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.

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.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.