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Orin Bloch and Geoffrey T. Manley

✓Despite decades of research into the pathogenesis of cerebral edema, nonsurgical therapy for brain swelling has advanced very little after more than half a century. Recent advancements in our understanding of molecular water transport have generated interest in new targets for edema therapy. Aquaporin-4 (AQP4) is the primary cellular water channel in the brain, localized to astrocytic foot processes along the blood–brain barrier and brain–cerebrospinal fluid interface. Multiple studies of transgenic mice with a complete deficiency or altered expression of AQP4 suggest a prominent role for AQP4 in cerebral water transport. In models of cellular (cytotoxic) edema, AQP4 deletion or alteration has been shown to be protective, reducing edema burden and improving overall survival. In contrast, AQP4 deletion in extra-cellular (vasogenic) edema results in decreased edema clearance and greater progression of disease. The data strongly support the conclusion that AQP4 plays a pivotal role in cerebral water transport and is an essential mediator in the formation and resorption of edema fluid from the brain parenchyma. These findings also suggest that drug therapy targeting AQP4 function and expression may dramatically alter our ability to treat cerebral edema.

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Langston T. Holly, Orin Bloch, and J. Patrick Johnson

Object

Paired point matching alone and paired point matching combined with surface matching are the two techniques used for the registration step in preoperative computerized tomography–based spinal image guidance. In the present study the authors sought to compare paired point–matching registration alone with paired point matching supplemented with surface matching to determine if the addition of surface matching improves navigational accuracy.

Methods

Pedicle screws were placed in three embalmed human cervicothoracic spinal specimens during image guidance to serve as a reference points. The specimens were then rescanned, and each level was registered using paired point matching alone and then by paired point supplemented with surface matching. Navigational accuracy was assessed by placing the stereotactic probe in the center of the screw head, and measuring the apparent distance between the screw head and probe on the computer monitor. Statistical analysis was used to compare the registration error and navigational error between the two techniques.

Seventy-five screws were placed at 46 vertebral levels. The mean registration error for the paired point matching/surface matching technique (0.5 mm) was significantly lower (p < 0.001) than that of the paired point matching alone technique (1.2 mm); however, the intertechnique difference in navigational error was nearly equivalent (1.3 mm compared with 1.4 mm) and statistically insignificant (p > 0.05).

Conclusions

Although the addition of surface matching to paired point registration significantly decreased the mean registration error, the actual navigational accuracy between the two techniques was equivalent when easily distinguishable points were meticulously selected. The use of paired point matching alone did not compromise the accuracy of navigation and is likely to result in decreased operating time.

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Langston T. Holly, Orin Bloch, Chinyere Obasi, and J. Patrick Johnson

Object. Intraoperative image guidance provides real-time three-dimensional visualization and has been successfully applied in many posterior spinal procedures. The feasibility of applying these techniques to anterior spinal surgery has not been studied systematically because the anterior spine, in contrast to the posterior spine, lacks distinct anatomical landmarks for registration. The authors sought to evaluate the practicality of performing stereotaxy in the anterior spine in a cadaveric model.

Methods. Unilateral C4—L4 pedicle screws were placed posteriorly in three cadaveric specimens to serve as unknown markers within each vertebral body. The specimens then underwent computerized tomography (CT) scanning, and the CT data were transferred to an optical tracking system. The anterior surface of the spine was registered for use with the stereotactic system by using a paired point—matching technique. Attached to a surgical drill, K-wires were placed under stereotactic guidance in a tip-to-tip orientation with the posterior pedicle screws. A second postoperative CT scan was obtained, and accuracy was determined by measuring the distance between the tips of the K-wire and pedicle screw.

The K-wires were placed tip to tip with pedicle screw markers in 57 vertebral levels. The mean registration error was 1.47 ± 0.04 mm, and when combined with the universal instrument registration error of 0.7 mm yielded an overall registration error of 2.17 ± 0.04 mm. The mean tip-to-tip distance for all K-wires placed was 2.46 ± 0.23 mm. The difference between the mean tip-to-tip distance and overall registration error was not statistically significant (p > 0.05), indicating that the K-wires were placed within the expected range of error.

Conclusions. The results of this study confirmed the feasibility of performing anterior stereotactic procedures throughout the spine. The accuracy of the findings in this study indicates that anterior stereotaxy should be applicable in clinical practice.

