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Gennadiy A. Katsevman, Ryan C. Turner, Ogaga Urhie, Joseph L. Voelker and Sanjay Bhatia

OBJECTIVE

It is commonly reported that achieving gross-total resection of contrast-enhancing areas in patients with glioblastoma (GBM) improves overall survival. Efforts to achieve an improved resection have included the use of both imaging and pharmacological adjuvants. The authors sought to investigate the role of sodium fluorescein in improving the rates of gross-total resection of GBM and to assess whether patients undergoing resection with fluorescein have improved survival compared to patients undergoing resection without fluorescein.

METHODS

A retrospective chart review was performed on 57 consecutive patients undergoing 64 surgeries with sodium fluorescein to treat newly diagnosed or recurrent GBMs from May 2014 to June 2017 at a teaching institution. Outcomes were compared to those in patients with GBMs who underwent resection without fluorescein.

RESULTS

Complete or near-total (≥ 98%) resection was achieved in 73% (47/64) of fluorescein cases. Of 42 cases thought not to be amenable to complete resection, 10 procedures (24%) resulted in gross-total resection and 15 (36%) resulted in near-total resection following the use of sodium fluorescein. No patients developed any local or systemic side effects after fluorescein injection. Patients undergoing resection with sodium fluorescein, compared to the non–fluorescein-treated group, had increased rates of gross- or near-total resection (73% vs 53%, respectively; p < 0.05) as well as improved median survival (78 weeks vs 60 weeks, respectively; p < 0.360).

CONCLUSIONS

This study is the largest case series to date demonstrating the beneficial effect of utilizing sodium fluorescein as an adjunct in GBM resection. Sodium fluorescein facilitated resection in cases in which it was employed, including dominant-side resections particularly near speech and motor regions. The cohort of patients in which sodium fluorescein was utilized had statistically significantly increased rates of gross- or near-total resection. Additionally, the fluorescein group demonstrated prolonged median survival, although this was not statistically significant. This work demonstrates the promise of an affordable and easy-to-implement strategy for improving rates of total resection of contrast-enhancing areas in patients with GBM.

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Ju Hyung Moon, Eui Hyun Kim and Sun Ho Kim

OBJECTIVE

Endonasal surgery of the skull base requires watertight reconstruction of the skull base that can seal the dural defect to prevent postoperative CSF rhinorrhea and consequent intracranial complications. Although the incidence of CSF leakage has decreased significantly since the introduction in 2006 of the vascularized nasoseptal flap (the Hadad-Bassagasteguy flap), reconstruction of extensive skull base dural defects remains challenging. The authors describe a new, modified vascularized nasoseptal flap for reconstruction of extensive skull base dural defects.

METHODS

A retrospective review was conducted on 39 cases from 2010 to 2017 that involved reconstruction of the skull base with an endonasal vascularized flap. Extended nasoseptal flaps were generated by adding the nasal floor and inferior meatus mucosa, inferior turbinate mucosa, or entire lateral nasal wall mucosa. The authors specifically highlight the surgical techniques for flap design and harvesting of these various modifications of the vascularized nasoseptal flap.

RESULTS

Thirty-nine endonasal vascularized flaps were used to reconstruct skull base defects in 37 patients with nonsurgical or postoperative CSF rhinorrhea. Of the 39 procedures, extended nasoseptal flaps were used in 5 cases (13%). These included 2 extended nasoseptal flaps including the inferior turbinate mucosa and 3 extended nasoseptal flaps including the entire lateral nasal wall mucosa. These 5 extended nasoseptal flaps were used in patients who had nonsurgical CSF rhinorrhea due to extensive skull base destruction by invasive pituitary tumors. All flaps healed completely and sealed off the CSF leaks. Olfactory function slightly decreased in the 3 patients with extended nasoseptal flaps including the entire lateral nasal wall mucosa. One patient experienced nasolacrimal duct obstruction, which was treated by dacryocystorhinostomy. The authors encountered no wound complication in this series, while crusting at the donor site required daily nasal toilette and frequent debridement until the completion of mucosalization, which usually takes 8 to 12 weeks after surgery.

