Publications by authors named "Mitchel S Berger"

463 Publications

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

J Neurosurg 2021 Oct 1:1-7. Epub 2021 Oct 1.

1Department of Neurological Surgery, University of California, San Francisco.

Objective: 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.
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http://dx.doi.org/10.3171/2021.4.JNS21187DOI Listing
October 2021

Glioblastoma Surgery Imaging-Reporting and Data System: Validation and Performance of the Automated Segmentation Task.

Cancers (Basel) 2021 Sep 17;13(18). Epub 2021 Sep 17.

Department of Clinical Epidemiology and Biostatistics, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands.

For patients with presumed glioblastoma, essential tumor characteristics are determined from preoperative MR images to optimize the treatment strategy. This procedure is time-consuming and subjective, if performed by crude eyeballing or manually. The standardized GSI-RADS aims to provide neurosurgeons with automatic tumor segmentations to extract tumor features rapidly and objectively. In this study, we improved automatic tumor segmentation and compared the agreement with manual raters, describe the technical details of the different components of GSI-RADS, and determined their speed. Two recent neural network architectures were considered for the segmentation task: nnU-Net and AGU-Net. Two preprocessing schemes were introduced to investigate the tradeoff between performance and processing speed. A summarized description of the tumor feature extraction and standardized reporting process is included. The trained architectures for automatic segmentation and the code for computing the standardized report are distributed as open-source and as open-access software. Validation studies were performed on a dataset of 1594 gadolinium-enhanced T1-weighted MRI volumes from 13 hospitals and 293 T1-weighted MRI volumes from the BraTS challenge. The glioblastoma tumor core segmentation reached a Dice score slightly below 90%, a patientwise F1-score close to 99%, and a 95th percentile Hausdorff distance slightly below 4.0 mm on average with either architecture and the heavy preprocessing scheme. A patient MRI volume can be segmented in less than one minute, and a standardized report can be generated in up to five minutes. The proposed GSI-RADS software showed robust performance on a large collection of MRI volumes from various hospitals and generated results within a reasonable runtime.
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http://dx.doi.org/10.3390/cancers13184674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465753PMC
September 2021

The benefit of early surgery on overall survival in incidental low grade glioma patients: a multicenter study.

Neuro Oncol 2021 Sep 8. Epub 2021 Sep 8.

Department of Neurological Surgery, Brain Tumor Research Center, University of California, San Francisco, California.

Background: The role of surgery for incidentally discovered diffuse low-grade gliomas (iLGGs) is debatable and poorly documented in current literature.

Objective: The aim was to identify factors that influence survival for patients that underwent surgical resection of iLGGs in a large multicenter population.

Methods: Clinical, radiological, and surgical data were retrospectively analyzed in 267 patients operated for iLGG from 4 neurosurgical Centers. Univariate and multivariate analyses were performed to identify predictors of overall survival (OS) and tumor recurrence (TR).

Results: The OS rate was 92.41%. The 5- and 10-year estimated OS rates were 98.09% and 93.2% respectively. OS was significantly longer for patients with a lower preoperative tumor volume (p=0.001) and higher extent of resection (EOR) (p=0.037), regardless the WHO defined molecular class (p=0.2). In the final model, OS was influenced only by the preoperative tumor volume (p=0.006), while TR by early surgery (p=0.028). A negative association was found between preoperative tumor volumes and EOR (rs = -0.44, p<0.001).The median preoperative tumor volume was 15 cm 3. The median EOR was 95%. Total or supratotal resection of FLAIR abnormality was achieved in 61.62% of cases.Second surgery was performed in 26.22%. The median time between surgeries was 5.5 years. Histological evolution to high grade glioma was detected in 22.85% of cases (16/70). Permanent mild deficits were observed in 3.08% of cases.

Conclusions: This multicenter study confirms the results of previous studies investigating surgical management of iLGGs and thereby strengthens the evidence in favour of early surgery for these lesions.
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http://dx.doi.org/10.1093/neuonc/noab210DOI Listing
September 2021

Mouse models of glioblastoma for the evaluation of novel therapeutic strategies.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab100. Epub 2021 Jul 26.

Department of Neurological Surgery, University of California, San Francisco, California, USA.

Glioblastoma (GBM) is an incurable brain tumor with a median survival of approximately 15 months despite an aggressive standard of care that includes surgery, chemotherapy, and ionizing radiation. Mouse models have advanced our understanding of GBM biology and the development of novel therapeutic strategies for GBM patients. However, model selection is crucial when testing developmental therapeutics, and each mouse model of GBM has unique advantages and disadvantages that can influence the validity and translatability of experimental results. To shed light on this process, we discuss the strengths and limitations of 3 types of mouse GBM models in this review: syngeneic models, genetically engineered mouse models, and xenograft models, including traditional xenograft cell lines and patient-derived xenograft models.
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http://dx.doi.org/10.1093/noajnl/vdab100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403483PMC
July 2021

5-ALA in Suspected Low-Grade Gliomas: Current Role, Limitations, and New Approaches.

Front Oncol 2021 30;11:699301. Epub 2021 Jul 30.

Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.

