Stimulation of frontal pathways disrupts hand muscle control during object manipulation.

The activity of frontal motor areas during hand-object interaction is coordinated by dense communication along specific white matter pathways. This architecture allows the continuous shaping of voluntary motor output but, despite extensive investigation in non-human primate studies, remains poorly understood in humans. Disclosure of this system is crucial for predicting and treatment of motor deficits after brain lesions. For this purpose, we investigated the effect of direct electrical stimulation on white matter pathways within the frontal lobe on hand-object manipulation. This was tested in 34 patients (15 left hemisphere, mean age 42 years, 17 male, 15 with tractography) undergoing awake neurosurgery for frontal lobe tumour removal with the aid of the brain mapping technique. The stimulation outcome was quantified based on hand-muscle activity required by task execution. The white matter pathways responsive to stimulation with an interference on muscles were identified by means of probabilistic density estimation of stimulated sites, tract-based lesion-symptom (disconnectome) analysis and diffusion tractography on the single patient level. Finally, we assessed the effect of permanent tract disconnection on motor outcome in the immediate postoperative period using a multivariate lesion-symptom mapping approach. The analysis showed that stimulation disrupted hand-muscle activity during task execution at 66 sites within the white matter below dorsal and ventral premotor regions. Two different EMG interference patterns associated with different structural architectures emerged: (i) an 'arrest' pattern, characterized by complete impairment of muscle activity associated with an abrupt task interruption, occurred when stimulating a white matter area below the dorsal premotor region. Local middle U-shaped fibres, superior fronto-striatal, corticospinal and dorsal fronto-parietal fibres intersected with this region. (ii) a 'clumsy' pattern, characterized by partial disruption of muscle activity associated with movement slowdown and/or uncoordinated finger movements, occurred when stimulating a white matter area below the ventral premotor region. Ventral fronto-parietal and inferior fronto-striatal tracts intersected with this region. Finally, only resections partially including the dorsal white matter region surrounding the supplementary motor area were associated with transient upper-limb deficit (P = 0.05; 5000 permutations). Overall, the results identify two distinct frontal white matter regions possibly mediating different aspects of hand-object interaction via distinct sets of structural connectivity. We suggest the dorsal region, associated with arrest pattern and postoperative immediate motor deficits, to be functionally proximal to motor output implementation, while the ventral region may be involved in sensorimotor integration required for task execution.

Intraoperative AIRO mobile computer tomography in frameless stereotactic procedures.

BACKGROUND: Multiple factors can affect the accuracy of neuronavigation, that is a relevant issue, particularly for frameless stereotactic procedures, where precision and optimal image-guidance is crucial for the surgical performance, workflow, and outcome. OBJECTIVE: To investigate the impact of AIRO Mobile Computer Tomography in frameless stereotactic approaches. METHODS: A retrospective study on 12 patients was performed. All the procedures were deployed using a frameless stereotactic technique, both for the collection of biopsy pathological specimens for diagnosis and insertion of drainage in the treatment of intracranial cystic lesions. RESULTS: Twelve patients (eight males, four females) underwent the frameless stereotactic procedure. Mean age at surgery was 55 (±5 SE). The mean volume of the lesion was 23.85 cm3 (±3.13). Six diagnostic biopsies and six cyst drainages were performed. The mean trajectory length was 75.9 ± 11.8 mm. Three posterior fossa lesions (27%) were approached through a retro-sigmoidal burr-hole. A craniotomy for draining a haematoma was performed after detection with AIRO-CT. No permanent neurological dysfunction, in-hospital or 30-day mortality were recorded. CONCLUSION: The AIRO-CT resulted feasible with a potential utility for stereotactic procedures. We showed how it could grant the efficacy of the stereotactic procedures reducing some technical and physical sources of inaccuracy, also enhancing safety and allowing prompt detection and management of intraoperative complications.

Frontal pathways in cognitive control: direct evidence from intraoperative stimulation and diffusion tractography.