CONCLUSIONS

Extended nasoseptal flaps are a reliable and versatile option that can be used to reconstruct extensive skull base dural defects resulting from destruction by large invasive tumors or complex endoscopic endonasal surgery. An extended nasoseptal flap that includes the entire lateral nasal wall mucosa (360° flap) is the largest endonasal vascularized flap reported to date and may be an alternative for the reconstruction of extensive skull base defects while avoiding the need for additional external approaches.

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Francis Lovecchio, Jeffrey G. Stepan, Ajay Premkumar, Michael E. Steinhaus, Maria Sava, Peter Derman, Han Jo Kim and Todd Albert

OBJECTIVE

Patients with lumbar spine pathology are at high risk for opioid misuse. Standardizing prescribing practices through an institutional intervention may reduce the overprescribing of opiates, leading to a decrease in the risk for opioid misuse and the number of pills available for diversion. Without quantitative data on the “minimum necessary quantity” of opioids appropriate for postdischarge prescriptions, the optimal method for changing existing prescribing practices is unknown. The purpose of this study was to determine whether mandatory provider education and prescribing guidelines could modify prescriber behavior and lead to a decreased amount of opioids prescribed at hospital discharge following lumbar spine surgery.

METHODS

Qualified staff were required to attend a mandatory educational conference, and a consensus method among the spine service was used to publish qualitative prescribing guidelines. Prescription data for 2479 patients who had undergone lumbar spine surgery were captured and compared based on the timing of surgery. The preintervention group consisted of 1177 patients who had undergone spine surgery in the period before prescriber education and guidelines (March 1, 2016–November 1, 2016). The postintervention group consisted of 1302 patients who had undergone spine surgery after the dissemination of the guidelines (February 1, 2017–October 1, 2017). Surgeries were classified as decompression or fusion procedures. Patients who had undergone surgeries for infection and patients on long-acting opioids were excluded.

RESULTS

For all lumbar spine surgeries (decompression and fusion), the mean amount of opioids prescribed at discharge was lower after the educational program and distribution of prescribing guidelines (629 ± 294 oral morphine equivalent [OME] preintervention vs 490 ± 245 OME postintervention, p < 0.001). The mean number of prescribed pills also decreased (81 ± 26 vs 66 ± 22, p < 0.001). Prescriptions for 81 or more tablets dropped from 65.5% to 25.5%. Tramadol was prescribed more frequently after prescriber education (9.9% vs 18.6%, p < 0.001). Refill rates within 6 weeks were higher after the institutional intervention (7.6% vs 12.4%, p < 0.07).

CONCLUSIONS

Qualitative guidelines and prescriber education are effective in reducing the amount of opioids prescribed at discharge and encouraging the use of weaker opioids. Coupling provider education with prescribing guidelines is likely synergistic in achieving larger reductions. The sustainability of these changes is yet to be determined.

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Xijie Zhou, Bin Zhao, Keshav Poonit, Weidong Weng, Chenglun Yao, Chao Sun and Hede Yan

OBJECTIVE

Traumatic neuromas represent a prevalent source of neuropathic pain. As of yet, there has been no single treatment method that can guarantee permanent relief of symptoms. Although nerve-capping techniques have shown promise, their exact mechanisms remain elusive. The authors’ aim was to examine the role of the RhoA/ROCK signaling pathway in the prevention of neuroma formation after neurectomy utilizing a nerve-capping technique.

METHODS

An aligned nanofiber tube was fabricated to cap the sciatic nerve in Sprague Dawley rats. The rats (n = 60) were randomly divided into the aligned SF/P (LLA-CL) capping group (capping group, n = 20), the capping and Y-27632 (ROCK pathway inhibitor) intervention group (intervention group, n = 20), and the no-capping group (control group, n = 20). The authors undertook a comprehensive assessment of the capping group, examining the animals’ behavior, the extent of neuroma development, histology, gene and protein expression, and ultrastructural changes associated with the RhoA/ROCK signaling pathway. These findings were compared with those in the intervention and control groups.