Radiologically suspected low-grade gliomas (LGG) represent a special challenge for the neurosurgeon during surgery due to their histopathological heterogeneity and indefinite tumor margin. Therefore, new techniques are required to overcome these current surgical drawbacks. Intraoperative visualization of brain tumors with assistance of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence is one of the major advancements in the neurosurgical field in the last decades. Initially, this technique was exclusively applied for fluorescence-guided surgery of high-grade glioma (HGG). In the last years, the use of 5-ALA was also extended to other indications such as radiologically suspected LGG. Here, we discuss the current role of 5-ALA for intraoperative visualization of focal malignant transformation within suspected LGG. Furthermore, we discuss the current limitations of the 5-ALA technology in pure LGG which usually cannot be visualized by visible fluorescence. Finally, we introduce new approaches based on fluorescence technology for improved detection of pure LGG tissue such as spectroscopic PpIX quantification fluorescence lifetime imaging of PpIX and confocal microscopy to optimize surgery.
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http://dx.doi.org/10.3389/fonc.2021.699301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362830PMC
July 2021

Correlation of natural language assessment results with health-related quality of life in adult glioma patients.

J Neurosurg 2021 Jul 30:1-7. Epub 2021 Jul 30.

1Department of Neurological Surgery and.

Objective: Impairments of speech are common in patients with glioma and negatively impact health-related quality of life (HRQoL). The benchmark for clinical assessments is task-based measures, which are not always feasible to administer and may miss essential components of HRQoL. In this study, the authors tested the hypothesis that variations in natural language (NL) correlate with HRQoL in a pattern distinct from task-based measures of language performance.

Methods: NL use was assessed using audio samples collected unobtrusively from 18 patients with newly diagnosed low- and high-grade glioma. NL measures were calculated using manual segmentation and correlated with Quality of Life in Neurological Disorders (Neuro-QoL) outcomes. Spearman's rank-order correlation was used to determine relationships between Neuro-QoL scores and NL measures.

Results: The distribution of NL measures across the entire patient cohort included a mean ± SD total time speaking of 11.5 ± 2.20 seconds, total number of words of 27.2 ± 4.44, number of function words of 10.9 ± 1.68, number of content words of 16.3 ± 2.91, and speech rate of 2.61 ± 0.20 words/second. Speech rate was negatively correlated with functional domains (rho = -0.62 and p = 0.007 for satisfaction with social roles; rho = -0.74 and p < 0.001 for participation in social roles) but positively correlated with impairment domains (rho = 0.58 and p = 0.009 for fatigue) of Neuro-QoL.

Conclusions: Assessment of NL at the time of diagnosis may be a useful measure in the context of treatment planning and monitoring outcomes for adult patients with glioma.
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http://dx.doi.org/10.3171/2021.1.JNS203387DOI Listing
July 2021

A Crowdsourced Consensus on Supratotal Resection Versus Gross Total Resection for Anatomically Distinct Primary Glioblastoma.

Neurosurgery 2021 09;89(4):712-719

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Background: Gross total resection (GTR) of contrast-enhancing tumor is associated with increased survival in primary glioblastoma. Recently, there has been increasing interest in performing supratotal resections (SpTRs) for glioblastoma.

Objective: To address the published results, which have varied in part due to lack of consensus on the definition and appropriate use of SpTR.

Methods: A crowdsourcing approach was used to survey 21 neurosurgical oncologists representing 14 health systems nationwide. Participants were presented with 11 definitions of SpTR and asked to rate the appropriateness of each definition. Participants reviewed T1-weighed postcontrast and fluid-attenuated inversion-recovery magnetic resonance imaging for 22 anatomically distinct glioblastomas. Participants were asked to assess the tumor location's eloquence, the perceived equipoise of enrolling patients in a randomized trial comparing gross total to SpTR, and their personal treatment plans.

Results: Most neurosurgeons surveyed (n = 18, 85.7%) agree that GTR plus resection of some noncontrast enhancement is an appropriate definition for SpTR. Overall, moderate inter-rater agreement existed regarding eloquence, equipoise, and personal treatment plans. The 4 neurosurgeons who had performed >10 SpTRs for glioblastomas in the past year were more likely to recommend it as their treatment plan (P < .005). Cases were divided into 3 anatomically distinct groups based upon perceived eloquence. Anterior temporal and right frontal glioblastomas were considered the best randomization candidates.

Conclusion: We established a consensus definition for SpTR of glioblastoma and identified anatomically distinct locations deemed most amenable to SpTR. These results may be used to plan prospective trials investigating the potential clinical utility of SpTR for glioblastoma.
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http://dx.doi.org/10.1093/neuros/nyab257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440068PMC
September 2021

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

J Neurosurg 2021 Jul 9:1-11. Epub 2021 Jul 9.

1Department of Neurosurgery, Amsterdam UMC, Vrije Universiteit, Cancer Center Amsterdam.

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.
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http://dx.doi.org/10.3171/2020.11.JNS202897DOI Listing
July 2021

Glioblastoma Surgery Imaging-Reporting and Data System: Standardized Reporting of Tumor Volume, Location, and Resectability Based on Automated Segmentations.

Cancers (Basel) 2021 Jun 8;13(12). Epub 2021 Jun 8.

Department of Neurosurgery, Amsterdam University Medical Centers, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.

