Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?

J Neurosurg 140:357–366, 2024

Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration–cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied.

METHODS Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0–2) and a high tumor probability (HTP) group (scores 3–5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated.

RESULTS Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86–0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40–0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40–0.83]) and HTP group (0.68 [0.39–0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group.

CONCLUSIONS CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE.

Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

Confocal laser endomicroscopy in glial tumors—a histomorphological analysis

Neurosurgical Review (2024) 47:65

The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.

Material and methods One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.

Results All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).

Conclusion Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis

Neurosurgery 94:38–52, 2024

Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day).

RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD]= MD= 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30).

CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Microsurgical management of midbrain gliomas: surgical results and long-term outcome in a large, single-surgeon, consecutive series

J Neurosurg 140:104–115, 2024

The authors report on a large, consecutive, single-surgeon series of patients undergoing microsurgical removal of midbrain gliomas. Emphasis is put on surgical indications, technique, and results as well as long-term oncological follow-up.

METHODS A retrospective analysis was performed of prospectively collected data from a consecutive series of patients undergoing microneurosurgery for midbrain gliomas from March 2006 through June 2022 at the authors’ institution. According to the growth pattern and location of the lesion in the midbrain (tegmentum, central mesencephalic structures, and tectum), one of the following approaches was chosen: transsylvian (TS), extreme anterior interhemispheric transcallosal (eAIT), posterior interhemispheric transtentorial subsplenial (PITS), paramedian supracerebellar transtentorial (PST), perimedian supracerebellar (PeS), perimedian contralateral supracerebellar (PeCS), and transuvulotonsillar fissure (TUTF). Clinical and radiological data were gathered according to a standard protocol and reported according to common descriptive statistics. The main outcomes were rate of gross-total resection; extent of resection; occurrence of any complications; variation in Karnofsky Performance Status score at discharge, 3 months, and last follow-up; progression-free survival (PFS); and overall survival (OS).

RESULTS Fifty-four patients (28 of them pediatric) met the inclusion criteria (6 with high-grade and 48 with low-grade gliomas [LGGs]). Twenty-two tumors were in the tegmentum, 7 in the central mesencephalic structures, and 25 in the tectum. In no instance did the glioma originate in the cerebral peduncle. TS was performed in 2 patients, eAIT in 6, PITS in 23, PST in 16, PeS in 4, PeCS in 1, and TUTF in 2 patients. Gross-total resection was achieved in 39 patients (72%). The average extent of resection was 98.0% (median 100%, range 82%–100%). There were no deaths due to surgery. Nine patients experienced transient and 2 patients experienced permanent new neurological deficits. At a mean follow-up of 72 months (median 62, range 3–193 months), 49 of the 54 patients were still alive. All patients with LGGs (48/54) were alive with no decrease in their KPS score, whereas 42 showed improvement compared with their preoperative status.

CONCLUSIONS Microneurosurgical removal of midbrain gliomas is feasible with good surgical results and long-term clinical outcomes, particularly in patients with LGGs. As such, microneurosurgery should be considered as the first therapeutic option. Adequate microsurgical technique and anesthesiological management, along with an accurate preoperative understanding of the tumor’s exact topographic origin and growth pattern, is crucial for a good surgical outcome.

Unique molecular, clinical, and treatment aspects of gliomas in adolescents and young adults

J Neurosurg 139:1619–1627, 2023

Adolescent and young adult (AYA) patients with glioma have historically had poorer outcomes than similar patients of younger or older age, a disparity thought to be attributable to the social and economic challenges faced by this group in the transition from childhood to adult life, delays in diagnosis, low participation of AYA patients in clinical trials, and the lack of standardized treatment approaches specific to this patient group.

Recent work from many groups has informed a revision of the World Health Organization classification schema for gliomas to identify biologically divergent pediatric and adult-type tumors, both types of which may occur in AYA patients, and revealed exciting opportunities for the use of targeted therapies for many of these patients. In this review, the authors focus on the glioma types of specific concern to practitioners caring for AYA patients and the factors that should be considered in the development of multidisciplinary teams to facilitate their care.

Circulating Brain Injury Biomarkers: A Novel Method for Quantification of the Impact on the Brain After Tumor Surgery

Neurosurgery 93:847–856, 2023

Clinical methods to quantify brain injury related to neurosurgery are scarce. Circulating brain injury biomarkers have recently gained increased interest as new ultrasensitive measurement techniques have enabled quantification of brain injury through blood sampling.

OBJECTIVE: To establish the time profile of the increase in the circulating brain injury biomarkers glial fibrillary acidic protein (GFAP), tau, and neurofilament light (NfL) after glioma surgery and to explore possible relationships between these biomarkers and outcome regarding volume of ischemic injury identified with postoperative MRI and new neurological deficits.

METHODS: In this prospective study, 34 adult patients scheduled for glioma surgery were included. Plasma concentrations of brain injury biomarkers were measured the day before surgery, immediately after surgery, and on postoperative days 1, 3, 5, and 10.

RESULTS: Circulating brain injury biomarkers displayed a postoperative increase in the levels of GFAP (P < .001), tau (P < .001), and NfL (P < .001) on Day 1 and a later, even higher, peak of NFL at Day 10 (P = .028). We found a correlation between the increased levels of GFAP, tau, and NfL on Day 1 after surgery and the volume of ischemic brain tissue on postoperative MRI. Patients with new neurological deficits after surgery had higher levels of GFAP and NfL on Day 1 compared with those without new neurological deficits.

CONCLUSION: Measuring circulating brain injury biomarkers could be a useful method for quantification of the impact on the brain after tumor surgery or neurosurgery in general.

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.