Pseudoprogression versus true progression in glioblastoma: what neurosurgeons need to know

J Neurosurg 139:748–759, 2023

Management of patients with glioblastoma (GBM) is complex and involves implementing standard therapies including resection, radiation therapy, and chemotherapy, as well as novel immunotherapies and targeted small-molecule inhibitors through clinical trials and precision medicine approaches. As treatments have advanced, the radiological and clinical assessment of patients with GBM has become even more challenging and nuanced.

Advances in spatial resolution and both anatomical and physiological information that can be derived from MRI have greatly improved the noninvasive assessment of GBM before, during, and after therapy.

Identification of pseudoprogression (PsP), defined as changes concerning for tumor progression that are, in fact, transient and related to treatment response, is critical for successful patient management. These temporary changes can produce new clinical symptoms due to mass effect and edema. Differentiating this entity from true tumor progression is a major decision point in the patient’s management and prognosis.

Providers may choose to start an alternative therapy, transition to a clinical trial, consider repeat resection, or continue with the current therapy in hopes of resolution. In this review, the authors describe the invasive and noninvasive techniques neurosurgeons need to be aware of to identify PsP and facilitate surgical decision-making.

Application of Intraoperative Rapid Molecular Diagnosis in Precision Surgery for Glioma: Mimic the World Health Organization CNS5 Integrated Diagnosis

Neurosurgery 92:762–771, 2023

With the advent of the molecular era, the diagnosis and treatment systems of glioma have also changed. A single histological type cannot be used for prognosis grade. Only by combining molecular diagnosis can precision medicine be realized.

OBJECTIVE: To develop an automatic integrated gene detection system (AIGS) for intraoperative detection in glioma and to explore its positive role in intraoperative diagnosis and treatment.

METHODS: We analyzed the isocitrate dehydrogenase 1 (IDH1) mutation status of 105 glioma samples and evaluated the product’s potential value for diagnosis; 37 glioma samples were detected intraoperatively to evaluate the feasibility of using the product in an actual situation. A blinding method was used to evaluate the effect of the detection technology on the accuracy of intraoperative histopathological diagnosis by pathologists. We also reviewed the current research status in the field of intraoperative molecular diagnosis.

RESULTS: Compared with next-generation sequencing, the accuracy of AIGS in detecting IDH1 was 100% for 105 samples and 37 intraoperative samples. The blind diagnostic results were compared between the 2 groups, and the molecular information provided by AIGS increased the intraoperative diagnostic accuracy of glioma by 16.2%. Using the technical advantages of multipoint synchronous detection, we determined the tumor molecular margins for 5 IDH-positive patients and achieved accurate resection at the molecular level. CONCLUSION: AIGS can quickly and accurately provide molecular information during surgery. This methodology not only improves the accuracy of intraoperative pathological diagnosis but also provides an important molecular basis for determining tumor margins to facilitate precision surgery.

Occurrence, Risk Factors, and Consequences of Postoperative Ischemia After Glioma Resection

Neurosurgery 92:125–136, 2023

Postoperative ischemia can lead to neurological deficits and is a known complication of glioma resection. There is inconsistency in documented incidence of ischemia after glioma resection, and the precise cause of ischemia is often unknown.

OBJECTIVE: To assess the incidence of postoperative ischemia and neurological deficits after glioma resection and to evaluate their association with potential risk factors.

METHODS: One hundred thirty-nine patients with 144 surgeries between January 2012 and September 2014 for World Health Organization (WHO) 2016 grade II-IV diffuse supratentorial gliomas with postoperative MRI within 72 hours were retrospectively included. Patient, tumor, and perioperative data were extracted from the electronic patient records. Occurrence of postoperative confluent ischemia, defined as new confluent areas of diffusion restriction, and new or worsened neurological deficits were analyzed univariably and multivariably using logistic regression models.

RESULTS: Postoperative confluent ischemia was found in 64.6% of the cases. Occurrence of confluent ischemia was associated with an insular location (P = .042) and intraoperative administration of vasopressors (P = .024) in multivariable analysis. Glioma location in the temporal lobe was related to an absence of confluent ischemia (P = .01). Any new or worsened neurological deficits occurred in 30.6% and 20.9% at discharge from the hospital and at first follow-up, respectively. Occurrence of ischemia was significantly associated with the presence of novel neurological deficits at discharge (P = .013) and after 3 months (P = .024).

