Faculty Bibliography

OBJECTIVE:Recent large-cohort sequencing studies have investigated the genomic landscape of meningiomas, identifying somatic coding alterations in NF2, SMARCB1, SMARCE1, TRAF7, KLF4, POLR2A, BAP1, and members of the PI3K and Hedgehog signaling pathways. Initial associations between clinical features and genomic subgroups have been described, including location, grade, and histology. However, further investigation using an expanded collection of samples is needed to confirm previous findings, as well as elucidate relationships not evident in smaller discovery cohorts. METHODS:Targeted sequencing of established meningioma driver genes was performed on a multiinstitution cohort of 3016 meningiomas for classification into mutually exclusive subgroups. Relevant clinical information was collected for all available cases and correlated with genomic subgroup. Nominal variables were analyzed using Fisher's exact tests, while ordinal and continuous variables were assessed using Kruskal-Wallis and 1-way ANOVA tests, respectively. Machine-learning approaches were used to predict genomic subgroup based on noninvasive clinical features. RESULTS:Genomic subgroups were strongly associated with tumor locations, including correlation of HH tumors with midline location, and non-NF2 tumors in anterior skull base regions. NF2 meningiomas were significantly enriched in male patients, while KLF4 and POLR2A mutations were associated with female sex. Among histologies, the results confirmed previously identified relationships, and observed enrichment of microcystic features among "mutation unknown" samples. Additionally, KLF4-mutant meningiomas were associated with larger peritumoral brain edema, while SMARCB1 cases exhibited elevated Ki-67 index. Machine-learning methods revealed that observable, noninvasive patient features were largely predictive of each tumor's underlying driver mutation. CONCLUSIONS:Using a rigorous and comprehensive approach, this study expands previously described correlations between genomic drivers and clinical features, enhancing our understanding of meningioma pathogenesis, and laying further groundwork for the use of targeted therapies. Importantly, the authors found that noninvasive patient variables exhibited a moderate predictive value of underlying genomic subgroup, which could improve with additional training data. With continued development, this framework may enable selection of appropriate precision medications without the need for invasive sampling procedures.

OBJECTIVE:Granular cell tumors (GCTs), pituicytomas, and spindle cell oncocytomas are rare, nonfunctioning pituitary tumors sharing positive staining of thyroid transcription factor 1. We present our series, the first single-institutional report with long-term surgical follow-up of all 3 tumor types. METHODS:Our institutional pathology database was queried for these 3 pathologic diagnoses. Clinical records were assessed for clinical presentation, preoperative and postoperative endocrine status, tumor location on imaging, surgical characteristics, pathology results, and tumor recurrence. RESULTS:Data were analyzed for 4 patients with GCTs, 4 with pituicytomas, and 3 with spindle cell oncocytomas. The most common symptoms at presentation were vision changes (64%), headache (55%), endocrine abnormalities (55%), and fatigue (46%). GCTs were the only subtype to present exclusively in the infundibulum and the only subtype in our series to be treated with a transcranial transsylvian approach to resection (n = 2). In our study, in contrast to other reports, estimated blood loss was less than 300 mL in all patients. Imaging confirmed gross total resection in all 11 cases with no known recurrences at a mean (standard deviation) follow-up of 4.7 (3.7) years. CONCLUSIONS:We present a single-institution series of rare thyroid transcription factor 1-staining posterior pituitary tumors of the sellar region. Key novel findings include gross total resection with no tumor recurrence at nearly 5 years of mean follow-up and no cases of excess or uncontrolled blood loss. Our findings reinforce the observation that GCTs present in the suprasellar space.

BACKGROUND:Indications for reconstruction of the common carotid artery (CCA) include trauma, iatrogenic injury, neoplastic growth (such as invasive neck carcinomas), postoperative infection, and cervical carotid aneurysm. Although various techniques and conduits have been described, the clinical scenario may preclude the use of the most commonly used grafts. We describe a case using a superficial femoral artery (SFA) interposition graft to repair the CCA and review the available literature, highlighting the feasibility of this technique for carotid artery reconstruction. CASE DESCRIPTION/METHODS:A patient aged 51 years presented with a ruptured mycotic CCA pseudoaneurysm that developed in the setting of a pharyngeal-carotid fistula. Because of the presence of a pharyngeal-carotid fistula and active infection within the vessel wall, endovascular treatment of the pseudoaneurysm was not feasible, and open surgical correction was required to repair the fistulous connection. Furthermore, owing to the extensive soft tissue infection, the use of a synthetic or venous autograft conduit for repair of the artery was contraindicated. Therefore, we harvested a segment of the SFA and used it as an interposition graft to reconstruct the diseased CCA, achieving an excellent anatomic and clinical result. CONCLUSIONS:This case highlights the feasibility of using an SFA interposition graft for short-segment CCA reconstruction, which can provide significant utility in the setting of a hostile operative field due to prior infection or radiation.