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Eli T. Sayegh, Shayan Fakurnejad, Taemin Oh, Orin Bloch, and Andrew T. Parsa

Patients who undergo craniotomy for brain tumor resection are prone to experiencing seizures, which can have debilitating medical, neurological, and psychosocial effects. A controversial issue in neurosurgery is the common practice of administering perioperative anticonvulsant prophylaxis to these patients despite a paucity of supporting data in the literature. The foreseeable benefits of this strategy must be balanced against potential adverse effects and interactions with critical medications such as chemotherapeutic agents and corticosteroids. Multiple disparate metaanalyses have been published on this topic but have not been applied into clinical practice, and, instead, personal preference frequently determines practice patterns in this area of management. Therefore, to select the current best available evidence to guide clinical decision making, the literature was evaluated to identify meta-analyses that investigated the efficacy and/or safety of anticonvulsant prophylaxis in this patient population. Six meta-analyses published between 1996 and 2011 were included in the present study. The Quality of Reporting of Meta-analyses and Oxman-Guyatt methodological quality assessment tools were used to score these meta-analyses, and the Jadad decision algorithm was applied to determine the highest-quality meta-analysis. According to this analysis, 2 metaanalyses were deemed to be the current best available evidence, both of which conclude that prophylactic treatment does not improve seizure control in these patients. Therefore, this management strategy should not be routinely used.

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John D. Rolston, Seunggu J. Han, Orin Bloch, and Andrew T. Parsa

Object

Venous thromboembolisms (VTEs) occur frequently in surgical patients and can manifest as pulmonary emboli (PEs) or deep venous thromboses (DVTs). While many medical therapies have been shown to prevent VTEs, neurosurgeons are concerned about the use of anticoagulants in the postoperative setting. To better understand the prevalence of and the patient-level risk factors for VTE, the authors analyzed data from the National Surgical Quality Improvement Program (NSQIP).

Methods

Retrospective data on 1,777,035 patients for the years from 2006 to 2011 were acquired from the American College of Surgeons NSQIP database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as “neurological surgery.” Univariate statistics were calculated using the chi-square test, with 95% confidence intervals used for the resultant risk ratios. Multivariate models were constructed using binary logistic regression with a maximum number of 20 iterations.

Results

Venous thromboembolisms were found in 1.7% of neurosurgical patients, with DVTs roughly twice as common as PEs (1.3% vs 0.6%, respectively). Significant independent predictors included ventilator dependence, immobility (that is, quadriparesis, hemiparesis, or paraparesis), chronic steroid use, and sepsis. The risk of VTE was significantly higher in patients who had undergone cranial procedures (3.4%) than in those who had undergone spinal procedures (1.1%).

Conclusions

Venous thromboembolism is a common complication in neurosurgical patients, and the frequency has not changed appreciably over the past several years. Many factors were identified as independently predictive of VTEs in this population: ventilator dependence, immobility, and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Venous thromboembolisms appear significantly more likely to occur in patients undergoing cranial procedures than in those undergoing spinal procedures. A better appreciation of the prevalence of and the risk factors for VTEs in neurosurgical patients will allow targeting of interventions and a better understanding of which patients are most at risk.

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Orin Bloch, Langston T. Holly, Jongsoo Park, Chinyere Obasi, Kee Kim, and J. Patrick Johnson

Object. In recent studies some authors have indicated that 20% of patients have at least one ectatic vertebral artery (VA) that, based on previous criteria in which preoperative computerized tomography (CT) and standard intraoperative fluoroscopic techniques were used, may prevent the safe placement of C1–2 transarticular screws. The authors conducted this study to determine whether frameless stereotaxy would improve the accuracy of C1–2 transarticular screw placement in healthy patients, particularly those whom previous criteria would have excluded.

Methods. The authors assessed the accuracy of frameless stereotaxy for C1–2 transarticular screw placement in 17 cadaveric cervical spines. Preoperatively obtained CT scans of the C-2 vertebra were registered on a stereotactic workstation. The dimensions of the C-2 pars articularis were measured on the workstation, and a 3.5-mm screw was stereotactically placed if the height and width of the pars interarticularis was greater than 4 mm. The specimens were evaluated with postoperative CT scanning and visual inspection. Screw placement was considered acceptable if the screw was contained within the C-2 pars interarticularis, traversed the C1–2 joint, and the screw tip was shown to be within the anterior cortex of the C-1 lateral mass.

Transarticular screws were accurately placed in 16 cadaveric specimens, and only one specimen (5.9%) was excluded because of anomalous VA anatomy. In contrast, a total of four specimens (23.5%) showed significant narrowing of the C-2 pars interarticularis due to vascular anatomy that would have precluded atlantoaxial transarticular screw placement had previous nonimage-guided criteria been used.

