperative MRI. Over the average follow-up duration of 31 months, no patient experienced a progression or recurrence. Long-term seizure control was excellent in 6 patients who achieved Engel Class I outcomes. Neurologically, all 7 patients experienced mild temporary deficits or seizures that completely resolved, and 1 patient continues to have mild expressive aphasia. Conclusions Significant resection of diffuse, infiltrating LGGs is possible, even in presumed eloquent cortex. Aggressive resection maximizes seizure control and does not necessarily cause permanent neurological deficits. Individualized preoperative neuroimaging evaluation, including tractography and awake craniotomy with intraoperative speech and motor mapping, is an essential tool in achieving these outcomes.

scholarly journals SURG-08. AWAKE CRANIOTOMY WITH BRAIN MAPPING FOR DIFFUSE LOW-GRADE GLIOMA: CASE REPORT OF INSTITUTIONAL EXPERIENCE IN OVERCOMING HURDLES IN A LOW-RESOURCE SETTING

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii204-ii205
Author(s):  
Kirby Manigos ◽  
Kevin Paul Ferraris ◽  
Joseph Erroll Navarro ◽  
Kenny Seng ◽  
Jose Carlos Alcazaren
Keyword(s):  
Brain Mapping ◽  
Diffusion Tensor ◽  
Low Grade Glioma ◽  
Awake Craniotomy ◽  
Limited Resources ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Neurologic Deficits ◽  
Weighted Sequence ◽  
Low Middle Income Countries

Abstract Maximal safe resection of low-grade gliomas located in functional areas of the cortex while avoiding postsurgical neurologic deficits can be achieved by awake craniotomy with brain mapping. The effectiveness of this surgical technique is fairly established in the developed world, however it remains to be routinely applied in low-middle income countries due to limited resources and lack of equipment. We present the case of a 44 year-old, right-handed male who had a 2-year history of focal aware motor seizures but was otherwise neurologically intact. Neuropsychological testing revealed no cognitive impairment. Cranial magnetic resonance imaging (MRI) revealed a non-enhancing, ill-defined tumor centered on the left insula and extending into the frontotemporal opercula, corona radiata, and posterior limb of the internal capsule—hypointense by T1-weighted sequence and hyperintense by T2-weighted sequence, thus radiographically consistent with diffuse low-grade glioma. Blood-oxygen-level-dependent functional MRI revealed left hemispheric language dominance in the cortex overlying the tumor, but with no motor cortex involvement. The patient underwent a protocol-driven awake craniotomy, intraoperative positive brain mapping using standard cortical stimulator, transsylvian and transcortical transopercular microsurgical approaches to achieve greater than 80% excision of the tumor. Postoperatively, the patient was seizure-free and with similar neurocognitive status prior to the surgery. The patient had been following up for standard adjuvant chemotherapy and radiotherapy. Avoidance of postsurgical neurologic deficits and maximal cytoreduction can still be achieved by awake craniotomy with brain mapping in settings with limited resources. Despite the lack of other perioperative tools and adjuncts such as diffusion tensor imaging, intraoperative ultrasonography, and even intraoperative MRI that are routinely available in high-resource settings, we illustrate in this case that comparable outcomes could be achieved by overcoming hurdles and aiming for the asymptote to the up-to-date and ideal neurosurgical treatment for diffuse low-grade gliomas.

scholarly journals LGG-18. EVEROLIMUS TREATMENT IN PEDIATRIC PATIENTS AFFECTED BY LOW-GRADE GLIOMAS (pLGG) NON-TSC, BRAF v600-WT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii369-iii369
Author(s):  
Antonella Cacchione ◽  
Evelina Miele ◽  
Maria Chiara Lodi ◽  
Andrea Carai ◽  
Giovanna Stefania Colafati ◽  
...  
Keyword(s):  
Adverse Event ◽  
Disease Progression ◽  
Mapk Pathway ◽  
Brain Mri ◽  
Mammalian Target Of Rapamycin ◽  
Low Grade ◽  
Duration Of Treatment ◽  
Tumor Biopsy ◽  
Low Grade Gliomas ◽  
Personalized Approach

Abstract BACKGROUND MAPK pathway is the hallmark of pediatric low grade gliomas (pLGGs); hyperactivation of mTOR (mammalian target of rapamycin) might be a suitable biomarker for therapeutic response. We investigated the feasibility of Everolimus, mTOR inhibitor, in patients affected by pLGGs. METHODS Patients 1 to 18 years old, diagnosed with pLGG, with a positive tumor biopsy for mTOR/phospho-mTOR and radiological and / or clinical disease progression, treated at Bambino Gesù Children’s Hospital in Rome were evaluated. Tumor DNA methylation analysis was performed in 10 cases. Exclusion criteria included: Tuberous Sclerosis patients, Sub Ependymal Giant Astrocytoma. Everolimus was administered orally at a dose of 2.5 mg or 5 mg daily based on body weight. Patients were evaluated with brain MRI every 4, 8 and 12 months after treatment start and every six months thereafter. RESULTS 16 patients were enrolled from September 2014 and 2019. The median age was 7.5 years old. All patients had at least one adverse event. Events rated as severe (grade 3/4) were reported in 6 patients. Stomatitis was the most frequent adverse event. One patient discontinued treatment due to grade 4 toxicity (ulcerative stomatitis and fatigue). The median duration of treatment was 21 months (4–57 months). Brain MRI evaluations have showed disease stability in 11 patients, partial response in 2 patients and disease progression in 3 patients. CONCLUSIONS Everolimus has proven to be well tolerated and effective treatment in terms of disease stability in patients with pLGGs. It’s also an excellent example of chemo-free personalized approach.

