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Glioblastoma (GBM), an incurable primary brain tumor, typically requires surgical intervention followed by chemoradiation; however, recurrences remain fatal. Our previous work demonstrated that a nanomedicine hydrogel (GemC12-LNC) delays recurrence when administered post-surgery. However, tumor debulking also triggers time-dependent immune reactions that promote recurrence at the resection cavity borders. We hypothesized that combining the hydrogel with an immunomodulatory drug could enhance therapeutic outcomes. A thorough characterization of the post-surgical microenvironment (SMe) is crucial to guide combinatorial approaches. In this study, we performed cellular resolution imaging, flow cytometry and spatial hyperplexed immunofluorescence imaging to characterize the SMe in a syngeneic mouse model of tumor resection. Owing to our dynamic approach, we observed transient opening of the blood–brain barrier (BBB) during the first week after surgery. BBB permeability post-surgery was also confirmed in GBM patients. In our murine model, we also observed changes in immune cell morphology and spatial location post-surgery over time in resected animals as well as the accumulation of reactive microglia and anti-inflammatory macrophages in recurrences compared to unresected tumors since the first steps of recurrence growth. Therefore we investigated whether starting a systemic treatment with the SMAC mimetic small molecule (GDC-0152) directly after surgery would be beneficial for enhancing microglial anti-tumoral activity and decreasing the number of anti-inflammatory macrophages around the GemC12-LNC hydrogel-loaded tumor cavity. The immunomodulatory effects of this drug combination was firstly shown in patient-derived tumoroids. Its efficacy was confirmed in vivo by survival analysis and correlated with reversal of the immune profile as well as delayed tumor recurrence. This comprehensive study identified critical time frames and immune cellular targets within the SMe, aiding in the rational design of combination therapies to delay recurrence onset. Our findings suggest that post-surgical systemic injection of GDC-0152 in combination with GemC12-LNC local treatment is a promising and innovative approach for managing GBM recurrence, with potential for future translation to human patient. [ABSTRACT FROM AUTHOR]

Background: One of the challenges in surgery of tumors in motor eloquent areas is the individual risk assessment for postoperative motor disorder. Previously a regression model was developed that permits estimation of the risk prior to surgery based on topographical and neurophysiological data derived from investigation with nTMS (navigated Transcranial Magnetic Stimulation). This study aims to analyze the impact of including additional neurophysiological TMS parameters into the established risk stratification model for motor outcome after brain tumor surgery. Methods: Biometric and clinical data of 170 patients with glioma in motor eloquent areas were collected prospectively. In addition, the following nTMS parameters were collected bihemispherically prior to surgery: resting motor threshold (RMT), recruitment curve (RC), cortical silent period (CSP) and a nTMS based fibertracking to measure the tumor tract distance (TTD). Motor function was quantified by Medical Research Council Scale (MRCS) preoperatively, seven days and three months postoperatively. Association between nTMS parameters and postoperative motor outcome was investigated in bivariate and multivariable analyses. Results: The bivariate analysis confirmed the association of RMT ratio with the postoperative motor outcome after seven days with higher rates of worsening in patients with RMT ratio > 1.1 compared to patients with RMT ratio ≤ 1.1 (31.6% vs. 15.1%, p = 0.009). Similarly, an association between a pathological CSP ratio and a higher risk of new postoperative motor deficits after seven days was observed (35.3% vs. 16.7% worsening, p = 0.025). A pathological RC Ratio was associated postoperative deterioration of motor function after three months (42.9% vs. 16.2% worsening, p = 0.004). In multiple regression analysis, none of these associations were statistically robust. Conclusions: The current results suggest that the RC ratio, CSP ratio and RMT ratio individually are sensitive markers associated with the motor outcome 7 days and 3 months after tumor resection in a presumed motor eloquent location. They can therefore supply valuable information during preoperative risk–benefit-balancing. However, underlying neurophysiological mechanisms might be too similar to make the parameters meaningful in a combined model. [ABSTRACT FROM AUTHOR]

Purpose: Neuronavigation, explored as an intra-operative adjunct for brain tumor surgery three decades ago, has become globally utilized with a promising upward trajectory. This study aims to chart its success from idea to adoption and evolution within the US and globally. Methods: A three-pronged methodology included a systematic literature search, impact analysis using NIH relative citation ratio (RCR) and Altmetric scores, and assessment of patent holdings. Data was dichotomized for US and international contexts. Results: The first neuronavigation publication stemmed from Finland in 1993, marking its inception. Over three decades, the cumulative number of 323 studies, along with the significantly increasing publication trend (r = 0.74, p < 0.05) and distribution across 34 countries, underscored its progressive and global adoption. Neuronavigation, mostly optical systems (58%), was utilized in over 19,000 cases, predominantly for brain tumor surgery (84%). Literature impact showed a robust cumulative median RCR score surpassing that for NIH-funded studies (1.37 vs. 1.0), with US studies having a significantly higher median RCR than international (1.71 vs. 1.21, p < 0.05). Technological evolution was characterized by adjuncts, including micro/exo/endoscope (21%), MRI (17%), ultrasound (10%), and CT (7%). Patent analysis demonstrated academic and industrial representation with an interdisciplinary convergence of medical and computational sciences. Conclusion: Since its inception thirty years ago, neuronavigation has been adopted worldwide, and it has evolved with adjunct technology integration to enhance its meaningful use. The current neuronavigation innovation pipeline is progressing, with academic and industry partnering to advance its further application in treating brain tumor patients. [ABSTRACT FROM AUTHOR]

Abstract Glioblastoma (GBM), an incurable primary brain tumor, typically requires surgical intervention followed by chemoradiation; however, recurrences remain fatal. Our previous work demonstrated that a nanomedicine hydrogel (GemC12-LNC) delays recurrence when administered post-surgery. However, tumor debulking also triggers time-dependent immune reactions that promote recurrence at the resection cavity borders. We hypothesized that combining the hydrogel with an immunomodulatory drug could enhance therapeutic outcomes. A thorough characterization of the post-surgical microenvironment (SMe) is crucial to guide combinatorial approaches. In this study, we performed cellular resolution imaging, flow cytometry and spatial hyperplexed immunofluorescence imaging to characterize the SMe in a syngeneic mouse model of tumor resection. Owing to our dynamic approach, we observed transient opening of the blood–brain barrier (BBB) during the first week after surgery. BBB permeability post-surgery was also confirmed in GBM patients. In our murine model, we also observed changes in immune cell morphology and spatial location post-surgery over time in resected animals as well as the accumulation of reactive microglia and anti-inflammatory macrophages in recurrences compared to unresected tumors since the first steps of recurrence growth. Therefore we investigated whether starting a systemic treatment with the SMAC mimetic small molecule (GDC-0152) directly after surgery would be beneficial for enhancing microglial anti-tumoral activity and decreasing the number of anti-inflammatory macrophages around the GemC12-LNC hydrogel-loaded tumor cavity. The immunomodulatory effects of this drug combination was firstly shown in patient-derived tumoroids. Its efficacy was confirmed in vivo by survival analysis and correlated with reversal of the immune profile as well as delayed tumor recurrence. This comprehensive study identified critical time frames and immune cellular targets within the SMe, aiding in the rational design of combination therapies to delay recurrence onset. Our findings suggest that post-surgical systemic injection of GDC-0152 in combination with GemC12-LNC local treatment is a promising and innovative approach for managing GBM recurrence, with potential for future translation to human patient. Graphical Abstract