Treatment decisions for patients with presumed glioblastoma are based on tumor characteristics available from a preoperative MR scan. Tumor characteristics, including volume, location, and resectability, are often estimated or manually delineated. This process is time consuming and subjective. Hence, comparison across cohorts, trials, or registries are subject to assessment bias. In this study, we propose a standardized Glioblastoma Surgery Imaging Reporting and Data System (GSI-RADS) based on an automated method of tumor segmentation that provides standard reports on tumor features that are potentially relevant for glioblastoma surgery. As clinical validation, we determine the agreement in extracted tumor features between the automated method and the current standard of manual segmentations from routine clinical MR scans before treatment. In an observational consecutive cohort of 1596 adult patients with a first time surgery of a glioblastoma from 13 institutions, we segmented gadolinium-enhanced tumor parts both by a human rater and by an automated algorithm. Tumor features were extracted from segmentations of both methods and compared to assess differences, concordance, and equivalence. The laterality, contralateral infiltration, and the laterality indices were in excellent agreement. The native and normalized tumor volumes had excellent agreement, consistency, and equivalence. Multifocality, but not the number of foci, had good agreement and equivalence. The location profiles of cortical and subcortical structures were in excellent agreement. The expected residual tumor volumes and resectability indices had excellent agreement, consistency, and equivalence. Tumor probability maps were in good agreement. In conclusion, automated segmentations are in excellent agreement with manual segmentations and practically equivalent regarding tumor features that are potentially relevant for neurosurgical purposes. Standard GSI-RADS reports can be generated by open access software.
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http://dx.doi.org/10.3390/cancers13122854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229389PMC
June 2021

In Reply: Functional Outcomes and Health-Related Quality of Life Following Glioma Surgery.

Neurosurgery 2021 08;89(3):E189

Department of Neurological Surgery University of California, San Francisco San Francisco, California, USA.

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http://dx.doi.org/10.1093/neuros/nyab218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364820PMC
August 2021

A single institution retrospective analysis on survival based on treatment paradigms for patients with anaplastic oligodendroglioma.

J Neurooncol 2021 Jul 14;153(3):447-454. Epub 2021 Jun 14.

Division of Neuro-Oncology, Department of Neurological Surgery, University of California, San Francisco, CA, USA.

Introduction: Anaplastic oligodendrogliomas are high-grade gliomas defined molecularly by 1p19q co-deletion. There is no curative therapy, and standard of care includes surgical resection followed by radiation and chemotherapy. However, the benefit of up-front radiation with chemotherapy compared to chemotherapy alone has not been demonstrated in a randomized control trial. Given the potential long-term consequences of radiation therapy, such as cognitive impairment, arteriopathy, endocrinopathy, and hearing/visual impairment, there is an effort to balance longevity with radiation toxicity.

Methods: We performed a retrospective single institution analysis of survival of patients with anaplastic oligodendroglioma over 20 years.

Results: 159 patients were identified as diagnosed with an anaplastic oligodendroglioma between 1996 and 2016. Of those, 40 patients were found to have AO at original diagnosis and had documented 1p19q co-deletion with a median of 7.1 years of follow-up (range: 0.6-16.7 years). After surgery, 45 % of patients were treated with radiation and chemotherapy at diagnosis, and 50 % were treated with adjuvant chemotherapy alone. The group treated with chemotherapy alone had a trend of receiving more cycles of chemotherapy than patients treated with radiation and chemotherapy upfront (p = 0.051). Median overall survival has not yet been reached. The related risk of progression in the upfront, adjuvant chemotherapy only group was almost 5-fold higher than the patients who received radiation and chemotherapy (hazard ratio = 4.85 (1.74-13.49), p = 0.002). However, there was no significant difference in overall survival in patients treated with upfront chemotherapy compared to patients treated upfront with chemotherapy and radiation (p = 0.8). Univariate analysis of age, KPS, extent of resection, or upfront versus delayed radiation was not associated with improved survival.

Conclusions: Initial treatment with adjuvant chemotherapy alone, rather than radiation and chemotherapy, may be an option for some patients with anaplastic oligodendroglioma, as it is associated with similar overall survival despite shorter progression free survival.
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http://dx.doi.org/10.1007/s11060-021-03781-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279971PMC
July 2021

Detection of glioma infiltration at the tumor margin using quantitative stimulated Raman scattering histology.

Sci Rep 2021 06 9;11(1):12162. Epub 2021 Jun 9.

Department of Neurological Surgery, University of California, 505 Parnassus Ave., Rm. M-779, San Francisco, CA, 94143-0112, USA.

In the management of diffuse gliomas, the identification and removal of tumor at the infiltrative margin remains a central challenge. Prior work has demonstrated that fluorescence labeling tools and radiographic imaging are useful surgical adjuvants with macroscopic resolution. However, they lose sensitivity at the tumor margin and have limited clinical utility for lower grade histologies. Fiber-laser based stimulated Raman histology (SRH) is an optical imaging technique that provides microscopic tissue characterization of unprocessed tissues. It remains unknown whether SRH of tissues taken from the infiltrative glioma margin will identify microscopic residual disease. Here we acquired glioma margin specimens for SRH, histology, and tumor specific tissue characterization. Generalized linear mixed models were used to evaluate agreement. We find that SRH identified residual tumor in 82 of 167 margin specimens (49%), compared to IHC confirming residual tumor in 72 of 128 samples (56%), and H&E confirming residual tumor in 82 of 169 samples (49%). Intraobserver agreements between all 3 modalities were confirmed. These data demonstrate that SRH detects residual microscopic tumor at the infiltrative glioma margin and may be a promising tool to enhance extent of resection.
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http://dx.doi.org/10.1038/s41598-021-91648-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190264PMC
June 2021

5-ALA Fluorescence Is a Powerful Prognostic Marker during Surgery of Low-Grade Gliomas (WHO Grade II)-Experience at Two Specialized Centers.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Neurosurgery, Medical University of Vienna, 1090 Vienna, Austria.

