Recent and Emerging Advances in Spinal Deformity

DEFORMITY

Recent and Emerging Advances in Spinal Deformity Justin S. Smith, MD, PhD∗ Christopher I. Shaffrey, MD∗ Shay Bess, MD‡ Mohammed F. Shamji, MD,PhD§ Darrel Brodke, MD¶ Lawrence G. Lenke, MD|| Michael G. Fehlings, MD, PhD§ Virginie Lafage, PhD# Frank Schwab, MD# Alexander R. Vaccaro, MD, PhD∗∗ Christopher P. Ames, MD‡‡ ∗ Department of Neurosurgery, University of Virginia Medical Center, Charlottesville, Virginia; ‡ Rocky Mountain Scoliosis and Spine Center, Denver, Colorado; § Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; ¶ Department of Orthopaedic Surgery, University of Utah, Salt Lake City, Utah; || Department of Orthopaedic Surgery, Columbia University, New York, New York; # Department of Orthopaedic Surgery, Hospital for Special Surgery, New York, New York; ∗∗ Department of Orthopaedics, Thomas Jefferson University, Philadelphia, Pennsylvania; ‡‡ Department of Neurosurgery, University of California San Francisco, San Francisco, California

Correspondence: Justin S. Smith, MD, PhD, Department of Neurosurgery, University of Virginia Health Sciences Center, PO Box 800212, Charlottesville, VA 22908. E-mail: [email protected] Received, August 9, 2016. Accepted, October 14, 2016. C 2016 by the Copyright Congress of Neurological Surgeons

BACKGROUND: Over the last several decades, significant advances have occurred in the assessment and management of spinal deformity. OBJECTIVE: The primary focus of this narrative review is on recent advances in adult thoracic, thoracolumbar, and lumbar deformities, with additional discussions of advances in cervical deformity and pediatric deformity. METHODS: A review of recent literature was conducted. RESULTS: Advances in adult thoracic, thoracolumbar, and lumbar deformities reviewed include the growing applications of stereoradiography, development of new radiographic measures and improved understanding of radiographic alignment objectives, increasingly sophisticated tools for radiographic analysis, strategies to reduce the occurrence of common complications, and advances in minimally invasive techniques. In addition, discussion is provided on the rapidly advancing applications of predictive analytics and outcomes assessments that are intended to improve the ability to predict risk and outcomes. Advances in the rapidly evolving field of cervical deformity focus on better understanding of how cervical alignment is impacted by thoracolumbar regional alignment and global alignment and how this can affect surgical planning. Discussion is also provided on initial progress toward development of a comprehensive cervical deformity classification system. Pediatric deformity assessment has been substantially improved with low radiation-based 3-D imaging, and promising clinical outcomes data are beginning to emerge on the use of growth-friendly implants. CONCLUSION: It is ultimately through the reviewed and other recent and ongoing advances that care for patients with spinal deformity will continue to evolve, enabling better informed treatment decisions, more meaningful patient counseling, reduced complications, and achievement of desired clinical outcomes. KEY WORDS: Advances, Alignment, Complications, Cervical, Pediatric, Spinal deformity, Thoracolumbar Neurosurgery 80:S70–S85, 2017

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DOI:10.1093/neuros/nyw048

ver the last few decades, remarkable advances have been made in the treatment of spinal deformity. Improvements in imaging, instrumentation, surgical techniques, anesthesia, and critical care have enabled almost routine treatment of some deformities and have enabled surgeons to address increasingly more complex deformities.1–4 We also now have a better understanding of the profound disability that these patients experience, and the changes in function and mobility afforded by treatment.1,3,5 Although many advances are rapidly incorporated into practice and soon taken for granted, it is through ongoing research and innovation that continued improvements in care are achieved. This narrative review provides an overview of several recent and ongoing advances in the field

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of spinal deformity, including adult deformities of the thoracic, thoracolumbar, and lumbar regions (hereafter referred to collectively as thoracolumbar deformities), as well as cervical and pediatric deformities.