RESULTS

The inciting injury resulted in the expression of the RhoA/ROCK signaling pathway, as well as its further upregulation in peripheral neurons. Axon outgrowth was significantly increased when RhoA/ROCK signaling pathway was suppressed. The average autotomy score in the capping group was observed to be much lower than that of the intervention and control groups. At 30 days postneurectomy, the capping group displayed no obvious neuroma formation, while a bulbous neuroma was found in the nerve stumps of both the control and intervention groups. Quantitative real-time polymerase chain reaction and the Western blot analysis demonstrated that the expression of myelin-associated glycoprotein was substantially upregulated in the capping group; in contrast, the expression of NF-200 was significantly downregulated. The expression of myosin light chain was notably lower in the intervention group, but there was no significant difference when compared with the control group (p > 0.05).

CONCLUSIONS

The RhoA/ROCK signaling pathway has emerged as a critical player in the process of traumatic neuroma formation after neurectomy. It is possible that the nerve-capping technique could generate a “regenerative brake” based on the regulation of the RhoA/ROCK signaling pathway in this event. These findings may provide concrete evidence that could help develop new strategies for the management of painful neuromas.

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Qing-Song Lin, Wei-Xiong Wang, Yuan-Xiang Lin, Zhang-Ya Lin, Liang-Hong Yu, Yin Kang and De-Zhi Kang

OBJECTIVE

Glutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.

METHODS

Endovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction.

RESULTS

ANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression.

CONCLUSIONS

ANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.

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Nicolas Asquier, Guillaume Bouchoux, Michael Canney, Cyril Martin, Bruno Law-Ye, Delphine Leclercq, Jean-Yves Chapelon, Cyril Lafon, Ahmed Idbaih and Alexandre Carpentier

OBJECTIVE

One of the goals in this study was to set up a semiautomatic method to estimate blood-brain barrier disruption obtained in patients with glioblastoma by using an implantable, unfocused, ultrasound device. Another goal was to correlate the probability of significant ultrasound-induced signal enhancement (SUISE) with local acoustic pressure in the brain.

METHODS

Gd-enhanced MR images acquired before and after ultrasound treatments were analyzed prospectively. The image sets were segmented, normalized, and coregistered to evaluate contrast enhancement. The volume of SUISE was calculated with voxels labeled as gray or white matter, in a cylindrical region of interest, and with enhancement above a given threshold. To validate the method, the resulting volumes of SUISE were compared to qualitative grades previously assigned by 3 clinicians for 40 ultrasound treatments in 15 patients. A parametric study was performed to optimize the algorithm prediction of the qualitative grades. The 3D acoustic field in the brain was estimated from measurements in water combined with simulations accounting for ultrasound attenuation in brain and overlaid on each MR image to correlate local acoustic pressure with the probability of SUISE (defined as enhancement > 10%).

RESULTS

The algorithm predicted grade 2 or 3 and grade 3 openings with areas under the receiver operating characteristic curve of 0.831 and 0.995, respectively. The probability of SUISE was correlated with local acoustic pressure (R2 = 0.98) and was 3.33 times higher for gray matter than for white matter.

CONCLUSIONS

An algorithm for evaluating blood-brain barrier disruption was validated and can be used for future clinical trials to further understand and quantify this technique in humans.

Clinical trial registration no.: NCT02253212 (clinicaltrials.gov)

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Hongzhou Duan, Dapeng Mo, Yang Zhang, Jiayong Zhang and Liang Li

OBJECTIVE

Symptomatic steno-occlusion of the proximal vertebral artery (VA) or subclavian artery (ScA) heralds a poor prognosis and high risk of stroke recurrence despite medical therapy, including antiplatelet or anticoagulant drugs. In some cases, the V2 segment of the cervical VA is patent and perfused via collateral vessels. The authors describe 7 patients who were successfully treated by external carotid artery (ECA)–saphenous vein (SV)–VA bypass.

METHODS

Seven cases involving symptomatic patients were retrospectively studied: 3 cases of V1 segment occlusion, 2 cases of severe in-stent restenosis in the V1 segment, and 2 cases of occlusion of the proximal ScA. All patients underwent ECA-SV-VA bypass. The ECA was isolated and retracted, and the anterior wall of the transverse foramen was unroofed. The VA was exposed, and then the 2 ends of the SV were anastomosed to the VA and ECA in an end-to-side fashion.

