Precuneal gliomas promote behaviorally relevant remodeling of the functional connectome

J Neurosurg 138:1531–1541, 2023

The precuneus hosts one of the most complex patterns of functional connectivity in the human brain. However, due to the extreme rarity of neurological lesions specifically targeting this structure, it remains unknown how focal damage to the precuneus may impact resting-state functional connectivity (rsFC) at the brainwide level. The aim of this study was to investigate glioma-induced rsFC modulations and to identify patterns of rsFC remodeling that accounted for the maintenance of cognitive performance after awake-guided surgical excision.

METHODS In a unique series of patients with IDH1-mutated low-grade gliomas (LGGs) infiltrating the precuneus who were treated at a single neurosurgical center (Montpellier University Medical Center, 2014–2021), the authors gauged the dynamic modulations induced by tumors on rsFC in comparison with healthy participants. All patients received a preoperative resting-state functional MRI and underwent operation guided by awake cognitive mapping. Connectome multivariate pattern analysis (MVPA), seed-network analysis, and graph theoretical analysis were conducted and correlated to executive neurocognitive scores (i.e., phonological and semantic fluencies, Trail-Making Test [TMT] parts A and B) obtained 3 months after surgery.

RESULTS Seventeen patients with focal precuneal infiltration were selected (mean age 38.1 ± 11.2 years) and matched to 17 healthy participants (mean age 40.5 ± 10.4 years) for rsFC analyses. All patients underwent awake cognitive mapping, allowing total resection (n = 3) or subtotal resection (n = 14), with a mean extent of resection of 90.6% ± 7.3%. Using MVPA (cluster threshold: p–false discovery rate corrected < 0.05, voxel threshold: p-uncorrected < 0.001), remote hotspots with significant rsFC changes were identified, including both insulas, the anterior cingulate cortex, superior sensorimotor cortices, and both frontal eye fields. Further seed-network analyses captured 2 patterns of between-network redistribution especially involving hyperconnectivity between the salience, visual, and dorsal attentional networks. Finally, the global efficiency of the salience-visual-dorsal attentional networks was strongly and positively correlated to 3-month postsurgical scores (n = 15) for phonological fluency (r 15 = 0.74, p = 0.0027); TMT-A (r 15 = 0.65, p = 0.012); TMTB (r 15 = 0.70, p = 0.005); and TMT-B-A (r 15 = 0.62, p = 0.018).

CONCLUSIONS In patients with LGGs infiltrating the precuneus, remote and distributed functional connectivity modulations in the preoperative setting are associated with better maintenance of cognitive performance after surgery. These findings provide a new vision of the mechanistic principles underlying neural plasticity and cognitive compensation in patients with LGGs.

Personalized surgery of brain tumors in language areas: the role of preoperative brain mapping in patients not eligible for awake surgery

Neurosurg Focus 53 (6):E3, 2022

Awake surgery represents the gold standard for resection of brain tumors close to the language network. However, in some cases patients may be considered not eligible for awake craniotomy. In these cases, a personalized brain mapping of the language network may be achieved by navigated transcranial magnetic stimulation (nTMS), which can guide resection in patients under general anesthesia. Here the authors describe their tailored nTMS-based strategy and analyze its impact on the extent of tumor resection (EOR) and language outcome in a series of patients not eligible for awake surgery.

METHODS The authors reviewed data from all patients harboring a brain tumor in or close to the language network who were considered not eligible for awake surgery and were operated on during asleep surgery between January 2017 and July 2022, under the intraoperative guidance of nTMS data. The authors analyzed the effectiveness of nTMS-based mapping data in relation to 1) the ability of the nTMS-based mapping to stratify patients according to surgical risks, 2) the occurrence of postoperative language deficits, and 3) the EOR.

RESULTS A total of 176 patients underwent preoperative nTMS cortical language mapping and nTMS-based tractography of language fascicles. According to the nTMS-based mapping, tumors in 115 patients (65.3%) were identified as true-eloquent tumors because of a close spatial relationship with the language network. Conversely, tumors in 61 patients (34.7%) for which the nTMS mapping disclosed a location at a safer distance from the network were identified as false-eloquent tumors. At 3 months postsurgery, a permanent language deficit was present in 13 patients (7.3%).