ADULT THORACOLUMBAR DEFORMITY Advances in Radiographic Assessment and Surgical Planning Evolving Understanding and Application of Radiographic Measures Historically, the diagnosis and management of adult spinal deformity (ASD) was based primarily on assessment of the coronal plane. Over the last decade, there has been a growing


EMERGING ADVANCES IN SPINAL DEFORMITY

TABLE. General Radiographic Spinopelvic Alignment Objectives for Adult Spinal Deformity Correctiona

Radiographic parameter

Alignment objective

Pelvic tilt (PT) C7-S1 sagittal vertical axis (SVA) Pelvic incidence to lumbar lordosis

40) were a CBVA < –4.8◦ or CBVA > 17.7◦ .

Surgical Treatment of Cervical Deformity and Cervical Osteotomy Classification Through the ISSG, Smith and colleagues80 recently demonstrated a very marked lack of consensus on recommended surgical approaches, osteotomies, and fusion levels for ACSD among a panel of deformity surgeons. This lack of consensus suggests that further study is warranted to assess whether specific surgical

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FIGURE 8. Illustrations depicting the 7 grades of soft-tissue release and osteotomies for cervical deformity correction, as described by Ames and colleagues.81 Copyright Kenneth X. Probst. Published with permission from Xavier Studio.

treatment strategies may be associated with better outcomes, fewer complications, and potentially be more cost effective. Ames and colleagues81 recently proposed a standardized nomenclature for cervical soft-tissue release and osteotomy for cervical deformity correction as a means of providing a common language among spine surgeons. This nomenclature has 7 anatomic grades of increasing extent of bone/soft-tissue resection and destabilization, ranging from partial facet resection to complete vertebral column resection (Figure 8).81 The safest region to achieve such correction is at the cervicothoracic junction because of the entry location of the vertebral artery, although considerations of manipulation at C7/T1 include potential injury to the C8 nerve root and spinal cord. Neurophysiological monitoring is recommended to enhance the safety of these procedures. Progress Toward a Cervical Deformity Classification Despite the complexity and potential for substantial impact on patient’s quality of life and function, there has been no widely accepted, standardized classification for ACSD.82 Recently, Ames and colleagues,83 through the ISSG, proposed a novel cervical deformity classification using a modified Delphi approach. This classification includes a deformity descriptor and 5 modifiers that incorporate sagittal, regional, and global spinopelvic alignment (Figure 9).83 The authors acknowledged that the proposed classification is likely to undergo revision as progress is made in understanding the critical factors in managing these complex deformities.83


PEDIATRIC DEFORMITY Three-Dimensional Imaging and Improved Understanding of AIS Despite the complex 3-D nature of AIS, assessment has historically been based on 2-D imaging. It is now recognized that measurement of the Cobb angle based on 2-D images is insufficient for the assessment of AIS, since it only measures the collapse of the spine, and completely neglects the horizontal plane.84 Since creation of the 3-D Classification Committee of the SRS, substantial progress has been made in defining the 3D features of AIS and in developing a 3-D AIS deformity classi fication.84–89 EOS (EOS Imaging SA) has revolutionized the 3-D assessment of AIS, since this technology enables standing assessment of global alignment that includes all of the elements of the chain of alignment, including the lower limbs, cervical spine, and head.84 Recent advances in the 3-D assessment of AIS have focused on defining the sagittal plane. Newton and colleagues87 obtained EOS imaging (EOS Imaging SA) of 120 AIS patients with primary thoracic curves and compared this imaging with the corresponding 2-D imaging.87 They reported that 2-D measurements of TK underestimated the preoperative loss of TK in AIS because of errors associated with axial plane rotation and that the difference between the 2-D and 3-D measurements of the T5-T12 kyphosis was strongly correlated with the degree of apical vertebral rotation.87 Pasha and colleagues88 reported similar findings in a series of 36 consecutive AIS patients. R

