Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

Transcortical approach for insular gliomas: a series of 253 patients.

PURPOSE: The object of this study was to identify the distribution characteristics of insular gliomas and evaluate the efficiency of transcortical approach. METHODS: Insular gliomas patients who underwent transcortical approach for the first time between March 2011 and July 2019 at our institute were analyzed. RESULTS: A total of 253 primary insular gliomas patients were enrolled in the study. Of all patients, 176 patients (69.6%) underwent gross total resection, 61 patients (24.1%) underwent subtotal resection and 16 patients (6.3%) underwent partial resection. According to Berger-Sanai classification, the gross total resection rates of different types of insular gliomas were as follows: Zone I (90.1%), zone II (50.0%), zone III (40.0%), zone IV (89.5%), zone I + II (43.5%), zone I + IV (74.6%), zone II + III (44.4%), zone III + IV (41.7%), Giant (34.5%). According to our modified classification, the gross total resection rates were as follows: anterior type (84.9%), posterior type (45.8%), anterior-posterior type (42.9%), giant type (34.5%). After surgery, new limb motor deficit was observed in 28 patients (11.1%), and 5 patients (2.0%) were left long-term limb motor disability. New language impairment occurred in 23 patients (9.1%), and 3 patients (1.2%) were left long-term language disability. The patients were followed up for 1 to 89.2 months (average, 39.9 ± 20.3 months). At the end of follow-up, tumor progression occurred in 98 (38.7%) patients and 71 (28.1%) patients died of their disease. CONCLUSION: This study demonstrated that the maximal safe resection of insular gliomas can be achieved by transcortical approach. Insular gliomas had the characteristic of forward distribution, anterior transcortical approach can provide enough surgical freedom for anterior type of insular gliomas. If anterior tumors can make route to the posterior parts, anterior transcortical approach was also applied to some anterior-posterior and giant types of insular gliomas without resection of excessive brain, which may reduce the incidence of neurological complications.

Insular Gliomas. Experience in a Latin-American center and assessment of variables related to surgical management and prognosis.

OBJECTIVE: To describe our experience in the resection of gliomas involving the insula and analyze the variables implicated in the management and prognosis of these tumors. MATERIALS AND METHODS: This retrospective, single-center, analytical study included a cohort of 83 patients who underwent surgery for insular gliomas by the same surgeon in a third-level Argentine center, in the period between 2010-2023. We analyzed the population's demographic, clinical, and radiological features and surgical variables associated with postoperative results and prognosis using multivariate regression analysis. RESULTS: A total of 53 patients (54% males) were included with a mean follow-up of 40.7 months. Mean age at surgery was 41 years (range 21-73) and 66.1% corresponded to low-grade gliomas. Seizures were the initial symptom in the majority of cases. There was evidence of tumor extension over the insula to temporal or/and frontal lobe in 64.2% of patients. An EOR over 90% was achieved in 62.3% of cases (27% of GTR) with an average resected volume of 89.4%. Awake craniotomy was indicated in 47% of patients and iMRI was performed in 24%. Recurrence was observed in 44% of patients with a mean Progression-Free survival of 31 months (42 months in LGG and 10 months in HGG). A total of 9 patients were re-operated. By the time of 2 years, survival rates were 100% for LGG and 46% for HGG, while 4-year overall survival rates were 92% for patients with LGG and 15.4% for those with HGG. CONCLUSION: Surgery for insular gliomas is a complex task that needs to be managed with adequate preoperative and intraoperative assessment in order to achieve maximum safe resection with low morbidity for better functional and oncological outcomes. Adequate anatomical understanding, radiological analysis, awake craniotomy, cortical and subcortical mapping are paramount to pursue this aim.

Connectomic insights into the impact of 1p/19q co-deletion in dominant hemisphere insular glioma patients.