A key aspect of cognitive control is the management of conflicting incoming information to achieve a goal, termed 'interference control'. Although the role of the right frontal lobe in interference control is evident, the white matter tracts subserving this cognitive process remain unclear. To investigate this, we studied the effect of transient network disruption (by means of direct electrical stimulation) and permanent disconnection (resulting from neurosurgical resection) on interference control processes, using the Stroop test in the intraoperative and extraoperative neurosurgical setting. We evaluated the sites at which errors could be produced by direct electrical stimulation during an intraoperative Stroop test in 34 patients with frontal right hemisphere glioma. Lesion-symptom mapping was used to evaluate the relationship between the resection cavities and postoperative performance on the Stroop test of this group compared with an additional 29 control patients who did not perform the intraoperative test (63 patients in total aged 17-77 years; 28 female). We then examined tract disruption and disconnection in a subset of eight patients who underwent both the intraoperative Stroop test and high angular resolution diffusion imaging (HARDI) tractography. The results showed that, intraoperatively, the majority of sites associated with errors during Stroop test performance and concurrent subcortical stimulation clustered in a region of white matter medial to the right inferior frontal gyrus, lateral and superior to the striatum. Patients who underwent the intraoperative test maintained cognitive control ability at the 1-month follow-up (P = 0.003). Lesion-symptom analysis showed resection of the right inferior frontal gyrus was associated with slower postoperative Stroop test ability (corrected for multiple comparisons, 5000 permutations). The stimulation sites associated with intraoperative errors most commonly corresponded with the inferior fronto-striatal tracts and anterior thalamic radiation (over 75% of patients), although the latter was commonly resected without postoperative deficits on the Stroop test (in 60% of patients). Our results show converging evidence to support a critical role for the inferior frontal gyrus in interference control processes. The intraoperative data combined with tractography suggests that cortico-subcortical tracts, over cortico-cortical connections, may be vital in maintaining efficiency of cognitive control processes. This suggests the importance of their preservation during resection of right frontal tumours.

Frameless stereotactic biopsy for precision neurosurgery: diagnostic value, safety, and accuracy.

BACKGROUND: Stereotactic biopsy is consistently employed to characterize cerebral lesions in patients who are not suitable for microsurgical resection. In the past years, technical improvement and neuroimaging advancements contributed to increase the diagnostic yield, the safety, and the application of this procedure. Currently, in addition to histological diagnosis, the molecular analysis is considered essential in the diagnostic process to properly select therapeutic and prognostic algorithms in a personalized approach. The present study reports our experience with frameless stereotactic brain biopsy in this molecular era. METHODS: One hundred forty consecutive patients treated from January 2013 to September 2018 were analyzed. Biopsies were performed using the Brainlab Varioguide® frameless stereotactic system. Patients' clinical and demographic data, the time of occupation of the operating room, the surgical time, the morbidity, and the diagnostic yield in providing a histological and molecular diagnosis were recorded and evaluated. RESULTS: The overall diagnostic yield was 93.6% with nine procedures resulting non-diagnostic. Among 110 patients with glioma, the IDH-1 mutational status was characterized in 108 cases (98.2%), resulting wild-type in all subjects but 3; MGMT methylation was characterized in 96 cases (87.3%), resulting present in 60 patients, and 1p/19q codeletion was founded in 6 of the 20 cases of grade II-III gliomas analyzed. All the specimens were apt for molecular analysis when performed. Bleeding requiring surgical drainage occurred in 2.1% of the cases; 8 (5.7%) asymptomatic hemorrhages requiring no treatment were observed. No biopsy-related mortality was recorded. Median length of hospital stay was 5 days (IQR 4-8) with mean surgical time of 60.77 min (± 23.12) and 137.44 ± 24.1 min of total occupation time of the operative room. CONCLUSIONS: Stereotactic frameless biopsy is a safe, feasible, and fast procedure to obtain a histological and molecular diagnosis.

Object-oriented hand dexterity and grasping abilities, from the animal quarters to the neurosurgical OR: a systematic review of the underlying neural correlates in non-human, human primate and recent findings in awake brain surgery.