In particular, a permanent deficit was observed in 12 of 115 patients (10.4%) with true-eloquent tumors and in 1 of 61 patients (1.6%) with false-eloquent lesions. With nTMS-based mapping, neurosurgeons were able to distinguish trueeloquent from false-eloquent tumors in a significant number of cases based on the occurrence of deficits at discharge (p < 0.0008) and after 3 months from surgery (OR 6.99, p = 0.03). Gross-total resection was achieved in 80.1% of patients overall and in 69.5% of patients with true-eloquent lesions and 100% of patients with false-eloquent tumors.

CONCLUSIONS nTMS-based mapping allows for reliable preoperative mapping of the language network that may be used to stratify patients according to surgical risks. nTMS-guided asleep surgery should be considered a good alternative for personalized preoperative brain mapping of the language network that may increase the possibility of safe and effective resection of brain tumors in the dominant hemisphere whenever awake mapping is not feasible.

Recurrent Low-Grade Gliomas: Does Reoperation Affect Neurocognitive Functioning?

Neurosurgery 90:221–232, 2022

Reoperations in patients with recurrent low-grade gliomas (RLGG) were proposed to control tumor residual and delay the risk of malignant transformation over time.

OBJECTIVE: To investigate neurocognitive outcomes in patients with RLGG who underwent a second surgery with awake monitoring.

METHODS: In this retrospective study, patients who underwent a second awake surgery for RLGG were included. Patients had presurgical and 3-mo postsurgical neuropsychological assessments. Data were converted into Z-scores and combined by the cognitive domain. Number of patients with cognitive deficits (Z-score <À1.65), variations of Z-scores, and extent of resection (EOR) were analyzed.

RESULTS: Sixty-two patients were included (mean age: 41.2 ± 10.0 yr). None had permanent neurological deficits postoperatively. Eight patients (12.9%) had a cognitive deficit preoperatively. Four additional patients (6.5%) had a cognitive deficit 3 mo after reoperation. Among other patients, 13 (21.0%) had a mild decline without cognitive deficits while 29 (46.8%) had no change of their performances and 8 (12.9%) improved. Overall, 94.2% of the patients returned to work. There were no correlations between EOR and Z-scores. Total/ subtotal resections were achieved in 91.9% of the patients (mean residual: 3.1 cm3 ). Fiftyeight patients (93.5%) were still alive after an overall follow-up of 8.3 yr.

CONCLUSION: Reoperation with awake monitoring in patients with RLGG was compatible with an early recovery of neuropsychological abilities. Four patients (6.5%) presented a new cognitive deficit at 3 mo postoperatively. Total/subtotal resections were achieved in most patients. Based on these favorable outcomes, reoperation should be considered in a more systematic way.

Surgery of Insular Diffuse Gliomas—Part 2: Probabilistic Cortico-Subcortical Atlas of Critical Eloquent Brain Structures and Probabilistic Resection Map During Transcortical Awake Resection

Neurosurgery 89:579–590, 2021

Insular diffuse glioma surgery is challenging, and tools to help surgical planning could improve the benefit-to-risk ratio.

OBJECTIVE: To provide a probabilistic resection map and frequency atlases of critical eloquent regions of insular diffuse gliomas based on our surgical experience.

METHODS: We computed cortico-subcortical “eloquent” anatomic sites identified intraoperatively by direct electrical stimulations during transcortical awake resection of insular diffuse gliomas in adults.

RESULTS: From 61 insular diffuse gliomas (39 left, 22 right; all left hemispheric dominance for language), we provided a frequency atlas of eloquence of the opercula (left/right; pars orbitalis: 0%/5.0%; pars triangularis: l5.6%/4.5%; pars opercularis: 37.8%/27.3%; precentral gyrus: 97.3%/95.4%; postcentral and supramarginal gyri: 75.0%/57.1%; temporal pole and superior temporal gyrus: 13.3%/0%), which tailored the transcortical approach (frontal operculum to reach the antero-superior insula, temporal operculum to reach the inferior insula, parietal operculum to reach the posterior insula). We provided a frequency atlas of eloquence identifying the subcortical functional boundaries (36.1% pyramidal pathways, 50.8% inferior fronto-occipital fasciculus, 13.1% arcuate and superior longitudinal fasciculi complex, 3.3% somatosensory pathways, 8.2% caudate and lentiform nuclei). Vascular boundaries and increasing errors during testing limited the resection in 8.2% and 11.5% of cases, respectively. We provided a probabilistic 3-dimensional atlas of resectability.

