Results from a first-in-human phase I safety trial to evaluate the use of a vascularized pericranial/temporoparietal fascial flap to line the resection cavity following resection of newly diagnosed glioblastoma.

PURPOSE: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM. METHODS: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure. RESULTS: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm3 (range 14-145 cm3). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months. CONCLUSIONS: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018.

Impact of Cerebral Revascularization on Pial Collateral Flow in Patients With Unilateral Moyamoya Disease Using Quantitative Magnetic Resonance Angiography.

BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a chronic steno-occlusive disease of the intracranial circulation that depends on neoangiogenesis of collateral vessels to maintain cerebral perfusion and is primarily managed with cerebral revascularization surgery. A quantitative assessment of preoperative and postoperative collateral flow using quantitative magnetic resonance angiography with noninvasive optimal vessel analysis (NOVA) was used to illustrate the impact of revascularization on cerebral flow distribution. METHODS: A retrospective review of patients with unilateral MMD who underwent direct, indirect, or combined direct/indirect cerebral revascularization surgery was conducted between 2011 and 2020. Using NOVA, flow was measured at the anterior cerebral artery (ACA), ACA distal to the anterior communicating artery (A2), middle cerebral artery (MCA), posterior cerebral artery (PCA), and PCA distal to the posterior communicating artery (P2). Pial flow (A2 + P2) and collateral flow (ipsilateral [A2 + P2])-(contralateral [A2 + P2]) were measured and compared before and after revascularization surgery. Total hemispheric flow (MCA + A2 + P2) with the addition of the bypass graft flow postoperatively was likewise measured. RESULTS: Thirty-four patients with unilateral MMD underwent cerebral revascularization. Median collateral flow significantly decreased from 68 to 39.5 mL/min (P = .007) after bypass. Hemispheres with maintained measurable bypass signal on postoperative NOVA demonstrated significant reduction in median collateral flow after bypass (P = .002). Median total hemispheric flow significantly increased from 227 mL/min to 247 mL/min (P = .007) after bypass. Only one patient suffered an ipsilateral ischemic stroke, and no patients suffered a hemorrhage during follow-up. CONCLUSION: NOVA measurements demonstrate a reduction in pial collateral flow and an increase in total hemispheric flow after bypass for MMD, likely representing a decrease in leptomeningeal collateral stress on the distal ACA and PCA territories. Further studies with these measures in larger cohorts may elucidate a role for NOVA in predicting the risk of ischemic and hemorrhagic events in MMD.

Troubleshooting the bypass: intraoperative management of initially failed anastomosis in direct cerebral revascularization surgery.

OBJECTIVE: Direct cerebral revascularization is considered as one of the most technically challenging operations in neurosurgery. Technical errors are often not identified during the case, but only after the recirculation stage, making management crucial at that time of the procedure. In this study, the authors sought to describe troubleshooting of the technical errors encountered in initially failed bypass cases. METHODS: A retrospective analysis describing a single-surgeon, single-institution experience between 2014 and 2021 was performed, based on operative reports and videos, including a 30-day follow-up period. Initially failed bypass was defined if the bypass was not patent or had a significant leak after recirculation, irrespective of the final result. RESULTS: One hundred thirty-eight bypass cases were reviewed for complex aneurysms (n = 49), moyamoya disease (n = 59), and atherosclerosis (n = 30). Fifty-one initially failed anastomoses were identified; 43 of these were the result of a technical error. Etiologies of these failed anastomoses included a clot (n = 14), vessel kinking (n = 4), spasm (n = 5), suture-related cause (n = 5), inappropriate donor or recipient (n = 3), or lack of demand (n = 8). A major leak was attributed to an uncoagulated side branch (n = 4), vessel injury due to suture/clip placement (n = 1), or inadequate suture line coverage (n = 7). Thirty-seven (86%) of 43 cases were troubleshot successfully, as salvage maneuvers included papaverine vessel massage, donor repositioning, re-anastomosis for occlusion in select cases, local hemostatic agents, and suturing or coagulating side branches in a leak. Thirty-day follow-up revealed similar rates of patency between successfully troubleshot patients (35/37) and the rest of the cases (80/87, p = 0.6). CONCLUSIONS: Three major patterns of a noncompatible bypass were found: a major leak, an acute occlusion, or a delayed occlusion. Based on the authors' experience, salvage strategies proved successful, showing an eventual high patency rate. The authors suggest a gradual, structured algorithm to address this stage in surgery that may contribute specifically to cerebrovascular neurosurgeons at the beginning of their careers.