CONCLUSION: Postoperative ischemia and neurological deficit were significantly correlated. Intraoperative administration of vasopressors, insular glioma involvement, and absence of temporal lobe involvement were significantly associated with postoperative ischemia.

Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas

J Neurosurg 137:1015–1025, 2022

Many neurosurgeons resect nonenhancing low-grade gliomas (LGGs) by using an inside-out piecemeal resection (PMR) technique. At the authors’ institution they have increasingly used a circumferential, perilesional, sulcusguided resection (SGR) technique. This technique has not been well described and there are limited data on its effectiveness. The authors describe the SGR technique and assess the extent to which SGR correlates with extent of resection and neurological outcome.

METHODS The authors identified all patients with newly diagnosed LGGs who underwent resection at their institution over a 22-year period. Demographics, presenting symptoms, intraoperative data, method of resection (SGR or PMR), volumetric imaging data, and postoperative outcomes were obtained. Univariate analyses used ANOVA and Fisher’s exact test. Multivariate analyses were performed using multivariate logistic regression.

RESULTS Newly diagnosed LGGs were resected in 519 patients, 208 (40%) using an SGR technique and 311 (60%) using a PMR technique. The median extent of resection in the SGR group was 84%, compared with 77% in the PMR group (p = 0.019). In multivariate analysis, SGR was independently associated with a higher rate of complete (100%) resection (27% vs 18%) (OR 1.7, 95% CI 1.1–2.6; p = 0.03). SGR was also associated with a statistical trend toward lower rates of postoperative neurological complications (11% vs 16%, p = 0.09). A subset analysis of tumors located specifically in eloquent brain demonstrated SGR to be as safe as PMR.

CONCLUSIONS The authors describe the SGR technique used to resect LGGs and show that SGR is independently associated with statistically significantly higher rates of complete resection, without an increase in neurological complications, than with PMR. SGR technique should be considered when resecting LGGs.

Functional outcomes after resection of middle frontal gyrus diffuse gliomas

J Neurosurg 137:1–8, 2022

The clinical outcomes for patients undergoing resection of diffuse glioma within the middle frontal gyrus (MFG) are understudied. Anatomically, the MFG is richly interconnected to known language areas, and nearby subcortical fibers are at risk during resection. The goal of this study was to determine the functional outcomes and intraoperative mapping results related to resection of MFG gliomas. Additionally, the study aimed to evaluate if subcortical tract disruption on imaging correlated with functional outcomes.

METHODS The authors performed a retrospective review of 39 patients with WHO grade II–IV diffuse gliomas restricted to only the MFG and underlying subcortical region that were treated with resection and had no prior treatment. Intraoperative mapping results and postoperative neurological deficits by discharge and 90 days were assessed. Diffusion tensor imaging (DTI) tractography was used to assess subcortical tract integrity on pre- and postoperative imaging.

RESULTS The mean age of the cohort was 37.9 years at surgery, and the median follow-up was 5.1 years. The mean extent of resection was 98.9% for the cohort. Of the 39 tumors, 24 were left sided (61.5%). Thirty-six patients (92.3%) underwent intraoperative mapping, with 59% of patients undergoing an awake craniotomy. No patients had positive cortical mapping sites overlying the tumor, and 12 patients (33.3%) had positive subcortical stimulation sites. By discharge, 8 patients had language dysfunction, and 5 patients had mild weakness. By 90 days, 2 patients (5.1%) had persistent mild hand weakness only. There were no persistent language deficits by 90 days. On univariate analysis, preoperative tumor size (p = 0.0001), positive subcortical mapping (p = 0.03), preoperative tumor invasion of neighboring subcortical tracts on DTI tractography (p = 0.0003), and resection cavity interruption of subcortical tracts on DTI tractography (p < 0.0001) were associated with an increased risk of having a postoperative deficit by discharge. There were no instances of complete subcortical tract transections in the cohort.

