Alba Díaz-Baamonde

Background: Brain tumours impose complex, spatially heterogeneous disturbances on neural circuits that extend far beyond the immediate lesion site. While gross anatomical displacement of the cortico-spinal tract (CST) has been extensively studied, the topological reorganization of the functionally informed structural connectome—and its dependence on tumour molecular phenotype—remains incompletely understood. Objectives: This study aimed to characterize upper-limb functionally informed network topology in brain tumour patients, identify histological and molecular patterns of structural reorganization at the cortical and subcortical level, and determine the impact on neurophysiological parameters. Methods: Forty-eight patients with supratentorial motor-eloquent tumours (MET’s) underwent diffusion-weighted imaging (DWI) as part of their preoperative motor mapping. Connectivity matrices based on streamline passing counts were extracted from 426 nodes of the HCPex atlas using DSI Studio^® upon seeding the structural connectome in the motor hotspot (best motor response) for the functional area of the upper limb identified using preoperative navigated transcranial magnetic stimulation (nTMS). Paired-sample t-tests compared tumour versus healthy hemispheres across network topology metrics. The impact of nTMS-derived excitability metrics—interhemispheric resting motor threshold ratio (iRMTr) and cortical silent period (CSP)—and tumour histological and molecular characteristics on the connectome was assessed. Results: The global network topology of the tumour hemisphere was preserved when compared to the healthy baseline hemisphere across all tumour types (p > 0.05). Subcortical analysis revealed significant hyper-connectivity in the tumour hemisphere, with elevated degree, strength, clustering coefficient, local efficiency, and eigenvector centrality (p < 0.05). Basal ganglia motor loop degree was increased in the tumour hemisphere (mean 7.37 versus 5.19; p = 0.0009). IDH-mutant tumours generated significantly more topologically organized compensatory networks than IDH-wildtype tumours (Clustering Coefficient 0.345 versus 0.273; p = 0.018). Of the cortical nodes on the side of the tumour, significant hyper-connectivity was seen in the supplementary motor area (p = 0.0011), premotor cortex (Area 6), with increased connection seen in 6 mp (medial premotor at p =0.0033) and 6 d (dorsal premotor at p = 0.025) and primary somatosensory cortex (p = 0.027). The presence of the tumour induced significant changes across all three domains: loss of CST volume (p < 0.001), prolongation of the cortical silent period indicative of intracortical inhibition (p < 0.0001), with significant prolongation in glioblastoma versus an oligodendroglioma. Conclusions: Brain tumours significantly impact the upper limb-centred structural connectome. While global network topology is preserved, tumours induce substantial subcortical and basal ganglia network reorganization by inducing compensatory hyper-connectivity. These findings suggest that structural connectomics offers a novel framework for non-invasive tumour characterization and surgical planning.

Minimally invasive parafascicular surgery (MIPS) represents a paradigm shift in the management of deep-seated brain tumors, enabling function-sparing resections previously limited to biopsy and/or medical therapy. Central to MIPS are structured frameworks guiding preoperative planning and intraoperative execution. The six-pillar concept—comprising imaging, navigation, atraumatic access, optics, resection, and postoperative care—provides a comprehensive approach to integrate advanced neuroimaging, tractography, tubular retractor systems, fluorescence-guided resection, and neuromonitoring to optimize functional outcomes. Five-point target-trajectory complex planning—craniotomy, outer radial corridor, inner radial corridor, target, and resection margins—translates preoperative imaging and functional mapping into a precise surgical trajectory, balancing maximal tumor resection with minimal disruption of eloquent brain structures. Preoperative assessment of tumor characteristics, vascular relationships, and cortical eloquence informs trajectory planning and intraoperative adjustments. A critical determinant of MIPS success is the intraoperative golden hour, referring to the high-risk period surrounding brain cannulation with a tubular retractor. Key principles include (1) precannulation system checks to ensure instrument readiness; (2) access injury prevention through optimized craniotomy sizing and sulcal preparation; (3) tubular-tumor targeting accuracy addressing brain and tubular translation, tumor displacement, and white-matter sleeves; and (4) intracranial pressure control strategies to minimize tissue strain and venous congestion. Overcoming this period enables a controlled resection phase guided by the above-mentioned surgical adjuncts. The six-pillar concept and five-point target-trajectory complex planning are the foundations of MIPS planning, whereas the intraoperative golden hour provides a roadmap for successful intraoperative delivery of the surgical plan.

