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Aaron P. Kamer, Jose M. Bonnin, Robert J. Spinner and Aaron A. Cohen-Gadol

Intracranial extension of temporomandibular joint (TMJ) ganglion cysts is very rare. Two previously reported cases presented clinically due to effects on cranial nerves and had obvious association with the TMJ on imaging. To the authors’ knowledge, intracranial extension of a TMJ ganglion cyst presenting with seizures and mimicking a primary brain tumor has not been previously reported. The patient underwent resection of a presumptive primary cystic temporal lobe tumor, but the lesion had histopathological features of a nonneoplastic cyst with a myxoid content. He was followed with serial imaging for 5 years before regrowth of the lesion caused new episodes of seizures requiring a repeat operation, during which the transdural defect was repaired after the adjacent segment of the TMJ was curetted. A thorough review of all imaging studies and the histopathological findings from the repeat operation led to the correct diagnosis of a TMJ ganglion cyst. This case highlights an unusual presentation of this rare lesion, as well as its potential for recurrence. TMJ ganglion cysts should be included in the differential diagnosis of cystic tumors involving the anterior temporal lobe, presenting with or without seizures. Focused imaging evaluation of the TMJ can be helpful to rule out the possible role of associated TMJ lesions.

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Clint M. Alfaro, Valentina Pirro, Michael F. Keating, Eyas M. Hattab, R. Graham Cooks and Aaron A. Cohen-Gadol

OBJECTIVE

The authors describe a rapid intraoperative ambient ionization mass spectrometry (MS) method for determining isocitrate dehydrogenase (IDH) mutation status from glioma tissue biopsies. This method offers new glioma management options and may impact extent of resection goals. Assessment of the IDH mutation is key for accurate glioma diagnosis, particularly for differentiating diffuse glioma from other neoplastic and reactive inflammatory conditions, a challenge for the standard intraoperative diagnostic consultation that relies solely on morphology.

METHODS

Banked glioma specimens (n = 37) were analyzed by desorption electrospray ionization–MS (DESI-MS) to develop a diagnostic method to detect the known altered oncometabolite in IDH-mutant gliomas, 2-hydroxyglutarate (2HG). The method was used intraoperatively to analyze tissue smears obtained from glioma patients undergoing resection and to rapidly diagnose IDH mutation status (< 5 minutes). Fifty-one tumor core biopsies from 25 patients (14 wild type [WT] and 11 mutant) were examined and data were analyzed using analysis of variance and receiver operating characteristic curve analysis.

RESULTS

The optimized DESI-MS method discriminated between IDH-WT and IDH-mutant gliomas, with an average sensitivity and specificity of 100%. The average normalized DESI-MS 2HG signal was an order of magnitude higher in IDH-mutant glioma than in IDH-WT glioma. The DESI 2HG signal intensities correlated with independently measured 2HG concentrations (R2 = 0.98). In 1 case, an IDH1 R132H–mutant glioma was misdiagnosed as a demyelinating condition by frozen section histology during the intraoperative consultation, and no resection was performed pending the final pathology report. A second craniotomy and tumor resection was performed after the final pathology provided a diagnosis most consistent with an IDH-mutant glioblastoma. During the second craniotomy, high levels of 2HG in the tumor core biopsies were detected.

CONCLUSIONS

This study demonstrates the capability to differentiate rapidly between IDH-mutant gliomas and IDH-WT conditions by DESI-MS during tumor resection. DESI-MS analysis of tissue smears is simple and can be easily integrated into the standard intraoperative pathology consultation. This approach may aid in solving differential diagnosis problems associated with low-grade gliomas and could influence intraoperative decisions regarding extent of resection, ultimately improving patient outcome. Research is ongoing to expand the patient cohort, systematically validate the DESI-MS method, and investigate the relationships between 2HG and tumor heterogeneity.