R



FIGURE 9. Summary of the Ames–Smith cervical deformity classification.83

Role of Tether Constructs for AIS Nonfusion treatment for AIS offers several potential advantages, including preservation of growth potential and mobility. Moal and colleagues90 performed a corrective tether analysis based on a porcine scoliosis model. After inducing a 50◦ Cobb angle, the authors removed the inducing tether and treated a subset with a nonfusion anterior corrective tether. After 20 wk, postmortem CT imaging with 3-D reconstructions demonstrated significant realignment in the corrective tether group compared with the untreated group that was a product of both mechanical action and growth modulation. The mean coronal Cobb angles for the corrective tether and untreated groups at postmortem were 27.9◦ and 52.7◦ , respectively.90 Clinical data on the use of tether for AIS are limited. Samdani and colleagues91 reported 2-yr results for 11 consecutive patients with thoracic idiopathic scoliosis who underwent anterior vertebral body tethering. The mean patient age was 12.3 yr, and the mean number of tethered levels was 7.8 (range of 7-9). The preoperative thoracic Cobb averaged 44.2◦ , and over 2-yr follow-up, the curves corrected to a mean of 13.5◦ (mean 70% correction). The authors reported no major complications and concluded that the technique is promising for skeletally immature patients with AIS.91 Vertebral body tethering is not approved by the US Food and Drug Administration (US FDA) for deformity treatment and is off-label for this purpose. In their report, Samdani and colleagues91 indicated that they currently consider anterior vertebral body tethering in skeletally immature

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patients with thoracic curves ranging from 35◦ to 60◦ , which demonstrate flexibility to less than 30◦ . Although they note that the general upper limit of curve magnitude is 60◦ , they will consider tethering in larger curves as long as they demonstrate flexibility to less than 30◦ . Further, they indicate that absolute contraindications include thoracic hyperkyphosis greater than 40◦ and a rotational prominence greater than 20◦ . Sun and colleagues92 recently reported a novel approach for tether treatment of AIS. Noting that current approaches for anterior tether require entry into the chest which can compromise pulmonary function, they explored a posterior tethering procedure, in which a tether is passed via the costotransverse foramen along the convex side. They performed this procedure in a porcine model and noted significant curve correction and recommended further study. Role of Growth-Friendly Spine Implants in Early Onset Scoliosis Growth-friendly implants are used in the treatment of early onset scoliosis to maximize spine and thorax growth potential and preserve lung function, while controlling curve progression. These implants are classified into 3 categories: distraction based (spine-based or rib-based growing rods, vertical expandable titanium rib prosthesis, and remotely expandable devices), compression based (vertebral staples and tethers), and guided growth (Luque trolley and Shilla).93 Except for the vertical expandable titanium rib prosthesis (used with a humanitarian


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exemption), other growth-friendly devices mentioned in this manuscript are not approved by the US FDA and are used offlabel. Several recent reports have documented clinical outcomes of growth-friendly implants. Shah and colleagues94 reported minimum 2-yr follow-up for a series of 43 early onset scoliosis patients treated with posterior distraction-based growing rods, with focus on sagittal and pelvic parameters. The mean preoperative age was 5.6 yr, and the mean number of lengthenings was 6.4.94 They demonstrated that posterior-based growing rods had an overall positive effect on SVA, with return of patients to a more neutral alignment.94 Kamaci and colleagues95 assessed the effect of dual growing rod instrumentation on the apical vertebral rotation in early onset scoliosis.95 They reported that dual growing rod instrumentation had no negative effect on transverse plane deformities and provided significant correction of the apical vertebra rotation. McCarthy and McCullough96 recently reported minimum 5-yr follow-up for 33 patients treated with the Shilla growth guidance technique. The average age at index surgery was 6.9 yr, and the mean follow-up was 7 yr. At baseline, curves averaged 69◦ and improved to a mean of 38.4◦ at follow-up. Although the reported complication rate was high (73%), the results are promising and suggest that children can be safely treated with the Shilla procedure. 96 Traditional growing rods (TGR) require multiple operative procedures for lengthening. Magnetically controlled growing rods (MCGR) can be lengthened noninvasively with an external controller.97 Several recent studies have reported outcomes based on MCGR. Hosseini and colleagues98 reported 2-yr followup in a multicenter series of 23 early onset scoliosis patients treated with MCGR. Single-rod implantation was performed in 8 patients, and dual-rod implantation was performed in 15 patients. Coronal curve magnitude improved from 61.3◦ to 34.3◦ in the de novo cases (n = 15) and improved from 49.4◦ to 43.8◦ in the conversion cases (n = 8). The T1-S1 height improved from 253 to 289 mm in the de novo cases, but did not significantly change in the conversion cases (from 294 to 290 mm). A total of 41 adverse events, including 14 that were implant related, occurred in 11 patients. The authors concluded that use of MCGR for early onset scoliosis is safe and has fewer overall complications than TGR, but that further study is needed. Teoh and colleagues99 reported 8 early onset scoliosis patients treated with MCGR with minimum 44-mo follow-up. They documented improvement in Cobb angle (60◦ to 42◦ ), but had 6 patients (75%) who required 8 revision surgeries. All 3 patients with a single-rod construct required a revision and they cautioned against using single-rod constructs. This group also reported on complication rates with MCGR compared with TGR and concluded that MCGR was associated with lower rates of infections, but that MCGR treatment was associated with an increased risk of instrumentation complications and unplanned returns to the operating room.100