RESULTS

Surgical procedures were all performed as planned, with no intraoperative complications. There were 2 postoperative complications (severe laryngeal edema in one case and shoulder weakness in another), but both patients recovered fully and measures were taken to minimize laryngeal edema and its effects in subsequent cases. All patients experienced improvement of their symptoms. No new neurological deficits were reported. Postoperative angiography demonstrated that the anastomoses were all patent, and analysis of follow-up data (range of follow-up 12–78 months) revealed no further ischemic events in the vertebrobasilar territory.

CONCLUSIONS

The ECA-SV-VA bypass is a useful treatment for patients who suffer medically refractory ischemic events in the vertebrobasilar territory when the proximal part of the VA or ScA is severely stenosed or occluded but the V2 segment of the cervical VA is patent.

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Timothy G. White, Hussam Abou-Al-Shaar, Jung Park, Jeffrey Katz, David J. Langer and Amir R. Dehdashti

OBJECTIVE

Cerebral revascularization for carotid occlusion was previously a mainstay procedure for the cerebrovascular neurosurgeon. However, the 1985 extracranial-intracranial bypass trial and subsequently the Carotid Occlusion Surgery Study (COSS) provided level 1 evidence via randomized controlled trials against bypass for symptomatic atherosclerotic carotid occlusion disease. However, in a small number of patients optimal medical therapy fails, and some patients with flow-limiting stenosis develop a perfusion-dependent neurological examination. Therefore it is necessary to further stratify patients by risk to determine who may most benefit from this intervention as well as to determine perioperative morbidity in this high-risk patient population.

METHODS

A retrospective review was performed of all revascularization procedures done for symptomatic atherosclerotic cerebrovascular steno-occlusive disease. All patients undergoing revascularization after the publication of the COSS in 2011 were included. Perioperative morbidity and mortality were assessed as the primary outcome to determine safety of revascularization in this high-risk population. All patients had documented hypoperfusion on hemodynamic imaging.

RESULTS

At total of 35 revascularization procedures were included in this review. The most common indication was for patients with recurrent strokes, who were receiving optimal medical therapy and who suffered from cerebrovascular steno-occlusion. At 30 days only 3 perioperative ischemic events were observed, 2 of which led to no long-term neurological deficit. Immediate graft patency was good, at 94%. Long term, no further strokes or ischemic events were observed, and graft patency remained high at 95%. There were no factors associated with perioperative ischemic events in the variables that were recorded.

CONCLUSIONS

Cerebral revascularization may be done safely at high-volume cerebrovascular centers in high-risk patients in whom optimal medical therapy has failed. Further research must be done to develop an improved methodology of risk stratification for patients with symptomatic atherosclerotic cerebrovascular steno-occlusive disease to determine which patients may benefit from intervention. Given the high risk of recurrent stroke in certain patients, and the fact that patients fail medical therapy, surgical revascularization may provide the best method to ensure good long-term outcomes with manageable up-front risks.

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Mohamed Somji, James McEachern and Joseph Silvaggio

OBJECTIVE

Cerebral proliferative angiopathy (CPA) is considered a discrete vascular malformation of the brain separate from classical brain arteriovenous malformations (AVMs). It has unique angiographic characteristics and has been hypothesized to result from chronic cortical ischemia and perinidal oligemia. Treatment with cerebral revascularization has been proposed in an attempt to disrupt regional hypoperfusion and interrupt the angiogenesis that defines CPA. A systematic review of the literature pertaining to the role of cerebral revascularization may highlight a treatment paradigm for this rare disease.

METHODS

A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE and Embase were searched from inception for papers relating to CPA. Included articles were categorized according to methodology (case series or imaging study) and treatment modality (conservative, radiation, endovascular, or revascularization). A synthesis was compiled summarizing the current evidence regarding cerebral revascularization in CPA.

RESULTS

The initial search revealed 43 articles, of which 28 studies met the inclusion criteria. Nine studies were identified that described imaging findings, which suggested hemodynamic dysregulation and perinidal impairments in the cerebrovascular reserve could be identified compared to unaffected hemispheres and classical brain AVMs. Six studies including 7 patients undergoing indirect forms of cerebral revascularization were identified. Clinical and radiological outcomes following revascularization were favorable in all but one study.

CONCLUSIONS

A small body of radiological and clinical studies has emerged, suggesting that CPA is a response to perinidal oligemia. While the long-term clinical efficacy of revascularization remains unclear, early results suggest that this may be a novel treatment paradigm for patients with CPA.