Simple Summary: Glioblastoma is a highly aggressive type of brain tumor that is very difficult to treat, and surgery is crucial for improving patient survival. However, there are significant differences in access to brain tumor surgery based on factors like income, location, and available healthcare resources. People in low- and middle-income countries often struggle to receive the surgery they need due to a lack of specialized doctors, inadequate healthcare facilities, and financial challenges. As a result, patients in these regions are often diagnosed later, receive less effective treatment, and have lower survival rates compared to those in wealthier countries. This not only affects the patients but also adds economic and social burdens to their communities. The study calls for urgent actions to address these inequalities through international cooperation, better healthcare policies, and fair distribution of resources, with the goal of improving access to brain tumor surgeries for everyone, no matter where they live. Glioblastoma: a highly aggressive brain tumor, presents substantial challenges in treatment and management, with surgical intervention playing a pivotal role in improving patient outcomes. Disparities in access to brain tumor surgery arise from a multitude of factors, including socioeconomic status, geographical location, and healthcare resource allocation. Low- and middle-income countries (LMICs) often face significant barriers to accessing surgical services, such as shortages of specialized neurosurgical expertise, limited healthcare infrastructure, and financial constraints. Consequently, glioblastoma patients in LMICs experience delays in diagnosis, suboptimal treatment, and poorer clinical outcomes compared to patients in high-income countries (HICs). The clinical impact of these disparities is profound. Patients in LMICs are more likely to be diagnosed at advanced disease stages, receive less effective treatment, and have lower survival rates than their counterparts in HICs. Additionally, disparities in access to surgical care exacerbate economic and societal burdens, emphasizing the urgent need for targeted interventions and health policy reforms to address healthcare inequities. This review highlights the importance of addressing global disparities in access to brain tumor surgery for glioblastoma through collaborative efforts, policy advocacy, and resource allocation, aiming to improve outcomes and promote equity in surgical care delivery for all glioblastoma patients worldwide. [ABSTRACT FROM AUTHOR]

Background: Intraoperative ultrasound (IOUS) is a profitable tool for neurosurgical procedures' assistance, especially in neuro-oncology. It is a rapid, ergonomic and reproducible technique. However, its known handicap is a steep learning curve for neurosurgeons. Here, we describe an interesting postoperative analysis that provides extra feedback after surgery, accelerating the learning process. Method: We conducted a descriptive retrospective unicenter study including patients operated from intra-axial brain tumors using neuronavigation (Curve, Brainlab) and IOUS (BK-5000, BK medical) guidance. All patients had preoperative Magnetic Resonance Imaging (MRI) prior to tumor resection. During surgery, 3D neuronavigated IOUS studies (n3DUS) were obtained through craniotomy N13C5 transducer's integration to the neuronavigation system. At least two n3DUS studies were obtained: prior to tumor resection and at the resection conclusion. A postoperative MRI was performed within 48 h. MRI and n3DUS studies were posteriorly fused and analyzed with Elements (Brainlab) planning software, permitting two comparative analyses: preoperative MRI compared to pre-resection n3DUS and postoperative MRI to post-resection n3DUS. Cases with incomplete MRI or n3DUS studies were withdrawn from the study. Results: From April 2022 to March 2024, 73 patients were operated assisted by IOUS. From them, 39 were included in the study. Analyses comparing preoperative MRI and pre-resection n3DUS showed great concordance of tumor volume (p < 0,001) between both modalities. Analysis comparing postoperative MRI and post-resection n3DUS also showed good concordance in residual tumor volume (RTV) in cases where gross total resection (GTR) was not achieved (p < 0,001). In two cases, RTV detected on MRI that was not detected intra-operatively with IOUS could be reviewed in detail to recheck its appearance. Conclusions: Post-operative comparative analyses between IOUS and MRI is a valuable tool for novel ultrasound users, as it enhances the amount of feedback provided by cases and could accelerate the learning process, flattening this technique's learning curve. [ABSTRACT FROM AUTHOR]

Cognitive impairment has a profound deleterious impact on long-term outcomes of glioma surgery. The human insula, a deep cortical structure covered by the operculum, plays a role in a wide range of cognitive functions including interceptive thoughts and salience processing. Both low-grade (LGG) and high-grade gliomas (HGG) involve the insula, representing up to 25% of LGG and 10% of HGG. Surgical series from the past 30 years support the role of primary cytoreductive surgery for insular glioma patients; however, reported cognitive outcomes are often limited to speech and language function. The breath of recent neuroscience literature demonstrates that the insula plays a broader role in cognition including interoceptive thoughts and salience processing. This article summarizes the vast functional role of the healthy human insula highlighting how this knowledge can be leveraged to improve the care of patients with insular gliomas. [ABSTRACT FROM AUTHOR]

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Hydrocephalus following brain tumor surgery is found, although cause of hydrocephalus is optimally eradicated. This study aimed to investigate factors associated with development of postoperative hydrocephalus that requires shunt procedure and generate predictive scoring model of this condition. Demographic, clinical, radiographic, treatment, laboratory, complication, and postoperative data were collected. Binary logistic regression was used to investigate final model for generating predictive scoring system of postoperative hydrocephalus. A total of 179 patients undergoing brain tumor surgery were included. Forty-five (25.1%) patients had postoperative hydrocephalus that required shunt surgery. In univariate analysis, several factors were found to be associated with postoperative hydrocephalus. Strong predictors of postoperative hydrocephalus revealed in multivariate analysis included tumor recurrence before surgery (odds ratio [OR], 4.38; 95% confidence interval [CI], 1.28-14.98; p= 0.018), preoperative hydrocephalus (OR, 6.52; 95% CI, 2.44-17.46; p < 0.001), glial tumor (OR, 3.76; 95% CI, 1.14-12.43; p= 0.030), metastasis (OR, 5.19; 95% CI, 1.72-15.69; p= 0.004), intraventricular hemorrhage (OR, 7.08; 95% CI, 1.80-27.82; p= 0.005), and residual tumor volume (OR, 1.05; 95% CI, 1.01-1.09; p= 0.007). A cutoff predictive score with the best area under curve and optimum cutoff point was utilized for discriminating patients with high risk from individuals with low risk in occurrence of postoperative hydrocephalus. This study reported predictive factors strongly associated with development of postoperative hydrocephalus. Predictive scoring system is useful for identifying patients with an increased risk of postoperative hydrocephalus. Patients classified in the high-risk group require closed surveillance of the hydrocephalus. [ABSTRACT FROM AUTHOR]

Cognitive impairment has a profound deleterious impact on long-term outcomes of glioma surgery. The human insula, a deep cortical structure covered by the operculum, plays a role in a wide range of cognitive functions including interceptive thoughts and salience processing. Both low-grade (LGG) and high-grade gliomas (HGG) involve the insula, representing up to 25% of LGG and 10% of HGG. Surgical series from the past 30 years support the role of primary cytoreductive surgery for insular glioma patients; however, reported cognitive outcomes are often limited to speech and language function. The breath of recent neuroscience literature demonstrates that the insula plays a broader role in cognition including interoceptive thoughts and salience processing. This article summarizes the vast functional role of the healthy human insula highlighting how this knowledge can be leveraged to improve the care of patients with insular gliomas.