Objectives: This study aimed to elucidate the influences of 1p/19q co-deletion on structural connectivity alterations in patients with dominant hemisphere insular diffuse gliomas. Methods: We incorporated 32 cases of left insular gliomas and 20 healthy controls for this study. Using diffusion MRI, we applied correlational tractography, differential tractography, and graph theoretical analysis to explore the potential connectivity associated with 1p/19q co-deletion. Results: The study revealed that the quantitative anisotropy (QA) of key deep medial fiber tracts, including the anterior thalamic radiation, superior thalamic radiation, fornix, and cingulum, had significant negative associations with 1p/19q co-deletion (FDR = 4.72 × 10-5). These tracts are crucial in maintaining the integrity of brain networks. Differential analysis further supported these findings (FWER-corrected p < 0.05). The 1p/19q non-co-deletion group exhibited significantly higher clustering coefficients (FDR-corrected p < 0.05) and reduced betweenness centrality (FDR-corrected p < 0.05) in regions around the tumor compared to HC group. Graph theoretical analysis indicated that non-co-deletion patients had increased local clustering and decreased betweenness centrality in peritumoral brain regions compared to co-deletion patients and healthy controls (FDR-corrected p < 0.05). Additionally, despite not being significant through correction, patients with 1p/19q co-deletion exhibited lower trends in weighted average clustering coefficient, transitivity, small worldness, and global efficiency, while showing higher tendencies in weighted path length compared to patients without the co-deletion. Conclusion: The findings of this study underline the significant role of 1p/19q co-deletion in altering structural connectivity in insular glioma patients. These alterations in brain networks could have profound implications for the neural functionality in patients with dominant hemisphere insular gliomas.

Avoiding vascular complications in insular glioma surgery - A microsurgical anatomy study and critical reflections regarding intraoperative findings.

Introduction: Vascular lesions in insular glioma surgery can severely impact patients' quality of life. This study aims to present the results of our dissections and authors' reflections on the insular vascular anatomy. Matherials and Methods: The insular vascularization was examined using ×3 to ×40 magnification in 20 cadaveric cerebral hemispheres in which the arteries and veins had been perfused with colored silicone. Results: In insular gliomas, this individualization of the anatomical structures is rarely possible, as the gyri are swollen by the tumor and lose their individuality. In the transsylvian approaches, the anatomical parameters for delimiting the insula in tumors are best provided by the superior and inferior circular sulci. The branches of the MCA are easily identified in the transcortical approach, but only at the end of the surgery after the tumor is resected.). One of the factors under-discussed in the literature is the involvement of the lenticulostriate arteries by the medial part of the tumor. In our experience of 52 patients (article submitted to publishing), LSTa were founded to be involved by the tumor in 13 cases. In 39 patients, there was no involvement of the LSTa, which allowed a more aggressive resection. Early preoperative identification of the anterior perforated substance on the MRI and its proximity to the tumor may help determine the route of the LSTa over the medial tumor boundaries. Discussion: Our reflections introduced our imaging and anatomical concept regarding LSTa in insular glioma surgery. Accurate identification of origin, route, and distribution of the LSTa is pivotal to surgical success, especially in the lateral group. The anatomical knowledge of their path directly impacts the extent of tumor resection and functional preservation. Conclusion: Knowledge of microsurgical anatomy, brain mapping, and surgical experience counts a lot in this type of surgery, creating a reasonable procedure flowchart to be taken intraoperatively.

Incidence of ischemic complications and technical nuances of arteries preservation for insular gliomas resection.

Introduction: Insular gliomas have complex anatomy and microvascular supply that make resection difficult. Furthermore, resection of insular glioma is associated with a significant risk of postoperative ischemic complications. Thus, this study aimed to assess the incidence of ischemic complications related to insular glioma resection, determine its risk factors, and describe a single surgeon's experience of artery-preserving tumor resection. Methods: We enrolled 75 consecutive patients with insular gliomas who underwent transcortical tumor resection. Preoperative and postoperative demographic, clinical, radiological [including diffusion-weighted imaging (DWI)], intraoperative neurophysiological data, and functional outcomes were analyzed. Motor evoked potentials (MEPs) and radiological characteristics like the relationship between the proximal segment of the lateral lenticulostriate arteries (LLSAs) and the tumor, the flat inner edge sign (the inner edge of the insular glioma is well-defined) or obscure inner edge sign, the distance between the lesion and posterior limb of the internal capsule and the invasion of the superior limiting sulcus by the tumor were analyzed. Strategies such as "residual triangle," "basal ganglia outline reappearance," and "sculpting" technique were used to preserve the LLSAs and the main branches of M2 for maximal tumor resection according to the Berger-Sinai classification. Results: Postoperative DWI showed acute ischemia in 44 patients (58.7%). Moreover, nine patients (12%) had developed new motor deficits, as determined by the treating neurosurgeons. The flat inner edge sign [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.024-0.876) and MEPs (>50%) (OR, 18.182; 95% CI, 3.311-100.00) were significantly associated with postoperative core ischemia, which affected the posterior limb of the internal capsule or corona radiata. Conclusions: Insular glioma resection was associated with a high incidence of ischemia, as detected by DWI, as well as new motor deficits that were determined by the treating neurosurgeons. Insular glioma patients with obscure inner edge signs and intraoperative MEPs decline >50% had a higher risk of developing core ischemia. With our strategies, maximal safe resection of insular gliomas may be achieved.