CONCLUSION: Functional mapping under awake conditions has to be performed intraoperatively in each patient to guide surgical approach and resection of insular diffuse gliomas in right and left hemispheres. Frequency atlases of opercula eloquence and of subcortical eloquent anatomic boundaries, and probabilistic 3-dimensional atlas of resectability could guide neurosurgeons.

Surgery of Insular Diffuse Gliomas—Part 1: Transcortical Awake Resection Is Safe and Independently Improves Overall Survival

Neurosurgery 89:565–578, 2021

Insular diffuse glioma resection is at risk of vascular injury and of postoperative new neurocognitive deficits.

OBJECTIVE: To assess safety and efficacy of surgical management of insular diffuse gliomas.

METHODS: Observational, retrospective, single-institution cohort analysis (2005-2019) of 149 adult patients surgically treated for an insular diffuse glioma: transcortical awake resection with intraoperative functional mapping (awake resection subgroup, n = 61), transcortical asleep resection without functional mapping (asleep resection subgroup, n = 50), and stereotactic biopsy (biopsy subgroup, n = 38). All cases were histopathologically assessed according to the 2016World Health Organization classification and cIMPACTNOW update 3.

RESULTS: Following awake resection, 3/61 patients had permanent motor deficit, seizure control rates improved (89% vs 69% preoperatively, P = .034), and neurocognitive performance improved from 5% to 24% in tested domains, despite adjuvant oncological treatments. Resection rates were higher in the awake resection subgroup (median 94%) than in the asleep resection subgroup (median 46%; P < .001). There was more gross total resection (25% vs 12%) and less partial resection (34% vs 80%) in the awake resection subgroup than in the asleep resection subgroup (P< .001). Karnofsky Performance Status score <70 (adjusted hazard ratio [aHR] 2.74, P = .031), awake resection (aHR 0.21, P = .031), isocitrate dehydrogenase (IDH)-mutant grade 2 astrocytoma (aHR 5.17, P = .003), IDHmutant grade 3 astrocytoma (aHR 6.11, P < .001), IDH-mutant grade 4 astrocytoma (aHR 13.36, P = .008), and IDH-wild-type glioblastoma (aHR 21.84, P < .001) were independent predictors of overall survival.

CONCLUSION:Awake surgery preserving the brain connectivity is safe, allows larger resections for insular diffuse gliomas than asleep resection, and positively impacts overall survival.

A focal brain-cooling device as an alternative to electrical stimulation for language mapping during awake craniotomy

J Neurosurg Case Lessons 2(2):CASE21131, 2021

Functional mapping in awake craniotomy has the potential risk of electrical stimulation-related seizure. The authors have developed a novel mapping technique using a brain-cooling device. The cooling probe is cylindrical in shape with a thermoelectric cooling plate (10  10 mm) at the bottom. A proportional integration and differentiation-controlled system adjusts the temperature accurately (Japan patent no. P5688666). The authors used it in two patients with glioblastoma. Broca’s area was identified by electrical stimulation, and then the cooling probe set at 5°C was attempted on it.

OBSERVATIONS Electrocorticogram was suppressed, and the temperature dropped to 8°C in 50 sec. A positive aphasic reaction was reproduced on Broca’s area at a latency of 7 sec. A negative reaction appeared on the adjacent cortices despite the temperature decrease. The sensitivity and specificity were 60% and 100%, respectively. No seizures or other adverse events related to the cooling were recognized, and no histological damage to the cooled cortex was observed.

LESSONS The cooling probe suppressed topographical brain function selectively and reversibly. Awake functional mapping based on thermal neuromodulation technology could substitute or compensate for the conventional electrical mapping.

Intraoperative Cognition Mapping and Monitoring “à la carte” in Brain Tumor Patients

Neurosurgery 88:919–930, 2021

The purpose of surgery for brain tumors involving eloquent neural circuits is to maximize the extent of resection while preserving an optimal quality of life. To this end, especially in diffuse glioma, the goal is to remove the cerebral parenchyma invaded by the neoplasm up to the individual cortico-subcortical networks critical for brain functions.

Intraoperative mapping combined with real-time cognitive monitoring throughout the resection in awake patient is thus highly recommended to resume a normal life. Indeed, beyond avoiding hemiplegia or aphasia, enjoying a familial, social, and professional life implies that motor and language mapping is not sufficient.

Identifying and sparing neural networks that subserve cognition (movement control, visuospatial cognition, executive functions, multimodal semantics, metacognition) andmentalizing (theory ofmind, which plays a key role for social cognition) is essential to preserve an adapted behavior.