The prediction of the individual prognosis of low-grade glioma (LGG) patients is limited in routine clinical practice. Nowadays, 5-aminolevulinic acid (5-ALA) fluorescence is primarily applied for improved intraoperative visualization of high-grade gliomas. However, visible fluorescence is also observed in rare cases despite LGG histopathology and might be an indicator for aggressive tumor behavior. The aim of this study was thus to investigate the value of intraoperative 5-ALA fluorescence for prognosis in LGG patients. We performed a retrospective analysis of patients with newly diagnosed histopathologically confirmed LGG and preoperative 5-ALA administration at two independent specialized centers. In this cohort, we correlated the visible intraoperative fluorescence status with progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS). Altogether, visible fluorescence was detected in 7 (12%) of 59 included patients in focal intratumoral areas. At a mean follow-up time of 5.3 ± 2.9 years, patients with fluorescing LGG had significantly shorter PFS (2.3 ± 0.7 vs. 5.0 ± 0.4 years; 0.01), MTFS (3.9 ± 0.7 vs. 8.0 ± 0.6 years; = 0.03), and OS (5.4 ± 1.0 vs. 10.3 ± 0.5 years; = 0.01) than non-fluorescing tumors. Our data indicate that visible 5-ALA fluorescence during surgery of pure LGG might be an already intraoperatively available marker of unfavorable patient outcome and thus close imaging follow-up might be considered.
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http://dx.doi.org/10.3390/cancers13112540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196836PMC
May 2021

Timing of glioblastoma surgery and patient outcomes: a multicenter cohort study.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab053. Epub 2021 Apr 8.

Amsterdam University Medical Centers, location VU University Medical Center, Neurosurgical Center Amsterdam, Amsterdam, Netherlands.

Background: The impact of time-to-surgery on clinical outcome for patients with glioblastoma has not been determined. Any delay in treatment is perceived as detrimental, but guidelines do not specify acceptable timings. In this study, we relate the time to glioblastoma surgery with the extent of resection and residual tumor volume, performance change, and survival, and we explore the identification of patients for urgent surgery.

Methods: Adults with first-time surgery in 2012-2013 treated by 12 neuro-oncological teams were included in this study. We defined time-to-surgery as the number of days between the diagnostic MR scan and surgery. The relation between time-to-surgery and patient and tumor characteristics was explored in time-to-event analysis and proportional hazard models. Outcome according to time-to-surgery was analyzed by volumetric measurements, changes in performance status, and survival analysis with patient and tumor characteristics as modifiers.

Results: Included were 1033 patients of whom 729 had a resection and 304 a biopsy. The overall median time-to-surgery was 13 days. Surgery was within 3 days for 235 (23%) patients, and within a month for 889 (86%). The median volumetric doubling time was 22 days. Lower performance status (hazard ratio [HR] 0.942, 95% confidence interval [CI] 0.893-0.994) and larger tumor volume (HR 1.012, 95% CI 1.010-1.014) were independently associated with a shorter time-to-surgery. Extent of resection, residual tumor volume, postoperative performance change, and overall survival were not associated with time-to-surgery.

Conclusions: With current decision-making for urgent surgery in selected patients with glioblastoma and surgery typically within 1 month, we found equal extent of resection, residual tumor volume, performance status, and survival after longer times-to-surgery.
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http://dx.doi.org/10.1093/noajnl/vdab053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156977PMC
April 2021

Balancing task sensitivity with reliability for multimodal language assessments.

J Neurosurg 2021 May 28:1-8. Epub 2021 May 28.

1Department of Neurological Surgery, University of California, San Francisco, California; and.

Objective: Intraoperative tasks for awake language mapping are typically selected based on the language tracts that will likely be encountered during tumor resection. However, diminished attention and arousal secondary to perioperative sedatives may reduce a task's usefulness for identifying eloquent cortex. For instance, accuracy in performing select language tasks may be high preoperatively but decline in the operating room. In the present study, the authors sought to identify language tasks that can be performed with high accuracy in both situational contexts so the neurosurgical team can be confident that speech errors committed during awake language mapping result from direct cortical stimulation to eloquent cortex, rather than from poor performance in general.

Methods: We administered five language tasks to 44 patients: picture naming (PN), text reading (TR), auditory object naming (AN), repetition of 4-syllable words (4SYL), and production of syntactically intact sentences (SYNTAX). Performance was assessed using the 4-point scale of the quick aphasia battery 24 hours preoperatively and intraoperatively. We next determined whether or not accuracy on each task was higher preoperatively than intraoperatively. We also determined whether 1) intraoperative accuracy on a given task predicted intraoperative performance on the other tasks and 2) low preoperative accuracy on a task predicted a decrease in accuracy intraoperatively.

