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Ali Rajabian, Saman Vinke, Joseph Candelario-Mckeown, Catherine Milabo, Maricel Salazar, Abdul Karim Nizam, Nadia Salloum, Jonathan Hyam, Harith Akram, Eileen Joyce, Thomas Foltynie, Patricia Limousin, Marwan Hariz, and Ludvic Zrinzo

OBJECTIVE

Suboptimal lead placement is one of the most common indications for deep brain stimulation (DBS) revision procedures. Confirming lead placement in relation to the visible anatomical target with dedicated stereotactic imaging before terminating the procedure can mitigate this risk. In this study, the authors examined the accuracy, precision, and safety of intraoperative MRI (iMRI) to both guide and verify lead placement during frame-based stereotactic surgery.

METHODS

A retrospective analysis of 650 consecutive DBS procedures for targeting accuracy, precision, and perioperative complications was performed. Frame-based lead placement took place in an operating room equipped with an MRI machine using stereotactic images to verify lead placement before removing the stereotactic frame. Immediate lead relocation was performed when necessary. Systematic analysis of the targeting error was calculated.

RESULTS

Verification of 1201 DBS leads with stereotactic MRI was performed in 643 procedures and with stereotactic CT in 7. The mean ± SD of the final targeting error was 0.9 ± 0.3 mm (range 0.1–2.3 mm). Anatomically acceptable lead placement was achieved with a single brain pass for 97% (n = 1164) of leads; immediate intraoperative relocation was performed in 37 leads (3%) to obtain satisfactory anatomical placement. General anesthesia was used in 91% (n = 593) of the procedures. Hemorrhage was noted after 4 procedures (0.6%); 3 patients (0.4% of procedures) presented with transient neurological symptoms, and 1 experienced delayed cognitive decline. Two bleeds coincided with immediate relocation (2 of 37 leads, 5.4%), which contrasts with hemorrhage in 2 (0.2%) of 1164 leads implanted on the first pass (p = 0.0058). Three patients had transient seizures in the postoperative period. The seizures coincided with hemorrhage in 2 of these patients and with immediate lead relocation in the other. There were 21 infections (3.2% of procedures, 1.5% in 3 months) leading to hardware removal. Delayed (> 3 months) retargeting of 6 leads (0.5%) in 4 patients (0.6% of procedures) was performed because of suboptimal stimulation benefit. There were no MRI-related complications, no permanent motor deficits, and no deaths.

CONCLUSIONS

To the authors’ knowledge, this is the largest series reporting the use of iMRI to guide and verify lead location during DBS surgery. It demonstrates a high level of accuracy, precision, and safety. Significantly higher hemorrhage was encountered when multiple brain passes were required for lead implantation, although none led to permanent deficit. Meticulous audit and calibration can improve precision and maximize safety.

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Shengyu Fang, Shimeng Weng, Lianwang Li, Yuhao Guo, Xing Fan, Zhong Zhang, Tao Jiang, and Yinyan Wang

OBJECTIVE

It is important to identify language deficit and recovery in the week following a tumor resection procedure. The homotopic Broca’s area and the superior longitudinal fasciculus in the right hemisphere participate in language functional compensation. However, the nodes in these structures, as well as their contributions to language rehabilitation, remain unknown. In this study, the authors investigated the association of homotopic areas in the right hemisphere with language deficit.

METHODS

The authors retrospectively reviewed the records of 50 right-handed patients with left hemispheric lower-grade glioma that had been surgically treated between June 2020 and May 2022. The patients were divided into normal and aphasia groups based on their postoperative aphasia quotient (AQ) from the Western Aphasia Battery. Preoperative (within 24 hours before surgery) and postoperative (7 days after tumor resection) diffusion tensor images were used to reveal alterations of structural networks by using graphic theory analysis. The shortest distance between the glioma and the nodes belonging to the language network (SDTN) was quantitatively assessed. Pearson’s correlation and causal mediation analyses were used to identify correlations and mediator factors among SDTN, topological properties, and AQs.