Among the largest reported series of early onset scoliosis, patients treated with MCGR to date are from Ridderbusch and colleagues.101 They reported minimum 12-mo follow-up (mean of 21 mo) for 24 patients and documented significant mean improvement of the primary curve (from 63◦ to 29◦ ). Complications included: 1 patient who required rod exchange, 3 patients who required revision for PJK, and 1 patient revised for screw pull out.

CONCLUSIONS There are numerous recent and ongoing advances in the field of spinal deformity. In adult thoracolumbar deformity, these advances include stereoradiography, improved understanding of alignment objectives and enhanced tools for radiographic analysis, strategies to reduce complications and to better predict risk and outcomes, and advances in MIS techniques. Substantial progress has been made in the understanding of how cervical alignment is impacted by thoracolumbar regional alignment and global alignment and how this can affect surgical planning, and progress has been made toward a cervical deformity classification system. Assessment of pediatric deformities has been markedly improved with 3-D imaging, and promising outcomes data are beginning to emerge on the use of growth-friendly implants. Disclosures Dr Smith is a consultant for, and has received royalties and an honorarium for teaching for Zimmer Biomet; is a consultant and received an honorarium for teaching from Nuvasive; is a consultant for Cerapedics; received an honorarium from K2M; and has received fellowship funding from AOSpine and NREF. Dr Shaffrey holds patents with, receives royalties from, and is a consultant for Medtronic, Nuvasive, and Zimmer Biomet; is a stockholder in Nuvasive; is a consultant for K2M, Stryker, and In Vivo; and has received grants from NIH, Department of Defense, ISSG, DePuy Synthes, and AOSpine. Dr Bess is a consultant for, and receives royalties and research support from K2M; is a consultant for Allosource; receives royalties from Pioneer; receives royalties and research support from Innovasis and Nuvasive; and has received research support from DePuy Synthes, Zimmer Biomet, and Stryker. Dr Shamji is a consultant for Medtronic and has received research grants from the Canadian Pain Society and from AOSpine NA. Dr Brodke receives royalties from Amedica, DePuy Synthes, and Medtronic; is a consultant for Vallum; and has received fellowship funding from AOSpine. Dr Lenke is a consultant for Medtronic; has received royalties from Medtronic and Quality Medical Publishing; has received research grants from AOSpine, Scoliosis Research Society, EOS Technologies, Harms Study Group/Setting Scoliosis Straight Foundation, and Fox Family Foundation; held the position of Deputy Editor for Spine Deformity and Journal of Neurosurgery/Spine and been a reviewer for Spine, JBJS, and Journal of Pediatric Orthopedics; and serves/d on the Board of Directors for OREF and GSO (Global Spine Outreach). Dr Fehlings has received institutional fellowship support and research grant support from AOSpine and is a consultant for In Vivo Therapeutics. Dr Lafage has given paid lectures for DePuy Synthes, Nuvasive, K2M, and Medtronic and is a Board member and shareholder at Nemaris. Dr Schwab has received grants from SRS and DePuy Spine (through ISSGF); has had speaking/teaching arrangements/consulted for Zimmer Bioment, Nuvasive, K2M, MSD, and Medicrea; is a shareholder and sits on the Board of Directors for Nemaris INC; receives royalties from K2M and MSD, anticipating future royalties from ZB, Medicrea, and Nuvasive; and has patents with Nuvasive, Medicrea, K2M, and MSD. Dr Vaccaro