An algorithm for the treatment of concurrent pituitary adenoma and cavernous sinus aneurysm: A systematic review & case report.

BACKGROUND: Rarely, Pituitary adenomas (PA) can co-occur with intrasellar or intracavernous aneurysms. There is currently no clear guidance for the management of this dual pathology. We attempt to provide an algorithm to help guide clinical decision making for treatment of PAs co-occurring with adjacent cerebral aneurysms. METHODS: A comprehensive literature search was conducted following PRISMA guidelines using various databases. Search terms included "(Pituitary Adenoma OR Prolactinoma OR Macroadenoma OR Adenoma) AND (ICA OR Internal Carotid Artery OR paracliniod OR clinoid) Aneurysm AND (Intra-cavernous OR intracavernous OR intrasellar OR Cavernous)." RESULTS: A total of 24 studies with 24 patients were included. Twelve (50%) patients experienced visual symptoms. Ten patients (42%) had an aneurysm embedded within the adenoma. Fourteen patients (58%) had an aneurysm adjacent to the adenoma. Embedded aneurysms were significantly associated with rupture events. CONCLUSION: Vision loss is the most pressing determinant of treatment. In the absence of visual symptoms, the aneurysm should be treated first by coil embolization. If not amenable to coiling, place flow diverting stent followed by six months of anticoagulation and antiplatelet therapy. If visual loss is apparent, the adenoma-aneurysm spatial relationship becomes critical. In cases of an adjacent aneurysm, the adenoma should be removed transsphenoidally with extreme care and aneurysm rupture protocols in place. If the aneurysm is embedded within the adenoma, then a BTO is favored with permanent ICA occlusion followed by transsphenoidal resection if adequate collateral supply is demonstrated. If there is inadequate collateral supply, then an open-approach for amenable aneurysms with transcranial adenoma debulking should be performed.

Neuromonitoring Identifies Occlusion of Femoral Artery in STA-MCA Bypass Procedure: A Case Report.

Intraoperative neurophysiological monitoring (IONM) is a technique used to assess the somatosensory and gross motor systems during surgery. While it is primarily used to detect and prevent surgically induced nervous system trauma, it can also detect and prevent injury to the nervous system that is the result of other causes such as trauma or ischemia that occur outside of the operative field as a result of malpositioning or other problematic physiologic states. We present a case study where a neuromonitoring alert altered the surgical procedure, though the alert was not correlated to the site of surgery. A 69-year-old male with a history of bilateral moyamoya disease and a left middle cerebral artery infarct underwent a right-sided STA-MCA bypass and encephaloduroarteriosynangiosis (EDAS) with multimodal IONM. During the procedure, the patient experienced a loss of motor evoked potential (MEP) recordings in the right lower extremity. Blood pressure was elevated, which temporarily restored the potentials, but they were lost again after the angiography team attempted to place an arterial line in the right femoral artery. The operation was truncated out of concern for left hemispheric ischemia, and it was later discovered that the patient had an acute right external iliac artery occlusion caused by a fresh thrombus in the common femoral artery causing complete paralysis of the limb. This case highlights the importance of heeding IONM alerts and evaluating for systemic causes if the alert is not thought to be of surgical etiology. IONM can detect adverse systemic neurological sequelae that is not necessarily surgically induced.

Improvement in visual outcomes of patients with base of skull meningioma as a result of evolution in the treatment techniques in the last three decades: a systematic review.

PURPOSE: We systematically reviewed visual outcomes over the last three decades in patients undergoing treatment for base of skull (BOS) meningiomas and provide recommendations to preserve vision. METHODS: In accordance with the PRISMA guidelines for systematic reviews, a search was conducted from 6/1/2022-9/1/2022 using PubMed and Web of Science. Inclusion criteria included (1) patients treated for BOS meningiomas (2) treatment modality specified (3) specifics of surgical techniques and/or dose/fractions of radiotherapy (4) individual patient outcomes of treatment. Each study was assessed for bias based on study design and heterogeneity of results. RESULTS: A total of 50 studies were included (N = 2911). When comparing improved vision versus unchanged or worsened vision, studies investigating surgery alone published from 2006 and onward had significantly better visual outcomes compared to pre-2006 studies (p = 0.02). When comparing improved vision versus unchanged or worsened vision, studies investigating combined therapy with surgery and radiation published from 2008 and onward had significantly better visual outcomes compared to pre-2008 studies (p < 0.01). Combined modality therapy was less likely to worsen vision compared to either surgery or radiation monotherapy (p < 0.01). However, surgery and radiation monotherapy were more likely to actually improve outcomes compared to combination therapy (p < 0.01). CONCLUSION: For over a decade we have observed improvement in visual outcomes in patients managed for meningioma of BOS, likely attributing the innovation in microsurgical and more targeted and conformal radiation techniques. Combination therapy may be the safest option for preventing worsening of vision, but the highest rates of improving visual function are achieved through monotherapy when indicated.

