Integrated insular phenotype (IIP) versus Berger–Sanai and Yasargil classifications: comparative prognostic value in surgery of insular gliomas

Acta Neurochirurgica (2025) 167:324

This study compares the Integrated Insular Phenotype (IIP), a three-level ordinal topographic classification of insular gliomas, with Berger–Sanai and Yasargil systems to evaluate prognostic performance for extent of resection, seizure control, and persistent neurological deficit at 90 days. Using retrospective analysis of 167 surgically treated patients, logistic regression and model metrics (AUC, AIC, LR χ2) assessed associations between classification complexity and outcomes.

Results show increasing IIP complexity strongly predicted lower resectability, poorer seizure control, and higher persistent deficit risk; IIP produced more stable odds ratios, lower AIC, and higher LR χ2 than traditional systems. The authors propose IIP as a practical risk-stratification tool to balance oncological radicality and functional safety, recommending multicenter prospective validation and integration with molecular and intraoperative technologies.

Integrated Insular Phenotype (IIP): An ordinal classification system for insular gliomas that incorporates tumor topographic complexity and multizonal involvement, outperforming traditional Berger–Sanai and Yasargil systems in prognostic accuracy for surgical outcomes.

Prognostic Value: IIP demonstrates superior and more stable associations with key surgical outcomes—extent of resection, seizure control, and persistent neurological deficit at 90 days—compared to Berger–Sanai and Yasargil classifications, as shown by higher informativeness, lower AIC, and more reproducible odds ratios.

Surgical Complexity: Higher IIP complexity (IIP-M) is linked to reduced likelihood of total/subtotal resection, poorer seizure control, and increased risk of persistent neurological deficits, while simpler phenotypes (IIP-L) are associated with more favorable outcomes.

Traditional Classifications: Berger–Sanai and Yasargil systems provide limited prognostic value; Berger–Sanai yields high but unstable odds ratios with wide confidence intervals, while Yasargil offers consistent but less discriminative results.

Clinical Implications: IIP can guide individualized surgical strategies by balancing oncological radicality against functional safety, supporting the principle of maximal safe resection and informing risk stratification.

Seizure Outcomes: Multizonal and widespread IIP phenotypes (IIP-M) are associated with poorer postoperative seizure control, reflecting the challenge of eliminating diffuse epileptogenic networks.

Study Limitations: The findings are based on a single-center retrospective cohort; external validation and integration with molecular, histopathological, and neurocognitive factors are needed for broader applicability.

Future Directions: Prospective multicenter validation, integration with intraoperative technologies, and use of AI/ML for risk stratification and personalized planning are recommended to enhance the utility of IIP in clinical practice

Navigated Transcranial Magnetic Stimulation and Diffusion Tensor Imaging Tractography in Insular Glioma Surgery

Operative Neurosurgery 29:62–70, 2025

Navigated transcranial magnetic stimulation (nTMS) and DTI tractography enable precise preoperative risk stratification in insular glioma surgery, identifying patients at higher risk for postoperative motor deficits by assessing resting motor threshold, tumor proximity to the corticospinal tract, and fiber tract integrity, thus improving surgical planning and outcomes.

• Navigated transcranial magnetic stimulation (nTMS) and nTMS-based DTI tractography were evaluated for preoperative risk stratification in insular glioma surgery.

• Thirty-two patients with insular gliomas underwent preoperative nTMS mapping and DTI tractography to assess motor cortex and corticospinal tract (CST) involvement.

• Higher resting motor threshold (RMT) ratios, CST-tumor distances <3 mm, and decreased peritumoral fractional anisotropy (pFA) ratios were significantly associated with new postoperative motor deficits.

• All patients with new postoperative motor deficits had a CST-tumor distance below 3 mm; lower pFA ratios also correlated with deficits.

• One-third of patients with intraoperative ischemic events developed permanent motor deficits, suggesting additional mediating factors such as CST integrity and cortical excitability.

• A risk model combining RMT ratio, CST distance <3 mm, and low pFA ratio predicted an 82% risk for new motor deficits.

• Preoperative nTMS-based DTI tractography may improve individual risk stratification and surgical planning for insular glioma patients.