Here, the aim is to review when and how to map these critical functions, which have nonetheless been neglected for many decades by neurosurgeons. In fact, the disorders generated by surgical injuries of circuits underpinning nonmotor and nonspeech functions are usually not immediately visible on postoperative standard clinical examination, leading the physician to believe that the patient has no deficit. Yet, cognitive or emotional disturbances may subsequently prevent to resume an active life, as to work full time.

Therefore, a systematic neuropsychological assessment should be performed before, during, and after mapping-guided surgery, regardless of the tumor location, to preserve the functional connectome intraoperatively and to plan a postoperative tailored cognitive rehabilitation according to the patient’s needs.

Predictors of early postoperative epileptic seizures after awake surgery in supratentorial diffuse gliomas

J Neurosurg 134:683–692, 2021

Functional-based resection under awake conditions had been associated with a nonnegligible rate of intraoperative and postoperative epileptic seizures. The authors assessed the incidence of intraoperative and early postoperative epileptic seizures after functional-based resection under awake conditions.

METHODS The authors prospectively assessed intraoperative and postoperative seizures (within 1 month) together with clinical, imaging, surgical, histopathological, and follow-up data for 202 consecutive diffuse glioma adult patients who underwent a functional-based resection under awake conditions.

RESULTS Intraoperative seizures occurred in 3.5% of patients during cortical stimulation; all resolved without any procedure being discontinued. No predictor of intraoperative seizures was identified. Early postoperative seizures occurred in 7.9% of patients at a mean of 5.1 ± 2.9 days. They increased the duration of hospital stay (p = 0.018), did not impact the 6-month (median 95 vs 100, p = 0.740) or the 2-year (median 100 vs 100, p = 0.243) postoperative Karnofsky Performance Status score and did not impact the 6-month (100% vs 91.4%, p = 0.252) or the 2-year (91.7 vs 89.4%, p = 0.857) postoperative seizure control. The time to treatment of at least 3 months (adjusted OR [aOR] 4.76 [95% CI 1.38–16.36], p = 0.013), frontal lobe involvement (aOR 4.88 [95% CI 1.25–19.03], p = 0.023), current intensity for intraoperative mapping of at least 3 mA (aOR 4.11 [95% CI 1.17–14.49], p = 0.028), and supratotal resection (aOR 6.24 [95% CI 1.43–27.29], p = 0.015) were independently associated with early postoperative seizures.

CONCLUSIONS Functional-based resection under awake conditions can be safely performed with a very low rate of intraoperative and early postoperative seizures and good 6-month and 2-year postoperative seizure outcomes. Intraoperatively, the use of the lowest current threshold producing reproducible responses is mandatory to reduce seizure occurrence intraoperatively and in the early postoperative period.

Clinical Pearls and Methods for Intraoperative Motor Mapping

Neurosurgery 88:457–467, 2021

Resection of brain tumors involving motor areas and pathways requires the identification and preservation of various cortical and subcortical structures involved in motor control at the time of the procedure, in order to maintain the patient’s full motor capacities. The use of brain mapping techniques has now been integrated into clinical practice for many years, as they help the surgeon to identify the neural structures involved in motor functions. A common definition of motor function, as well as knowledge of its neural organization, has been continuously evolving, underlining the need for implementing intraoperative strategies at the time of the procedure. Similarly, mapping strategies have been subjected to continuous changes, enhancing the likelihood of preservation of full motor capacities. As a general rule, the motor mapping strategy should be as flexible as possible and adapted strictly to the individual patient and clinical context of the tumor.

In this work, we present an overview of current knowledge of motor organization, indications for motor mapping, available motor mapping, and monitoring strategies, as well as their advantages and limitations. The use of motor mapping improves resection and outcomes in patients harboring tumors involving motor areas and pathways, and should be considered the gold standard in the resection of this type of tumor.

Awake vs. asleep motor mapping for glioma resection: a systematic review and meta-analysis

Acta Neurochirurgica (2020) 162:1709–1720

Intraoperative stimulation (IS) mapping has become the preferred standard treatment for eloquent tumors as it permits a more accurate identification of functional areas, allowing surgeons to achieve higher extents of resection (EOR) and decrease postoperative morbidity. For lesions adjacent to the perirolandic area and descending motor tracts, mapping can be done with both awake craniotomy (AC) and under general anesthesia (GA). Objective We aimed to determine which anesthetic protocol—AC vs. GA—provides better patient outcomes by comparing EOR and postoperative morbidity for surgeries using IS mapping in gliomas located near or in motor areas of the brain.

