Bilateral sacroiliac joint fusion in long constructs using self-harvesting porous S2-alar iliac screws with an integrated tulip: technical considerations and early clinical and radiographic experience.

OBJECTIVE: The incidence of sacroiliac joint (SIJ) dysfunction after lumbosacral fusion is high. Upfront bilateral SIJ fusion using novel fenestrated self-harvesting porous S2-alar iliac (S2AI) screws could reduce the incidence of SIJ dysfunction and need for subsequent SIJ fusion. In this study, the authors report their early clinical and radiographic results of SIJ fusion using this novel screw. METHODS: The authors began using self-harvesting porous screws in July 2022. This is a retrospective review of consecutive patients at a single institution who underwent long thoracolumbar surgery with extension to the pelvis using this porous screw. Radiographic parameters of regional and global alignment were collected preoperatively and at the time of last follow-up. The incidence of intraoperative complications and need for revision were collected. The incidences of mechanical complications, including screw breakage, implant loosening/pullout, and screw cap dislocation at the time of last follow-up were also collected. RESULTS: Ten patients with a mean age of 67 years were included, 6 of whom were male. Seven patients had a thoracolumbar construct with extension to the pelvis. Three patients had upper instrumented vertebrae at the proximal lumbar spine. Intraoperative breach was not encountered in any of the patients (0%). Postoperatively, 1 patient (10%) had screw breakage at the neck of the tulip of the modified iliac screw discovered at routine follow-up without clinical sequalae. CONCLUSIONS: Use of self-harvesting porous S2AI screws incorporated into long thoracolumbar constructs was safe and feasible, demanding unique technical considerations. Long-term clinical and radiographic follow-up with a large patient cohort is necessary to determine their durability and efficacy to achieve SIJ arthrodesis and prevent SIJ dysfunction.

ZAP-X Gyroscopic Radiosurgery System: A Preliminary Analysis of Clinical Applications within a Retrospective Case Series.

INTRODUCTION: The ZAP-X Gyroscopic Radiosurgery system (ZAP Surgical Systems, Inc., San Carlos, CA, USA) is a novel high-dose targeted stereotactic radiosurgery platform for outpatient use that includes self-shielding, X-ray image guidance, and the capacity to aim the radiation beam gyroscopically at an intracranial lesion using 5 independent degrees of freedom. The ZAP-X Gyroscopic Radiosurgery system accomplishes these actions while meeting widely accepted standards for dose gradient and accuracy. This retrospective study examined data of patients treated with gyroscopic radiosurgery (GRS) to document clinical outcomes. METHODS: Medical records of all outpatients treated with GRS over a 20-month period from January 2019 to August 2020 were searched to extract relevant details, including follow-up data until August 2021 (32-month study interval). Patients with <6 months of radiographical follow-up data were excluded unless death occurred. Data collection included pretreatment clinical history, pathological diagnosis, radiographical features, treatment parameters, and long-term clinical and radiographical follow-up. RESULTS: Sixty-eight patients received outpatient treatment with GRS during the 20-month treatment interval, with 59 patients remaining after exclusion for the minimum follow-up threshold, with a mean (standard deviation [SD]) fractionation of 1.85 (1.63). Eighty-two lesions were treated across a very heterogeneous patient population, including meningiomas (42.4%), metastases (39.0%), gliomas (6.8%), schwannomas (1.7%), and pituitary tumor (1.7%). Mean (SD) radiographical follow-up data (14.7 [6.60] months) were available for 56 patients. During that interval, 13 treated lesions in 13 patients (15.9%) demonstrated progression, 9 of which were stable during the initial posttreatment imaging surveillance period. Mean lesion volume was stable from pretreatment (2.54 cm3 [4.37 cm3]) to most recent follow-up (2.80 cm3 [8.20 cm3]) (t [79] = -0.310; p = 0.76). Minor adverse clinical events were noted in 3 (5.1%) of the 59 patients during the posttreatment phase that may have been related to the treatment. Ten (16.9%) patients died within the 32-month study interval. DISCUSSION/CONCLUSION: This preliminary assessment of the first series of patients treated with the Zap-X Gyroscopic Radiosurgery system documents its overall feasibility in clinical applications. Although the duration of follow-up was brief, GRS appeared to be both safe and effective. Additional analysis, with an ongoing prospective registry, is underway.