Conclusions. Frameless stereotaxy provides precise image guidance that improves the safety of C1–2 transarticular screw placement and potentially allows this procedure to be performed in patients previously excluded because of the inaccuracy of nonimage-guided techniques.

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Jonathan B. Lamano, Robert A. Riestenberg, Aden P. Haskell-Mendoza, Dennis Lee, Michael T. Sharp, and Orin Bloch

OBJECTIVE

Patients increasingly utilize online physician review websites (PRWs) and social media to inform healthcare-related decisions. This provides neurosurgeons with opportunities for increased patient engagement. And despite the growing use of social media among neurosurgeons, the relationship between social media utilization and online reviews remains unknown. The goal of this study was to characterize the relationship between social media utilization and PRW ratings across academic neurosurgery departments.

METHODS

Social media accounts (Twitter, Facebook, YouTube, Instagram) of academic neurosurgery departments were identified. Online reviews for individual faculty were obtained from Healthgrades, Vitals, WebMD, and Google. Reviews were aggregated to identify the total number of reviews per department, to generate a composite departmental rating, and to calculate a summed departmental score. US News & World Report (USNWR) and Doximity rankings were recorded for each department. Social media utilization by individual neurosurgeons and associated ratings were investigated within the departments with the highest social media utilization.

RESULTS

Seventy-eight percent of academic neurosurgery departments utilized social media. The most prevalent platform was YouTube (49.1%), followed by Twitter (46.5%), Facebook (38.6%), and Instagram (16.7%). Higher patient ratings on PRWs were associated with the utilization of YouTube (p = 0.048) or Twitter (p = 0.02). The number of social media platforms utilized demonstrated a significant, positive correlation with patient ratings (p = 0.006) and summed patient ratings (p = 0.048). Although USNWR (p = 0.02) and Doximity (p = 0.0008) rankings correlated with patient ratings, only the number of social media platforms utilized remained a significant predictor of patient ratings on multivariate analysis (p = 0.0001). Thirty-one percent of academic neurosurgeons from departments with high social media utilization were active on social media. The most prevalent social media platform among individual neurosurgeons was Twitter (27.4%), followed by Instagram (8.4%), Facebook (4.9%), and YouTube (2.2%). Higher summed patient scores were associated with individual neurosurgeon utilization of YouTube (p = 0.04), Facebook (p < 0.0001), and Instagram (p = 0.01). Increased social media utilization among neurosurgeons was correlated with a greater number of patient reviews (p = 0.006) and higher summed patient scores (p = 0.003). On multivariate analysis, only Facebook use remained a significant predictor of the number of patient reviews received (p = 0.002) and summed patient satisfaction scores (p < 0.001).

CONCLUSIONS

An increased social media presence is associated with higher ratings on PRWs. As neurosurgeons continue to expand their online presence, they should be aware of the possible impact of social media on online patient reviews.

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Orin Bloch, Seunggu J. Han, Soonmee Cha, Matthew Z. Sun, Manish K. Aghi, Michael W. McDermott, Mitchel S. Berger, and Andrew T. Parsa

Object

Extent of resection (EOR) has been shown to be an important prognostic factor for survival in patients undergoing initial resection of glioblastoma (GBM), but the significance of EOR at repeat craniotomy for recurrence remains unclear. In this study the authors investigate the impact of EOR at initial and repeat resection of GBM on overall survival.

Methods

Medical records were reviewed for all patients undergoing craniotomy for GBM at the University of California San Francisco Medical Center from January 1, 2005, through August 15, 2009. Patients who had a second craniotomy for pathologically confirmed recurrence following radiation and chemotherapy were evaluated. Volumetric EOR was measured and classified as gross-total resection (GTR, > 95% by volume) or subtotal resection (STR, ≤ 95% by volume) after independent radiological review. Overall survival was compared between groups using univariate and multivariate analysis accounting for known prognostic factors, including age, eloquent location, Karnofsky Performance Status (KPS), and adjuvant therapies.

Results

Multiple resections were performed in 107 patients. Fifty-two patients had initial GTR, of whom 31 (60%) had GTR at recurrence, with a median survival of 20.4 months (standard error [SE] 1.0 months), and 21 (40%) had STR at recurrence, with a median survival of 18.4 months (SE 0.5 months) (difference not statistically significant). Initial STR was performed in 55 patients, of whom 26 (47%) had GTR at recurrence, with a median survival of 19.0 months (SE 1.2 months), and 29 (53%) had STR, with a median survival of 15.9 months (SE 1.2 months) (p = 0.004). A Cox proportional hazards model was constructed demonstrating that age (HR 1.03, p = 0.004), KPS score at recurrence (HR 2.4, p = 0.02), and EOR at repeat resection (HR 0.62, p = 0.02) were independent predictors of survival. Extent of initial resection was not a statistically significant factor (p = 0.13) when repeat EOR was included in the model, suggesting that GTR at second craniotomy could overcome the effect of an initial STR.