CONCLUSIONS MFG diffuse gliomas may undergo extensive resection with minimal risk for long-term morbidity. Partial subcortical tract interruption may lead to transient but not permanent deficits. Subcortical mapping is essential to reduce permanent morbidity during resection of MFG tumors by avoiding complete transection of critical subcortical tracts.


Supraorbital and mini-pterional keyhole craniotomies for brain tumors

J Neurosurg 136:1314–1324, 2022

The authors’ objective was to compare the indications, outcomes, and anatomical limits of supraorbital (SO) and mini-pterional (MP) craniotomies in patients with intra- and extraaxial brain tumors, and to assess approach selection, utility of endoscopy, and surgical field overlap.

METHODS A retrospective analysis was conducted of all brain tumor patients who underwent an SO or MP approach. The analyzed characteristics included pathology, endoscopy use, extent of resection, length of stay (LOS), and complications. On the basis of preoperative MRI data, tumor heatmaps were constructed to compare surgical access provided by both routes, including coronal projection heatmaps for parasellar tumors.

RESULTS From 2007 to 2020, 158 patients underwent 173 (84.8%) SO craniotomies and 30 patients underwent 31 (15.2%) MP craniotomies; 71 (34.8%) procedures were reoperations. Of these 204 operations, 110 (63.6%) SO and 21 (67.7%) MP approaches were for extraaxial tumors (meningiomas in 65% and 76.2%, respectively). Gliomas and metastases together represented 84.1% and 70% of intraaxial tumors accessed with SO and MP approaches, respectively. Overall, 56.1% of tumors accessed with the SO approach and 41.9% of those accessed with the MP approach were in the parasellar region. Axial projection heatmaps showed that SO access extended along the entire ipsilateral and medial contralateral anterior cranial fossa, parasellar region, ipsilateral sylvian fissure, medial middle cranial fossa, and anterior midbrain, whereas MP access was limited to the ipsilateral middle cranial fossa, sylvian fissure, lateral parasellar region, and posterior aspect of anterior cranial fossa. Coronal projection heatmaps showed that parasellar access extended further superiorly with the SO approach compared with that of the MP approach. Endoscopy was utilized in 98 (56.6%) SO craniotomies and 7 (22.6%) MP craniotomies, with further tumor resection in 48 (49%) and 5 (71.4%) cases, respectively. Endoscope-assisted tumor removal was clustered in areas that were generally at farther distances from the craniotomy or in angled locations such as the cribriform plate region where microscopic visualization is limited. Gross-total or neartotal resection was achieved in 120/173 (69%) SO approaches and 21/31 (68%) MP approaches. Major complications occurred in 11 (6.4%) SO approaches and 1 (3.2%) MP approach (p = 0.49). The median LOS decreased to 2 days in the last 2 years of the study.

CONCLUSIONS This clinical experience suggests the SO and MP craniotomies are versatile, safe, and complementary approaches for tumors located in the anterior and middle cranial fossae and perisylvian and parasellar regions. The SO route, used in 85% of cases, achieved greater overall reach than the MP route. Both approaches may benefit from expanded visualization with endoscopy.


Resection of supplementary motor area gliomas: revisiting supplementary motor syndrome and the role of the frontal aslant tract

J Neurosurg 136:1278–1284, 2022

The supplementary motor area (SMA) is an eloquent region that is frequently a site for glioma, or the region is included in the resection trajectory to deeper lesions. Although the clinical relevance of SMA syndrome has been well described, it is still difficult to predict who will become symptomatic. The object of this study was to define which patients with SMA gliomas would go on to develop a postoperative SMA syndrome.

METHODS The University of California, San Francisco, tumor registry was searched for patients who, between 2010 and 2019, had undergone resection for newly diagnosed supratentorial diffuse glioma (WHO grades II–IV) performed by the senior author and who had at least 3 months of follow-up. Pre- and postoperative MRI studies were reviewed to confirm the tumor was located in the SMA region, and the extent of SMA resection was determined by volumetric assessment. Patient, tumor, and outcome data were collected retrospectively from documents available in the electronic medical record. Tumors were registered to a standard brain atlas to create a frequency heatmap of tumor volumes and resection cavities.