Introduction: The sensorimotor integrations subserving object-oriented manipulative actions have been extensively investigated in non-human primates via direct approaches, as intracortical micro-stimulation (ICMS), cytoarchitectonic analysis and anatomical tracers. However, the understanding of the mechanisms underlying complex motor behaviors is yet to be fully integrated in brain mapping paradigms and the consistency of these findings with intraoperative data obtained during awake neurosurgical procedures for brain tumor removal is still largely unexplored. Accordingly, there is a paucity of systematic studies reviewing the cross-species analogies in neural activities during object-oriented hand motor tasks in primates and investigating the concordance with intraoperative findings during brain mapping. The current systematic review was designed to summarize the cortical and subcortical neural correlates of object-oriented fine hand actions, as revealed by fMRI and PET studies, in non-human and human primates and how those were translated into neurosurgical studies testing dexterous hand-movements during intraoperative brain mapping. Methods: A systematic literature review was conducted following the PRISMA guidelines. PubMed, EMBASE and Web of Science databases were searched. Original articles were included if they: (1) investigated cortical activation sites on fMRI and/or PET during grasping task; (2) included humans or non-human primates. A second query was designed on the databases above to collect studies reporting motor, hand manipulation and dexterity tasks for intraoperative brain mapping in patients undergoing awake brain surgery for any condition. Due to the heterogeneity in neurosurgical applications, a qualitative synthesis was deemed more appropriate. Results: We provided an updated overview of the current state of the art in translational neuroscience about the extended frontoparietal grasping-praxis network with a specific focus on the comparative functioning in non-human primates, healthy humans and how the latter knowledge has been implemented in the neurosurgical operating room during brain tumor resection. Discussion: The anatomical and functional correlates we reviewed confirmed the evolutionary continuum from monkeys to humans, allowing a cautious but practical adoption of such evidence in intraoperative brain mapping protocols. Integrating the previous results in the surgical practice helps preserve complex motor abilities, prevent long-term disability and poor quality of life and allow the maximal safe resection of intrinsic brain tumors.

Cognitive function in severe progressive multiple sclerosis.

Cognitive impairment is common in multiple sclerosis and negatively impacts quality of life. Cognitive status has yet to be described in people with severe progressive multiple sclerosis, in whom conventional neuropsychological testing is exceptionally difficult. The objective for the study was to characterize cognitive performance in severe progressive multiple sclerosis and compare them with age-, sex- and disease duration-matched less disabled people with multiple sclerosis using a specifically developed auditory, non-motor test of attention/cognitive processing speed-Auditory Test of Processing Speed. Also, we aimed to determine the relationship between cognitive performance and MRI-based outcomes in these matched cohorts. The Comprehensive Assessment of Severely Affected Multiple Sclerosis study was carried out at the University at Buffalo and the Boston Home, a skilled nursing facility in Dorchester, MA. Inclusion criteria were age 30-80 years and expanded disability status scale 3.0-6.5 for community-dwelling and 7.0-9.5 for skilled nursing facility people with multiple sclerosis. The cognitive assessment was performed using the Brief International Cognitive Assessment for Multiple Sclerosis consisting of Symbol Digit Modalities Test, Brief Visuospatial Memory Test-Revised, California Verbal Learning Test-2nd edition along with Auditory Test of Processing Speed, Paced Auditory Serial Addition Test-3 second and Controlled Oral Word Association Test. MRI scans were retrospectively collected and analysed for lesion and volumetric brain measurements. The rate of completion and performance of the cognitive tests was compared between the groups, and the relationship with MRI measures was determined using sex, age and years of education-adjusted linear regression models. Significantly greater percentage of the severe multiple sclerosis group completed Auditory Test of Processing Speed when compared with the current gold standard of Symbol Digit Modalities Test (93.2% versus 65.9%). Severe progressive multiple sclerosis had worse cognitive performance in all cognitive domains with greatest differences for cognitive processing speed (Symbol Digit Modalities Test > Paced Auditory Serial Addition Test-3 second > Auditory Test of Processing Speed, Cohen's d < 2.13, P < 0.001), learning and memory (Cohen's d < 1.1, P < 0.001) and language (Controlled Oral Word Association Test with Cohen's d = 0.97, P < 0.001). Multiple cognitive domains were significantly associated with lower thalamic (standardized ß < 0.419, P < 0.006) and cortical (standardized ß < 0.26, P < 0.031) volumes. Specially designed (auditory) cognitive processing speed tests may provide more sensitive screening of cognitive function in severe progressive multiple sclerosis. The cognitive profile of severe multiple sclerosis is proportional to their physical outcomes and best explained by decreased grey matter volume.

Dynamic disability measures decrease the clinico-radiological gap in people with severely affected multiple sclerosis.

