Brain tumor surgery guided by navigated transcranial magnetic stimulation mapping for arithmetic calculation.

OBJECTIVE: The onco-functional balance represents the primary goal in neuro-oncology. The increasing use of navigated transcranial magnetic stimulation (nTMS) allows the noninvasive characterization of cortical functional anatomy, and its reliability for motor and language mapping has previously been validated. Calculation and arithmetic processing has not been studied with nTMS so far. In this study, the authors present their preliminary data concerning nTMS calculation. METHODS: The authors designed a monocentric prospective study, adopting an internal protocol to use nTMS for preoperative planning, including arithmetic processing. When awake surgery was possible, according to the patients' conditions, nTMS points were used to guide direct cortical stimulation (DCS), i.e., the gold standard for cortical mapping. Navigated TMS-based tractography was used for surgical planning. Statistical analyses on the nTMS and DCS points were performed. RESULTS: From February 2021 to October 2023, 61 procedures for nTMS calculation mapping were performed. The clinical evaluation, including pre- and postoperative evaluations (3 months after surgery), demonstrated a good clinical outcome with preservation of arithmetic function and recovery (92.8% of patients). Between the awake and asleep surgery groups, the postoperative clinical results were comparable at the 3-month follow-up, with > 90% of the patients achieving improved calculation function. The surgical strategy adopted was aimed at sparing nTMS positive points in asleep procedures, whereas nTMS and DCS positive points were not removed in awake procedures. Overall, 62% of the positive points for calculation functions were exposed by craniotomy and 85% were spared during surgery. None of the patients developed nTMS-related seizures. Diffusion tensor imaging fiber tracking based on nTMS positive points for calculation was used. The white matter fiber tracts involved in calculation functions were the arcuate fasciculus (56%) and frontal aslant tract (22%). When nTMS and DCS points were compared in awake surgery (n = 10 patients), a sensitivity of 31.71%, specificity of 85.76%, positive predictive value of 22.41%, negative predictive value of 90.64%, and accuracy of approximately 69% were achieved. CONCLUSIONS: Based on the authors' preliminary data, nTMS can be an advantageous tool to study cognitive functions, aimed at minimizing neurological impairment. The postoperative clinical outcome for patients who underwent operation with nTMS was very good. Considering these results, nTMS has proved to be a feasible method to map cognitive areas including those for calculation functions. Further analyses are needed to validate these data. Finally, other cognitive functions (e.g., visuospatial) may be explored with nTMS.

Neurocognitive Assessment of Mathematics-Related Capacities in Neurosurgical Patients.

A precise neuropsychological assessment is of the utmost importance for neurosurgical patients undergoing the surgical excision of cerebral lesions. The assessment of mathematical abilities is usually limited to arithmetical operations while other fundamental visuo-spatial aspects closely linked to mathematics proficiency, such as the perception of numerical quantities and geometrical reasoning, are completely neglected. We evaluated these abilities with two objective and reproducible psychophysical tests, measuring numerosity perception and non-symbolic geometry, respectively. We tested sixteen neuro-oncological patients before the operation and six after the operation with classical neuropsychological tests and with two psychophysical tests. The scores of the classical neuropsychological tests were very heterogeneous, possibly due to the distinct location and histology of the tumors that might have spared (or not) brain areas subserving these abilities or allowed for plastic reorganization. Performance in the two non-symbolic tests reflected, on average, the presumed functional role of the lesioned areas, with participants with parietal and frontal lesions performing worse on these tests than patients with occipital and temporal lesions. Single-case analyses not only revealed some interesting exceptions to the group-level results (e.g., patients with parietal lesions performing well in the numerosity test), but also indicated that performance in the two tests was independent of non-verbal reasoning and visuo-spatial working memory. Our results highlight the importance of assessing non-symbolic numerical and geometrical abilities to complement typical neuropsychological batteries. However, they also suggest an avoidance of reliance on an excessively rigid localizationist approach when evaluating the neuropsychological profile of oncological patients.

Sodium fluorescein uptake by the tumor microenvironment in human gliomas and brain metastases.

OBJECTIVE: Intravenous sodium fluorescein (SF) is increasingly used during surgery of gliomas and brain metastases to improve tumor resection. Currently, SF is believed to permeate the brain regions where the blood-brain barrier (BBB) is damaged and to accumulate in the extracellular space but not in tumor or healthy cells, making it possible to demarcate tumor margins to guide resection. By evaluating the immune contexture of a number of freshly resected gliomas and brain metastases from patients undergoing SF-guided surgery, the authors recurrently observed fluorescence-positive cells. Therefore, the aim of this study was to determine if SF accumulates inside the cells of the tumor microenvironment (TME), and if so, in which type of cells, and whether incorporation can also be observed in the leukocytes of peripheral blood. METHODS: Freshly resected tumor specimens were dissociated to single cells and analyzed by multiparametric flow cytometry. Peripheral blood leukocytes, macrophages, and a glioma cell line were treated with SF in vitro, and their cell uptake was assessed by multiparametric and imaging flow cytometry and by confocal microscopy. RESULTS: The ex vivo and in vitro analyses revealed that SF accumulates intracellularly in leukocytes as well as in tumor cells, but with a high variability of incorporation in the different cell subsets analyzed. Myeloid cells showed the highest level of fluorescence. In vitro uptake experiments showed that SF accumulation increases over time. The imaging analyses confirmed the internalization of the compound inside the cells. CONCLUSIONS: SF is not just a marker of BBB damage, but its intracellular detection suggests that it selectively accumulates intracellularly. Future efforts should target the mechanisms of its differential uptake by the different TME cell types in depth.