RESULTS During the study period, 56 patients (64.3% male, 35.7% female) underwent resection of a newly diagnosed glioma in the SMA region. Postoperatively, 60.7% developed an SMA syndrome. Although the volume of tumor within the SMA region did not correlate with the development of SMA syndrome, patients with the syndrome had larger resection cavities in the SMA region (25.4% vs 14.2% SMA resection, p = 0.039). The size of the resection cavity in the SMA region did not correlate with the severity of the SMA syndrome. Patients who developed the syndrome had cavities that were located more posteriorly in the SMA region and in the cingulate gyrus. When the frontal aslant tract (FAT) was preserved, 50% of patients developed the SMA syndrome postoperatively, whereas 100% of the patients with disruption of the FAT during surgery developed the SMA syndrome (p = 0.06). Patients with SMA syndrome had longer lengths of stay (5.6 vs 4.1 days, p = 0.027) and were more likely to be discharged to a rehabilitation facility (41.9% vs 0%, p < 0.001). There was no difference in overall survival for newly diagnosed glioblastoma patients with SMA syndrome compared to those without SMA syndrome (1.6 vs 3.0 years, p = 0.33).

CONCLUSIONS For patients with SMA glioma, more extensive resections and resections involving the posterior SMA region and posterior cingulate gyrus increased the likelihood of a postoperative SMA syndrome. Although SMA syndrome occurred in all cases in which the FAT was resected, FAT preservation does not reliably avoid SMA syndrome postoperatively.


Awake craniotomy with transcortical motor evoked potential monitoring for resection of gliomas within or close to motor-related areas

J Neurosurg 136:1052–1061, 2022

The authors previously showed that combined evaluation of changes in intraoperative voluntary movement (IVM) during awake craniotomy and transcortical motor evoked potentials (MEPs) was useful for predicting postoperative motor function in 30 patients with precentral gyrus glioma. However, the validity of the previous report is limited to precentral gyrus gliomas. Therefore, the current study aimed to validate whether the combined findings of IVM during awake craniotomy and transcortical MEPs were useful for predicting postoperative motor function of patients with a glioma within or close to motor-related areas and not limited to the precentral gyrus.

METHODS The authors included 95 patients with gliomas within or close to motor-related areas who were treated between April 2000 and May 2020. All tumors were resected with IVM monitoring during awake craniotomy and transcortical MEP monitoring. Postoperative motor function was classified into four categories: “no change” or “declined,” the latter of which was further categorization as “mild,” “moderate,” or “severe.” The authors defined moderate and severe deficits as those that impact daily life.

RESULTS Motor function 6 months after surgery was classified as no change in 71 patients, mild in 18, moderate in 5, and severe in 1. Motor function at 6 months after surgery significantly correlated with IVM (p < 0.0001), transcortical MEPs (decline ≤ or > 50%) (p < 0.0001), age, preoperative motor dysfunction, extent of resection, and ischemic change on postoperative MRI. Thirty-two patients with no change in IVM showed no change in motor function at 6 months after surgery. Five of 34 patients (15%) with a decline in IVM and a decline in MEPs ≤ 50% had motor dysfunction with mild deficits 6 months after surgery. Furthermore, 19 of 23 patients (83%) with a decline in IVM and decline in MEPs > 50% had a decline in motor function, including 13 patients with mild, 5 with moderate, and 1 with severe deficits. Six patients with moderate or severe deficits had the lowest MEP values, at < 100 μV.

CONCLUSIONS This study validated the utility of combined application of IVM during awake craniotomy and transcortical MEP monitoring to predict motor function at 6 months after surgery in patients with a glioma within or close to motorrelated areas, not limited to the precentral gyrus. The authors also validated the usefulness of the cutoff value, 100 μV, in MEP monitoring.

Pretreatment patient‐reported cognitive function in patients with diffuse glioma

Acta Neurochirurgica (2022) 164:703–711

Cognitive function is frequently assessed with objective neuropsychological tests, but patient-reported cognitive function is less explored. We aimed to investigate the preoperative prevalence of patient-reported cognitive impairment in patients with diffuse glioma compared to a matched reference group and explore associated factors.