RESULTS

Postoperative nodal local efficiency of the node dorsal Brodmann area (BA) 44 (A44d; p = 0.0330), nodal clustering coefficient of the nodes A44d (p = 0.0402) and dorsal lateral BA6 (A6dl; p = 0.0097), and nodal degree centrality (p = 0.0058) of the node medial BA7 (A7m) were higher in the normal group than in the aphasia group. SDTN was positively correlated with postoperative AQ (r = 0.457, p = 0.0009) and ΔAQ (r = 0.588, p < 0.0001). The nodal local efficiency of node A44d and the nodal efficiency, nodal betweenness centrality, and degree centrality of node A7m were mediators of SDTN and postoperative AQs.

CONCLUSIONS

The decreased ability of nodes A44d, A6dl, and A7m to convey information in the right hemisphere was associated with short-term language deficits after tumor resection. A smaller SDTN induced a worsened postoperative language deficit through a significant decrease in the ability to convey information from these three nodes.

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*Yu Zhang, Huiwen Tan, Lu Jia, Jialing He, Pengfei Hao, Tiangui Li, Yangchun Xiao, Liyuan Peng, Yuning Feng, Xin Cheng, Haidong Deng, Peng Wang, Weelic Chong, Yang Hai, Lvlin Chen, Chao You, and Fang Fang

OBJECTIVE

Hyperglycemia is associated with worse outcomes in ambulatory settings and specialized hospital settings, but there are sparse data on the importance of preoperative blood glucose measurement before brain tumor craniotomy. The authors sought to investigate the association between preoperative glucose level and 30-day mortality rate in patients undergoing brain tumor resection.

METHODS

This retrospective cohort study included patients undergoing craniotomy for brain tumors at West China Hospital, Sichuan University, from January 2011 to March 2021. Surgical mortality rates were evaluated in patients who had normal glycemia (< 5.6 mmol/L) as well as mild (5.6–6.9 mmol/L), moderate (7.0–11.0 mmol/L), and severe hyperglycemia (> 11.0 mmol/L).

RESULTS

The study included 12,281 patients who underwent tumor resection via craniotomy. The overall 30-day mortality rate was 2.0% (242/12,281), whereas the rates for normal glycemia and mild, moderate, and severe hyperglycemia were 1.5%, 2.5%, 3.8%, and 6.5%, respectively. Compared with normal glycemia, the odds of mortality at 30 days were higher in patients with mild hyperglycemia (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.05–2.00), moderate hyperglycemia (OR 2.04, 95% CI 1.41–2.96), and severe hyperglycemia (OR 3.76, 95% CI 1.96–7.20; p < 0.001 for trend). When blood glucose was analyzed as a continuous variable, for each 1 mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.13 (95% CI 1.08–1.19). The addition of a preoperative glucose level significantly improved the area under the curve and categorical net reclassification index for prediction of mortality.

CONCLUSIONS

In patients undergoing craniotomy for brain tumors, even mild hyperglycemia was associated with an increased mortality rate, at a glucose level that was much lower than the commonly applied level.

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Victor M. Lu, Victoria A. Pinilla Escobar, Rebecca A. Saberi, Gareth P. Gilna, Joshua D. Burks, Toba N. Niazi, Chad M. Thorson, and Heather J. McCrea

OBJECTIVE

Civilian gunshot wounds (GSWs) involving the skeletal spine and spinal cord in pediatric patients are fortunately rare. Nevertheless, their presentation mandates judicious evaluation, and their clinical outcomes remain poorly defined. Thus, the authors aimed to characterize the clinical course of this traumatic presentation in the pediatric population based on their institutional experience.

METHODS

A retrospective review of a level I trauma center database was performed for the period 2011–2021. Clinical data were included for patients aged ≤ 18 years who had presented with radiographic and clinical evidence of a GSW to the spine and had at least one documented follow-up at least 6 months after injury. The primary outcomes of the study were the categorization of gunshot injuries and the results of neurological and functional examinations.

