MGMT promoter methylation is related to the increased sensitivity of tumour tissue to chemotherapy with temozolomide (TMZ) and thus to improved patient survival. However, it is unclear how the extent of MGMT promoter methylation affects outcomes. In our study, a single-centre retrospective study, we explore the impact of MGMT promoter methylation in patients with glioblastoma who were operated upon with 5-ALA. Demographic, clinical and histology data, and survival rates were assessed. A total of 69 patients formed the study group (mean age 53.75 ± 15.51 years old). Positive 5-ALA fluorescence was noted in 79.41%. A higher percentage of MGMT promoter methylation was related to lower preoperative tumour volume (p = 0.003), a lower likelihood of 5-ALA positive fluorescence (p = 0.041) and a larger extent of resection EoR (p = 0.041). A higher MGMT promoter methylation rate was also related to improved progression-free survival (PFS) and overall survival (OS) (p = 0.008 and p = 0.006, respectively), even when adjusted for the extent of resection (p = 0.034 and p = 0.042, respectively). A higher number of adjuvant chemotherapy cycles was also related to longer PFS and OS (p = 0.049 and p = 0.030, respectively). Therefore, this study suggests MGMT promoter methylation should be considered as a continuous variable. It is a prognostic factor that goes beyond sensitivity to chemotherapy treatment, as a higher percentage of methylation is related not only to increased EoR and increased PFS and OS, but also to lower tumour volume at presentation and a lower likelihood of 5-ALA fluorescence intraoperatively.

Brain tumour surgery in visual eloquent areas poses significant challenges to neurosurgeons and has reported inconsistent results. This is a single-centre prospective cohort study of patients admitted for asleep surgery of intra-axial lesions in visual eloquent areas. Demographic and clinical information, data from tractography and visual evoked potentials (VEPs) monitoring were recorded and correlated with visual outcomes. Thirty-nine patients were included (20 females, 19 males; mean age 52.51 ± 14.08 years). Diffuse intrinsic glioma was noted in 61.54% of patients. There was even distribution between the temporal, occipital and parietal lobes, while 55.26% were right hemispheric lesions. Postoperatively, 74.4% remained stable in terms of visual function, 23.1% deteriorated and 2.6% improved. The tumour infiltration of the optic radiation on tractography was significantly related to the visual field deficit after surgery (p = 0.016). Higher N75 (p = 0.036) and P100 (p = 0.023) amplitudes at closure on direct cortical VEP recordings were associated with no new postoperative visual deficit. A threshold of 40% deterioration of the N75 (p = 0.035) and P100 (p = 0.020) amplitudes correlated with a risk of visual field deterioration. To conclude, direct cortical VEP recordings demonstrated a strong correlation with visual outcomes, contrary to transcranial recordings. Invasion of the optic radiation is related to worse visual field outcomes.

Developing neurophysiological tools to predict WHO tumor grade can empower the treating teams for a better surgical decision-making process. A total of 38 patients with supratentorial diffuse gliomas underwent an asleep-awake-sedated craniotomies for tumor removal with intraoperative neuromonitoring. The resting motor threshold was calculated for different train stimulation paradigms during awake and asleep phases. Receiver operating characteristic analysis and Bayesian regression models were performed to analyze the prediction of tumor grading based on the resting motor threshold differences. Significant positive spearman correlations were observed between resting motor threshold excitability difference and WHO tumor grade for train stimulation paradigms of 5 (R = 0.54, P = 0.00063), 4 (R = 0.49, P = 0.002), 3 (R = 0.51, P = 0.001), and 2 pulses (R = 0.54, P = 0.0007). Kruskal–Wallis analysis of the median revealed a positive significant difference between the median of excitability difference and WHO tumor grade in all paradigms. Receiver operating characteristic analysis showed 3 mA difference as the best predictor of high-grade glioma across different patterns of motor pathway stimulation. Bayesian regression found that an excitability difference above 3 mA would indicate a 75.8% probability of a glioma being high grade. Our results suggest that cortical motor excitability difference between the asleep and awake phases in glioma surgery could correlate with tumor grade.

Surgical management of deep-seated brain tumors requires precise functional navigation and minimally invasive surgery. Preoperative mapping using navigated transcranial magnetic stimulation (nTMS), intraoperative neurophysiological monitoring (IONM), and minimally invasive parafascicular surgery (MIPS) act together in a functional-sparing approach. nTMS also provides a rehabilitation tool to maximize functional recovery. This is a single-center retrospective proof-of-concept cohort study between January 2022 and June 2023 of patients admitted for surgery with motor eloquent deep-seated brain tumors. The study enrolled seven adult patients, five females and two males, with a mean age of 56.28 years old. The lesions were located in the cingulate gyrus (three patients), the central core (two patients), and the basal ganglia (two patients). All patients had preoperative motor deficits. The most common histological diagnosis was metastasis (five patients). The MIPS approach to the mid-cingulate lesions involved a trajectory through the fronto-aslant tract (FAT) and the fronto-striatal tract (FST). No positive nTMS motor responses were resected as part of the outer corridor for MIPS. Direct cortical stimulation produced stable motor-evoked potentials during the surgeries with no warning signs. Gross total resection (GTR) was achieved in three patients and near-total resection (NTR) in four patients. Post-operatively, all patients had a deterioration of motor function with no ischemia in the postoperative imaging (cavity-to-CST distance 0–4 mm). After nTMS with low-frequency stimulation in the contralateral motor cortex, six patients recovered to their preoperative functional status and one patient improved to a better functional condition. A combined Tractography-MIPS-IONM-TMS approach provides a successful functional-sparing approach to deep-seated motor eloquent tumors and a rehabilitation framework for functional recovery after surgery.

Background: The tubular retractor-assisted minimally invasive parafascicular approach (trMIPS) is a transsulcal approach to deep-seated brain tumours. It is a safe surgical approach but its impact on the microvascular dynamics of the retracted cortex and its clinical implications are unknown. Methods: This was a single-centre prospective study including patients with deep-seated brain tumours operated on with a trMIPS (BrainPath Nico System^©). All patients underwent pre- and post-cannulation indocyanine green study using a FLOW 800 module in a KINEVO Zeiss^© microscope. Speed, delay, time-to-peak (TtP) rise-in-time and cerebral blood flow index (CBFI) metrics were assessed. Results: Thirty-five patients were included, with 144 regions-of-interest (ROIs) selected. The majority of patients were diagnosed with glioblastoma (51.43%), and 37.14% of patients had a preoperative focal neurological deficit (FND) at presentation. A ROI-based analysis concluded that an increase in speed and CBFI was related with a worse neurological outcome when comparing the pre- and post-brain cannulation assessments (speed: deterioration = 43.12 ± 80.60% versus stable = −14.51 ± 57.80% versus improvement = 6.93 ± 31.33%, p < 0.0001; CBFI: deterioration = 50.40 ± 88.17% versus stable = −2.70 ± 67.54% versus improvement = −38.98 ± 26.17%, p = 0.0005). These findings were reproducible in a combined-ROI per patient analysis and confirmed after adjustment for confounding. Conclusion: Microvascular flow dynamics impact trMIPS outcomes as an increase in the speed and CBFI after decannulation was related with worse neurological outcome.