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Figure 1. Brain edema related to ischemic lesions is very difficult to manage. New therapeutic strategies may improve clinical outcomes.
Glibenclamide is a member of the sulfonylurea class of drugs and has been in clinical use as an oral hypoglycemic agent since 1969. All sulfonylurea drugs work via a similar mechanism—inhibition of sulfonylurea receptor 1. Since the work of Simard et al. (4), in which newly expressed sulfonylurea receptor 1eregulated NC(Ca-ATP) channel mediated cerebral edema after ischemic stroke, more attention has been given to this
REFERENCES 1. Khanna A, Walcott BP, Kahle KT, Simard JM: Effect of glibenclamide on the prevention of secondary brain injury following ischemic stroke in humans. Neurosurg Focus 36:E11, 2014. 2. Kunte H, Busch MA, Trosdorf K, Vollnberg B, Harms L, Mehta RI, Castellani RJ, Mandava P, Kent TA, Simard JM: Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas. Ann Neurol 72:799-806, 2012. 3. Marks JA, Li S, Gong W, Sanati P, Eisenstadt R, Sims C, Smith DH, Reilly PM, Pascual JL: Similar
protein and its blockade in brain injuries, especially traumatic brain lesions. Depletion of adenosine triphosphate, as can frequently be observed in the pericontusional area after trauma, causes depolarization and opening of this channel. In situations of mechanical stress, inflammation, and hypoxia, an upregulation of the Abcc8 gene that encodes for sulfonylurea receptor could be observed. Zweckberger et al. (5), using an animal model of brain trauma, demonstrated a significant reduction in the development of tissue water content and smaller volumes of the brain lesions in glibenclamide-treated Sprague-Dawley rats. In addition to laboratory investigations, retrospective studies of patients with diabetes mellitus type 2 who experienced ischemic stroke suggest that taking a sulfonylurea drug and continuing to take it during hospitalization for stroke improves outcome at the time of discharge and reduces the incidence of symptomatic hemorrhagic transformation and mortality (2). Based on these preliminary results, a phase II trial is underway to examine the efficacy of intravenous glyburide (glibenclamide) in the prevention of malignant edema in severe anterior circulation ischemic stroke. The study is expected to be completed in February 2015 (1). Can we extrapolate the results of Zweckberger et al. to brain trauma? Can be it the light at the end of the tunnel for the prevention of cerebral edema? Keep calm and wait for the results ..
effects of hypertonic saline and mannitol on the inflammation of the blood-brain barrier microcirculation after brain injury in a mouse model. J Trauma Acute Care Surg 73:351-357, 2012. 4. Simard JM, Chen M, Tarasov KV, Bhatta S, Ivanova S, Melnitchencko L, Tsymbalyuk N, West GA, Gerzanich V: Newly expressed SUR-1 regulated NC Ca-ATP channel mediates cerebral edema after ischemic stroke. Nat Med 12:433-440, 2006.
brain damage after experimental traumatic brain injury. Neuroscience 272:199-206, 2014.
From the 1Department of Neurosurgery, State University of Ponta Grossa, Parana; and 2Department of Neurosurgery, University of Sao Paulo, Sao Paulo, Brazil 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2015.01.003
5. Zweckberger K, Hackenberg K, Jung CS, Hertle DN, Kiening KL, Unterberg AW, Sakowitz OW: Glibenclamide reduces secondary
Radiation Exposure in Scoliosis Surgery: Freehand Technique versus Image Guidance Corey T. Walker and Jay D. Turner
Pedicle screw fixation has become the cornerstone of adult and pediatric spinal deformity correction. There are 3 primary strategies for pedicle screw placement: 1) freehand
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placement with fluoroscopic confirmation of screw position, 2) fluoroscopy-assisted placement, and 3) placement with computed tomography (CT)ecoupled navigation (image
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guidance). In choosing a technique, several factors should be considered, including accuracy, efficiency, and radiation exposure. Numerous studies have been done in recent years to address these topics. Given the well-described dangers of radiation, there is great interest in protecting the patient and the surgical team from its adverse effects. The impact of radiation exposure is especially pronounced in spine surgery. As intraoperative imaging applications have expanded, an increased incidence of various cancers has been seen in spine surgeons. For example, thyroid cancer, which has a clear dose-response relationship with radiation exposure, has increased in prevalence among spine surgeons by 25-fold as use of intraoperative x-rays has increased (9). There is a growing body of literature aimed at better understanding the relative radiation doses that can be expected with each technique of pedicle screw placement. In this light, two recent studies have examined radiation burden during the surgical treatment of pediatric patients with scoliotic deformity (1, 4). This population is particularly relevant given the greater lifetime risk of radiation-related adverse effects in young patients. Correction of scoliotic deformity often involves instrumentation of numerous vertebral levels and the potential for relatively high radiation doses to the patient and the surgeon. In the first study, Erken et al. (1) performed a prospective multicenter study evaluating the radiation burden to the operating surgeon during placement of pedicle screws with the freehand technique. Screws were placed using anatomic landmarks, and fluoroscopy was used solely for placement confirmation. The study included 125 pediatric patients with scoliosis with a mean of 11 instrumented levels per patient. With their preferred technique, the mean radiation dose to the surgeon per case was 0.0005 mSv. The authors comment on the stark contrast of their results compared with the previously published mean dose to the surgeon per case of 0.096 mSv found with fluoroscopy-assisted placement (7). In comparison doses, the United States Nuclear Regulatory Commission states that total effective occupational exposures should not exceed 50 mSv annually (8). Although the primary goal of this study was to evaluate the dose of radiation to the surgeon, the relatively short total fluoroscopy time (mean 40.5 seconds) also implies a low dose to the patient. In the second study, O’Donnell et al. (4) focused on the radiation dose of patients with adolescent idiopathic scoliosis
REFERENCES 1. Erken HY, Burc H, Saka G, Akmaz I, Aydogan M: Can radiation exposure to the surgeon be reduced with freehand pedicle screw fixation technique in pediatric spinal deformity correction? A prospective multicenter study. Spine 39: 521-525, 2014.