Early postoperative seizures (EPS) are a common complication of brain tumor surgery. EPS can lead to hemorrhage, cerebral hypoxia, increased intracranial pressure, longer hospitalization, reduced quality of life, decreased overall survival, and increased morbidity. However, there are no formal guidelines on perioperative antiseizure medication (ASM) management in patients with tumor-related epilepsy who are deemed high risk for EPS. In this study, we describe the case of a 38-year-old man with isocitrate dehydrogenase-mutant mixed glioma and two episodes of EPS manifesting with status epilepticus during prior tumor surgeries and who presented with tumor progression. The Tumor Board recommended awake craniotomy with direct electrical stimulation (DES). The patient was administered aggressive preoperative “prophylactic” ASMs by increasing the maintenance doses of lacosamide and levetiracetam by 25% 48 h before surgery. An intravenous load of fosphenytoin (20 mg/kg) was administered in the operating room before DES, followed by a maintenance dosing of 300 mg/day for 14 days. EPS did not occur, and he was discharged home on postoperative day 4. Our case illustrates that aggressive perioperative prophylactic ASM therapy beyond the maintenance ASM regimen can be considered in patients with tumor-related epilepsy at risk of EPS.

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile. [ABSTRACT FROM AUTHOR]

Although unplanned readmission is a postoperative outcome metric associated with significant morbidity and financial burden, precise assessment tools for its prediction have not yet been developed. The Risk Analysis Index (RAI) could potentially be used to help improve the prediction of unplanned readmissions for patients undergoing intracranial tumor resection (ITR). In the present study, we evaluate the predictive accuracy of frailty on 30-day unplanned readmission after ITR using the RAI. Data were obtained from the American College of Surgeons National Surgical Quality Improvement Program database. The baseline characteristics, preoperative clinical status, and outcomes were compared between patients with and without unplanned readmission. Frailty was calculated using the RAI. Univariate and multivariate logistic regression analyses were performed to identify independent associations between unplanned readmissions and patient characteristics. The unplanned readmission rate for this cohort (n = 31,776) was 10.8% (n = 3420). Of the 3420 readmitted patients, 958 required unplanned reoperation. Multiple characteristics were significantly different between the 2 groups, including age, body mass index, comorbidities, and RAI groups (P < 0.05). The common causes of unplanned readmission included infection (9.4%), seizures (6%), and pulmonary embolism (4%). The patient characteristics identified as reliable predictors of unplanned readmission included age, body mass index, functional status, diabetes, hypertension, hyponatremia, and the patient's RAI score (P < 0.05). Frail status, hyponatremia, leukocytosis, hypertension, and thrombocytosis were significant predictors of unplanned readmissions. The RAI is a reliable preoperative frailty index for predicting unplanned readmissions after ITR. Using the RAI could decrease unplanned readmissions by identifying high-risk patients and enabling future implementation of appropriate management guidelines. [ABSTRACT FROM AUTHOR]

Imaging has always been fundamental to neurosurgery, and its evolution over the last century has made a dramatic transformation in the ability of neurosurgeons to define pathology and preserve normal tissue during their operations. In the mid-70 s, the development of computerized cross-sectional imaging with CT scan and subsequently MRI have revolutionized the practice of neurosurgery. Later, further advances in computer technology and medical engineering have allowed the combination of many modalities to bring them into the operating theater. This evolution has allowed real-time intraoperative imaging, in the hope of helping neurosurgeons achieve accuracy, maximal safe resection, and the implementation of minimally invasive techniques in brain and spine pathologies. Augmented reality and robotic technologies are also being applied as useful intra-operative techniques that will improve surgical planning and outcomes in the future. In this article, we will review imaging modalities and provide our institutional perspective on how we have integrated them into our practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Brain tumors are difficult to treat, and surgeons need the best tools to safely remove them. This review looks at the various technologies that help surgeons see tumors more clearly during surgery. These technologies range from special microscopes and exoscopes to advanced imaging like handheld molecular diagnostic tools. While these tools have made surgery safer and more effective, they are not without challenges, such as complex usage and interpretation. Our aim is to present an overview of these technologies, discuss their pros and cons, and look at the future, where artificial intelligence and virtual reality could make these surgeries even more precise. This research could guide future innovations that improve patient outcomes. Advancements in intraoperative visualization and imaging techniques are increasingly central to the success and safety of brain tumor surgery, leading to transformative improvements in patient outcomes. This comprehensive review intricately describes the evolution of conventional and emerging technologies for intraoperative imaging, encompassing the surgical microscope, exoscope, Raman spectroscopy, confocal microscopy, fluorescence-guided surgery, intraoperative ultrasound, magnetic resonance imaging, and computed tomography. We detail how each of these imaging modalities contributes uniquely to the precision, safety, and efficacy of neurosurgical procedures. Despite their substantial benefits, these technologies share common challenges, including difficulties in image interpretation and steep learning curves. Looking forward, innovations in this field are poised to incorporate artificial intelligence, integrated multimodal imaging approaches, and augmented and virtual reality technologies. This rapidly evolving landscape represents fertile ground for future research and technological development, aiming to further elevate surgical precision, safety, and, most critically, patient outcomes in the management of brain tumors. [ABSTRACT FROM AUTHOR]

The article discusses the use of Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRg-LiTT) in the minimally invasive surgical treatment of epilepsy and brain neoplasms. MRg-LiTT has been a significant breakthrough in neurosurgery, providing a therapeutic alternative with demonstrated safety and efficacy. It offers advantages such as reduced surgical complications, shorter hospital stays, and faster recovery. The article includes six papers that explore various topics related to MRg-LiTT, including treating deep brain lesions and testing physics and new therapeutic hypotheses. Overall, MRg-LiTT is a viable option for treating epileptogenic conditions and complements established surgical techniques. [Extracted from the article]

Background: Diffusion tensor imaging (DTI) tractography facilitates maximal safe resection and optimizes planning to avoid injury during subcortical dissection along descending motor pathways (DMPs). We provide an affordable, safe, and timely algorithm for preoperative DTI motor reconstruction for gliomas adjacent to DMPs. Methods: Preoperative DTI reconstructions were extracted from a prospectively acquired registry of glioma resections adjacent to DMPs. The surgeries were performed over a 7-year period. Demographic, clinical, and radiographic data were extracted from patients' electronic medical records. Results: Nineteen patients (12 male) underwent preoperative tractography between January 1, 2013, and May 31, 2020. The average age was 44.5 years (range, 19-81 years). A complete radiological resection was achieved in nine patients, a subtotal resection in five, a partial resection in three, and a biopsy in two. Histopathological diagnoses included 10 patients with high-grade glioma and nine with low-grade glioma. A total of 16 perirolandic locations (10 frontal and six frontoparietal) were recorded, as well as two in the insula and one in the basal ganglia. In 9 patients (47.3%), the lesion was in the dominant hemisphere. The median preoperative and postoperative Karnofsky Performance Scores were 78 and 80, respectively. Motor function was unchanged or improved over time in 15 cases (78.9%). Conclusion: This protocol of DTI reconstruction for glioma removal near the DMP shows good results in low-term neurological functional outcomes. [ABSTRACT FROM AUTHOR]