is a consultant for DePuy Synthes, Medtronic, Stryker Spine, Globus, Stout Medical, Gerson Lehrman Group, Guidepoint Global, Medacorp, Innovative Surgical Design, Orthobullets, Expert testimony, and Nuvasive; has served on a Scientific Advisory Board/Board of Directors/Committees for Progressive Spinal Technologies, Flagship Surgical, AOSpine, Innovative Surgical Design, Association of Collaborative Spine Research, Prime Surgeons, and Spine Therapy Network, Inc.; has received royalties from Medtronic, Stryker Spine, Globus, Aesculap, Thieme, Jaypee, Elsevier, and Taylor Francis/Hodder and Stoughton; has stock/stock option ownership interests with Replication Medica, Globus, Paradigm Spine, Sout Medica, Progressive Spinal Technologies, Advanced Spinal Intellectual Properties, Spine Medica, Computational Biodynamics, Spinology, In Vivo, Flagship Surgical, Cytonics, Bonovo Orthopaedics, Electrocore, Gamma Spine, Location Based Intelligence, FlowPharma, Rothman Institute and Related Properties, Innovative Surgical Design, Vertiflex, Avaz Surgical, Prime Surgeons, and Dimension Orthotics, LLC; and has been/is Deputy Editor/Editor of Clinical Spine Surgery and Spine Journal. Dr Ames is a consultant with DePuy Synthes and Medtronic; is a consultant for and receives royalties from Stryker; receives royalties from Zimmer Biomet; and has patents with Fish & Richardson, PC.

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58. Scheer JK, Smith JS, Schwab F, et al. Development of a preoperative predictive model for intra- or peri-operative major complications with high accuracy validated with 558 ASD patients. 84th Annual Meeting of the American Association of Neurological Surgeons; April 30-May 4, 2016; Chciago, IL. 59. Scheer JK, Osorio JA, Smith JS, et al. Development of validated computer-based preoperative predictive model for proximal junction failure (PJF) or clinically significant PJK with 86% accuracy based on 510 ASD patients with 2-year followup. Spine. 2016;41(22):E1328-E1335. 60. Sciubba D, Jain A, Neuman BJ, et al. Development of a preoperative adult spinal deformity frailty index that correlates to common quality and value metrics: length of stay, major complications, and patient-reported outcomes. 22nd International Meeting on Advanced Spine Techniques; July 8-11, 2015; Kuala Lumpur, Malaysia. 61. Miller EK, Jain A, Daniels A, et al. Assessment of a novel adult spinal deformity frailty index to assist with risk stratification for adult spinal deformity surgery. 51 Annual Meeting of the Scoliosis Research Society; September 21-24, 2016; Prague, Czech Republic. 62. Miller EK, Vila-Casademunt A, Sciubba D, et al. Development and external validation of the adult spine deformity frailty index. 51 Annual Meeting of the Scoliosis Research Society; September 21-24, 2016; Prague, Czech Republic. 63. Miller EK, Ailon T, Neuman BJ, et al. Assessment of a novel adult cervical deformity frailty index as a componenet of preoperative risk stratification. International Meeting on Advanced Spine Techniques; July 13-16, 2016; Washington, DC, USA. 64. Neuman BJ, Scheer JK, Ailon T, et al. Development and validation of a novel adult spinal deformity surgical invasiveness score: analysis of 464 patients. 22nd International Meeting on Advanced Spine Techniques; July 8-11, 2015; Kuala Lumpur, Malaysia. 65. Pellise F, Vila-Casademunt A, Ferrer M, et al. Impact on health related quality of life of adult spinal deformity (ASD) compared with other chronic conditions. Eur Spine J. 2015;24(1):3-11. 66. Bridwell KH, Berven S, Glassman S, et al. Is the SRS-22 instrument responsive to change in adult scoliosis patients having primary spinal deformity surgery? Spine. 2007;32(20):2220-2225. 67. Hung M, Hon SD, Franklin JD, et al. Psychometric properties of the PROMIS physical function item bank in patients with spinal disorders. Spine. 2014;39(2):158-163. 68. Hung M, Stuart A, Cheng C, et al. Predicting the DRAM mZDI using the PROMIS anxiety and depression. Spine. 2015;40(3):179-183. 69. Ames CP, Blondel B, Scheer JK, et al. Cervical radiographical alignment: comprehensive assessment techniques and potential importance in cervical myelopathy. Spine. 2013;38(22 suppl 1):S149-S160. 70. Scheer JK, Tang JA, Smith JS, et al. Cervical spine alignment, sagittal deformity, and clinical implications: a review. J Neurosurg Spine. 2013;19(2): 141-159. 71. Smith JS, Lafage V, Ryan DJ, et al. Association of myelopathy scores with cervical sagittal balance and normalized spinal cord volume: analysis of 56 preoperative cases from the AOSpine North America Myelopathy study. Spine. 2013;38(22 suppl 1):S161-S170. 72. Smith JS, Shaffrey CI, Lafage V, et al. Spontaneous improvement of cervical alignment after correction of global sagittal balance following pedicle subtraction osteotomy. J Neurosurg Spine. 2012;17(4):300-307. 73. Ramchandran S, Smith JS, Ailon T, et al. Assessment of impact of longcassette standing x-rays on surgical planning for cervical pathology: an international survey of spine surgeons. Neurosurgery. 2016;78(5):717-724. 74. Diebo BG, Challier V, Henry JK, et al. Predicting cervical alignment required to maintain horizontal gaze based on global spinal alignment. Spine. (Phila Pa 1976). 2016;41(23):1795-1800. 75. Passias PG, Oh C, Jalai CM, et al. Predictive model for cervical alignment and malalignment following surgical correction of adult spinal deformity. Spine. 2016;41(18):1096-1103. 76. Tang JA, Scheer JK, Smith JS, et al. The impact of standing regional cervical sagittal alignment on outcomes in posterior cervical fusion surgery. Neurosurgery. 2012;71(3):662-669; discussion 669. 77. Mohanty C, Massicotte EM, Fehlings MG, Shamji MF. Association of preoperative cervical spine alignment with spinal cord magnetic resonance imaging hyperintensity and myelopathy severity: analysis of a series of 124 cases. Spine. 2015;40(1):11-16.