The Transtemporal Isthmus Approach for Insular Glioma Surgery

Operative Neurosurgery 28:478–486, 2025

This study presents a transtemporal isthmus approach for insular glioma surgery, achieving maximal safe resection. This method utilizes a widened temporal isthmus to access the insular lobe, ensuring significant tumor removal while preserving neurological function. The approach is shown effective for both low- and high-grade gliomas.

• The study introduces a transtemporal isthmus approach for the resection of insular gliomas, aiming for maximal and safe tumor removal.

• This surgical method involves the use of MRI and functional neuronavigation guidance, along with intraoperative electrophysiological monitoring.

• The approach is particularly beneficial for tumors involving zones III and IV of the Berger-Sanai classification.

Gross total resection was achieved in 64.9% of low-grade and 87.5% of high-grade gliomas.

• The temporal isthmus is widened by the tumor, providing a surgical corridor for resection.

• The median postoperative Karnofsky performance score was 90, indicating good functional preservation.

Muscle strength and speech were nearly normal in all patients three months post-surgery.

• The study suggests this approach is effective for safe and maximal tumor resection, while preserving essential functions.

The transfrontal isthmus approach for insular glioma surgery

J Neurosurg 139:20–28, 2023

The classic transopercular or transsylvian approach to insular gliomas removes the tumor laterally through the insular cortex. This study describes a new anteroposterior approach through the frontal isthmus for insular glioma surgery.

METHODS The authors detailed the surgical techniques for resection of insular gliomas through the transfrontal isthmus approach. Fifty-nine insular gliomas with at least Berger-Sanai zone I involvement were removed with the new approach, and extent of resection and postoperative neurological outcomes were assessed.

RESULTS Fifty-nine patients were enrolled in the study, including 35 men and 24 women, with a mean (range) age 44.3 (19–75) years. According to the Berger-Sanai classification system, the most common tumor was a giant glioma (67.8%), followed by involvement of zones I and IV (18.6%). Twenty-two cases were Yaşargil type 3A/B, and 37 cases were Yaşargil type 5A/B. The average angle between the lateral plane of the putamen and sagittal line was 33.53°, and the average width of the isthmus near the anterior insular point was 33.33 mm. The average angle between the lateral plane of the putamen and the sagittal line was positively correlated with the width of the isthmus near the anterior insular point (r = 0.935, p < 0.0001). The median (interquartile range [IQR]) preoperative tumor volume was 67.82 (57.64–92.19) cm 3 . Of 39 low-grade gliomas, 26 (66.67%) were totally resected; of 20 high-grade gliomas, 19 (95%) were totally resected. The median (IQR) extent of resection of the whole group was 100% (73.7%–100%). Intraoperative diffusion-weighted imaging showed no cases of middle cerebral artery– or lenticulostriate artery–related stroke. Extent of insular tumor resection was positively correlated with the angle of the lateral plane of the putamen and sagittal line (r = −0.329, p = 0.011) and the width of the isthmus near the anterior insular point (r = −0.267, p = 0.041). At 3 months postoperatively, muscle strength grade exceeded 4 in all cases, and all patients exhibited essentially normal speech. The median (IQR) Karnofsky performance score at 3 months after surgery was 90 (80–90).

CONCLUSIONS The transfrontal isthmus approach changes the working angle from lateral-medial to anterior-posterior, allowing for maximal safe removal of insular gliomas.

Correlation of anatomical involvement patterns of insular gliomas with subnetworks of the limbic system

J Neurosurg 136:323–334, 2022

Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort.

METHODS Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21–71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters).

RESULTS The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2   2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator.

CONCLUSIONS The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

 

Insular glioma surgery: an evolution of thought and practice


J Neurosurg 130:9–16, 2019

The goal of this article is to review the history of surgery for low- and high-grade gliomas located within the insula with particular focus on microsurgical technique, anatomical considerations, survival, and postoperative morbidity.

METHODS The authors reviewed the literature for published reports focused on insular region anatomy, neurophysiol- ogy, surgical approaches, and outcomes for adults with World Health Organization grade II–IV gliomas.

RESULTS While originally considered to pose too great a risk, insular glioma surgery can be performed safely due to the collective efforts of many individuals. Similar to resection of gliomas located within other cortical regions, maximal resection of gliomas within the insula offers patients greater survival time and superior seizure control for both newly diagnosed and recurrent tumors in this region. The identification and the preservation of M2 perforating and lateral len- ticulostriate arteries are critical steps to preventing internal capsule stroke and hemiparesis. The transcortical approach and intraoperative mapping are useful tools to maximize safety.