Results: Relative to preoperative accuracy, intraoperative accuracy declined on PN (3.90 vs 3.82, p = 0.0001), 4SYL (3.96 vs 3.91, p = 0.0006), and SYNTAX (3.85 vs 3.67, p = 0.0001) but not on TR (3.96 vs 3.94, p = 0.13) or AN (3.70 vs 3.58, p = 0.058). Intraoperative accuracy on PN and AN independently predicted intraoperative accuracy on the remaining language tasks (p < 0.001 and p < 0.01, respectively). Finally, low preoperative accuracy on SYNTAX predicted a decrease in accuracy on this task intraoperatively (R2 = 0.36, p = 0.00002).

Conclusions: While TR lacks sensitivity in identifying language deficits at baseline, accuracy on TR is stable across testing settings. Baseline accuracy on the other four of our five language tasks was not predictive of intraoperative performance, signifying the need to repeat language tests prior to stimulation mapping to confirm reliability.
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http://dx.doi.org/10.3171/2020.10.JNS202947DOI Listing
May 2021

Robust Deep Learning-based Segmentation of Glioblastoma on Routine Clinical MRI Scans Using Sparsified Training.

Radiol Artif Intell 2020 Sep 30;2(5):e190103. Epub 2020 Sep 30.

Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands (R.S.E., M.v.H., M.G.W.); Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (M.V., F.B., H.V., J.C.d.M.); Neurosurgical Center Amsterdam, Amsterdam UMC, Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands (D.M.J.M., P.C.D.W.H.); Institutes of Neurology & Healthcare Engineering, University College London, London, England (F.B.); Faculty of Biology, Medicine & Health, Division of Cancer Sciences, University of Manchester and Christie NHS Trust, Manchester, England (M.v.H.); Neurosurgical Oncology Unit, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Humanitas Research Hospital, IRCCS, Milan, Italy (L.B., M.C.N., M.R., T.S.); Department of Neurologic Surgery, University of California-San Francisco, San Francisco, Calif (M.S.B., S.H.J.); Department of Neurosurgery, Medical University Vienna, Vienna, Austria (B.K., G.W.); Department of Biomedical Imaging and Image-guided Therapy, Medical University Vienna, Vienna, Austria (J.F.); Department of Neurology & Neurosurgery, University Medical Center Utrecht, Utrecht, the Netherlands (P.A.J.T.R.); and Department of Neurologic Surgery, Hôpital Lariboisière, Paris, France (E.M.).

Purpose: To improve the robustness of deep learning-based glioblastoma segmentation in a clinical setting with sparsified datasets.

Materials And Methods: In this retrospective study, preoperative T1-weighted, T2-weighted, T2-weighted fluid-attenuated inversion recovery, and postcontrast T1-weighted MRI from 117 patients (median age, 64 years; interquartile range [IQR], 55-73 years; 76 men) included within the Multimodal Brain Tumor Image Segmentation (BraTS) dataset plus a clinical dataset (2012-2013) with similar imaging modalities of 634 patients (median age, 59 years; IQR, 49-69 years; 382 men) with glioblastoma from six hospitals were used. Expert tumor delineations on the postcontrast images were available, but for various clinical datasets, one or more sequences were missing. The convolutional neural network, DeepMedic, was trained on combinations of complete and incomplete data with and without site-specific data. Sparsified training was introduced, which randomly simulated missing sequences during training. The effects of sparsified training and center-specific training were tested using Wilcoxon signed rank tests for paired measurements.

Results: A model trained exclusively on BraTS data reached a median Dice score of 0.81 for segmentation on BraTS test data but only 0.49 on the clinical data. Sparsified training improved performance (adjusted < .05), even when excluding test data with missing sequences, to median Dice score of 0.67. Inclusion of site-specific data during sparsified training led to higher model performance Dice scores greater than 0.8, on par with a model based on all complete and incomplete data. For the model using BraTS and clinical training data, inclusion of site-specific data or sparsified training was of no consequence.

Conclusion: Accurate and automatic segmentation of glioblastoma on clinical scans is feasible using a model based on large, heterogeneous, and partially incomplete datasets. Sparsified training may boost the performance of a smaller model based on public and site-specific data.Published under a CC BY 4.0 license.
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http://dx.doi.org/10.1148/ryai.2020190103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082349PMC
September 2020

Are preoperative chlorhexidine gluconate showers associated with a reduction in surgical site infection following craniotomy? A retrospective cohort analysis of 3126 surgical procedures.

J Neurosurg 2021 Apr 30:1-9. Epub 2021 Apr 30.

Departments of1Neurological Surgery.

Objective: Surgical site infection (SSI) is a complication linked to increased costs and length of hospital stay. Prevention of SSI is important to reduce its burden on individual patients and the healthcare system. The authors aimed to assess the efficacy of preoperative chlorhexidine gluconate (CHG) showers on SSI rates following cranial surgery.

Methods: In November 2013, a preoperative CHG shower protocol was implemented at the authors' institution. A total of 3126 surgical procedures were analyzed, encompassing a time frame from April 2012 to April 2016. Cohorts before and after implementation of the CHG shower protocol were evaluated for differences in SSI rates.

Results: The overall SSI rate was 0.6%. No significant differences (p = 0.11) were observed between the rate of SSI of the 892 patients in the preimplementation cohort (0.2%) and that of the 2234 patients in the postimplementation cohort (0.8%). Following multivariable analysis, implementation of preoperative CHG showers was not associated with decreased SSI (adjusted OR 2.96, 95% CI 0.67-13.1; p = 0.15).