Quantitative Diffusion Tensor Imaging Analysis of Low-Grade Gliomas: From Preclinical Application to Patient Care

2017 ◽  
Vol 97 ◽  
pp. 333-343 ◽  
Author(s):  
Tamara Ius ◽  
Luca Turella ◽  
Giada Pauletto ◽  
Miriam Isola ◽  
Marta Maieron ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Patient Care ◽  
Diffusion Tensor ◽  
Low Grade ◽  
Imaging Analysis ◽  
Low Grade Gliomas

scholarly journals Survival and Seizure Control have improved for Adult Low-Grade Gliomas over the last eleven years

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv4-iv4
Author(s):  
Matt Solomons ◽  
Rimona Weil ◽  
Zane Jaunmuktan ◽  
Tedani El-Hassan ◽  
Sebastian Brandner ◽  
...  
Keyword(s):  
Seizure Control ◽  
Molecular Subtype ◽  
Intractable Epilepsy ◽  
Progression Free Survival ◽  
Morbidity Rate ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Tumour Location ◽  
The Cost

Abstract Background There has been a trend towards earlier and more aggressive resection for adult Low-Grade Gliomas (LGG) in the last decade. This study set out to compare seizure control and survival of unselected adults with LGG seen in the same neuro-oncology clinic over 11 years and to determine if a change in surgical philosophy has led to a corresponding improvement in outcomes. Methods Retrospective analysis using case-note review of 153 adults with histologically verified or radiologically suspected LGG, collecting data on patient, tumour and seizure characteristics in 2006 and 2017. Results We studied 79 patients in 2006 and 74 patients in 2017. There were no significant differences between the two groups in age at presentation, tumour location or histological or molecular subtype. The numbers of complete or partial resections increased from 21.5 % in 2006 to 60.8% in 2017 (p<0.05). There was a highly significant improvement in 5- and 10-year survival from 81.8% and 51.7% in 2006 to 100% and 95.8% in 2017 (p<0.001); and a similar improvement was seen in progression free survival. The proportion of patients with intractable epilepsy reduced from 72.2% in 2006 to 43.2% in 2017 (p<0.05). The neurosurgical morbidity rate was identical in both groups (11.8% in 2006 vs 11.1% in 2017). Conclusion Increasing use of surgery for LGG over the last eleven years has led to substantial improvements in survival and seizure control but not at the cost of long-term morbidity.

scholarly journals Confocal-Assisted Fluorescence Resection of Low-Grade Gliomas

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Cleopatra Charalampaki ◽  
Juergen Schlegel
Keyword(s):  
Normal Tissue ◽  
Imaging Modality ◽  
Brain Structures ◽  
Cellular Level ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Low Grade ◽  
Normal Brain ◽  
Low Grade Gliomas ◽  
Tumor Identification

Abstract INTRODUCTION Low-grade gliomas (LGG) are the most common intra-axial brain tumors. Intraoperatively it's not possible to distinguish optically between the tumor and the normal tissue. Furthermore, it can not be detected with fluorescent agents like 5-aminolevulinacid (5-ALA). Those reasons often lead to inaccurate resection of the tumor. Confocal laser endomicroscopy (CLE) is a cellular imaging modality used for optical biopsies. The aim of this study was to use intraoperative CLE to differentiate tumor from normal tissue and to define borders during resection of LGG on a cellular level. METHODS We investigated the use of intraoperative CLE on 6 patients with LGG. We used a confocal system that is able to detect fluorescence on the infrared spectrum and we applied indocyanine green as a detecting fluorescent agent. We analyzed the accuracy of the intraoperative cellular CLE optical biopsies in comparison with the hematoxylin and eosin stains of the biopsies taken from the tumor and normal tissue borders area. RESULTS With CLE we were able intraoperatively to diagnose the tumor entity, normal brain structures, and vascularization modalities and to control the resection zone on a cellular level. Furthermore, CLE pictures showed exactly the cellular borders between tumor and normal tissue. The correlation of the CLE pictures with the H&E staining was 100%. CONCLUSION CLE, on one hand, allows intraoperative detection and differentiation of single tumor cells, while, on the other hand, it allows defining borders between tumor and normal tissue on a cellular level, dramatically improving the accuracy of surgical resection of LGG. The application and implementation of CLE-assisted surgery increases not only the options for real-tumor identification but also the therapeutic options by extending the resection borders of LGG on a cellular level and, more importantly, by protecting the functionality of normal tissue on the adjacent areas of the human brain.