BACKGROUND: Expanded Disability Status Scale (EDSS) is limited when utilized in highly disabled people with multiple sclerosis (pwMS). OBJETIVE: To explore the relationship between disability measures and MRI outcomes in severely-affected pwMS. METHODS: PwMS recruited from The Boston Home (TBH), a specialized residential facility for severly-affected pwMS and University at Buffalo (UB) MS Center were assessed using EDSS, MS Severity Scale, age-related MSS, Scripps Neurological Rating Scale (SNRS) and Combinatorial Weight-Adjusted Disability Score (CombiWISE). In all scores except SNRS, higher score indicates greater disability. MRI measures of T1, T2-lesion volume (LV), whole brain, gray matter, medulla oblongata and thalamic volumes (WBV, GMV, MOV, TV) and thalamic dysconnectivity were obtained. RESULTS: Greatest disability differences between the TBH and UB pwMS were in SNRS (24.4 vs 71.9, p < 0.001, Cohen's d = 4.05) and CombiWISE (82.3 vs. 38.9, p < 0.001, Cohen's d = 4.02). In combined analysis of all pwMS, worse SNRS scores were correlated with worse MRI pathology in 8 out of 9 outcomes. EDSS only with 3 measures (GMV, MOV and TV). In severely-affected pwMS, SNRS was associated with T1-LV, T2-LV and WBV (not surviving false discovery rate (FDR) correction for multiple comparisons) whereas EDSS did not. CONCLUSION: Granular and dynamic disability measures may bridge the clinico-radiologcal gap present in severely affected pwMS.

Neuroimaging assessment of facility-bound severely-affected MS reveals the critical role of cortical gray matter pathology: results from the CASA-MS case-controlled study.

BACKGROUND: A subgroup of people with multiple sclerosis (pwMS) will develop severe disability. The pathophysiology underlying severe MS is unknown. The comprehensive assessment of severely affected MS (CASA-MS) was a case-controlled study that compared severely disabled in skilled nursing (SD/SN) (EDSS ≥ 7.0) to less-disabled (EDSS 3.0-6.5) community dwelling (CD) progressive pwMS, matched on age-, sex- and disease-duration (DDM). OBJECTIVES: To identify neuroimaging and molecular biomarker characteristics that distinguish SD/SN from DDM-CD progressive pwMS. METHODS: This study was carried at SN facility and at a tertiary MS center. The study collected clinical, molecular (serum neurofilament light chain, sNfL and glial acidic fibrillary protein, sGFAP) and MRI quantitative lesion-, brain volume-, and tissue integrity-derived measures. Statistical analyses were controlled for multiple comparisons. RESULTS: 42 SD/SN and 42 DDM-CD were enrolled. SD/SN pwMS showed significantly lower cortical volume (CV) (p < 0.001, d = 1.375) and thalamic volume (p < 0.001, d = 0.972) compared to DDM-CD pwMS. In a logistic stepwise regression model, the SD/SN pwMS were best differentiated from the DDM-CD pwMS by lower CV (p < 0.001) as the only significant predictor, with the accuracy of 82.3%. No significant differences between the two groups were observed for medulla oblongata volume, a proxy for spinal cord atrophy and white matter lesion burden, while there was a statistical trend for numerically higher sGFAP in SD/SN pwMS. CONCLUSIONS: The CASA-MS study showed significantly more gray matter atrophy in severe compared to less-severe progressive MS.

Surgical management and outcome of newly diagnosed glioblastoma without contrast enhancement (low-grade appearance): a report of the RANO resect group.

BACKGROUND: Resection of the contrast-enhancing (CE) tumor represents the standard of care in newly diagnosed glioblastoma. However, some tumors ultimately diagnosed as glioblastoma lack contrast enhancement and have a 'low-grade appearance' on imaging (non-CE glioblastoma). We aimed to (a) volumetrically define the value of non-CE tumor resection in the absence of contrast enhancement, and to (b) delineate outcome differences between glioblastoma patients with and without contrast enhancement. METHODS: The RANO resect group retrospectively compiled a global, eight-center cohort of patients with newly diagnosed glioblastoma per WHO 2021 classification. The associations between postoperative tumor volumes and outcome were analyzed. Propensity score-matched analyses were constructed to compare glioblastomas with and without contrast enhancement. RESULTS: Among 1323 newly diagnosed IDH-wildtype glioblastomas, we identified 98 patients (7.4%) without contrast enhancement. In such patients, smaller postoperative tumor volumes were associated with more favorable outcome. There was an exponential increase in risk for death with larger residual non-CE tumor. Accordingly, extensive resection was associated with improved survival compared to lesion biopsy. These findings were retained on a multivariable analysis adjusting for demographic and clinical markers. Compared to CE glioblastoma, patients with non-CE glioblastoma had a more favorable clinical profile and superior outcome as confirmed in propensity score analyses by matching the patients with non-CE glioblastoma to patients with CE glioblastoma using a large set of clinical variables. CONCLUSIONS: The absence of contrast enhancement characterizes a less aggressive clinical phenotype of IDH-wildtype glioblastomas. Maximal resection of non-CE tumors has prognostic implications and translates into favorable outcome.

Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group.

BACKGROUND: Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit. METHODS: The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected. RESULTS: We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with "maximal CE resection" (class 2) had superior outcome compared to patients with "submaximal CE resection" (class 3) or "biopsy" (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 ("supramaximal CE resection"). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. CONCLUSIONS: The proposed "RANO categories for extent of resection in glioblastoma" are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such "supramaximal CE resection."

Segmentation of glioblastomas in early post-operative multi-modal MRI with deep neural networks.

Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61% Dice score, and the best classification performance was about 80% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection.

Multi-class glioma segmentation on real-world data with missing MRI sequences: comparison of three deep learning algorithms.

This study tests the generalisability of three Brain Tumor Segmentation (BraTS) challenge models using a multi-center dataset of varying image quality and incomplete MRI datasets. In this retrospective study, DeepMedic, no-new-Unet (nn-Unet), and NVIDIA-net (nv-Net) were trained and tested using manual segmentations from preoperative MRI of glioblastoma (GBM) and low-grade gliomas (LGG) from the BraTS 2021 dataset (1251 in total), in addition to 275 GBM and 205 LGG acquired clinically across 12 hospitals worldwide. Data was split into 80% training, 5% validation, and 15% internal test data. An additional external test-set of 158 GBM and 69 LGG was used to assess generalisability to other hospitals' data. All models' median Dice similarity coefficient (DSC) for both test sets were within, or higher than, previously reported human inter-rater agreement (range of 0.74-0.85). For both test sets, nn-Unet achieved the highest DSC (internal = 0.86, external = 0.93) and the lowest Hausdorff distances (10.07, 13.87 mm, respectively) for all tumor classes (p < 0.001). By applying Sparsified training, missing MRI sequences did not statistically affect the performance. nn-Unet achieves accurate segmentations in clinical settings even in the presence of incomplete MRI datasets. This facilitates future clinical adoption of automated glioma segmentation, which could help inform treatment planning and glioma monitoring.

Prognostic evaluation of re-resection for recurrent glioblastoma using the novel RANO classification for extent of resection: A report of the RANO resect group.

BACKGROUND: The value of re-resection in recurrent glioblastoma remains controversial as a randomized trial that specifies intentional incomplete resection cannot be justified ethically. Here, we aimed to (1) explore the prognostic role of extent of re-resection using the previously proposed Response Assessment in Neuro-Oncology (RANO) classification (based upon residual contrast-enhancing (CE) and non-CE tumor), and to (2) define factors consolidating the surgical effects on outcome. METHODS: The RANO resect group retrospectively compiled an 8-center cohort of patients with first recurrence from previously resected glioblastomas. The associations of re-resection and other clinical factors with outcome were analyzed. Propensity score-matched analyses were constructed to minimize confounding effects when comparing the different RANO classes. RESULTS: We studied 681 patients with first recurrence of Isocitrate Dehydrogenase (IDH) wild-type glioblastomas, including 310 patients who underwent re-resection. Re-resection was associated with prolonged survival even when stratifying for molecular and clinical confounders on multivariate analysis; ≤1 cm3 residual CE tumor was associated with longer survival than non-surgical management. Accordingly, "maximal resection" (class 2) had superior survival compared to "submaximal resection" (class 3). Administration of (radio-)chemotherapy in the absence of postoperative deficits augmented the survival associations of smaller residual CE tumors. Conversely, "supramaximal resection" of non-CE tumor (class 1) was not associated with prolonged survival but was frequently accompanied by postoperative deficits. The prognostic role of residual CE tumor was confirmed in propensity score analyses. CONCLUSIONS: The RANO resect classification serves to stratify patients with re-resection of glioblastoma. Complete resection according to RANO resect classes 1 and 2 is prognostic.

Transcranial versus direct electrical stimulation for intraoperative motor-evoked potential monitoring: Prognostic value comparison in asleep brain tumor surgery.

