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  • Author or Editor: Joshua D. Bernstock x
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Florian Gessler, Markus Bruder, Stephan Duetzmann, Stephanie Tritt, Joshua D. Bernstock, Volker Seifert and Christian Senft

OBJECTIVE

Neurosurgical intervention may increase the risk of developing cerebral vein and dural sinus thrombosis (CVT). The clinical management of CVT in postoperative patients remains unclear. This retrospective study explores the disease occurrence, associated risk factors, and outcomes in patients with tumors who developed CVT after craniotomy.

METHODS

A retrospective analysis and review of patient records in those who had undergone cranial tumor removal within the authors' neurosurgical department was performed. In so doing, the authors identified a cohort of patients who developed CVT postoperatively. The study included patients who presented to the department between January 2004 and December 2013.

RESULTS

Of 2286 patients with intracranial lesions who underwent craniotomy, 35 (1.5%) went on to develop CVT. The authors identified the semisitting position (OR 7.55, 95% CI 3.73–15.31, p < 0.001); intraoperative sinus injury (OR 1.5, 95% CI 3.57–15.76, p < 0.001); and known CVT risk factors (OR 7.77, 95% CI 2.28–21.39, p < 0.001) as predictors of CVT development. Of note, 19 patients (54.3%) had good outcomes (modified Rankin Scale Score 0–1), whereas 9 patients (25.7%) had suffered dependency or death (modified Rankin Scale Score 4–6) at last follow-up. Intracerebral hemorrhage (OR 21.27, 95% CI 1.59–285.01, p = 0.02) and delayed delivery of an intermediate dose of low-molecular-weight heparin anticoagulation (OR 24.12, 95% CI 2.08–280.13, p = 0.01) were associated with unfavorable outcomes.

CONCLUSIONS

Only a minority of patients undergoing craniotomy for tumor removal develop CVT, and the majority of those who do develop CVT recover well. Early administration of an intermediate dose of low-molecular-weight heparin anticoagulation might be considered once CVT is diagnosed.

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Joshua D. Bernstock, James H. Mooney, Adeel Ilyas, Gustavo Chagoya, Dagoberto Estevez-Ordonez, Ahmed Ibrahim and Ichiro Nakano

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is associated with significant morbidity and mortality despite maximal safe resection followed by chemo- and radiotherapy. GBMs contain self-renewing, tumorigenic glioma stem cells that contribute to tumor initiation, heterogeneity, therapeutic resistance, and recurrence. Intratumoral heterogeneity (ITH) of GBMs is also a major contributing factor to poor clinical outcomes associated with these high-grade glial tumors. Herein, the authors summarize recent discoveries and advances in the molecular and phenotypic characterization of GBMs with particular focus on ITH. In so doing, they attempt to highlight recent advances in molecular signatures/properties and metabolic alterations in an effort to clarify translational implications that may ultimately improve clinical outcomes.

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Joshua D. Bernstock, James H. Mooney, Adeel Ilyas, Gustavo Chagoya, Dagoberto Estevez-Ordonez, Ahmed Ibrahim and Ichiro Nakano

Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is associated with significant morbidity and mortality despite maximal safe resection followed by chemo- and radiotherapy. GBMs contain self-renewing, tumorigenic glioma stem cells that contribute to tumor initiation, heterogeneity, therapeutic resistance, and recurrence. Intratumoral heterogeneity (ITH) of GBMs is also a major contributing factor to poor clinical outcomes associated with these high-grade glial tumors. Herein, the authors summarize recent discoveries and advances in the molecular and phenotypic characterization of GBMs with particular focus on ITH. In so doing, they attempt to highlight recent advances in molecular signatures/properties and metabolic alterations in an effort to clarify translational implications that may ultimately improve clinical outcomes.