We investigated the appropriate D-dimer cutoff value for each brain tumor type for acute or subacute deep vein thrombosis (DVT) following transcranial brain tumor surgery. In this single-center retrospective study, a cumulative total of 128 patients who underwent transcranial brain tumor surgery were enrolled and classified into the glioma group, the other intracranial malignant tumor group, and the intracranial benign tumor group. Venous ultrasonography was performed if the D-dimer plasma levels were positive (1 μg/mL) before surgery and on postoperative day (POD) 3 or 7. Of the 128 cases, DVT developed in 32 (25.0%). Among those, acute or subacute DVT was diagnosed in 22 cases on POD 3 and in 8 cases on POD 7. Compared with DVT-negative cases on POD 3, acute or subacute DVT-positive cases on POD 3 revealed a significant increase in the D-dimer level in all groups combined and in the benign tumor group but not in the glioma group. With regard to DVT on POD 3 in all groups, the receiver operating characteristic curve for the D-dimer level on POD 3 demonstrated a cutoff value of 3.3 μg/mL (sensitivity [0.636] and specificity [0.750]). However, if this cutoff value was used in practice, eight cases would be false-negative with a minimum D-dimer level of 1.5 μg/mL. The D-dimer cutoff value for acute or subacute DVT on POD 3 could be set to 3.3 μg/mL; however, the setting resulted in several false-negative cases. Practically, 1.5 μg/mL of the D-dimer cutoff value on POD 3 might be appropriate to avoid false-negative results.

Diffusion tensor imaging (DTI)-tractography and functional magnetic resonance imaging (fMRI) have dynamically entered the presurgical evaluation context of brain surgery during the past decades, providing novel perspectives in surgical planning and lesion access approaches. However, their application in the presurgical setting requires significant time and effort and increased costs, thereby raising questions regarding efficiency and best use. In this work, we set out to evaluate DTI-tractography and combined fMRI/DTI-tractography during intra-operative neuronavigation in resective brain surgery using lesion-related preoperative neurological deficit (PND) outcomes as metrics. We retrospectively reviewed medical records of 252 consecutive patients admitted for brain surgery. Standard anatomical neuroimaging protocols were performed in 127 patients, 69 patients had additional DTI-tractography, and 56 had combined DTI-tractography/fMRI. fMRI procedures involved language, motor, somatic sensory, sensorimotor and visual mapping. DTI-tractography involved fiber tracking of the motor, sensory, language and visual pathways. At 1 month postoperatively, DTI-tractography patients were more likely to present either improvement or preservation of PNDs (p = 0.004 and p = 0.007, respectively). At 6 months, combined DTI-tractography/fMRI patients were more likely to experience complete PND resolution (p < 0.001). Low-grade lesion patients (N = 102) with combined DTI-tractography/fMRI were more likely to experience complete resolution of PNDs at 1 and 6 months (p = 0.001 and p < 0.001, respectively). High-grade lesion patients (N = 140) with combined DTI-tractography/fMRI were more likely to have PNDs resolved at 6 months (p = 0.005). Patients with motor symptoms (N = 80) were more likely to experience complete remission of PNDs at 6 months with DTI-tractography or combined DTI-tractography/fMRI (p = 0.008 and p = 0.004, respectively), without significant difference between the two imaging protocols (p = 1). Patients with sensory symptoms (N = 44) were more likely to experience complete PND remission at 6 months with combined DTI-tractography/fMRI (p = 0.004). The intraoperative neuroimaging modality did not have a significant effect in patients with preoperative seizures (N = 47). Lack of PND worsening was observed at 6 month follow-up in patients with combined DTI-tractography/fMRI. Our results strongly support the combined use of DTI-tractography and fMRI in patients undergoing resective brain surgery for improving their postoperative clinical profile.

Background: Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model. Methods: We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits. Results: Two hundred and three patients with a median age of 50 years (range: 20–81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72–0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71–0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55–0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65–0.83). Conclusion: The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography.

Brain tumor surgery has witnessed significant advancements over the past few decades, resulting in improved patient outcomes. Despite these advancements, brain tumors remain a formidable public health challenge due to their high morbidity and mortality rates. This review explores the evolution of neurosurgical techniques for brain tumor resection, emphasizing the balance between minimizing invasiveness and maximizing precision. Traditional approaches like craniotomy and keyhole surgery remain crucial, but the rise of minimally invasive techniques such as endoscopic endonasal surgery and laser interstitial thermal therapy (LITT) has revolutionized the field. Awake craniotomy has been a substantial stepping stone towards the preservation of neurological function among brain tumor patients. Additionally, the integration of brain mapping technologies including intraoperative MRI, ultrasound and fluorescence-guided surgery has enhanced the precision of tumor resections, particularly in eloquent brain areas. These innovations, while promising, also come with challenges, including steep learning curves and limited access to advanced technology in certain regions. As the field progresses, ongoing research is essential to refine these techniques and improve accessibility, ultimately aiming to increase survival rates and preserve neurological function in patients with brain tumors. The integration of advanced imaging techniques refined surgical tools, and artificial intelligence (AI) in surgical planning is expected to further improve the safety and effectiveness of neurosurgical procedures in the future. This review provides a comprehensive analysis of current surgical strategies and explores potential future directions in brain tumor surgery., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vadhavekar et al.)

Background: Since its introduction to surgery, the CO2 laser has been used in the treatment of various neurosurgical pathologies as it combines cutting, vaporizing, and coagulating properties in one tool and has a safe penetration depth. In this case series of 29 patients, we present the evaluation of the usefulness of the closed system type – sealed tube surgical CO2 laser in the surgical removal of brain tumors. Methods: The Sharplan 40C model SurgiTouch, sealed tube type CO2 laser, was used in the resection of 29 brain tumors; 13 meningiomas, six metastases, nine gliomas, and one acoustic neuroma. The same senior surgeon (BT) assessed and classified the benefit provided by the CO2 laser in the resection of the neoplasms to considerable (Group 1), moderate (Group 2), and poor (Group 3). Results: Group 1 included 14 patients with 13 meningiomas and one acoustic neuroma, Group 2 included six patients, all of whom had metastases, and Group 3 included nine patients of which six had glioblastoma and three astrocytoma. No complications or technical problems occurred due to the use of the CO2 laser. Conclusion: The CO2 laser is a valuable complementary tool in brain tumor surgery displaying high efficacy and practicality in the resection of neoplasms which are fibrous and have hard consistency. It has high acquisition and maintenance cost and cannot replace the bipolar diathermy. The newest generation of flexible CO2 laser fiber provides more ergonomy and promises new perspectives of its neurosurgical use in the modern era. [ABSTRACT FROM AUTHOR]