Bone grafting and biologics for spinal fusion in the pediatric population: current understanding and future perspective.

Pediatric spinal fusions have been associated with nonunion rates of approximately 25%, putting patients at risk for neurological complications while simultaneously incurring significant costs for revision surgery. In an effort to decrease nonunion rates, various bone grafts and biologics have been developed to increase osseous formation and arthrosis. The current gold-standard bone graft is autologous bone taken from the iliac crest or ribs, but this procedure is associated with significant morbidity and postoperative pain due to an additional graft harvesting procedure. Other bone graft substitutes and biologics include allografts, demineralized bone matrix, bone morphogenetic protein, and bioactive glass. Ultimately, these substitutes have been studied more extensively in the adult population, and there is a paucity of strong evidence for the use of these agents within the pediatric population. In this review, the authors will discuss in detail the characteristics of the various bone graft substitutes, their fusion efficacy, and their safety profile in this subpopulation.

Immunomonitoring in glioma immunotherapy: current status and future perspectives.

Given the continued poor clinical outcomes and refractory nature of glioblastoma multiforme to traditional interventions, immunotherapy is gaining traction due to its potential for specific tumor-targeting and long-term antitumor protective surveillance. Currently, development of glioma immunotherapy relies on overall survival as an endpoint in clinical trials. However, the identification of surrogate immunologic biomarkers can accelerate the development of successful immunotherapeutic strategies. Immunomonitoring techniques possess the potential to elucidate immunological mechanisms of antitumor responses, monitor disease progression, evaluate therapeutic effect, identify candidates for immunotherapy, and serve as prognostic markers of clinical outcome. Current immunomonitoring assays assess delayed-type hypersensitivity, T cell proliferation, cytotoxic T-lymphocyte function, cytokine secretion profiles, antibody titers, and lymphocyte phenotypes. Yet, no single immunomonitoring technique can reliably predict outcomes, relegating immunological markers to exploratory endpoints. In response, the most recent immunomonitoring assays are incorporating emerging technologies and novel analysis techniques to approach the goal of identifying a competent immunological biomarker which predicts therapy responsiveness and clinical outcome. This review addresses the current status of immunomonitoring in glioma vaccine clinical trials with emphasis on correlations with clinical response.

Vaccine therapies in malignant glioma.

Glioblastoma is a grade IV astrocytoma that is widely accepted in clinical neurosurgery as being an extremely lethal diagnosis. Long-term survival rates remain dismal, and even when tumors undergo gross resection with confirmation of total removal on neuroimaging, they invariably recur with even greater virulence. Standard therapeutic modalities as well as more contemporary treatments have largely resulted in disappointing improvements. However, the therapeutic potential of vaccine immunotherapy for malignant glioma should not be underestimated. In contrast to many of the available treatments, vaccine immunotherapy is unique because it offers the means of delivering treatment that is highly specific to both the patient and the tumor. Peptide, heat-shock proteins, and dendritic cell vaccines collectively encapsulate the majority of research efforts involving vaccine-based treatment modalities. In this review, important recent findings for these vaccine types are discussed in the context of ongoing clinical trials. Broad challenges to immunotherapy are also considered.

Posterior Interhemispheric-Transtentorial Approach for Resection of an Arteriovenous Malformation of the Superior Medullary Velum and Fourth Ventricle: 2-Dimensional Operative Video.

Brain arteriovenous malformations (AVMs) of the fourth ventricle represent a rare subtype associated with an aggressive natural course.1,2 In this case, a woman in her early 50s presented with dizziness. An AVM was diagnosed in the left superior cerebellar peduncle extending into the fourth ventricle. The AVM was supplied by superior cerebellar artery branches and classified as a Spetzler-Martin grade III and a Lawton-Young grade III, with a supplemented grade of 6.3,4 Being a single case report, institutional review board approval was not needed. Patient consent was obtained. The lesion was accessed through a torcular craniotomy and posterior interhemispheric-transtentorial approach, employing gravity to naturally retract the parietooccipital lobe.5-7 Dissection continued into the quadrigeminal and ambient cisterns, where the tentorium was incised parallelling the straight sinus to reach the superior vermis. Partial resection of the lingual and central lobules of the vermis facilitated access to the superior medullary velum. The superior cerebellar artery feeders were divided and followed to the superior cerebellar peduncle and through the superior medullary vellum. A vertical incision in the superior medullary velum facilitated entry into the fourth ventricle, where the AVM nidus was dissected circumferentially and resected en bloc. Intraoperative indocyanine green videoangiography and postoperative digital subtraction angiography confirmed complete obliteration of the AVM. After surgery, the patient experienced mild ataxia, but motor symptoms greatly improved during 3-month follow-up. This video illustrates resection of a complex fourth ventricular AVM through a posterior interhemispheric-transtentorial approach, highlighting pivotal considerations of patient positioning and approach selection to optimize treatment outcome for complex posterior fossa AVM resection.