Conclusions: This is the largest study, according to sample size, to examine the association between CHG showers and SSI following craniotomy. CHG showers did not significantly alter the risk of SSI after a cranial procedure.
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http://dx.doi.org/10.3171/2020.10.JNS201255DOI Listing
April 2021

Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas.

Neuro Oncol 2021 Apr 5. Epub 2021 Apr 5.

Department of Neurological Surgery, University of California, San Francisco, CA, USA.

Background: Chemotherapy improves overall survival after surgery and radiotherapy for newly diagnosed high-risk IDH-mutant low-grade gliomas, but a proportion of patients treated with temozolomide (TMZ) will develop recurrent tumors with TMZ-induced hypermutation. We aimed to determine the prevalence of TMZ-induced hypermutation at recurrence and prognostic implications.

Methods: We sequenced recurrent tumors from 82 patients with initially low-grade IDH-mutant gliomas who underwent re-operation and correlated hypermutation status with grade at recurrence and subsequent clinical outcomes.

Results: Hypermutation was associated with high-grade disease at the time of re-operation (OR 12.0 95% CI 2.5-115.5, p=0.002) and was identified at transformation in 57% of recurrent LGGs previously exposed to TMZ. After anaplastic (grade III) transformation, hypermutation was associated with shorter survival on univariate and multivariate analysis (HR 3.4, 95% CI 1.2-9.9, p=0.024), controlling for tumor grade, subtype, age, and prior radiotherapy. The effect of hypermutation on survival after transformation was validated in an independent, published dataset. Hypermutated (HM) tumors were more likely to develop discontiguous foci of disease in the brain and spine (p=0.003). To estimate the overall incidence of high-grade transformation among low-grade IDH-mutant tumors, data from a phase II trial of TMZ for LGG were analyzed. 8-year transformation-free survival was 53.8% (95% CI 42.8-69.2) and 61% of analyzed transformed cases were HM.

Conclusions: TMZ-induced hypermutation is a common event in transformed LGG previously treated with TMZ, and is associated with worse prognosis and development of discontiguous disease after recurrence. These findings impact tumor classification at recurrence, prognostication, and clinical trial design.
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http://dx.doi.org/10.1093/neuonc/noab081DOI Listing
April 2021

Evidence-based recommendations on categories for extent of resection in diffuse glioma.

Eur J Cancer 2021 05 2;149:23-33. Epub 2021 Apr 2.

Department of Neurosurgery, Ludwig-Maximilians-University School of Medicine, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Germany. Electronic address:

Surgical resection represents the standard of care in diffuse glioma, and more extensive tumour resection appears to be associated with favourable outcome. Up to now, terminology to describe extent of resection has been inconsistently applied across clinical trials which hampers comparative analysis of cohorts between different studies. Based on a comprehensive literature review, we developed evidence-based expert recommendations on categories for extent of resection. Recommendations are formulated for the categories 'biopsy', 'partial resection', 'subtotal resection', 'near total resection', 'complete resection' and 'supramaximal resection'. Definitions rest on reduction of contrast- and non-contrast-enhancing tumour in glioblastoma, and on reduction of T2/FLAIR-hyperintense tumour in gliomas WHO grade 2 or 3. Both relative reduction of tumour volume (in percentage) as a measurement of surgical efficacy and absolute residual tumour volume (in cm) as a measurement of remaining tumour burden are incorporated into the categories for extent of resection. Class of evidence for the proposed categories ranges from class IIB to IV. Limitations of the suggested categories are discussed. The proposed categories on extent of resection offer a framework to standardize nomenclature based on previous studies, and will need to be evaluated in prospective, molecularly well-defined cohorts. Our categories may eventually help as a stratification factor for future clinical trials.
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http://dx.doi.org/10.1016/j.ejca.2021.03.002DOI Listing
May 2021

Functional maps of direct electrical stimulation-induced speech arrest and anomia: a multicentre retrospective study.

Brain 2021 Sep;144(8):2541-2553

Department of Neurological Surgery, University of California, San Francisco, CA 94143, USA.

Direct electrical stimulation, the transient 'lesional' method probing brain function, has been utilized in identifying the language cortex and preserving language function during epilepsy and neuro-oncological surgeries for about a century. However, comparison of functional maps of the language cortex across languages/continents based on cortical stimulation remains unclear. We conducted a retrospective multicentre study including four cohorts of direct electrical stimulation mapping from four centres across three continents, where three indigenous languages (English, French and Mandarin) are spoken. All subjects performed the two most common language tasks: number counting and picture naming during stimulation. All language sites were recorded and normalized to the same brain template. Next, Spearman's correlation analysis was performed to explore the consistency of the distributions of the language cortex across centres, a kernel density estimation to localize the peak coordinates, and a hierarchical cluster analysis was performed to detect the crucial epicenters. A total of 598 subjects with 917 speech arrest sites (complete interruption of ongoing counting) and 423 anomia sites (inability to name or misnaming) were included. Different centres presented highly consistent distribution patterns for speech arrest (Spearman's coefficient r ranged from 0.60 to 0.85, all pair-wise correlations P < 0.05), and similar patterns for anomia (Spearman's coefficient r ranged from 0.37 to 0.80). The combinational speech arrest map was divided into four clusters: cluster 1 mainly located in the ventral precentral gyrus and pars opercularis, which contained the peak of speech arrest in the ventral precentral gyrus; cluster 2 in the ventral and dorsal precentral gyrus; cluster 3 in the supplementary motor area; cluster 4 in the posterior superior temporal gyrus and supramarginal gyrus. The anomia map revealed two clusters: one was in the posterior part of the superior and middle temporal gyri, which peaked at the posterior superior temporal gyrus; and the other within the inferior frontal gyrus, peaked at the pars triangularis. This study constitutes the largest series to date of language maps generated from direct electrical stimulation mapping. The consistency of data provides evidence for common language networks across languages, in the context of both speech and naming circuit. Our results not only clinically offer an atlas for language mapping and protection, but also scientifically provide better insight into the functional organization of language networks.
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http://dx.doi.org/10.1093/brain/awab125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453410PMC
September 2021