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.

Background: Transcranial Magnetic Stimulation–Electroencephalography (TMS-EEG) is a non-operative technique that allows for magnetic cortical stimulation (TMS) and analysis of the electrical currents generated in the brain (EEG). Despite the regular utilization of both techniques independently, little is known about the potential impact of their combination in neurosurgical practice. Methods: This scoping review, conducted following PRISMA guidelines, focused on TMS-EEG in epilepsy, neuro-oncology, and general neurosurgery. A literature search in Embase and Ovid MEDLINE returned 3596 records, which were screened based on predefined inclusion and exclusion criteria. After full-text review, three studies met the inclusion criteria. Two independent investigators conducted study selection and data extraction, with mediators resolving disagreements. The NHLBI tool was used to assess risk of bias in the included studies. Results: A total of 3596 articles were screened following the above-mentioned criteria: two articles and one abstract met the inclusion criteria. TMS-EEG is mentioned as a promising tool to evaluate tumor–brain interaction, improve preoperative speech mapping, and for lateralization epileptic focus in patients undergoing epilepsy surgery. Lack of detailed patient and outcome information preclude further considerations about TMS-EEG use beyond the potential applications of this technique. Conclusions: TMS-EEG research in neurosurgery is required to establish the role of this non-invasive brain stimulation-recording technique. Tumor–brain interaction, preoperative mapping, and seizure lateralization are in the front row for its future applications.

Background/Objectives: 5-aminulevulinic acid (5-ALA)-guided surgery for high-grade gliomas remains a challenge in neuro-oncological surgery. Inconsistent fluorescence visualisation, subjective quantification and false negatives due to blood, haemostatic agents or optical impediments from the external light source are some of the limitations of the present technology. Methods: The preliminary results from this single-centre retrospective study are presented from the first 35 patients operated upon with the novel Nico Myriad Spectra System©. The microdebrider (Myriad) with an additional in situ light system (Spectra) can alternately provide white and blue light (405 nm) to within 15 mm of the tissue surface to enhance the morphology of the anatomical structures and the fluorescence of the pathological tissues. Results: A total of 35 patients were operated upon with this new technology. Eight patients (22.85%) underwent tubular retractor-assisted minimally invasive parafascicular surgery (tr-MIPS). The majority had high-grade gliomas (68.57%). Fluorescence was identified in 30 cases (85.71%), with residual fluorescence in 11 (36.66%). The main applications were better white–blue light alternation and visualisation during tr-MIPS, increase in the extent of resection at the border of the cavity, identification of satellite lesions in multifocal pathology, the differentiation between radionecrosis and tumour recurrence in redo surgery and the demarcation between normal ependyma versus pathological ependyma in tumours infiltrating the subventricular zone. Conclusions: This proof-of-concept study confirms that the novel in situ light-source delivery technology integrated with the usual intraoperative armamentarium provides a spatially, functionally and oncologically informed framework for glioblastoma surgery. It allows for the enhancement of the morphology of anatomical structures and the fluorescence of pathological tissues, increasing the extent of resection and, possibly, the prognosis for patients with high-grade gliomas.

Human reflexes are simple motor responses that are automatically elicited by various sensory inputs. These reflexes can provide valuable insights into the functioning of the nervous system, particularly the brainstem and spinal cord. Reflexes involving the brainstem, such as the blink reflex, laryngeal adductor reflex, trigeminal hypoglossal reflex, and masseter H reflex, offer immediate information about the cranial-nerve functionality and the overall state of the brainstem. Similarly, spinal reflexes such as the H reflex of the soleus muscle, posterior root muscle reflexes, and sacral reflexes provide crucial information about the functionality of the spinal cord and peripheral nerves. One of the critical benefits of reflex monitoring is that it can provide continuous feedback without disrupting the surgical process due to no movement being induced in the surgical field. These reflexes can be monitored in real time during surgical procedures to assess the integrity of the nervous system and detect potential neurological damage. It is particularly noteworthy that the reflexes provide motor and sensory information on the functional integrity of nerve fibers and nuclei. This article describes the current techniques used for monitoring various human reflexes and their clinical significance in surgery. We also address important methodological considerations and their impact on surgical safety and patient outcomes. Utilizing these methodologies has the potential to advance or even revolutionize the field of intraoperative continuous monitoring, ultimately leading to improved surgical outcomes and enhanced patient care.

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.