RESULTS

A total of 13 patients satisfied the study selection criteria. The mean patient age was 15.7 ± 1.6 years, and all presentations were assault in nature. Most of the patients were male (n = 12, 92%) in gender, Black in race (n = 11, 85%), and from zip codes with a median household income below the local county average (n = 10, 77%). All patients presented with a minimum Glasgow Coma Scale score of 14. Examination at presentation revealed American Spinal Injury Association Impairment Scale (AIS) grade A in 3 cases (23%), grade B in 2 (15%), grade C in 1 (8%), grade D in 2 (15%), and grade E in 5 (38%). Gunshot injury involved all regions of the spine, most commonly the cervical and thoracic spine (n = 6 for each, 46%). In terms of skeletal injury, the most common injuries were to the facet (n = 10, 77%) and the pedicle (n = 8, 62%), with evidence of intracanal injury in 9 patients (69%). Neurosurgical intervention was pursued in 1 patient (8%). Overall, 7 patients (54%) experienced a complication during admission, and the median length of hospitalization was 12 days (range 1–88 days) without any mortality events. Within 90 days from discharge, 2 patients (15%) were readmitted to the hospital for further care. The mean follow-up was 28.9 months (range 6–74 months), by which only 1 patient (8%) had an improved AIS examination; all other patients remained at their initial AIS grade.

CONCLUSIONS

Pediatric GSWs involving the spine are typically nonfatal presentations, and their long-term functional outlook appears contingent on clinical examination findings at initial presentation. Although neurosurgical intervention is not necessary in most cases, judicious evaluation of radiographic and clinical examinations by a neurosurgical team is strongly recommended to optimize recovery.

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Mitch R. Paro, Michal Dyrda, Srinath Ramanan, Grant Wadman, Stacey-Ann Burke, Isabella Cipollone, Cory Bosworth, Sarah Zurek, and Patrick B. Senatus

OBJECTIVE

Stroke remains the leading cause of disability in the United States. Even as acute care for strokes advances, there are limited options for improving function once the patient reaches the subacute and chronic stages. Identification of new therapeutic approaches is critical. Deep brain stimulation (DBS) holds promise for these patients. A number of case reports and small case series have reported improvement in movement disorders after strokes in patients treated with DBS. In this systematic review, the authors have summarized the patient characteristics, anatomical targets, stimulation parameters, and outcomes of patients who have undergone DBS treatment for poststroke movement disorders.

METHODS

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The PubMed, Scopus, and SpringerLink databases were searched for the keywords "DBS," "stroke," "movement," and "recovery" to identify patients treated with DBS for movement disorders after a stroke. The Joanna Briggs Institute Critical Appraisal checklists for case reports and case series were used to systematically analyze the quality of the included studies. Data collected from each study included patient demographic characteristics, stroke diagnosis, movement disorder, DBS target, stimulation parameters, complications, and outcomes.

RESULTS

The authors included 29 studies that described 53 patients who underwent placement of 82 total electrodes. Movement disorders included tremor (n = 18), dystonia (n = 18), hemiballism (n = 6), spastic hemiparesis (n = 1), chorea (n = 1), and mixed disorders (n = 9). The most common DBS targets were the globus pallidus internus (n = 32), ventral intermediate nucleus of thalamus (n = 25), and subthalamic area/subthalamic nucleus (n = 7). Monopolar stimulation was reported in 43 leads and bipolar stimulation in 13. High-frequency stimulation was used in 57 leads and low-frequency stimulation in 6. All patients but 1 had improvement in their movement disorders. Two complications were reported: speech impairment in 1 patient and hardware infection in another. The median (interquartile range) duration between stroke and DBS treatment was 6.5 (2.1–15.8) years.

CONCLUSIONS

This is the first systematic review of DBS for poststroke movement disorders. Overall, most studies to date have been case reports and small series reporting heterogeneous patients and surgical strategies. This review suggests that DBS for movement disorders after a stroke has the potential to be effective and safe for diverse patients, and DBS may be a feasible option to improve function even years after a stroke.