Dolichoectatic vertebrobasilar aneurysms: a systematic review and meta-analysis of management strategies and outcomes.

OBJECTIVE: The aim of this study was to describe the efficacy, clinical outcomes, and complications of open cerebrovascular surgery, endovascular surgery, and conservative management of dolichoectatic vertebrobasilar aneurysms (DVBAs). METHODS: Relevant articles were retrieved from PubMed, Scopus, Web of Science, and Cochrane databases according to PRISMA guidelines. A meta-analysis was conducted for clinical presentation, treatment protocols, and clinical outcomes-good (improved or stable clinical status) or poor (deteriorated clinical status or death)-and mortality rates. RESULTS: The 9 identified articles described 41 cases (27.5%) of open cerebrovascular surgery, 61 endovascular procedures (40.9%), and 47 cases (31.5%) of conservative management for DVBAs. The total cohort had a good outcome rate of 51.9% (95% CI 28.3%-74.6%), a poor outcome rate of 45.5% (95% CI 23.0%-70.1%), and a mortality rate of 22.3% (95% CI 11.8%-38.0%). The treatment groups had comparable good clinical outcome rates (open cerebrovascular surgery group: 24.7% [95% CI 2.9%-78.2%]; endovascular surgery group: 69.0% [95% CI 28.7%-92.5%]; conservative management group: 57.7% [95% CI 13.0%-92.5%]; p = 0.19) and poor outcome rates (open vascular surgery group: 75.3% [95% CI 21.8%-97.1%]; endovascular surgery group: 27.2% [95% CI 5.6%-0.70.2%]; conservative management group: 39.9% [95% CI 9.1%-81.6%]; p = 0.15). The treatment groups also had comparable mortality rates (open vascular surgery group: 39.5% [95% CI 11.4%-76.8%]; endovascular surgery group: 15.8% [95% CI 4.4%-43.0%]; conservative management group: 19.2% [95% CI 6.8%-43.5%]; p = 0.23). CONCLUSIONS: The current study of DVBAs illustrated poor outcomes and high mortality rates regardless of the treatment modality. The subgroup analysis showed heterogeneity among the subgroups and advice for personalized management.

Short and long-term prognostic value of intraoperative motor evoked potentials in brain tumor patients: a case series of 121 brain tumor patients.

PURPOSE: Iatrogenic neurologic deficits adversely affect patient outcomes following brain tumor resection. Motor evoked potential (MEP) monitoring allows surgeons to assess the integrity of motor-eloquent areas in real-time during tumor resection to lessen the risk of iatrogenic insult. We retrospectively associate intraoperative transcranial and direct cortical MEPs (TC-MEPs, DC-MEPs) to early and late post-operative motor function to prognosticate short- and long-term motor recovery in brain tumor patients undergoing surgical resection in peri-eloquent regions. METHODS: We reviewed 121 brain tumor patients undergoing craniotomies with DC-MEP and/or TC-MEP monitoring. Motor function scores were recorded at multiple time-points up to 1 year postoperatively. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated at each time point. RESULTS: The sensitivity, specificity, PPV, and NPV of TC-MEP in the immediate postoperative period was 17.5%, 100%, 100%, and 69.4%, respectively. For DC-MEP monitoring, the respective values were 25.0%, 100%, 100%, and 68.8%. By discharge, sensitivity had increased for both TC-MEP and DC MEPs to 43.8%, and 50.0% respectively. Subset analysis on patients without tumor recurrence/progression at long term follow-up (n = 62 pts, 51.2%) found that all patients with stable monitoring maintained or improved from preoperative status. One patient with transient intraoperative TC-MEP loss and permanent DC-MEP loss suffered a permanent deficit. CONCLUSION: Brain tumor patients who undergo surgery with intact MEP monitoring and experience new postoperative deficits likely suffer transient deficits that will improve over the postoperative course in the absence of disease progression.

#Neurosurgery: A Cross-Sectional Analysis of Neurosurgical Content on TikTok.