Methods We included 237 patients with diffuse glioma and 474 age- and gender-matched controls from the general population. Patient-reported cognitive function was measured using the cognitive function subscale in the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The transformed scale score (0–100) was dichotomized, with a score of ≤ 75 indicating clinically important patient-reported cognitive impairment. Factors associated with preoperative patient-reported cognitive impairment were explored in a multivariable regression analysis.

Results Cognitive impairment was reported by 49.8% of the diffuse glioma patients and by 23.4% in the age- and gendermatched reference group (p < 0.001). Patients with diffuse glioma had 3.2 times higher odds (95% CI 2.29, 4.58, p < 0.001) for patient-reported cognitive impairment compared to the matched reference group. In the multivariable analysis, large tumor volume, left tumor lateralization, and low Karnofsky Performance Status score were found to be independent predictors for preoperative patient-reported cognitive impairment.

Conclusions Our findings demonstrate that patient-reported cognitive impairment is a common symptom in patients with diffuse glioma pretreatment, especially in patients with large tumor volumes, left tumor lateralization, and low functional levels. Patient-reported cognitive function may provide important information about patients’ subjective cognitive health and disease status and may serve as a complement to or as a screening variable for subsequent objective testing.

Impact of awake mapping on overall survival and extent of resection in patients with adult diffuse gliomas within or near eloquent areas

Acta Neurochirurgica (2022) 164:395–404

Awake craniotomy (AC) with intraoperative mapping is the best approach to preserve neurological function for glioma surgery in eloquent or near eloquent areas, but whether AC improves the extent of resection (EOR) and overall survival (OS) is controversial. This study aimed to compare the long-term clinical outcomes of glioma resection under AC with those under general anesthesia (GA).

Methods Data of 335 patients who underwent surgery with intraoperative magnetic resonance imaging for newly diagnosed gliomas of World Health Organization (WHO) grades II-IV between 2000 and 2013 were reviewed. EOR and OS were quantitatively compared between the AC and GA groups after 1:1 propensity score matching. The two groups were matched for age, preoperative Karnofsky performance status (KPS), tumor location, and pathology.

Results After propensity score matching, 91 pairs were obtained. The median EOR was 96.1% (interquartile range [IQR] 7.3) and 97.4% (IQR 14.4) in the AC and GA groups, respectively (p = 0.31). Median KPS score 3 months after surgery was 90 (IQR 20) in both groups (p = 0.384). The median survival times were 163.3 months (95% confidence interval [CI] 77.9–248.7) and 143.5 months (95% CI 94.4–192.7) in the AC and GA groups, respectively (p = 0.585).

Conclusion Even if the glioma was within or close to the eloquent area, AC was comparable with GA in terms of EOR and OS. In case of difficulties in randomizing patients with eloquent or near eloquent glioma, our propensity score-matched analysis provides retrospective evidence that AC can obtain EOR and OS equivalent to removing glioma under GA.

Asleep or awake motor mapping for resection of perirolandic glioma in the nondominant hemisphere?

J Neurosurg 136:16–29, 2022

Resection of glioma in the nondominant hemisphere involving the motor areas and pathways requires the use of brain-mapping techniques to spare essential sites subserving motor control. No clear indications are available for performing motor mapping under either awake or asleep conditions or for the best mapping paradigm (e.g., resting or active, high-frequency [HF] or low-frequency [LF] stimulation) that provides the best oncological and functional outcomes when tailored to the clinical context. This work aimed to identify clinical and imaging factors that influence surgical strategy (asleep motor mapping vs awake motor mapping) and that are associated with the best functional and oncological outcomes and to design a “motor mapping score” for guiding tumor resection in this area.

METHODS The authors evaluated a retrospective series of patients with nondominant-hemisphere glioma—located or infiltrating within 2 cm anteriorly or posteriorly to the central sulcus and affecting the primary motor cortex, its fibers, and/ or the praxis network—who underwent operations with asleep (HF monopolar probe) or awake (LF and HF probes) motor mapping. Clinical and imaging variables were used to design a motor mapping score. A prospective series of patients was used to validate this motor mapping score.