Methods A systematic literature search was carried out to identify relevant studies from 1983 to 2019. Seven databases were screened. A total of 2351 glioma patients from 17 studies were analyzed.

Results A random-effects meta-analysis revealed a trend towards a higher mean EOR in AC [90.1% (95% C.I. 85.8–93.8)] than with GA [81.7% (95% C.I. 72.4–89.7)] (p = 0.06). Neurological deficits were divided by timing and severity for analysis. There was no significant difference in early neurological deficits [20.9% (95% C.I. 4.1–45.0) vs. 25.4% (95% C.I. 13.6–39.2)] (p = 0.74), late neurological deficits [17.1% (95% C.I. 0.0–50.0) vs. 3.8% (95% C.I. 1.1–7.6)] (p = 0.06), or in non-severe [28.4% (95% C.I. 0.0–88.5) vs. 20.1% (95% C.I. 7.1–32.2)] (p = 0.72), and severe morbidity [2.6% (95% C.I. 0.0–15.5) vs. 4.5% (95% C.I. 1.1–9.6)] (p = 0.89) between patients who underwent AC versus GA, respectively.

Conclusion Mapping during resection of gliomas located in or near the perirolandic area and descending motor tracts can be safely carried out with both AC and GA.

Intraoperative perception and estimates on extent of resection during awake glioma surgery: overcoming the learning curve

J Neurosurg 128:1410–1418, 2018

There is ample evidence that extent of resection (EOR) is associated with improved outcomes for glioma surgery. However, it is often difficult to accurately estimate EOR intraoperatively, and surgeon accuracy has yet to be reviewed. In this study, the authors quantitatively assessed the accuracy of intraoperative perception of EOR during awake craniotomy for tumor resection.

METHODS A single-surgeon experience of performing awake craniotomies for tumor resection over a 17-year period was examined. Retrospective review of operative reports for quantitative estimation of EOR was recorded. Definitive EOR was based on postoperative MRI. Analysis of accuracy of EOR estimation was examined both as a general outcome (gross-total resection [GTR] or subtotal resection [STR]), and quantitatively (5% within EOR on postoperative MRI). Patient demographics, tumor characteristics, and surgeon experience were examined. The effects of accuracy on motor and language outcomes were assessed.

RESULTS A total of 451 patients were included in the study. Overall accuracy of intraoperative perception of whether GTR or STR was achieved was 79.6%, and overall accuracy of quantitative perception of resection (within 5% of postoperative MRI) was 81.4%. There was a significant difference (p = 0.049) in accuracy for gross perception over the 17- year period, with improvement over the later years: 1997–2000 (72.6%), 2001–2004 (78.5%), 2005–2008 (80.7%), and 2009–2013 (84.4%). Similarly, there was a significant improvement (p = 0.015) in accuracy of quantitative perception of EOR over the 17-year period: 1997–2000 (72.2%), 2001–2004 (69.8%), 2005–2008 (84.8%), and 2009–2013 (93.4%). This improvement in accuracy is demonstrated by the significantly higher odds of correctly estimating quantitative EOR in the later years of the series on multivariate logistic regression. Insular tumors were associated with the highest accuracy of gross perception (89.3%; p = 0.034), but lowest accuracy of quantitative perception (61.1% correct; p < 0.001) compared with tumors in other locations. Even after adjusting for surgeon experience, this particular trend for insular tumors remained true. The absence of 1p19q co-deletion was associated with higher quantitative perception accuracy (96.9% vs 81.5%; p = 0.051). Tumor grade, recurrence, diagnosis, and isocitrate dehydrogenase-1 (IDH-1) status were not associated with accurate perception of EOR. Overall, new neurological deficits occurred in 8.4% of cases, and 42.1% of those new neurological deficits persisted after the 3-month follow-up. Correct quantitative perception was associated with lower postoperative motor deficits (2.4%) compared with incorrect perceptions (8.0%; p = 0.029). There were no detectable differences in language outcomes based on perception of EOR.

CONCLUSIONS The findings from this study suggest that there is a learning curve associated with the ability to accurately assess intraoperative EOR during glioma surgery, and it may take more than a decade to be truly proficient. Understanding the factors associated with this ability to accurately assess EOR will provide safer surgeries while maximizing tumor resection.