Trends in medical device company payments in neurosurgery: a nationwide, multidatabase, geospatial analysis.

OBJECTIVE: Industry partnerships help advance the field of neurosurgery. Given the nature of the field and its close relationship with innovation, neurosurgeons frequently partner with the medical device industry to advance technology and improve outcomes. However, this can create important ethical concerns for patients. In this paper, the authors sought to comprehensively study how physician payments from medical device companies have changed and what geographic parameters influence the trends observed over the years. METHODS: The authors queried and merged several large databases, including Medicare and Medicaid provider usage data and databases from the Open Payments Program, National Plan and Provider Enumeration System, and US Census Bureau. Geospatial analysis was performed using Moran's I and II clustering. Univariate and multivariable analyses were performed using the Mann-Whitney U-test and geospatially weighted multivariable regression for hot spot and cold spot membership. RESULTS: Data for 952 counties across the continental United States were analyzed. Ninety-seven counties constituted geographic hot spots. These hot spots were primarily concentrated in Florida, the New York-Pennsylvania region, central Colorado, and southwestern United States. Independent predictors of hot spot membership included greater unemployment rates, the percentage of White patients, the presence of mobile homes, and the percentage of county Hispanic and Black populations. Company-based differences were examined. The vast majority of Medtronic's payments were in the form of royalties and licensing (86.6%). Royalties and licensing accounted for the majority of payments for DePuy (69.4%), Globus Medical (62%), and NuVasive (77.1%). In contrast, other companies, such as Boston Scientific, opted to pay physicians in the form of ownership and investment interests (42.1%). The impact of the COVID-19 pandemic was also assessed. During the onset of the pandemic in 2020, physician payments fell or remained the same across all regions with the exception of the South Atlantic region. However, it was observed that nearly all regions rebounded, with stark elevations in physician payments immediately in 2021. CONCLUSIONS: This analysis demonstrates that there are national hot spots and cold spots of physician payments, and offers some social, economic, and company-dependent predictors that may influence the magnitude of payments. Further analysis is needed to better understand this clinical-commercial partnership in healthcare, specifically within neurosurgical practice.

Metastasis of Intracranial Meningioma to the Osseous Spine: Systematic Literature Review and Case Report.

BACKGROUND: Osseous spinal metastases from intracranial meningiomas are rare but represent a serious disease progression. A literature review was performed on this topic to understand the clinical course of patients with this disease entity. We also present a case of spinal metastasis in a patient with a World Health Organization grade III meningioma. METHODS: The PubMed/MEDLINE database was queried on August 15, 2021, using the keywords (meningioma) AND (metastasis) AND (vertebra∗ OR spin∗). All publications reporting outcomes of patients with meningioma metastatic to the spine were included. Disease characteristics, treatment modality, and outcomes were extracted from each study. Because data availability varied widely between studies, no meta-analysis was performed. RESULTS: A total of 30 articles with 33 cases were included. Outcome data varied greatly in terms of quality and length of follow-up. Of 28 cases with reported outcomes data, 20 resulted in patient mortality ranging from a few weeks to 5 years after spinal metastasis. Mean (standard deviation) survival time was 5.8 (6.4) years following initial diagnosis, but only 1.4 (3.2) years from spinal metastasis. The longest survivor was noted to have no recurrence of disease 4 years after spinal metastasis. CONCLUSIONS: Bony spinal metastasis from intracranial meningioma is an extremely rare occurrence. Within the limits of the available literature, outcomes of patients with this disease appear to be poor. However, data reporting is inconsistent, and several articles did not report any outcome data. Further study is needed to better clarify the course and prognosis of this disease.