BACKGROUND:Ruptured aneurysms causing intraventricular hemorrhage (IVH) are associated with high morbidity. The presence of blood that completely fills the fourth ventricle (cast fourth ventricle, CFV) is thought to be particularly ominous, but studies documenting the outcome of such cases are lacking. OBJECTIVE:To investigate the outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) and CFV. METHODS:We reviewed 406 patients enrolled in the Barrow Ruptured Aneurysm Trial (BRAT, NCT01593267, clinicaltrials.gov); 238 patients with aSAH and IVH were identified, and imaging was reviewed for the presence of CFV. Outcome was evaluated at the 1-yr follow-up. A poor outcome was defined as modified Rankin Scale score >2. RESULTS:CFV was identified in 25 patients. Admission Glasgow Coma Score was lower in CFV patients, 7.8 versus 11.5 (P < .001). At discharge and the 1-yr follow-up, patients with CFV had a greater risk of a poor outcome (P < .001 and P = .002, respectively). In a subgroup analysis of 79 patients with IVH and initial Glasgow Coma Score ≤ 8, almost 50% of the patients with IVH but without CFV had made a good recovery versus 7% of patients with CFV (odds ratio [OR] 15, P = .002). On multivariate analysis, CFV was a greater predictor of a poor prognosis at 1 yr post-aSAH than Hunt and Hess grade >3 (6.4 OR vs 2.9 OR [P < .001], respectively). CONCLUSION:The presence of CFV is a predictor of poor outcome in patients with aSAH. When compared to other patients with IVH and aSAH, CFV is a stronger predictor of a poor outcome than a poor Hunt and Hess Grade.

Fractionated CyberKnife radiosurgery (CKRS) treatment for acoustic neuromas may reduce the risk of long-term radiation toxicity to nearby critical structures compared to that of single-fraction radiosurgery. However, tumor control rates and clinical outcomes after CKRS for acoustic neuromas are not well described. We retrospectively reviewed all acoustic neuroma patients treated with CKRS (2004-2011) in a prospectively maintained clinical and radiographic database. Treatment failure, the need for additional surgical intervention, was evaluated using Kaplan-Meier analysis. For 119 treated patients, median values were 49 months (range, 6-133 months) of follow-up, 1.6 cm³ (range, 0.02-17 cm³) tumor volume, and 18 Gy (range, 13-25 Gy) prescribed dose delivered in 3 fractions (range, 1-5 fractions). Thirty-five of 59 patients (59%) with pre-radiosurgery serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery class A or B) maintained serviceable hearing at the last audio follow-up (median, 21 months). Two of 111 patients (2%) with facial nerve function House-Brackmann (HB) grade ≤3 progressed to HB grade >3 after radiosurgery. Koos grade IV was predictive of radiographic tumor growth after radiosurgery compared to grades I to III (p = 0.02). Treatment failure occurred in 9 of 119 patients (8%); median time to failure was 29 months (range, 4-70 months). The actuarial rates of tumor control at 1, 3, 5, and 7 years were 96%, 94%, 88%, and 88%, respectively. CKRS affords effective tumor control for acoustic neuromas with an acceptable rate of hearing preservation. Further studies are needed to compare CKRS to single-fraction radiosurgery for acoustic neuromas.

OBJECTIVE:The choice of transsylvian versus transcortical corridors for resection of insular gliomas remains controversial. Functional pathway compromise from transcortical transgression and vascular injury during transsylvian dissection are the primary concerns. In this study, data from a single-center experience with both approaches were compared to determine whether one approach was associated with a higher rate of morbidity than the other. METHODS:The authors identified 100 consecutive patients who underwent resection of pure insular gliomas at the Barrow Neurological Institute. Volumetric analysis was performed using FLAIR and contrast-enhanced T1-weighted MRI for low- and high-grade gliomas, respectively, for extent of resection (EOR) and diffusion-weighted sequences were used to detect for postoperative ischemia. Step-wise logistic regression analysis was performed to identify predictors of neurological morbidity. RESULTS:Data from 100 patients with low-grade or high-grade insular gliomas were analyzed. Fifty-two patients (52%) underwent a transsylvian approach, and 48 patients (48%) underwent a transcortical approach. The mean (± SD) EOR was 91.6% ± 12.4% in the transsylvian group and 88.6% ± 14.2% in the transcortical group (p = 0.26). Clinical outcome metrics for the 2 groups were similar. Overall, 13 patients (25%) in the transsylvian group and 10 patients (21%) in the transcortical group had evidence of ischemia on postoperative MR images. For both approaches, high-grade histology was associated with permanent morbidity (p = 0.01). For patients with gliomas located within the superior-posterior quadrant of the insula, development of postoperative ischemia was associated with only the transsylvian approach (46% vs 0%, p = 0.02). CONCLUSIONS:Areas of restricted diffusion are common on postoperative MRI following resection of insular gliomas, but only a minority of these patients develop permanent neurological deficits. Insular glioma patients with high-grade histology may be at particular risk for developing symptomatic postoperative ischemia. Both the transcortical and transsylvian corridors are associated with reasonable morbidity profiles, although gliomas situated within the superior-posterior quadrant of the insula are more safely accessed with a transcortical approach.

OBJECTIVE:The Barrow Innovation Center comprises an educational program in medical innovation that enables residents to identify problems in patient care and rapidly develop and implement solutions to these problems. Residents involved in this program noted an elevated risk of iatrogenic spinal cord injury during posterior cervical and thoracic procedures. The objective of this study was to describe this complication, and a novel solution was developed through a new innovation training program. METHODS:A case report demonstrates the risk of iatrogenic spinal cord injury during posterior cervical decompression and fusion. Solutions to this problem were developed at the innovation center via an iterative process of prototype creation, cadaveric testing, and redesign. Patent law students who partnered with the center wrote and filed a provisional patent protecting the novel prototype designs. RESULTS:The concept of a protective shield for the spinal cord was developed, and within only 6 weeks the devices were provisionally patented and used in the operating room. This device was named the Myeloshield. Initial clinical experience indicates that the Myeloshield can be used without impeding the flow of surgery and has the potential to prevent iatrogenic spinal cord injury; this experience is presented through 2 case reports demonstrating the use of Myeloshields in the operating room. CONCLUSIONS:This report demonstrates how programs like the Barrow Innovation Center can provide neurosurgery residents with a unique educational experience in medical device innovation and intellectual property development and can serve as an avenue of surgical quality improvement and problem solving.