Intraoperative ultrasound (IOUS) is becoming progressively more common during brain tumor surgery. We present data from our case series of brain tumor surgery performed with the aid of IOUS in order to identify IOUS advantages and crucial aspects that may improve the management of neurosurgical procedures for brain tumors. From January 2021 to September 2021, 17 patients with different brain tumors underwent brain tumor surgery aided by the use of IOUS. During surgery, the procedure was supported by the use of multiples ultrasonographic modalities in addition to standard B-mode: Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS). In selected cases, the use of IOUS during surgical procedure was combined with neuronavigation and the use of intraoperative fluorescence by the use of 5-aminolevulinic acid (5-ALA). In one patient, a preoperative ultrasound evaluation was performed through a former iatrogenic skull defect. This study confirms the role of IOUS in maximizing the EOR, which is strictly associated with postoperative outcome, overall survival (OS), and patient's quality of life (QoL). The combination of ultrasound advanced techniques such as Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS) is crucial to improve surgical effectiveness and patient's safety while expanding surgeon's view. [ABSTRACT FROM AUTHOR]

Intraoperative ultrasound (IOUS) is becoming progressively more common during brain tumor surgery. We present data from our case series of brain tumor surgery performed with the aid of IOUS in order to identify IOUS advantages and crucial aspects that may improve the management of neurosurgical procedures for brain tumors. From January 2021 to September 2021, 17 patients with different brain tumors underwent brain tumor surgery aided by the use of IOUS. During surgery, the procedure was supported by the use of multiples ultrasonographic modalities in addition to standard B-mode: Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS). In selected cases, the use of IOUS during surgical procedure was combined with neuronavigation and the use of intraoperative fluorescence by the use of 5-aminolevulinic acid (5-ALA). In one patient, a preoperative ultrasound evaluation was performed through a former iatrogenic skull defect. This study confirms the role of IOUS in maximizing the EOR, which is strictly associated with postoperative outcome, overall survival (OS), and patient’s quality of life (QoL). The combination of ultrasound advanced techniques such as Doppler, color Doppler, elastosonography, and contrast-enhanced intraoperative ultrasound (CEUS) is crucial to improve surgical effectiveness and patient’s safety while expanding surgeon’s view.

Objective: Intraoperative neuromonitoring (IONM) is nowadays a gold standard during brain tumor resections, but visual function mapping is less frequently performed in clinical practice. This article aims to report two transcortical brain tumor surgery cases affecting optic radiation, where the application of intraoperative visual evoked potentials (VEP) combined with tractography was beneficial to protect the patients' vision., Methods: Two patients with brain tumors compressing the left posterior visual pathways underwent surgery under general anesthesia using IONM and VEP with neurologic improvement and preservation of vision., Results: VEP is beneficial in the surgery of intra-axial lesions affecting the posterior visual pathways (optic radiation, visual cortex) and parasellar lesions involving the anterior visual pathways (chiasm). They can also be effectively combined with other mapping methods such as tractography., Conclusions: According to our experience, IONM with VEPs and neuronavigation with tractography protect visual function in transcortical approaches to resecting tumors near the optic radiation and should be considered a standard monitoring method for such operations., Competing Interests: The authors state no conflict of interest., (© 2024 The Authors.)

• Direct cortical somatosensory evoked potential (SSEP) recordings are feasible and can reliably monitor thalamocortical input to fronto-parietal regions. • SSEP changes influence management and predict neurologic outcome. • Concomitant activation of thalamocortical afferents modulates excitability of the motor cortex. Neuromonitoring of primary motor regions allows preservation of motor strength and is frequently employed during cranial procedures. Less is known about protection of sensory function and ability to modulate movements, both of which rely on integrity of thalamocortical afferents (TCA) to fronto-parietal regions. We describe our experience with TCA monitoring and their cortical relays during brain tumor surgery. To study its feasibility and usefulness, continuous somatosensory evoked potentials (SSEP) recording via a subdural electrode was attempted in 32 consecutive patients. Median and posterior tibial SSEP were successfully monitored in 31 and 17 patients respectively. SSEP improved lesion localization and prevented unnecessary cortical stimulation in 9 and 16 cases respectively. A threshold of ≥30% SSEP amplitude decrease influenced management in 10 patients while a decrement of ≥50 % had a sensitivity of 0.89 and specificity of 1 in detecting worsening of sensory function. Simultaneous motor evoked potentials (MEP) and SSEP monitoring were performed in 10 cases, 9 of which showed short-lived fluctuations of the former. Direct cortical SSEP monitoring is feasible, informs management and predicts outcome. Early intervention prevents sensory deficit. Concomitant MEP fluctuations may reflect modulation of motor activity by TCA. [ABSTRACT FROM AUTHOR]

BackgroundThe resection of a motor-eloquent glioma should be guided by intraoperative neurophysiological monitoring (IOM) but its interpretation is often difficult and may (unnecessarily) lead to subtotal resection. Navigated transcranial magnetic stimulation (nTMS) combined with diffusion-tensor-imaging (DTI) is able to stratify patients with motor-eloquent lesion preoperatively into high- and low-risk cases with respect to a new motor deficit.ObjectiveTo analyze to what extent preoperative nTMS motor risk stratification can improve the interpretation of IOM phenomena.MethodsIn this monocentric observational study, nTMS motor mapping with DTI fiber tracking of the corticospinal tract was performed before IOM-guided surgery for motor-eloquent gliomas in a prospectively collected cohort from January 2017 to October 2020. Descriptive analyses were performed considering nTMS data (motor cortex infiltration, resting motor threshold (RMT), motor evoked potential (MEP) amplitude, latency) and IOM data (transcranial MEP monitoring, intensity of monopolar subcortical stimulation (SCS), somatosensory evoked potentials) to examine the association with the postoperative motor outcome (assessed at day of discharge and at 3 months).ResultsThirty-seven (56.1%) of 66 patients (27 female) with a median age of 48 years had tumors located in the right hemisphere, with glioblastoma being the most common diagnosis with 39 cases (59.1%). Three patients (4.9%) had a new motor deficit that recovered partially within 3 months and 6 patients had a persistent deterioration (9.8%). The more risk factors of the nTMS risk stratification model (motor cortex infiltration, tumor-tract distance (TTD) ≤8mm, RMTratio 110%) were detected, the higher was the risk for developing a new postoperative motor deficit, whereas no patient with a TTD >8mm deteriorated. Irreversible MEP amplitude decrease >50% was associated with worse motor outcome in all patients, while a MEP amplitude decrease ≤50% or lower SCS intensities ≤4mA were particularly correlated with a postoperative worsened motor status in nTMS-stratified high-risk cases. No patient had postoperative deterioration of motor function (except one with partial recovery) when intraoperative MEPs remained stable or showed only reversible alterations.ConclusionsThe preoperative nTMS-based risk assessment can help to interpret ambiguous IOM phenomena (such as irreversible MEP amplitude decrease ≤50%) and adjustment of SCS stimulation intensity.