Anatomical Reduction of Spondylolisthesis Through Lateral Lumbar Interbody Fusion With Percutaneous Pedicle Screw Fixation: An Intraoperative Technical Note.

BACKGROUND: Surgical management of lumbar spondylolisthesis requires neural decompression, stabilization, and alignment restoration. Minimally invasive spine approaches offer a wide variety of advantages for spondylolisthesis management. This intraoperative note describes the treatment of L4-L5 lumbar spondylolisthesis with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screw fixation (PSF). METHODS: The surgical technique for treating L4-L5 lumbar spondylolisthesis using a minimally invasive approach with LLIF and percutaneous PSF is described. This operative technique is illustrated with figures, and an intraoperative case example of its application is described. RESULTS: LLIF with percutaneous PSF can be a safe, effective, and reliable option for treating lumbar spondylolisthesis when applied with appropriate surgical technique in a selected patient population. This technique is a valuable addition to the range of available spine surgical options. CONCLUSIONS: LLIF with percutaneous PSF can be an effective technique for treating lumbar L4-L5 spondylolisthesis.

Does comorbid depression and anxiety portend poor long-term outcomes following surgery for lumbar spondylolisthesis? Five-year analysis of the Quality Outcomes Database.

OBJECTIVE: Depression and anxiety are associated with poor outcomes following spine surgery. However, the influence of these conditions on achieving a minimal clinically important difference (MCID) following lumbar spine surgery, as well as the potential compounding effects of comorbid depression and anxiety, is not well understood. This study explores the impact of comorbid depression and anxiety on long-term clinical outcomes following surgical treatment for degenerative lumbar spondylolisthesis. METHODS: This study was a retrospective analysis of the multicenter, prospectively collected Quality Outcomes Database (QOD). Patients with surgically treated grade 1 lumbar spondylolisthesis from 12 centers were included. Preoperative baseline characteristics and comorbidities were recorded, including self-reported depression and/or anxiety. Pre- and postoperative patient-reported outcomes (PROs) were recorded: the numeric rating scale (NRS) score for back pain (NRS-BP), NRS score for leg pain (NRS-LP), Oswestry Disability Index (ODI), and EQ-5D. Patients were grouped into 3 cohorts: no self-reported depression or anxiety (non-SRD/A), self-reported depression or anxiety (SRD/A), or presence of both comorbidities (SRD+A). Changes in PROs over time, satisfaction rates, and rates of MCID were compared. A multivariable regression analysis was performed to establish independent associations. RESULTS: Of the 608 patients, there were 452 (74.3%) with non-SRD/A, 81 (13.3%) with SRD/A, and 75 (12.3%) with SRD+A. Overall, 91.8% and 80.4% of patients had ≥ 24 and ≥ 60 months of follow-up, respectively. Baseline PROs were universally inferior for the SRD+A cohort. However, at 60-month follow-up, changes in all PROs were greatest for the SRD+A cohort, resulting in nonsignificant differences in absolute NRS-BP, NRS-LP, ODI, and EQ-5D across the 3 groups. MCID was achieved for the SRD+A cohort at similar rates to the non-SRD/A cohort. All groups achieved > 80% satisfaction rates with surgery without significant differences across the cohorts (p = 0.79). On multivariable regression, comorbid depression and anxiety were associated with worse baseline PROs, but they had no impact on 60-month PROs or 60-month achievement of MCIDs. CONCLUSIONS: Despite lower baseline PROs, patients with comorbid depression and anxiety achieved comparable rates of MCID and satisfaction after surgery for lumbar spondylolisthesis to those without either condition. This quality-of-life benefit was durable at 5-year follow-up. These data suggest that patients with self-reported comorbid depression and anxiety should not be excluded from consideration of surgical intervention and often substantially benefit from surgery.

Predictors of patient satisfaction in the surgical treatment of cervical spondylotic myelopathy.