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Lorenzo Rinaldo, David S. Priemer, Alexander O. Vortmeyer, Aaron A. Cohen-Gadol, Daniel J. Brat, Anita Mahajan, Caterina Giannini and Terry C. Burns

Chordomas are neoplasms that typically arise from midline skeletal structures and rarely originate within the intradural compartment of the CNS. A chordoma arising from the corpus callosum has not been previously described. The authors report the surgical management of a chordoma originating within the splenium of the corpus callosum. To determine the incidence and distribution of intracranial intradural chordoma, a literature search for additional cases was performed. MEDLINE was searched using the MeSH keyword “chordoma,” yielding 2010 articles. These articles were screened for cases of primary intradural chordoma rostral to the craniocervical junction, which led to the identification of 46 relevant articles. The authors report the case of a 69-year-old man who initially presented with nonspecific neurological symptoms including spatial disorientation and cognitive decline. These symptoms eventually prompted intracranial imaging, including MRI, which revealed a ring-enhancing, heterogeneous, cystic mass localized within the splenium of the corpus callosum and extending into the bilateral ventricles. The lesion was believed to represent a high-grade glioma and the patient underwent a left interhemispheric approach and subtotal resection. After pathologic evaluation confirmed a diagnosis of an anaplastic chordoma, the patient underwent further resection. A gross-total resection (GTR) was achieved with a transfalcine approach to the contralateral portion of the tumor. Postoperatively, the patient had a partial left homonymous quadrantanopsia, but was otherwise at his neurological baseline. Proton beam radiotherapy was performed to the resection cavity but diffuse intraventricular disease ensued. The results of a literature search suggest that a chordoma arising in the corpus callosum has not been previously described. The present case demonstrates that chordomas can occur in the corpus callosum, and illustrates the utility of a transfalcine approach for GTR of lesions in this location, as well as the need for improved strategies to prevent intraventricular dissemination.

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Frank J. Attenello, Ian A. Buchanan, Timothy Wen, Daniel A. Donoho, Shirley McCartney, Steven Y. Cen, Alexander A. Khalessi, Aaron A. Cohen-Gadol, Joseph S. Cheng, William J. Mack, Clemens M. Schirmer, Karin R. Swartz, J. Adair Prall, Ann R. Stroink, Steven L. Giannotta and Paul Klimo Jr.

OBJECTIVE

Excessive dissatisfaction and stress among physicians can precipitate burnout, which results in diminished productivity, quality of care, and patient satisfaction and treatment adherence. Given the multiplicity of its harms and detriments to workforce retention and in light of the growing physician shortage, burnout has garnered much attention in recent years. Using a national survey, the authors formally evaluated burnout among neurosurgery trainees.

METHODS

An 86-item questionnaire was disseminated to residents in the American Association of Neurological Surgeons database between June and November 2015. Questions evaluated personal and workplace stressors, mentorship, career satisfaction, and burnout. Burnout was assessed using the previously validated Maslach Burnout Inventory. Factors associated with burnout were determined using univariate and multivariate logistic regression.

RESULTS

The response rate with completed surveys was 21% (346/1643). The majority of residents were male (78%), 26–35 years old (92%), in a stable relationship (70%), and without children (73%). Respondents were equally distributed across all residency years. Eighty-one percent of residents were satisfied with their career choice, although 41% had at some point given serious thought to quitting. The overall burnout rate was 67%. In the multivariate analysis, notable factors associated with burnout included inadequate operating room exposure (OR 7.57, p = 0.011), hostile faculty (OR 4.07, p = 0.008), and social stressors outside of work (OR 4.52, p = 0.008). Meaningful mentorship was protective against burnout in the multivariate regression models (OR 0.338, p = 0.031).

CONCLUSIONS

Rates of burnout and career satisfaction are paradoxically high among neurosurgery trainees. While several factors were predictive of burnout, including inadequate operative exposure and social stressors, meaningful mentorship proved to be protective against burnout. The documented negative effects of burnout on patient care and health care economics necessitate further studies for potential solutions to curb its rise.

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Bradley N. Bohnstedt, Mary Ziemba-Davis, Rishabh Sethia, Troy D. Payner, Andrew DeNardo, John Scott and Aaron A. Cohen-Gadol

OBJECTIVE

The deep and difficult-to-reach location of basilar apex aneurysms, along with their location near critical adjacent perforating arteries, has rendered the perception that microsurgical treatment of these aneurysms is risky. As a result, these aneurysms are considered more suitable for treatment by endovascular intervention. The authors attempt to compare the immediate and long-term outcomes of microsurgery versus endovascular therapy for this aneurysm subtype.

