Faculty Bibliography

INTRODUCTION/BACKGROUND:Cranial defects following the removal of tumor involved bone require repair and reconstruction for brain protection and cosmesis. A variety of autologous bone substrates and synthetic materials can be employed, alone or in combination. In this article, we describe the use of dual thin and thick titanium mesh, connected together using plate hardware, to repair a right frontotemporal sphenoidal bone defect following resection of a hyperostosing sphenoid wing meningioma. METHODS:Reconstruction of the pterion was done with a dual mesh cranioplasty. After replacement of the native orbitozygomatic and frontotemporal bone pieces, a piece of thinner mesh was molded to the pterional defect connecting the two bone pieces and re-creating the concave shape of the pterion below the superior temporal line. The circular area of the bony defect overlying the frontal and temporal lobes was supplemented by cutting and molding an additional piece of thicker mesh which was secured to the thinner mesh with burr hole cover sectors using rescue screws. RESULTS:A 30-year-old woman presented with painless proptosis and was found to have a hyperostosing right sphenoid wing meningioma. The patient underwent a frontotemporal orbitozygomatic craniotomy for tumor resection and extensive bony osteotomy. Repair and reconstruction of the cranial defect in the region were accomplished at the time of open operation using two thicknesses of mesh connected one to another with titanium plate pieces and rescue screws. The patient underwent gross total resection of the meningioma and near total resection of the soft tissue and bony components (Simpson Grade II). The external cosmetic results following the orbital-cranial reconstruction with the dual mesh technique was deemed "very good" by the surgeon and patient. Postoperative CT imaging demonstrated symmetric re-approximation of the shape of the pterion as compared to the opposite side. CONCLUSIONS:We present a method for connecting two titanium mesh sheets with available hardware to improve the strength in compression while maintaining the ability to mold thinner sheets as necessary for the best cosmetic results. This method is an option for coverage of bony defects in the region of the pterion for young, physically active patients providing them with additional mesh cranioplasty strength.

OBJECT Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs-the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process. METHODS A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period. RESULTS Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0-1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs). CONCLUSIONS Surgery should be regarded as the "gold standard" therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.

OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.

STUDY DESIGN/METHODS:Systematic review of literature. OBJECTIVE:To perform a comprehensive English language systematic literature review of proximal junctional kyphosis (PJK) and proximal junctional failure (PJF), concentrating on incidence, risk factors, health related quality of life impact, prevention strategy, and classification systems. SUMMARY OF BACKGROUND DATA/BACKGROUND:PJK and PJF are well described clinical pathologies and are a frequent cause of revision surgery. The development of a PJK classification that correlates with clinical outcomes and guides treatment decisions and possible prevention strategies would be of significant benefit to patients and surgeons. METHODS:The phrases "proximal junctional," "proximal junctional kyphosis," and "proximal junctional failure" were used as search terms in PubMed for all years up to 2014 to identify all articles that included at least one of these terms. RESULTS:Fifty-three articles were identified overall. Eighteen articles assessed for risk factors. Eight studies specifically reviewed prevention strategies. There were no randomized prospective studies. There were 3 published studies that have attempted to classify PJK. The reported incidence of PJK ranged widely, from 5% to 46% in patients undergoing spinal instrumentation and fusion for adult spinal deformity. It is reported that 66% of PJK occurs within 3 months and 80% within 18 months after surgery. The reported revision rates due to PJK range from 13% to 55%. Modifiable and nonmodifiable risk factors for PJK have been characterized. CONCLUSION/CONCLUSIONS:PJK and PJF affect many patients after long segment instrumentation after the correction of adult spinal deformity. The epidemiology and risk factors for the disease are well defined. A PJK and PJF scoring system may help describe the severity of disease and guide the need for revision surgery. The development and prospective validation of a PJK classification system is important considering the prevalence of the problem and its clinical and economic impact. LEVEL OF EVIDENCE/METHODS:N/A.

OBJECT/OBJECTIVE:Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma. METHODS:A systematic search was performed with the phrase "(name of particular agent) and glioblastoma" as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies. RESULTS:A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10-15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%-20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%-20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied. CONCLUSIONS:Recurrent glioblastoma remains very difficult to treat, even with molecular targeted therapies and anticancer agents. The currently available targeted therapy regimens have poor to modest activity against recurrent glioblastoma. As newer agents are actively being developed, combination regimens have provided the most promising results for improving outcomes. Targeted therapies matched to molecular profiles of individual tumors are predicted to be a critical component necessary for improving efficacy in future trials.

Malignant peripheral nerve sheath tumors (MPNSTs) are rare, affecting only a small portion of the general population. In many cases, MPNSTs occur in association with neurofibromatosis Type 1 and at times arise secondary to previous radiation therapy (RT). These tumors can be found essentially anywhere a peripheral nerve is present, but they rarely originate primarily from the spinal nerve or cauda equina and cause leptomeningeal spread. This report describes the treatment course of a 43-year-old man with a history of testicular seminoma treated with RT a decade before, who was found to have a large sacral MPNST. The patient underwent complete sacrectomy for gross-total resection. Despite this effort, he was eventually found to have metastatic lesions throughout the spine and brain, ultimately resulting in acute hydrocephalus and death. Biopsy results of these metastatic lesions proved to be characteristic of his original MPNST. The literature is also reviewed and the diagnostic modalities, management strategies, and prognosis of MPNST are discussed.