Background: The resection of a motor-eloquent glioma should be guided by intraoperative neurophysiological monitoring (IOM) but its interpretation is often difficult and may (unnecessarily) lead to subtotal resection. Navigated transcranial magnetic stimulation (nTMS) combined with diffusion-tensor-imaging (DTI) is able to stratify patients with motor-eloquent lesion preoperatively into high- and low-risk cases with respect to a new motor deficit. Objective: To analyze to what extent preoperative nTMS motor risk stratification can improve the interpretation of IOM phenomena. Methods: In this monocentric observational study, nTMS motor mapping with DTI fiber tracking of the corticospinal tract was performed before IOM-guided surgery for motor-eloquent gliomas in a prospectively collected cohort from January 2017 to October 2020. Descriptive analyses were performed considering nTMS data (motor cortex infiltration, resting motor threshold (RMT), motor evoked potential (MEP) amplitude, latency) and IOM data (transcranial MEP monitoring, intensity of monopolar subcortical stimulation (SCS), somatosensory evoked potentials) to examine the association with the postoperative motor outcome (assessed at day of discharge and at 3 months). Results: Thirty-seven (56.1%) of 66 patients (27 female) with a median age of 48 years had tumors located in the right hemisphere, with glioblastoma being the most common diagnosis with 39 cases (59.1%). Three patients (4.9%) had a new motor deficit that recovered partially within 3 months and 6 patients had a persistent deterioration (9.8%). The more risk factors of the nTMS risk stratification model (motor cortex infiltration, tumor-tract distance (TTD) ≤8mm, RMTratio <90%/>110%) were detected, the higher was the risk for developing a new postoperative motor deficit, whereas no patient with a TTD >8mm deteriorated. Irreversible MEP amplitude decrease >50% was associated with worse motor outcome in all patients, while a MEP amplitude decrease ≤50% or lower SCS intensities ≤4mA were particularly correlated with a postoperative worsened motor status in nTMS-stratified high-risk cases. No patient had postoperative deterioration of motor function (except one with partial recovery) when intraoperative MEPs remained stable or showed only reversible alterations. Conclusions: The preoperative nTMS-based risk assessment can help to interpret ambiguous IOM phenomena (such as irreversible MEP amplitude decrease ≤50%) and adjustment of SCS stimulation intensity. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme remains a therapeutic challenge. We offer a historical review of the outcomes of patients with glioblastoma from the earliest report of surgery for this lesion through the introduction of modern chemotherapeutics and aggressive approaches to tumor resection. We reviewed all major surgical series of patients with glioblastoma from the introduction of craniotomy for glioma (1884) to 2020. The earliest reported craniotomy for glioblastoma resulted in the patient's death less than a month after surgery. Improved intracranial pressure management resulted in improved outcomes, reducing early postoperative mortality from 50% to 6% in Harvey Cushing's series. In the first major surgical series (1912), the mean survival was 10.1 months. This figure did not improve until the introduction of radiotherapy in the 1950s, which doubled survival relative to those who had surgery alone. The most recent significant advance, chemotherapy with the alkylating agent temozolomide, extended survival by 2.5 months compared with surgery and radiotherapy alone (14.6 and 12.1 months, respectively). This protocol remains the standard regimen for newly diagnosed glioblastoma. The innovative treatments being investigated have yet to show a survival benefit. With advancements in localization, imaging, anesthesia, surgical technique, control of cerebral edema, and adjuvant therapies, outcomes in glioblastoma improved incrementally from Cushing's time until the introduction of magnetic resonance imaging enabled better degrees of resection in the 1990s. Modest improvements came with the advent of biomarker-driven targeted chemotherapy in the first decade of the current century. [ABSTRACT FROM AUTHOR]

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported.Case Report: A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome.Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery.

Background: Maximum safe resection of infiltrative brain tumors in eloquent area is the primary objective in surgical neuro-oncology. This goal can be achieved with direct electrical stimulation (DES) to perform a functional mapping of the brain in patients awake intraoperatively. When awake surgery is not possible, we propose a pipeline procedure that combines advanced techniques aiming at performing a dissection that respects the anatomo-functional connectivity of the peritumoral region. This procedure can benefit from intraoperative monitoring with computerized tomography scan (iCT-scan) and brain shift correction. Associated with this intraoperative monitoring, the additional value of preoperative investigation combining brain mapping by navigated transcranial magnetic stimulation (nTMS) with various neuroimaging modalities (tractography and resting state functional MRI) has not yet been reported. Case Report: A 42-year-old left-handed man had increased intracranial pressure (IICP), left hand muscle deficit, and dysarthria, related to an infiltrative tumor of the right frontal lobe with large mass effect and circumscribed contrast enhancement in motor and premotor cortical areas. Spectroscopy profile and intratumoral calcifications on CT-scan suggested an WHO grade III glioma, later confirmed by histology. The aforementioned surgical procedure was considered, since standard awake surgery was not appropriate for this patient. In preoperative time, nTMS mapping of motor function (deltoid, first interosseous, and tibialis anterior muscles) was performed, combined with magnetic resonance imaging (MRI)-based tractography reconstruction of 6 neural tracts (arcuate, corticospinal, inferior fronto-occipital, uncinate and superior and inferior longitudinal fasciculi) and resting-state functional MRI connectivity (rs-fMRI) of sensorimotor and language networks. In intraoperative time, DES mapping was performed with motor evoked response recording and tumor resection was optimized using non-rigid image transformation of the preoperative data (nTMS, tractography, and rs-fMRI) to iCT data. Image guidance was updated with correction for brain shift and tissue deformation using biomechanical modeling taking into account brain elastic properties. This correction was done at crucial surgical steps, i.e., when tumor bulged through the craniotomy after dura mater opening and when approaching the presumed eloquent brain regions. This procedure allowed a total resection of the tumor region with contrast enhancement as well as a complete regression of IICP and dysarthria. Hand paresis remained stable with no additional deficit. Postoperative nTMS mapping confirmed the good functional outcome. Conclusion: This case report and technical note highlights the value of preoperative functional evaluation by nTMS updated intraoperatively with correction of brain deformation by iCT. This multimodal approach may become the optimized technique of reference for patients with brain tumors in eloquent areas that are unsuitable for awake brain surgery. [ABSTRACT FROM AUTHOR]

Objective: Language dominance in the developing brain can vary widely across anatomical and pathological conditions as well as age groups. Repetitive navigated transcranial magnetic stimulation (rnTMS) has been applied to calculate the hemispheric dominance ratio (HDR) in adults. In this study, the authors aimed to assess the feasibility of using rnTMS to identify language lateralization in a pediatric neurosurgical cohort and to correlate the preoperative rnTMS findings with the postoperative language outcome., Methods: A consecutive prospectively collected cohort of 19 children with language-associated lesions underwent bihemispheric rnTMS mapping prior to surgery (100 stimulation sites on each hemisphere). In addition to feasibility and adverse effects, the HDR (ratio of the left hemisphere to right hemisphere error rate) was calculated. The anatomical surgical site and postoperative language outcome at 3 months after surgery were assessed according to clinical documentation., Results: Repetitive nTMS mapping was feasible in all 19 children (mean age 12.5 years, range 4-17 years; 16 left-sided lesions) without any relevant adverse events. Thirteen children (68%) showed left hemispheric dominance (HDR > 1.1), and 2 children (11%) showed right hemispheric dominance (HDR < 0.9). In 4 children (21%), the bihemispheric error rates were nearly the same (HDR ≥ 0.9 and ≤ 1.1). Sixteen children underwent surgery (14 tumor/lesion resections and 2 hemispherotomies) and 3 patients continued conservative therapy. After surgery, 4 patients (25%) showed an improvement in language function, 10 (63%) presented with stable language function, and 2 (12.5%) experienced deterioration in language function. Of the 6 patients with right hemispheric language involvement, 4 (80%) had glial tumors, 1 (20%) had focal cortical dysplasia, and 1 (20%) experienced hypoxic brain injury. Children with right hemispheric language involvement (HDR ≤ 1.1) did not show any language deterioration postoperatively., Conclusions: Bihemispheric rnTMS language mapping as a noninvasive mapping technique to assess lateralization of language function in the pediatric neurosurgical population is safe and feasible. Why relevant right hemispheric language function (HDR ≤ 1.1) was associated with postoperative unaltered language function needs to be validated in future studies. Bihemispheric rnTMS language mapping strengthens risk-benefit considerations prior to pediatric tumor/epilepsy surgery in language-associated areas.