RESULTS One hundred thirty-five patients were retrospectively analyzed: 69 underwent operations with asleep (HF stimulation) motor mapping, and 66 underwent awake (LF and HF stimulation and praxis task evaluation) motor mapping. Previous motor (strength) deficit, previous treatment (surgery/radiotherapy), tumor volume > 30 cm3, and tumor involvement of the praxis network (on MRI) were identified and used to design the mapping score. Motor deficit, previous treatment, and location within or close to the central sulcus favor use of asleep motor mapping; large tumor volume and involvement of the praxis network favor use of awake motor mapping. The motor mapping score was validated in a prospective series of 52 patients—35 underwent operations with awake motor mapping and 17 with asleep motor mapping on the basis of the score indications—who had a low rate of postoperative motor-praxis deficit (3%) and a high extent of resection (median 97%; complete resection in > 70% of patients).

CONCLUSIONS Extensive resection of tumor involving the eloquent areas for motor control is feasible, and when an appropriate mapping strategy is applied, the incidence of postoperative motor-praxis deficit is low. Asleep (HF stimulation) motor mapping is preferable for lesions close to or involving the central sulcus and/or in patients with preoperative strength deficit and/or history of previous treatment. When a patient has no motor deficit or previous treatment and has a lesion (> 30 cm3) involving the praxis network, awake mapping is preferable.

Prevalence of incidental meningiomas and gliomas on MRI: a meta‐analysis and meta‐regression analysis

Acta Neurochirurgica (2021) 163:3401–3415

The chance of incidentally detecting brain tumors is increasing as the utilization of magnetic resonance imaging (MRI) becomes more prevalent. In this background, knowledge is accumulating in relation to the prediction of their clinical sequence. However, their prevalence—especially the prevalence of glioma—has not been adequately investigated according to age, sex, and region.

Method We systematically reviewed the articles according to the PRISMA statement and calculated the prevalence of meningiomas and diffuse gliomas in adults using a generalized linear mixed model. Specifically, the differences related to age, sex, and region were investigated.

Results The pooled prevalence of incidental meningiomas in MRI studies was 0.52% (95% confidence interval (CI) [0.34– 0.78]) in 37,697 individuals from 36 studies. A meta-regression analysis showed that the prevalence was significantly higher in elderly individuals, women, and individuals outside Asia; this remained statistically significant in the multivariate meta-regression analysis. The prevalence reached to 3% at 90 years of age. In contrast, the prevalence of gliomas in 30,918 individuals from 18 studies was 0.064% (95%CI [0.040 – 0.104]). The meta-regression analysis did not show a significant relationship between the prevalence and age, male sex, or region. The prevalence of histologically confirmed glioma was 0.026% (95%CI [0.013–0.052]).

Conclusions Most of meningiomas, especially those in elderlies, remained asymptomatic, and their prevalence increased with age. However, the prevalence of incidental gliomas was much lower and did not increase with age. The number of gliomas that developed and the number that reached a symptomatic stage appeared to be balanced.

Brain infarctions after glioma surgery

Acta Neurochirurgica (2021) 163:3097–3108

Prevalence, radiological characteristics, and risk factors for peritumoral infarctions after glioma surgery are not much studied. In this study, we assessed shape, volume, and prevalence of peritumoral infarctions and investigated pos- sible associated factors.

Methods In a prospective single-center cohort study, we included all adult patients operated for diffuse gliomas from January 2007 to December 2018. Postoperative infarctions were segmented using early postoperative MRI images, and volume, shape, and location of postoperative infarctions were assessed. Heatmaps of the distribution of tumors and infarctions were created.

Results MRIs from 238 (44%) of 539 operations showed restricted diffusion in relation to the operation cavity, interpreted as postoperative infarctions. Of these, 86 (36%) were rim-shaped, 103 (43%) were sector-shaped, 40 (17%) were a combination of rim- and sector-shaped, and six (3%) were remote infarctions. Median infarction volume was 1.7 cm3 (IQR 0.7–4.3, range 0.1–67.1). Infarctions were more common if the tumor was in the temporal lobe, and the map shows more infarctions in the periventricular watershed areas. Sector-shaped infarctions were more often seen in patients with known cerebrovascular dis- ease (47.6% vs. 25.5%, p = 0.024). There was a positive correlation between infarction volume and tumor volume (r = 0.267, p < 0.001) and infarction volume and perioperative bleeding (r = 0.176, p = 0.014). Moreover, there was a significant positive association between age and larger infarction volumes (r = 0.193, p = 0.003). Infarction rates and infarction volumes varied across individual surgeons, p = 0.037 (range 32–72%) and p = 0.026.