Study Design Systematic review. Clinical Questions Compared with no stimulation, does electrical stimulation promote bone fusion after lumbar spinal fusion procedures? Does the effect differ based on the type of electrical stimulation used? Methods Electronic databases and reference lists of key articles were searched up to October 15, 2013, to identify randomized controlled trials (RCTs) comparing the effect of electrical stimulation to no electrical stimulation on fusion rates after lumbar spinal fusion for the treatment of degenerative disease. Two independent reviewers assessed the strength of evidence using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria. Results Six RCTs met the inclusion criteria. The following types of electrical stimulation were investigated: direct current (three studies), pulsed electromagnetic field (three studies), and capacitive coupling (one study). The control groups consisted of no stimulation (two studies) or placebo (four studies). Marked heterogeneity in study populations, characteristics, and design prevented a meta-analysis. Regardless of the type of electrical stimulation used, cumulative incidences of fusion varied widely across the RCTs, ranging from 35.4 to 90.6% in the intervention groups and from 33.3 to 81.9% in the control groups across 9 to 24 months of follow-up. Similarly, when stratified by the type of electrical stimulation used, fusion outcomes from individual studies varied, leading to inconsistent and conflicting results. Conclusion Given the inconsistency in study results, possibly due to heterogeneity in study populations/characteristics and quality, we are unable to conclude that electrical stimulation results in better fusion outcomes compared with no stimulation. The overall strength of evidence for the conclusions is low.

OBJECT/OBJECTIVE:Smoking is one of the leading causes of preventable morbidity and death in the U.S. and has been associated with perioperative complications. In this study, the authors examined the effects of smoking on perioperative outcomes and pseudarthrosis rates following anterior cervical corpectomy. METHODS:All adult patients from 2006 to 2011 who underwent anterior cervical corpectomy were identified. Patients were categorized into 3 groups: patients who never smoked (nonsmokers), patients who quit for at least 1 year (quitters), and patients who continue to smoke (current smokers). Demographic, medical, and surgical covariates were collected. Multivariate analysis was used to define the relationship between smoking and blood loss, 30-day complications, length of hospital stay, and pseudarthrosis. RESULTS:A total of 160 patients were included in the study. Of the 160 patients, 49.4% were nonsmokers, 25.6% were quitters, and 25.0% were current smokers. The overall 30-day complication rate was 20.0%, and pseudarthrosis occurred in 7.6% of patients. Mean blood loss was 368.3 ml and mean length of stay was 6.5 days. Current smoking status was significantly associated with higher complication rates (p < 0.001) and longer lengths of stay (p < 0.001); current smoking status remained an independent risk factor for both outcomes after multivariate logistic regression analysis. The complications that were experienced in current smokers were mostly infections (76.5%), and this proportion was significantly greater than in nonsmokers and quitters (p = 0.013). Current smoking status was also an independent risk factor for pseudarthrosis at 1-year follow-up (p = 0.012). CONCLUSIONS:Smoking is independently associated with higher perioperative complications (especially infectious complications), longer lengths of stay, and higher rates of pseudarthrosis in patients undergoing anterior cervical corpectomy.

A major goal of the Section on Tumors of the American Association of Neurological Surgery (AANS) and Congress of Neurological Surgeons (CNS) since it was founded in 1984 has been to foster both education and research in the field of brain tumor treatment and development. In support of this goal, the Section sponsors a number of awards, named lectures, and fellowships at the annual meetings of the AANS and CNS. In this article, we describe the awards given by the AANS/CNS Section on Tumors since its foundation, the recipients of the awards, and their philanthropic donors. The subsequent history of awardees and their work is briefly examined. Specifically for the Preuss and Mahaley Awards, this article also examines the rates of publication among the award-winning abstracts and achievement of grant funding by awardees.

Stereotactic frame placement for radiosurgery is assumed to be an uncomfortable experience. We developed angled anterior posts for the Leksell frame to avoid pin penetration of the temporalis muscle. This study aimed to determine the frequency of angled post requirement and quantify the patient pain experience from frame placement. We prospectively enrolled 63 patients undergoing radiosurgery. Angled posts were used when conventional post trajectory was posterior or within 3mm of the superior temporal line to avoid temporalis muscle penetration. Pain scores (0 to 10) were collected prior to frame placement, immediately after frame placement, before radiosurgery, after radiosurgery, and a day after radiosurgery. A total of 63 patients were enrolled: 33 (48%) patients required angled posts. Women were significantly more likely to require angled posts than men (60.0% versus 33.3%, respectively; p=0.034). Mean pain scores were very low, ranging from 0.33 to 2.23. There were no significant differences in pain outcomes between both groups at all time points. Stereotactic frame placement is not perceived to be a painful procedure. This information may be useful when counseling patients about the pain experience with frame application and the option of using angled anterior posts.