Preservation of hearing following awake surgery via the retrosigmoid approach for vestibular schwannomas in eight consecutive patients

Acta Neurochir (2017) 159:1579–1585

Hearing preservation in patients with vestibular schwannomas remains difficult by microsurgery or radiosurgery.

Method: In this study, awake surgery via the retrosigmoid approach was performed for vestibular schwannomas (volume, 11.6 ± 11.2 ml; range, 1.3–26.4 ml) in eight consecutive patients with preoperative quartering of pure tone audiometry (PTA) of 53 ± 27 dB.

:Results After surgery, hearing was preserved in seven patients and improved in one patient. The postoperative quartering PTA was 51 ± 21 dB. Serviceable hearing (class A + B + C) using the American Association of Otolaryngology-Head and Neck Surgery (AAO-HNS) classification was preserved in all patients. Preoperative useful hearing (AAO-HNS class A + B) was observed in three patients, and useful hearing was preserved in all three of these patients after surgery. In addition, useful facial nerve function (House-Blackmann Grade 1) was preserved in all patients.

:Conclusions These results suggest that awake surgery for vestibular schwannomas is associated with low patient morbidity, including with respect to hearing and facial nerve function.

Variability of intraoperative electrostimulation parameters in conscious individuals: language cortex

J Neurosurg 126:1641–1652, 2017

Electrostimulation in awake brain mapping is widely used to guide tumor removal, but methodologies can differ substantially across institutions. The authors studied electrostimulation brain mapping data to characterize the variability of the current intensity threshold across patients and the effect of its variations on the number, type, and surface area of the essential language areas detected.

METHODS Over 7 years, the authors prospectively studied 100 adult patients who were undergoing intraoperative brain mapping during resection of left hemisphere tumors. In all 100 cases, the same protocol of electrostimulation brain mapping (a controlled naming task—bipolar stimulation with biphasic square wave pulses of 1-msec duration and 60-Hz trains, maximum train duration 6 sec) and electrocorticography was used to detect essential language areas.

RESULTS The minimum positive thresholds of stimulation varied from patient to patient; the mean minimum intensity required to detect interference was 4.46 mA (range 1.5–9 mA), and in a substantial proportion of sites (13.5%) interference was detected only at intensities above 6 mA. The threshold varied within a given patient for different naming areas in 22% of cases. Stimulation of the same naming area with greater intensities led to slight changes in the type of response in 19% of cases and different types of responses in 4.5%. Naming sites detected were located in subcentimeter cortical areas (50% were less than 20 mm2), but their extent varied with the intensity of stimulation. During a brain mapping session, the same intensity of stimulation reproduced the same type of interference in 94% of the cases. There was no statistically significant difference between the mean stimulation intensities required to produce interfereince in the left inferior frontal lobe (Broca’s area), the supramarginal gyri, and the posterior temporal region.

CONCLUSIONS Intrasubject and intersubject variations of the minimum thresholds of positive naming areas and changes in the type of response and in the size of these areas according to the intensity used may limit the interpretation of data from electrostimulation in awake brain mapping. To optimize the identification of language areas during electrostimulation brain mapping, it is important to use different intensities of stimulation at the maximum possible currents, avoiding afterdischarges. This could refine the clinical results and scientific data derived from these mapping sessions.

Efficacy of the transtemporal approach with awake brain mapping to reach the dominant posteromedial temporal lesions

Acta Neurochir (2017) 159: 177

Surgeries for lesions in the dominant hippocampal and parahippocampal gyrus involving the posteromedial temporal regions are challenging to perform because they are located close to Wernicke’s area; white matter fibers related with language; the optic radiations; and critical neurovascular structures. We performed a transtemporal approach with awake functional mapping for lesions affecting the dominant posteromedial temporal regions. The aim of this study was to assess the feasibility, safety, and efficacy of awake craniotomy for these lesions.

Methods: We retrospectively reviewed four consecutive patients with tumors or cavernous angiomas located in the left hippocampal and parahippocampal gyrus, which further extended to the posteromedial temporal regions, who underwent awake surgery between December 2014 and January 2016.

Results: Four patients with lesions associated with the left hippocampal and parahippocampal gyrus, including the posteromedial temporal area, who underwent awake surgery were registered in the study. In all four patients, cortical and subcortical eloquent areas were identified via direct electrical stimulation. This allowed determination of the optimal surgical route to the angioma or tumor, even in the language-dominant hippocampal and parahippocampal gyrus. In particular, this approach enabled access to the upper part of posteromedial temporal lesions, while protecting the subcortical language-related fibers, such as the superior longitudinal fasciculus.