OBJECTIVE: Patients with cervical spondylotic myelopathy (CSM) experience progressive neurological impairment. Surgical intervention is often pursued to halt neurological symptom progression and allow for recovery of function. In this paper, the authors explore predictors of patient satisfaction following surgical intervention for CSM. METHODS: This is a retrospective review of prospectively collected data from the multicenter Quality Outcomes Database. Patients who underwent surgical intervention for CSM with a minimum follow-up of 2 years were included. Patient-reported satisfaction was defined as a North American Spine Society (NASS) satisfaction score of 1 or 2. Patient demographics, surgical parameters, and outcomes were assessed as related to patient satisfaction. Patient quality of life scores were measured at baseline and 24-month time points. Univariate regression analyses were performed using the chi-square test or Student t-test to assess patient satisfaction measures. Multivariate logistic regression analysis was conducted to assess for factors predictive of postoperative satisfaction at 24 months. RESULTS: A total of 1140 patients at 14 institutions with CSM who underwent surgical intervention were included, and 944 completed a patient satisfaction survey at 24 months postoperatively. The baseline modified Japanese Orthopaedic Association (mJOA) score was 12.0 ± 2.8. A total of 793 (84.0%) patients reported satisfaction (NASS score 1 or 2) after 2 years. Male and female patients reported similar satisfaction rates (female sex: 47.0% not satisfied vs 48.5% satisfied, p = 0.73). Black race was associated with less satisfaction (26.5% not satisfied vs 13.2% satisfied, p < 0.01). Baseline psychiatric comorbidities, obesity, and length of stay did not correlate with 24-month satisfaction. Crossing the cervicothoracic junction did not affect satisfactory scores (p = 0.19), and minimally invasive approaches were not associated with increased patient satisfaction (p = 0.14). Lower baseline numeric rating scale neck pain scores (5.03 vs 5.61, p = 0.04) and higher baseline mJOA scores (12.28 vs 11.66, p = 0.01) were associated with higher satisfaction rates. CONCLUSIONS: Surgical treatment of CSM results in a high rate of patient satisfaction (84.0%) at the 2-year follow-up. Patients with milder myelopathy report higher satisfaction rates, suggesting that intervention earlier in the disease process may result in greater long-term satisfaction.

Bortezomib-induced sensitization of malignant human glioma cells to vorinostat-induced apoptosis depends on reactive oxygen species production, mitochondrial dysfunction, Noxa upregulation, Mcl-1 cleavage, and DNA damage.

Glioblastomas are invasive tumors with poor prognosis despite current therapies. Histone deacetylase inhibitors (HDACIs) represent a class of agents that can modulate gene expression to reduce tumor growth, and we and others have noted some antiglioma activity from HDACIs, such as vorinostat, although insufficient to warrant use as monotherapy. We have recently demonstrated that proteasome inhibitors, such as bortezomib, dramatically sensitized highly resistant glioma cells to apoptosis induction, suggesting that proteasomal inhibition may be a promising combination strategy for glioma therapeutics. In this study, we examined whether bortezomib could enhance response to HDAC inhibition in glioma cells. Although primary cells from glioblastoma multiforme (GBM) patients and established glioma cell lines did not show significant induction of apoptosis with vorinostat treatment alone, the combination of vorinostat plus bortezomib significantly enhanced apoptosis. The enhanced efficacy was due to proapoptotic mitochondrial injury and increased generation of reactive oxygen species. Our results also revealed that combination of bortezomib with vorinostat enhanced apoptosis by increasing Mcl-1 cleavage, Noxa upregulation, Bak and Bax activation, and cytochrome c release. Further downregulation of Mcl-1 using shRNA enhanced cell killing by the bortezomib/vorinostat combination. Vorinostat induced a rapid and sustained phosphorylation of histone H2AX in primary GBM and T98G cells, and this effect was significantly enhanced by co-administration of bortezomib. Vorinostat/bortezomib combination also induced Rad51 downregulation, which plays an important role in the synergistic enhancement of DNA damage and apoptosis. The significantly enhanced antitumor activity that results from the combination of bortezomib and HDACIs offers promise as a novel treatment for glioma patients.

Complications associated with single-position prone lateral lumbar interbody fusion: a systematic review and pooled analysis.