78. Shamji MF, Mohanty C, Massicotte EM, Fehlings MG. The association of cervical spine alignment with neurologic recovery in a prospective cohort of patients with surgical myelopathy: analysis of a series of 124 cases. World Neurosurg. 2016;86:112-119. 79. Lafage R, Challier V, Liabaud B, et al. Natural head posture in the setting of sagittal spinal deformity: validation of chin-brow vertical angle, slope of line of sight, and McGregor’s slope with health-related quality of life. Neurosurgery. 2016;79(1):108-115. 80. Smith JS, Klineberg E, Shaffrey CI, et al. Assessment of surgical treatment strategies for moderate to severe cervical spinal deformity reveals marked variation in approaches, osteotomies, and fusion levels. World Neurosurg. 2016;91:228-237. 81. Ames CP, Smith JS, Scheer JK, et al. A standardized nomenclature for cervical spine soft-tissue release and osteotomy for deformity correction: clinical article. J Neurosurg Spine. 2013;19(3):269-278. 82. Smith JS, Line B, Bess S, et al. The health impact of symptomatic adult cervical deformity: comparison to United States population norms and chronic disease states based on the EQ5D. 23rd International Meeting on Advanced Spine Techniques; July 13-16, 2016; Washington, DC, USA. 83. Ames CP, Smith JS, Eastlack R, et al. Reliability assessment of a novel cervical spine deformity classification system. J Neurosurg Spine. 2015;23(6):673-683. 84. Ilharreborde B, Dubousset J, Le Huec JC. Use of EOS imaging for the assessment of scoliosis deformities: application to postoperative 3D quantitative analysis of the trunk. Eur Spine J. 2014;23(suppl 4):S397-S405. 85. Eijgenraam SM, Boselie TF, Sieben JM, et al. Development and assessment of a digital X-ray software tool to determine vertebral rotation in adolescent idiopathic scoliosis. Spine J. 2017;17(2):260-265. 86. Labelle H, Aubin CE, Jackson R, Lenke L, Newton P, Parent S. Seeing the spine in 3D: how will it change what we do? J Pediatr Orthop. 2011;31(1 suppl):S37-S45. 87. Newton PO, Fujimori T, Doan J, Reighard FG, Bastrom TP, Misaghi A. Defining the "Three-Dimensional Sagittal Plane" in thoracic adolescent idiopathic scoliosis. J Bone Joint Surg Am. 2015;97(20):1694-1701. 88. Pasha S, Cahill PJ, Dormans JP, Flynn JM. Characterizing the differences between the 2D and 3D measurements of spine in adolescent idiopathic scoliosis. Eur Spine J. 2016;25(10):3137-3145.

NEUROSURGERY

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