(AIS) who were treated with the same freehand technique using fluoroscopy-mediated confirmation. This retrospective study included 43 AIS patients with a mean number of 11 levels per case. Mean radiation dose to the patients was 0.189 mSv, and mean total fluoroscopy time was 26 seconds. The authors compared the radiation exposure using their freehand technique with CT-coupled intraoperative navigation as reported in the literature. They cited radiation doses with CT-based image guidance of 7.29e9.72 mSv per case and twice those levels when intraoperative CT was also used for confirmation of screw placement. Based on these historical controls, CT-based navigation results in 42-fold to 85-fold more radiation than with the authors’ freehand technique. Taken together, these studies suggest that the freehand technique may allow for a dramatic decrease in radiation exposure to the surgeon and patient compared with screws placed using either x-ray assistance or CT-based intraoperative navigation. Although radiation exposure is an important consideration in choosing a technique, it must be considered within the context of the surgical goals. Accurate screw placement is the primary objective, and this was not evaluated in either study. The consideration of accuracy is especially important when dealing with the abnormal anatomy that is often encountered in patients with scoliosis, which can complicate freehand screw placement. Since the inception of image guidance, multiple studies have suggested that improvements in accuracy are seen with its use (5). Most studies suggest that CT-coupled navigation leads to marginally decreased breach rates (2, 3, 6). However, a direct comparison of techniques has been difficult because of widespread heterogeneity. Specifically, significant variation is often present with regard to surgeon experience, indications for surgery, region of the spine being instrumented, and number of levels treated. Many of the studies also fail to address whether or not the reported differences in screw accuracy affect clinical outcomes. The studies by Erken et al. (1) and O’Donnell et al. (4) highlight that freehand pedicle screw placement allows for very low radiation exposure to the patient and surgeon. However, given the sole reliance on anatomic landmarks, freehand placement should be reserved for surgeons well versed in the technique. In less experienced hands or in cases of highly abnormal anatomy (independent of experience), fluoroscopy-assisted or CT-navigated screw placement may be required to achieve acceptable accuracy—and may be at the cost of greater radiation exposure.
2. Gelalis ID, Paschos NK, Pakos EE, Politis AN, Arnaoutoglou CM, Karageorgos AC, Ploumis A, Xenakis TA: Accuracy of pedicle screw placement: a systematic review of prospective in vivo studies comparing free hand, fluoroscopy guidance and navigation techniques. Eur Spine J 21: 247-255, 2012.
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3. Mason A, Paulsen R, Babuska JM, Rajpal S, Burneikiene S, Nelson EL, Villavicencio AT: The accuracy of pedicle screw placement using intraoperative image guidance systems. J Neurosurg Spine 20:196-203, 2014. 4. O’Donnell C, Maertens A, Bompadre V, Wagner TA, Krengel W 3rd: Comparative radiation
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R: Pedicle and metacomputerNeurosurg
7. Ul Haque M, Shufflebarger HL, O’Brien M, Macagno A: Radiation exposure during pedicle screw placement in adolescent idiopathic scoliosis: is fluoroscopy safe? Spine 31:2516-2520, 2006. 8. US Nuclear Regulatory Commission: 10 CFR 20.1201: Occupational Dose Limits for Adults. Washington, DC: U.S. Government Printing Office; 1991. 9. Wagner TA, Lai SM, Asher MA: SRS surgeon members’ risk for thyroid cancer: is it increased? Scoliosis Research Society 41st Annual Meeting Abstracts. Spine: p. 44, 2006. Available at: http://
journals.lww.com/spinejournalabstracts/toc/2007/ 00011. Accessed on March 3, 2015.
Division of Neurological Surgery, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, USA 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.wneu.2015.01.004
WORLD FEDERATION OF NEUROSURGICAL SOCIETIES Mission Statement To facilitate the personal association of neurological surgeons throughout the world. To aid in the exchange and dissemination of knowledge and ideas in the field of neurological surgery. To encourage research in neurological surgery and allied sciences. To address issues of neurosurgical demography. To address issues of Public Health. To implement, improve and promote the standards of neurosurgical care and training worldwide.
Membership Services (www.wfns.org) Teresa Chen Hsiao-Hui (Teresa) Chen Office Manager, WFNS Central Office World Federation of Neurosurgical Societies 5 Rue du Marché 1260 Nyon, Vaud, Switzerland Tel: +41 (0) 22 3624303 Fax: +41 (0) 22 3624352 Email:
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