METHODS

A prospectively maintained database of 208 consecutive patients treated for basilar apex aneurysms between 2000 and 2012 was reviewed. In this group, 161 patients underwent endovascular treatment and 47 were managed microsurgically. The corresponding records were analyzed for presenting characteristics, postoperative complications, discharge status, and Glasgow Outcome Scale (GOS) scores up to 1 year after treatment and compared using chi-square and Student t-tests.

RESULTS

Among these 208 aneurysms, 116 (56%) were ruptured, including 92 (57%) and 24 (51%) of the endovascularly and microsurgically managed aneurysms, respectively. The average Hunt and Hess grade was 2.4 (2.4 in the endovascular group and 2.2 in the microsurgical group; p = 0.472). Postoperative complications of cranial nerve deficits and hemiparesis were more common in patients treated microsurgically than endovascularly (55.3% vs 16.2%, p < 0.05; and 27.7% vs 10.6%, p < 0.05, respectively). However, aneurysm remnants and need for retreatment were more common in the endovascular than the microsurgical group (41.3% vs 2.3%, p < 0.05; and 10.6% vs 0.0%, p < 0.05, respectively). Stent placement significantly reduced the need for retreatment. Rehemorrhage rates and average GOS score at discharge and 1 year after treatment were not statistically different between the two treatment groups.

CONCLUSIONS

Patients with basilar apex aneurysms were significantly more likely to be treated via endovascular management, but compared with those treated microsurgically, they had higher rates of recurrence and need for retreatment. The current study did not detect an overall difference in outcomes at discharge and 1 year after either treatment modality. Therefore, in a select group of patients, microsurgical treatment continues to play an important role.

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Ryan P. Morton, Louis J. Kim and Laligam N. Sekhar

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Khadijeh Bijangi-Vishehsaraei, M. Reza Saadatzadeh, Haiyan Wang, Angie Nguyen, Malgorzata M. Kamocka, Wenjing Cai, Aaron A. Cohen-Gadol, Stacey L. Halum, Jann N. Sarkaria, Karen E. Pollok and Ahmad R. Safa

OBJECTIVE

Defects in the apoptotic machinery and augmented survival signals contribute to drug resistance in glioblastoma (GBM). Moreover, another complexity related to GBM treatment is the concept that GBM development and recurrence may arise from the expression of GBM stem cells (GSCs). Therefore, the use of a multifaceted approach or multitargeted agents that affect specific tumor cell characteristics will likely be necessary to successfully eradicate GBM. The objective of this study was to investigate the usefulness of sulforaphane (SFN)—a constituent of cruciferous vegetables with a multitargeted effect—as a therapeutic agent for GBM.

METHODS

The inhibitory effects of SFN on established cell lines, early primary cultures, CD133-positive GSCs, GSC-derived spheroids, and GBM xenografts were evaluated using various methods, including GSC isolation and the sphere-forming assay, analysis of reactive oxygen species (ROS) and apoptosis, cell growth inhibition assay, comet assays for assessing SFN-triggered DNA damage, confocal microscopy, Western blot analysis, and the determination of in vivo efficacy as assessed in human GBM xenograft models.

RESULTS

SFN triggered the significant inhibition of cell survival and induced apoptotic cell death, which was associated with caspase 3 and caspase 7 activation. Moreover, SFN triggered the formation of mitochondrial ROS, and SFN-triggered cell death was ROS dependent. Comet assays revealed that SFN increased single- and double-strand DNA breaks in GBM. Compared with the vehicle control cells, a significantly higher amount of γ-H2AX foci correlated with an increase in DNA double-strand breaks in the SFN-treated samples. Furthermore, SFN robustly inhibited the growth of GBM cell–induced cell death in established cell cultures and early-passage primary cultures and, most importantly, was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence. In vivo studies revealed that SFN administration at 100 mg/kg for 5-day cycles repeated for 3 weeks significantly decreased the growth of ectopic xenografts that were established from the early passage of primary cultures of GBM10.

CONCLUSIONS

These results suggest that SFN is a potent anti-GBM agent that targets several apoptosis and cell survival pathways and further preclinical and clinical studies may prove that SFN alone or in combination with other therapies may be potentially useful for GBM therapy.

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Osamu Akiyama, Ken Matsushima, Abuzer Gungor, Satoshi Matsuo, Dylan J. Goodrich, R. Shane Tubbs, Paul Klimo Jr., Aaron A. Cohen-Gadol, Hajime Arai and Albert L. Rhoton Jr.