Aspirin is widely used for primary or secondary prevention of ischemic events. At the same time, chronic aspirin consumption can affect blood clot formation during surgical intervention and increase intraoperative blood loss . This is especially important for high-risk surgery, including neurosurgery. Current European Society of Cardiology guidelines recommend aspirin interruption for at least 7 d before neurosurgical intervention, but this suggestion is not supported by clinical evidence. This narrative review presents evidence that challenges the necessity for aspirin interruption in neurosurgical patients, describes options for aspirin effect monitoring and the clinical implication of these methods, and summarizes current clinical data on bleeding risk associated with chronic aspirin therapy in neurosurgical patients, including brain tumor surgery, cerebrovascular procedures, and spinal surgery., Competing Interests: Conflict-of-interest statement: The authors declare having no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The principal aim of neurointensive care in patients with intracranial tumor surgery is prevention, prediction, early detection, and the prompt treatment of postoperative complications. Maintenance of proper hemodynamic and adequate respiratory support is necessary to prevent postoperative mass effect due to cerebral edema, hydrocephalus, hematoma, and infarct causing cerebral herniation syndromes. Invasive blood pressure monitoring is usually recommended along with measuring intracranial pressure to allow the proper evaluation of cerebral perfusion pressure and an effective cerebral blood flow. For the effective neurocritical intensive care of surgical patients with brain tumors, good harmony, interaction, and communication between the neurosurgeon and the neurointensive team is of paramount importance.

Background: With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. Methods: We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients' professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. Results: We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p <.001). Multivariable regression analysis showed that patient age < 40 years as well as occupational group and self-reported fatigue were factors independently associated with the ability to return to work. Conclusion: The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life. [ABSTRACT FROM AUTHOR]

Guidelines on the administration of prophylactic antiepileptic drugs (AED), and specifically levetiracetam, for brain tumor surgery are still lacking. In this two-center matched cohort study, we aim to compare the proportion of postoperative seizures during follow-up after supratentorial tumor surgery in patients receiving no seizure prophylaxis, and those treated with levetiracetam perioperatively. Three hundred sixteen consecutive patients undergoing supratentorial tumor surgery, without history of seizures were included: 207 patients did not receive AED (no AED group), and 109 patients received levetiracetam perioperatively (levetiracetam group). The primary outcome measure was the rate of postoperative seizures. Additionally, uni- and multivariate analyses assessing possible risk factors for postoperative seizures were performed. No statistically significant difference for the occurrence of postoperative seizures was found between the two groups (10.1%, n = 21 in the no AED group vs. 9.2%, n = 10, in the levetiracetam group; p = 0.69, OR 0.9 [0.4–2.0), NNT 103 [12.9–17.1]). After propensity score matching, the primary outcome was observed in 13 patients (12.4%) from the no AED group and in 9 patients (8.6%) from the levetiracetam group (p = 0.50, OR 0.7 [0.3–1.6], NNT 26.3 [8.3–22.4]). Among all analyzed possible risk factors for postoperative seizures, only postoperative infarction showed a statistically significant association with higher seizure rates in multivariate analysis (OR 8.2 [1.1–60.6], p = 0.04). Prophylactic treatment with levetiracetam after brain tumor surgery showed no statistically significant effect in preventing postoperative seizures. However, in case a postoperative infarction occurs, its administration might be indicated. [ABSTRACT FROM AUTHOR]

Objective: Among imaging modalities, ultrasonography (US) is one of the most versatile choice, with its low cost, lack of radiation exposure, and minimally disrupted surgery flow. We described the use and characteristics of intraoperative ultrasonography (US) in selected cases in our center to assist the intracranial tumor resection. Methods : Seventy patients were operated from 2011 to 2018 at Kariadi Hospital with the help of intraoperative US. Fifty six percents of cases were cystic tumors, 25% were abscess and 19% were metastatic tumors We used seven parameters to measure the utility of intraoperative US and a utility score was devised (0 minimum, 7 maximum). Results: The utility score for intraoperative US was 7 in 3 cases (4%), 6 in 28 cases (54%), 5 in 21 cases (31%), 4 in 8 cases (11%), while no case had score ≤3. Conclusion: Intraoperative US is not only helpful in localizing lesions but also it can be used in determining the morphology of the lesion for some cases, which was glioma in our case. Intraoperative US is also helpful when to start planning the site of entry and complete resection. [ABSTRACT FROM AUTHOR]

We describe frontal language reorganization in a 50–60 year-old right-handed patient with a low-grade left frontotemporal insular glioma. Pre-operative fMRI revealed robust activation in the left superior temporal gyrus (Wernicke Area, WA) and in the right inferior frontal gyrus (right anatomical homolog of Broca Area, BA). Intra-operative cortical stimulation of the left inferior frontal gyrus and adjacent cortices elicited no speech deficits, and gross total resection including the expected location of BA resulted in no speech impairment. We employed statistical inference methods to reconstruct the functional brain network and determined how different brain areas connect with one another. We found that the right homolog of the BA in this patient functionally connected to the same areas as the left BA in a typical healthy control. As opposed to the functional connection of the left BA in a healthy brain, the right BA did not connect directly with the left WA, but connected indirectly, mediated by the pre-Supplementary Motor Area and the Middle Frontal Gyrus. This case illustrates that pre-surgical fMRI may be used to identify atypical hemispheric language reorganization in the presence of brain tumor and that network theory opens the possibility for future insight into the neural mechanism underlying the language reorganization.