Conclusions In the present study, peritumoral infarctions occurred in 44% after diffuse glioma operations. Infarctions were more common in patients operated for tumors in the temporal lobe but were not more common following recurrent surgeries. Sector-shaped infarctions were more common in patients with known cerebrovascular disease. Increasing age, larger tumors, and more perioperative bleeding were factors associated with infarction volumes. The risk of infarctions and infarction volumes may also be surgeon-dependent.

Central Nervous System Plasticity Influences Language and Cognitive Recovery in Adult Glioma

Neurosurgery 89:539–548, 2021

Gliomas exist within the framework of complex neuronal circuitry in which network dynamics influence both tumor biology and cognition. The generalized impairment of cognition or loss of language function is a common occurrence for glioma patients.

The interface between intrinsic brain tumors such as gliomas and functional cognitive networks are poorly understood. The ability to communicate effectively is critically important for receiving oncological therapies and maintaining a high quality of life.

Although the propensity of gliomas to infiltrate cortical and subcortical structures and disrupt key anatomic language pathways is well documented, there is new evidence offering insight into the network and cellular mechanisms underpinning glioma-related aphasia and aphasia recovery.

In this review, we will outline the current understanding of the mechanisms of cognitive dysfunction and recovery, using aphasia as an illustrative model.

Machine Learning for the Prediction of Molecular Markers in Glioma on Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis

Neurosurgery 89:31–44, 2021

Molecular characterization of glioma has implications for prognosis, treatment planning, and prediction of treatment response. Current histopathology is limited by intratumoral heterogeneity and variability in detection methods. Advances in computational techniques have led to interest in mining quantitative imaging features to noninvasively detect genetic mutations.

OBJECTIVE: To evaluate the diagnostic accuracy of machine learning (ML) models in molecular subtyping gliomas on preoperative magnetic resonance imaging (MRI).

METHODS: A systematic search was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines to identify studies up to April 1, 2020. Methodological quality of studies was assessed using the Quality Assessment for Diagnostic Accuracy Studies (QUADAS)-2. Diagnostic performance estimates were obtained using a bivariate model and heterogeneity was explored using metaregression.

RESULTS: Forty-four original articles were included. The pooled sensitivity and specificity for predicting isocitrate dehydrogenase (IDH) mutation in training datasets were 0.88 (95% CI 0.83-0.91) and 0.86 (95% CI 0.79-0.91), respectively, and 0.83 to 0.85 in validation sets. Use of data augmentation and MRI sequence type were weakly associated with heterogeneity. Both O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation and 1p/19q codeletion could be predicted with a pooled sensitivity and specificity between 0.76 and 0.83 in training datasets.

CONCLUSION: ML application to preoperative MRI demonstrated promising results for predicting IDHmutation, MGMT methylation, and 1p/19q codeletion in glioma. Optimized ML models could lead to a noninvasive, objective tool that captures molecular information important for clinical decisionmaking. Future studies should use multicenter data, external validation and investigate clinical feasibility of ML models.

Stereotactic posterior midline approach under direct microscopic view for biopsy of medulla oblongata tumors: technical considerations

Acta Neurochirurgica (2021) 163:1965–1968

Open and stereotactic transfrontal or transcerebellar approaches have been used to biopsy brainstem lesions.

Method In this report, a stereotactic posterior and midline approach to the distal medulla oblongata under microscopic view is described. The potential advantages and limitations are discussed, especially bilateral damage of the X nerve nuclei.

Conclusion This approach should be considered for biopsy of distal and posterior lesions. We strongly recommend the use of direct microscopic view to identify the medullary vessels, confirm the midline entry point, and avoid potential shift of the medulla. Further experience is needed to confirm safety and success rate of this approach.

A Neurosurgeon’s Guide to Cognitive Dysfunction in Adult Glioma

Neurosurgery 89:1–10, 2021

Cognitive decline is common among patients with low- and high-grade glioma and can significantly impact quality of life. Although cognitive outcomes have been studied after therapeutic interventions such as surgery and radiation, it is important to understand the impact of the disease process itself prior to any interventions.