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Travis J. Atchley, Galal A. Elsayed, Blake Sowers, Harrison C. Walker, Gustavo Chagoya, Matthew C. Davis, Joshua D. Bernstock, Nidal B. Omar, Daxa M. Patel and Barton L. Guthrie

OBJECTIVE

The objective of this study was to determine the incidence of seizures following deep brain stimulation (DBS) electrode implantation and to evaluate factors associated with postoperative seizures.

METHODS

The authors performed a single-center retrospective case-control study. The outcome of interest was seizure associated with DBS implantation. Univariate analyses were performed using the Student t-test for parametric continuous outcomes. The authors used the Kruskal-Wallis test or Wilcoxon rank-sum test for nonparametric continuous outcomes, chi-square statistics for categorical outcomes, and multivariate logistic regression for binomial variables.

RESULTS

A total of 814 DBS electrode implantations were performed in 645 patients (478 [58.7%] in men and 520 [63.9%] in patients with Parkinson’s disease). In total, 22 (3.4%) patients who had undergone 23 (2.8%) placements experienced seizure. Of the 23 DBS implantation–related seizures, 21 were new-onset seizures (3.3% of 645 patients) and 2 were recurrence or worsening of a prior seizure disorder. Among the 23 cases with postimplantation-related seizure, epilepsy developed in 4 (17.4%) postoperatively; the risk of DBS-associated epilepsy was 0.50% per DBS electrode placement and 0.63% per patient. Nine (39.1%) implantation-related seizures had associated postoperative radiographic abnormalities. Multivariate analyses suggested that age at surgery conferred a modest increased risk for postoperative seizures (OR 1.06, 95% CI 1.02–1.10). Sex, primary diagnosis, electrode location and sidedness, and the number of trajectories were not significantly associated with seizures after DBS surgery.

CONCLUSIONS

Seizures associated with DBS electrode placement are uncommon, typically occur early within the postoperative period, and seldom lead to epilepsy. This study suggests that patient characteristics, such as age, may play a greater role than perioperative variables in determining seizure risk. Multiinstitutional studies may help better define and mitigate the risk of seizures after DBS surgery.

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Daisuke Yamashita, Joshua D. Bernstock, Galal Elsayed, Hirokazu Sadahiro, Ahmed Mohyeldin, Gustavo Chagoya, Adeel Ilyas, James Mooney, Dagoberto Estevez-Ordonez, Shinobu Yamaguchi, Victoria L. Flanary, James R. Hackney, Krishna P. Bhat, Harley I. Kornblum, Nicola Zamboni, Sung-Hak Kim, E. Antonio Chiocca and Ichiro Nakano

OBJECTIVE

Despite an aggressive multimodal therapeutic regimen, glioblastoma (GBM) continues to portend a grave prognosis, which is driven in part by tumor heterogeneity at both the molecular and cellular levels. Accordingly, herein the authors sought to identify metabolic differences between GBM tumor core cells and edge cells and, in so doing, elucidate novel actionable therapeutic targets centered on tumor metabolism.

METHODS

Comprehensive metabolic analyses were performed on 20 high-grade glioma (HGG) tissues and 30 glioma-initiating cell (GIC) sphere culture models. The results of the metabolic analyses were combined with the Ivy GBM data set. Differences in tumor metabolism between GBM tumor tissue derived from within the contrast-enhancing region (i.e., tumor core) and that from the peritumoral brain lesions (i.e., tumor edge) were sought and explored. Such changes were ultimately confirmed at the protein level via immunohistochemistry.

RESULTS

Metabolic heterogeneity in both HGG tumor tissues and GBM sphere culture models was identified, and analyses suggested that tyrosine metabolism may serve as a possible therapeutic target in GBM, particularly in the tumor core. Furthermore, activation of the enzyme tyrosine aminotransferase (TAT) within the tyrosine metabolic pathway influenced the noted therapeutic resistance of the GBM core.

CONCLUSIONS

Selective inhibition of the tyrosine metabolism pathway may prove highly beneficial as an adjuvant to multimodal GBM therapies.