Heads-Up Micronavigation Reliability of Preoperative Transcranial Magnetic Stimulation Maps for the Motor Function: Comparison With Direct Cortical Stimulation.

BACKGROUND AND OBJECTIVES: We aimed to assess the reliability of preoperative navigated transcranial magnetic stimulation (nTMS) maps for motor function as visualized intraoperatively with augmented reality heads-up display and to assess its accuracy via direct point-by-point comparison with the gold-standard direct cortical stimulation (DCS). METHODS: From January 2022 to January 2023, candidates for surgical removal of lesions involving the motor pathways underwent preoperative nTMS assessment to obtain cortical maps of motor function. Intraoperatively and before tumor removal, nTMS maps were superimposed on the cortical surface, and DCS was performed on positive points with increasing current intensity until obtaining a positive response at 16 mA. The outcome of each stimulation was recorded to obtain discrimination metrics. RESULTS: Twelve patients were enrolled (5 females [42%] vs 7 males [58%], mean age 62.9 ± 12.8 years), for a total of 304 investigated points. Agreement between nTMS and DCS was moderate (κ = 0.43, P < .005), with 0.66 (0.53-0.78) sensitivity, 0.87 (0.82-0.90) specificity, 0.50 (0.39-0.62) positive predictive values, 0.93 (0.89-0.95) negative predictive value, and 0.83 (0.79-0.87) accuracy. A loss of accuracy was observed with higher DCS current intensities. CONCLUSION: We performed a point-by-point validation of preoperative nTMS maps for motor function using augmented reality visualization. The high negative predictive value and low positive predictive values highlight nTMS reliability to visualize safe cortical zones but not to identify critical functional areas, confirming previous findings of nTMS maps for the language function and suggesting the need for combined use of nTMS maps and DCS for optimal maximal safe resection.

Is the Patient State Index a reliable parameter as guide to anaesthesiology in cranial neurosurgery? A first intraoperative study and a literature review.

BACKGROUND: Patient State Index (PSI) and Suppression Ratio (SR) are two indices calculated by quantitative analysis of EEG used to estimate the depth of anaesthesia but their validation in neurosurgery must be done. Our aim was to investigate the congruity PSI and SR with raw EEG monitoring in neurosurgery. METHODS: We included 34 patients undergoing elective cranial neurosurgery. Each patient was monitored by a SedLine device (PSI and SR) and by raw EEG. To appraise the agreement between PSI, SR and EEG Suppr%, Bland-Altman analysis was used. We also correlated the PSI and SR recorded at different times during surgery to the degree of suppression of the raw EEG data by Spearman's rank correlation coefficient. For a comparison with previous data we made an international literature review according to PRISMA protocol. RESULTS: At all recording times, we found that there is a strong agreement between PSI and raw EEG. We also found a significant correlation for both PSI and SR with the EEG suppression percentage (p < 0.05), but with a broad dispersion of the individual values within the confidence interval. CONCLUSION: The Masimo SedLine processed EEG monitoring system can be used as a guide in the anaesthetic management of patients during elective cranial neurosurgery, but the anaesthesiologist must be aware that previous correlations between PSI and SR with the suppression percentage may not always be valid in all individual patients. The use of an extended visual raw EEG evaluated by an expert electroencephalographer might help to provide better guidance.

Ileoanal pouch-related fistulae: A systematic review with meta-analysis on incidence, treatment options and outcomes.

BACKGROUND: Ileoanal pouch related fistulae (PRF) are a complication of restorative proctocolectomy often requiring repeated surgical interventions and with a high risk of long-term recurrence and pouch failure. AIMS: To assess the incidence of PRF and to report on the outcomes of available surgical treatments. METHODS: A PRISMA-compliant systematic literature search for articles reporting on PRF in patients with inflammatory bowel diseases (IBD) or familial adenomatous polyposis (FAP) from 1985 to 2020. RESULTS: 34 studies comprising 770 patients with PRF after ileal-pouch anal anastomosis (IPAA) were included. Incidence of PRF was 1.5-12%. In IBD patients Crohn's Disease (CD) was responsible for one every four pouch-vaginal fistulae (PVF) (OR 24.7; p=0.001). The overall fistula recurrence was 49.4%; procedure-specific recurrence was: repeat IPAA (OR 42.1; GRADE +); transvaginal repair (OR 52.3; GRADE ++) and transanal ileal pouch advancement flap (OR 56.9; GRADE ++). The overall failure rate was 19%: pouch excision (OR 0.20; GRADE ++); persistence of diverting stoma (OR 0.13; GRADE +) and persistent fistula (OR 0.18; GRADE +). CONCLUSION: PVFs are more frequent compared to other types of PRF and are often associated to CD; surgical treatment has a risk of 50% recurrence. Repeat IPAA is the best surgical approach with a 42.1% recurrence rate.