Neurocognitive domains of interest in this disease context include intellectual function and premorbid ability, executive function, learning and memory, attention, language function, processing speed, visuospatial function, motor function, and emotional function.

Here, we review oncologic factors associated with more neurocognitive impairment, key neurocognitive tasks relevant to glioma patient assessment, as well as the relevance of the human neural connectome in understanding cognitive dysfunction in glioma patients.

A contextual understanding of glioma-functional network disruption and its impact on cognition is critical in the surgical management of eloquent area tumors.

Triple motor mapping: transcranial, bipolar, and monopolar mapping for supratentorial glioma resection adjacent to motor pathways

J Neurosurg 134:1728–1737, 2021

Maximal safe resection of gliomas near motor pathways is facilitated by intraoperative mapping. The authors and other groups have described the use of bipolar or monopolar direct stimulation to identify functional tissue, as well as transcranial or transcortical motor evoked potentials (MEPs) to monitor motor pathways. Here, the authors describe their initial experience using all 3 modalities to identify, monitor, and preserve cortical and subcortical motor systems during glioma surgery.

METHODS Intraoperative mapping data were extracted from a prospective registry of glioma resections near motor pathways. Additional demographic, clinical, pathological, and imaging data were extracted from the electronic medical record. All patients with new or worsened postoperative motor deficits were followed for at least 6 months.

RESULTS Between January 2018 and August 2019, 59 operations were performed in 58 patients. Overall, patients in 6 cases (10.2%) had new or worse immediate postoperative deficits. Patients with temporary deficits all had at least Medical Research Council grade 4/5 power. Only 2 patients (3.4%) had permanently worsened deficits after 6 months, both of which were associated with diffusion restriction consistent with ischemia within the corticospinal tract. One patient’s deficit improved to 4/5 and the other to 4/5 proximally and 3/5 distally in the lower limb, allowing ambulation following rehabilitation. Subcortical motor pathways were identified in 51 cases (86.4%) with monopolar high-frequency stimulation, but only in 6 patients using bipolar stimulation. Transcranial or cortical MEPs were diminished in only 6 cases, 3 of which had new or worsened deficits, with 1 permanent deficit. Insula location (p = 0.001) and reduction in MEPs (p = 0.01) were the only univariate predictors of new or worsened postoperative deficits. Insula location was the only predictor of permanent deficits (p = 0.046). The median extent of resection was 98.0%.

CONCLUSIONS Asleep triple motor mapping is safe and resulted in a low rate of deficits without compromising the extent of resection.

Gravity-assisted endoscopic cingulate gyrus glioma resection

Acta Neurochirurgica (2021) 163:1323–1326

The cingulate gyrus is part of the limbic systemwith extensive connectivity to different anatomical and functional areas. The traditional transcortical approach for a cingulate gyrus glioma contains high risk of transient or even irreversible postoperative hemiplegia.

Method We present a case of gravity-assisted, fully endoscopic resection of a cingulate gyrus glioma with improvement of motor dysfunction while preserving the paracentral lobule, corticospinal tracts, and supplementary motor area.

Conclusion This case demonstrates the value of gravity-assisted endoscopic resection in the dominant cingulate gyrus tumor which is surrounded by eloquent parenchyma.

Mapping and anatomo-surgical techniques for SMA-cingulum-corpus callosum gliomas

Acta Neurochirurgica (2021) 163:1239–1246

Awake brain mapping paradigms are variable, particularly in SMA, and not personalised to each patient. In addition, subpial resections do not offer full protection to vascular injury, as the pia can be easily violated.

Methods Mapping paradigms developed by a multidisciplinary brain mapping team. During resection, a combined subpial/ interhemispheric approach allowed early identification and arterial skeletonization. Precise anatomo-surgical dissection of the affected cingulum and corpus callosum was achieved.

Conclusions In SMA-cingulum-CC tumours, a combined subpial/interhemispheric approach reduces risk of vascular injury allowing precise anatomo-surgical dissections. Knowledge of cognitive functions of affected parcels is likely to offer best outcomes.

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