Elderly patients with surgically accessible brain tumors are often not offered clinically indicated brain tumor surgery (BTS) because of to assumptions of greater risk for perioperative morbidity and mortality. Because brain tumor incidence is highest in the geriatric population, and because the global population is aging, accurate understanding of BTS risk in elderly patients is critical. We aimed to compare safety of BTS in elderly patients with younger counterparts to better understand the risk–benefit profile of BTS for elderly patients. Retrospective cohort study of young (20–29 years), senior (60–79 years), and elderly (80+ years) patients who underwent BTS with a single neurosurgeon. Differences between pre- and postoperative modified Rankin score (ΔmRS), length of hospitalization (LOH), complication rate, and 30-day readmission rates (30DRR) were recorded. A total of 741 patients (83 elderly, 570 senior, and 88 young) were identified. No significant difference in preoperative mRS between different age groups, χ2 = 0.269, P = 0.874. Elderly complication rate was 6.0%, not significantly different from young (4.5%, P = 0.667) or senior (7.2%, P = 0.696) complication rate. Elderly LOH was 1.93 ± SD 0.176 days; not significantly different from young (3.01 ± 0.384 days, P = 0.081) or senior (2.47 ± 0.144 days, P = 0.881). Statistical equivalence testing showed with 95% confidence that there was equivalence in ΔmRS among age groups. Elderly patients did not have significantly different ΔmRS, LOH, 30DRR, or complication rates after BTS compared with younger counterparts. Therefore, in healthy patients, advanced age alone should not prevent patients from being offered BTS. [ABSTRACT FROM AUTHOR]

Background: Besides 5-aminolevulinic acid (5-ALA), liver enzyme elevation after brain tumor surgery can be caused by anesthesia and medications. In this retrospective study, we determined whether preoperative 5-ALA administration is associated with postoperative elevation of liver enzymes (PELE) in brain tumor patients and identified predictive factors for PELE in patients treated with 5-ALA. Methods: In 179 patients undergoing brain tumor surgery with preoperative normal values of liver enzymes, laboratory data on serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (T.bil) levels were collected preoperatively and through postoperative day (POD) 45. Results: Ninety-nine PELEs (ALT, 56; AST, 34; ALP, 5; and TB, 4) were observed in 62 (34.6%) patients. Four (4.2%) patients treated with 5-ALA showed grade 3 elevation of transaminases based on the Common Terminology Criteria for Adverse Effects. Preoperative 5-ALA treatment was predictive of PELE (odds ratio [95% confidence interval], 2.30 [1.14–4.67]; P = 0.021). In patients treated with 5-ALA (n = 95), 70 PELEs (ALT, 39; AST, 22; ALP, 5; and TB, 4) were observed in 41 (43.2%) patients and significant predictive factors for PELE were preoperative ALT level (1.10 [1.04–1.17]; P = 0.001) and body mass index (BMI, 1.29 [1.08–1.56]; P = 0.006). In patients treated with 5-ALA, 13 and 36 patients, of 39 patients whose maximum postoperative ALT levels > 40 U/L, showed the normal value of serum ALT on PODs 14 and 45, respectively. Only three patients showed ALT elevation > 40 U/L on PODs 15–45, with a downward trend. Conclusions: The use of 5-ALA for brain tumor surgery in patients with preoperative normal values of liver enzymes was associated with increased transient PELE, but a low incidence of severely elevated liver transaminases levels. When 5-ALA is administered to patients with the upper normal value of preoperative serum ALT and overweight, attention is paid to PELE. [ABSTRACT FROM AUTHOR]

To determine the effect of vitamin D supplementation on postoperative pain and analgesic requirement in brain tumor surgery. A total of 60 patients with vitamin D serum levels ≤20 ng/dL were randomly assigned to 2 groups equally. The study group (n = 30) received intramuscular injection of 300,000 IU vitamin D before surgery. Preoperative serum level of vitamin D was 15.9 ± 3.8 ng/dL and 14.5 ± 3.6 ng/dL in the study and control groups, respectively (P = 0.13). Serum level of vitamin D on day 5 of surgery was 22.5 ± 4.3 and 13.7 ± 3.8 in the study and control groups, respectively (P < 0.001). A percentage of 50% had pain scores >4 on the first postoperative day, which decreased with time. The median (interquartile range) of the visual analogue scale score during the 3 postoperative days was 3 (5), 3 (5), 1 (3), and 5 (7), 2 (5), 1 (3) in the study and control groups, respectively, with no significant difference. There was no difference in analgesic consumption between the 2 groups. Analysis through the generalized estimating equation model indicated that patients who had received vitamin D for a longer time before the operative time had an insignificantly less pain score. On the basis of the study results, one half of our patients reported moderate-to-severe pain scores on the first day after surgery. The pain in the study group was insignificantly less than that in the control group, but it seems that chronic high level of vitamin D may lead to promising results. [ABSTRACT FROM AUTHOR]

Objective: Feasibility and value of non-invasive transcranial magnetic brain stimulation (TMS MAGVENTURE® MagPro R30 Denmark) for preoperative diagnosis and surgical planning of brain tumor operations in everyday clinical practice. Methods: A prospective monocentric study was conducted, which included preoperative neurological and electrophysiological examination, TMS, and display of functional data in the navigation system (LOCALITE® TMS Navigator Germany). During surgery, the TMS data were correlated with the intraoperative monitoring (IOM). Twenty-four hours to 96 h and after at least 3 months, follow-ups with neurological, electrophysiological examinations and TMS stimulation were performed. Results: Twenty-five patients with tumors in or near by the primary motor cortex region were included in the study. Twenty-one patients completed preoperative and first postoperative TMS and the neurological examination. Eight of 21 patients showed slight worsening of primary motor cortex function, 8 patients had an unchanged state, and 4 patients showed an improvement early after surgery. The changes of the electrophysiological examination like significant delay of the latency and/or reduced amplitudes matched well with the postoperative neurological outcome: if patients showed a worsening of the SEP's and MEP's, the postoperative results revealed deterioration. Conclusion: A preoperatively performed TMS using the MAGVENTURE® MagPro R30 and the LOCALITE® TMS Navigator could be established in our clinical daily practice and allowed a safe and reliable mapping of the primary motor cortex in order to minimize the risk of postoperative neurological deficits and improve the neurological outcome of the patients. [ABSTRACT FROM AUTHOR]

Background: Prolonged seizures generate cerebral hypoxia and increased intracranial pressure, resulting in an increased risk of neurological deterioration, increased long-term morbidity, and shorter survival. Seizures should be recognized early and treated promptly. The aim of the study was to investigate the occurrence of postoperative seizures in patients undergoing craniotomy for primary brain tumors and to determine if non-convulsive seizures could explain some of the postoperative neurological deterioration that may occur after surgery. Methods: A single-center prospective study of 100 patients with suspected glioma. Participants were studied with EEG and video recording for at least 24 h after surgery. Results: Seven patients (7%) displayed seizure activity on EEG recording within 24 h after surgery and another two patients (2%) developed late seizures. One of the patients with early seizures also developed late seizures. In five patients (5%), there were non-convulsive seizures. Four of these patients had a combination of clinically overt and non-convulsive seizures and in one patient, all seizures were non-convulsive. The non-convulsive seizures accounted for the majority of total seizure time in those patients. Non-convulsive seizures could not explain six cases of unexpected postoperative neurological deterioration. Postoperative ischemic lesions were more common in patients with early postoperative seizures. Conclusions: Early seizures, including non-convulsive, occurred in 7% of our patients. Within this group, non-convulsive seizure activity had longer durations than clinically overt seizures, but only 1% of patients had exclusively non-convulsive seizures. Seizures were not associated with unexpected neurological deterioration. [ABSTRACT FROM AUTHOR]