Conclusions

Extent of resection at recurrence is an important predictor of overall survival. If GTR is achieved at recurrence, overall survival is maximized regardless of initial EOR, suggesting that patients with initial STR may benefit from surgery with a GTR at recurrence.

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Gurvinder Kaur, Orin Bloch, Brian J. Jian, Rajwant Kaur, Michael E. Sughrue, Manish K. Aghi, Michael W. McDermott, Mitchel S. Berger, Susan M. Chang, and Andrew T. Parsa

Object

The presence of cystic features in glioblastoma (GBM) has been described as a favorable prognostic factor. The aim of this study was to determine the survival outcome in patients undergoing surgery for newly diagnosed primary GBM with a large cystic component as compared with a large cohort of patients with noncystic GBM, while controlling for well-characterized prognostic factors.

Methods

A retrospective review of 354 consecutive patients treated with resection of primary GBM was performed using medical records and imaging information obtained at the University of California, San Francisco from 2005 to 2009. Within this cohort, 37 patients with large cysts (≥ 50% of tumor) were identified. Clinical presentations and surgical outcomes were statistically compared between the cystic and noncystic patients.

Results

There were no statistically significant differences in clinical presentation between groups, including differences in age, sex, presenting symptoms, tumor location, or preoperative functional status, with the exception of tumor size, which was marginally larger in the cystic group. Surgical outcomes, including extent of resection and postoperative functional status, were equivalent. The median actuarial survival for the patients with cystic GBM was 17.0 months (95% CI 12.6–21.3 months), and the median survival for patients with noncystic GBM was 15.9 months (95% CI 14.6–17.2 months). There was no significant between-groups difference in survival (p = 0.99, log-rank test). A Cox multivariate regression model was constructed, which identified only age and extent of resection as independent predictors of survival. The presence of a cyst was not a statistically significant prognostic factor.

Conclusions

This study, comprising the largest series of cases of primary cystic GBM reported in the literature to date, demonstrates that the presence of a large cyst in patients with GBM does not significantly affect overall survival as compared with survival in patients without a cyst. Preoperative discussions with patients with GBM should focus on validated prognostic factors. The presence of cystic features does not confer a survival advantage.

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Matthew Z. Sun, Taemin Oh, Michael E. Ivan, Aaron J. Clark, Michael Safaee, Eli T. Sayegh, Gurvinder Kaur, Andrew T. Parsa, and Orin Bloch

OBJECT

There are few and conflicting reports on the effects of delayed initiation of chemoradiotherapy on the survival of patients with glioblastoma. The standard of care for newly diagnosed glioblastoma is concurrent radiotherapy and temozolomide chemotherapy after maximal safe resection; however, the optimal timing of such therapy is poorly defined. Given the lack of consensus in the literature, the authors performed a retrospective analysis of The Cancer Genome Atlas (TCGA) database to investigate the effect of time from surgery to initiation of therapy on survival in newly diagnosed glioblastoma.

METHODS

Patients with primary glioblastoma diagnosed since 2005 and treated according to the standard of care were identified from TCGA database. Kaplan-Meier and multivariate Cox regression analyses were used to compare overall survival (OS) and progression-free survival (PFS) between groups stratified by postoperative delay to initiation of radiation treatment.

RESULTS

There were 218 patients with newly diagnosed glioblastoma with known time to initiation of radiotherapy identified in the database. The median duration until therapy was 27 days. Delay to radiotherapy longer than the median was not associated with worse PFS (HR = 0.918, p = 0.680) or OS (HR = 1.135, p = 0.595) in multivariate analysis when controlling for age, sex, KPS score, and adjuvant chemotherapy. Patients in the highest and lowest quartiles for delay to therapy (≤ 20 days vs ≥ 36 days) did not statistically differ in PFS (p = 0.667) or OS (p = 0.124). The small subset of patients with particularly long delays (> 42 days) demonstrated worse OS (HR = 1.835, p = 0.019), but not PFS (p = 0.74).

CONCLUSIONS

Modest delay in initiation of postoperative chemotherapy and radiation does not appear to be associated with worse PFS or OS in patients with newly diagnosed glioblastoma, while significant delay longer than 6 weeks may be associated with worse OS.