Convergence of heteromodal lexical retrieval in the lateral prefrontal cortex.

Sci Rep 2021 03 18;11(1):6305. Epub 2021 Mar 18.

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, 94143, USA.

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.
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http://dx.doi.org/10.1038/s41598-021-85802-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973515PMC
March 2021

Endovascular embolization versus surgical clipping in a single surgeon series of basilar artery aneurysms: a complementary approach in the endovascular era.

Acta Neurochir (Wien) 2021 05 10;163(5):1527-1540. Epub 2021 Mar 10.

Department of Neurological Surgery, University of California, San Francisco, CA, USA.

Background: Currently, most basilar artery aneurysms (BAAs) are treated endovascularly. Surgery remains an appropriate therapy for a subset of all intracranial aneurysms. Whether open microsurgery would be required or utilized, and to what extent, for BAAs treated by a surgeon who performs both endovascular and open procedures has not been reported.

Methods: Retrospective analysis of prospectively maintained, single-surgeon series of BAAs treated with endovascular or open surgery from the first 5 years of practice.

Results: Forty-two procedures were performed in 34 patients to treat BAAs-including aneurysms arising from basilar artery apex, trunk, and perforators. Unruptured BAAs accounted for 35/42 cases (83.3%), and the mean aneurysm diameter was 8.4 ± 5.4 mm. Endovascular coiling-including stent-assisted coiling-accounted for 26/42 (61.9%) treatments and led to complete obliteration in 76.9% of cases. Four patients in the endovascular cohort required re-treatment. Surgical clip reconstruction accounted for 16/42 (38.1%) treatments and led to complete obliteration in 88.5% of cases. Good neurologic outcome (mRS ≤ 2) was achieved in 88.5% and 75.0% of patients in endovascular and open surgical cohorts, respectively (p = 0.40). Univariate logistic regression analysis demonstrated that advanced age (OR 1.11[95% CI 1.01-1.23]) or peri-procedural adverse event (OR 85.0 [95% CI 6.5-118.9]), but not treatment modality (OR 0.39[95% CI 0.08-2.04]), was the predictor of poor neurologic outcome.

Conclusions: Complementary implementation of both endovascular and open surgery facilitates individualized treatment planning of BAAs. By leveraging strengths of both techniques, equivalent clinical outcomes and technical proficiency may be achieved with both modalities.
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http://dx.doi.org/10.1007/s00701-021-04803-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053658PMC
May 2021

Sport-Related Structural Brain Injury and Return to Play: Systematic Review and Expert Insight.

Neurosurgery 2021 05;88(6):E495-E504

Department of Neurosurgery, Johns Hopkins University Medical Center, Baltimore, Maryland, USA.

Background: Sport-related structural brain injury (SRSBI) is intracranial pathology incurred during sport. Management mirrors that of non-sport-related brain injury. An empirical vacuum exists regarding return to play (RTP) following SRSBI.

Objective: To provide key insight for operative management and RTP following SRSBI using a (1) focused systematic review and (2) survey of expert opinions.

Methods: A systematic literature review of SRSBI from 2012 to present in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and a cross-sectional survey of RTP in SRSBI by 31 international neurosurgeons was conducted.

Results: Of 27 included articles out of 241 systematically reviewed, 9 (33.0%) case reports provided RTP information for 12 athletes. To assess expert opinion, 31 of 32 neurosurgeons (96.9%) provided survey responses. For acute, asymptomatic SRSBI, 12 (38.7%) would not operate. Of the 19 (61.3%) who would operate, midline shift (63.2%) and hemorrhage size > 10 mm (52.6%) were the most common indications. Following SRSBI with resolved hemorrhage, with or without burr holes, the majority of experts (>75%) allowed RTP to high-contact/collision sports at 6 to 12 mo. Approximately 80% of experts did not endorse RTP to high-contact/collision sports for athletes with persistent hemorrhage. Following craniotomy for SRSBI, 40% to 50% of experts considered RTP at 6 to 12 mo. Linear regression revealed that experts allowed earlier RTP at higher levels of play (β = -0.58, 95% CI -0.111, -0.005, P = .033).

Conclusion: RTP decisions following structural brain injury in athletes are markedly heterogeneous. While individualized RTP decisions are critical, aggregated expert opinions from 31 international sports neurosurgeons provide key insight. Level of play was found to be an important consideration in RTP determinations.
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http://dx.doi.org/10.1093/neuros/nyab041DOI Listing
May 2021

Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas.