CONCLUSIONS The insula’s proximity to middle cerebral and lenticulostriate arteries, primary motor areas, and perisyl- vian language areas makes accessing and resecting gliomas in this region challenging. Maximal safe resection of insular gliomas not only is possible but also is associated with excellent outcomes and should be considered for all patients with low- and high-grade gliomas in this area.

Autonomic Function in Insular Glioma

World Neurosurg. (2018) 118:e951-e955

Autonomic nervous system dysfunction is a known entity in strokes involving insula. It causes significant morbidity and mortality. No study to date has demonstrated autonomic nervous system dysfunction in patients with insular glioma. This is an exploratory study to identify the
subclinical autonomic dysfunctions in insular glioma.

METHODS: A total 50 patients with newly diagnosed insular glioma in the age group of 18e60 years were evaluated with heart rate variability (HRV). All the HRV parameters in patients with insular glioma were compared with normal healthy age- and sex-matched control patients.

RESULTS: There was a significant difference (P < 0.05) in most of the HRV parameters between patients and control patients. Patients with left insular glioma showed significantly increased heart rate (P [ 0.027), low-frequency normalized units (P [ 0.048), and also increased low-frequency/highfrequency ratio (P [ 0.015), which indicates sympathetic
dominance. Patients with seizures had significantly lower values of total power (P [ 0.042). No significant difference was found in terms of the extent and size of the tumor or histopathologic grades of gliomas.

CONCLUSIONS: Patients with insular gliomas have significant impairment of autonomic functions, with left insular glioma showing sympathetic dominance. Suppression of autonomic function is greater in those presenting with seizures.

Putamen involvement and survival outcomes in patients with insular low-grade gliomas

J Neurosurg 126:1788–1794, 2017

Insular glioma has a unique origin and biological behavior; however, the associations between its anatomical features and prognosis have not been well established. The object of this study was to propose a classification system of insular low-grade gliomas based on preoperative MRI findings and to assess the system’s association with survival outcome.

METHODS A total of 211 consecutively collected patients diagnosed with low-grade insular gliomas was analyzed. All patients were classified according to whether tumor involved the putamen on MR images. The prognostic role of this novel putaminal classification, as well as that of Yaşargil’s classification, was examined using multivariate analyses.

RESULTS Ninety-nine cases (46.9%) of insular gliomas involved the putamen. Those tumors involving the putamen, as compared with nonputaminal tumors, were larger (p < 0.001), less likely to be associated with a history of seizures (p = 0.04), more likely to have wild-type IDH1 (p = 0.003), and less likely to be totally removed (p = 0.02). Significant favorable predictors of overall survival on univariate analysis included a high preoperative Karnofsky Performance Scale score (p = 0.02), a history of seizures (p = 0.04), gross-total resection (p = 0.006), nonputaminal tumors (p < 0.001), and an IDH1 mutation (p < 0.001). On multivariate analysis, extent of resection (p = 0.035), putamen classification (p = 0.014), and IDH1 mutation (p = 0.026) were independent predictors of overall survival. No prognostic role was found for Yaşargil’s classification.

CONCLUSIONS The current study’s findings suggest that the putamen classification is an independent predictor of survival outcome in patients with insular low-grade gliomas. This newly proposed classification allows preoperative survival prediction for patients with insular gliomas.

Technical nuances for surgery of insular gliomas: lessons learned

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Neurosurgical Focus Feb 2013 / Vol. 34 / No. 2 / Page E6

Insular gliomas were traditionally considered a nonsurgical entity due to the high morbidity associated with resection. For the past 20 years, advances in microsurgical and brain mapping techniques have allowed neurosurgeons to resect insular gliomas with acceptable morbidity rates. Maximizing the extent of resection is nowadays the goal of surgery since this has proven to be an independent factor contributing to longer survival. Despite much progress, insular tumors remain a challenge for the neurosurgeon due to the complex anatomy of the region and technical expertise required to minimize morbidity during surgery.

Herein, the authors describe the current surgical nuances, based on their experience and a literature review, that will allow the surgeon to achieve a thorough resection while ensuring patient safety. The key factors for successful surgery in the insular region include detailed knowledge of the surgical anatomy, mastery of the nuances of cortical and subcortical mapping methods, and meticulous microsurgical technique.