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*Yosef M. Dastagirzada, Nikita G. Alexiades, David B. Kurland, Sebastián N. Anderson, Douglas L. Brockmeyer, David B. Bumpass, Sandip Chatterjee, Mari L. Groves, Todd C. Hankinson, David Harter, Daniel Hedequist, Andrew Jea, Jeffrey R. Leonard, Jonathan E. Martin, Matthew E. Oetgen, Joshua Pahys, Curtis Rozzelle, Jennifer M. Strahle, Dominic Thompson, Burt Yaszay, and Richard C. E. Anderson

OBJECTIVE

Cervical spine disorders in children are relatively uncommon; therefore, paradigms for surgical and nonsurgical clinical management are not well established. The purpose of this study was to bring together an international, multidisciplinary group of pediatric cervical spine experts to build consensus via a modified Delphi approach regarding the clinical management of children with cervical spine disorders and those undergoing cervical spine stabilization surgery.

METHODS

A modified Delphi method was used to identify consensus statements for the management of children with cervical spine disorders requiring stabilization. A survey of current practices, supplemented by a literature review, was electronically distributed to 17 neurosurgeons and orthopedic surgeons experienced with the clinical management of pediatric cervical spine disorders. Subsequently, 52 summary statements were formulated and distributed to the group. Statements that reached near consensus or that were of particular interest were then discussed during an in-person meeting to attain further consensus. Consensus was defined as ≥ 80% agreement on a 4-point Likert scale (strongly agree, agree, disagree, strongly disagree).

RESULTS

Forty-five consensus-driven statements were identified, with all participants willing to incorporate them into their practice. For children with cervical spine disorders and/or stabilization, consensus statements were divided into the following categories: A) preoperative planning (12 statements); B) radiographic thresholds of instability (4); C) intraoperative/perioperative management (15); D) postoperative care (11); and E) nonoperative management (3). Several important statements reaching consensus included the following recommendations: 1) to obtain pre-positioning baseline signals with intraoperative neuromonitoring; 2) to use rigid instrumentation when technically feasible; 3) to provide postoperative external immobilization for 6–12 weeks with a rigid cervical collar rather than halo vest immobilization; and 4) to continue clinical postoperative follow-up at least until anatomical cervical spine maturity was reached. In addition, preoperative radiographic thresholds for instability that reached consensus included the following: 1) translational motion ≥ 5 mm at C1–2 (excluding patients with Down syndrome) or ≥ 4 mm in the subaxial spine; 2) dynamic angulation in the subaxial spine ≥ 10°; and 3) abnormal motion and T2 signal change on MRI seen at the same level.

CONCLUSIONS

In this study, the authors have demonstrated that a multidisciplinary, international group of pediatric cervical spine experts was able to reach consensus on 45 statements regarding the management of pediatric cervical spine disorders and stabilization. Further study is required to determine if implementation of these practices can lead to reduced complications and improved outcomes for children.

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Brandon A. Sherrod, Giorgos D. Michalopoulos, Graham Mulvaney, Nitin Agarwal, Andrew K. Chan, Anthony L. Asher, Domagoj Coric, Michael S. Virk, Kai-Ming Fu, Kevin T. Foley, Paul Park, Cheerag D. Upadhyaya, John J. Knightly, Mark E. Shaffrey, Eric A. Potts, Christopher I. Shaffrey, Oren N. Gottfried, Khoi D. Than, Michael Y. Wang, Luis M. Tumialán, Dean Chou, Praveen V. Mummaneni, Mohamad Bydon, and Erica F. Bisson

OBJECTIVE

Patients who undergo surgery for cervical spondylotic myelopathy (CSM) will occasionally develop postoperative neck pain that was not present preoperatively, yet the incidence of this phenomenon is unclear. The authors aimed to elucidate patient and surgical factors associated with new-onset sustained pain after CSM surgery.