Conclusions: This study revealed that awake brain mapping can enable the safe resection of dominant posteromedial temporal lesions, while protecting cortical and subcortical eloquent areas. Furthermore, our experience with four patients demonstrates the feasibility, safety, and efficacy of awake surgery for these lesions.

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation

Combined noninvasive language mapping by navigated transcranial magnetic stimulation and functional MRI and its comparison with direct cortical stimulation


J Neurosurg 123:212–225, 2015

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS’s specificity and positive predictive value, the authors aim to provide thresholds for rTMS’s positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods.

Methods The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery.

Results The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%.

Conclusions In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

Intraoperative subcortical mapping of a language-associated deep frontal tract connecting the superior frontal gyrus to Broca’s area in the dominant hemisphere of patients with glioma

Intraoperative subcortical mapping of a language-associated deep frontal tract connecting the superior frontal gyrus to Broca’s area in the dominant hemisphere of patients with glioma

J Neurosurg 122:1390–1396, 2015

The deep frontal pathway connecting the superior frontal gyrus to Broca’s area, recently named the frontal aslant tract (FAT), is assumed to be associated with language functions, especially speech initiation and spontaneity. Injury to the deep frontal lobe is known to cause aphasia that mimics the aphasia caused by damage to the supplementary motor area. Although fiber dissection and tractography have revealed the existence of the tract, little is known about its function. The aim of this study was to determine the function of the FAT via electrical stimulation in patients with glioma who underwent awake surgery.

Methods The authors analyzed the data from subcortical mapping with electrical stimulation in 5 consecutive cases (3 males and 2 females, age range 40–54 years) with gliomas in the left frontal lobe. Diffusion tensor imaging (DTI) and tractography of the FAT were performed in all cases. A navigation system and intraoperative MRI were used in all cases. During the awake phase of the surgery, cortical mapping was performed to find the precentral gyrus and Broca’s area, followed by tumor resection. After the cortical layer was removed, subcortical mapping was performed to assess language-associated fibers in the white matter.

Results In all 5 cases, positive responses were obtained at the stimulation sites in the subcortical area adjacent to the FAT, which was visualized by the navigation system. Speech arrest was observed in 4 cases, and remarkably slow speech and conversation was observed in 1 case. The location of these sites was also determined on intraoperative MR images and estimated on preoperative MR images with DTI tractography, confirming the spatial relationships among the stimulation sites and white matter tracts. Tumor removal was successfully performed without damage to this tract, and language function did not deteriorate in any of the cases postoperatively.

Conclusions The authors identified the left FAT and confirmed that it was associated with language functions. This tract should be recognized by clinicians to preserve language function during brain tumor surgery, especially for tumors located in the deep frontal lobe on the language-dominant side.

Is there a risk of seizures in “preventive” awake surgery for incidental diffuse low-grade gliomas?

Is there a risk of seizures in “preventive” awake surgery for incidental diffuse low-grade gliomas?

J Neurosurg 122:1397–1405, 2015

Although a large amount of data supports resection for symptomatic diffuse low-grade glioma (LGG), the therapeutic strategy regarding incidental LGG (ILGG) is still a matter of debate. Indeed, early “preventive” surgery has recently been proposed in asymptomatic patients with LGG, after showing that the extent of resection was larger than in symptomatic patients with LGG. However, the quality of life should be preserved by avoiding both neurological deficit and epilepsy. The aim of this study was to determine the risk of seizures related to such a prophylactic surgical treatment in ILGG.

Methods The authors report a prospective series of 21 patients with ILGG who underwent awake surgery with a minimum follow-up of 20 months following resection. Data regarding clinicoradiological features, surgical procedures, and outcomes were collected and analyzed. In particular, the eventual occurrence and type of seizures in the intra- and postoperative periods were studied, as follows: early (< 3 months) and long-term (until last follow-up) periods.