Cancers (Basel) 2021 Feb 7;13(4). Epub 2021 Feb 7.

Department of Neurosurgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.
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http://dx.doi.org/10.3390/cancers13040662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916021PMC
February 2021

Preoperative Applications of Navigated Transcranial Magnetic Stimulation.

Front Neurol 2020 22;11:628903. Epub 2021 Jan 22.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.

Preoperative mapping of cortical structures prior to neurosurgical intervention can provide a roadmap of the brain with which neurosurgeons can navigate critical cortical structures. In patients undergoing surgery for brain tumors, preoperative mapping allows for improved operative planning, patient risk stratification, and personalized preoperative patient counseling. Navigated transcranial magnetic stimulation (nTMS) is one modality that allows for highly accurate, image-guided, non-invasive stimulation of the brain, thus allowing for differentiation between eloquent and non-eloquent cortical regions. Motor mapping is the best validated application of nTMS, yielding reliable maps with an accuracy similar to intraoperative cortical mapping. Language mapping is also commonly performed, although nTMS language maps are not as highly concordant with direct intraoperative cortical stimulation maps as nTMS motor maps. Additionally, nTMS has been used to localize cortical regions involved in other functions such as facial recognition, calculation, higher-order motor processing, and visuospatial orientation. In this review, we evaluate the growing literature on the applications of nTMS in the preoperative setting. First, we analyze the evidence in support of the most common clinical applications. Then we identify usages that show promise but require further validation. We also discuss developing nTMS techniques that are still in the experimental stage, such as the use of nTMS to enhance postoperative recovery. Finally, we highlight practical considerations when utilizing nTMS and, importantly, its safety profile in neurosurgical patients. In so doing, we aim to provide a comprehensive review of the role of nTMS in the neurosurgical management of a patient with a brain tumor.
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http://dx.doi.org/10.3389/fneur.2020.628903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862711PMC
January 2021

Functional Outcomes and Health-Related Quality of Life Following Glioma Surgery.

Neurosurgery 2021 03;88(4):720-732

University of California San Francisco, Department of Neurological Surgery, San Francisco, California.

Functional outcome following glioma surgery is defined as how the patient functions or feels. Functional outcome is a coprimary end point of surgery in patients with diffuse glioma, together with oncological outcome. In this review, we structure the functional outcome measurements following glioma surgery as reported in the last 5 yr. We review various perspectives on functional outcome of glioma surgery with available measures, and offer suggestions for their use. From the recent neurosurgical literature, 160 publications were retrieved fulfilling the selection criteria. In these publications, neurological outcomes were reported most often, followed by activities of daily living, seizure outcomes, neurocognitive outcomes, and health-related quality of life or well-being. In more than a quarter of these publications functional outcome was not reported. A minimum essential consensus set of functional outcome measurements would benefit comparison across neurosurgical reports. The consensus set should be based on a combination of clinician- and patient-reported outcomes, assessed at a predefined time before and after surgery. The selected measurements should have psychometric properties supporting the intended use including validity-related evidence, reliability, and sensitivity to detect meaningful change with minimal burden to ensure compliance. We circulate a short survey as a start towards reporting guidelines. Many questions remain to better understand, report, and improve functional outcome following glioma surgery.
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http://dx.doi.org/10.1093/neuros/nyaa365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955971PMC
March 2021

Data-Driven, Visual Framework for the Characterization of Aphasias Across Stroke, Post-resective, and Neurodegenerative Disorders Over Time.

Front Neurol 2020 29;11:616764. Epub 2020 Dec 29.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.

Aphasia classifications and specialized language batteries differ across the fields of neurodegenerative disorders and lesional brain injuries, resulting in difficult comparisons of language deficits across etiologies. In this study, we present a simplified framework, in which a widely-used aphasia battery captures clinical clusters across disease etiologies and provides a quantitative and visual method to characterize and track patients over time. The framework is used to evaluate populations representing three disease etiologies: stroke, primary progressive aphasia (PPA), and post-operative aphasia. A total of 330 patients across three populations with cerebral injury leading to aphasia were investigated, including 76 patients with stroke, 107 patients meeting criteria for PPA, and 147 patients following left hemispheric resective surgery. Western Aphasia Battery (WAB) measures (Information Content, Fluency, answering Yes/No questions, Auditory Word Recognition, Sequential Commands, and Repetition) were collected across the three populations and analyzed to develop a multi-dimensional aphasia model using dimensionality reduction techniques. Two orthogonal dimensions were found to explain 87% of the variance across aphasia phenotypes and three disease etiologies. The first dimension reflects shared weighting across aphasia subscores and correlated with aphasia severity. The second dimension incorporates fluency and comprehension, thereby separating Wernicke's from Broca's aphasia, and the non-fluent/agrammatic from semantic PPA variants. Clusters representing clinical classifications, including late PPA presentations, were preserved within the two-dimensional space. Early PPA presentations were not classifiable, as specialized batteries are needed for phenotyping. Longitudinal data was further used to visualize the trajectory of aphasias during recovery or disease progression, including the rapid recovery of post-operative aphasic patients. This method has implications for the conceptualization of aphasia as a spectrum disorder across different disease etiology and may serve as a framework to track the trajectories of aphasia progression and recovery.
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http://dx.doi.org/10.3389/fneur.2020.616764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801263PMC
December 2020
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