Objective: Safe resection of gliomas involving motor pathways in asleep-anesthesia requires the combination of brain mapping, to identify and spare essential motor sites, and continuous monitoring of motor-evoked potentials (MEPs), to detect possible vascular damage to the corticospinal tract (CST). MEP monitoring, according to intraoperative neurophysiology societies, is generally recommended by transcranial electrodes (TES), and no clear indications of direct cortical stimulation (DCS) or the preferential use of one of the two techniques based on the clinical context is available. The main aim of the study was to identify the best technique(s) based on different clinical conditions, evaluating the efficacy and prognostic value of both methodologies. Methods: A retrospective series of patients with tumors involving the motor pathways who underwent surgical resection with the aid of brain mapping and combined MEP monitoring via TES and DCS was evaluated. Irreversible MEP amplitude reduction (>50% compared to baseline) was used as an intraoperative warning and correlated to the postoperative motor outcome. Selectivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were computed for both techniques. Results: Four hundred sixty-two patients were retrospectively analyzed, and only 1.9% showed a long-term motor impairment. Both TES and DCS obtained high specificity and NPV for the acute and 1-month motor deficit. Sensitivity was rather low for the acute deficit but excellent considering the 1-month follow-up for both techniques. DCS was extremely reliable in predicting a postoperative motor decline (PPV of 100% and 90% for acute and long-term deficit, respectively). Conversely, TES produced a high number of false-positive results, especially for long-term deficits (65, 87.8% of all warnings) therefore obtaining poor PPV values (18% and 12% for acute and 1-month deficits, respectively). TES false-positive results were significantly associated with parietal tumors and lateral patient positioning. Conclusions: Data support the use of mapping and combined monitoring via TES and DCS. The sole TES monitoring is reliable in most procedures but not in parietal tumors or those requiring lateral positioning. Although no indications are available in international guidelines, DCS should be recommended, particularly for cases approached by a lateral position.

Asleep or awake motor mapping for resection of perirolandic glioma in the nondominant hemisphere? Development and validation of a multimodal score to tailor the surgical strategy.

OBJECTIVE: 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.

Preoperative Brain Tumor Imaging: Models and Software for Segmentation and Standardized Reporting.

For patients suffering from brain tumor, prognosis estimation and treatment decisions are made by a multidisciplinary team based on a set of preoperative MR scans. Currently, the lack of standardized and automatic methods for tumor detection and generation of clinical reports, incorporating a wide range of tumor characteristics, represents a major hurdle. In this study, we investigate the most occurring brain tumor types: glioblastomas, lower grade gliomas, meningiomas, and metastases, through four cohorts of up to 4,000 patients. Tumor segmentation models were trained using the AGU-Net architecture with different preprocessing steps and protocols. Segmentation performances were assessed in-depth using a wide-range of voxel and patient-wise metrics covering volume, distance, and probabilistic aspects. Finally, two software solutions have been developed, enabling an easy use of the trained models and standardized generation of clinical reports: Raidionics and Raidionics-Slicer. Segmentation performances were quite homogeneous across the four different brain tumor types, with an average true positive Dice ranging between 80 and 90%, patient-wise recall between 88 and 98%, and patient-wise precision around 95%. In conjunction to Dice, the identified most relevant other metrics were the relative absolute volume difference, the variation of information, and the Hausdorff, Mahalanobis, and object average symmetric surface distances. With our Raidionics software, running on a desktop computer with CPU support, tumor segmentation can be performed in 16-54 s depending on the dimensions of the MRI volume. For the generation of a standardized clinical report, including the tumor segmentation and features computation, 5-15 min are necessary. All trained models have been made open-access together with the source code for both software solutions and validation metrics computation. In the future, a method to convert results from a set of metrics into a final single score would be highly desirable for easier ranking across trained models. In addition, an automatic classification of the brain tumor type would be necessary to replace manual user input. Finally, the inclusion of post-operative segmentation in both software solutions will be key for generating complete post-operative standardized clinical reports.

On the cutting edge of glioblastoma surgery: where neurosurgeons agree and disagree on surgical decisions.