METHODS

The authors reviewed data from the Quality Outcomes Database (QOD) CSM module. The presence of neck pain was defined using the neck pain numeric rating scale (NRS). Patients with no neck pain at baseline (neck NRS score ≤ 1) were then stratified based on the presence of new postoperative pain development (neck NRS score ≥ 2) at 12 and 24 months postoperatively.

RESULTS

Of 1141 patients in the CSM QOD, 224 (19.6%) reported no neck pain at baseline. Among 170 patients with no baseline neck pain and available 12-month follow-up, 46 (27.1%) reported new postoperative pain. Among 184 patients with no baseline neck pain and available 24-month follow-up, 53 (28.8%) reported new postoperative pain. The mean differences in neck NRS scores were 4.3 for those with new postoperative pain compared with those without at 12 months (4.4 ± 2.2 vs 0.1 ± 0.3, p < 0.001) and 3.9 at 24 months (4.1 ± 2.4 vs 0.2 ± 0.4, p < 0.001). The majority of patients reporting new-onset neck pain reported being satisfied with surgery, but their satisfaction was significantly lower compared with patients without pain at the 12-month (66.7% vs 94.3%, p < 0.001) and 24-month (65.4% vs 90.8%, p < 0.001) follow-ups. The baseline Neck Disability Index (NDI) was an independent predictor of new postoperative neck pain at both the 12-month and 24-month time points (adjusted OR [aOR] 1.04, 95% CI 1.01–1.06; p = 0.002; and aOR 1.03, 95% CI 1.01–1.05; p = 0.026, respectively). The total number of levels treated was associated with new-onset neck pain at 12 months (aOR 1.34, 95% CI 1.09–1.64; p = 0.005), and duration of symptoms more than 3 months was a predictor of 24-month neck pain (aOR 3.22, 95% CI 1.01–10.22; p = 0.048).

CONCLUSIONS

Increased NDI at baseline, number of levels treated surgically, and duration of symptoms longer than 3 months preoperatively correlate positively with the risk of new-onset neck pain following CSM surgery. The majority of patients with new-onset neck pain still report satisfaction from surgery, suggesting that the risk of new-onset neck pain should not hinder indicated operations from being performed.

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Shoji Yomo, Kyota Oda, and Kazuhiro Oguchi

OBJECTIVE

Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from renal cell carcinoma (RCC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic RCC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for RCC BM prolongs overall survival (OS) and improves intracranial disease control and whether there are any safety concerns.

METHODS

Patients who underwent SRS for RCC BMs at the authors’ institution between January 2010 and January 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The time-to-event analysis of OS and intracranial progression-free survival (IC-PFS) between the groups with and without ICIs (ICI+SRS and SRS, respectively) was performed using inverse probability of treatment weighting (IPTW) based on propensity scores (PSs) to control for selection bias. Four baseline covariates (Karnofsky Performance Scale score, extracranial metastases, hemoglobin, and number of BMs) were selected to calculate PSs.

RESULTS

In total, 57 patients with 147 RCC BMs were eligible. The median OS for all patients was 9.1 months (95% CI 6.0–18.9 months), and the median IC-PFS was 4.4 months (95% CI 3.1–6.8 months). Twelve patients (21%) received concurrent ICIs. The IPTW-adjusted 1-year OS rates in the ICI+SRS and SRS groups were 66% and 38%, respectively (HR 0.30, 95% C 0.13–0.69; p = 0.005), and the IPTW-adjusted 1-year IC-PFS rates were 52% and 16%, respectively (HR 0.30, 95% CI 0.14–0.62; p = 0.001). Severe tumor hemorrhage (Common Terminology Criteria for Adverse Events [CTCAE] grade 4 or 5) occurred immediately after SRS in 2 patients in the SRS group. CTCAE grade 2 or 3 toxicity was observed in 2 patients in the ICI+SRS group and 5 patients in the SRS group.