Avoiding Complications in Surgical Resection of Insular Gliomas - Single Surgeon Experience.

BACKGROUND AND AIMS: Insular gliomas remain one of most challenging locations for aggressive resection. We report our experience and strategies we employed to avoid complications in immediate post-operative period of surgical resection of insular gliomas. METHODS: Retrospective analysis of data collected in 61 consecutive patients who underwent surgical resection of insular gliomas between May 2013 and May 2016 was done. Primary outcome measures were neurological deficits and death in the immediate post-operative period to three months follow-up. RESULTS: The average age of the study population was 42.57 ± 10.98 years with 41 (67.2%) men. Glioma was on the right side in 35 (57.3%) patients. Surgery for recurrent glioma was performed in three (4.9%) patients. The average MIB index of the entire group was 10.1 ± 13.9. While 23 (37.7%) patients underwent the TO approach, 38 (62.3%) underwent TS approach. In the immediate post-operative period, significantly higher number of patients under TS approach had post-surgical complications (8.6% vs 34.2%; P = 0.032). The surgical approaches did not differ significantly for outcome, mortality and complications at three month post-operatively (0.0% vs 10.5%; P = 0.287). However, a trend for lower complications at three months was observed with TO approach. CONCLUSION: We report that morbidity and mortality in immediate post-operative period can be reduced by: a) pre-surgical assessment of confinement of glioma in respect to lenticulo-striate arteries, b) Intra-operative use of functional-MRI, DTI tractography and ICG angiography, c) Application of Berger-Sinai classification to localize the glioma, d) selecting either TS or TO approach based on Berger-Sinai classification.

MRI venous architecture of insula.

PURPOSE: The purpose of this paper is to describe the venous anatomy of the insula using conventional MR brain imaging and confocal reconstructions in cases with glioma induced venous dilatation (venous gliography). METHODS: Routine clinical MRI brain scans that included thin cut (1.5-2 mm) post contrast T1 weighted imaging were retrospectively reviewed to assess the insular venous anatomy in 19 cases (11 males and 8 females) with insular gliomas. Reconstruction techniques (Anatom-e and Osirix) were used to improve understanding of the venous anatomy. RESULTS: We identified the following insular and peri-insular veins on MRI: the superficial middle cerebral vein (SMCV), peri-insular sulcus vein, vein of the anterior limiting sulcus, the precentral, central, and posterior sulcus veins of the insula, the communicating veins and deep MCV. CONCLUSIONS: We concluded that venous anatomy of insula is complicated and is often overlooked by radiologists on MR brain imaging. Use of confocal imaging in different planes helped us to identify the superficial and deep middle cerebral veins and their relationship to the insula. The understanding of the insular venous architecture is also useful to distinguish these vessels from insular arteries. This knowledge may be helpful for presurgical planning prior to insular glioma resection.

Surgical Resection of Insular Gliomas and Roles of Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging Tractography-Single Surgeon Experience.

OBJECTIVE: In gliomas located in proximity to eloquent areas, near total resection and subsequent radiotherapy is often preferred to avoid postoperative neurologic complications. Preoperative functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) tractography provide new insights into surgeries of insular gliomas. In this study we report our experience of surgical management of insular gliomas and the role of fMRI and DTI tractography in planning the resection. METHODS: We retrospectively compared the clinical and outcome variables of 61 patients who underwent surgical resection of insular gliomas. The study population was divided into 2 groups according to the use of fMRI and DTI tractography in planning the resection. RESULTS: The average age of the study population was 44.1 ± 12.6 years with 21 (34.4%) of the patients women. Nearly two thirds of them (40, or 65.6%) had World Health Organization grade II tumors, and 16 patients (26.2%) had grade IV tumors. The most common tumor was glioblastoma, observed in 16 patients (26.2%). In 10 (16.4%) patients, fMRI and DTI tractography were used. The overall mortality in the study population was 15 (24.6%). None of the patients where fMRI and DTI were used for planning the surgery died (29.4% vs. 0.0%; P = 0.05), and all of them had normal functioning (70.5% vs. 100.0%; P = 0.05) at 3 months' follow-up. CONCLUSION: Surgical resection of insular gliomas remains a challenge to the neurosurgeon and demands good knowledge of anatomic landmarks. Use of fMRI and DTI tractography may help achieve a good outcome.