OBJECTIVE: The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity. Standards are lacking for surgical decision-making, and previous studies indicate treatment variations. These shortcomings reflect the need to evaluate larger populations from different care teams. In this study, the authors used probability maps to quantify and compare surgical decision-making throughout the brain by 12 neurosurgical teams for patients with glioblastoma. METHODS: The study included all adult patients who underwent first-time glioblastoma surgery in 2012-2013 and were treated by 1 of the 12 participating neurosurgical teams. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to identify and compare patient treatment variations. Brain regions with different biopsy and resection results between teams were identified and analyzed for patient functional outcome and survival. RESULTS: The study cohort consisted of 1087 patients, of whom 363 underwent a biopsy and 724 a resection. Biopsy and resection decisions were generally comparable between teams, providing benchmarks for probability maps of resections and biopsies for glioblastoma. Differences in biopsy rates were identified for the right superior frontal gyrus and indicated variation in biopsy decisions. Differences in resection rates were identified for the left superior parietal lobule, indicating variations in resection decisions. CONCLUSIONS: Probability maps of glioblastoma surgery enabled capture of clinical practice decisions and indicated that teams generally agreed on which region to biopsy or to resect. However, treatment variations reflecting clinical dilemmas were observed and pinpointed by using the probability maps, which could therefore be useful for quality-of-care discussions between surgical teams for patients with glioblastoma.

Surgery for Glioblastoma in Elderly Patients.

The management of glioblastoma in the elderly population represents a field of growing interest owing a longer life expectancy. In this age group, more than in the young adult, biological age is much more important than chronologic one. The date of birth should not exclude a priori access of treatments. Maximal safe resection is proved to be the first option when performance status and general health is good. Adjuvant therapy and decision about management of recurrence should be choose in a multidisciplinary group according to performance of the patients and O6-methylguanine-DNA methyl-transferase methylation.

Advancing Imaging to Enhance Surgery: From Image to Information Guidance.

Conventional magnetic resonance imaging (cMRI) has an established role as a crucial disease parameter in the multidisciplinary management of glioblastoma, guiding diagnosis, treatment planning, assessment, and follow-up. Yet, cMRI cannot provide adequate information regarding tissue heterogeneity and the infiltrative extent beyond the contrast enhancement. Advanced magnetic resonance imaging and PET and newer analytical methods are transforming images into data (radiomics) and providing noninvasive biomarkers of molecular features (radiogenomics), conveying enhanced information for improving decision making in surgery. This review analyzes the shift from image guidance to information guidance that is relevant for the surgical treatment of glioblastoma.

Challenging Giant Insular Gliomas With Brain Mapping: Evaluation of Neurosurgical, Neurological, Neuropsychological, and Quality of Life Results in a Large Mono-Institutional Series.

OBJECTIVE: Giant insular tumors are commonly not amenable to complete resection and are associated with a high postoperative morbidity rate. Transcortical approach and brain mapping techniques allow to identify peri-insular functional networks and, with neurophysiological monitoring, to reduce vascular-associated insults. Cognitive functions to be mapped are still under debate, and the analysis of the functional risk of surgery is currently limited to neurological examination. This work aimed to investigate the neurosurgical outcome (extent of resection, EOR) and functional impact of giant insular gliomas resection, focusing on neuropsychological and Quality of Life (QoL) outcomes. METHODS: In our retrospective analysis, we included all patients admitted in a five-year period with a radiological diagnosis of giant insular glioma. A transcortical approach was adopted in all cases. Resections were pursued up to functional boundaries defined intraoperatively by brain mapping techniques. We examined clinical, radiological, and intra-operative factors possibly affecting EOR and postoperative neurological, neuropsychological, and Quality of Life (QoL) outcomes. RESULTS: We finally enrolled 95 patients in the analysis. Mean EOR was 92.3%. A Gross Total Resection (GTR) was obtained in 70 cases (73.7%). Five patients reported permanent morbidity (aphasia in 3, 3.2%, and superior quadrantanopia in 2, 2.1%). Suboptimal EOR associated with poor seizures control postoperatively. Extensive intraoperative mapping (inclusive of cognitive, visual, and haptic functions) decreased long-term neurological, neuropsychological, and QoL morbidity and increased EOR. Tumor infiltration of deep perforators (vessels arising either medial to lenticulostriate arteries through the anterior perforated substance or from the anterior choroidal artery) associated with a higher chance of postoperative ischemia in consonant areas, with the persistence of new-onset motor deficits 1-month post-op, and with minor EOR. Ischemic insults in eloquent sites represented the leading factor for long-term neurological and neuropsychological morbidity. CONCLUSION: In giant insular gliomas, the use of a transcortical approach with extensive brain mapping under awake anesthesia ensures broad insular exposure and extension of the surgical resection preserving patients' functional integrity. The relation between tumor mass and deep perforators predicts perioperative ischemic insults, the most relevant risk factor for long-term and permanent postoperative morbidity.