Objectives: TikTok is a social media platform that has gained popularity and become a powerful engine to disseminate public health and medical information. To date, no study has characterized the qualities of popular TikTok videos related to neurosurgery, or assessed biases in the content of these videos. Methods: The TikTok web browser application was queried using "#neurosurgery" to identify neurosurgery-related videos. The top 100 videos meeting inclusion criteria were analyzed and video characteristics determined. Bias was assessed by the DISCERN scoring system using 3 independent reviewers. A Kruskal-Wallis H test was used to correlate video popularity with video characteristics and to correlate bias with creator and video type. Results: The 100 videos evaluated totaled 8.8 million likes, 104,718 comments, and 100,856 shares. The oldest video was posted February 2020 and the most recent March 2022. Videos were most commonly entertaining (n = 64, 64%), and educational (n = 46, 46%). Video popularity was associated with videos that aimed to entertain, and least associated with videos depicting neurosurgery lifestyle. Low DISCERN scores, indicating more biased content, were seen across the neurosurgical content with the entertaining video category demonstrating the highest bias. Conclusions: Neurosurgical content on TikTok contains a high degree of bias across all creator and video types. Entertaining videos are associated with the highest numbers of likes but also the greatest bias. These data may be used to guide institutions and neurosurgeons to grow interest in the field of neurosurgery and disseminate unbiased information while expanding their social media presence.

Stroke mechanisms in adult moyamoya disease: The association between infarction patterns and quantitative magnetic resonance angiography flow state.

INTRODUCTION: Flow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state. METHODS: A retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria. RESULTS: Mixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ- (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ- population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ- (345.0 % vs. 214.7 %, p = 0.04). CONCLUSION: Mixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism.

Reconstruction of the Anterior Skull Base Using the Nasoseptal Flap: A Review.

The nasoseptal flap is a workhorse reconstructive option for anterior skull base defects during endonasal surgery. This paper highlights the versatility of the nasoseptal flap. After providing a brief historical perspective, this review will focus on the relevant primary literature published in the last ten years. We will touch upon new applications of the flap, how the flap has been modified to expand its reach and robustness, and some of the current limitations. We will conclude by discussing what the future holds for improving upon the design and use of the nasoseptal flap in anterior skull base reconstruction.

Does Advanced Imaging Aid in the Preoperative Evaluation of Patients With Moyamoya Disease?

Background Moyamoya disease is characterized by progressive nonatherosclerotic stenosis and eventual occlusion of the supraclinoid cerebral arteries with the associated development of abnormal collateral vessels. Treatment of moyamoya disease revolves around restoring cerebral blood flow (CBF) distal to the steno-occlusive disease. Numerous modalities can be used to assess hemodynamic parameters. We sought to determine the impact of preoperative imaging on surgical decision-making. Methods A retrospective review was performed of all patients seen with the diagnosis of moyamoya. Patients were grouped on presentation based on CT/MRI findings of infarction, hemorrhage, or normal. Patients who did not have all of the preoperative tests were excluded. Preoperative radiological results were dichotomized as either normal or abnormal. Results During a five-year period, 34 patients with moyamoya met the inclusion criteria. All patients had an abnormal magnetic resonance angiography (MRA) Non-invasive Optimal Vessel Analysis (NOVA; VasSol, Inc, River Forest, IL). Three patients had normal initial MRI. All symptomatic patients had abnormal preoperative workup and underwent revascularization, as all were found to have abnormal single photon emission computed tomography (SPECT). The only occasion where the decision for surgery or type of surgery was influenced by imaging findings was in patients with nonclassical or minimal symptoms. Conclusion Although hemodynamic imaging studies can aid in establishing a preoperative baseline of CBF and cerebral vascular reserve (CVR) for follow-up studies, the true implication of these tests in the preoperative evaluation of clearly symptomatic moyamoya patients is debatable. In asymptomatic/mildly symptomatic patients, hemodynamic studies are necessary to determine the need for treatment. For symptomatic patients, surgery can be performed without an exhaustive and costly preoperative hemodynamic evaluation.

Exoscopic Cerebrovascular Neurosurgery.

The exoscope is the technological successor to the operating microscope in cerebrovascular neurosurgery. It offers advantages including improved operative field magnification, resolution, lighting, ergonomics, team cohesiveness, and microsurgical training However, these advantages of using the exoscope must be weighed against the learning curve during its adoption, especially for senior microneurosurgeons. As exoscope technology is refined, seamless integration of robotics, automation, augmented reality, and hands-free real-time neuronavigation is anticipated.