Results There were no intraoperative seizures in this series. During the early postoperative period, the authors observed only a single episode of partial seizures in a patient with no antiepileptic drug (AED) prophylaxis—all other patients were given antiepileptic treatment following resection. The AEDs were discontinued in all cases, with a mean delay of 8 months after surgery (range 3–24 months). No patient had permanent neurological deficits. All 21 patients returned to an active familial, social, and professional life (working full time in all cases). Total or even “supratotal” resection (the latter meaning that a margin around the tumor visible on FLAIR-weighted MRI was removed) was achieved in 14 cases (67%). In 7 patients (33%) subtotal resection was performed, with a mean residual tumor volume of 1.5 ml (range 1–7 ml). No oncological treatment was administered in the postsurgical period. The mean follow-up after surgery was 49 months (range 20–181 months). Only 2 patients had seizures during the long-term follow-up. Indeed, due to tumor progression after incomplete resection, seizures occurred in 2 cases, 39 and 78 months postsurgery, leading to administration of AEDs and adjuvant treatment. So far, all patients are still alive and enjoy a normal life.

Conclusions: The risk of inducing seizures is very low in ILGG, and it does not represent an argument against early surgery. These data strongly support the proposal of a screening policy for LGG that will evolve toward a preventive treatment in a more systematic manner.

Subcortical language and non-language mapping in awake brain surgery: the use of multimodal tests

Subcortical language and non-language mapping in awake brain surgery- the use of multimodal tests

Acta Neurochir (2015) 157:577–588

Awake craniotomy is currently considered the gold standard to maximise the extent of resection and to minimise postoperative deficits in patients with supratentorial tumours near eloquent areas. In addition to direct electrical stimulation (DES) of the cortex, intraoperative subcortical mapping is increasingly used as it optimises the benefit-to-risk ratio by decreasing (permanent) postoperative neurological deficits. However, only little attention has been paid to subcortical mapping procedures and especially the tasks to be used.

Methods In this article, language and non-language testing at the subcortical level is described and discussed by means of three right-handed cases with a glioma in the left hemisphere. To assess subcortical functions, a multimodal test named the Quick Mixed Test was developed (QMT). Pre-, intra- and postoperative test results are described and discussed in detail.

Results Based on the analysis of these preliminary observations, a number of clinical recommendations for intraoperative subcortical mapping may be made: (1) the selection of a set of language and non-language tests needs to be tailored according to the functional corticosubcortical regions affected by the tumoral lesion and the patient’s characteristics (job/hobby/daily life activities); (2) language and non-language tests should be presented in a multimodal and alternating way during subcortical stimulation since this approach enables screening various functions simultaneously or in a very short period of time and (3) spontaneous speech is a useful adjunct to standardised tests since it most resembles daily life conversation.

Conclusion Administration of multimodal tests during subcortical DES such as the experimental QMT may facilitate identification of eloquent pathways leading to avoidance of permanent neurological impairments.

New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach

New concepts in the management of diffuse low-grade glioma- Proposal of a multistage and individualized therapeutic approach

Neuro-Oncology 17(3), 332–342, 2015

Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a “wait and see” policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity.

However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation.

Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring.

This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL.

New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology.

Insular low-grade glioma and postoperative seizure outcome

Surgery for insular low-grade glioma- predictors of postoperative seizure outcome

J Neurosurg 120:12–23, 2014

Although a number of recent studies on the surgical treatment of insular low-grade glioma (LGG) have demonstrated that aggressive resection leads to increased overall patient survival and decreased malignant progression, less attention has been given to the results with respect to tumor-related epilepsy. The aim of this investigation was to evaluate the impact of volumetric, histological, and intraoperative neurophysiological factors on seizure outcome in patients with insular LGG.

Methods. The authors evaluated predictors of seizure outcome with special emphasis on both the extent of tumor resection (EOR) and the tumor’s infiltrative pattern quantified by computing the difference between the preoperative T2- and T1-weighted MR images (DVT2T1) in 52 patients with preoperative drug-resistant epilepsy.

Results. The 12-month postoperative seizure outcome (Engel class) was as follows: seizure free (Class I), 67.31%; rare seizures (Class II), 7.69%; meaningful seizure improvement (Class III), 15.38%; and no improvement or worsening (Class IV), 9.62%. Poor seizure control was more common in patients with a longer preoperative seizure history (p < 0.002) and higher frequency of seizures (p = 0.008). Better seizure control was achieved in cases with EOR ≥ 90% (p < 0.001) and DVT2T1 < 30 cm3 (p < 0.001). In the final model, DVT2T1 proved to be the strongest independent predictor of seizure outcome in insular LGG patients (p < 0.0001).

Conclusions. No or little postoperative seizure improvement occurs mainly in cases with a prevalent infiltrative tumor growth pattern, expressed by high DVT2T1 values, which consequently reflects a smaller EOR.