OBJECTIVE: Lateral lumbar interbody fusion (LLIF) is a workhorse surgical approach for lumbar arthrodesis. There is growing interest in techniques for performing single-position surgery in which LLIF and pedicle screw fixation are performed with the patient in the prone position. Most studies of prone LLIF are of poor quality and without long-term follow-up; therefore, the complication profile related to this novel approach is not well known. The objective of this study was to perform a systematic review and pooled analysis to understand the safety profile of prone LLIF. METHODS: A systematic review of the literature and a pooled analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies reporting prone LLIF were assessed for inclusion. Studies not reporting complication rates were excluded. RESULTS: Ten studies meeting the inclusion criteria were analyzed. Overall, 286 patients were treated with prone LLIF across these studies, and a mean (SD) of 1.3 (0.2) levels per patient were treated. The 18 intraoperative complications reported included cage subsidence (3.8% [3/78]), anterior longitudinal ligament rupture (2.3% [5/215]), cage repositioning (2.1% [2/95]), segmental artery injury (2.0% [5/244]), aborted prone interbody placement (0.8% [2/244]), and durotomy (0.6% [1/156]). No major vascular or peritoneal injuries were reported. Sixty-eight postoperative complications occurred, including hip flexor weakness (17.8% [21/118]), thigh and groin sensory symptoms (13.3% [31/233]), revision surgery (3.8% [3/78]), wound infection (1.9% [3/156]), psoas hematoma (1.3% [2/156]), and motor neural injury (1.2% [2/166]). CONCLUSIONS: Single-position LLIF in the prone position appears to be a safe surgical approach with a low complication profile. Longer-term follow-up and prospective studies are needed to better characterize the long-term complication rates related to this approach.

Radiographic and Clinical Outcomes After Stand-Alone Anterior Lumbar Interbody Fusion for Symptomatic L5-S1 Retrolisthesis.

BACKGROUND AND OBJECTIVES: Degenerative lumbar spondylolisthesis is associated with significant pain and disability. The literature on the treatment options and clinical outcomes for lumbar anterolisthesis is robust, but very few reports specifically evaluate lumbar retrolisthesis. This study investigated surgical outcomes for symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 anterior lumbar interbody fusion (ALIF). METHODS: All patients with symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 ALIF at a single institution over a 7-year period were identified. Exhaustive nonoperative management had failed for all patients. Patients with previous lumbar fusion were excluded. Preoperative and postoperative radiographic images and patient-reported outcome measures for 20 patients (14 males and 6 females; mean [SD] age, 50.3 [13.7] years) were analyzed. RESULTS: The mean (SD) follow-up was 43.0 (23.7) months (range, 12.1-102.5 months). Patients experienced postoperative improvements in L5-S1 retrolisthesis (P = .048), L5-S1 disk height and angle (P < .001), L5 foraminal height (P < .001), L5-S1 lordosis (P < .001), and lumbar lordosis (P = .01). There were no significant changes in spinopelvic parameters. At the most recent follow-up, minimal clinically important differences in Oswestry Disability Index score, 36-Item Short-Form Survey (SF-36), and numerical rating scale score for leg pain were achieved in 11 of 20 (55%), 7 of 14 (50%), and 7 of 13 (54%) patients, respectively. All patients demonstrated fusion with no graft subsidence at up to 32 months. No patient experienced intraoperative complications, was readmitted, or required a subsequent posterior decompression or fusion because of refractory symptoms. CONCLUSION: In our cohort, stand-alone L5-S1 ALIF was associated with radiographic and clinical improvement in patients with symptomatic L5-S1 retrolisthesis.

Back to basal: contemporary cerebrovascular cohort study of the supratentorial-infraoccipital approach.

OBJECTIVE: The objective of this paper was to assess applications of the supratentorial-infraoccipital (STIO) approach for cerebrovascular neurosurgery. METHODS: The authors conducted a cohort study of all consecutive cases in which the STIO approach was used during the study period, December 1995 to January 2021, as well as a systematic review of the literature. RESULTS: Twenty-five cerebrovascular cases were identified in which the STIO approach was used. Diagnoses included arteriovenous malformation (n = 15), cerebral cavernous malformation (n = 5), arteriovenous fistula (n = 4), and aneurysm (n = 1). The arteriovenous malformations consisted of Spetzler-Martin grade II (n = 3), grade III (n = 8), and grade IV (n = 4) lesions. Lesion locations included the occipital lobe (n = 15), followed by the tentorial dural (n = 4), temporal-occipital (n = 3), temporal (n = 1), thalamic (n = 1), and quadrigeminal cistern (n = 1) regions. Many patients (75%) experienced transient visual deficits attributable to retraction of the occipital lobe, all of which resolved. As of last follow-up (n = 12), modified Rankin Scale scores had improved for 6 patients and were unchanged for 6 patients compared with the preoperative baseline. CONCLUSIONS: The STIO approach is a safe and effective skull base approach that provides a specialized access corridor for appropriately selected cerebrovascular lesions.