Simulation of anisotropic growth of low-grade gliomas using diffusion tensor imaging

2005 ◽  
Vol 54 (3) ◽  
pp. 616-624 ◽  
Author(s):  
Saâd Jbabdi ◽  
Emmanuel Mandonnet ◽  
Hugues Duffau ◽  
Laurent Capelle ◽  
Kristin Rae Swanson ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Low Grade ◽  
Anisotropic Growth ◽  
Low Grade Gliomas

Novel RAF Fusions in Pediatric Low-Grade Gliomas Demonstrate MAPK Pathway Activation

2021 ◽  
Author(s):  
Katherine T Lind ◽  
Hannah V Chatwin ◽  
John DeSisto ◽  
Philip Coleman ◽  
Bridget Sanford ◽  
...  
Keyword(s):  
Mapk Pathway ◽  
Enrichment Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Immunofluorescent Staining ◽  
Low Grade ◽  
Normal Brain ◽  
Mapk Activation ◽  
Low Grade Gliomas ◽  
Pathway Activation ◽  
Mitogen Activated Protein

Abstract Brain tumors are the most common solid tumor in children, and low-grade gliomas (LGGs) are the most common childhood brain tumor. Here, we report on 3 patients with LGG harboring previously unreported or rarely reported RAF fusions: FYCO1-RAF1, CTTNBP2-BRAF, and SLC44A1-BRAF. We hypothesized that these tumors would show molecular similarity to the canonical KIAA1549-BRAF fusion that is the most widely seen alteration in pilocytic astrocytoma (PA), the most common pediatric LGG variant, and that this similarity would include mitogen-activated protein kinase (MAPK) pathway activation. To test our hypothesis, we utilized immunofluorescent imaging and RNA-sequencing in normal brain, KIAA1549-BRAF-harboring tumors, and our 3 tumors with novel fusions. We performed immunofluorescent staining of ERK and phosphorylated ERK (p-ERK), identifying increased p-ERK expression in KIAA1549-BRAF fused PA and the novel fusion samples, indicative of MAPK pathway activation. Geneset enrichment analysis further confirmed upregulated downstream MAPK activation. These results suggest that MAPK activation is the oncogenic mechanism in noncanonical RAF fusion-driven LGG. Similarity in the oncogenic mechanism suggests that LGGs with noncanonical RAF fusions are likely to respond to MEK inhibitors.

Seizure Characteristics and Postoperative Seizure Control in Patients with Low-grade Gliomas

Neurosurgery ◽  
2005 ◽  
Vol 57 (2) ◽  
pp. 430-430 ◽  
Author(s):  
Edward F. Chang ◽  
Evren G. Keles ◽  
Matt Potts ◽  
Susan Chang ◽  
Kathleen L. Lamborn ◽  
...  
Keyword(s):  
Seizure Control ◽  
Low Grade ◽  
Low Grade Gliomas ◽  
Postoperative Seizure

Biological significance of tissue plasminogen activator content in brain tumors

1991 ◽  
Vol 74 (3) ◽  
pp. 480-486 ◽  
Author(s):  
Raymond Sawaya ◽  
O. Juhani Rämö ◽  
Mei Lin Shi ◽  
George Mandybur
Keyword(s):  
Brain Tumors ◽  
Plasminogen Activator ◽  
Tumor Necrosis ◽  
Tumor Tissue ◽  
Biological Significance ◽  
Low Grade ◽  
Normal Brain ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Fine Print

✓ Fresh brain-tumor samples were obtained at operation and analyzed for their content of tissue type plasminogen activator (tPA) using an activity assay (gel chromatography zymogram) and an enzyme-linked immunospecific assay. The specimens were taken from 23 glioblastomas, 35 metastatic tumors, 42 meningiomas, 16 low-grade gliomas, and seven acoustic neurinomas; seven specimens were from normal brain. A strong correlation was found between the results of the two assays (r = 0.77, p < 0.0001). There was a threefold difference in the tPA content of the benign tumors as compared to malignant tumors (p = 0.0006), the latter having less tPA. Histologically benign meningiomas contained higher tPA than malignant meningiomas (p = 0.01); however, the difference between low-grade gliomas and high-grade gliomas was less evident. Overall regression analysis data have shown an inverse relationship between the tissue content in tPA and the presence and degree of tumor necrosis and peritumoral brain edema (p = 0.004 and p = 0.0004, respectively). This finding was most consistent in the glioblastoma group where the correlation coefficient values were r = 0.53 and r = −0.55, respectively. There was no significant correlation between the tissue tPA content and the age and sex, steroid use, or plasma tPA of the patients or the duration of symptoms. In summary, this is the first demonstration of tPA in a large series of human brain tumors and in normal brain. The differences observed have clear biological significance and, although the source of tPA in tumor tissue is still unknown, a relative reduction in tPA in tumor tissue may play an integral role in the development of tissue necrosis and tissue edema. The lack of tPA in tumor necrosis was not due to tissue destruction and cell death since urokinase was readily detectable in that tissue.

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