OBJECTIVE

Approaches to the pulvinar remain challenging because of the depth of the target, surrounding critical neural structures, and complicated arterial and venous relationships. The purpose of this study was to compare the surgical approaches to different parts of the pulvinar and to examine the efficacy of the endoscope as an adjunct to the operating microscope in this area.

METHODS

The pulvinar was examined in 6 formalin-fixed human cadaveric heads through 5 approaches: 4 above and 1 below the tentorium. Each approach was performed using both the surgical microscope and 0° or 45° rigid endoscopes.

RESULTS

The pulvinar has a lateral ventricular and a medial cisternal surface that are separated by the fornix and the choroidal fissure, which wrap around the posterior surface of the pulvinar. The medial cisternal part of the pulvinar can be further divided into upper and lower parts. The superior parietal lobule approach is suitable for lesions in the upper ventricular and cisternal parts. Interhemispheric precuneus and posterior transcallosal approaches are suitable for lesions in the part of the pulvinar forming the anterior wall of the atrium and adjacent cisternal part. The posterior interhemispheric transtentorial approach is suitable for lesions in the lower cisternal part and the supracerebellar infratentorial approach is suitable for lesions in the inferior and medial cisternal parts.

The microscope provided satisfactory views of the ventricular and cisternal surfaces of the pulvinar and adjacent neural and vascular structures. The endoscope provided multi-angled and wider views of the pulvinar and adjacent structures.

CONCLUSIONS

A combination of endoscopic and microsurgical techniques allows optimal exposure of the pulvinar.

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Mahdi Malekpour, Charles Kulwin, Bradley N. Bohnstedt, Golnar Radmand, Rishabh Sethia, Stephen K. Mendenhall, Jonathan Weyhenmeyer, Benjamin K. Hendricks, Thomas Leipzig, Troy D. Payner, Mitesh V. Shah, John Scott, Andrew DeNardo, Daniel Sahlein and Aaron A. Cohen-Gadol

OBJECTIVE

Aneurysmal rebleeding before definitive obliteration of the aneurysm is a cause of mortality and morbidity. There are limited data on the role of short-term antifibrinolytic therapy among patients undergoing endovascular intervention.

METHODS

All consecutive patients receiving endovascular therapy for their ruptured saccular aneurysm at the authors' institution between 2000 and 2011 were included in this study. These patients underwent endovascular coiling of their aneurysm within 72 hours of admission. In patients receiving ε-aminocaproic acid (EACA), the EACA administration was continued until the time of the endovascular procedure. Complications and clinical outcomes of endovascular treatment after aneurysmal subarachnoid hemorrhage (aSAH) were compared between EACA-treated and untreated patients.

RESULTS

During the 12-year study period, 341 patients underwent endovascular coiling. Short-term EACA treatment was administered in 146 patients and was withheld in the other 195 patients. EACA treatment did not change the risk of preinterventional rebleeding in this study (OR 0.782, 95% CI 0.176–3.480; p = 0.747). Moreover, EACA treatment did not increase the rate of thromboembolic events. On the other hand, patients who received EACA treatment had a significantly longer duration of hospital stay compared with their counterparts who were not treated with EACA (median 19 days, interquartile range [IQR] 12.5–30 days vs median 14 days, IQR 10–23 days; p < 0.001). EACA treatment was associated with increased odds of shunt requirement (OR 2.047, 95% CI 1.043–4.018; p = 0.037) and decreased odds of developing cardiac complications (OR 0.138, 95% CI 0.031–0.604; p = 0.009) and respiratory insufficiency (OR 0.471, 95% CI 0.239–0.926; p = 0.029). Short-term EACA treatment did not affect the Glasgow Outcome Scale score at discharge, 6 months, or 1 year following discharge.

CONCLUSIONS

In this study, short-term EACA treatment in patients who suffered from aSAH and received endovascular aneurysm repair did not decrease the risk of preinterventional rebleeding or increase the risk of thrombotic events. EACA did not affect outcome. Randomized clinical trials are required to provide robust clinical recommendation on short-term use of EACA.

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René Post, Bert A. Coert, W. Peter Vandertop, Dagmar Verbaan and Menno R. Germans