ABT-737 synergizes with bortezomib to induce apoptosis, mediated by Bid cleavage, Bax activation, and mitochondrial dysfunction in an Akt-dependent context in malignant human glioma cell lines.

We observed that glioma cells are differentially sensitive to N-{4-[4-(4'-chloro-biphenyl-2-ylmethyl)-piperazin-1-yl]-benzoyl}-4-(3-dimethylamino-1-phenylsulfanylmethyl-propylamino)-3-nitro-benzenesulfonamide (ABT-737) and administration of ABT-737 at clinically achievable doses failed to induce apoptosis. Although elevated Bcl-2 levels directly correlated with sensitivity to ABT-737, overexpression of Bcl-2 did not influence sensitivity to ABT-737. To understand the molecular basis for variable and relatively modest sensitivity to the Bcl-2 homology domain 3 mimetic drug ABT-737, the abundance of Bcl-2 family members was assayed in a panel of glioma cell lines. Bcl-2 family member proteins, Bcl-xL, Bcl-w, Mcl-1, Bax, Bak, Bid, and Noxa, were found to be expressed ubiquitously at similar levels in all cell lines tested. We then examined the contribution of other apoptosis-resistance pathways to ABT-737 resistance. Bortezomib, an inhibitor of nuclear factor-kappaB (NF-κB), was found to enhance sensitivity of ABT-737 in phosphatase and tensin homolog on chromosome 10 (PTEN)-wild type, but not PTEN-mutated glioma cell lines. We therefore investigated the association between phosphatidylinositol 3-kinase (PI3K)/Akt activation and resistance to the combination of ABT-737 and bortezomib in PTEN-deficient glioma cells. Genetic and pharmacological inhibition of PI3K inhibition sensitized PTEN-deficient glioma cells to bortezomib- and ABT-737-induced apoptosis by increasing cleavage of Bid protein, activation and oligomerization of Bax, and loss of mitochondrial membrane potential. Our data further suggested that PI3K/Akt-dependent protection may occur upstream of the mitochondria. This study demonstrates that interference with multiple apoptosis-resistance signaling nodes, including NF-κB, Akt, and Bcl-2, may be required to induce apoptosis in highly resistant glioma cells, and therapeutic strategies that target the PI3K/Akt pathway may have a selective role for cancers lacking PTEN function.

Unique Presentation and Novel Surgical Approach to a Transcribriform Penetrating Head Injury Caused by a Nail Gun.

A penetrating head injury caused by a nail gun is an infrequent clinically diverse condition that varies in severity by the neurovascular structures involved. The authors present the case of a patient whose frontal lobe was pierced by a nail that entered via a transnasal transcribriform trajectory without causing vascular injury or intracranial hemorrhage; the man was unaware of the nail's presence and presented with headache five days after the incident. The nail was extracted using a bifrontal craniotomy for direct visualization and for defect repair of the skull base combined with endoscopic endonasal extraction of the nail.

Residual Tumor Volume and Tumor Progression after Subtotal Resection and Observation of WHO Grade I Skull Base Meningiomas.