CONCLUSIONS

Although the patient number was small and the analysis preliminary, the present study found that SRS with concurrent ICIs for RCC BM patients prolonged survival and provided durable intracranial disease control, with no apparent increase in treatment-related adverse events.

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Jean Raymond, Jean-Christophe Gentric, Elsa Magro, Lorena Nico, Emma Bacchus, Ruby Klink, Christophe Cognard, Anne-Christine Januel, Jean-François Sabatier, Daniela Iancu, Alain Weill, Daniel Roy, Michel W. Bojanowski, Chiraz Chaalala, Xavier Barreau, Vincent Jecko, Chrysanthi Papagiannaki, Stéphane Derrey, Eimad Shotar, Philippe Cornu, Omer F. Eker, Isabelle Pelissou-Guyotat, Michel Piotin, Sorin Aldea, Rémy Beaujeux, François Proust, René Anxionnat, Vincent Costalat, Marine Le Corre, Jean-Yves Gauvrit, Xavier Morandi, Hervé Brunel, Pierre-Hugues Roche, Thomas Graillon, Emmanuel Chabert, Denis Herbreteau, Hubert Desal, Denis Trystram, Charlotte Barbier, Thomas Gaberel, Thanh N. Nguyen, Geraldine Viard, Guylaine Gevry, Tim E. Darsaut, and

OBJECTIVE

The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries.

METHODS

Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2.

RESULTS

From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%–22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%–28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%–25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%–21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%–37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%–20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%–40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%–21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%–35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%–29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%–33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%–34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%–26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%–34%).

CONCLUSIONS

Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.

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*Bianca M. Dijkstra, Julie Nonnekens, Wouter Nagengast, Schelto Kruijff, Gert Jan Meersma, Wilfred F. A. den Dunnen, Frank A. E. Kruyt, and Rob J. M. Groen

OBJECTIVE

Meningiomas are frequently occurring, often benign intracranial tumors. Molecular fluorescence can be used to intraoperatively identify residual meningioma tissue and optimize safe resection; however, currently no clinically approved agent is available for this specific tumor type. In meningiomas, vascular endothelial growth factor α (VEGFα) is upregulated, and this biomarker could be targeted with bevacizumab-IRDye800CW, a fluorescent agent that is already clinically applied for the resection of other tumors and neoplasms. Here, the authors investigated the feasibility of using bevacizumab-IRDye800CW to target VEGFα in a CH-157MN xenografted mouse model.

METHODS

Five mice with CH-157MN xenografts with volumes of 500 mm3 were administered intravenous bevacizumab-IRDye800CW. Mice were imaged in vivo at 24 hours, 48 hours, and 72 hours after injection with the FMT2500 fluorescence imaging system. Biodistribution was determined ex vivo using the Pearl fluorescent imager at 72 hours after injection. To mimic a clinical scenario, 2 animals underwent postmortem xenograft resection using both white-light and fluorescence guidance. Lastly, fresh and frozen human meningioma specimens were incubated ex vivo with bevacizumab-IRDye800CW, stained with anti-VEGFα, and microscopically examined.

RESULTS

In vivo, tumors fluoresced at all time points after tracer administration and background fluorescence decreased with time. Ex vivo analyses of tracer biodistribution showed the highest fluorescence in resected tumor tissue. Brain, skull, and muscle tissue showed very low fluorescence. Microscopically, fluorescence was observed in the cytoplasm and was correlated with VEGFα expression patterns. During postmortem surgery, both the tumor bulk and a small tumor remnant were detected. Bevacizumab-IRDye800CW bound specifically to all tested human meningioma samples, as indicated by a high fluorescent signal in the tumor bulk compared with the surrounding healthy dura mater.

CONCLUSIONS

Bevacizumab-IRDye800CW showed meningioma specificity, as illustrated by high VEGFα-mediated uptake in the meningioma xenograft mouse model. Small tumor lesions were detected using fluorescence guidance. Thus, the next step will be to assess the feasibility of using already available clinical grade bevacizumab-IRDye800CW to optimize meningioma resection in a human trial.