Objective This study investigated the impact of residual tumor volume (RTV) on tumor progression after subtotal resection and observation of WHO grade I skull base meningiomas. Study Design This study is a retrospective volumetric analysis. Setting This study was conducted at a single institution. Participants Patients who underwent subtotal resection of a WHO grade I skull base meningioma and postsurgical observation (July 1, 2007-July 1, 2017). Main Outcome Measure The main outcome was radiographic tumor progression. Results Sixty patients with residual skull base meningiomas were analyzed. The median (interquartile range) RTV was 1.3 (5.3) cm 3 . Tumor progression occurred in 23 patients (38.3%) at a mean duration of 28.6 months postsurgery. The 1-, 3-, and 5-year actuarial progression-free survival (PFS) rates were 98.3, 58.6, and 48.7%, respectively. The Cox multivariate analysis identified increasing RTV ( p = 0.01) and history of more than 1 previous surgery ( p = 0.03) as independent predictors of tumor progression. In a Kaplan-Meier analysis for PFS, the RTV threshold of 3 cm 3 maximized log-rank testing significance between groups of patients dichotomized at 0.5 cm 3 thresholds ( p < 0.01). The 3-year actuarial PFS rates for meningiomas with RTV ≤3 cm 3 and >3 cm 3 were 76.2 and 32.1%, respectively. When RTV >3 cm 3 was entered as a covariate in the Cox model, it was the only factor independently associated with tumor progression ( p < 0.01). Conclusion RTV was associated with tumor progression after subtotal resection of WHO grade I skull base meningioma in this cohort. An RTV threshold of 3 cm 3 was identified that minimized progression of the residual tumor when gross total resection was not safe or feasible.

Ketogenic Metabolic Therapy for Glioma.

PURPOSE: This study describes a retrospective case series of patients with glioma who received ketogenic metabolic therapy through dietary adherence and intermittent fasting. METHODS: A retrospective chart review of a single surgeon's clinic records was performed to identify patients who maintained nutritional ketosis for at least four months between January 2015 and October 2020. RESULTS: Sixteen patients who met the inclusion criteria constituted a heterogeneous population of patients with diagnoses including eight World Health Organization (WHO) grade IV gliomas (seven glioblastoma, one gliosarcoma), seven WHO grade III gliomas (three oligodendroglioma, four astrocytoma), and one WHO grade II oligodendroglioma. IDH1 mutation status was present for 12 patients, and MGMT methylation status was present for eight patients. The mean (standard deviation [SD]) duration of ketogenic metabolic therapy was 20.6 (13.8) months. The Response Assessment in Neuro-oncology Criteria was applied during the ketogenic metabolic therapy interval, indicating a complete response in eight patients and partial response in eight patients. The mean (SD) progression-free survival while patients maintained ketogenic metabolic therapy was 20.0 (14.4) months. CONCLUSION: Ketogenic metabolic therapy appears to convey a survival advantage within this patient series, which highlights the possibility that this therapy, when strictly applied, can augment the standard of care. Further exploration of this modality in a prospective series is warranted to formally explore this therapy.

Comparison of Intraoperative Indocyanine Green Videoangiography vs Postoperative Catheter Angiography to Confirm Microsurgical Occlusion of Spinal Dorsal Intradural Arteriovenous Fistulas.

BACKGROUND: Dorsal intradural arteriovenous fistulas (DI-AVFs) represent 80% of spinal AVFs. Microsurgical clip occlusion is a durable treatment that uses preoperative and postoperative digital subtraction angiography (DSA) as standard practice. Intraoperative indocyanine green videoangiography (ICG-VA) is a valuable intraoperative adjunct in these cases. Intraoperative ICG-VA findings have not been compared with postoperative DSA findings. OBJECTIVE: To assess the diagnostic value of intraoperative ICG-VA vs postoperative DSA for spinal DI-AVFs. METHODS: A multi-institutional database of vascular malformations was queried for all surgically managed cases of DI-AVF. Patients with both intraoperative ICG-VA and postoperative DSA were included. Demographic and radiologic data, intraoperative findings, and surgical outcomes data were retrospectively analyzed. RESULTS: Forty-five patients with DI-AVF were identified (male sex, 32; mean age, 61.9 [range, 26-85] years). All DI-AVFs were treated with interruption of the fistula with clip occlusion of the draining vein. Intraoperative ICG-VA showed complete obliteration in all patients. Postoperative DSA was performed for 40 patients and confirmed complete obliteration in all patients. The negative predictive value of ICG-VA confirming complete occlusion of the DI-AVFs was 100%. Eighteen patients (47%) experienced clinical improvement, and 16 (42%) experienced no change in condition. CONCLUSION: ICG-VA is useful for intraoperative identification of DI-AVFs and confirmation of complete microsurgical occlusion. Correlation between intraoperative ICG-VA and postoperative DSA findings demonstrates the diagnostic power of ICG-VA. This finding suggests that postoperative DSA is unnecessary when intraoperative ICG-VA confirms complete occlusion of the DI-AVF, which will spare patients the procedural risk and cost of this invasive procedure.